Professional Documents
Culture Documents
nd
22 United European
UEG gratefully acknowledges the support
Gastroenterology Week
of this years Premium Partners: Vienna 2014
Disclaimer: United European Gastroenterology (UEG) is not responsible for errors or omissions in the
abstracts. This abstract book was nalized on August 7, 2014, any changes received after this date have not
been incorporated. Changes to presenters received after August 7 have been included in the online version of the
programme and can be obtained at: www.ueg.eu/education/library.
Disclosure policy: UEG is committed to ensuring scientic rigour and objectivity in all of its educational
activities. These include all aspects of the educational programme at UEG Week including those that are
directly and jointly sponsored activities.
All presenters, whether invited Faculty or abstract presenters, are required to disclose to those organising and
attending meetings any relevant nancial or other relationship that may lead to a potential bias. UEG reserves
the right to review the information disclosed for potential conicts of interest. Please note that the sole
responsibility for the content of each presentation lies with the presenting author.
The UEG Scientic Committee requires all presenters to disclose any advisory or consultancy roles in the
Biomedical Industry during the past two years. These and any other potential conicts of interest should be
disclosed verbally during introductory comments to the presentation. Invited speakers and oral abstract pre-
senters are requested to disclose potential conicts of interest on a PowerPoint slide to be shown immediately at
the beginning of the presentation. Poster presenters are requested to disclose potential conicts of interest at the
bottom of their poster.
Conicts of interest may exist through a nancial relationship or when the individual has the opportunity to
inuence the content of a presentation, and can involve grants, honoraria, shares, paid positions on advisory
boards, etc. Conicts of interest are frequent and expected, and do not preclude an individual from making a
presentation providing the conict is disclosed. If there is any doubt about the relevance of a potential conict
of interest UEG requires all presenters to err on the safe side and to disclose it.
Editor
Jan Tack, University of Leuven, Belgium
Associate Editors
Tim Greten, NIH, USA
Arthur Kaser, University of Cambridge, UK
Oliver Pech, St John of God Hospital, Regensburg, Germany
Editorial Board
Alberto Arezzo, University of Turin, Italy
David Armstrong, McMaster University, Canada
Michael Bourke, Westmead Hospital, Australia
Guido Costamagna, Catholic University of the Sacred Heart, Italy
Carlo Di Lorenzo, Childrens Hospital of Colombus, USA
Wouter De Jonge, Academic Medical Center, The Netherlands
Doug Drossman, University of North Carolina at Chapel Hill, USA
Mohamad Eloubeidi, American University of Beirut School of Medicine, Lebanon
Johanna C Escher, Erasmus MC, The Netherlands
Ronnie Fass, The Neuro-Enteric Clinical Research Group, USA
Richard Hunt, McMaster University, Canada
Michael P Jones, Macquarie University, Australia
John Kellow, The University of Sydney, Australia
Markus Lerch, University Medicine Greifswald, Germany
Lars Lundell, Karolinska Institute, Sweden
Hendrik Manner, HSK Wiesbaden, Germany
Helmut Neumann, University of Erlangen-Nuremberg, Germany
Qin Ouyang, West China Hospital, China
Stefan Schreiber, UKSH Campus Kiel, Germany
Vincenzo Stanghellini, University of Bologna, Italy
Jaap Stoker, Academic Medical Centre, The Netherlands
Hidekazu Suzuki, Keio University School of Medicine, Japan
Michael Vieth, University of Bayreuth, Germany
Michael Wallace, Mayo Clinic, USA
Heiner Wedemeyer, Hannover Medical School, Germany
Frank Zerbib, CHU Bordeaux, France
Aims and scope
Launched in 2013, United European Gastroenterology Journal is the official Journal of United European Gastroenterology (UEG), a professional non-
profit organisation combining all the leading European societies concerned with digestive disease. UEGs member societies represent over 22,000
specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and
the exchange of knowledge.
United European Gastroenterology Journal provides an international forum for research in gastroenterology, publishing original articles which
describe basic research, translational and clinical studies of interest to gastroenterologists and researchers in related fields. Articles from across
all fields of gastroenterology are be welcomed by the Editor-in-Chief, including luminal, liver and pancreatic diseases, gastrointestinal surgery,
gastrointestinal oncology, paediatric gastroenterology and nutrition as well as endoscopy.
Published article types include original research, reviews, guidelines papers and news items. The journal is a member of the Committee on
Publication Ethics (COPE).
Commercial sales
For information on reprints and supplements please contact reprints@sagepub.co.uk and for advertising, please contact
UKAdvertising@sagepub.co.uk.
Disclaimer: The authors, editors, and publisher will not accept any legal responsibility for any errors or omissions that may be made in this
publication. The publisher makes no warranty, express or implied, with respect to the material contained herein.
Printed on acid-free paper by Page Bros., Norwich, UK.
XML Template (2014) [9.9.20143:24pm] [11]
//blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/UEGJ/Vol0025s/140055/APPFile/SG-UEGJ140055.3d (UEG) [INVALID Stage]
Dear Colleagues,
On behalf of the UEG Scientic Committee, I would like to take this opportunity to thank you most sincerely for
your contribution as an abstract reviewer for the original programme of UEG Week Vienna 2014.
The abstract reviewing process has been again very important this year with a number of innovations intro-
duced to improve especially the poster abstract presentations. I know just how much time and eort reviewing
abstracts takes, but without your expertise we would not have the quality that I believe we have achieved in the
free paper and poster sessions, and the UEG Week would not be the top international digestive diseases meeting
that it has become today. Thank you!
I am delighted to announce that we received a total of 3,339 abstracts for UEG Week Vienna 2014, excluding
late breakers and video cases. 2,127 of these were accepted, giving an acceptance rate of 63.7%. 406 abstracts will
be delivered as oral presentations and 1,721 as posters. I am even more pleased to tell you that standards have
again reached a very high level and we can expect to be exposed to most interesting research and great
presentations.
This high volume and high standard conrm that UEG Week is the most important forum at which to present
your best research. Additionally, we have received 57 video cases which were formally evaluated by the Scientic
Committee for presentation in Vienna. The quality of reviewing this year was excellent but if you have any further
(positive or negative) comments, please do let us know!
Finally, but most importantly, many thanks to all investigators both within and outside Europe who have
submitted their research to the meeting, and who are clearly contributing to making UEG Week Vienna 2014 such
a great success!
Magnus Simren
Chair, UEG Scientific Committee, Vienna 2014
United European Gastroenterology Journal
2(5S) viiviii
! Author(s) 2014
Thanks to Partners, Sponsors and Exhibitors Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2050640614548988
ueg.sagepub.com
Premium Partners
AbbVie Inc.
FUJIFILM Europe GmbH
OLYMPUS EUROPA SE
Shire International GmbH
Takeda Pharmaceuticals International GmbH
Major Partners
Almirall, S.A.
Covidien
Merck & Co., Inc.
Norgine Limited
PENTAX Europe GmbH
General Sponsors and Exhibitors
8th Paris Hepatitis Conference Chongqing Jinshan Science & Technology (Group)
Abbott Products Operations AG Co., Ltd. / OMOM Capsule
ACTIAL FARMACEUTICA Lda CONMED Europe
Alfa Wassermann S.p.A. Cook Medical
ALTON (Shanghai) Medical Instruments Co., Ltd DDW Digestive Disease Week
ANEMGI onlus Associazione per la Diagnoplex SA
NeUroGastroenterologia e la Motilita` Dr. Falk Pharma GmbH
Gastrointestinale EAES European Association for Endoscopic Surgery
Anrei Medical (Hangzhou) Co., Ltd. EAGEN European Association for
Apollo Endosurgery, Inc. Gastroenterology, Endoscopy and Nutrition
APTALIS PHARMA SAS EASL European Association for the Study of the
ARC Medical Design Ltd Liver
AstraZeneca EB Neuro S.p.A.
BALTON Sp. z o.o. ECCO European Crohns and Colitis Organisation
Bedfont Scientic Ltd ECOSTER SYSTEMS
BIOCODEX EDS European Digestive Surgery
Biohit Oyj EFISDS International Society of Digestive Surgery
Boehringer Ingelheim Pharma GmbH & Co. KG (European Federation)
Boston Scientic International S.A. EFSUMB European Federation of Societies for
BOWA-electronic GmbH & Co. KG Ultrasound in Medicine and Biology
Bracco Diagnostics Inc. EGYPT GASTRO HEP
BUHLMANN Laboratories AG EHSG European Helicobacter Study Group
CALPRO AS ELLA-CS, s.r.o.
CapsoVision Inc. Elsevier Ltd.
CBC (Europe) GmbH EMcision International Inc.
Celltrion Healthcare Co., Ltd. EMED SP. Z O. O. SP. K.
viii United European Gastroenterology Journal 2(5S)
OP010 PRE-TREATMENT DIFFERENTIAL MICRORNA EXPRESSION SNP Wild Type (WT) n (%) Heterozygous n (%) Homozygous n (%)
PROFILE IN ULCERATIVE COLITIS PATIENTS ACCORDING TO
THEIR RESPONSE TO CORTICOSTEROIDS rs10951982 41 (69) 15 (25) 3 (5)
J. Naves1,*, J. Mane2, V Loren2, M. Manosa1, I. Moret3, A. Garcia- rs4720672 45 (76) 12 (20) 2 (3)
Jaraquemada2, G. Bastida3, B. Beltran3, E. Cabre2, E. Dome`nech2 rs34932801 45 (90) 5 (10) 0
1
GASTROENTEROLOGY DEPARTMENT, 2HOSPITAL UNIVERSITARI
GERMANS TRIAS I PUJOL, BADALONA, 3HOSPITAL UNIVERSITARI There was no association between genotype and disease type. Baseline PGA was
LA FE DE VALENCIA, VALENCIA, Spain similar for all genotypes except for rs4720672 homozygotes, who had a lower
Contact E-mail Address: navesjuan@gmail.com baseline PGA than WT (p 0.003). At 12 months, 16/41 (39%) WT and 8/15
(53%) heterozygotes for rs10951982 were in remission (p0.38), while 18/45
INTRODUCTION: Corticosteroids (CS) remain the first-line treatment for mod- (40%) WT and 7/12 (58%) heterozygotes for rs4720672 were in remission
erate-to-severe active ulcerative colitis (UC). However, up to 40% of patients do (p0.33); 22/45 (49%) WT and 2/5 (40%) heterozygotes for rs34932801 were
not have an adequate response, an event that to date, cannot be predicted yet. in remission (p1.0). All 3 homozygotes for the former 2 SNPs were in remission.
microRNA (miRNA) are small non-coding RNA fragments that modulate gene CONCLUSION: These three Rac1 SNPs of RAC1 were not found to be asso-
expression at posttranscriptional level, thus playing a critical role in many bio- ciated with 1-year response to thiopurines in a prospective study of pediatric
logical processes. Little is known about the influence of miRNA in the response IBD.
to CS in UC. Disclosure of Interest: None declared
AIMS & METHODS: To compare the miRNA profile in rectal mucosa of
patients with active UC responding and non-responding to CS.
Methods: Rectal biopsies were obtained from consecutive UC patients before OP012 DIFFERENT PROFILE OF EFFICACY OF THIOPURINES IN
starting CS therapy for a moderate-to-severe flare. Patients were grouped accord- ULCERATIVE COLITIS AND CROHNS DISEASE
ing to clinical response (non-responder moderate or severe activity according to A. Testa1,*, A. Rispo1, M. Rea1, G.D. De Palma1, M. Diaferia1, D. Musto1,
Montreals classification at day 7 or need for rescue therapy before day 7; respon- F. Sasso1, N. Caporaso1, F. Castiglione1
der Less than moderate activity without need for rescue therapy at day 7). 1
Clinical Medicine and Surgery, University "Federico II" of Naples, Naples, Italy
miRNA were identified by means of a sequencing method (TruSeq SmallRNA
kit from Illumina) on those fresh-frozen rectal biopsies that reached a RNA INTRODUCTION: Azathioprine (AZT) and 6-mercaptopurine (6-MP) are
Integrity Number (RIN) 8. Comparison of miRNA profile between groups effective drugs in treating ulcerative colitis (UC) and Crohns disease (CD) as
was carried out on the miRanalyzer D.E. tool through DESeq package. Those they can induce/maintain clinical remission (CR) and mucosal healing (MH) in
miRNA with a fold change 1.5 and adjusted p-value 0.05 were further steroid-dependent patients. Nevertheless, even if trials and meta-analyses have
studied. Potential targets of selected miRNA were checked in Target Human confirmed the efficacy of thiopurines in UC and CD, studies directly investigat-
Scan database (www.targetscan.org), and their impact on biological activity was ing a possible different profile of efficacy in UC in comparison with CD are
searched in GeneCodis database (http://genecodis.cnb.csic.es). scarce.
RESULTS: 15 out of 24 tissue samples (8 responders and 7 non-responders) AIMS & METHODS: To explore the rate of CR and MH in UC patients treated
reached a RIN value 8 allowing miRNA sequencing. We found more than by thiopurines compared to that of subjects with CD. From September 2011 to
1,300 known miRNA and about 70 new miRNA. Responders to CS had an April 2014 we performed an observational longitudinal study evaluating steroid-
up-regulated expression of has-miR-5701 and has-miR-625-3p, and down- free CR and MH in all UC and CD patients who would complete 2 years of
regulated expression of has-miR-1246 and has-miR-1291 as compared to non- maintenance treatment with thiopurines (AZT 2-2.5 mg/kg/day; 6-MP 1-1.5 mg/
responders. Bioanalysis using miRNA targets database showed up to 2,000 kg/day). Patients characteristics were classified according to the ECCO guide-
potential targets for the aforementioned miRNA, most of them involved in lines. CR and MH were assessed before starting treatment and 2 years later by
MAPK signalling pathways, cytoskeleton organization pathway, and cell differ- Mayo score for UC (CR Mayo score 52; MH Mayo sub-score 51); CR and
entiation endocytosis and autophagy mechanisms. MH were assessed at same time-points by Crohns disease activity index
CONCLUSION: Patients with active UC not responding to CS show a differ- (CRCDAI5 150) and Simplified Endoscopic Score for Crohns Disease
ential mucosal miRNA expression profile before starting therapy. These findings (MHSES-CD 52) for CD. Statistical analysis was performed using chi-
suggest that regulation of gene expression by miRNA might play a role in the square, MannWhitney U test and odd ratio (OR) where appropriate. To test
response to treatment in UC patients. the concordance between CR and MH in UC and CD, the Cohens k measure
Disclosure of Interest: None declared was applied. Regarding the differences in outcomes for CR and MH we esti-
mated that a total sample size of 120 patients would allow detection of a 20%
difference between the 2 groups. A p value lower than 0.05 was considered
significant.
RESULTS: The study included 70 patients with UC (AZT/6-MP60/10; M/
F37/33; mean age39 years; E10, E224, E346; mean baseline Mayo
score8.5) and 70 subjects with CD (AZT/6-MP62/8; M/F 39/31; mean
age33 years; L134, L226, L310; B154, B210, B36; mean baseline
United European Gastroenterology Journal 2(5S) A5
CDAI290) treated with thiopurines for 2 years. At the end of the study, steroid- treatment given many pre-treatment observed covariates. By using the probabil-
free CR was recorded in 43 patients with UC and 37 with CD (61% vs 53%; ity that a subject would have been treated with low dose (1.25mg/kg/day
p0.3). MH was obtained in 38 patients with UC and 17 with CD (54% vs 25%; methylprednisolone-equivalent, max 50mg) vs. high-dose IVCS (41.25mg/kg/d
p50.01; O.R.4.5). The concordance between CR and MH was higher in UC or 450mg/d) we individually matched children from both groups, thus creating a
patients than in subjects with CD (k0.71 in UC; k0.41 in CD). quasi-randomized trial (matching according to the nearest value of the logit of
CONCLUSION: Thiopurines are equally effective in maintaining steroid-free the propensity score within the determined caliper size in a blinded fashion to all
clinical remission in both UC and CD even if with a better profile of efficacy outcomes). Secondary analyses utilized a high cutoff value (42mg/kg/d or
in UC in terms of mucosal healing. Our data confirm the higher concordance 480mg/d).
between clinical and endoscopic findings in UC compared to that observed in CD RESULTS: Of the total cohort, 208 were matched (104 in each of the high and
patients. low dose groups). The mean age was 12.14 years, median disease duration 2
Disclosure of Interest: None declared (IQR 0-13.8) months, 47% males and mean PUCAI at admission 7112 points,
implying severe disease. The two groups were similar in important pre-treatment
basic variables alluding to successful matching. Median IVCS dose was 0.84
OP013 RANDOMIZED CONTROLLED TRIAL COMPARING THE (IQR 0.7-1.02; min 0.5) mg/kg/d in the low dose group and 1.57 (1.03-1.99;
EFFICACY OF MEASALAMINE AND ORAL STEROIDS IN max 30.3) mg/kg/d in the high dose group. There were no significant differences
PATIENTS WITH MODERATELY ACTIVE ULCERATIVE COLITIS in clinically relevant outcomes between the high and the low-dose groups (i.e.
A. Raj1,*, Y.R. Reddy1, S.K. Sinha1, C. Vaishnavi1, K.K. Prasad1, need for salvage therapy by discharge (35% vs 32%, respectively; P0.77) and
M.L. Thakur1, P.K. Siddappa1, K. Singh1, R. Kochhar1 time to salvage therapy, rate of children achieving PUCAI535 points by day 5
1
Gastroenterology, Postgraduate Institute of Medical Education and (41% vs. 43% P0.92) and mean day-5 albumin (P0.36), CRP (P0.26), plate-
Research(PGIMER), Chandigarh, India lets (P0.72) and hemoglobin (P0.32)). The low-dose group had significantly
Contact E-mail Address: dr_kochhar@hotmail.com lower mean admission-days by 3.8 days (P0.02) and mean day-5 ESR (lower by
9mm; P0.04). In the secondary analysis, 84 children were matched in the high-
INTRODUCTION: The treatment of active ulcerative colitis (UC) has been dose cutoff. Among the measured outcomes, the only different outcome was the
aimed at the alleviation of symptoms. However, mounting evidence suggests mean admission days, which was higher by 3.67 (P0.04) in the high dose group.
mucosal healing better marker of long-term outcomes. CONCLUSION: Our data suggest that IVCS doses up to 1.25mg/kg/d (max
AIMS & METHODS: To compare the efficacy of oral mesalamine with that of 50mg/d) are at least as effective as higher doses in ASC. These results should
oral prednisolone in patients with moderately active ulcerative colitis (UC). be considered for inclusion in clinical guidelines.
In this open label randomized controlled study between June 2012 and December Disclosure of Interest: None declared
2013 consecutive patients of moderately active UC were randomly assigned to
two treatment groups. One group (ASA) received mesalamine tablets 800mg, two
tablets TID (total dosage-4.8gm/day) and the other group (CS) received predni- MONDAY, OCTOBER 20, 2014 11:0012:30
solone in tapering doses (40mg OD for 1 week, then 30mg for next 1 week and ADVANCES IN ERCP HALL N_____________________
then 20mg for next 4 weeks). All patients were followed for 6 weeks. Mayo score,
sigmoidoscopy with biopsy, and fecal calprotectin (FC) were determined at the OP015 BILIARY DYSPLASIA SCREENING IN PSC - THE VALUE OF
baseline and at the end of treatment. Mucosal healing was defined as decrease in BRUSH CYTOLOGY AND ERCP SCORING
sigmoidoscopy subscore to 1. Clinical response was defined as a decrease of 3 S. Boyd1,*, A. Tenca2, K. Jokelainen2, L. Krogerus3, J. Arola1, M. Farkkila2
points from the baseline Mayo score. Clinical remission was defined as achieve- 1
Department of Pathology, 2Clinic of Gastroenterology, Helsinki University and
ment of Mayo score 2. Data was recorded in excel sheet and statistical analysis Helsinki University Central Hospital, Helsinki, 3Department of Pathology,
was done using SPSS v17.0 Helsinki University and Helsinki University Central Hospital Jorvi, Espoo, Finland
RESULTS: Twenty nine patients received mesalamine and 25 patients received Contact E-mail Address: sonja.boyd@hus.fi
steroids. Mucosal healing was achieved in 19 (65.5%) of the patients in ASA
group and 17 (68%) of the patients in CS group (p0.847). There was significant INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic cholestatic
improvement in Mayo score from 8.51.2 to 3.51.7 in ASA group as well as biliary disease associated with inflammatory bowel disease (IBD). The risk for
from 8.11.6 to 3.11.8 in CS group (p0.001). Clinical response was achieved malignancies, especially cholangiocarcinoma (CCA) is elevated among PSC
in 26 (89.7%) patients in ASA group and 23 (92%) patients in the CS group. patients. Biliary intraepithelial neoplasia (BilIN) is the precursor of CCA.
Clinical remission was achieved in 8 (27.6%) patients in ASA group and 12 AIMS & METHODS: We performed brush cytology (BC) for 261 consecutive
(48%) patients in the CS group. There was no statistically significant difference patients referred for their first endoscopic retrograde cholangiography (ERCP)
between ASA and CS groups with regard to treatment response or remission. due to suspicion of PSC between 1st of January 2006 and 31th of October 2011.
Total histopathology score in CS group decreased from 11.92.4 to 8.13 Macroscopic biliary duct changes (i.e. strictures and dilations) were graded
(p0.001), but at the end of treatment total score in both ASA and CS groups according to the modified Amsterdam score (Ponsioen 2010). BC was graded
was not significantly different from each other (9.73.4 vs 8.13; p0.088). as benign (normal or benign atypia), suspicious (cytologic dysplasia) or malig-
There was improvement in FC levels in both the groups (132136.6 mg/g stool nant. End points were follow up for at least two years, liver transplantation or
to 75.977.1 mg/g stool in ASA group and 165.7116.4 mg/g stool to 115.683.1 development of CCA.
mg/g stool in CS group) although the difference between paired samples could not RESULTS: BC was classified as benign (93.1%), suspicious (6.1%) or malignant
reach a significant level (p0.057 and p0.136 respectively). In subgroup analy- (0.8%). All patients with nonadvanced PSC based on ERC-scoring had benign
sis, we observed a significant (p0.007) improvement in FC level from BC, with the exception of one without known end-point. During the follow up
163.7133.2 mg/g stool to 89.986.6 mg/g stool on follow up at 6 weeks in time for at least two years (mean 4.8 years) most patients (n249, 95.4%)
patients who achieved mucosal healing as compared to those who did not reached the end point (follow up for 2 years without evidence of CCA, no biliary
(p0.783). There was significant improvement in erythrocyte sedimentation neoplasia in the explanted liver, BilIN, or CCA). Seven patients were diagnosed
rate in ASA group; from 28.413.5 to 20.711.8 (p0.002) as well as in CS with CCA, five of them within 5 months after diagnosis of PSC. Eight out of nine
group; from 33.518.8 to 21.313.7 (p0.003). patients with liver transplantation had BilIN. Two patients were diagnosed with
CONCLUSION: Prednisolone and mesalamine are equally effective in inducing gallbladder carcinoma. Most patients (n232, 93.2%) who reached end-point
mucosal healing and clinical response in moderately severe UC. Both the drugs were classified as having benign disease course. Majority of patients with BilIN
were associated with significant improvement in endoscopic as well as clinical or CCA were male (n11, 73.3%), and the first BC was suspicious or malignant
activity of the disease. Mucosal healing was positively correlated with fall in FC in eight (53.3%) of them.
levels. CONCLUSION: In unselected patient population coming for the first time for
Disclosure of Interest: None declared diagnostic ERCP for PSC 7% had already a suspicion of malignancy or biliary
malignancy in brush cytology. Advanced PSC and male sex were associated with
biliary neoplasia.
OP014 CORTICOSTEROID DOSING IN PEDIATRIC ACUTE SEVERE REFERENCES
ULCERATIVE COLITIS: A MULTICENTER PROPENSITY SCORE Validation of a cholangiographic prognostic model in primary sclerosing
STUDY cholangitis.
S. Choshen1, H. Finnamore2, M. Auth2, T. Bdolah3, E. Shteyer3, D. Mack4, Ponsioen et al. Endoscopy 2010: 742-747.
J. Hyams5, N. Leleiko6, A.M. Griffiths7, D. Turner1,* Disclosure of Interest: None declared
1
Shaare Zedek Medical Center, Jerusalem, Israel, Jerusalem, Israel, 2University of
Liverpool, Liverpool, United Kingdom, 3Hadassah Medical Center, Jerusalem,
Israel, 4CHEO, Ottawa, Canada, 5Connecticut Childrens Medical Center, OP016 COMPARATIVE ANALYSIS OF ERCP, IDUS, EUS AND CT IN
Hartford, 6Brown University, Providence, United States, 7HSC, Toronto, Canada PREDICTING MALIGNANT BILE DUCT STRICTURES RESULTS
Contact E-mail Address: turnerd@szmc.org.il OF A TERTIARY REFERRAL CENTER WITH 234 PATIENTS
H.S. Heinzow1,*, S. Kammerer2, D. Domagk1, T. Meister3
INTRODUCTION: Data to support dosing of intravenous corticosteroids 1
Department of Medicine B, 2Department of Radiology, UNIVERSITY OF
(IVCS) in pediatric acute severe ulcerative colitis (ASC) are lacking and extra- MUENSTER, Muenster, 3Department of Medicine II, Helios Albert-Schweitzer-
polated from adult literature. We aimed to explore the optimal dosing of IVCS Klinik Northeim, Northeim, Germany
using a robust statistical method called propensity score analysis on the largest Contact E-mail Address: hauke.heinzow@ukmuenster.de
pediatric cohort of ASC to date.
AIMS & METHODS: 283 children treated with IVCS for ASC were included INTRODUCTION: There are no definite guidelines for the management and
from the OSCI studies (n227) and another 55 newly reviewed patients from diagnostics of biliary strictures of indeterminate etiology so far. Various endo-
Jerusalem and Liverpool, which uses high IVCS doses as part of local practice. scopic and radiographic imaging modalities such as endoscopic retrograde cho-
As children were treated according to physician discretion, a simple comparison langio-pancreatography (ERCP), intraductal ultrasound (IDUS),
of the dosing may lead to confounding-by-indication bias. This was addressed by endosonography (EUS) and computed tomography (CT) are available and com-
the propensity score method, which is the conditional probability of receiving the pete with each other.
A6 United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We aimed to evaluate the diagnostic yield of IDUS, EUS OP018 ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION
and CT in a large patient cohort of 234 scheduled for ERCP with IDUS, CT and (EPLBD) VERSUS ADDITIONAL FULL ENDOSCOPIC
EUS due to indeterminate strictures or filling defects of the common bile duct. SPHINCTEROTOMY (EST) FOR THE ENDOSCOPIC REMOVAL OF
Sensitivity, specificity and accuracy rates of the diagnostic procedures were cal- RECURRENT LARGE BILE DUCT STONES AFTER NON-FULL EST
culated relating to the definite diagnoses proved by histopathology or long-term D. Kim1,1,*, G. Song1, B. Lee1, D. Baek1, J. Seo1, S. Lee1, T. Kim1, K. Lee1, J. Lee
follow-up in those patients who did not undergo surgery. For each of the diag- 1
nostic measures, sensitivity, specificity and accuracy rates were calculated. In all 1
Department of Internal Medicine, Pusan National University School of Medicine,
cases, gold standard was the histopathologic staging of specimens or long-term Busan, Korea, Republic Of
follow-up of at least 12 months. Contact E-mail Address: dhbeak@naver.com
RESULTS: Comparison of the different diagnostic tools for detecting bile duct
malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92% INTRODUCTION: There were no reports about the comparative study between
(IDUSETP), 74% (EUS) and 73% (CT), respectively. In the subgroup analysis endoscopic papillary large balloon diation (EPLBD) and additional endoscopic
accuracy rates (%, ERCPIDUS/ETP/IDUSETP; EUS; CT) for each tumor sphincterotomy (EST) for endoscopic treatment of common bile duct stones
entity were as follows: cholangiocellular carcinoma: 92/74/92/70/79; pancreatic which were recurred after endoscopic stone removal with previous non-full EST.
carcinoma: 90/68/90/81/76; ampullary carcinoma: 88/90/90/76/76. The detection AIMS & METHODS: The aim of this study was to compare the safety and
rate of malignancy by ERCP/IDUS was superior to ETP (91 vs. 59% p50.0001), efficacy of EPLBD with additional EST for recurrent difficult bile duct stones
EUS (91 vs. 74% p50.0001) and CT (91 vs. 73%p50.0001), EUS was compar- after previous non-full EST.
able to CT (74 vs. 73%, p0.649). When analyzing accuracy rates with regard to We retrospectively reviewed the records from twelve hundred four patients who
localization of the bile duct stenosis the accuracy rate of EUS for proximal vs. received the first ERCP for the removal of bile duct stones from August 2004 to
distal stenosis was significantly higher for distal stenosis (79 vs. 57%, p50.0001). July 2013. We enrolled a total of 89 patients who had large bile duct stones
CONCLUSION: ERCP/IDUS is superior to EUS and CT in accurate diagnos- recurred after previous non-full EST, and need to receive the additional papillo-
tics of bile duct strictures of uncertain etiology. However, multimodal diagnostics plasty. The patients were classified into three groups: Group A who underwent
due to even better accuracy rates is recommended. EPLBD (group A, n 59) by using 12 18 mm sized balloon, and group B who
Disclosure of Interest: None declared underwent additional full EST (group B, n 30). When necessary, mechanical
lithotripsy was performed. The therapeutic outcomes and complications were
reviewed and compared between two groups.
OP017 SMART ATLAS FOR SUPPORTING THE INTERPRETATION OF RESULTS: There were no differences between two groups with regard to age,
PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY (PCLE) OF stone size, number of stones and mean procedure time. Complete stone removal
BILIARY STRICTURES: FIRST CLASSIFICATION RESULTS OF A was achieved in all patients, but group B had higher using rate of mechanical
COMPUTER-AIDED DIAGNOSIS SOFTWARE BASED ON IMAGE lithotripsy for complete removal of the large bile duct stones, compared to group
RECOGNITION A (16.9% vs. 36.7%, P .037). There were no differences in procedure-related
M. Kohandani Tafreshi1,*, M. Giovannini2, V. Joshi3, C. Lightdale4, complications between two groups: pancreatitis(1.7% vs 0%, P .663),
A. Meining5, N. Ayache1, B. Andre6 Hyperamylasemia (5.1% vs 6.7%, P .550) and bleeding (1.7% vs 13.3%, P
1
INRIA, Sophia Antipolis, 2Institut Paoli Calmettes, Marseille, France, 3Ochsner 0.042).
Clinic Foundation, New Orleans, 4Columbia University Medical Center, New York, CONCLUSION: EPLBD showed results similar to those with additional full
United States, 5Klinikum rechts der Isar, Munchen, Germany, 6Mauna Kea EST for removing recurrent large stone. But additional full EST group had
Technologies, Paris, France more bleeding and increasing the need for lithotripsy, compared with EPLBD
Contact E-mail Address: marzieh.kohandani-tafreshi@inria.fr group.
Disclosure of Interest: None declared
INTRODUCTION: pCLE enables microscopic imaging of biliary strictures,
in vivo and in real time, during an ERCP procedure. Results of a multicentric
study (Meining et al., GIE 2011) have shown that pCLE allows endoscopists to OP019 IMPACT OF PCLE ON THE MANAGEMENT OF PATIENTS
differentiate benign from malignant strictures in real time with high sensitivity WITH INDETERMINATE BILIARY STRICTURE: RESULTS OF A
and NPV. A computer-aided diagnosis software called Smart Atlas has been LARGE MULTICENTRIC STUDY
developed to assist endoscopists with the interpretation of pCLE sequences. M. Giovannini1,*, A. slivka2, G. costamagna3, M. Kahaleh4, P. jamidar5, I. Gan6,
This study aims at evaluating the performance of this software for the differen- P. Cesaro7
tiation of benign and malignant strictures. 1
GI, Institu Paoli Calmettes, Marseille, France, 2UPMC, Pittsburgh, United
AIMS & METHODS: Several high quality pCLE sequences were retrospectively States, 3Gemelli, Rome, Italy, 4GI, Cornell, New York, 5Yale, New Haven,
collected from pCLE procedures performed in multiple clinical centers. These 6
VMMC, Seattle, United States, 7Fondazione Poliambulanza, Brescia, Italy
sequences, along with their annotated final diagnosis, were used to train a clas- Contact E-mail Address: giovaninim@wanadoo.fr
sification software that uses a content-based image retrieval algorithm to predict
the diagnosis of a query video based on the diagnoses of the most visually similar INTRODUCTION: Diagnosis of indeterminate biliary strictures remains a clin-
atlas videos. For all cases, final diagnosis was based on histology, positive tissue ical problem largely due to a low sensitivity of ERCP with tissue sampling
sampling, or one year follow-up. All evaluations were performed using leave-one- (550%). It has been previously shown that the use of probe-based confocal
patient-out cross-validation to avoid bias. To evaluate binary classification, a laser endomicroscopy during ERCP for indeterminate biliary strictures, detects
receiver operating curve was generated, allowing optimization of the trade-of more malignant lesions, doubles sensitivity compared to that of standard tissue
between false positives and negatives. sampling (98% vs. 45%).
RESULTS: Among the 60 pCLE sequences collected from 30 patients, 14 were This study presents the final results of an international multicenter trial (FOCUS,
representative of healthy bile duct, 10 of inflammatory strictures and 36 of NCT01392274) aiming at evaluating the impact of optical biopsy in patients with
malignant strictures. The resulting receiver operating curve shows two points indeterminate biliary stricture using criteria for normal, inflammatory and malig-
of interest: the first (reps. second) point has a high sensitivity of 88.9% (reps. nant strictures.
high specificity of 91.7%), an acceptable specificity of 70.8% (reps. acceptable AIMS & METHODS: Patients were enrolled at 6 international centers (2
sensitivity of 69.4%), an accuracy of 81.7% (resp. 78.3%), a PPV of 82.1% (resp. European, 4 US) from April 2012 to September 2013 and underwent pCLE
92.6%) and a NPV of 81.0% (resp. 66.7%). In comparison, Meining et al. during standard ERCP. For each patient, the investigator was asked to provide
reported that, for in vivo pCLE diagnosis of malignant stricture, endoscopists a diagnosis and a patient management recommendation based on clinical data
achieve overall sensitivity, specificity, accuracy, PPV and NPV of 98%, 67%, and ERCP findings before and after pCLE and again after tissue results returned.
81%, 71% and 97%, respectively. Malignancy was confirmed by positive tissue sampling at ERCP or surgery or by
CONCLUSION: These first results demonstrate that benign and malignant stric- a deteriorating clinical course with consistent radiographs. Benign disease man-
tures can be automatically discriminated by the Smart Atlas software using only dated negative histology at surgery or at least a 6 month follow period for a
the image content of pCLE sequences of high quality, with an accuracy compar- benign course after negative ERCP tissue sampling.
able to that achieved in real-time by endoscopists. The software is also able to RESULTS: 107 patients presenting with an indeterminate stricture where
achieve high specificity and PPV to help reduce false positives caused by inflam- enrolled (68 benign, 39 malignant).
matory strictures. Future work will focus on improving the software to handle Presumptive diagnosis based on clinical history and ERCP alone resulted in a
pCLE sequences of various quality. The resulting case-based reasoning software sensitivity of 84.6% and a specificity of 74.3%. The addition of pCLE increased
could be used as an educational tool to train non-expert endoscopists, but also as specificity up to 88.3% whereas the specificity declined to 89.7%. Finally, The
a second- reader tool to assist any endoscopist in real-time diagnosis of biliary addition of tissue sampling resulted in a sensitivity of 89.7% and a specificity of
strictures using pCLE. 87.2%. Investigators would have immediately proceed with patient management
Disclosure of Interest: None declared in 24 cases based on clinical history and ERCP, and in 33 cases based on clinical
history, ERCP and pCLE. Out of the 33 patients, pCLE would have had a
positive impact on 37% of them, a negative impact on 6% of them and would
have been in accordance with the actual patient management in 57% of the
patients.
CONCLUSION: pCLE is a safe and sensitive minimally invasive method for
evaluating patients with indeterminate biliary stricture Our observations further
suggest that the results of pCLE may have a favorable impact on patient manage-
ment. In centers in which pCLE expertise is available, our results suggest a more
rationalized approach to the diagnosis and management of biliary tumors.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A7
OP020 ESWL FOR LARGE PANCREATIC CALCULI. A DECADES OP022 THE PHENOMENON OF BONE MARROW DERIVED STEM
EXPERIENCE CELLS MOBILIZATION IN PANCREATIC DISEASES IS PRESENT
M. Tandan1,*, D. N. REDDY2 ONLY IN CANCER PATIENTS
1
GASTROENTEROLOGY, ASIAN INSTITUTE OF K. Dabkowski1,*, W. Blogowski1, A. Labedz Maslowska2, E. Zuba-Surma2,
GASTROENTEROLOGY, 2GASTROENTEROLOGY, ASIAN INSTITUTE M. Ratajczak3,4, T. Starzynska5
1
OF GASTROENTROLOGY, HYDERABAD, India Department of Gastroenterology, Pomeranian Medical University, Szczecin,
2
Contact E-mail Address: mantan_05@rediffmail.com Department of Cell Biology, Jagiellonian University, Krakow, 3Department of
Physiology, Pomeranian Medical Univeristy, Szczecin, Poland, 4Stem Cell Biology
INTRODUCTION: ESWL is established as the standard of care for management Institute, James Graham Brown Cancer Center, University of Louisville, Louisville,
of pancreatic ductal calculi larger than 5mm in size. We share a single tertiary KY, United States, 5Department of Gastroenterology, Pomeranian Medical
care centre experience of 10 years using this technique. Univeristy, Szczecin, Poland
AIMS & METHODS: This is a retrospective analysis of prospectively collected Contact E-mail Address: dabkowskikrzysztof@wp.pl
data at the Asian Institute of Gastroenterology Hyderabad India from February
2004 to February 2014. All patients having pain as the dominant symptom, with INTRODUCTION: Various studies indicate potential involvement of various
main pancreatic ductal calculi not amenable to standard endoscopic extraction, populations of bone marrow derived stem cells (BMDSCs) into process of
were subjected to lithotripsy using a 3rd generation electro magnetic lithotripter. tissue regeneration and tumor development. Our team demonstrated recently
Fragmentation was considered successful when the calculi were broken down to that in patients with pancreatic cancer intensified peripheral trafficking of
53mm in size. Upto 5000 shocks were delivered per session till this result was selected populations of BMSCs occurres (J Cell Mol Med 2013: 17:792-9).
achieved. ERCP was done within 24 - 48 hours after successful fragmentation There is no data on this phenomenon in benign pancreatic disorders.
and the main pancreatic duct was cleared following a sphincterotomy. Stents AIMS & METHODS: The purpose of the study was to comprehensively analyze
were placed as and when required. systemic trafficking of various populations of BMSCs: mesenchymal, hemato-
RESULTS: A total of 2779 patients underwent ESWL during this period. A poietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), as
majority (69%) were under the age of 40 years and did not consume alcohol. well as, of recently discovered population of very small embryonic/epiblast-like
Males accounted for 64% of patients. Single stones were seen in 24%, whereas in SCs (VSELs) in patients chronic and acute pancreatitis with comparison to pan-
the rest they were multiple. The head was the commonest location of the calculi creatic cancer patients and controls. The circulating CD133/Lin-/CD45-/
(59%). Sixty eight percent of patients needed 3 sessions or less for fragmentation. CD34 cells enriched for HSCs, CD105/STRO-1/CD45- cells enriched for
Endoscopic sphincterotomy was done in 69% of patients. Complete clearance MSCs, CD34/KDR/CD31/CD45- cells enriched for EPCs, and small
was achieved in 79%, partial in 14% while in the rest it was unsuccessful. CXCR4CD34CD133 subsets of Lin-CD45- cells that correspond to
Complications were minimum and not life threatening. From our earlier experi- VSELs were enumerated and sorted from blood samples derived from 16 patients
ence short term pain relief was seen in 84% and long term relief (upto 8 years) in with acute pancreatitis, 13 with chronic pancreatitis, 30 cancer patients and 19
60% of patients. There war significant improvement in quality of life. healthy controls.
CONCLUSION: ESWL should be offered as first line therapy in properly RESULTS: We noticed significant decrease of a number of circulating CD45(-
selected patients with large main pancreatic duct calculi. )STRO-1()CD105() (P0.03); CD45(-)STRO-1()CD105(-) (P0.02) LIN(-
Disclosure of Interest: None declared )CD45()CD133() (P0.04), and LIN(-)CD45(-)CD133() (P50.04) in
patients with acute pancreatitis and decrease of number of circulating LIN(-
)CD45()CD133() (P0.04); LIN(-)CD45(-)CD133() (P50.04); LIN(-
MONDAY, OCTOBER 20, 2014 11:0012:30 )CD45()CD34 () (P50.04) in patients with chronic pancreatitis. The
CELLULAR CROSSTALK IN PANCREATIC CANCER HALL O_____________________ number of circulating CD45(-)STRO-1()CD105(-)(p0,02) cells was signifi-
cantly higher in patients with chronic pancreatitis than in patients with acute
OP021 PARASYMPATHOMIMETIC AGENTS LIMIT PANCREATIC pancreatitis.
CANCER GROWTH BY SUPPRESSION OF THE P44/42 MAPK CONCLUSION: In contrast to heart infarction, brain stroke, skin burns and
SIGNALING PATHWAY pancreatic cancer, there is no significant mobilization of the BMDSCs to the
P.L. Pfitzinger1,*, I.E. Demir1, E. Tieftrunk1, K. Wang1, H. Friess1, peripherial blood in patients with acute and chronic pancreatitis. Interestingly,
G.O. Ceyhan1 even significant decrease of the number of circulating cells was noted. The mobi-
1
Surgery, Klinikum Rechts der Isar, Munich, Germany lization of BMDSCs to the peripherial blood, in pancreatic disorders, seems to be
Contact E-mail Address: paulo.pfitzinger@online.de connected only with pancreatic cancer.
Acknowledgment:Study financed from Ministry of Science and Higher
INTRODUCTION: The vagus nerve and parasympathetic nervous system play a Education Grant(402423038)
major role in the regulation of pancreatic physiology and also feature a suppres- REFERENCES
sive effect on acute and chronic inflammation. It is therefore conceivable that the 1. Paczkowska E, Kucia M, Koziarska D, et al. Clinical evidence that very small
parasympathetic nervous system may also play a role in pancreatic embryonic-like stem cells are mobilized into peripheral blood in patients after
carcinogenesis. stroke. Stroke 2009; 40: 1237-1244.
AIMS & METHODS: The aim of this study was to investigate the potential 2. Starzynska T, Dabkowski K, Blogowski W, et al. An intensified systemic
effect of the parasympathetic nervous system on proliferation and invasion of trafficking of bone marrow-derived stem/progenitor cells in patients with pan-
pancreatic cancer (PCa) and enlighten the linked intracellular signalling path- creatic cancer. J Cell Mol Med 2013; 17: 792-799.
ways in vitro and in vivo. Therefore, human PCa cell lines were exposed in vitro to 3. Wojakowski W, Landmesser U, Bachowski R, et al. Mobilization of stem and
direct and indirect parasympathomimetic agents (Carbachol, Physiostigmine and progenitor cells in cardiovascular diseases. Leukemia 2012; 26: 23-33.
Pyridostigmine) and their proliferation was quantified via the MTT proliferation Disclosure of Interest: None declared
assay, their invasiveness via the matrigel invasion assay, and the extent of phos-
phorylation of p44/42 mitogen-activated protein kinase (MAPK) was determined
by immunoblotting. In an in vivo xenograft model, human PCa cells were injected OP023 INCREASING THE INFLAMMATORY COMPETENCE OF
subcutaneously into Crl:NMRI-Foxn1nu nude mice and tumor area and metas- MACROPHAGES WITH IL-6 OR WITH COMBINATION OF IL-4
tasis were compared between treated and untreated groups. AND LPS RESTRAIN THE INVASION OF PANCREATIC CANCER
RESULTS: The MTT proliferation assay showed significant dose dependent CELLS
suppression of PCa cell proliferation after treatment with both direct and indirect A. Koski1,*, H. Mustonen1, S. Vainionpaa1, Z. Shen2, E. Kemppainen1,
parasympathomimetic agents. The matrigel invasion assay experiments revealed H. Seppanen1, P. Puolakkainen1
a dose dependent inhibition of PCa cell invasiveness. These results were asso- 1
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland,
ciated with a lower intracellular phosphorylation of p44/42 MAPK and corre- 2
Department of Gastroenterological Surgery, Peking University Peoples Hospital,
sponded with the results obtained in the in vivo experiments, in which both tumor Beijing, China
size and local invasiveness were inhibited subsequent to prophylactic and ther- Contact E-mail Address: aino.koski@helsinki.fi
apeutic treatment.
CONCLUSION: The systemic administration of activators of the parasympa- INTRODUCTION: Inflammation plays a critical role in the development and
thetic nervous system restrains PCa proliferation and invasiveness via suppres- progression of cancer; local inflammation in chronic pancreatitis multiplies the
sing the intracellular phosphorylation of the p44/42 MAPK signalling pathway, risk of pancreatic cancer. Recent studies suggest that pro-inflammatory type M1
implicating a potential novel understanding of neuro-cancer interactions and macrophages work against tumour progression and anti-inflammatory M2
treatment of human malignancies. macrophages enhance tumour progression.
Disclosure of Interest: None declared AIMS & METHODS: The aim of this study was to examine the interaction of
pro-inflammatory M1 and anti-inflammatory M2 macrophages with pancreatic
cancer cells.
We studied the migration rate of fluorescein stained pancreatic cancer cells
(MiaPaCa-2 and HPAF-II) in Matrigel cultured alone or with GM-CSF differ-
entiated M1 macrophages or with M-CSF differentiated M2 macrophages. We
studied the changes the pancreatic cancer cells induce in the differently stimulated
macrophages cytokine expression with cytokine array. Cytokine array results are
given as percentage between negative and positive control recorded on each
array.
RESULTS: GM-CSF differentiated M1 macrophages increased the migration
rate of primary pancreatic adenocarcinoma cell line (MiaPaCa) from 11.5m/h
0.2 to 24.7m/h 0.3 (p50.001) and metastatic cell line (HPAF) from 4.0m/h
0.2 to 19.1m/h 0.3 (p50.001). M-CSF differentiated macrophages M2
increased the invasion rate of MiaPaCa cells from 8.4m/h 0.1 to 14.8m/h
A8 United European Gastroenterology Journal 2(5S)
0.1 and of HPAF from 4.5m/h 0.2 to 20.8m/h 0.3 (p50.001). When the AIMS & METHODS: To assess whether NFATc1 controls transcription of
cells were stimulated with IL6 or IL4LPS, the macrophages increasing effect EMT genes and stemness in PDAC, particularly upon p53 inactivation. We
on the migration rate was completely reversed in the case of primary pancreatic generated mouse strains with combined pancreas-specific expression of
cancer cell line and partly reversed in the case of metastatic cancer cell line. When KrasG12D, p53R172H or p53fl/wt and NFATc using Cre-Lox technology. These
stimulated with IL6 (GM-CSF differentiated M1 cells) the migration rate of mice showed a highly aggressive tumor growth (median survival of 550 or 61
MiaPaCa cells was 11.7m/h 0.2 and of HPAF cells 13.8m/h 0.2. The days). Mouse primary tumour cells were used to identify NFATc1 targets by gene
migration rate of MiaPaCa cells co-cultured with IL4LPS stimulated macro- expression profiling and pathway analyses (ChIP seq, miRNA analyses and
phages (M-CSF differentiated M2) was 8.5m/h 0.4 and with HPAF 8.3m/h GSEA). NFATc1 mediated EMT and stemness were assessed in human and
0.4. murine pancreatic cancer models using migration and spheroid assay as well as
GM-CSF differentiated M1 macrophages co-cultured with MiaPaCa cells xenograft mouse models.
released less inflammatory cytokines than macrophages cultured alone (TNF RESULTS: Here, we reveal the inflammation-induced transcription factor
from 0.64% to 0.03% 0.30, p0.009; IL23 from 1.14 to 0.63% 0.15, p0.009; NFATc1 as a central regulator of pancreatic cancer cell plasticity. We show
INF
from 1.30 to 0.54% 0.26, p0.038). Adding IL6 to GM-CSF differen- that NFATc1 drives EMT programming and maintains cancer cells in a stem
tiated cell culture with macrophages and MiaPaCa cells increases the expression cell-like state through Sox2-dependent transcription. Intriguingly, NFATc1-Sox2
of inflammatory cytokines IL23 (from 0.65 to 1.22% 0.12 p0.013), TNF complex mediated PDAC dedifferentiation is opposed by antithetical p53-
(from 0.58 to 1.34% 0.10, p0.007). M-CSF differentiated M2 macrophages miR200c signalling. Inactivation of the tumour suppressor pathway is essential
did not secrete inflammatory cytokines but adding IL4LPS to the cell culture for tumour dissemination and dedifferentiation both in genetically engineered
with macrophages and MiaPaCa cells increased the expression of IL6 (from 0.52 mouse models and human PDAC.
to 5.03% 2.21, p50.001), CCL5 (from 0.58 to 23.27% 7.65, p50.001), TNF CONCLUSION: Based on these findings, we propose a hierarchical signalling
(from 0.84 to 5.81% 0.52, p50.001) but also anti-inflammatory IL10 expres- network regulating PDAC cell plasticity and suggest that molecular decisions
sion increased (from 0.31 to 1.08% 0.10, p0.007). between epithelial cell preservation and conversion into a dedifferentiated
CONCLUSION: Our study shows that pancreatic cancer cells have an ability to cancer stem cell-like phenotype depends on opposing levels of p53 and
reduce the inflammatory cytokine expression of GM-CSF differentiated pro- NFATc1 activities.
inflammatory M1 macrophages. This explains why both GM-CSF (M1) and REFERENCES
M-CSF (anti-inflamatory M2) differentiated macrophages promoted the inva- Rhim AD et al. EMT and dissemination precede pancreatic tumor formation.
sion of pancreatic cancer cells. IL6 and IL4LPS activated the inflammatory Cell 2012; 148: 349361.
cytokine expression in macrophages and this might contribute to the reversion of Hezel AF, Kimmelman AC, Stanger BZ, et al. Genetics and biology of pancreatic
the macrophage induced increase of cancer cell migration rate. ductal adenocarcinoma. Gene Dev 2006; 20: 12181249.
Disclosure of Interest: None declared Rustgi AK. The molecular pathogenesis of pancreatic cancer: clarifying a com-
plex circuitry. Gene Dev 2006; 20: 30493053.
Disclosure of Interest: None declared
OP024 LOSS OF ATM ACCELERATES PANCREATIC CANCER
FORMATION AND EPITHELIAL-MESENCHYMAL-TRANSITION
VIA AN AUTOCRINE BMP4-SIGNALLING LOOP OP026 NEURAL REMODELING IN PANCREATIC NEUROPATHY IS
A. Kleger1,*, R. Russell1, Q. Lin2, J. Lennerz3, M. Wagner1, T. Seufferlein4 CHARACTERIZED BY NEUROTROPHIN-3-MEDIATED INCREASE
1
Department of Internal Medicine 1, Ulm University Hospital, Ulm, 2Department IN THE PANCREATIC NOCICEPTIVE INNERVATION,
of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University, DEMYELINATION AND SELECTIVE GLIAL ACTIVATION
Aachen, 3Institute of Pathology, Ulm, Germany, 4Ulm University Hospital, Ulm, I.E. Demir1,*, D. Carty1, K. Wang1, C. Waldbaur1, L. Krauss1, E. Tieftrunk1,
Germany H. Friess1, G.O. Ceyhan1
1
Department of Surgery, Klinikum rechts der Isar, TU Munchen, Munchen,
INTRODUCTION: Onset and progression of pancreatic ductal adenocarcinoma Germany
(PDAC) is associated with accumulation of particular oncogenic mutations. Contact E-mail Address: ekin.demir@tum.de
Recent genome-wide exome sequencing studies have identified ATM mutations
in independent PDAC cohorts but to date, the role of ATM in PDAC tumour INTRODUCTION: Neural remodelling in pancreatic cancer (PDAC) and
biology is unclear. chronic pancreatitis (CP) is characterized by reduced sympathetic pancreas inner-
AIMS & METHODS: We use a conditional PDAC mouse modell and ex vivo vation among patients with severe pain. However, it remains unknown which
acinar cultures to delineate the role of ATM during mouse pancreatic types of nerve fibers replace sympathetic fibers in panful PDAC and in CP.
carcinogenesis. AIMS & METHODS: In the current study, we aimed to elucidate wheter the
RESULTS: Here we report that conditional deletion of ATM in a mouse model sympathetic innervation in PDAC and CP is replaced by increased nociceptive
of PDAC enhanced pancreatic cancer formation via enhanced ductal reprogram- innervation and glial activation, and which molecular agents mediate this switch.
ming. ATM-targeted mice had significantly shortened survival compared to con- For this purpose, normal human pancreas (NP, n16), CP (n 26) and PCa
trols and interestingly, loss of a single ATM allele was sufficient to induce this (n25) tissues were quantitatively analyzed for the neuro-immunoreactivity of a)
phenotype. Depletion of ATM gave rise to a greater number of proliferative nociceptive fiber markers substance-P (SP) and calcitonin-gene-related-peptide
acinar-to-ductal metaplastic (ADM) lesions and pancreatic intraepithelial neo- (CGRP), b) myelination markers neurofilament-H (NFH) and peripheral-
plasias (PanIN), coupled with a pronounced fibrotic reaction. These precursor myelin-protein-22 (PMP22), c) glial activation markers p75NTR and glial-fibril-
lesions in ATM-deficient mice were broadly associated with altered epithelial-to- lary-acidic-protein (GFAP) and correlated to pain, neural invasion (NI) and
mesenchymal transition (EMT) and a gain of tumor initiating cells. Finally, pancreatic neuritis. Nociceptive neurite density of dorsal-root-ganglia-(DRG)-
we are able to define a Bmp4-signalling loop originating within the acinar com- neurons that were cultivated in human NP, CP or PDAC tissue extracts was
partment, which initiates ductal programming in an autocrine manner and analyzed in the presence of neutralizing antibodies against nerve-growth-factor
subsequent EMT. Notably, our mouse model recapitulates many features of (NGF), neurotrophin-3 (NT-3) or brain-derived-neurotrophic-factor (BDNF).
more aggressive human PDAC subtypes, namely mesenchymally differentiated RESULTS: SP- and CGRP-containing nerve fibers were prominently increased
PDAC. in CP independently of the pain status. Accordingly, the neuro-immunoreactivity
CONCLUSION: We show that ATM also acts as a tumor suppressor molecule of NFH and PMP22 was remarkably decreased in CP and PCa. NI and pan-
in human PDAC, where low expression of ATM serves as an independent pre- creatic neuritis were more pronounced around nerves with decreasing SP- and
dictor for EMT and poor prognosis. Taken together, our data suggests an inti- CGRP-content, increasing myelination and enhanced glial activation.
mate link between ATM expression and pancreatic cancer progression in mice Cultivation of DRG neurons in CP extracts induced the sprouting of SP- and
and men. CGRP-containing neurites, which was reversed upon blockade of NT-3 within
Disclosure of Interest: None declared CP extracts.
CONCLUSION: Neural remodeling in CP and PDAC involves pain-indepen-
dent, NT-3-mediated upregulation of nociceptive innervation, loss of myelina-
OP025 ANTITHETICAL NFATC1-SOX2 AND P53-MIR-200 SIGNALLING tion, and glial activation around nerves with NI and pancreatic neuritis. These
NETWORKS GOVERN PANCREATIC CANCER CELL PLASTICITY alterations show that the sympathetic innervation in CP is replaced by pain-
AND TUMOUR PROGRESSION transmitting, i.e. nociceptive innervation. This switch to increased nociception,
S. Singh1,2,*, N.-M. Chen1, E. Hessmann1, A. Koenig1, I. Esposito3, M. Hebrok4, myelination and glial activity may be the determinants of the pathologic pain
V. Ellenrieder5 response in PDAC and CP.
1
Gastroenterology, Philipps-Unoversity of Marburg, Marburg, Germany, 2Barrow Disclosure of Interest: None declared
Brain Tumor Research Center, The Barrow Neurological Institute, Phoenix, United
States, 3Gastroenterology, 5Institute of Pathology, Helmholtz Zentrum, Munich,
Germany, 4Diabetes Center, USCF, California, United States, 5Gastroenterology,
Georg-August-Universitat, Gottingen, Germany
Contact E-mail Address: shivkishor@gmail.com
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) cells undergo
epithelialmesenchymal transdifferentiation (EMT) in adaption to environmen-
tal clues, including inflammation, a process that combines tumour cell dediffer-
entiation with dissemination and acquisition of stemness features. However, the
mechanisms coupling inflammation-induced signalling pathways with EMT and
stemness remain largely unknown. We have shown that activation of the
NFATc1 transcription factor promotes pancreatic cancer development and
metastasis through its ability to integrate extrinsic stimuli into coordinated
gene regulation.
United European Gastroenterology Journal 2(5S) A9
MONDAY, OCTOBER 20, 2014 11:0012:30 NETs showed immunoreactivity for gastrin, somatostatin, and serotonin in 75.7
CLINICO-PATHOLOGICAL FEATURES OF GI CANCER LOUNGE 5_____________________ %, 35.1 %, and 37.8 % of the cases, respectively, all of which were not significantly
associated with metastasis. Two of patients with immunoreactivity for gastrin
OP027 INTERVAL GASTRIC CANCERS: PRECISE REVIEW OF PAST showed Zollinger-Ellison syndrome. On univariate analysis, risk factors for metas-
ENDOSCOPIC IMAGES, CLINICOPATHOLOGICAL FEATURES tasis were lymphatic invasion (OR 31.0; 95% CI: 3.37-282; P 0.002), venous
AND MICROSATELLITE INSTABILITY invasion (OR 14.5; 95% CI: 1.98-106; P 0.009), and G2 (OR 10.0; 95% CI:
K. Yamashita1,*, Y. Arimura1, K. Onodera1, H. Isshiki1, K. Murakami1, 1.36-73.3; P 0.024). Five-year overall survival was 78.9 %, and 5-year disease-
M. Saito1, Y. Shinomura1, T. Endo2 specific survival was 94.7 %. In one patient with 2 mm NAD-NET which had
1
Department of Gastroenterology, SAPPORO MEDICAL UNIVERSITY, vascular invasion and classified as G2 (Ki-67 index; 20 %), lymph node and liver
2
Department of Gastroenterology, SAPPORO SHIRAKABA-DAI HOSPITAL, metastases were confirmed 18 months after ER, resulting in death.
Sapporo, Japan CONCLUSION: To our knowledge, this is the first study to demonstrate that
lymphatic invasion, venous invasion, and WHO grading G2 were risk factors for
INTRODUCTION: There are few studies about interval gastric cancers, which metastasis in NAD-NET less than 20 mm. These pathological findings could
are diagnosed after preceding negative upper endoscopy. Microsatellite instabil- provide useful information in considering additional treatment after ER.
ity (MSI), frequently observed in interval colorectal cancers, might be also a Disclosure of Interest: None declared
genetic feature of interval gastric cancers.
AIMS & METHODS: The aims of this study were to speculate natural history of
early gastric cancer from precise review of past endoscopic images of interval gastric OP029 DUODENAL POLYPOSIS OUTCOMES IN MYH-ASSOCIATED
cancers and to elucidate clinicopathological features of internal gastric cancers. The POLYPOSIS
study cohort consisted of 260 gastric cancer patients diagnosed at Sapporo Medical S.-J. Walton1,*, S. Clark1, A. Latchford1
University Hospital. Patients who had experience of upper endoscopy within the 1
The Polyposis Registry, St Marks Hospital, London, United Kingdom
past 10 years were stratified according to interval between past and current endo- Contact E-mail Address: s.j.walton@hotmail.co.uk
scopy. Images of past endoscopy performed at our hospital were scrutinized by two
endoscopy specialists independently. Five microsatellite markers were used for MSI INTRODUCTION: MUTYH-associated polyposis (MAP) is an autosomal reces-
analysis and instability of two or more markers was defined as MSI-H. sive adenomatous condition. MAP (like familial adenomatous polyposis (FAP)),
RESULTS: Of 260 gastric cancer patients, 60 (23%) had experience of upper predisposes to colorectal and duodenal adenoma formation. However, duodenal
endoscopy within 10 years prior to the cancer diagnosis; 27 patients with endo- polyposis is less frequently seen in MAP than in FAP, occurring in up to 25% and
scopy interval of 24 months or less (short interval), 19 patients with 25 to 48 90%, respectively. The rationale for adopting the same upper gastrointestinal
months interval (intermediate) and 14 patients with 49 to 120 months interval (UGI) surveillance protocol for both polyposis syndromes is questionable.
(long interval). Rates of advanced gastric cancers (T2 or more) to all cancers were AIMS & METHODS: The aim of this study was to assess the incidence, extent
19%, 37% and 57% for the short, the intermediate and the long interval group, and progression of duodenal adenomas in an MAP population over time and
respectively. For patients with over 120 months interval or without experience of evaluate the suitability of the current FAP UGI surveillance protocol in MAP.
endoscopy, rate of advanced gastric cancer was 51%. All genetically confirmed MAP cases followed-up at a single institution were
High-quality images of past endoscopy performed at our hospital were available identified from a prospectively maintained registry database. Case notes, endo-
for precise review in 32 patients. Rates of advanced gastric cancers of these 32 scopy and histology reports were analysed. The primary outcome measure was
patients were 0%, 33% and 43% for the short, the intermediate and the long the occurrence of duodenal adenomas. Secondary outcomes included age of
interval group, respectively. At past endoscopy, existence of early (T1) gastric adenoma onset, time interval to advancing Spigelman stage, MAP mutation,
cancers were strongly suspected in 17 patients while there were no lesions at current polyp morphology and distribution.
cancer sites in 15 patients. Of 17 early gastric cancers observed at past endoscopy, RESULTS: 34 MAP patients were identified, of which 13 (38%) developed
11 were unchanged for an average of 20.4 months (range 12-40) while 6 had grown duodenal adenomas, with a median follow-up of 7.5 years (range 0-16 years).
in 43.0 months (20-64). Of 6 growing gastric cancers, 3 had grown but remained as Median age at first (baseline) OGD in the adenoma group was 50 years (range
T1 for 36.7 months while another 3 had become unresectable in 49.7 months. 38-66) with a median age of adenoma development of 52 years (range 39-66). In
Interval gastric cancers had no clinicopathological features such as age, site, 92% (12/13 cases) only 1 to 4 polyps were found. 8/13 patients had a polyp
macroscopic and histological type. Seven percent (3/41) of interval gastric cancers detected at their baseline OGD (median age 51 years), with the remaining 5
while 11% (12/106) of all other gastric cancers were MSI-H (P0.35). All MSI-H (with normal baseline OGDs) developing polyps over an average of 12 years
interval gastric cancers were intramucosal (T1a) and Laurens intestinal type. subsequently. All polyps involved D2, whilst most spared D1 and the ampulla.
CONCLUSION: Most early gastric cancers are unchanged for 2 years while 8/13 cases were Spigelman stage 1 at first adenoma detection, and in only 1 case
some will become advanced or unresectable in 3 to 5 years. Endoscopy with 2- did progression of Spigelman stage occur between OGDs (from stage 1 to 2, over
year interval might be reasonable for gastric cancer surveillance, if quality of 5 years, due to an increase in polyp size only). Stage 3 disease was seen in only 2
endoscopy is warranted. MSI was not frequent in interval gastric cancers. cases, both over 60 years and at their first OGD.
Disclosure of Interest: None declared CONCLUSION: Duodenal polyposis is seen much less frequently in MAP com-
pared to FAP patients and this study supports that finding. Adenomas had a late
age of onset, although many had their 1st OGD at a late stage due to the timing
OP028 MANAGEMENTS AND CLINICAL OUTCOMES OF NON- of their MAP diagnosis. Duodenal polyps appear to progress slowly in MAP and
AMPULLARY NEUROENDOCRINE TUMORS OF THE it may be inappropriate to determine surveillance interval using the Spigelman
DUODENUM: A RETROSPECTIVE, MULTICENTER STUDY IN staging system given the lack of polyp multiplicity and histological progression.
JAPAN A new protocol for MAP duodenal polyposis surveillance is therefore proposed.
W. Hatta1,*, T. Koike1, K. Iijima1, G. Kusaka1, Y. Kondo1, N. Ara1, K. Uno1, Disclosure of Interest: None declared
N. Asano1, A. Imatani1, T. Shimosegawa1
1
Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Contact E-mail Address: waku-style@festa.ocn.ne.jp OP030 POST COLONOSCOPY COLORECTAL CANCER (PCCRC). HOW
SHOULD WE CALCULATE A RATE? IMPLICATIONS FOR QUALITY
INTRODUCTION: Duodenal neuroendocrine tumor (D-NET) is a rare tumor. PROGRAMS
According to the latest European Neuroendocrine Tumor Society, surgical resec- D.C. Sadowski1,*, Q., I. Ibrahim2
tion is recommended for ampullary D-NET, due to the anatomical location and 1
Division of Gastroenterology, Royal Alexandra Hospital, Edmonton,
different growth patterns from non-ampullary D-NET (NAD-NET). In contrast, 2
Epidemiology Coordinating and Research Centre (EPICORE), University of
endoscopic resection (ER) is recommended for small size (5 10 mm) NAD-NET, Alberta, Edmonton, Canada
and there is no standardized therapeutic approach for intermediate size (10 to
20mm) NAD-NET. However, it is reported that 13.2 % of small D-NET had INTRODUCTION: A significant proportion of detected colorectal cancers are
lymph node metastases. Furthermore, there are no reports on the criteria for found in individuals who have had a colonoscopy in the previous 36 months.
deciding the additional treatment after ER in NAD-NET. These malignancies can be due to missed cancer, or cancer arising from missed or
AIMS & METHODS: The aim of this study was to investigate the detailed char- incompletely removed polyps. The rate of post-colonoscopy colorectal cancer
acteristics of NAD-NET for detecting risk factors for metastasis by a multicenter, (PCCRC) has been proposed as a key quality indicator for colonoscopy. A quality
retrospective study. The patients with NAD-NETs diagnosed and treated between indicator should be clearly defined, reproducible over time and relevant to colonos-
1992 and 2012 at 7 institutions in Japan were enrolled. The patients with follow-up copists. Studies to date have calculated the rate of PCCRC as a percentage of
period of less than 24 months, except for NAD-NET-related death, were excluded
w n
detected colorectal cancers. This rate calculation is problematic for quality pro-
a
ithdr
from this study. As a result, a total of 39 patients with NAD-NETs were analyzed, grams in that the rate may fluctuate due to changes in the incidence of detected
comprising 29 men and 10 women, with a median follow-up of 46 months. The cancers quite apart from any real improvements in colonoscopy quality. We propose
clinical and pathological records were reviewed to investigate the therapeutic pro- that PCCRC rates be expressed relative to the number of screening colonoscopies.
W
cedure, tumor size, presence of lymph node and distant metastasis, and prognosis. AIMS & METHODS: The aim of our study was to examine the feasibility of
In addition, depth of invasion, presence of lymphatic or venous invasion, World reporting PCCRC rates relative to the number of screening colonoscopies as a
Health Organization (WHO) grading (Ki-67 index, mitotic count per 10 high denominator and to test whether meaningful comparisons can be made when
power microscopic fields), peptide products (gastrin, somatostatin, and serotonin) rates vary due to colonoscopy quality interventions. We used service log data to
were re-evaluated by one pathologist who was blind to the clinical information. To identify colonoscopies carried out during the last fiscal year in a regional color-
identify the risk factors for metastasis, we calculated odds ratio (OR) and 95 % ectal cancer-screening program (Edmonton, Canada). This program serves a
confidence interval (CI) of age (over 60 years), size (over 10 mm), location (bulbs), population of 817,000 and delivers colonoscopy in 8 separate endoscopy units
number of lesions (multiple), each peptide product, lymphatic invasion, venous in response to positive FIT tests, positive family history and previous history of
invasion, and WHO grading (G2, compared to G1) by univariate analysis. colonic neoplasms. A PCCRC was defined as the diagnosis of a colorectal cancer
RESULTS: Thirty patients were treated with ER, and 9 were treated surgically, in a patient who had undergone colonoscopy in the time period of 6-36 months
and all of the tumors were less than 20 mm. There were 6 lymph node metastases prior to diagnosis. We estimated the occurrence PCCRC from previous Canadian
(15.4 %) and 2 distant metastases (5.1 %). With regard to peptide products, NAD- studies that observed the rate of PCCRC to be approximately 8% of detected
A10 United European Gastroenterology Journal 2(5S)
cancers. From this data we normalized PCCRC as a rate relative to the number the percentage of fibrosis (5 25%, 5 50%, 5 75%, 100%). Measurements were
of screening colonoscopies performed. We then hypothesized a colonoscopy performed on all axial images including the tumor. MR-TRG evaluated on the
quality intervention that would reduce the rate of PCCRCs by 50%. We calcu- second examination (during therapy) was correlated to the pathological finding
lated PCCRC rates for the region, individual endoscopy unit and individual after surgery, defined as partial response or complete response.
physician to determine the granularity by which meaningful statistical compar- RESULTS: A complete pathologic response was observed only in patients (17)
isons could be made. Confidence intervals for proportions were constructed using with MR-TRG 4 (100% fibrosis) with a negative predictive value of 100%. In
RESULTS:
a w n
a Poisson distributions for rare events. lower MR-TRG groups (1, 2 and 3) a partial response was observed (20 patients).
CONCLUSION: MR-TRG 4 is a accurate predictor of complete response after
ithdr
CRT. When a lower MR-TRG is observed the persistence of disease should be
suspected. This method, applied during therapy, may reduce the time to surgery.
W
Estimated # # of ScreeningRate/1000 REFERENCES
of PCCRCsColonoscopies Colonoscopies95% CI Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative
chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351: 17311740.
Regional Screening Program 10 11,374 0.88 0.42-1.62 Valentini V, Aristei C, Glimelius B et al. Multidisciplinary Rectal Cancer
50% Reduction in PCCRC Rate5 11,374 0.44 0.14-1.03 Management: 2nd European Rectal Cancer Consensus Conference (EURECA-
CC2). Radiother Oncol 2009; 92: 148163.
Single Endoscopy Unit 2 3680 0.54 0.07-1.96 Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome fol-
Single Physician 0.4 460 0.87 0-3.56 lowing preoperative combined modality therapy and total mesorectal excision of
Polish Program (6-36 Months) 33 45,000 0.73 0.50-1.03 locally advanced rectal cancer. Ann Surg 2005; 241: 829836.
50% Reduction in PCCRC Rate17 45,000 0.37 0.22-0.60 Ruo L, Tickoo S, Klimstra DS, et al. Long-term prognostic significance of extent
of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg
Kaiser Permanente (10 year) 712 314,872 2.26 2.10-2.43 2002; 236: 7581.
50% Reduction in PCCRC Rate356 314,872 1.13 1.02-1.25 Rodel C, Martus P, Papadoupolos T, et al. Prognostic signif- icance of tumor
regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol
CONCLUSION: Expressing PCCRC as a rate relative to number of screening 2005; 23: 86888696.
colonoscopies is a feasible method to provide meaningful comparisons of colo- Disclosure of Interest: None declared
noscopy quality. However, since PCCRC is a relatively rare event relative to the
number of colonoscopies performed, meaningful comparisons can only be pro-
vided for programs of more than 300,00 of colonoscopies per year. MONDAY, OCTOBER 20, 2014 11:0012:30
Benchmarking of PCCRC across programs requires a standard definition and SMALL BOWEL IMAGING AND ENDOSCOPIC INTERVENTIONS LOUNGE
calculation method. 6_____________________
Disclosure of Interest: None declared
OP033 DIAGNOSTIC VALUE OF FECAL CALPROTECTIN TO DETECT
SMALL BOWEL PATHOLOGY IN PATIENTS WITH PREVIOUS
OP031 GENETIC VARIANTS ASSOCIATED WITH COLORECTAL NEGATIVE ENDOSCOPY
CANCER AND ADENOMA SUSCEPTIBILITY E. Burri1,2,*, N. Meuli2, C. Beglinger2
M. Andreu1,*, A. Abul 1, A. Castells2, L. Bujanda3, J.J. Lozano4, X. Bessa1, 1
Medical University Clinic, Cantonal Hospital Liestal, Liestal, 2Gastroenterology
C. Hernandez5, A.C. Alvarez-Urturi1, M. Pellise2, E. Hijona6, A. Buron5, and Hepatology, University Hospital Basel, Basel, Switzerland
F. Macia`5, J. Grau7, R. Guayta8, S. Castellvi2 Contact E-mail Address: emanuel.burri@ksbl.ch
1
Gastroenterology, Hospital del Mar, 2Gastroenterology, Hospital Clnic,
CIBERehd, IDIBAPS, Barcelona, 3Gastroenterology, Hospital Donostia/Instituto INTRODUCTION: The assessment of small bowel pathology with capsule endo-
Biodonostia, San Sebastian, 4Plataforma de Bioinformatica, CIBERehd, scopy is laborious and costly. Therefore, the appropriate selection of patients to
5
Epidemiology and Evaluation, Hospital del Mar, 6Gastroenterology, Hospital increase diagnostic yield is highly anticipated. Increased levels of fecal calprotec-
Donostia/Instituto Biodonostia, 7 Evaluation and prevention, Hospital Clnic, tin have been measured in NSAID enteropathy and Crohns disease of the small
8
Planning and Research Unit, Consell de Col.legis Farmace`utics de Catalunya, bowel.
Barcelona, Spain AIMS & METHODS: Our aim was to examine the diagnostic value of fecal
calprotectin to detect significant small bowel pathology. We performed a post-
INTRODUCTION: Thirty common, low-penetrant genetic variants have been hoc analysis of a prospective cohort of 70 consecutive patients who had received
consistently associated with colorectal cancer (CRC) risk, but only few studies capsule endoscopy (Pillcam, Given Imaging, Israel), after negative bidirectional
have explored the contribution of these variants in colorectal adenoma suscept- endoscopy. Calprotectin was measured in stool samples collected within 24 hours
ibility. Age over 50 is the only identified and implemented stratification variable before the investigation using an enzyme-linked immunosorbent assay
in population-based CRC screening programs. (Buhlmann Laboratories, Switzerland). The presence of mucosal breaks in the
AIMS & METHODS: We assessed whether genetic variants associated to ade- small bowel (erosion, ulcer, tumor) was the primary endpoint of the study. Final
noma susceptibility could improve selection of average-risk population for CRC. diagnoses were adjudicated blinded to calprotectin values.
We selected 1,326 patients with high-risk adenomas (HRA) and 1,252 controls RESULTS: Indications for capsule endoscopy were anemia (51.4%), hematochezia
were selected from population-based CRC screening programs at 3 hospitals (14.3%), suspected Crohns disease (14.3%), abdominal pain (10%), suspected
from Spain. We conducted a case-control association study analyzing 30 CRC malignant disease (8.6%) and unexplained diarrhea (1.4%). The prevalence of
susceptibility variants in order to investigate the contribution of these variants to mucosal breaks was 48.6% (n34) but 4 patients had significant lesions strictly
the development of HRA. In addition, we built an individualized risk prediction outside the small bowel and were not included in the analysis. Calprotectin testing
model in which common genetic variants were incorporated as risk factors. was more often positive (450g/g) in patients with mucosal findings (61.4% vs.
RESULTS: We found that 14 of the 30 SNPs analyzed showed a statistically 38.6%, P0.001) and mean calprotectin values were higher (meanstandard devia-
significant association for HRA. We also observed that the risk of developing tion, 305289g/g vs 148228g/g, P50.001). Receiver Operating Characteristics
HRA increased with increasing number of risk alleles, with a 2.3-fold increased analysis showed an area under the curve of 0.760 (95% confidence interval 0.639-
risk in individuals with 17 risk alleles. In the predictive model for HRA, ROC 0.857). At the optimal cut-off (63g/g), fecal calprotectin had 90.0% sensitivity and
curves demonstrated better discrimination ability for individuals at a younger 63.9% specificity to detect mucosal inflammation. This translated in a positive and
age, although with modest predictive performance. negative likelihood ratio of 2.49 and 0.16, respectively, and resulted in a high nega-
CONCLUSION: Our results provided strong evidence that most genetic variants tive predictive value (88.5%). The overall accuracy (true positive test results true
increase CRC risk by adenoma predisposition. The risk of developing HRA negative test results)/total population was 69.7%. In a subgroup analysis we
increased with multiple number of risk alleles, which may allow identifying a excluded patients with gross intestinal bleeding (N10) as this may increase fecal
subgroup of individuals at a higher risk. However, there are limitations of using concentrations of calprotectin in absence of mucosal inflammation. Fecal calpro-
genetic variants associated with HRA to assess the risk at the individual level. tectin performed slightly better in this subset of patients (area under the curve 0.787,
Disclosure of Interest: None declared overall accuracy 71.4%) but the positive and negative likelihood ratios remained
virtually unchanged (2.64 and 0.17, respectively).
CONCLUSION: Fecal calprotectin is a valid marker of intestinal inflammation
OP032 EVALUATION OF RECTAL CANCER RESPONSE TO THERAPY: in the small bowel and might be helpful to guide diagnostic investigations.
ROLE OF MAGNETIC RESONANCE TUMOR REGRESSION GRADE Disclosure of Interest: None declared
(MR-TRG) TO PREDICT PATHOLOGICAL COMPLETE RESPONSE
M. Rengo1,*, D. Caruso1, C.N. De Cecco1, D. Bellini1, A. Laghi1
1
Department of Radiological Sciences, Oncology and Pathology, SAPIENZA OP034 CONFOCAL LASER ENDOMICROSCOPY A NEW METHOD
University of Rome, rome, Italy FOR ENDOSCOPIC ASSESSMENT OF CROHNS DISEASE
Contact E-mail Address: marco.rengo@uniroma1.it J.G. Karstensen1,*, J. Brynskov1, L.B. Riis2, P. Klausen1, J. Hendel1,
A. Saftoiu1,3, P. Vimann1
INTRODUCTION: To determine if a pathological complete response to therapy 1
Gastro Unit, Division of Endoscopy, 2Department of Pathology, Copenhagen
in rectal cancer can be predicted by tumor regression grade evaluated by MR University Hospital Herlev, Herlev, Denmark, 3Research Center of
(MR-TRG). Gastroenterology and Hepatology, University of Medicine and Pharmacy, Craiova,
AIMS & METHODS: Thirty-seven patients, diagnosed with locally advanced Romania
rectal cancer were prospectively enrolled in the study. All patients underwent Contact E-mail Address: johngkarstensen@hotmail.com
MRI on a 3 Tesla before, during and after chemoradiotherapy (CRT). All
patients underwent total mesorectal excision (TME). MR-TRG was evaluated INTRODUCTION: Endoscopy is crucial to evaluate the extent and severity of
on T2-weighted fast spin-echo (FSE) multi-planar imaging. The MR-TRG was inflammation in patients with Crohns disease (CD), including the response to
determined by the fibrosis/tumor ratio and was divided into 4 grades based on treatment. Endoscopic remission is a predictor for extended surgery-free periods;
United European Gastroenterology Journal 2(5S) A11
however, approximately 50% of patients in deep remission on biological treat- OP036 CLINICAL USEFULNESS OF VIRTUAL ENTEROSCOPY FOR
ment relapse within the first year after treatment cessation. Recently, confocal CROHNS DISEASE
laser endomicroscopy (CLE) has enabled in vivo microscopic evaluation during T. Yoshikawa1,*, N. Suzuki1, N. Shirane1, T. Kurokami1, M. Shigetomo1,
endoscopy. H. Aoyama1, K. Enokida1, M. Kikuyama1
AIMS & METHODS: The aim of this study was to evaluate whether CLE can 1
Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
identify subtle lesions in CD patients, and thus delineate deep remission and Contact E-mail Address: t-yoshi@med.nagoya-u.ac.jp
contribute to better treatment algorithms. Patients with CD referred for ileoco-
lonoscopy were included in the study using the endoscope-based CLE system (EC INTRODUCTION: The technique of virtual colonoscopy can be used to explore
3830FK; Pentax, Tokyo, Japan). CLE images, macroscopic assessment (simple the colon as well as the small bowel. The clinical performance of Virtual
endoscopic score for Crohns disease - SES-CD), and histopathological features Enteroscopy (VE) was analyzed to evaluate the safety, feasibility, and the useful-
from biopsies obtained from the terminal ileum were registered. CLE findings in ness in Crohns disease.
terminal ileum were analysed assessing the images for fluorescein leakage over AIMS & METHODS: VE was performed using the protocol reported pre-
the mucosal barrier and microerosions using the Watson Grading system, which viously1) with some modifications. The data of 130 examinations of VE per-
scores endomicroscopic changes as normal (1), functional defects (2) or structural formed in our hospital from November 2006 to February 2014 were reviewed,
defects (3)[1]. These findings were correlated with the severity of disease (Fishers and the data of patients with Crohns disease were analyzed.
Exact Test and two-side t-test). In patients with inactive CD, CLE changes were RESULTS: Thirty-nine VEs were performed in Crohns disease, for 27 males and
registered and correlated to treatment escalation and all surgical interventions 12 females. The examinations were indicated when Crohns disease was suspected
during the follow-up period. in 3, when diagnosis of Crohns disease was made in 8, when biologic response
RESULTS: A total of 51 patients were enrolled in the study. Two patients were modifier was planned or started in 4, when the disease was exacerbated in 19, and
excluded due to indeterminate colitis. Of the 49 patients in the final study group, during remission in 5 cases. The mean years after the diagnosis of Crohns disease
38 were known with CD (19 in endoscopic remission), while 11 patients (polyp was 10.1; mean age was 35.4 /- 11.0 at the examination. The volume of air and
control or irritable bowel syndrome) served as controls. The mean age was 42 intraintestinal pressure were recorded in 19 examinations for patients without
(18-71) years and 26 patients were female. The ileal intubation rate was 92% and previous resection of the small bowel with the indicators specially produced for
CLE imaging was obtained in 86% of patients. Comparing CD patients with the this examination. The mean total volume of the injected air was 1802 /- 784 ml,
control group fluorescein leakage and microerosions were seen in 50% vs. 10% the mean maximum intraintestinal pressure was 2.45 /- 0.67 kPa, the mean
(p0.03) and 24% vs. 0 patients (p0.09), respectively. The Watson Score was length of depicted small bowel was 472 /- 80 cm, and whole small bowel
significantly higher in CD patients compared to controls (1,7 vs 1,2, p0.02). Of trace was achieved in 79% of these 19 examinations. In 39 examinations, stenoses
note, fluorescein leakage and microerosions were also identified in patients with with wall thickness were found in 35. Resection of the small bowel was performed
quiescent CD (35% and 12%, respectively) despite no macroscopically or histo- and comparisons of the findings in the VE examination and the resected sample
pathological abnormalities. Moreover, the Watson score was increased (2 or 3) in were possible in 5 patients. The appearance of new stenoses was observed
35% of these patients. Three patients with endoscopic remission relapsed within between two examinations in one patient. The cobble stone appearance was
the limited follow-up period of 34 weeks (2-69); all of them had a Watson score of depicted and confirmed by balloon enteroscopy in one case. The ileo sigmoid
2 or 3. In contrast, all of the patients with a Watson score of 1 remained in colonic fistula was depicted in one case. Balloon dilation therapy was planned
remission. according to the results of the examination and performed successfully. The
CONCLUSION: CLE identified microscopic changes in the terminal ileum of mean length of the remaining small bowel was 246.5 /- 133.9 cm in 11 patients
CD patients, even in patients with otherwise quiescent disease, suggesting that with previous resection of the small bowel and the risk of short small bowel
this method may be a useful adjunct to routine endoscopy to predict relapse. syndrome was assessed when re-resection was considered. In 39 examinations,
REFERENCES vomiting and abdominal pain (requiring pain medication) were noted in 4 and 3
[1] Kiesslich R et al. Local barrier dysfunction identified by confocal laser endo- patients, respectively, but no additional treatments were necessary. No other
microscopy predicts relapse in inflammatory bowel disease. Gut 2012; 61: 1146- complication was observed.
1153. CONCLUSION: VE can be performed safely and examination of the whole
Disclosure of Interest: None declared small bowel was possible in most of the cases with Crohns disease, despite the
presence of stenosis. VE can depict characteristic findings, locate the position of
the lesions, and measure the length of the small bowel objectively. VE is a power-
OP035 CAN NARROW BAND IMAGING PREDICT DUODENAL ful new tool for diagnosis, pre-treatment evaluation, and follow up for Crohns
HISTOLOGY IN CELIAC DISEASE? A PROSPECTIVE DOUBLE disease.
BLIND PILOT STUDY REFERENCES
S.K. Sinha1, P.K. Siddappa1,*, J. Basha1, K. Vaiphei2, K.K. Prasad1, 1) Yoshikawa T, Takehara Y, Kikuyama M, et al. Computed tomographic
S. Appasani1, N. Berry1, M. Ashat1, K. Singh1, R. Kochhar1 enteroclysis with air and virtual enteroscopy: protocol and feasibility for small
1
Gastroenterology, 2Postgraduate Institute of Medical Education and bowel evaluation. Dig Liver Dis 2012; 44; 297-302.
Research(PGIMER), Chandigarh, India Disclosure of Interest: None declared
Contact E-mail Address: dr_kochhar@hotmail.com
INTRODUCTION: Celiac disease (CD) is characterized by varying degrees of OP037 EFFECTIVENESS AND SAFETY OF ENDOSCOPIC BALLOON
villous atrophy. Image enhancement with narrow band imaging(NBI) delineates DILATATION FOR STRICTURES IN CROHNS DISEASE A
villous patterns better than routine endoscopy. Role of NBI in delineating villous MULTICENTER STUDY
morphology of CD is sparsely reported. Z. Szepes1,*, A. Balint1, D. Torocsik1, K. Palatka2, M. Szucs3, F. Nagy1,
AIMS & METHODS: To compare the diagnostic accuracy of NBI with histo- K. Farkas1, R. Bor1, T. Wittmann1, T. Molnar1
pathology in predicting the duodenal villous morphology in CD. 1
First Department of Medicine, University of Szeged, Szeged, 22nd Department of
Amongst the 80 subjects (mean age-26.5 12.24 years, 35-females) included in Medicine, University of Debrecen, Debrecen, 3Department of Medical Physics and
the study, 60 were suspected to have CD (serology positive), 6 were follow up Informatics, University of Szeged, Szeged, Hungary
patients of CD on gluten free diet and 14 had dyspepsia with no evidence of CD Contact E-mail Address: molnar.tamas@med.u-szeged.hu
on complete evaluation. CD was diagnosed on the basis of modified ESPGHAN
criteria. They underwent esophagogastroduodenoscopy (EGD) along with NBI INTRODUCTION: Crohns disease (CD) is a chronic inflammatory disease
using an Olympus GIF-180 gastroscope to evaluate the villous pattern of duo- which frequently complicates by obstructive symptoms secondary to develop-
denal mucosa. These images were digitally recorded for further characterization. ment of intestinal strictures.
Four duodenal biopsies were taken from second part of duodenum for histo- AIMS & METHODS: The aim of this study was to assess effectiveness, safety of
pathology. Digitally recorded images were analyzed by two experienced endos- endoscopic balloon dilatation (EBD). Data of 92 EBD in 45 CD patients were
copists and biopsy specimens by an experienced pathologist all of whom were retrospectively analyzed. 15.2 % of procedures were performed in upper gastro-
blinded to clinical details and serological investigations. Villous patterns on NBI intestinal (GI) tract and 84.8% in lower GI tract. Short-term success rate was
were classified into normal-villous pattern (NVP), distorted & blunted-villous defined as the ability of endoscope to traverse the stenosis after dilatation. Long-
pattern (DVP) and absent-villous pattern (AVP). NBI findings were correlated term clinical success rate was claimed if a patient remained asymptomatic and did
with histopathology. not require surgery or further EBD, following technical success. Prognostic fac-
RESULTS: NBI revealed AVP in 27, DVP in 27 and NVP in 26 patients. In the tors of outcome were statistically assessed.
study group of CD (n60), 26 had AVP, 24 had DVP and 10 had NVP on NBI, RESULTS: 63.04 % of strictures were de novo and 36.96% anastomotic. The
while on histopathology 27 had total villous atrophy, 20 had partial villous mean time between diagnosis and development of strictures with symptoms was
atrophy and 13 had no villous atrophy. 4 CD patients on gluten free diet(n6) 7.26 (0-27) years. The elapsed time between diagnosis and the first balloon dila-
and the 12 dyspepsia patients (control group) had normal villous pattern on both tation was 9.55 (0-35) years. 72.8 % of dilatations were successful on short-term
NBI and histopathology. Significant correlation was observed between NBI and period without serious complications. 21 (46.6 %) patients showed that EBD is
histopathological examination(p50.001). The overall sensitivity and specificity effective on long-term period. Type of strictures, biological therapy before or
of NBI for delineating villous pattern were 87.03% and 84.61% and the positive after dilatation, immunomodulatory therapy and the time between diagnosis and
and negative predictive values were 92.16 % &75% respectively. first EBD did not have influence on long-term effectiveness. 7 subjects had need
CONCLUSION: NBI can predict villous atrophy with high sensitivity and nega- for surgery due to strictures after EBD.
tive predictive value in CD. CONCLUSION: The result of this study highlights that EBD is an effective
Disclosure of Interest: None declared therapy of the short strictures in CD with low complication rate. Using this
endoscopic method we can avoid surgical interventions in most of the cases.
The success rate is independent of the previous and current therapy, duration
of the disease and the type of stenosis.
Disclosure of Interest: None declared
A12 United European Gastroenterology Journal 2(5S)
OP038 EFFICACY OF ENDOSCOPIC BALLOON DILATION FOR OP040 ASSOCIATION OF SERUM ADIPOCYTOKINE AND GUT
SMALL BOWEL STRICTURES IN PATIENTS WITH CROHNS HORMONE LEVELS WITH GASTRIC EMPTYING AND SYMPTOM
DISEASE: A NATIONWIDE, MULTI-CENTER, OPEN-LABEL, PERCEPTION IN PATIENTS WITH FUNCTIONAL DYSPEPSIA
PROSPECTIVE COHORT STUDY P.-H. Tseng1,*, J.-M. Liou1, Y.-C. Lee1, J.-T. Lin1,2, M.-S. Wu1 on behalf of
F. Hirai1,*, T. Matsumoto2, T. Matsui1 Taiwan, GI disease and, Helicobacter consortium
1 1
Department of Gastroenterology, Fukuoka University Chikushi Hospital, Department of Internal Medicine, National Taiwan University Hospital, Taipei,
Chikushino, 2Division of Gastroenterology, Department of Internal Medicine, Iwate 2
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan,
Medical University, Morioka, Japan Province of China
Contact E-mail Address: pinghuei@ntu.edu.tw
INTRODUCTION: Endoscopic balloon dilation (EBD) has been known to be
useful for strictures in Crohns disease (CD) that can be approached by colono- INTRODUCTION: The pathogenesis of functional dyspepsia (FD) is complex
scopy. Recently, EBD by means of balloon-assisted enteroscopy (BAE) has and has been associated with a variety of gastrointestinal motor and sensory
become a possible procedure for small bowel strictures as an alternative to dysfunction. Several peptide hormones secreted by the adipose tissue and the
surgery. gut play an important role in regulating food intake, gastrointestinal motility
AIMS & METHODS: The efficacy and safety of this treatment remain unclear. and energy balance.
Therefore, a nationwide, multi-center, open-label, prospective cohort study was AIMS & METHODS: To investigate the association of circulating adipocyto-
conducted.This study was carried out prospectively within the framework of a kines and gut hormones with gastric emptying and symptom perception in FD
study project undertaken by the Study Group on Intractable Diseases, the Health patients, we conducted a case-control study in 40 FD patients (16 male and 24
and Labor Sciences Research Grants from the Ministry of Health, Labour and female; age: 5012) and 40 asymptomatic healthy volunteers matched for age
Welfare of Japan. Subjects from twenty-three institutions were registered in this and gender. Basic demographics, including complete anthropometric measures,
study. The study subjects were CD patients who had symptomatic small bowel were obtained. All subjects underwent a 3-h gastric emptying scintigraphy using
strictures. Patients with strictures of the colon or in the neo-terminal ileum were radiolabeled oatmeal as the test meal and quantitative emptying parameters were
excluded. Symptoms associated with small bowel strictures (abdominal pain, determined. On the day of scintigraphy, dyspeptic symptoms during the preced-
abdominal bloating, and nausea) were evaluated by visual analogue scale ing two weeks were evaluated using the 9-item Gastroparesis Cardinal Symptom
(VAS) scores before and 4 weeks after the initial EBD. A short-term success of Index. Fasting serum levels of adipocytokines (adiponectin and leptin) and gut
EBD was defined as improvement of all three VAS scores. As an interim analysis, hormones (ghrelin, obestatin and peptide YY) were assayed in all subjects with
the short-term success rate and the adverse events in patients registered from Aug ELISA methods.
2011 to Oct 2013 were analyzed. RESULTS: Anthropometric measures, including body mass index and waist
RESULTS: One hundred and twelve patients were included in this study. EBD circumference, were similar between the 2 groups. FD patients had significantly
could not be performed in 10 patients for various reasons. Of the remaining 102 longer gastric half-emptying time T1/2(57.119.2 vs. 48.78.0 min, p50.001) and
patients, VAS scores of both before and 4 weeks after EBD were available in 69 greater gastric retention at 1 h and 2 h (46.418.8 vs. 39.411.3, p0.046;
patients at the time of this analysis. The treatment outcome was therefore ana- 11.710.3 vs. 7.54.8, p0.023) when compared with healthy controls. Five
lyzed in those 69 patients (50 male, 19 female, disease duration: 10.7 8.2 years). patients with FD (12.5%) had delayed gastric emptying. FD patients had sig-
The short-term success rate was 73% (50/69). After EBD, the scope could pass nificantly lower adiponectin levels (7.63.4 vs. 11.45.0, p50.001) but higher
through the stricture in 76% (54/69). There was not any significant difference in obestatin levels (4.91.8 vs. 3.90.6, p0.003). Both adiponectin and leptin
patients characteristics or in the nature of stricture between successful and levels correlated with gastric retention at 1 h (r0.619 and -0.582; p0.011
unsuccessful cases. Complications were encountered in two of the 69 patients and 0.018, respectively) in male but not in female FD patients. All adipocytokine
(2.9%). These were all hemorrhage and the patients recovered by conservative and gut hormone levels were not significantly different between FD subjects with
therapy. or without delayed gastric emptying. Leptin levels positively correlated with
CONCLUSION: EBD was effective and safe for small bowel strictures in CD visibly larger stomach or belly after a meal (r0.358, p0.024) while ghrelin
patients. We are going to clarify the long-term outcome of EBD in this study. levels positively correlated with early satiety (r0.364, p0.023) and loss of
Disclosure of Interest: None declared appetite (r0.353, p0.028).
CONCLUSION: Gastric dysmotility and derangement of various circulating
adipocytokines and gut hormones might participate in the heterogenous mani-
MONDAY, OCTOBER 20, 2014 14:0015:30 festations of FD patients. Further studies to elucidate the potential roles of these
NEW THOUGHTS ON FUNCTIONAL DYSPEPSIA HALL B_____________________ peptide hormones in the pathophysiology of FD and their clinical implication are
warranted.
OP039 FASTING PYLORIC PRESSURE AND COMPLIANCE IN Disclosure of Interest: None declared
GASTROPARESIS
F. Tissier1,2, C. Melchior1, O. Touchais1, A.-M. Leroi1,3, P. Ducrotte1,2, MONDAY, OCTOBER 20, 2014 14:0015:30
G. Gourcerol1,4,* CLINICAL CHALLENGES IN HEPATITIS C VIRUS THERAPY HALL
1
Digestive Physiology Department, 2HepatoGastroenterology Department,
3 F1_____________________
Clinical Investigation Center, 4Nutrition, Brain and Gut Laboratory, INSERM
unit 1073, Rouen University Hospital, Rouen, France
OP041 NORMALIZATION OF LIVER-RELATED LABORATORY
INTRODUCTION: Gastroparesis is defined by a delayed of gastric emptying PARAMETERS IN HCV GENOTYPE 1-INFECTED PATIENTS WITH
associated with dyspeptic symptoms. Delayed gastric emptying may result from CIRRHOSIS AFTER TREATMENT WITH ABT-450/R/OMBITASVIR,
impairment in gastric and/or pyloric motility. To date, the role of pyloric pres- DASABUVIR AND RIBAVIRIN
sure and/or compliance in gastroparesis has however been poorly investigated. S. Zeuzem1,*, P. Andreone2, S. Pol3, M. Bourlie`re4, A. Castro5, M. Berenguer6,
AIMS & METHODS: Fasting pyloric pressure and compliance were assessed S. Lee7, G. Everson8, S. Lovell9, M. Pedrosa9, R. Trinh9
using EndoFLIP technique (intrapyloric balloon inflated to 40 ml) in 21 1
J.W. Goethe University, Frankfurt, Germany, 2University of Bologna, Bologna,
healthy volunteers (HV), 24 Gastroparetic Patients (GP; diabetic: n3; post- Italy, 3Groupe Hospitalier Cochin-Saint Vincent De Paul, Paris, 4Hopital Saint
surgical: n3; idiopathic: n16), and in 4 patients who underwent esophagect- Joseph, Marseille, France, 5Hospital Universitario La Fe, Valencia, 6Complejo
omy without pyloroplasty as positive controls. Endoflip probe was positioned Hospitalario Universitario A Coruna, A Coruna, Spain, 7University of Calgary,
without anesthesia, under videofluoroscopic control. Gastric half-emptying time Calgary, Canada, 8University of Colorado Denver and Hospital, Aurora, 9AbbVie
(T1/2) was measured using the 13Coctanoic acid breath test. Dyspeptic symp- Inc., North Chicago, United States
toms were recorded using a 5 point-rated scale and quality of life using gastro-
intestinal quality of life index (GIQLI). INTRODUCTION: HCV-infected patients with cirrhosis are at increased risk for
RESULTS: Using Endoflip, the mean fasted pyloric compliance was 25.22.4 hepatocellular carcinoma and liver-related mortality, which can be significantly
mm2/mmHg in HV. Fasted pyloric compliance decreased both in GP (17.62.4 reduced if treated and the patient achieves a sustained virologic response. We
mm2/mmHg; p50.05) and patients with esophagectomy (11.23.7 mm2/mmHg; report the changes in liver-related laboratory parameters after 12 or 24 weeks of
p50.05). By contrast, fasting pyloric pressure was not different between HV treatment with the 3 direct-acting antiviral (3D) regimen of ABT-450/r/ombitas-
(9.61.0), GP (12.11.0 mmHg; p40.05) and control (12.51.6 mmHg; vir, dasabuvir, and ribavirin (RBV) among 380 treatment-na ve and peginter-
p40.05). Fasting pyloric compliance was inversely correlated with T1/2 in GP feron/RBV-experienced HCV genotype 1-infected patients with cirrhosis.
(R-0.43; p0.03), while fasting pyloric pressure did not (R0.28; p0.15). AIMS & METHODS: 380 patients with Child-Pugh A cirrhosis were rando-
Fasting pyloric compliance was also inversely correlated with nausea, vomiting, mized (approximately 1:1) to receive the 3DRBV regimen for 12 or 24 weeks.
regurgitation, gastric fullness, early satiety, and dyspeptic symptomatic score. In Key eligibility criteria included platelet count 60,000 cells/mm3, serum albumin
contrast, fasting pyloric pressure was only correlated with nausea and regurgita- 2.8 g/dL, and total bilirubin 53 mg/dL. Laboratory testing, including chem-
tion. Fasting pyloric compliance, but not pressure, was correlated with the istry, hematology, and urinalysis, were conducted at each study visit during the
GIQLI score (R0.31; p0.02 and R-0.23; p0.10). In 8 GP with low fasting treatment and post-treatment periods, and summarized by treatment group.
pyloric compliance (510 mm2/mmHg) an hydraulic dilation of the pylorus RESULTS: SVR12 was achieved in 92% and 96% of patients receiving the 12-
(20mm), improved fasting pyloric compliance from 7.40.4 to 20.14.9 mm2/ and 24-week treatments, respectively. At the end of treatment with 3DRBV,
mmHg (p50.01). Dilatation also improved the T1/2 in 6/7 patients and quality liver enzymes were normalized in most patients with baseline elevations regard-
of life in 5/8 patients. less of treatment duration (ALT, 323/347 [93.1%]; AST, 316/360 [87.8%]; GGT,
CONCLUSION: This study is the first to assess the pyloric compliance in GP. 284/307 [92.5%]). Mean liver enzyme values were normalized by Week 4. Of
Fasting pyloric compliance seems to be decreased in GP. Fasting pyloric com- patients with platelet counts 5LLN at baseline, counts were normalized in
pliance, but not pressure, was inversely correlated with T1/2, dyspeptic symptoms 28.8% of patients at the end of treatment. Activated partial thromboplastin
and quality of life. This suggests that pyloric compliance may play a role in time was normalized at the end of treatment in 47/67 (70.1%) and 46/51
gastric emptying. (90.2%) of 12-week and 24-week 3DRBV patients with values 4ULN at base-
Disclosure of Interest: None declared line. Mean total bilirubin values peaked at Week 1 (predominantly indirect),
subsequently decreased to the end of treatment, and normalized post-treatment.
United European Gastroenterology Journal 2(5S) A13
OP041
Post-treatment Post-treatment
Parameter Baseline Wk12 Wk12 Baseline Wk12 Wk24 Wk12
CONCLUSION: Treating HCV genotype 1-infected patients with the 3DRBV OP043 REVISITING LIVER DISEASE PROGRESSION IN HIV/HCV-
regimen resulted in high SVR rates and normalization of liver-related chemistry COINFECTED PATIENTS: THE INFLUENCE OF VITAMIN D,
and coagulation profile abnormalities often present in patients with cirrhosis. INSULIN RESISTANCE, IMMUNE STATUS, IL28B AND PNPLA3
Disclosure of Interest: S. Zeuzem Consultancy for: AbbVie, Achillion, BMS, M. Mandorfer1,*, B.A. Payer1, P. Schwabl1, S. Steiner1, A. Ferlitsch1,
Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Novartis, Roche, M.C. Aichelburg2, A.F. Stattermayer1, P. Ferenci1, B. Obermayer-Pietsch3,
Santaris, Vertex, P. Andreone Financial support for research from: Roche, K. Grabmeier-Pfistershammer2, M. Trauner1, M. Peck-Radosavljevic1,
Merck, Gilead, Consultancy for: Roche, Merck, Janssen Cilag, AbbVie, T. Reiberger1 on behalf of Vienna HIV &, Liver Study Group
Boehringer Ingelheim, Gilead, BMS, S. Pol Lecture fee(s) from: GSK, 1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
Consultancy for: Sanofi, BMS, Boehringer Ingelheim, Tibotec, Janssen Cilag, III, 2Division of Immunology, Allergy and Infectious Diseases, Department of
Vertex, Gilead, Roche, MSD, Novartis, AbbVie, M. Bourlie`re Lecture fee(s) Dermatology, Medical University of Vienna, Vienna, 3Division of Endocrinology
from: D, Janssen, Gilead, AbbVie, Consultancy for: BMS, Vertex, MSD, and Metabolism, Department of Internal Medicine, Medical University Graz, Graz,
Janssen, Gilead, AbbVie, Roche, A. Castro Consultancy for: AbbVie, BMS, Austria
Janssen, Merck, Roche, M. Berenguer Consultancy for: BMS, Janssen, Roche, Contact E-mail Address: thomas.reiberger@meduniwien.ac.at
MSD, Novartis, AbbVie, S. Lee Financial support for research from: AbbVie,
BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, Vertex, INTRODUCTION: The importance of endocrine, metabolic, genetic and immu-
Lecture fee(s) from: BMS, Gilead, Merck, Roche, Vertex, Consultancy for: nologic factors in the natural history of HIV/hepatitis C virus (HCV) coinfection
AbbVie, BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, has increasingly gained recognition.
Vertex, G. Everson Financial support for research from: AbbVie, Vertex, BMS, AIMS & METHODS: We aimed to perform a comprehensive study on indepen-
Merck, Roche/Genentech, Gilead/Pharmasset, GSK, Novartis, Tibotec, Janssen, dent modulators of liver fibrosis progression and determinants of portal pressure
Consultancy for: AbbVie, Vertex, BMS, Merck, Roche/Genentech, Gilead, considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D
GSK, Novartis, Esai, Biotest, Other: HepQuant LLC, S. Lovell Shareholder levels (25(OH)D), genetic variants of patatin-like phospholipase domain-contain-
of: AbbVie, Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: ing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documen-
AbbVie, R. Trinh Shareholder of: AbbVie, Other: AbbVie ted cohort of HIV/HCV-coinfected patients.
25. OH)D deficiency (25(OH)DDEF), IR and low CD4 T-lymphocyte nadir
(lowCD4NAD) were defined as 25(OH)D520ngxmL-1, HOMA-IR42 and
OP042 CORRECTION OF VITAMIN D DEFICIENCY CORRELATED CD4nadir5200cellsxL-1, respectively. Liver fibrosis progression rate (FPR)
WITH SUPPRESSION OF SOLUBLE CD26 LEVELS (SCD26) AND was calculated as METAVIR F units divided by the number of years since
INTERFERON-GAMMA-INDUCIBLE PROTEIN 10 (IP-10) IN HCV-infection. Patients with a FPR 4median FPR were assigned to the
PATIENTS WITH CHRONIC HEPATITIS C: A RANDOMIZED, highFPR group.
DOUBLE-BLINDED, PLACEBO-CONTROLLED PILOT STUDY RESULTS: Among 86 HIV/HCV, the median FPR was 0.1667unitsxyears-1.
K. Charoensuk1,2,*, C. Chirathaworn3, S. Suksawatamnuay2, P. Komolmit2 While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF
1
Gastroenterology, Department of Internal Medicine, Buddhachinaraj hospital was higher among highFPR patients, the prevalence of IR was comparable. The
School of Medicine, Phitsanulok, 2Gastroenterology, Department of Internal association between 25(OH)DDEF and FPR
medicine, Chulalongkorn university, 3Division of Immunology, Department of (highFPR:90%vs.lowFPR:31%;P50.001) was confirmed in a subgroup of
Microbiology, Chulalongkorn university, Bangkok, Thailand patients with METAVIR F0/F1/F2 in which 25(OH)D levels are not affected
Contact E-mail Address: hut_kriangsak@hotmail.com by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-
C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR
INTRODUCTION: Vitamin D deficiency, serum IP-10 levels and IL28B poly- patients.
morphisms are used to predicted favorable treatment outcome in chronic hepa-
titis C (CHC). CD26 (DPPIV) truncates the chemokine IP-10 into a shorter
antagonistic form. Previous studies, this truncated IP-10 and CD26 has been Patient characteristics lowFPR n49 highFPR n37 P value
shown to correlate with disease activity and also influence treatment outcome
in CHC patients. We hypothesized that vitamin D supplement, which shown to Prior alcohol abuse 12 (25%) 17 (46%) 0.037
improve CHC treatment response, might restore immune dysregulation in these 25(OH)DDEF 20 (41%) 29 (78%) 50.001
patients through a pathway linked to the Th1/Th2 cytokines, IP-10 or CD26. The
purpose of this study was to investigate the association between vitamin D sup- IR 27 (55%) 18 (49%) 0.553
plement, IP-10 and sCD26 levels in these patients. lowCD4NAD 11 (22%) 16 (43%) 0.04
AIMS & METHODS: We conducted the double-blind, placebo-controlled, inter- IL28B C/C 15 (31%) 14 (38%) 0.483
ventional study; CHC patients with vitamin D deficiency were assigned to receive PNPLA3 non-C/C 21 (43%) 17 (46%) 0.775
vitamin D supplement or placebo for 6 weeks. 25-hydroxyvitamin D (25(OH)D)
levels, Th1/Th2 cytokines, IP-10 and sCD26 levels were measured at baseline and PNPLA3 G/G 0 (0%) 4 (11) 0.031
at 6 weeks. Baseline characteristics were assessed. LowCD4NAD (OR:2.947;95%CI:1.05-8.24;P=0.034) and 25(OH)DDEF
RESULTS: A total of 80 CHC patients with vitamin D deficiency were rando- (OR:5.62;95%CI:2.05-15.38;P50.001) were independently associated with
mized into two groups, 40 patients in each group. There were no significant highFPR and showed an additive effect. Portal pressure correlated with prior
differences in all baseline characteristics between two groups. At the end of alcohol abuse (=0.447;P50.001), HCV-genotype 3 (=0.252;P=0.034),
study, only the mean 25(OH)D levels in vitamin D group were significantly CD4+ nadir (=-0.288;P=0.015), lowCD4NAD (=0.286;P=0.016) and
increased from 21.07 to 48.44 ng/ml, (p50.001).While no significant changes 25(OH)D (=-0.246;P=0.038).
of the IP-10 levels was demonstrated in placebo group, there were significant CONCLUSION: Two potentially modifiable factors, CD4 nadir and
decreasedin serum IP-10 and sCD26 in vitamin D group after 6-week of vitamin 25(OH)D, were both independent modulators of liver fibrosis progression and
D supplement (p5 0.05). However, there were no significant differences in serum determinants of portal pressure. Further studies are warranted to assess the
levels of all Th1/Th2 cytokines studied both groups. relevance of PNPLA3 for FPR in HIV/HCV. The findings of our study suggest,
CONCLUSION: This study demonstrated that vitamin D supplement and that early initiation of combined antiretroviral therapy, as well as vitamin D
restoration of 25(OH)D level in CHC patients resulted in suppression of serum supplementation and vitamin D receptor ligands could be of therapeutic value
IP-10 and sCD26 levels without changes in systemic Th1/Th2 immune cytokines. for the reduction liver fibrosis progression in HIV/HCV-coinfected patients.
These results connect the link and give one explanation of why vitamin D defi- Disclosure of Interest: None declared
ciency, pre-treatment high serum IP-10 levels, sCD26 level and by treatment of
vitamin D deficiency could have effects on CHC treatment responses.
Disclosure of Interest: None declared
A14 United European Gastroenterology Journal 2(5S)
OP044 MICRORNA-21 AND PTEN: A SIMPLE PREDICTIVE MODEL hospital (adjusted HR, 1.99; 95% CI, 1.18-3.36) were associated with excessive
FOR FIBROSIS IN CHC PATIENTS risks. Intriguingly, the risk was not attenuated in patients receiving incomplete
S.J. Chowdhury1,*, V. Karra1, P. Gumma1, P. Kar1 therapy shorter than 16 weeks.
1
Medicine, Maulana Azad Medical College, New Delhi, India, New Delhi, India CONCLUSION: Antiviral treatment for HCV is associated with risk reduction
Contact E-mail Address: soumya.molbio@gmail.com in ESRD. These findings suggest the extrahepatic effectiveness of treating HCV
infection in improving renal outcome.
INTRODUCTION: Down regulation of PTEN in Chronic Hepatitis C has been REFERENCES
associated with steatosis and increase in fibrosis. Even though many predictive 1. Su FH, Su CT, Chang SN, et al. Association of hepatitis C virus infection with
model have been evaluated on the basis of biochemical parameter, PTEN expres- risk of ESRD: a population-based study. Am J Kidney Dis 2012; 60: 553-560.
sion and factors affectng its expression has not been studied. 2. Hsu YC, Lin JT, Ho HJ, et al. Antiviral treatment for hepatitis C virus
AIMS & METHODS: This study aims at finding if there is any correlation infection is associated with improved renal and cardiovascular outcomes in dia-
between increasing fibrosis and variables like PTEN, miR-21, HCV RNA betic patients. Hepatology 2014; 59: 1293-302.
levels, HCV genotype and other biochemical parameters and to draw a predic- Disclosure of Interest: None declared
tion model out from the dependable variables. Study consisted of 84 CHC
patients whose miR-21, PTEN expression, HCV RNA levels were estimated by
Real Time QPCR. All the CHC patients had undergone liver biopsy and were OP046 MANAGEMENT OF HAEMOGLOBIN DECREASE IN PATIENTS
grouped into 3 fibrosis group, viz. F0 (Fibrosis score 0), FM(Fibrosis 1& 2), TREATED WITH ABT-450/RITONAVIR/OMBITASVIR AND
FH (Fibrosis 3). 76 Healthy blood donors were selected randomly and were DASABUVIR WITH OR WITHOUT RIBAVIRIN IN HCV GENOTYPE
evaluated for any history of liver disease. The PTEN and mir21a expression levels 1-INFECTED PATIENTS
have been described in 2Cp where CpCt (Household gene)-Ct(target gene) and so M. Diago1, P. Andreone2, D. Forton3, H. Reesink4, V. Rustgi5, D. Bernstein6,
positive 2Cp values depicts decrease in expression against the housekeeping gene T. Sepe7, J. Vierling8, W. King9, Y. Hu10, J. Enejosa10, D. Cohen10, Y. Luo10,
concentration which is, in this case, GAPDH for RNA expression and U6 for M. Pedrosa10, P. Ferenci11,*
micro RNA. 1
Hospital Quiron de Valencia, Valencia, Spain, 2Azienda Ospedaliero Universitaria
RESULTS: The average age (MeanS.D) of CHC and control group was Policlinico S. Orsola Malpighi, Bologna, Italy, 3St. Georges, University of
42.5511.258 and 33.426.293 years respectively. There was statistical signifi- London, London, United Kingdom, 4Academisch Medisch Centrum, Universiteit
cant difference in PTEN(2Cp) between the mean rank of control (22.93) and van Amsterdam, Amsterdam, Netherlands, 5Metropolitan Research, Fairfax,
Cases(56.93) (U130.5, p50.001). There was statistical significant difference 6
North Shore University Hospital (BRANY), Manhasset, 7University
miR-21(2Cp) levels between the mean rank of control (60.09) and CHC(22.7) Gastroenterology, Providence, 8St. Lukes Episcopal Hospital / St. Lukes
(U53.5, p50.001). Univariate analysis and post-Hoc test between the fibrosis Advanced Liver Therapies, Houston, 9Trial Management Associates, LLC,
group (F0,FM&FH) resulted in statistical significant difference in T.Bil Wilmington, 10AbbVie, North Chicago, United States, 11Medical University of
FM(0.70.306)mg/dl & FH(1.13.563)mg/dl (p.014), PTEN(2Cp) expression Vienna, Vienna, Austria
FM(4.770.415) & FH(37.5210.37) (p50.0001), miR21(2Cp) expression Contact E-mail Address: moisesdiagom@gmail.com, laurinda.cooker@abbvie.com
F0(3.66.08), FM(2.70.50)&FH (1.480.09), (p50.0001). Multinominal logis-
tic regression was done to find out the predictor of increasing fibrosis with above INTRODUCTION: Ribavirin (RBV), which may be associated with anaemia, is
variables and it was found that only PTEN(2Cp) predicted FH from FM with commonly prescribed with direct-acting antivirals for treatment of hepatitis C
statistical significance (B-1.5, p50.0001). Multiple regression was carried virus (HCV) infection. The randomized phase 3 PEARL trials evaluated the
out to predict PTEN(2Cp) from T.Bil and miR21(2Cp). These variables signifi- safety and efficacy of the 3D regimen of ABT-450/ritonavir/ombitasvir (for-
cantly predicted PTEN(2Cp), F(2,39)46.69, p50.0001, R20.705 and the merly ABT-267) and dasabuvir (formerly ABT-333) with or without RBV in
two variables added statistically significantly to the prediction, p50.001. The HCV genotype 1b-infected treatment-experienced (PEARL-II) or treatment-
regression equation obtained predicted PTEN(2Cp)40.63- na ve (PEARL-III) patients, and in genotype 1a-infected treatment-na ve
(13.85xmi21a(2Cp))(10.65xT.Bil). Using this model new cut-off value of (PEARL-IV) patients.
PTEN(2Cp) was calculated using ROC with Area under curve 0.983 and cut- AIMS & METHODS: The management of decreased haemoglobin was deter-
off level 424.22 was found to predict advance fibrosis (Fibrosis 3) mined using data from the 910 patients enrolled in PEARL-II (n186), PEARL-
(sensitivity92.86, Specificity89.29). It had a positive predictive value (PPV) III (n419), and PEARL-IV (n305) trials. In each trial, HCV genotype 1-
of 82.35% and negative predictive value (NPV) of 100%. infected patients were randomized to 12 weeks of treatment with the 3D regimen
CONCLUSION: From our study we conclude that decrease in PTEN mRNA RBV (co-formulated ABT-450/r/ombitasvir [150mg/100mg/25mg QD] and
expression is significantly associated with increase in fibrosis and that there is dasabuvir [250mg BID] with weight-based RBV [1000 or 1200 mg daily divided
negative correlation between PTEN expression and miR21 expression. Other BID]), or 3Dplacebo for RBV (PEARL-III and -IV) or 3D without RBV
than PTEN, miR21 expression levels and Total bilirubin none of the other fac- (PEARL-II). Haemoglobin was assessed at baseline and throughout treatment
tors significantly correlated to either PTEN, miR21 or fibrosis. Our predicitive and follow-up periods. Decreases from baseline in haemoglobin during the treat-
model predicted PTEN(2Cp) using T.Bil and miR21(2Cp) which predicted advance ment period and patient outcomes are reported.
fibrosis(fibrosis 3) with PPV and NPV of 92.86 and 89.2 respectively. RESULTS: Among patients with normal baseline haemoglobin values, on-treat-
Disclosure of Interest: None declared ment grade 2 haemoglobin decrease (8 to 10 g/dL) occurred in 23 patients
(5.7%) receiving 3DRBV; grade 3 decrease (6.5 to 8 g/dL) occurred in 2
patients (0.5%). No patients receiving 3D without RBV experienced grade 2 or
OP045 ANTIVIRAL TREATMENT AND RISK OF END-STAGE RENAL greater haemoglobin decrease while on treatment (Table). There were no grade 4
DISEASE IN PATIENTS WITH HEPATITIS C VIRUS INFECTION haemoglobin decreases (56.5 g/dL). RBV dose was reduced in 23 patients
Y.-C. Hsu1,*, J.-T. Lin2, H.J. Ho3, C.-Y. Chang1, C.-Y. Wu4 (5.7%) to manage anaemia or haemoglobin decrease, and all patients with
1
Department of Internal Medicine, E-DA HOSPITAL/I-SHOU UNIVERSITY, RBV dose modification achieved SVR12. Mean haemoglobin values decreased
Kaohsiung, 2School of Medicine, Fu Jen Catholic University, 3School of Medicine, by the second week of treatment, and returned to near-baseline by 4 weeks post-
Fu Jen Catholic University, New Taipei, 4Department of Internal Medicine, treatment. 1 patient (0.1%) received a blood transfusion for haemoglobin 58 g/
Taichung Veterans General Hospital, Taichung, Taiwan, Province of China dL. No erythropoietin use was required. No patient discontinued the study due
Contact E-mail Address: holdenhsu@gmail.com to decreased haemoglobin.
OP052-LB5 ASSOCIATION OF THE 3UTR HLA-G 3187A/G Timing of adjuvant chemotherapy initiation Hazard Ratio (95% CI) Sig.
POLYMORPHISM WITH RELAPSE AND SURVIVAL IN
COLORECTAL CANCER PATIENTS IN ADJUVANT REGIMEN. A 0-4 weeks Ref
MULTICENTER STUDY 5-8 weeks 0.81 (0.75-0.87) 50.001
M. Garziera1,*, E. Bidoli2, E. Cecchin1, C. Zanusso1, F. De Marchi3, A. De 9-12 weeks 0.92 (0.85-0.99) 0.028
Paoli4, E. Mini5, G. Toffoli1
1 13-16 weeks 1.10 (1.01-1.19) 0.029
Experimental and Clinical Pharmacology Unit, 2Epidemiology Unit, 3Dept
Surgical Oncology, 4Dept Radiotherapy, CRO Aviano National Cancer Institute, 17-20 weeks 1.35 (1.23-1.48) 50.001
Aviano, 5Experimental and Clinical Medicine, University of Florence, Florence, 21-24 weeks 1.31 (1.18-1.45) 50.001
Italy
Contact E-mail Address: mgarziera@cro.it 33,435 (82.6%) of the 40479 patients received it within 12 weeks. Adjuvant
chemotherapy beyond 12 weeks resulted in poorer survival, compared to
INTRODUCTION: HLA-G is involved in cancer immune tolerance. HLA-G within 12 [Hazard Ratio (HR) 1.39, 95% CI 1.34-1.44, p50.001]. Reoperation
expression is linked to 3UTR regulation. To date, the prognostic value of was an independent predictor of adjuvant chemotherapy delay (HR 2.22, CI
3UTR HLA-G SNPs has never been explored in colorectal cancer (CRC) in 1.98-2.48, p50.001). Patients who avoided a reoperation and received timely
the adjuvant chemotherapy (ADJ-CT) regimen. adjuvant chemotherapy demonstrated the greatest median survival [no delay
AIMS & METHODS: To quantify in CRC patients the association between SNPs, no reoperation 90 months (m); no delay reoperation 75m, delay no
alleles and haplotypes of HLA-G 3 UTR region with disease free survival (DFS) reoperation 50m, delay reoperation 50m, Log rank p value50.001)].
and OS. 274 CRC patients (stage II-III) after primary surgery were included in 2 CONCLUSION: Twelve weeks may be an appropriate cut-off for timely initia-
independent cohorts: 1) the discovery set (N124); 2) the validation set (N150). tion of adjuvant chemotherapy and with such a delay adversely impacting color-
All patients received fluoropyrimidines (FL) as ADJ-CT; of them, 164 received FL ectal cancer patients overall survival. Reoperation is a significant cause of
plus oxaliplatin. 3UTR of the HLA-G gene was amplified by PCR from genomic delayed adjuvant chemotherapy. Efforts to prevent complications necessitating
DNA. 9SNPs: 14bp INDEL, 3003T/C, 3010G/C, 3027C/A, 3035C/T, reoperation and to improve access to chemotherapy services will improve survi-
3142C/G, 3187A/G, 3196C/G, 3227G/A, were analysed by direct sequen- val in this patient group.
cing. UTR haplotypes frequencies were determined by PHASE method. We eval- REFERENCES
uated data by means of Cox models. Multivariate Hazard ratios (HRs) and 95% CIs 1. Biagi JJ et al. PMID: 21642686
of DFS and OS were computed adjusting for age, sex, stadium and type of ADJ-CT. 2. Des Guetz G et al. PMID: 20138505
Data validation was performed between the 2 cohorts. Disclosure of Interest: None declared
RESULTS: Relapses were 79/274 and deaths were 45/274. Mean follow-up time
was 67.2 months (range: 4.6-186.3). The association between DFS and 3UTR
3187G/G genotype was statistically significant (HR2.2; 95%CI:1.1-4.6). The OP052-LB7 ADM RECEPTOR WAS RELATED WITH THE METASTASIS
3187A/G SNP was also significantly associated to DFS under a recessive OF COLORECTAL CANCERS THROUGH WNT AND NO
genetic model (HR2.1; 95%CI:1.1-4.3). 20 haplotypes were identified (6 PATHWAYS
novel); 8 with frequencies 41% (93% of total): UTR-2(33%), UTR-1(24%), L. Wang1,2,*, Y. Fang2,3, S. Chen2,3
UTR-3(13%), UTR-4(12%), UTR-7 (5%), UTR-5(3%), UTR-18(2%) and 1
Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang
UTR-15(1%). The 3UTR-1 in homozygous state was significantly associated University, 2Institute of Gastroenterology, Zhejiang University School of Medicine,
to DFS (HR2.2;95%CI:1.0-4.5). OS was directly associated to these variants 3
Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University School of
but not statistically significant. HR heterogeneity tests across the two cohorts, Medicine, Hangzhou, China
were not significant for 3187A/G and 3UTR1/UTR1 (i.e. p0.24 for DFS and Contact E-mail Address: 1400927291@qq.com
p0.61 for OS).
CONCLUSION: For the first time, the 3UTR of the HLA-G gene was explored INTRODUCTION: ADM is significantly overexpressed in human colorectal
in CRC patients. Analyses showed that 3UTR 3187A/G and 3UTR-1, which cancer (CRC) samples with a mutant KRAS oncogene and it can promote cell
includes 3187G allele, were associated to an unfavourable DFS and OS. invasion. ADM acts as a peptide ligand that activates receptors including the
3187A allele was related to a decreased HLA-G expression, while 3187G adrenomedullin receptor (ADMR, also known as L1-R) and the calcitonin-recep-
allele and UTR-1 haplotype were associated to higher soluble HLA-G levels. tor-like-receptor (CRLR). However, the role of ADM receptors remains
Next analyses will explore, at germinal level, the 3UTR HLA-G region novel unknown.
prognostic role to better manage CRC patients in FL based ADJ treatment. AIMS & METHODS: We first detected the expression of ADM, ADMR and
Disclosure of Interest: None declared CRLR in human colon tissues by immunohistochemistry and correlated the
expression levels with clinicopathological features. The expression of ADMR
and CRLR was interfered by lentivirus and their effects on the proliferation,
cell cycle, apoptosis, migration and invasion were evaluated by MTS, flow cyto-
metry and transwell assays, respectively. We screened the downstream targets
related with the metastasis-related signaling pathways of ADMR and CRLR in
CRC by metastasis Gene-expression Array and validated the results by PCR.
RESULTS: The expression level of ADM and CRLR were statistically higher in
CRC tissues than those in adjacent tumor-free tissues (p50.01). The expression
of ADMR and CRLR mRNA was correlated with lymph node metastasis of
colon cancer (p50.01). ADMR or CRLR shRNA-transfected RKO and HT-29
cells inhibit the cell viability and induced a significant increase in early and
total apoptosis of RKO and HT-29 cells. In addition, dual interference with
ADMR and CRLR significantly inhibited cell migration and invasion in RKO
United European Gastroenterology Journal 2(5S) A19
and HT-29 cells (p50.01). Exogenous ADM administration (50nmol/L) can examine the entire GI tract. This study compares the diagnostic yield of
promote cell migration and invasions, and these effects were blocked with silen- PillCamCD to IC.
cing of ADMR and CRLR. cDNA microarray and qPCR validation analysis AIMS & METHODS: In 8 centers, the PillCamCD capsule (Given Imaging,
showed that APC, EGF, PIK3CA, PIK3CB and DVL1 were up-regulated, while Yoqneam, Israel) was prospectively compared to IC in a cohort of patients
NOS2 is down-regulated by silencing of ADMR and CRLR. with known CD presenting with objective signs and symptoms of active disease.
CONCLUSION: High expression of ADM and its receptors- ADMR and CRLR Patients underwent patency capsule testing if they did not have recent radio-
was associated with lymph node metastasis. Silencing expression of ADMR and graphic evidence of small bowel patency. Subjects underwent standardized
CRLR significantly inhibited proliferation, impaired migration and invasion of bowel prep. Ingestion of PillCamCD was followed by IC the same or following
colon cancer cells, which might be mediated through Wnt and NO signaling day per investigator discretion. RAPID videos were reviewed by one of three
pathways. central readers. Mucosal lesions identified during PillCamCD and IC were ana-
Disclosure of Interest: None declared lyzed by type and location. A priori, Active CD was defined as the presence of
aphthae, ulcerations, inflammatory stricture or bleeding. Other lesions were
defined Non-active CD. Localization was to SB, ileum, cecum, ascending,
MONDAY, OCTOBER 20, 2014 14:0015:30 transverse, descending, sigmoid or rectum. Each segment was reported as
NEW IMAGING TOOLS FOR IBD HALL N_____________________ Active disease likely or Active disease NOT likely.
RESULTS: Total of 114 subjects screened; 76 enrolled. Screen failures were due
OP053 DEVELOPMENT AND INITIAL VALIDATION OF A UNIQUE to lack of evidence of inflammation or failure to pass the patency capsule. Of 76
SCORE FOR IN VIVO DIFFERENTIATION OF ULCERATIVE subjects, 66 were included in the efficacy analysis (mean age 37yrs, 67% F). The
COLITIS AND CROHNS DISEASE FEATURING CONFOCAL LASER majority of exclusions was due to capsule retention in the SB or stomach. Forty-
ENDOMICROSCOPY six of 66 (70%) had Active CD likely by IC. PillCamCD identified 43 (94%)
G.E. Tontini1,2,*, J. Mudter1, M. Vieth3, R. Atreya1, C. Gunther1, R. Kiesslich4, similarly. There was no significant difference between PillCamCD and IC for
M. Vecchi2,5, M.F. Neurath1, H. Neumann1 classifying subjects as having active CD (p 0.43). Fifty-five subjects (83%) were
1
Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany, identified with Active CD likely by PillCamCD including 12 identified by
2
Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, PillCamCD only. The proximal SB was evaluated only by PillCamCD; however,
Milano, Italy, 3Institute of Pathology, Klinikum Bayreuth, Bayreuth, 4Medicine, 5 of 12 were found to have lesions in the TI as defined by the last 10 minutes of
St. Marienkrankenhaus Katharina-Kasper, Frankfurt am Main, Germany, the SB portion of the study. Thirty subjects (46%) were identified with Active
5
Biomedical Sciences for Health, University of Milan, Milano, Italy CD likely in the SB. There was no significant difference between PillCamCD
Contact E-mail Address: gianeugeniotontini@libero.it and IC in classifying segments as having Active CD likely (p50.09). There
were three (3%) adverse events: 1 bowel obstruction due to CD capsule retention,
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) allows on demand 1 abdominal pain due to prep, 1 episode of fever, nausea, vomiting, abdominal
in vivo characterization of architectural and cellular tissue details during endo- pain and bloating (without obstruction) related to the patency capsule.
scopy. Recent evidences have shown that CLE can detect Crohns disease (CD) CONCLUSION: As compared to IC, the novel PillCamCD capsule was equally
and ulcerative colitis (UC) associated histological changes in vivo. effective in identifying active CD in the colon and TI in patients with signs and
AIMS & METHODS: We prospectively assessed the efficacy of CLE for in vivo symptoms of active CD, identified more overall patients with active CD, and
differentiation of IBD by developing a unique CLE scoring system based on provides the advantage of imaging the entire small bowel and colon in a single
histopathological hallmarks of colonic IBD involvement. Consecutive patients procedure.
with a well-established diagnosis of UC and CD and no disease reclassification Disclosure of Interest: D. Helper Financial support for research from: Given
during the last three years underwent colonoscopy with biopsies and blind fluor- Imaging, P. Malik Financial support for research from: Given Imaging, R.
esceine-aided confocal imaging. Analysis of contingency tables was performed Havranek Financial support for research from: Given Imaging, Lecture fee(s)
using the Fishers Exact test, thereby considering significant a two-sided P value from: Given Imaging, K. Isaacs Financial support for research from: Given
50.05. Imaging, I. Dotan Financial support for research from: Given Imaging, A.
RESULTS: Seventy-nine patients were prospectively included (40 CD, 39 UC). Lahat Financial support for research from: Given Imaging, J. Horlander
In CD, CLE showed significantly more often discontinuous inflammation (90% Financial support for research from: Given Imaging, A. Tinsley Financial sup-
vs. 5%), focal cryptitis (75% vs. 13%) and discontinuous crypt architectural port for research from: Given Imaging, J. Leighton Financial support for
abnormality (90% vs. 5%). Conversely, UC was associated with severe, wide- research from: Given Imaging, Consultancy for: Given Imaging, I. Fernandez-
spread crypt distortion (87% vs. 17%), decreased crypt density (79% vs. 22%) Urien Sainz Financial support for research from: Given Imaging, B. Rosa
and frankly, irregular surface (90% vs. 17%). Significant differences were not Financial support for research from: Given Imaging, G. Mullin Financial sup-
seen for heavy, diffuse lamina propria cell increase or mucin preservation. port for research from: Given Imaging, I. Gralnek Consultancy for: Given
Granulomas were not visible in any case. Based on these findings, we developed Imaging
a scoring system for in vivo IBD differentiation based on endomicroscopic assess-
ment (IDEA). Compared to the historical clinical diagnosis and histopathology,
the IDEA score revealed excellent validity measures in both UC and CD subjects OP055 CONFOCAL LASER ENDOMICROSCOPY PREDICTS
(sensitivity 97% and 90%, specificity 90% and 97%, positive predictive value RELEVANT CLINICAL OUTCOMES IN CROHNS DISEASE: A
91% and 97%, negative predictive value 97% and 91%, accuracy 94% for both). PROSPECTIVE, OBSERVATIONAL, FOLLOW-UP STUDY
CONCLUSION: CLE enables in vivo characterization of most microscopic tissue G.E. Tontini1,2,*, J. Mudter1, M. Vieth3, R. Atreya1, C. Gunther1, M. Vecchi2,4,
features and inflammatory changes of tissue and cellular characteristics conven- M.F. Neurath1, H. Neumann1
tionally used by standard histopathology both to confirm diagnosis and to dis- 1
Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany,
tinguish UC from CD. However, according to the penetration depths of CLE, 2
Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato,
submucosal details or granulomas are not visible. The new scoring system Milano, Italy, 3Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany,
"IDEA" allows for on demand in vivo differential diagnosis of UC and CD 4
Biomedical Sciences for Health, University of Milan, Milano, Italy
with high accuracy. Contact E-mail Address: gianeugeniotontini@libero.it
Disclosure of Interest: G. E. Tontini Financial support for research from: Italian
Group for the study of IBD (IG-IBD), J. Mudter: None declared, M. Vieth: INTRODUCTION: Assessment of prognostic factors in Crohns disease (CD)
None declared, R. Atreya: None declared, C. Gunther: None declared, R. patients is crucial for early intervention and treat to target strategies [1].
Kiesslich: None declared, M. Vecchi: None declared, M. Neurath: None Confocal Laser Endomicroscopy (CLE) enables on demand in vivo characteriza-
declared, H. Neumann: None declared tion of architectural changes during endoscopy [2].
AIMS & METHODS: Here, we prospectively evaluated the value of CLE, endo-
scopic index of severity (CDEIS) and serum C-reactive protein (CRP) for pre-
OP054 THE NOVEL PILLCAM CROHNS DISEASE CAPSULE diction of clinical outcomes in CD. Consecutive CD patients undergoing
DEMONSTRATES SIMILAR DIAGNOSTIC YIELD AS colonoscopy with fluoresceine-aided confocal imaging were enrolled in a blind,
ILEOCOLONOSCOPY IN PATIENTS WITH ACTIVE CROHNS observational, follow-up study. Consistent with previous reports [2], CLE ana-
DISEASE - A PROSPECTIVE MULTICENTER INTERNATIONAL lysis focused on two highly reproducible architectural microscopic tissue changes
COHORT STUDY referred as histological hallmarks of acute inflammation in CD: focal cryptitis
D. Helper1,*, P. Malik2, R. Havranek3, K. Isaacs4, I. Dotan5, A. Lahat6, and discontinuous crypt architectural abnormality.
J. Horlander7, A. Tinsley8, J. Leighton9, I. Fernandez-Urien Sainz10, B. Rosa11, RESULTS: Thirty-two CD patients were included (14 men; median age/range
G. Mullin12, I. Gralnek13 37/18-60 years; mean distance from diagnosis 11 years). Baseline CRP was 5
1
Indiana University School of Medicine, Indianapolis, 2Gastroenterology mg/L in 46% and CDEIS 3 in 73% of patients. Mean follow-up period was 2.5
Associates of Tidewater, Chesapeake, 3Gastroenterology Clinic of San Antonio, years (range6-48 months). Focal cryptitis and discontinuous crypt architectural
San Antonio, 4University of North Carolina, Chapel Hill, United States, 5Tel Aviv abnormality were observed in 63% of patients. This finding showed a weak
Sourasky Medical Center, Ichilov, 6Sheba Medical Center, Ramat Gan, Israel, correlation with CDEIS (P0.068, RR1.6) and no correlation with CRP
7
Gastroenterology Associates of Louisville, Louisville, 8Penn State Hershey (P0.4, RR1.6). Focal cryptitis and discontinuous crypt architectural abnorm-
Medical Center, Hershey, 9Mayo Clinic Arizona, Scottsdale, United States, ality were significantly associated with an increased risk of medical treatment
10
Hospital de Navarra, Pamplona, Spain, 11CentroHospitalar do Alto Ave, escalation with biologics, immunosuppressant or systemic steroids within 6
Guimaraes, Portugal, 12Johns Hopkins Medical Center, Baltimore, United States, months (P0.045, RR2.0), showing 75% sensitivity and 70% specificity. This
13
Rambam Medical Center, Haifa, Israel finding was also confirmed at 12 month follow up (P0.012, RR2.1;
Contact E-mail Address: dhelper@iu.edu sensitivity76%, specificity78%). Patients with positive CLE findings devel-
oped significantly more transmural complications such as stenosis or perianal
INTRODUCTION: Mucosal lesions in Crohns disease (CD) can be found disease during the first 12 months (P0.023, RR6.0; sensitivity91%,
throughout the GI tract. While an endoscopist may visualize to D3 with EGD specificity52%). Conversely, basal CDEIS 3 was only associated with treat-
and from anus to terminal ileum with ileocolonoscopy (IC), visualization of the ment escalation at month 12th (P0.022, RR2.27; sensibility85%,
entire small bowel (SB) is challenging. The novel PillCamCD is designed to specificity37%). CRP was not correlated with prognostic clinical outcomes.
A20 United European Gastroenterology Journal 2(5S)
CONCLUSION: In vivo characterization of CD-related signs of acute inflamma- In addition, there is no widely accepted endoscopic or MR scoring system for the
tion by means of CLE showed moderate correlation with CDEIS but not with entire small intestine in CD. We evaluated the usefulness of MR enterocolono-
CRP. CLE appeared as a good predictor of relevant clinical outcomes such as graphy (MREC) by comparing its findings with those from balloon-assisted
treatment escalation and transmural complications, performing better than CRP enteroscopy.
and CDEIS. This finding was substantial in the short term but disappeared after AIMS & METHODS: MREC and enteroscopy were performed within 3 days on
one year follow up. Therefore, endomicroscopic assessment of acute mucosal 100 patients. The segmentation and assessment of the endoscopic findings were
inflammation appears to be a promising prognostic tool, which may allow defined based on modified SES-CD, and those of MREC findings were defined
early risk stratification of strong clinical outcomes with high sensitivity and based on modified MaRIA score as well. Physicians and radiologists were
moderate to good specificity, thereby potentially improving the timing of treat- blinded to results from other studies. Findings from MREC were directly com-
ment strategies targeting mucosal inflammation in CD. pared with those from enteroscopy; the sensitivity and specificity with which
REFERENCES MREC detected CD active lesions were assessed. Additionally, we are evaluating
1. Bouguen G, et al. Treat to target: a proposed new paradigm for the manage- the correlation between modified SES-CD and MaRIA scores.
ment of Crohns disease. Clin Gastroenterol Hepatol. Epub ahead of print 2013. RESULTS: The scope was passed in retrograde fashion and reached the prox-
2. Neumann H, et al. Assessment of Crohns disease activity by confocal laser imal ileum in 98 patients (98.0 %), the jejunum in 40 patients (40.0 %), and the
endomicroscopy. Inflamm Bowel Dis 2012; 18: 2261-2269. entire intestine in 11 patients (11.0 %). In the assessment of CD active lesions,
Disclosure of Interest: G. E. Tontini Financial support for research from: Italian MREC detected ulcerative lesions and all mucosal lesions in the small intestine
Group for the study of IBD (IG-IBD), J. Mudter: None declared, M. Vieth: with 82.4% sensitivity and 67.5% sensitivity, respectively; specificity values were
None declared, R. Atreya: None declared, C. Gunther: None declared, M. 87.6% and 94.8%, respectively. Modified MaRIA scores correlated with mod-
Vecchi: None declared, M. Neurath: None declared, H. Neumann: None ified SES-CD in the terminal ileum (r 0.75), but did not in the jejunum and
declared proximal ileum (r 0.48).
CONCLUSION: MREC is useful for detecting active lesions in deep small intes-
tine. Evaluation of active lesions is important to determine medical treatment.
OP056 MR ENTEROCOLONOGRAPHY CAN IDENTIFY PATIENTS Suitable imaging approaches should be selected to assess CD lesions in deep
WHO NEED ADDITIONAL TREATMENT BY PREDICTING small intestine. Alternatively, it is needed to develop the new scoring system of
RECURRENCE, HOSPITALIZATION AND SURGERY OF CROHNS enteroscopy or MR for the entire small intestine in CD.
DISEASE PATIENTS IN REMISSION Disclosure of Interest: None declared
T. Fujii1,*, M. Naganuma1, Y. Kitazume2, K. Takenaka1, M. Nagahori1,
E. Saito1, K. Ohtsuka1, M. Watanabe1
1
Gastroenterology, 2Radiology, TOKYO MEDICAL AND DENTAL UNIV, OP058 LOOKING BEYOND MUCOSAL HEALING: EFFECT OF
Tokyo, Japan BIOLOGIC THERAPY ON TRANSMURAL HEALING EVALUATED
Contact E-mail Address: tfujii.gast@tmd.ac.jp BY ULTRASOUND IN PEDIATRIC CROHNS DISEASE
F. Civitelli1,*, F. nuti1, S. oliva1, M. murciano1, M. aloi1, L. Messina1, F. Viola1,
INTRODUCTION: Crohns disease (CD) is a lifelong chronic inflammatory S. cucchiara1
bowel disease. Evaluating the extension and severity of the disease is critical to 1
Pediatrics, Gastroenterology and Liver Unit, Sapienza University of Rome, Italy,
determine appropriate therapeutic strategies in patients with CD. MR enterogra- Rome, Italy
phy (MRE) can investigate not only intraluminal changes, but also extraluminal Contact E-mail Address: fortunatacivitelli@gmail.com
abnormalities without ionizing radiation and anesthesia, which makes it appro-
priate for frequent examinations in CD patients. We developed novel magnetic INTRODUCTION: Therapeutic goals for Crohns disease (CD) have evolved
resonance enterocolonography (MREC) for simultaneously evaluating both from a mere control of symptoms to the concept of deep remission (DR), includ-
small and large bowel lesions in patients with CD and recently we reported its ing clinical and biomarker remission and mucosal healing (MH). Biologic ther-
excellent correlation with endoscopy. However, there are few reports about pre- apy with anti-TNF is effective in achieving MH. Yet, CD is a transmural
dictability of CD recurrence by MRE. The aim of this study was to evaluate the disease, characterized by a progressive bowel damage leading to complications.
capability of MREC for prediction of recurrence, hospitalization, and surgery AIMS & METHODS: This is the first pediatric study prospectively evaluating
among CD patients in clinical remission. the efficacy of anti-TNF therapy in inducing clinical remission, MH and TH in
AIMS & METHODS: A total of 284 patients with established CD were pro- ileal CD. Pediatric patients (pts) with ileal CD starting biological therapy with
spectively examined by MREC between July 2009 and February 2014. Among Infliximab or Adalimumab were prospectively enrolled. All pts were na ve to
them, 213 patients were in clinical remission (Crohns Disease Activity Index biologics. Clinical activity (Pediatric Crohns Disease Activity Index, PCDAI),
(CDAI) 150). Patients underwent ileocolonoscopy (ICS) after MREC on the laboratory tests (CRP, ESR), endoscopic activity (simple endoscopic score, SES-
same day. MREC score (0-60) was defined by modifying SES-CD. Presence and CD) and transmural disease assessed by small intestine contrast ultrasonography
size of ulcers, extent of ulcerated surface, extent of affected surface and presence (SICUS) were evaluated before starting (T0) and after 9-12 months of therapy
of narrowings were scored (0-3) in each segment of small and large intestine. (T1). Complete MH was defined as a SES-CD of 0-1, partial MH as 50%
MREC score, simplified endoscopic activity score for Crohns disease (SES-CD), decrease vs T0. At US the evaluated parameters were: extension of disease
CDAI and CRP was evaluated. The patients were followed up for a maximum of (cm), bowel wall thickness 43 mm (BWT), BW vascularity (BWV), stratification
58 months unless clinical recurrence occurred earlier. of the BW (BWS), presence of stricture, fistulae and abscess. Wilcoxon signed
RESULTS: 126 patients (59.2%) in clinical remission had active lesion on rank test was used for pair comparison (T1T0).
MREC (MREC score =2; reflecting active disease). Over a median follow up RESULTS:
of 12 months (3-58), 81 patients recurred, 57 needed hospitalization and 49 had
operation. Patients who had active lesion on MREC more often experienced
recurrence than those who didnt (88.9% vs 11.1%. p50.001). Higher SES- T0 T1 p value
CD, higher CDAI and higher CRP at baseline also predicted clinical recurrence.
But only active lesion on MREC was a predictor for both hospitalization (37.3% PCDAI 33.77 18.20 13.10 12.86 50.0001
vs 11.5%, p 50.001) and operation (32.5% vs 9.2%, p 50.001). Even in 152 Ileal SES-CD 6.6 3.6) 2 2.3 50.001
patients in remission with negative CRP, the detection of active lesion on MREC
significantly predicted clinical recurrence (52.6% vs 10.5%, p50.001), hospita- PCR (mg/l) 30609 24539 8744 16330 50.001
lization (40.8% vs 11.8%, p50.001) and operation (35.5% vs 10.5%, p50.001). ESR (mm/h) 69 35 35 26 50.0001
CONCLUSION: This prospective study suggested that MR enterocolonography BWT (mm) 5.98 1.67 4.31 1.71 50.0001
is useful for predicting recurrence of Crohns disease and identifying patients who Extension of ileal disease (cm) 13.63 5.78 9.08 5.74 50.0001
need additional treatment.
REFERENCES 26 pts (mean age 13.3 4, 16 males) were included. The mean PCDAI, ileal SES-
Hyun SB, Fujii T, et al. Magnetic resonance enterocolonography is useful for CD, CRP, ESR, BWT and disease extension values significantly decreased at T1
simultaneous evaluation of small and large intestinal lesions in Crohns disease. (table; mean SD values). Increased BWV was present in 80% of pts at T0 and
Inflamm Bowel Dis 2011. in 24% at T1 (p50.0001). In pts with complete and partial MH the extension of
Takenaka K, FujiiT, et al. Comparison of magnetic resonance and balloon disease and the mean BWT at US were significantly reduced at T1 (p50.02); in
enteroscopic examination of deep small intestine in patients with Crohns disease. pts without endoscopic response the US parameters didnt change significantly,
Gastroenterol 2014 in press. despite clinical response. Presence of strictures and BWS didnt modify during
Disclosure of Interest: None declared therapy in any group.
CONCLUSION: Biologics are effective in inducing clinical and laboratory
remission and in achieving MH in pediatric CD. Transmural inflammation sig-
OP057 MAGNETIC RESONANCE ENTEROCOLONOGRAPHY CAN nificantly improves during therapy, however when a substantial bowel damage
DETECT SMALL INTESTINAL ACTIVE LESIONS IN CROHNS (stricture) is present, the effect on TH might be poorer. Further studies are
DISEASE; COMPARISON WITH BALLOON ENTEROSCOPY needed to evaluate the impact of TH on the long term outcome of CD.
K. Takenaka1,*, K. Ohtsuka1, Y. Kitazume1, M. Nagahori1, T. Fujii1, E. Saito1, Disclosure of Interest: None declared
M. Watanabe1
1
Tokyo Medical and Dental University, Tokyo, Japan
Contact E-mail Address: ktakenaka.gast@tmd.ac.jp
INTRODUCTION: To assess active lesions such as ulcers or aphtha is important
in Crohns disease (CD). Magnetic resonance (MR) enterography is a recom-
mended imaging technique for detecting intestinal involvement in Crohns dis-
ease (CD). However, the diagnostic accuracy of MR enterograpy has not been
compared directly what that of enteroscopy of the jejunum and proximal ileum.
United European Gastroenterology Journal 2(5S) A21
MONDAY, OCTOBER 20, 2014 14:0015:30 were isovascular patterns (89%). 6 of 8 NETs were hypervascular patterns
IMAGING IN PANCREATIC CANCER: STILL A CHALLENGE HALL O_____________________ (75%). 8 of 11 inflammatory masses were isovascular patterns (73%). 3 of 5
invasive IPMNs were hypovascular patterns (60%). All 2 acinor carcinomas
OP059 PROSPECTIVE MULTICENTER RANDOMIZED CONTROLLED were isovascular patterns (100%). A hypovascular pattern, determined by CE-
TRIAL OF HISTOLOGICAL DIAGNOSTIC YIELD COMPARING 25G EUS, was calculated to diagnose ductal carcinoma with sensitivity and accuracy
EUS-FNA NEEDLES WITH AND WITHOUT A CORE TRAP IN SOLID of 95% and 89%, respectively.
PANCREATIC MASSES: ANALYSIS OF FACTORS AFFECTING CONCLUSION: CE-EUS was useful for characterization of pancreatic solid
TISSUE ACQUISITION AND DIAGNOSTIC ACCURACY masses with high sensitivity and accuracy.
H. Nebiki1,*, A. Yanagisawa2, S. Yasukawa2, K. Kamata3, M. Kudo3, Disclosure of Interest: None declared
T. Ogura4, K. Higuchi4, N. Fukutake5, R. Ashida5, T. Yamasaki1, S. Hirose6,
N. Hoki6, M. Asada7, S. Yazumi7, M. Takaoka8, K. Okazaki8, F. Matsuda9,
Y. Okabe9, M. Kitano3 OP061 LIQUID BIOPSY BASED ON CIRCULATING TUMOUR CELLS
1
Dept. of Gastroenterology, Osaka City General Hospital, Osaka, 2Dept. of (CTC) DETECTION IS A DIAGNOSTIC AND PROGNOSTIC
Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto, MARKER IN PATIENTS WITH PANCREATIC SOLID TUMOURS
3
Gastroenterology and Hepatology, Kinki University, Osaka-sayama, 4The Second P. Basile1,*, E. Toure2, D. Sefrioui1,3, I. Iwanicki-Caron1, C. Vasseur3,
dept. of Int. Med., Osaka Medical College, Takatsuki, 5Dept. of Cancer Survey M. Antonietti4, S. Lecleire4, F. Blanchard2, J.C. Sabourin2,3, F. Di Fiore1,3,
and Gastrointestinal Oncology, Osaka Medical Center for Cancer and P. Michel1,3
Cardiovascular Diseasis, Osaka, 6Dept. of Gastroenterology, Bell Land General 1
Digestive oncology unit, Department of hepatogastroenterology, 2Department of
hospital, Sakai, 7Digestive Disease Center, Kitano Hospital, Osaka, pathology, 3Inserm unit U1079, 4Endoscopy unit, Department of hepatogastroen-
8
Gastroenterology and Hepatology, Kansai Medical University, Hirakata, 9Dept. terology, Rouen University Hospital, ROUEN, France
of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan Contact E-mail Address: frederic.di-fiore@chu-rouen.fr
Contact E-mail Address: nebiki@nn.iij4u.or.jp
INTRODUCTION: The pancreatic cytology by endoscopic ultrasound-guided
INTRODUCTION: We have reported that a prospective multicenter randomized fine needle aspiration (EUS-FNA) is considered as the standard procedure for
controlled trial indicated that the novel EUS-FNA 25G needle with a core trap the diagnostic of pancreatic tumour. We recently showed that detection of cir-
by a single pass offers significantly higher tissue acquisition rate and the definite culating tumour cells (CTC) had a diagnostic accuracy of 70% for pancreatic
histological diagnosis rate of solid pancreatic tumors compared with the 25G adenocarcinoma (Am J Gastroenterol 2013;108:152-155). The aim of the study
standard needle (DDW May 3, 2014). was to evaluate both diagnostic and prognostic impact of CTC detection in an
AIMS & METHODS: The aim of the present study was to assess factors affect- extended series of patients referred for a EUS-FNA for a pancreatic solid
ing the tissue acquisition and diagnostic rates for both needles. Consecutive tumour.
patients with pancreatic solid masses presenting to 8 referral centers for EUS- AIMS & METHODS: It was a single center study including all consecutive
FNA from April 2013 to Sept 2013 were prospectively recruited. All patients patients referred from 01/2011 to 07/2013 for a EUS-FNA procedure in a context
were randomized to EUS-FNA performed with either the novel 25G EchoTip of pancreatic solid mass. EUS-FNA was performed with a 22 gauge needle and
ProCoreTM (PrC) with a core trap and the standard 25G EchoTip UltraTM analysed by two pathologists. A 10 ml peripheral blood sample was collected in
(Ult). Only a single pass was performed. The whole specimen was inserted into a each patient before the EUS-FNA procedure. Samples were filtered using the
formalin bottle and processed for histological analysis. All tissue samples were ScreencellsCyto method, stained with Giemsa and analyzed by a cytologist
brought to one facility where experienced pathologists reviewed them. All sam- blinded to clinical data and FNA results. The CTC detection was positive accord-
ples were divided into three groups based on quality (rich, moderate, and poor ing to the presence of the following parameters: nuclear diameter 4 7m, aniso-
cellularity). The tissue acquisition and diagnostic rates were assessed for different cytosis, membrane irregularities, presence of a large nucleolus.
access routes and compared between the needles. Also, the diagnostic rates in RESULTS: A total of 69 patients were included. Amon them, 57 (83%) have a
three groups with different sample quality were compared. confirmed pancreatic tumours corresponding to 47 primitive adenocarcinoma, 4
RESULTS: A total of 214 patients were enrolled with 106 patients in the PrC and others primitive tumours and 6 metastatic lesions. The sensitivity and the speci-
108 in the Ult. The tissue acquisition rate for histological analysis was signifi- ficity of EUS-FNA was 83% and 100%, respectively. CTC were positive in 36/69
cantly higher in the PrC than the Ult (90.6% vs. 79.6%; p0.025). The definite (52%) patients. The sensitivity and specificity of CTC was respectively 64.4%
histological diagnosis achieved by the PrC was significantly higher than the Ult and 73.3% in patients with pancreatic cancer and 64.1% and 81.8% in patients
(81.1% vs. 69.4%; p0.048). The samples of the PrC showed significantly super- with all types of cancer. The presence of CTC was significantly associated with
ior quality than the Ult (rich: moderate: poor 38: 29: 39cases in the PrC vs. 21: the diagnosis of cancer (p0.01) and with the presence of distant metastases
28: 59cases in the Ult; p0.003). In terms of tissue-sampling, the tissue acquisi- (p0.004). In contrast, tumour size, arterial involvement and CA19-9 serum
tion rate of the PrC (46/50 cases; 92.0%) was significantly higher than that of the level were not associated with CTC. The 18 months survival rate was significantly
Ult (33/43 cases; 76.7%) in transduodenal EUS-FNA (p0.04), although these lower in patients with positive CTC as compared to those without detectable
values did not differ significantly in transgastric EUS-FNA. Overall sensitivity, CTC (33 vs 44%, p0.03).
specificity, and accuracy in pathological diagnosis of malignancy were 100%, CONCLUSION: Ours results highlighted that liquid biopsy based on circulating
100%, and 100%, for rich group, 90%, 100%, and 92.5% for moderate group, tumour cells (CTC) detection may be a diagnostic and prognostic marker in
83%, 100%, and 84% for poor group respectively. The sensitivity and accuracy patients with pancreatic solid tumours.
were significantly higher in rich group than moderate group (p 0.027, p 0.028) REFERENCES
and significantly higher in rich group than poor group (p0.003, p0.002). Iwanicki-Caron I, Basile P, Toure E, et al. Am J Gastroenterol 2013; 108: 152-
CONCLUSION: The novel EUS-FNA 25G needle with a core trap by a single 155.
pass offers significantly better sample quality for histological diagnosis of solid Disclosure of Interest: None declared
pancreatic tumors compared with the 25G standard needle, especially in trans-
duodenal access. The high quality of EUS-FNA sample allows increasing accu-
racy for histological diagnosis. OP062 EUS AND MRI AS SCREENING TOOLS FOR PANCREATIC
Disclosure of Interest: None declared CANCER: A COMPARATIVE PROSPECTIVE BLINDED ANALYSIS
OF THEIR EFFECTIVENESS
I. Konings1,*, F. Harinck1, J.W. Poley1, N. Krak2, K. Biermann3, J. van Hooft4,
OP060 USEFULNESS OF CONTRAST-ENHANCED ENDOSCOPIC Y. Nio5, C. Aalfs6, A. van Rens7, C. van Eijck8, D. Gouma9, M. Dijkgraaf10,
ULTRASONOGRAPHY FOR DIFFERENTIAL DIAGNOSIS OF H. van Dullemen11, R. Sijmons12, P. Fockens4, M. Bruno1 on behalf of the Dutch
PANCEATIC SOLID LESIONS: A SINGLE-CENTER PROSPECTIVE research group on pancreatic cancer surveillance in high-risk individuals
STUDY 1
Department of Gastroenterology and Hepatology, 2Department of Radiology,
Y. Yamashita1,*, K. Ueda1, H. Abe1, T. Tamura1, M. Itonaga1, H. Maeda1, 3
Department of Pathology, Erasmus MC University Medical Center Rotterdam,
T. Maekita1, M. Iguchi1, H. Tamai1, J. Kato1, M. Ichinose1 Rotterdam, 4Department of Gastroenterology and Hepatology, 5Department of
1
Second Department of Internal Medicine, Wakayama Medical University, Radiology, 6Department of Clinical Genetics, Academic Medical Center
Wakayama, Japan Amsterdam, 7Department of Clinical Genetics, The Netherlands Cancer Institute,
Contact E-mail Address: yasunobu@wakayama-med.ac.jp Antoni van Leeuwenhoek, Amsterdam, 8Department of surgery, Erasmus MC
University Medical Center Rotterdam, Rotterdam, 9Department of surgery,
INTRODUCTION: Recently, contrast-enhanced endoscopic ultrasonography 10
Clinical Research Unit, Academic Medical Center Amsterdam, Amsterdam,
(CE-EUS) has become available in the diagnosis of pancreatic lesions. 11
Department of Gastroenterology and Hepatology, 12Department of Clinical
AIMS & METHODS: The aim of this study was to investigate the accuracy of Genetics, University Medical Center Groningen, Groningen, Netherlands
CE-EUS in differentiating pancreatic ductal carcinoma from other lesions. Contact E-mail Address: i.konings@erasmusmc.nl
Between, February 2009 and July 2013, we prospectively evaluated 147 patients
with pancreatic solid lesions. After intravenous injection of a contrast agent INTRODUCTION: Previous studies suggest that endoscopic ultrasonography
(Sonazoid), CE-EUS was performed using a radial-type endoscope. (EUS) and magnetic resonance imaging (MRI) are promising tests to detect
Pancreatic solid lesions were classified into three vascular patterns (hypervas- asymptomatic, non-invasive precursor lesions and early stage pancreatic cancer
cular, isovascular, and hypovascular) on the basis of CE-EUS imaging, and (PC) in high-risk individuals (HRI). However, most studies were not performed
these patterns were compared to the histological diagnosis. in a blinded fashion. Therefore, it is still unclear which screening technique is to
RESULTS: The lesions were diagnosed as ductal carcinoma (n109), acinor cell be preferred. We aimed to compare the effectiveness of EUS and MRI in a
carcinoma (n2), inflammatory mass (n11), neuroendocrine tumor (NET) prospective blinded fashion in their ability to detect clinical relevant lesions in
(n8), autoimmune pancreatitis (AIP) (n9), invasive intraductal papillary individuals at high risk for developing pancreatic cancer.
mucinous neoplasm (IPMN) (n5), metastatic lesion (n2; lung cancer 1, mel- AIMS & METHODS: In the interim-analysis of this ongoing Dutch multicenter
anoma 1) or intraductal tubular tumor (ITT) (n1) by operation, EUS-FNA, prospective study, the results of 139 asymptomatic HRI undergoing first time
biopsy of liver metastasis, or international consensus diagnostic criteria for AIP. screening by EUS and MRI are described. HRI (410% life time risk of PC) were
104 of 109 ductal carcinomas were hypovascular patterns (95%). 8 of 9 AIPs defined as (1) mutation carriers of pancreatic cancer prone gene mutations and
A22 United European Gastroenterology Journal 2(5S)
(2) first-degree relatives of patients with familial pancreatic cancer. Clinical rele- OP064 DETECTION OF KRAS GENE MUTATION BY LIQUID BIOPSY
vant lesions included all solid lesion, MB-IPMNs, and all cystic lesions 10mm IN PATIENTS WITH PANCREATIC CANCER
and/or with malignant features. Results were compared in a blinded, independent H. KINUGASA1,*, K. NOUSO1, K. MIYAHARA1, Y. MORIMOTO1, C.
fashion. DOI1, K. TSUTSUMI1, H. KATO1, H. OKADA1, K. YAMAMOTO1
RESULTS: Clinical relevant lesions were detected by either EUS and/or MRI in 1
GASTROENTEROLOGY, OKAYAMA UNIVERSITY, OKAYAMA, Japan
9 out of 139 HRI (6%). Within these 9 HRI, a total of 11 clinical relevant lesions Contact E-mail Address: gyacy14@gmail.com
were detected: 2 solid lesions and 9 cysts 10 mm. Both solid lesions were
detected by EUS only, one 11 mm and one 7 mm lesion, which, after resection, INTRODUCTION: Circulating nucleic acids in plasma or serum have been
proved to be a stage I adenocarcinoma and multifocal PanIN-2 lesions. Of the 10 considered to be a candidate for noninvasive cancer diagnosis which is called
cysts 10 mm, 6 were detected by both EUS and MRI and 3 were detected by liquid biopsy. However, conventional mutation detection assays have not been
MRI only. There was a slight agreement between EUS and MRI for the detection sufficiently sensitive, specific, nor quantitative for the clinical use, because the
of clinical relevant lesions with a Kappa-value of -0.279 (55% agreement) and a number of circulating tumor cells and serum free DNA with somatic mutations
good agreement between EUS and MRI for the location (Kappa 1.000, agree- are very low compared to those of wild type. Newly developed technologies on
ment 100%) and size of detected lesions (Spearmans rho 0.638). digital PCR such as droplet digital PCR (ddPCR) and next generation sequence
CONCLUSION: EUS and/or MRI showed clinical relevant pancreatic lesions in (NGS) have provided new insight to this area. The methods dramatically
6% of high risk individuals. There was a slight agreement between EUS and MRI improve the detection rate of rare mutations and are able to quantify the
on detection of lesions was, however, on location and size a good to perfect mutant fraction among normal DNA molecules.
agreement. EUS and MRI seem rather complementary of each other than corre- AIMS & METHODS: This study was designed to estimate the clinical utilities of
sponding: contrary to EUS, MRI proved very sensitive for cystic lesions, how- genetic analysis for circulating DNA in serum with pancreatic cancer by droplet
ever, MRI might have some important limitations with regard to the timely digital PCR (ddPCR) (QX200, Biorad). We compared KRAS mutation detected
detection of (small) solid lesions. in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy tissue
Disclosure of Interest: None declared DNA and in circulating serum DNA in 75 patients with pancreatic cancer
admitted in our institute between January 2008 and December 2010. Codon12
KRAS mutations were examined by ddPCR to detect circulating serum DNA
OP063 NEEDLE BASED CONFOCAL LASER ENDOMICROSCOPY with rare mutations and compared with survival.
(NCLE) FOR THE DIAGNOSIS OF PANCREATIC MASSES: RESULTS: Median age of the patients were 66 years old. Two patients, 5
CORRELATION BETWEEN PCLE AND HISTOLOGICAL CRITERIA patients, and 68 patients were diagnosed as stage I/II, III and stage IV, respec-
(CONTACT STUDY) tively. KRAS mutations were detected in 74.7% (56/75) of the EUS-FNA tissue
M. Giovannini1,*, F. Caillol1, D. Lucidarme2, B. Pujol3, F. Poizat1, G. Monges1, samples. The frequencies of the mutations at GTT, GAT, CGT, GCT, AGT and
B. Filoche2, A., I. Lemaistre4, B. Napoleon3 TGT in codon12 were 28/56 (50%), 22/56 (39.3%), 6/56 (10.7%), 0/56 (0%), 0/56
1
Institut Paoli Calmettes, Marseille, 2GHICL, Lille, 3Hopital Jean Mermoz, (0%) and 0/56 (0%), respectively. On the other hand, the rate of KRAS muta-
4
Centre Leon Berard, Lyon, France tions in circulating serum DNA was 68% (51/75). The mutations at GTT, GAT
Contact E-mail Address: giovanninim@wanadoo.fr and CGT in codon12 were 30/51 (58.8%), 29/51 (56.8%) and 4/51 (7.8%),
respectively. Although the mutations detected in EUS-FNA samples were not
INTRODUCTION: Needle-based Confocal Laser Endomicroscopy (nCLE) is an completely matched to those in serum DNA, the frequencies of mutations were
imaging technique, which enables microscopic observation of solid organs, in vivo very similar between them (N.S.). Interestingly 12/75 (16%) circulating DNA
and in real-time, during an EUS FNA procedure. The CONTACT study showed multiple mutations at GTT, GAT and/or CGT, whereas EUS-FNA
(Clinical evaluation Of NCLE in The lymph nodes Along with masses and revealed only one kind of KRAS mutation. Survival was not different by
Cystic Tumors of the pancreas) aims at building an image atlas, and define KRAS mutations at GTT, GAT, CGT, GCT, AGT and TGT in EUS-FNA
interpretation criteria for nCLE images in the pancreatic masses. tissue DNA, but it was shorter in patients with KRAS mutation at GTT com-
AIMS & METHODS: 3 centres in France (7 investigators) took part in this pared to others in circulating serum DNA analysis (P50.01).
prospective study. CONCLUSION: Analysis of circulating DNA in serum is a new useful procedure
34 patients with a pancreatic mass of unknown nature were included prospec- to detect genetic mutations in pancreatic cancer. This method is simple and
tively during the study (June 2012 to March 2013). There were 17 men, and 18 noninvasive, and may have great potential as a new strategy for the diagnosis
women, mean age 66 years, (range: 32-87 years old). The localization of the of pancreatic cancer as well as to predict patients survival. The findings in this
pancreatic masses was: head (17 cases), body (12 cases), tail (6 cases). Mean study warrant further verification in other populations.
size was 30mm (/- 9mm). The puncture of the mass was done in all cases Disclosure of Interest: None declared
with a 19G puncture needle with the nCLE probe preloaded. After examination
of the track of the puncture by nCLE, aspiration was done in the same track to
compare images and histological results. No complication occurred during the MONDAY, OCTOBER 20, 2014 14:0015:30
nCLE procedure or the puncture. A definitive histological diagnosis was CLINICAL AND MOLECULAR FACTORS IN OESOPHAGO-GASTRIC CANCER OUTCOMES
obtained in 30/34 patients: adenocarcinoma (21 cases), fibrous stroma adenocar- LOUNGE 5_____________________
cinoma (1 case), neuroendocrine tumor (4 cases), pseudopapillary tumor (1),
chronic pancreatitis (3 diagnosis confirmed by a one year follow-up)). OP065 SURVIVAL AFTER PATHOLOGIC COMPLETE RESPONSE IN
Preliminary characteristic descriptive criteria were previously described [1]. PATIENTS WITH CANCER OF THE ESOPHAGUS OR GASTRO-
To go further, nCLE sequences were re-visualized by two gastro-enterologists ESOPHAGEAL JUNCTION
and two pathologists to compare, for each type of lesion, their findings to the S. Lagarde1, M. Anderegg1,*, W. Borstlap1, S. Gisbertz1, S. Meijer2, M. Hulshof3,
pathology specimen. J. Bergman4, H. van Laarhoven5, M. van Berge Henegouwen1
RESULTS: During this review, normal pancreas shows an aspect of coffee beans 1
Surgery, 2Pathology, 3Radiation Oncology, 4Gastroenterology, 5Medical
corresponding to the histological structure of acinis. Oncology, Academic Medical Center, Amsterdam, Netherlands
Adenocarcinomas showed dark cells aggregates with pseudo-glandular aspects Contact E-mail Address: s.m.lagarde@amc.uva.nl
and straight hyperdense elements more or less thick. These criteria correlate with
the histological structure of those tumors which are characterized by tumoral INTRODUCTION: The preferred curative strategy for esophageal cancer
glands, surrounded by fibrosis in case of fibrous stroma tumor. patients with locally advanced tumors, but without distant metastases consists
Neuroendocrine tumors showed a dense network of small vessels on a dark of esophagectomy with preceding chemo(radio)therapy (CRT). In 10-40% of
background, which fits with the histological structure based on cord of cells patients who are neoadjuvantly treated, there is absence of viable tumor at the
surrounded by vessels and by fibrosis in case of fibrosis area. time of surgery (pathologic complete response (pCR)). The aim of the present
Chronic pancreatitis showed residual acinis, which corresponds to the pancreatic study was to define the outcome of patients with a pCR and identify predictive
regression. factors for survival in this group.
CONCLUSION: This preliminary classification of nCLE images obtained in AIMS & METHODS: Between March 1994 and September 2013 all consecutive
pancreatic masses could help in the differentiation of adenocarcinomas and neu- patients with cancer of the esophagus or gastroesophageal junction who under-
roendocrine tumors, and between malignant tumors from normal pancreatic went esophageal resection after neoadjuvant chemo (radio) therapy were
tissue. nCLE could therefore facilitate the diagnosis of these lesions, by bringing included in the present study. Multivariate Cox regression analysis was carried
in vivo microscopic information, in real-time. out to identify independent prognostic factors.
REFERENCES RESULTS: Of the 463 included patients, 86 (19%) patients had a pCR
[1] Giovannini M. Needle-based confocal laser endomicroscopy for the diagnosis (pyT0N0M0R0) (54 men, 32 women, median age: 63yrs (range 33-82 years)).
of pancreatic masses: preliminary criteria (CONTACT study). Oral presentation 48 (56%) patients had an adenocarcinoma. Eight (9%) patients underwent
UEGW 2013 (OP 205). neoadjuvant chemotherapy and 78 (91%) underwent neoadjuvant chemoradia-
Disclosure of Interest: None declared tion therapy. During follow-up, 25 (29%) patients developed recurrent disease.
Nineteen (76%) patients developed haematogenous metastases, 6 developed lym-
phatic metastases (of which 3 patients with a distant lymphatic location). 5-year
disease free survival was 61%, 5-year overall survival was 58%. Cox regression
analysis revealed no prognostic factor for any of the tested variables (sex, age,
histologic subtype, tumor location, type of neoadjuvant therapy, cTNM stage).
CONCLUSION: Patients with a pathologic complete response have a relatively
good survival. However, one third of these patients developed recurrent disease.
Thus far it is unclear how these patients can be identified.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A23
OP066 TUMOR MICROENVIRONMENT IN ESOPHAGEAL moderate to strong p53 expression in 6 cases, and the sarcomatoid and epithelial
ADENOCARCINOMA: CD80 EXPRESSION PEAKS IN EARLY tumor components showed almost concordant p53 expression patterns and inten-
STAGES, IT IS ENHANCED BY NEOADJUVANT THERAPY AND IT sities, except one case that had mutations only in sarcomatous components. Of
IS AN ACCURATE PREDICTOR OF SURVIVAL these 6 cases, 4 cases harbored TP53 mutations.
M. Scarpa1, A. Kotsafti1,*, M. Scarpa1, M. Cagol1, R. Alfieri1, E. Pinto1, CONCLUSION: We found that ZEB1 and Twist were significantly widely
I. Castagliuolo2, C. Castoro1 expressed in the sarcomatous component, and the expression of E-cadherin in
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), 2Dept the sarcomatous area was lost. We also detected identical TP53 mutation pat-
Molecular Medicine, University of Padova, Padova, Italy terns and nuclear p53 immunohistochemical staining in both carcinomatous and
sarcomatous components. These findings suggest that this uncommon tumor has
INTRODUCTION: Esophageal adenocarcinoma (EAC) is an increasingly a monoclonal origin and support the hypothesis that EMT may play an impor-
common cancer with a poor prognosis. EAC microenvironment is characterized tant role in the pathogenesis of carcinosarcoma of the esophagus, mainly through
by lack of cytokines with anti-cancer effect and by high expression of immuno- ZEB1 and Twist expression.
suppressive factors. The aim of the study is to characterize the antigen presenting REFERENCES
cells (APC) and lymphocyte function in EAC investigating their relationship with 1) Peinado H, Olmeda D and Cano A. Snail, ZEB and bHLH factors in tumor
stage, response to neoadjuvant therapy and prognosis. progression: an alliance against the epithelial phenotype? Nat Rev 2007; 7: 415-
AIMS & METHODS: Mucosa samples from cancer and from healthy esophagus 428.
were obtained during esophagectomy from 64 patients affected by EAC. Frozen Disclosure of Interest: None declared
samples were analysed with Real Time qPCR for costimulatory molecules (Cd80,
Cd86), and lymphocytes activation (Cd38, Cd69) genes expression.
Immunohistochemistry for CD8 and NK cells cytolytic activity (CD107a) of OP068 THE THERAPEUTIC EFFECT OF IRREVERSIBLE
tumor infiltrating lymphocytes and for CD80 was performed. Flow cytometry ELECTROPORATION ACCORDING TO TISSUE PROPERTIES OF
for epithelial cells (CytokeratineCd80 and CytokeratineHLA-ABC) acting UPPER GASTROINTESTINAL TRACT: GENE EXPRESSION
as APC and activated (CD8Cd28 and CD8CD38) tumor infiltrating lym- SIGNATURE ANALYSIS
phocyte (TIL) was performed. Non parametrical statistics, survival analysis and H.S. Choi1,*, J.M. Lee1, S.H. Kim1, S.J. Nam1, E.S. Kim1, B. Keum1, Y.T. Jeen1,
ROC curve analysis were used. H.S. Lee1, H.J. Chun1, C.D. Kim1, H.B. Kim1
RESULTS: In normal mucosa a lower level of epithelial cells expressing HLA- 1
Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic
ABC compared to neoplastic tissue was observed (p0.02) but the rate of Of
CD80epithelial cells was similar (p0.61) and well as the rate of activated Contact E-mail Address: mdkorea@gmail.com
CD8 lymphocytes. In normal mucosa, a significant upregulation of Cd80
mRNA expression in patients who underwent neoadjuvant therapy compared INTRODUCTION: Irreversible electroporation (IRE) is a promising novel tech-
to that from patients who had no neoadjuvant therapy was observed (p0.02). nique for the ablation of tumors. IRE has an advantage over other ablation
Immunohistochemistry showed a high level of CD80 expression in normal techniques in its mechanism to remove undesired cells by affecting the cell mem-
mucosa of patients with stage I EAC compared to stage III and to yT0N0 brane without thermally destroying blood vessels, nerves and the surrounding
(p0.02). A similar peak was observed in CD38 mRNA levels (p0.02). tissues. This therapeutic modality has been considered to apply to Barretts
Patients with CD80 normal mucosa survived significantly longer than CD80- dysplasia or epithelial neoplasm of upper gastrointestinal tract instead of pre-
patients (p0.02) while the stage distribution of the two groups was equivalent vious radiofrequency ablation. Recently, we have validated the effectiveness of
(p0.69). CD80 expression in normal mucosa had a great accuracy in predicting IRE tissue ablation on stomach, but there was no study about treatment effect of
cancer-related deaths (AUC0.87 (95% CI0,68-0,96): p0.001). IRE according to tissue property in upper gastrointestinal tract. Our purpose was
CONCLUSION: In EAC, tumor cells expressed more HLA-ABC but their CD80 to study effectiveness of IRE according to tissue properties in rat stomach.
expression was similar to normal tissue levels confirming an impaired APC func- AIMS & METHODS: The Sprague-Dawley rats were used throughout this
tion in cancer tissue. Neoadjuvant therapy seemed to induce a high expression of study. IRE ablation was applied in upper stomach (squamous cell epithelium)
CD80 in healthy mucosa suggesting an APC activation. CD80 expression was and lower stomach (columnar cell epithelium) with same energy parameters. The
highest in stage-1 EAC and this peak expression corresponded to a peak in energy delivered for each ablation was 50/100 pulses of 1KV/cm 3KV/cm. All
lymphocyte activation. Finally, CD80 expression in normal mucosa resulted an samples for histologic analysis and tunnel assay were got at 0hrs, 10hrs, 24hrs
accurate predictor of postoperative survival suggesting its possible role as a and 72hrs after IRE. And we used DNA microarrays to measure the expression
biomarker in EAC management. levels of large numbers of genes in rat stomach according to different electrical
Disclosure of Interest: None declared energy. And we measured several apoptotic gene expression using real time RT-
PCR.
RESULTS: All animals survived for their designated times. H-E staining showed
OP067 TRANSCRIPTIONAL FACTORS FOR EPITHELIAL- extensive cell death area, which were proved by a pyknotic nucleus and eosino-
MESENCHYMAL TRANSITION ARE ASSOCIATED WITH philic cytoplasm near absence of cell at 10 hours after IRE ablation in upper
PATHOGENESIS OF CARCINOSARCOMA OF THE ESOPHAGUS: (squamous cell epithelium) and lower (columnar cell epithelium) gastric tissue.
WITH EVIDENCE OF MONOCLONAL ORIGIN BY TP53 We confirmed apoptotic cell death by Tunnel assay. The number of significantly
MUTATIONAL ANALYSIS up-regulated apoptotic genes was higher in 2KV, 100 pulse and 10hr than that of
T. Nakazawa1,*, H. Ikota1, S. Nobusawa1, H. Yokoo1 other electrical energy groups. The significantly up-regulated genes related to
1
Department of Human Pathology, Gunma University Graduate School of apoptosis after IRE ablation in all IRE setting were s100a8/9, Ccl2, Timp1.
Medicine, Maebashi, Japan Aif1, Lcn2, hspb1 genes, but caspase-related genes were down-regulated in all
Contact E-mail Address: ntakuro3@yahoo.co.jp condition.
CONCLUSION: This study showed that IRE ablated stomach tissue through
INTRODUCTION: Carcinosarcoma of the esophagus is a rare malignant neo- cellular apoptosis. And the degree of apoptosis after IRE ablation was tissue and
plasm composed of both carcinomatous and sarcomatous elements. The histo- electric energy specific in gastrointestinal tract. This study suggests the potenti-
genesis of sarcomatous and carcinomatous components of the tumor has not ality of IRE application in the treatment of not only gastric neoplasm but also
been elucidated. Epithelial-mesenchymal transition (EMT) is the conversion of esophageal neoplasm including dysplasia of Barretts esophagus without
cells with an epithelial phenotype into cells with a highly motile fibroblastoid or metastasis.
mesenchymal phenotype1. It is unclear whether EMT is involved in sarcomatous Disclosure of Interest: None declared
differentiation in carcinosarcoma of the esophagus.
AIMS & METHODS: We carried out immunohistochemistry for Slug, Twist,
ZEB1 and ZEB2, genes associated with EMT1, in 14 cases of carcinosarcoma of OP069 THE RELEVANCE OF THE LOCATION OF INVOLVED NODES
the esophagus to assess whether there is evidence of expression of these genes. We IN PATIENTS WITH CANCER OF THE DISTAL ESOPHAGUS OR
also performed immunohistochemical analysis for E-cadherin, whose loss of GASTRO-ESOPHAGEAL JUNCTION
expression is considered as the key step of EMT1. The staining of Slug, Twist, S. Lagarde1, M. Anderegg1,*, S. Gisbertz1, S. Meijer2, M. Hulshof3, J. Bergman4,
ZEB1, ZEB2 and E-cadherin was scored as follows: -, 0% of positive cells; , 1- H. van Laarhoven5, M. van Berge Henegouwen1
10%; , 11-50%; , 51-80%; , 480%. To verify the neoplastic 1
Surgery, 2Pathology, 3Radiation Oncology, 4Gastroenterology, 5Medical
nature of sarcomatous components, we examined monoclonality between carci- Oncology, Academic Medical Center, Amsterdam, Netherlands
nomatous and sarcomatous components comparing TP53 mutation status and Contact E-mail Address: s.m.lagarde@amc.uva.nl
p53 expression of both areas by DNA sequencing and p53 immunohistochem-
istry, respectively. INTRODUCTION: Truncal node metastases as well as lymphatic dissemination
RESULTS: Nuclear ZEB1 was significantly more widely expressed in the sarco- in the proximal field (subcarinal, paratracheal and aortopulmonary window
matous component (P 5 0.0001). Twelve cases showed ZEB1 expression in 4 lymph nodes) after neoadjuvant chemoradiation therapy does not alter the
80% neoplastic cells in the sarcomatous component. In contrast, neoplastic cells TNM classification. The incidence and impact of these relatively distant lymph
in carcinomatous components were negative in these 12 cases. Nuclear Twist was node metastases on long-term survival remains unclear. Therefore the aim of the
also significantly more widely expressed in the sarcomatous component (P present study is to identify the incidence and prognostic significance of the loca-
0.0256). Membranous E-cadherin was significantly more widely expressed in tion of lymph node metastasis in patients who underwent neoadjuvant chemor-
the carcinomatous component in all cases (P 5 0.001), and neoplastic cells in adiation therapy followed by a transthoracic esophagectomy (TTE).
the sarcomatous component were largely negative. Nuclear Slug and ZEB2 AIMS & METHODS: Between March 1994 and September 2013 a total of 286
expression showed no significant difference between carcinomatous and sarco- consecutive patients with cancer of the mid-to-distal esophagus or gastroesopha-
matous components (P 0.1379, P 0.1292, respectively). TP53 mutation geal junction (GEJ) who underwent potentially curative esophageal resection
analysis was carried out in 13 cases. Seven cases had mutations in both carcino- after neoadjuvant chemoradiation therapy were included.
matous and sarcomatous components and the mutations patterns were identical. RESULTS: The majority of patients was male (219 patients, 76.6%) and had an
One case had mutation only in sarcomatous components. p53 immunohisto- adenocarcinoma (208 patients, 72.7%). The tumor was located in the mid-eso-
chemical study was carried out for all 14 cases. Immunohistochemistry detected phagus in 53 (18.5%), in the distal esophagus in 210 (73.4%) and at the GEJ /
A24 United European Gastroenterology Journal 2(5S)
cardia in 23 (8.0%) patients. 279 (97.6%) patients underwent a radical (R0) Methods: 17 non-diabetic, morbidly obese subjects (5M:12F; 45 3yrs, BMI: 48
resection. 112 (39.2%) patients had a complete or near complete pathologic 4kg/m2) and 11 lean controls (10M:1F; 44 6yrs, BMI: 25 1kg/m2) under-
response (tumor regression grade 1 or 2). 110 (38.5%) patients had nodal metas- went endoscopic duodenal biopsies immediately prior to intraduodenal (ID)
tases in the marked resection specimen. 63 (22.0%) patients were classified as N1, glucose infusion (30g glucose over 30 min, with 3g 3-O-methylglucose (3-
33 (11.5%) patients as N2 and 14 (4.8%) patients as N3. Of the patients with OMG) to assess glucose absorption). Blood glucose and plasma concentrations
tumorpositive lymph nodes, 40 (36.4%) patients had metastases localized in of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like
locoregional nodes, 35 (31.8%) patients had localisation of metastases in at peptide-1 (GLP-1), insulin, and glucagon were measured over 270 min. Absolute
least one truncal node, 14 (12.7%) patients had positive nodes in the proximal expression of duodenal SGLT-1, GLUT2 and STR transcripts was quantified by
field and 5 (4.5%) patients had positive truncal nodes as well as positive proximal PCR.
lymph nodes. Median disease free-survival was 90.3 months for N0 patients, 65.7 RESULTS: The rise in plasma 3-OMG (P50.001) and blood glucose
months for patients with nodal metastases limited to locoregional nodes, 18.8 (P50.0001) were greater in obese than lean subjects. Plasma 3-OMG was directly
months for patients with truncal nodes, 15.4 months for patients with lymph correlated with blood glucose (r0.78, P50.01). After ID glucose, plasma GIP
node in the proximal field and 10.1 months if nodes were positive in both the (P50.001), glucagon (P50.001), and insulin (P50.001) were higher, but GLP-1
truncal and the proximal field. In multivariate analysis yN stage as well as loca- (P50.001) was less, in the obese than in the lean. Expression of SGLT-1
tion of lymph nodes were independently associated with a worse survival. (P0.035), but not GLUT2 or T1R2, was higher in the obese than lean subjects,
CONCLUSION: The present study demonstrated that the location of positive and was related to peak plasma 3-OMG (r0.60, P0.01), GIP (r0.67,
nodes after neoadjuvant chemoradiation therapy harbors important prognostic P0.003) and insulin (r0.58, P0.02).
information. CONCLUSION: In morbid obesity, proximal intestine glucose absorption is
Disclosure of Interest: None declared accelerated and related to increased SGLT-1 expression, leading to an incretin
profile that promotes hyperinsulinemia and hyperglycemia. These findings are
consistent with the concept that accelerated glucose absorption in the proximal
OP070 ADIPOSE TISSUE PROMOTES PROLIFERATION, gut underlie the foregut theory of obesity and type 2 diabetes.
DIFFERENTIATION AND INVASION OF ESOPHAGEAL Disclosure of Interest: None declared
SQUAMOUS CELL CARCINOMA IN VITRO
A. Nakayama1,*, E. Takeshita1, N. Tsuruoka1, R. Shimoda1, T. Koyama2,
T. Noda3, H. Sakata1, R. Iwakiri1, K. Fujimoto1 OP072 IMPACT OF A 2-WEEK VERY LOW CALORIE DIET (VLCD) ON
1
Gastrointestinal Endoscopy, Saga university, Saga, 2Gastrointestinal Medicine, GLUCOSE SENSING, ABSORPTION, TRANSPORTERS, INCRETIN
Shimonoseki City Toyoura Hospital, Shimonoseki, 3Internal Medicine, Karatsu HORMONES AND GLYCEMIA IN MORBIDLY OBESE HUMANS
Red Cross Hospital, Karatsu, Japan N.Q. Nguyen1,*, T.L. Debreceni1, J.E. Bambrick1, B. Chia2, J.M. Wishart3,
Contact E-mail Address: sr20det14turbo@yahoo.co.jp G. Wittert3, C.K. Rayner1,3, M. Horowitz3, R.L. Young2,3
1
Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, 2Nerve-
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) develops Gut Laboratory, 3Discipline of Medicine, University of Adelaide, Adelaide,
within squamous epithelial layer, and progressively invades into submucosal to Australia
subadventitial layers. Given that abundant adipose tissue exists in the subadven- Contact E-mail Address: quocnam.nguyen@health.sa.gov.au
titia, adipose tissue seems critical for the progression of ESCC. However, their
interaction is unknown. INTRODUCTION: Glucose absorption is accelerated in the proximal
AIMS & METHODS: We aimed to address an interaction between ESCC and intestine of morbidly obese humans, which is associated with increased
adipose tissue in vitro. ESCC cells (well and poorly differentiated types, EC-GI- expression of sodium dependent glucose co-transporter 1 (SGLT1), an
10 and TE-9, respectively) were cultured on rat or human subcutaneous adipose altered incretin profile, hyperinsulinemia and hyperglycemia (Nguyen et al.
tissue-embedded or -nonembedded collagen gel. Culture assembly was analyzed DDW 2014).
by electron microscopy, immunohistochemistry, Western blotting, ELISA and AIMS & METHODS: This study aimed to examine the effects of energy restric-
small interfering RNA (siRNA) transfection, in terms of cell survival, growth, tion on glucose absorption, expression of intestinal glucose transporters and
differentiation and invasion. sweet taste receptors (STR), incretin hormone responses and glycemia in the
RESULTS: Adipose tissue promoted the expression of the growth markers, Ki- morbidly obese.
67 antigen and bromodeoxyuridine (at 24 h-labeling) in the cancer cell types, 14 morbidly obese subjects (BMI: 463kg/m2) were studied before and after a 2-
whereas it inhibited that of the apoptosis marker, cleaved caspase-3. Adipose week VLCD (750kcal/day). On each occasion, endoscopic duodenal biopsies
tissue promoted the basal and superficial expression of the differentiation mar- were collected before and after a 30-min duodenal glucose infusion (30g glucose
kers, p63 and involucrin, respectively, within the epithelial layer formed by with 3g 3-O-methylglucose (3-OMG)). Measurements of blood glucose, plasma
cancer cell types. Adipose tissue accelerated the invasion of cancer cell types 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like pep-
into the gel, together with increased expression of filamin A, laminin-5 and tide-1 (GLP-1), insulin, and absolute expression of SGLT-1, GLUT2 and STR
membrane type 1-matrix metalloproteinase (MT1-MMP), and with decreased (T1R2) transcripts obtained.
display of E-cadherin. Adipose tissue promoted the expression of mitogen-acti- RESULTS: Fasting expression of T1R2 (-5422%, P0.03), SGLT1 (-307%,
vated protein kinase (MAPK: pERK1/2) and phosphoinositide 3-kinase-AKT P0.004) and GLUT2 (-5015%, P0.008) were markedly reduced after 2
(PI3K-AKT: pAKT1/2/3, p4E-BP1 and pS6) pathways, and insulin-like growth weeks VLCD, which were associated with reductions in fasting blood glucose
factor-1 receptor (IGF-1R) in the cell types, while it decreased that of human (-0.50.1mmol/L, P0.02), insulin, GIP and GLP-1, body weight (-5.60.5kg,
epidermal growth factor receptor 2 (HER2). Cancer cell types in turn decreased P50.001), and HbA1c (-0.320.08%, P0.001). Although intra-duodenal glu-
IGF-1, adiponection, leptin and registin production in adipose tissue. IGF-1 (10 cose had no impact on T1R2, SGLT1 and GLUT2 expression prior to VLCD, it
nM) promoted the growth of cancer cell types, while IGF-1R inhibitor (picro- increased the expression of T1R2 (4530%, P0.03) and GLUT2 (5714%,
podophyllin, 1 mM) enhanced the apoptosis. Finally, IGF-1R siRNA-transfected P0.003) after 2-wk VLCD. The blood glucose (P0.002) and plasma insulin
EC-GI-10 cells did not replicated the adipose tissue-induced phenomena above. (P0.002) responses to intra-duodenal glucose were all reduced after VLCD,
CONCLUSION: The data suggest, first, that adipose tissue may influence the while plasma 3-OMG and GLP-1 concentrations were unchanged. The peak
progression of ESCC with the increased growth/invasion and the decreased plasma 3-OMG (at 60min), however, was higher after VLCD (0.570.04 vs.
apoptosis through MAPK, PI3K-AKT and IGF-1R up-regulation, although 0.510.04mmol/L; P0.05) and was associated with a small elevation of plasma
adipose tissue seems to induce the differentiation of the cancer cells; second, GIP (P0.03) at 60 to 90 min after glucose stimulation.
that adipose tissue may adversely affect the HER2-targeted therapy; and third, CONCLUSION: In morbid obesity, both fasting and glucose-stimulated expres-
that the cancer cells may affect adipokine production of adipose tissue. sion of intestinal STR and glucose transporters are modulated by short-term
Collectively, we conclude that adipose tissue may be involved in the progression VLCD. Further studies with inhibitors of STR and glucose transporters are
of ESCC under adipose tissue-cancer cell interaction. warranted to determine whether the changes in STR and GTs expression,
Disclosure of Interest: None declared rather than the associated weight loss, are responsible for the observed glycemic
and incretin responses.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
OBESITY AND THE GUT LOUNGE 6_____________________
OP073 EFFECTS OF VERTICAL SLEEVE GASTRECTOMY (VSG) AND
OP071 ACCELERATED INTESTINAL GLUCOSE ABSORPTION IN CALORIC RESTRICTION BY DIET ON GLUCOSE METABOLISM IN
MORBID OBESITY RELATIONSHIP TO GLUCOSE OBESE PATIENTS WITH TYPE 2 DIABETES
TRANSPORTERS, INCRETIN HORMONES AND GLYCAEMIA B.A. Aulinger1,*, K. Piotrowski1, K. Widynski1, J. Zugwurst1, T. To Viet1, J. De
N.Q. Nguyen1,*, T. DEBRECINI1, J. BAMBRICK1, C. RAYNER2, Heer1, B. Goke1, U. Brodl1, K.G. Parhofer1, J. Schirra1
M. HOROWITZ2, R. YOUNG2 1
Medizinische Klinik II, University of Munich, Munchen, Germany
1
GASTROENTEROLOGY, ROYAL ADELAIDE HOSPITAL, 2MEDICINE, Contact E-mail Address: benedikt.aulinger@med.uni-muenchen.de
UNIVERSITY OF ADELAIDE, ADELAIDE, Australia
Contact E-mail Address: QUOC.NGUYEN@HEALTH.SA.GOV.AU INTRODUCTION: Vertical sleeve gastrectomy (VSG) effectively induces weight
loss and ameliorates hyperglycemia making it a successful treatment option for
INTRODUCTION: Glucose absorption in the small intestine is mediated by obese diabetic patients. However, the exact mechanisms underlying its efficacy
sodium dependent glucose co-transporter 1 (SGLT-1) and glucose transporter- and a direct comparison with a dietary intervention to mimic these effects are
2 (GLUT2), and is potentially linked to sweet taste receptor (STR) signaling and elusive. Hence, we thought to compare the regulation of glucose metabolism
incretin hormone secretion. Both glucose absorption and expression of SGLT-1 before and after a hypolcaloric diet (HD) or VSG in morbidly obese patients
are increased in obese rats, but human data are lacking. with type 2 diabetes.
AIMS & METHODS: This study aimed to examine intestinal glucose absorption AIMS & METHODS: Obese diabetic subjects were studied before as well as 3
in morbidly obese humans, and its relationship to glycemia, incretin responses, months after VSG (N 9, BMI 54.2 kg/m2, HbA1c 7.0%) or a HD (14, 45.6 kg/m2,
and expression of SGLT-1, GLUT2, and STR. 6.7%). During each visit a hyperinsulinemic euglycemic clamp to determine
United European Gastroenterology Journal 2(5S) A25
insulin sensitivity as well as a hyperglycemic clamp 100 mg/dl above basal glucose (GI) tract including humans and are expressed by enteroendocrine cells (EECs).
was performed. After 120 min of stable hyperglycemia 50 ml of a liquid meal with Intraluminal bitter tastants actiate vagal afferent neurons, induce avoidance and
13C-acetate was consumed while constant hyperglycemia was maintained. This affect feeding behavior and gastric emptying. Bitter tastants also induce release of
allowed determining insulin in response to glucose during fasting as well as in a cholecystokinin (CCK) and glucagon like peptide 1 (GLP1) from EECs, peptides
postprandial state. Furthermore, postprandial changes in gut hormones, gastric that are involved in GI chemosensing. We have shown that T2R subtypes are
emptying and the incretin effect (greater insulin secretion in response to intestin- differentially regulated in the mouse GI tract by diet manipulation and that
ally delivered glucose over iv-glucose) were determined. Additionally, sensations T2R138 expression is upregulated by long-term high fat diet, which is known
of satiety, fullness, gastric distension and nausea were recorded by a visual ana- to alter the gut microflora and is associtated with chronic low grade
logue scale (VAS). inflammation.
RESULTS: Change in BMI, absolute weight loss and %4weight loss was sig- AIMS & METHODS: Test whether T2R38 expression is altered in the mucosa of
nificantly more pronounced in the VSG-group than after HD (18.91.0% vs. overweight or obese healthy subjects compared to lean subjects and to character-
8.80.5%, p50.001). While the relative reduction of fasting glucose was greater ize the cell types expressing T2R38 in human colonic mucosa.
in the VSG-group (15013 to 1008 mg/dl vs. 1326 to 1146 mg/dl, p50.05) Methods: Colonic mucosal biopsies were obtained during screening sigmoido-
absolute values did not differ 3 months after the intervention. Similarly, insulin scopy from 30 volunteers: 15 overweight to obese (OW/OB) (8 males and 7
resistance and insulin secretion in response to iv-glucose improved markedly in females; 20-55 year-old; mean BMI 320.7 kg/m2) and 15 normal weight
both cohorts but were not significantly different after diet or VSG. However, (NW) (7 males and 8 females; 22-55 year-old; mean BMI 200.5) subjects.
after the meal insulin secretion was significantly more pronounced (4.70.9 vs. Biopsies were processed for quantitative qRT-PCR using Taqman Gene expres-
2.20.2-fold increase over fasting, p40.01) in the VSG group than after diet. sion assays with hT2R38 and 18S RNA as the reference gene, and immunohis-
Furthermore, the incretin effect (717 vs. 486%, p50.05) was significantly tochemistry. For double immunolabeling, the following antibodies were used:
greater 3 months after VSG compared with diet alone. This was associated rabbit anti-T2R38 (1:2,000), goat anti-chromogranin (CgA, 1:600, a generalized
with significantly higher postprandial levels of incretin hormones, more rapid marker for EECs), mouse anti- GLP-1 (1:1,000), mouse anti-CCK (1:1,000), and
gastric emptying and greater satiety in the operated subjects. guinea pig anti-peptide YY (PYY, 1:600).
CONCLUSION: These results suggest that HD in the short term results in a RESULTS: The levels of hT2R38 mRNA in the mucosa of OW/OB subjects were
number of beneficial effects on glucose metabolism similar to VSG, particularly markedly increased compared to those in the mucosa of NW subjects (4.200.9
in the fasting state (insulin resistance, glucose stimulated insulin secretion, fasting vs. 1.680.5, respectively, P50.05). T2R38 immunoreactivity (-IR) was localized
glucose). However, in the postprandial state VSG mediates additional metabolic to EECs as shown by their labeling with CgA. T2R38-IR cells coexpressed CCK-,
effects that cannot be mimicked by caloric restriction per se. Particularly the GLP1- or PYY-IR. The number of T2R38/CgA cells in the OW/OB group was
faster rate of gastric emptying and the higher levels of anorexigenic gut hormones significantly increased compared to lean controls (124.515.9 vs. 55.888.0 in
as well as the more pronounced insulin response seem to be responsible for the 3.36 mm2, respectively) (P50.006). There was an increase in T2R38/GLP1 and
favorable and more durable effects of bariatric surgery compared to dietary T2R38/CCK cells in OW/OB vs. NW subjects (5114.2 vs. 24.63.9, and
interventions. 34.06.4 vs. 19.66.5, respectively) whereas there was no difference in the
Disclosure of Interest: None declared number of T2R38/PYY cells in OW/OB vs. NW subjects (8.62.1 vs. 9.24.8).
CONCLUSION: T2R38 upregulation observed in overweight / obese subjects
might be due to changes in luminal content including alteration of microbiome
OP074 IMPAIRED GLUCOSE REGULATION IN OBESE SUBJECTS: that has been associated with obesity. This is consistent with the proposal that
THE LINK TO HYPERINSULINEMIA IN OBESIY? T2R38 is activated by food-born toxins and quorum-sensing molecules released
A.C. Meyer-Gerspach1,*, D. Riva1, L. Cajacob1, R. Herzog1, T. Peters2, by bacteria to initiate a protective response, which could involve the release of
R. Peterli2, C. Beglinger1, B. Wolnerhanssen1 gut hormones such as GLP1, CCK and PYY.
1
University Hospital Basel, 2St. Claraspital, Basel, Switzerland Disclosure of Interest: None declared
OP084-LB7 EFFICACY AND TOLERABILITY OF LOW VOLUME OP086 EPITHELIAL IL-23R SIGNALING LICENSES PROTECTIVE IL-22
POLYETHYLENE GLYCOL PLUS ASCORBIC ACID VERSUS RESPONSES IN INTESTINAL INFLAMMATION
SODIUM PICOSULFATE MAGNESIUM CITRATE: A K. Aden1,2,*, A. Rehman1, R. Hasler1, S. Lipinski1, M. Paulsen1, A. Kaser3,
PROSPECTIVE RANDOMIZED TRIAL S. Schreiber2, P. Rosenstiel1
B. Choi1,*, K. Kim1, S. Seo1, J. Kang1, B. Yang1 1
Institut of clinical molecular biology, 2I. Medical Department, Kiel, Kiel
1
Kangdong sacred heart hospital, Seoul, Korea, Republic Of University, Kiel, Germany, 3Department of Medicine, Addenbrookes Hospital,
Contact E-mail Address: bygging@hanmail.net minsoksumin@hallym.or.kr University of Cambridge, Cambridge, United Kingdom
Contact E-mail Address: k.aden@ikmb.uni-kiel.de
INTRODUCTION: Colonoscopy is the standard method for the evaluation of
mucosa of large intestine. High quality bowel preparation is essential for improv- INTRODUCTION: The identification of the IL23R as a genetic risk factor in
ing patients compliance and the detection rate of colorectal lesions in screening inflammatory bowel disease (IBD) has highlighted the role of IL-23 signaling in
colonoscopy. Recently, a new Polyethylene glycol (PEG)-based solution has the intestinal immune response. However, the impact of IL-23 on the immune reg-
became available. It combines PEG with a high dose of ascorbic acid (PEG ulation is ambigious. Whereas IL-23 induced Th-17 polarization contributes to
Asc, Coolprep, Taejoon, Korea). Also, sodium picosulfate with magnesium pathogenesis of IBD5, IL-23 induced IL-22 in Thy-1 innate lymphoid cells is indis-
oxide and citric acid (MC-SP, Picolight, Pharmbio, Korea) is a commonly pensable in the innate immune response to bacterial pathogens and experimental
prescribed hyperosmolar bowel preparation in Korea. colitis. This study aimed to describe the role of the Il23R in the intestinal epithelium.
AIMS & METHODS: The aim of this study is to compare the efficacy, toler- AIMS & METHODS: Conditional knockout of the Il23R in the intestinal
ability, and safety of this new 2L PEG Asc with MC-SP. Patients were enrolled epithelium was established by crossing VillinCre mice with Il23Rfl/fl mice, result-
from the endoscopy unit at the Kangdong sacred heart hospital, Seoul, Korea, ing in IL23RIEC-KO or IL23Rfl.
between Feb 2014 and June 2014. Adult ambulatory outpatients scheduled for For chronic colitis induction, mice were supplied with 2% of DSS dissolved in
elective colonoscopy were randomized to receive 2L PEG Asc (Coolprep), or drinking water for 5 days followed by 5 days of regular drinking water with total
MC-SP (Picolight). Before colonoscopy, patients were asked to complete a 3 cycle repetitions.
questionnaire regarding the acceptability, the tolerability, and side effects of Diseased intestines were subjected to gene expression analysis was performed
the preparation. Six experienced endoscopists, who were blinded to the rando- using custom made TaqMan probes and post-mortem histopathological analysis.
mization and the study group of the patients, rated the quality of bowel cleansing Lumina faeces were subjected to pyrosequencing of bacterial DNA and
by using Ottawa bowel preparation scale immediately after colonoscopy. sequences with at least 97% similarity were clustered in to species level opera-
RESULTS: A total number of 223 consecutive individuals were randomly assigned tional taxonomical units (OTUs).
to receive either 2L PEG Asc solution (n109) or MC-SP solution (n114). Baseline RESULTS: Here we show that IL23R is expressed in intestinal epithelial cells
and demographic characteristics were not different between both groups. Comparing and profoundly affects the intestinal immune defense. IL23RIEC-KO mice produce
PEG Asc and MC-SP, there were no differences in overall quality of bowel cleansing less antimicrobial peptides, have a disturbed colonic microflora and succumb to
(p0.806). However, when dividing individual bowel segments, MC-SP was superior experimental colitis. IL23RIEC-KO intestinal lamina propria cells contain less
to the PEG Asc in right colon segment (p0.03). Side effects during preparation, immune cells and produce less IL-22 in response to IL-23 or Flagellin stimula-
such as nausea, vomiting, abdominal pain, abdominal bloating and dizziness, were less tion. Lastly, we could show, that IL-22 therapy fully restores epithelial immune
frequent in MC-SP group (p0.031). Overall satisfaction of patients was superior in defense in IL23RIEC-KO.
MC-SP group (p50.001) and more patients had an intention to do next colonoscopy CONCLUSION: These data contribute to the understanding of the IL-23 axis in
with same bowel preparation method in MC-SP group (p0.001). primary immune response and describes a so far unknown role of IL23R signal-
CONCLUSION: Our study suggest that MC-SP provided significantly better ing in the intestinal epithelium.
cleansing in the right colon, and showed better acceptability and tolerability Disclosure of Interest: None declared
profile to that achieved with 2L PEG Asc solution. However, for overall
quality of bowel cleansing, both solutions showed similar level of effectiveness.
REFERENCES
1) Moon W. Optimal and safe bowel preparation for colonoscopy. Clin Endosc
2013; 46: 219-223.
United European Gastroenterology Journal 2(5S) A31
MONDAY, OCTOBER 20, 2014 15:4517:15 CONCLUSION: This study demonstrates for the first time wide-spread NET
IMMUNOPATHOGENESIS OF PANCREATITIS AND HEPATITIS HALL formation in AP. We found that NET formation regulates local and remote
R_____________________ organ inflammation and damage in AP. These novel findings provide new
insights in the pathophysiology of pancreatitis and indicate that targeting
OP087 AUTOIMMUNE PANCREATITIS EXPLORING DISEASE NETs might be an effective way to ameliorate tissue damage severe AP.
PATHOPHYSIOLOGY AND NOVEL, STEROID SPARING Disclosure of Interest: None declared
THERAPEUTIC INTERVENTIONS
G.M. Seleznik1,*, T. Reding1, J. Browning2, S. Segerer3, M. Heikenwaelder4,
R. Graf1 OP089 EARLY INTRAACINAR EVENTS AND IMMUNE RESPONSE IN
1
Swiss HPB Center, Visceral & Transplantation Surgery, University Hospital ALCOHOLIC ACUTE PANCREATITIS IN HUMANS
Zurich, Zurich, Switzerland, 2Department of Microbiology, Boston University R. Talukdar1,*, A. Jakampudi2, R. Jangala2, P.U. Pelluri2, C. Ramji1, M. S2, G.,
School of Medicine, Boston, United States, 3Division of Nephrology, University V. Rao1, D.N. Reddy1
Hospital Zurich, Zurich, Switzerland, 4Institute of Virology, Technische 1
Asian Institute Of Gastroenterology, 2Asian Healthcare Foundation, Hyderabad,
Universitat MunchenHelmholtz Zentrum Munchen, Munich, Germany India
Contact E-mail Address: rup_talukdar@yahoo.com
INTRODUCTION: Autoimmune pancreatitis (AIP) is a recently identified, rare
form of chronic pancreatitis, which has become a new evolving field in gastro- INTRODUCTION: Acute pancreatitis (AP) continues to be a challenging pro-
enterology. Currently, the treatment options, especially the long-term manage- blem without specific solution. 20-25% of patients with AP develop severe dis-
ment for AIP are limited. The only therapy that has been established and ease. Systemic inflammatory response syndrome (SIRS) and associated
accepted so far is corticosteroids, but the relapse rate is significant (15-60%). multiorgan dysfunction (MODS) is responsible for early mortality. It is prudent
We previously demonstrated that acinar specific Lymphotoxin expression in mice to understand the early pathogenesis of AP and the associated immune
(Tg(Ela1-Lta, b)) induces autoimmunity with features reminiscent of human responses, so that effective focused treatment modalities can be developed.
AIP. This includes formation of tertiary lymphoid organs, increased serum Even though pathogenesis of AP has been studied extensively in murine experi-
IgGs, anti-nuclear antibodies and immune-complex glomerulonephritis. In this mental models, data are lacking for AP in humans.
model we have previously shown that in contrast to corticosteroids, which only AIMS & METHODS: In this study we evaluate the early intraacinar events and
diminished inflammation, inhibition of Lymphotoxin beta receptor signaling acinar-immune interactions in alcoholic AP in humans.
(LTR-Ig) also abrogated autoimmunity. Normal pancreatic tissues were obtained from samples of Whipples surgery for
AIMS & METHODS: The aim of the study is to investigate the effectiveness of symptomatic benign biliary and periampullary pathology and pancreatic resec-
LTR pathway inhibition compared to the depletion of specific subset of tion for pancreatic cystic lesions. Pancreatic slices and acini were prepared, trea-
immune cells (B-cells and CD4 T-cells), which are suggested to play a patho- ted with 50mM fatty acid ethyl esters/FAEE (alcohol metabolites) and incubated
logical role in AIP development. Therefore, Tg(Ela1-Lta, b) mice with estab- for different time intervals. Acinar injury was evaluated by trypsin and cathepsin
lished AIP were treated with anti-CD20 mAb (Rituximab), anti-CD4 mAb in B activation, H&E staining and transmission electron microscopy. McDonald &
order to deplete B- and CD4 T-cells respectively and with LTR-Ig fusion Ellis and Kawabata methods were used to evaluate for trypsin and cathepsin B
protein. Histology, autoantibody production, cytokine and chemokine expres- activity respectively. Subcellular fractionation was performed to evaluate intraa-
sion, TLO integrity and other organ involvement (in kidneys) were tested, and cinar redistribution of zymogen and lysosomal compartments. IHC and western
compared to LTR-Ig treatment. Furthermore, macrophage and T helper cell blotting was used to evaluate the type of cell injury. Flow cytometry was per-
polarization was evaluated upon different treatments. formed to evaluate cytokine release by stimulated acinar cells and peripheral
RESULTS: LTR-Ig and anti-CD20 treatment led to a significant decrease in blood mononuclear cells (PBMCs) exposed to conditioned medium from stimu-
autoantibody production, inflammatory cell infiltration in the pancreas and lated acinar cells.
reduced extrapancreatic manifestation in the kidneys. The molecular mechanism In order to validate our experimental findings, we evaluated cytokine expression
of this beneficial effect possibly involves the down regulation of Stat3 and non- from PBMCs isolated from patients with AP (n43) at different time points and
canonical NF-b activation. Additionally, in contrast to anti-CD20 and anti- studied the association with clinical severity.
CD4 treatments, blocking LTR-signaling reverted acinar cell proliferation RESULTS: FAEE induced acinar injury was evidenced by a 15- and 10-fold
and acinar-to-ductal metaplasia formation and also disrupted the formation of elevation of trypsin and cathepsin B activity within 30mins of exposure. This
TLOs. Anti-CD4 treatment resulted in reduced Th1 and Th2 polarization; how- was corroborated with histologic evidence of acinar injury. Subcellular fractiona-
ever this did not ameliorate AIP. tion demonstrated redistribution of cathepsin to zymogen-enriched compartment
CONCLUSION: In this unique genetic mouse model of AIP, we demonstrate after 30mins exposure. There was a time dependent secretion of predominantly
that therapy with LTR-Ig and anti-CD20 antibody is superior to CD4 T-cell IL-6 and IL-8 by the FAEE treated acini from 2hrs onwards which peaked at
depletion. With these targeted therapies we reveal novel anti-inflammatory and 18hrs (median values of 1052.18 pg/mL and 3933.99pg/mL respectively). A
anti-autoimmune mechanisms. Assessing numerous parameters associated with robust secretion of the cytokines IL-6, IL-8, IL-1b, IL-10 and TNF-a (median
AIP pathogenesis, LTR-Ig achieved the greatest improvements. Therefore, inhi- values of 13583.77 pg/mL, 1462.97 pg/mL, 4875.32 pg/mL, 1858 pg/mL and
bition of the LTR-signaling pathway could become an alternative or supple- 1121.71 pg/mL respectively) was observed from PBMCs exposed to conditioned
mentary approach for AIP treatment. media from FAEE treated acini. Interestingly, there was no secretion of IL-10
Disclosure of Interest: None declared and TNF-a by the FAEE treated acinar tissue.
PBMCs from patients with alcoholic AP showed a significant increase in IL-6
and IL-8 secretion from the first week to the second week compared to non-
OP088 NEUTROPHIL EXTRACELLULAR TRAPS TRIGGER TRYPSIN alcoholic AP. This was significantly associated with disease severity (persistent
ACTIVATION, PATHOLOGICAL INFLAMMATION AND TISSUE organ failure).
DAMAGE IN SEVERE ACUTE PANCREATITIS CONCLUSION: Alcoholic AP in humans is characterized by early autophagy
H. Throlacius1,*, H. Hartmen1, M. Merza1, M. Rahman1, R. Hwaiz1, S. Regner1 and redistribution of cathepsin B, which possibly causes intraacinar trypsinogen
1
Surgery, Lund University, Malmo, Sweden activation to active trypsin. There is also early secretion of pro-inflammatory
Contact E-mail Address: henrik.thorlacius@med.lu.se cytokines by the treated acini that causes activation of circulating monocytes to
further produce cytokines and initiate SIRS.
INTRODUCTION: Neutrophils play a pivotal role in local and systemic com- Disclosure of Interest: R. Talukdar Financial support for research from:
plications of acute pancreatitis (AP), but the mechanisms regulating neutrophil- Wellcome-DBT India Alliance, A. Jakampudi: None declared, R. Jangala:
induced tissue damage in the inflamed pancreas is not fully understood. Recently, None declared, P. Pelluri: None declared, C. Ramji: None declared, M. S:
neutrophil extracellular traps (NETs) have been demonstrated to contribute to None declared, G. Rao: None declared, D. Reddy: None declared
organ dysfunction in both infective and non-infective diseases. In the present
study, we investigated for the first time the potential role of NETs in AP.
AIMS & METHODS: AP was induced in male C57BL/6 mice by infusion of OP090 RESVERATROL IMPROVES THE PATHOGENESIS OF
taurocholate into the pancreatic duct. Extracellular DNA was stained by Sytox NONALCOHOLIC STEATOHEPATITIS THROUGH INHIBITION OF
green and NET formation was quantified by confocal microscopy and cell-free ENDOTOXIN-INDUCED LIVER INFLAMATION AND FIBROSIS
DNA in plasma. Pancreatic levels of chemokines and histone 3 and 4 as well as T. Kessoku1,1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, A. Nakajima1
cytokines and chemokines in plasma were determined by ELISA. Neutrophil 1
gastroenterology and hepatology, Yokohama city university, yokohama, Japan
expression of Mac-1 was determined by flow cytometry. To analyze the impact
of NET formation in AP, NET depletion was induced by DNAse I administra- INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in
tion. In separate experiments, signal transducer and activator of transcription-3 Asia Pacific region is close to 1224%, while in Western countries is about 20
(STAT-3) phophorylation and trypsin activation were analysed in isolated acinar 30% and NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrho-
cells exposed to NETs and histone 3 and 4. sis and hepatocellular carcinoma. In spite of its high prevalence, up till now here
RESULTS: Taurocholate challenge evoked formation of NET in the pancreas is no proven effective treatment for NAFLD. Although gut-derived endotoxin
and increased cell-free DNA in plasma. Formation of macrophage inflammatory (ET), such as lipopolysaccharide (LPS), plays a key role in the pathogenesis of
protein-2 (CXCL2), neutrophil infiltration and tissue damage in the inflamed nonalcoholic steatohepatitis (NASH), detailed mechanisms of this pathogenesis
pancreas and lung were significantly attenuated by DNAse I treatment. becomes clear. We previously reported that overexpression of CD14 via activa-
Moreover, DNAse I administration markedly reduced levels of blood amylase, tion of leptin-STAT3 signaling in Kupffer cells induced hyper-inflammatory
CXCL2, interleukin-6 and high-mobility groups protein 1 as well as macrophage- response to low-dose ET, resulting in progression from simple steatosis to stea-
1 antigen expression on circulating neutrophils in mice with pancreatitis. NETs tohepatitis with liver fibrosis. Therefore, we hypothesized that inhibition of
and histones triggered trypsin formation and activation of STAT-3 in isolated leptin-STAT3 signaling in Kupffer cells may lead to attenuate the progression
acinar cells. Pre-incubation of NETs with polysialic acid abolished NET-induced of steatohepatitis via inhibition of CD14 expression.
activation of trypsin in acinar cells, suggesting that histones are responsible for a AIMS & METHODS: The aim of this study was to investigate whether the
great part of NET-induced trypsin activation. resveratrol which is known to inhibit activation of STAT3, improves the patho-
genesis of steatosis or steatohepatitis in murine model. Eight-week-old male
A32 United European Gastroenterology Journal 2(5S)
C57BL/6J mice were randomly distributed into 3 groups of 10 animals each: a OP092 SIGNIFICANCE OF SELECTED BIOMARKERS OF
high fat diet group (HF), HF supplemented with 2mg/kg resveratrol daily INFLAMMATION, ANGIOGENESIS AND ADIPOKINES IN THE
(HFR2), and HF supplemented with 20mg/kg resveratrol daily (HFR20). After NON-INVASIVE ASSESSMENT OF PATIENTS WITH ALCOHOLIC
12 weeks of dietary treatment, the rats were euthanized and relevant tissues were LIVER DISEASE
prepared for subsequent analysis. In this study, E. coli-derived LPS (0.25 mg/kg) B. Kasztelan-Szczerbinska1,*, A. Surdacka2, M. Slomka1, J. Rolinski2,
was used. K. Celinski1, H. Cichoz_ -Lach1, M. Szczerbinski1
A) We investigated whether the resveratrol attenuates HFD-induced steatosis. 1
Dept. of Gastroenterology with Endoscopy Unit, 2Dept. of Clinical Immunology,
B) We investigated whether the resveratrol attenuates ET-induced liver damage Medical University of Lublin, Poland, Lublin, Poland
via inhibition of response to ET. Contact E-mail Address: beata.szczerbinska@op.pl
C) We investigated whether the resveratrol improves the pathogenesis of long-
term exposed ET-induced steatohepatitis with liver fibrosis. INTRODUCTION: Alcohol abuse is a major cause of liver disease in Europe.
RESULTS: Resveratrol prevented the high fatinduced steatosis assessed by The idea of using serum biomarkers for early risk stratification and decision
semiquantitative grading, which furthermore corresponded with a complete nor- making in patients with alcoholic liver disease (ALD) seems an attractive alter-
malization of the hepatic triglyceride content (P 5 .001), despite no change in native to invasive diagnostic methods (eg. liver biopsy, endoscopy) used in the
total body fat, and hepatic SREBP1c expression was significantly decreased as current clinical practice.
compared with HF. HFR showed significant inhibition of hepatic CD14 expres- AIMS & METHODS: Determination of serum profile of selected biomarkers of
sion through suppression of STAT3 activity in Kupffer cells, following inhibition three different processes showing synergism in the pathogenesis of ALD i.e.
of a single low-dose LPS-induced liver damage. Moreover, long-term low-dose inflammation, angiogenesis and adipose tissue secretion (adipokines). Two new
LPS-induced liver fibrosis in HFR is significantly decreased as compared with subsets of T helper cells: Th17 and Treg, vascular endothelial growth factor
HF. (VEGF), angiopoietin 1, 2 (Ang1, Ang2), as well as total adiponectin (Acrp30),
CONCLUSION: These data indicated that the resveratrol improves not only the leptin and resistin were investigated. 147 pts (40 females, 107 males) with ALD
pathogenesis of steatosis thorough inhibition of lipogenesis but also steatohepa- were prospectively recruited and compared with 30 healthy controls (HC). They
titis through inhibition of endotoxin-induced liver damage via suppression of were divided into subgroups based on their: 1. gender, 2. severity of liver dysfunc-
STAT3-CD14 signaling in Kupffer cells. The resveratrol may have application tion according to the Child-Turcotte-Pugh and MELD scores; and 3. the presence
for the treatment of NAFLD of ALD complications at the time of hospital admission (i.e. ascites, hepatic ence-
REFERENCES phalopathy, esophageal varices, cholestasis, renal dysfunction and death). In order
1) Imajo K, Fujita K, Yoneda M, et al. Hyperresponsivity to low-dose endotoxin to confirm alcohol misuse the AUDIT-C questionnaire was used. A FACSCalibur
during progression to nonalcoholic steatohepatitis is regulated by leptin- flow cytometer (Becton Dickinson, USA) with CellQuest software was used to
mediated signaling. Cell Metab 2012; 16:44-54. identify T cell phenotype. CD3CD4IL17 cells were considered Th17 and
Disclosure of Interest: None declared CD4CD25FOXP3 Tregs. They were expressed as the percentage of all
CD3CD4 and CD4CD25 lymphocytes, respectively. Serum levels of angio-
genic biomarkers and adipokines were assessed using immunoenzymatic ELISA
OP091 GUT-DERIVED LYMPHOCYTES MIGRATE TO THE LIVER IN A tests. Multivariable logistic regression was applied in order to select independent
MOUSE MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE predictors of advanced liver dysfunction and the disease complications.
Y. Hu1, H. Zhang2, J. Li1, X. Cong2, Y. Chen2, G. He2, Y. Chi3, Y. Liu1,* RESULTS: Twelve of 147 pts died within the 90-day follow up. The alteration of
1
Department of Gastroenterology, 2Peking University Hepatology Institute, Beijing the Th17/Treg balance was observed in the most severely ill patients. Frequency
Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking of Th17 cells was an independent predictor of mortality in the study group.
University Peoples Hospital, 3 Institute of Clinical Molecular Biology, Peking Significantly higher plasma concentrations of Ang2 and VEGF, as well as
University Peoples Hospital, Beijing, China Acrp30 and resistin in comparison with HC were found. Increased Ang2 con-
centrations turned out to be an independent predictor of severe liver dysfunction
INTRODUCTION: An intimate immunological relationship between the gut (MELD score 20) and the development of ascites, encephalopathy, renal dys-
and liver has been demonstrated, but the role of gut-derived lymphocytes in function, and death. Also Acrp30 concentrations revealed an independent asso-
the progression of non-alcoholic fatty liver disease (NAFLD) remains unknown. ciation with the severity of liver dysfunction and the development of ascites and
We investigated the migration of gut-derived lymphocytes to the liver in a mouse hepatic encephalopathy.
model of NAFLD. CONCLUSION: High frequency of Th17 cells, as well as Ang2 and Acrp30
AIMS & METHODS: The mice were fed a high-fat diet for 12 weeks to induce concentrations revealed the best individual predictive value for ALD complica-
NAFLD model. Control mice were fed a normal-fat diet. Lymphocytes from the tions. The predictive power of complex statistical models which included several
spleen, bone marrow, thymus and mesenteric lymph nodes (MLN) of NAFLD parameters from different pathways in the pathogenesis of ALD occurred to be
mice were intravenously injected into NAFLD and control mice for near-infrared superior to either biomarker alone.
scanning. The percent of the lymphocyte subsets were analysised by flow cyto- Disclosure of Interest: None declared
metry. The chemotactic index of MLN cells of NAFLD and control mice was
analyzed by chemotaxis assays.
RESULTS: The fraction of activated CD4T cell(CD4CD44highCD62low) in OP093 RESCUE FROM EXPERIMENTAL ALCOHOLIC
MLN was significantly increased in NAFLD mice. Meanwhile, the control STEATOHEPATITIS BY A PEPDUCIN-BASED BLOCKADE OF
memory CD4T cells and CD8T cells(CD4CD44highCD62Lhigh and INTERLEUKIN-8 RECEPTORS
CD8CD44highCD62Lhigh), B cells increased in liver of NAFLD mice. V. Wieser1, A. Kaser2, H. Tilg1, N.C. Kaneider2,*
Additionally, the fraction of CD4 effector T cells (Th1 and Th17) increased 1
Abteilung fur Innere Medizin 1, Medizinische Universitat Innsbruck, Innsbruck,
significantly in the liver, MLN and blood of NAFLD mice. The adoptive transfer Austria, 2Div. of Gastroenterology and Hepatology, Dept. of Medicine, University
model showed that MLN cells from the NAFLD donor mice predominately of Cambridge, Cambridge, United Kingdom
accumulated in the liver in both NAFLD and control recipient mice. Contact E-mail Address: nk428@cam.ac.uk
Compared to control recipient mice, NAFLD recipient mice accumulated
much more MLN cells from NAFLD donor mice in their livers. Whereas only INTRODUCTION: Alcoholic steatohepatitis (ASH), exhibiting short-term mor-
a few lymphocytes from the spleen, bone marrow and thymus of the NAFLD tality rates as high as 40%, is characterised by hepatic neutrophil infiltration and
donor mice migrated to the liver. Moreover, MLN cells from NAFLD mice peripheral blood neutrophilia. It is thought to evolve from an initial inflammatory
induced liver injury in both NAFLD and control recipient mice, as reflected response to end products of ethanol catabolism and ethanol-induced break-down of
by elevated levels of serum ALT and AST after adoptive transfer. After the the enteric barrier with consecutive bacteraemia and entotoxinaemia. Interleukin-8-
injection of MLN cells from NAFLD donor mice, the percent of activted induced signalling through CXCR1/2 G protein coupled receptors (GPCRs) is
CD4T cells, activated CD8T cells and B cells increased in liver. The CCL5 critical for the recruitment and activation of neutrophils at sites of inflammation.
mRNA expression increased significantly in liver of NAFLD mice. Meanwhile, We have previously shown that pepducins, short consciously designed lipopeptides,
the CCL5 receptor CCR3 expression increased in CD4T cell subsets, CD8T modulate GPCRs by interfering with the receptors activation of G-proteins.
cell subsets and CD19B cells in the MLN cells of NAFLD mice. Blocking the AIMS & METHODS: Pepducins were synthesised by standard fMOC and tested
CCL5 with the CCL5 antibody inhibited the migration of the MLN cells of in a murine model of ASH. Mice were fed a liquid high fat (Lieber DeCarli) diet
NAFLD mice migration to liver. for 5 weeks, followed by parenteral administration of endotoxin. Liver/body
CONCLUSION: Our study provides evidence that gut-derived lymphocytes weight ratio, histological hepatic inflammation, and neutrophil myeloperoxidase
from NAFLD mice have a strong propensity to migrate to the liver and were measured.
induce liver injury and that fatty liver promotes the migration of gut-derived RESULTS: We demonstrate that experimental ASH is driven by CXCR1/2-
lymphocytes. Meanwhile, the gut-derived lymphocytes promoted CD4T cells dependent activation of neutrophils. CXCR1/2-specific pepducins protected
and CD8T cells activation in liver of NAFLD mice. The propensity for the from histological inflammation, weight loss and mortality associated with experi-
migration of gut-derived lymphocytes to the liver was associated with the mental ASH. Importantly, pepducins were effective even when administration
mechanism of the upregulation of CCL5 in liver and CCL5 receptor CCR3 in was commenced late in established experimental ASH. Neutrophil infiltration
gut-derived lymphocytes. and lipid accumulation in hepatocytes were significantly reduced by CXCR1/2
Disclosure of Interest: None declared pepducin treatment. Hepatocyte cell lines were shown to secrete interleukin-8
upon ethanol stimulation, and CXCR1/2 pepducins blocked chemoattraction
of neutrophils toward hepatocyte supernatants.
CONCLUSION: Experimental ASH remarkably closely phenocopies human
ASH, which represents a major unmet therapeutic need. These data establish a
key role for CXCR1/2 signalling and hepatic neutrophil recruitment in the patho-
genesis of ASH. CXCR1/2 pepducins might therefore represent a pharmacolo-
gical approach that merits exploration in a clinical trial in ASH. Pepducins
directed against another GPCR are currently studied in a phase I clinical trial.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A33
MONDAY, OCTOBER 20, 2014 15:4517:15 laparoscopic observation. Subsequently, the sero-muscular layer was laparosco-
PROGRESS IN GASTRIC AND DUODENAL ENDOTHERAPY HALL pically dissected along the marking circumferentially using an ultrasonically acti-
N_____________________ vated device. After sero-muscular layer incision, submucosa-mucosal layer was
dissected along sero-muscular layer incision with ultrasonically activated device.
OP094 LONG TERM FOLLOW-UP OF UPPER GI NEOPLASIA The closure of the defect in the duodenal wall was performed by the laparoscopic
TREATED BY ENDOSCOPIC RESECTION hand-suturing technique.
C. Teixeira1, M. Maia1, R. Jobim1, N. Coelho1,*, L. Figueiredo1 RESULTS: 64 patients (50 males and 14 females, mean age 62.7) were treated by
1
END0SCOPY, FUGAST, Porto Alegre, Brazil EALFTR. In 2 patients, because 2 lesions were located quite closely, we resected
Contact E-mail Address: nelsoncoelho@urgegastro.com.br them at the same time. 37 lesions were located at the second portion, 24 at the
bulb and 5 at the third portion of the duodenum. En-bloc and R0 resection was
INTRODUCTION: Endoscopic mucosal resection (EMR), or mucosectomy achieved for 97.0 % (64/66), too. The mean resected lesion size was 12.0 mm, and
technique, developed by Japanese endoscopists consists of resecting flat and the mean resected specimen size was 26.0 mm. The mean procedure time was 136
polypoid neoplasms of the mucosa. Its a relatively simple technique and carries minutes. The mean length of hospital stay after EALFTR was 13.1 days.
a low morbidity. It represents an important advance for endoscopists in both Anastomotic leakage occurred in three patients and anastomotic stenosis
technical and cancer areas. Is based on the concept that endoscopy provides occurred in three patients postoperatively, but all cases recovered conservatively.
visualization and acess to the mucosa, the innermost lining of the gastrointestinal Histopathological examination confirmed that 31 were adenomas, 17 adenocar-
tract. EMR presents also the advantage of obtaining a complete specimen for cinomas, 13 neuroendcrine tumors and 5 hyperplastic polyps.
histologic analysis, allowing to know whether the resection has been complete CONCLUSION: EALFTR enables successful en bloc, R0 resection, and full-
laterally, in depth and the level of tumor invasion. Provides the opportunity to thickness excision was achieved with an adequate surgical margin in all patients
preserve organs anatomy and physiology avoiding surgery and long term hospi- without severe complications. We believe that in treatment of SDNs this method
tal stay. can be a feasible, safe, and minimally invasive treatment option for superficial
AIMS & METHODS: The aims of the study were to measure the success rate of nonampullary duodenum tumors.
achiving complete resection and the complication rate of EMR in a single center. Disclosure of Interest: None declared
A retrospective analysis was done among 137 EMRs procedures conducted in
our endoscopic department between December 1997 and March 2014. The pro-
cedure was done either with dual-channel gastroscope Fujinom and cap or band- OP096 HEMOSTATIC SECOND-LOOK ENDOSCOPY IS USEFUL FOR
ligation with regular scope. EUS was performed in the majority of patients with PREVENTING DELAYED BLEEDING AFTER ENDOSCOPIC
high frequence miniprobes or radial Fujinom System scope. In patients with SUBMUCOSAL DISSECTION (ESD) IN EARLY GASTRIC CANCERS
high-grade dysplasia (HGD) and intramucosal cancer who were treated by K. Nagao1,*, H. Noda1, N. Ogasawara1, Y. Hijikata1, S. Izawa1, Y. Kondo1,
EMR, careful follow-up and additional therapy to treat residual or recurrent Y. Ito1, A. Tanabe1, Y. Tamura1, M. Sasaki1, K. Kasugai1
cancer was done. 1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan
RESULTS: 81 of 137 patientes were men. The average age was 68 /- 9 Contact E-mail Address: nagao.kazuhiro.621@mail.aichi-med-u.ac.jp
years.EMR was done in outpatient basis and the patients were discharged after
4 hours in the recovering area. Twenty-five of 137 lesions were esophageal squa- INTRODUCTION: Endoscopic submucosal dissection (ESD) has been now
mous cell carcinoma (18.2%), nineteen HGD and esophageal adenocarcinoma standard therapy for early gastric cancers. Although safety of the ESD procedure
(13.8%), forty-eight gastric adenocarcinoma (35%), thirteen duodenal adenocar- has been substantiated, complications such as perforation and bleeding are still
cinoma (9.4%) and the remaining thirty-two (23%) benign lesions. Of the 137 serious problems. Second-look endoscopy for the purpose of hemostasis is rou-
patients treated by EMR during a mean follow-up of 49.8 months, only 6 tinely performed to prevent post-ESD bleeding in most hospitals, though there is
patients with HGD and intramucosal cancer presented recurrent lesions little solid evidence to support this practice. A few reports suggested that second-
(5.7%). 95.1% curative resection was achieved in patients with m1, m2 and look endoscopy after gastric ESD contributed little to preventing delayed bleed-
reaching m3 disease. En-bloc resection was possible initially in 91.2%. Minor ing. However, these results contradicted our experience. Hemostatic second-look
bleeding was present in 17 patients (12.4%), controlled endoscopically with endoscopy is considered to reduce delayed bleeding when it would be appropri-
clips. Prophylatic clips were used in 22 patients (16%). One large perforation ately performed according to Forrest classification. The aim of the present study
was treated by surgical repair. was to verify whether a second-look endoscopy after ESD is effective for the
CONCLUSION: EMR is well suited for superficial esophageal, gastric and duo- prevention of delayed bleeding and to investigate the clinicopathological features
denal cancer treatment with very little risk of complication and low recurrence of delayed bleeding after hemostatic second-look endoscopy to identify specific
rate, as shown in our long-term retrospective study. However in cases when lesions that may require third-look endoscopy.
lateral margins and depth of invasion of the specimen are not clear of neoplastic AIMS & METHODS: Subjects were 186 consecutive patients (142 males and44
changes (mainly in peace-meal resections), the patients should have careful females; mean age, 71.0 years) who underwent ESD for gastric cancers between
follow-up. January 2006 and December 2013. Properly preventative coagulation for all
REFERENCES exposed vessels on the artificial ulcer with hemostatic forceps was performed
1. Yamamoto H, Yube T, Isoda N, et al. A novel method of endoscopic mucosal routinely at the end of ESD procedure. The vessel types on artificial post-ESD
resection using using sodium hyaluronate. Gastrointestinal Endosc 1999; 50: ulcers were evaluated by Forrest classification at the next day after ESD. Ia, Ib or
251-256. IIa of Forrest classification were essentially required with endoscopic hemostasis.
2. Takekoshi T, Baba Y, Ota H, et al.Endoscopic mucosal resection of early On the other hand IIb or III of Forrest classification were not performed with
gastric carcinoma:results of a retrospective analysis of 308 cases. Endoscopy endoscopic hemostasis.
1994; 26: 352-358. RESULTS: Patients with hemodialysis significantly harbored Ia, Ib or IIa of
3. Lambert R. Endoscopic treatment of esophageal and gastric tumors. Forrest classification at second-look endoscopy. However, there were no signifi-
Endoscopy 1998; 30: 80-93. cant differences in patient-related factors (age, gender, and use of anticoagulants
4. Inoue H, Tani M, Nagai K, et al Treatment of esophageal and gastric tumors. and antiplatelet drugs) and tumor related factors (tumor location, histological
Endoscopy 199; 31: 47-55. type, depth, size of the resected specimen, and operation time) between Ia, Ib or
Disclosure of Interest: None declared IIa and IIb or III of Forrest classification. None of 136 patients with IIb or III of
Forrest classification at second-look endoscopy had delayed bleeding during
hospitalization. In 50 patients with Ia, Ib or IIa of Forrest classification at
OP095 FEASIBILITY AND SAFETY OF ENDOSCOPY-ASSISTED second-look endoscopy, there was only one patient (2%) with delayed bleeding
LAPAROSCOPIC FULL-THICKNESS RESECTION FOR which required hemostatic third-look endoscopy. The patient underwent hemo-
SUPERFICIAL DUODENAL NEOPLASMS dialysis and took an antiplatelet drug. The rate of bleeding after appropriately
Y. Minato1,*, K. Ohata1, M. Murakami2, K. Yamazaki2, M. Takita1, hemostatic second-look endoscopy was 0.5% (1 of 186 patients). The rate in our
Y. Matsuyama1, T. Tashima1, K. Nonaka1, N. Matsuhashi1 study was extremely low compared with previous reports in which second-look
1
Gastroenterology, NTT Medical Center Tokyo, 2Gastroenterological and General endoscopy was not performed.
Surgery, Showa University Hospital, Tokyo, Japan CONCLUSION: Appropriately hemostatic second-look endoscopy for early gas-
Contact E-mail Address: yoheiminato55925@gmail.com tric cancers removed by ESD was useful for preventing delayed bleeding. Precise
hemostasis based on Forrest classification at second-look endoscopy may exceed-
INTRODUCTION: Superficial duodenal neoplasms (SDNs) are a challenging ingly reduce delayed bleeding. Third-look endoscopy was not required when
target in the digestive tract. Endoscopic resection is technically difficult and appropriate hemostasis at second-look endoscopy was performed.
surgical approach is difficult to decide the borderline of the lesion precisely. Disclosure of Interest: None declared
We invent the new approach to remove SDNs that involves a combination of
endoscopic and laparascopic technics: endoscopy-assisted laparoscopic full-
thickness resection (EALFTR).
AIMS & METHODS: The aim of this study was to investigate the results of a
single center experience and assess the validity of EALFTR for SDNs. Between
January 2011 and March 2014, 64 patients with nonamupllary duodenal neo-
plasm without familial polyposis syndrome were included in this study. All cases
were assessed for their age, sex, location, en-bloc resection rate, R0 resection rate,
lesion size, sample size, procedure time, length of hospital stay after EALFTR,
complication, and histopathological report. EALFTR procedure: Under general
anesthesia, the duodenum was first mobilized laparoscopically under endoscopic
guidance. Then the tumor location was confirmed by endoscopy. The peripheral
margin was marked around the tumor endoscopically and each marking was
perforated intentionally using a needle knife in the coagulation mode under
A34 United European Gastroenterology Journal 2(5S)
OP097 ENDOSCOPIC TISSUE SHIELDING METHOD WITH cumulative incidence of MGC on surveillance endoscopy were 10.0% and 16.4%,
POLYGLYCOLIC ACID SHEETS AND FIBRIN GLUE DECREASES respectively. 296 MGCs in 215 patients were treated with endoscopic resection
THE RISK OF BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL (Upper/Middle/Lower62/125/109, Differentiated (D)-type/Undifferentiated
DISSECTION OF GASTRIC NEOPLASMS (UD)-type/Special/13/2, median tumor size 10 mm (1-50), intramucosa: M/
Y. Tsuji1,*, M. Fujishiro2, Y. Sakaguchi3, C. Minatsuki3, I. Asada-Hirayama3, minute submucosa (5500m): SM1/deeper submucosa (500m): SM2270/
K. Niimi4, S. Mochizuki3, S. Ono3, S. Kosdashima3, N. Yamamichi3, K. Koike3 15/11, ESD/strip biopsy294/2). En bloc resection, R0 resection and curative
1
Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, resection were 99.3% (294), 94.3% (279) and 88.8% (263), respectively. 183
The University of Tokyo, 2Department of Endoscopy and Endoscopic Surgery, patients were determined to have curative resection and 32 patients had non-
Graduate School of Medicine, 3Department of Gastroenterology, 4Center for curative resection. Of 183 patients with curative resection, one died of initial
Epidemiology and Preventive Medicine, Graduate School of Medicine, The EGC with local recurrence and distant metastasis (9.1 years after initial ESD)
University of Tokyo, Bunkyo-ku, Tokyo, Japan but none died of MGC. 14 of 32 patients with non-curative resection underwent
Contact E-mail Address: ytsuji-tky@umin.ac.jp additional surgery and 18 patients were followed up (the cause of non-curative
resection in 10 patients was only positive margin). Of 32 patients with non-
INTRODUCTION: Prevention of bleeding after endoscopic submucosal dissec- curative resection, one patient who underwent additional surgery and one who
tion (ESD) for gastric neoplasms is still an important problem, but there have was followed up died of MGC (2.7 and 4.6 years after initial ESD). 25 MGCs in
been no preventive measures other than proton pump inhibitor use and preven- 14 patients were treated surgically (Upper/Middle/Lower8/7/10, D-type/UD-
tive coagulation of visible vessels on the artificial ulcer after ESD. type17/8, median tumor size: 25.0 mm (1-108), M/SM1/SM2/advanced16/0/
AIMS & METHODS: We aimed to evaluate the efficacy and safety of the tissue 4/5). Two of 14 patients died of MGC (6.2 and 7.2 years after initial ESD). 3
shielding method with polyglycolic acid (PGA) sheets and fibrin glue for pre- patients with 3 clinically unresectable MGCs received palliative chemotherapy
venting bleeding after gastric ESD. This is a non-randomized historical con- and died of MGC (over 5 years after initial ESD). The remaining 10 lesions in 6
trolled study. We defined high-risk patients for post-ESD bleeding as follows: patients were observed without any intervention due to high age or co-morbidity
1) those who took antithrombotic drugs regularly; or 2) those who were expected but none died of MGC. 5-year and 10-year DFS in 238 patients with MGC was
to undergo large mucosal resection ( 40mm). We enrolled patients who were 99.2% and 92.5%, respectively. Both of 5-year and 10-year DFS in 1288 patients
scheduled to undergo gastric ESD and had above-mentioned risk factors from without MGC were 100%.
July 2013 as the study group (Group A). We placed PGA sheets on the mucosal CONCLUSION: Careful surveillance should be utilized for early detection of
defect and fixed with fibrin glue in the study group. Between January and July MGC not only for 5 years but also beyond 5 years after curative gastric ESD.
2013, before the first enrolment of a study patient, 126 gastric neoplasms in REFERENCES
101 consecutive patients were treated with ESD. From this cohort, we extracted 1) Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;
high-risk patients as the historical control group (Group B). We set the post-ESD 14: 113123.
bleeding rate as the primary endpoint to compare both groups. Disclosure of Interest: None declared
RESULTS: From July 2013 to February 2014, 45 ESD-induced ulcers in 41 high-
risk patients for bleeding were enrolled in the study group. In the historical
control group, 41 ESD-induced ulcers in 37 patients were extracted. The baseline OP099 INTERIM RESULTS OF A MULTI-CENTER, PROSPECTIVE,
characteristics were not significantly different between the two groups: sex CONTROLLED TRIAL OF THE DUODENAL-JEJUNAL BYPASS
(A: male 41/female 4, B: male 34/female 7; P 0.256); age (A: 73.6 7.5 yrs, LINER FOR THE TREATMENT OF TYPE 2 DIABETES IN OBESE
B: 74.8 7.0 yrs; P 0.482); antithrombotic drug use (A: 29 lesions, 66.4%, B: PATIENTS: ARE THERE ANY FACTORS PREDICTING A SUB-
23 lesions, 56.1%; P 0.429); Heparin bridging therapy (A: 7 lesions, 15.6%, B: OPTIMAL EFFECT?
3 lesions, 7.3%; P 0.319); and the diameter of resected specimens (A: 40.1 M. Benes1,*, T. Hucl1, P. Drastich1, J. Spicak1
12.4 mm, B: 43.9 15.1 mm; P 0.206). Neither intraoperative perforation or 1
Hepatology and Gastroenterology, IKEM, Prague, Czech Republic
delayed perforation occurred in the two groups. Post-ESD bleeding occurred at a
rate of 6.7% in the study group (3 lesions), and 22.0% in the historical control INTRODUCTION: The global increase in obesity incidence results in an increase
group (9 lesions). There was a significant difference in the post-ESD bleeding rate of type 2 diabetes mellitus (T2DM) incidence. Surgical treatment has proven to
between the two groups (P 0.041). In the study group, post-ESD bleeding be effective, however it carries a high risk of complications. The duodenal-jejunal
occurred only in heparin bridging therapy. In the study group, the procedural bypass liner (Endobarrier, GI Dynamics, DJBL) is an endoscopic implant that
time for applying PGA sheets and fibrin glue was 20.4 9.5 min. mimics the intestinal bypass portion of the Roux-en-Y gastric bypass. It results in
CONCLUSION: The endoscopic tissue shielding method with PGA sheets and weight loss and improvements in glucose control in obese patients with T2DM.
fibrin glue appears to be promising for the prevention of post-ESD bleeding. AIMS & METHODS: This is an interim report of an ongoing three years study.
Disclosure of Interest: Y. Tsuji: none, M. Fujishiro Financial support for research The aim of this prospective, controlled, multicentre study is to determine the
from: Astellas Pharmaceutical, Takeda Pharmaceutical, Zeria Pharmaceutical, effectiveness of DJBL and to identify clinical factors associated with a subopti-
Otsuka Pharmaceutical, Astrazeneca Pharmaceutical, Dainihon-Sumitomo mal outcome of DJBL.
Pharmaceutical, Taiho Pharmaceutical, Ajinomoto Pharmaceutical, and, Eisai RESULTS: Forty four subjects (24 with an implant, 20 controls) were included in
for his department outside the submitted work, Lecture fee(s) from: Olympus the study. The groups were comparable with respect to age, gender, BMI (mean
Medical Systems, HOYA Pentax, Eisai, MSD, Daiichi-Sankyo Pharmaceutical, 37.7 vs. 38.1 kg/m2), T2DM duration (7.2 vs. 8.3 years), HbA1c level (8.8 % vs
Astrazeneca Pharmaceutical, Aska Pharmaceutical, Taisho-Toyama 8.1 %) and T2DM treatment. In the stent group, all devices were successfully
Pharmaceutical, Otsuka Pharmaceutical, Zeria Pharmaceutical, Takeda implanted. Only three devices had to be explanted prior to the end of the 6
Pharmaceutical, Astellas Pharmaceutical, Seikagaku Corp., Johnson & months study period (bleeding, dislocation and need for ERCP because of cho-
Johnson, Ajinomoto Pharmaceutical, Amco, Novartis Pharmaceutical, Boston ledocholithiasis). The mean procedure time was 21.2 minutes for an implantation
Scientific, and, Boehringer-Ingelheim, outside the submitted work, Other: non- and 35.5 minutes for an explantation. At six months there was significantly
financial support from HOYA Pentax, Olympus Medical Systems, and, Fujifilm greater weight loss (27% vs. 9%) and significantly improved HbA1c % (2.3 vs.
for his department, Y. Sakaguchi: none, C. Minatsuki: none, I. Asada-Hirayama: 1.1) in the device group. T2DM medicinal treatment could be reduced in more
none, K. Niimi: none, S. Mochizuki: none, S. Ono: none, S. Kosdashima: none, device subjects than controls. There was no serious adverse event. Mild abdom-
N. Yamamichi: none, K. Koike: none inal pain and nausea after implantation were experienced by 75% of patients
during first 14 days after implantation, 40% of patients during the first month
and 11% of patients after one month. Lower initial BMI, distal position of the
OP098 LONG-TERM SURVEILLANCE AND TREATMENT OUTCOMES anchor and lower body height were identified as negative prognostic factors for
OF METACHRONOUS GASTRIC CANCER AFTER CURATIVE pain.
ENDOSCOPIC SUBMUCOSAL DISSECTION CONCLUSION: The DJBL is safe when implanted for 6 months, and results in
S. Abe1,*, I. Oda1, H. Suzuki1, S. Nonaka1, S. Yoshinaga1, M. Sekiguchi1, significant weight loss and HbA1c reduction. This suggests that this novel device
G. Mori1, H. Taniguchi2, S. Sekine2, H. Katai3, Y. Saito1 is a candidate for the primary therapy of morbid obesity and type 2 diabetes.
1
Endoscopy Division, 2Pathology Division, 3Gastric Surgery Division, National Lower initial BMI, distal position of the anchor and lower body height could be
Cancer Center Hospital, Tokyo, Japan negative prognostic factor for pain.
Contact E-mail Address: seabe@ncc.go.jp Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15 CONCLUSION: H. pylori colonization is negatively associated with both wheez-
CHANGING LANDSCAPE OF H. PYLORI INFECTION HALL O_____________________ ing and eczema in children of non-Western ethnicity, with the strongest inverse
effect found for CagA-positive strains. In contrast, in all children H. pylori-
OP100 INTERGENERATIONAL CHANGE IN HELICOBACTER PYLORI colonization was positively associated with physician-diagnosed asthma to the
COLONIZATION IN CHILDREN LIVING IN A MULTI-ETHNIC age of 6 years. Trends in the Western and non-Western children appear opposite.
WESTERN POPULATION Disclosure of Interest: None declared
W.J. Den Hollander1,2,*, I. L. Holster1, A. J. van Vuuren1, V. W. Jaddoe2, G.,
I. Perez-Perez3, E.J. Kuipers1, H.A. Moll4, M. Blaser3
1
Gastroenterology and Hepatology, 2The Generation R Study Group, Erasmus OP103 META-ANALYSIS OF SEQUENTIAL VS. STANDARD TRIPLE
MC, Rotterdam, Netherlands, 3Medicine and Microbiology, New York University THERAPY FOR HELICOBACTER PYLORI ERADICATION: FINAL
Langone Medical Centre, New York, United States, 4Paediatrics, Erasmus MC, RESULTS OF A COCHRANE SYSTEMATIC REVIEW
Rotterdam, Netherlands O.P. Nyssen1,*, A.G. McNicholl2, F. Megraud3, V. Savarino4, G. Oderda5,
Contact E-mail Address: w.denhollander@erasmusmc.nl C. Fallone6, L. Fischbach7, F. Bazzoli8, J.P. Gisbert2
1
Centre For Primary Care and Public Health, Barts and The London School of
INTRODUCTION: Helicobacter pylori (H. pylori) colonization rates in child- Medicine and Dentistry, London, United Kingdom, 2H. La Princesa and IP,
hood have declined in Western populations, but it is unknown whether this trend CIBERehd, Madrid, Spain, 3Bacteriologie-Enfants, Hopital Pellegrin, Bordeaux,
is similar in children of non-Western ethnic backgrounds, who are born in a France, 4Dipartimento di Medicina Interna e Specialita Mediche, Universita di
Western country. Insight into colonization and transmission of H. pylori could Genova, Genova, 5Paediatric Endoscopy Units, Universita del Piemonte Orientale,
improve approaches to assessing H. pylori-related diseases. Novara, Italy, 6carlo.fallone@muhc.mcgill.ca, McGill University Health Centre,
AIMS & METHODS: We aimed to identify H. pylori status in mothers and their Montreal, Canada, 7Epidemiology, University of North Texas Health Science
children, and to determine both mother-to-child transmission and factors asso- Center, Fort Worth, Texas, United States, 8Medicina Interna e Gastroenterologia,
ciated with loss of H. pylori in one generation. Antibodies against H. pylori and Universit degli Studi di Bologna, Bologna, Italy
cytotoxin-associated gene A (CagA) were measured in mothers and children Contact E-mail Address: olgapnyssen@yahoo.es
participating in a population-based prospective cohort study in Rotterdam, the
Netherlands. Information on demographics, maternal and childs characteristics INTRODUCTION: Sequential therapy (SEQ) has been suggested as a new first-
was collected using questionnaires. Logistic regression analysis was used to assess line treatment option to replace the standard triple therapy (STT), where eradi-
factors associated with loss of H. pylori, including the following: gender, ethni- cation rates have declined to unacceptable levels.
city, mothers educational level, delivery mode, breastfeeding, number of older AIMS & METHODS: To conduct a meta-analysis of studies comparing SEQ vs.
siblings, day-care attendance, and cumulative antibiotic exposures. STT for H. pylori eradication.
RESULTS: H. pylori and CagA status were determined in 3,185 mothers and Selection of studies: randomized controlled trials comparing SEQ (10 days) and
their children. In mothers (mean age of 30.5 5.0 years), the overall H. pylori STT (at least 7 days) for the eradication of H. pylori. Search strategy: bibliogra-
colonization rate was 42%, compared to 10% (p50.001) in their children phical searches in electronic databases, and manual search of abstracts from
(mean age of 6.2 0.5 years). An H. pylori-positive mother was associated Congresses, were conducted up to November 2013. Data synthesis: intention-
with an H. pylori-positive child (OR 3.22; 95% CI 2.52-4.12). Overall, the H. to-treat eradication rate.
pylori prevalence decreased 76% comparing mothers and their children. A sig- RESULTS: We included 33 randomized controlled studies with a total of 9,750
nificant and consistent decline in both H. pyloriCagA- and H. pyloriCagA- patients (4,542 in SEQ and 5,208 in STT). The overall analysis showed that SEQ
strains was observed across all nine ethnic groups studied. Multivariate analysis was significantly more effective than STT (84% vs. 74% in the intention-to-treat
of the loss of H. pylori in children with an H. pylori-positive mother (n 1,328) analysis; OR2.07; 95%C.I.1.64-2.61; p50.001). Results were highly hetero-
revealed male gender (OR 1.64; 95% CI 1.21-2.23), higher maternal education geneous (I277%) and 11 studies were unable to demonstrate differences
level (OR 1.78; 95% CI 1.15-2.76), and no older siblings (OR 1.37; 95% CI 1.01- between therapies. Subgroup analyses suggested that patients with clarithromy-
1.88) independently associated with an H. pylori-negative child. cin resistance and/or taking esomeprazole-rabeprazole could benefit more from
CONCLUSION: We identified a large decline in H. pylori colonization rate in the SEQ. However there were no differences when STT lasted 14 days. Although,
children living in a European city. The observed drop was uniform across all overall, mean eradication rate with SEQ was over 80%, a tendency towards
ethnic groups, implying the importance of environmental factors in H. pylori lower efficacy with this regimen was observed in the more recent studies
transmission in modern cities, independent of ethnicity. [weighted linear regression per year -0.02 (-2% per year) in SEQ vs. -0.005 (-
Disclosure of Interest: None declared 0.5% per year) in STT], and in studies performed outside Italy (OR 1.57 vs. 4.09).
CONCLUSION: The meta-analysis demonstrated that SEQ is more effective
than STT lasting less than 14 days. Nevertheless, the apparent advantage of
OP101 HELICOBACTER PYLORI COLONIZATION, RESPIRATORY sequential treatment seems to be decreasing over time; therefore further and
OUTCOMES AND ECZEMA IN SCHOOL-AGE CHILDREN continuous assessment is needed before a generalized change in all settings is
W.J. den Hollander1,2,*, A. M. M. Sonnenschein-van der Voort2, I. L. Holster1, J. recommended for first line H. pylori treatment.
C. de Jongste3, V. W. Jaddoe2, G., I. Perez-Perez4, H.A. Moll3, M. Blaser4, Disclosure of Interest: None declared
L. Duijts3, E.J. Kuipers1
1
Gastroenterology and Hepatology, 2The Generation R Study Group, 3Paediatrics,
Erasmus MC, Rotterdam, Netherlands, 4Medicine and Microbiology, New York OP104 THE EFFICACY OF PROBIOTICS AS ADJUVANT TREATMENT
University Langone Medical Centre, New York, United States IN ERADICATING HELICOBACTER PYLORI BY STANDARD
Contact E-mail Address: w.denhollander@erasmusmc.nl TRIPLE THERAPY: A RANDOMIZED CONTROLLED TRIAL
G. Hauser1,*, N. Salkic2, K. Vukelic3, V. K. Vrbanovic3, D. Stimac1
INTRODUCTION: The declined Helicobacter pylori (H. pylori) prevalence in 1
Department of Internal Med., Division of Gastroent, CLINICAL HOSPITAL
Western countries is suggested to be associated with the simultaneous increases in CENTRE, RIJEKA, CROATIA, Rijeka, Croatia, 2Gastroenterology, University
childhood asthma and allergic diseases. Bacterial exposure during childhood may Clinical Centre, Tuzla, Tuzla, Bosnia and Herzegovina, 3JGL d.d., Rijeka, Croatia
be protective for asthma and atopy. Contact E-mail Address: goran.hauser@medri.uniri.hr
AIMS & METHODS: We aimed to examine the association between childrens
H. pylori colonization and asthma or related diseases. This study was embedded INTRODUCTION: The current report of the European Helicobacter Study
in The Generation R Study, a population-based prospective multi-ethnic cohort Group considers probiotics as an adjuvant treatment in reducing side effects
study among children, followed from early pregnancy onwards. We measured during the standard Helicobacter pylori eradication therapy. The primary objec-
anti-H. pylori and anti-CagA-IgG antibodies in serum of children obtained at age tive in the study is determination of efficacy of probiotic preparation as a sup-
of 6 years. Also at age 6 years, asthma-related outcomes including ever wheezing, portive therapy in eradication of H. pylori.
physician-diagnosed asthma, and eczema were obtained by questionnaires. Data AIMS & METHODS: The study was multicenter, prospective, randomized, pla-
analyses were performed in the total cohort as well as in different ethnic groups cebo controlled, and double-blind. The enrolment of subjects into the trial was
(Western vs. non-Western). Multivariate logistic regression analyses were conducted in 121 general practitioners offices, in different regions in Croatia
adjusted for maternal educational level, history of asthma and atopy, smoking from September 2009 until June 2012. The study was reported according to the
during pregnancy, and parity, and for childs gender, ethnicity, gestational age at CONSORT guidelines and was registered at www.clinicaltrials.gov
birth, birth weight, breastfeeding habits, day-care attendance, pet keeping, and (NCT01969331).The initial diagnosis of H. pylori infection was established
lower respiratory tract infections. using rapid urease test, stool antigen, or urea breath test. The subjects first
RESULTS: In total 3,838 children (mean age 6.1 SD 0.5) were available for filled out a specially designed questionnaire in order to assess the severity of
these analyses. Of those, 328 (9%) were H. pylori-positive, of whom 100 (30%) the 10 symptoms which can be related to eradication therapy to be monitored
were CagA-positive. Univariate analyses revealed the following results of com- during the trial. Each subject then received 28 capsules of probiotic preparation
parison between H. pylori-positive versus negative children: ever wheezing or matching placebo capsules, which they were supposed to take over the follow-
[63.3% vs. 56.0% (p0.07)], physician-diagnosed asthma [11.2% vs. 6.6% ing 14 days, twice a day, at least two hours prior to or after the antibiotic therapy
(p0.01)], and eczema [27.0% vs. 22.2% (p0.07)]. In multivariate analyses H. administration.
pylori-positivity was associated with physician-diagnosed asthma (odds ratio RESULTS: A total of 804 patients were enrolled in the trial, of which
(OR) 1.63; 95% CI 1.02-2.61), but not with ever wheezing (OR 1.02; 95% CI 650(80.85%) were included in the analysis. The results show a significantly
0.85-1.23) or eczema (OR 1.06; 95% CI 0.79-1.41). A significant interaction larger share of cured subjects in the probiotic arm versus the placebo arm
between H. pylori and ethnicity was found for wheezing (p50.001) and eczema (87.38% vs. 72.55%; p50.001). Additionally, odds ratio, absolute and relative
(p0.006). Analyses stratified according to ethnicity showed that H. pylori-posi- risk reductions as well as number needed to treat all point strongly in favour of
tivity was inversely associated with ever wheezing (OR 0.66; 95% CI 0.48-0.91), probiotic arm. Overall, at baseline the average value of intensity for all 10 symp-
and eczema (OR 0.64; 95% CI 0.41-1.00) in children of non-Western ethnicity toms was 1.17 for subjects on probiotic and 1.07 for subjects on placebo
(n 1,155), but not in children of Western ethnicity (n 2,683). This negative (p50.001). At follow-up visit 15 days after the start of the trial, the intensity
association was mainly explained by the CagA-positive strains. of the same symptoms that were monitored at enrolment was again evaluated.
A36 United European Gastroenterology Journal 2(5S)
OP106
Procore FNA
ProCore FNA Pooled Estimate: Pooled Estimate: Pooled RR
Outcome Measure (n) (n) mean % (95% CI) mean % (95% CI) (95%CI) p-value
Diagnostic Adequacy: 742 745 82.7 (74.2-89.8) 79.3 (70.4-87.0) 1.06 (0.97-1.16) 0.221
All Masses
Diagnostic Adequacy: 317 324 84.8 (70.4-95.0) 88.5 (80.1-94.9) 0.98 (0.85-1.12) 0.721
Pancreatic Masses
Diagnostic Accuracy: 421 474 84.9 (76.1-92.0) 79.3 (71.8-85.9) 1.06 (0.99-1.14) 0.083
All Masses
Diagnostic Accuracy: 225 277 88.4 (82.4-93.3) 79.9 (73.6-85.5) 1.12 (0.99-1.26) 0.067
Pancreatic Masses
Histology: 104 108 66.8 (49.7-81.9) 68.7 (54.5-81.3) 1.02 (0.85-1.22) 0.864
All Masses
Histology: 66 70 75.4 (60.2-87.8) 75.2 (63.2-85.5) 1.03 (0.84-1.26) 0.756
Pancreatic Masses
Mean no. of passes 209 209 - - SMD -0.90 (-1.80 - 0.051
for diagnosis: 0.005)
All Masses
Overall, the average intensity value for all 10 symptoms was 0.55 for subjects on CONCLUSION: H. pylori management by gastroenterologists in Europe is
probiotic and 0.76 for subjects on placebo (p50.001). extremely diverse. It is important to notice that the achieved eradication rates
CONCLUSION: Adding probiotics to the standard triple therapy for H. pylori are clearly suboptimal, especially with the use of the commonly recommended
eradication significantly contributes to treatment efficacy and distinctly decreases standard triple therapy (76%). Continuation of this registry and deeper evalua-
the adverse effects of therapy and the symptoms of the underlying disease. tion of its data may offer valuable information to improve H. pylori
Disclosure of Interest: G. Hauser Financial support for research from: Company management.
sponsored trial, Consultancy for: principal investigator served as consultant, N. Disclosure of Interest: None declared
Salkic: None declared, K. Vukelic Other: emploee of the company, V. Vrbanovic
Other: emploee of the company, D. Stimac: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
MINIMALLY INVASIVE INTERVENTIONS IN THE PANCREAS LOUNGE
OP105 PAN-EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT: 5_____________________
INTERIM ANALYSIS OF 5,000 PATIENTS
A.G. Mcnicholl1,*, A. Gasbarrini2, B. Tepes3, F. Lerang4, D.S. Bordin5, OP106 ENDOSCOPIC ULTRASOUND-GUIDED TISSUE ACQUISITION:
O. Shvets6, T. Rokkas7, L. Kupcinskas8, M. Leja9, M. Katicic10, J.C. Machado11, META-ANALYSIS COMPARING THE PROCORE AND STANDARD
L. Boyanova12, K. Przytulski13, I. Simsek14, G.M. Buzas15, T. Axon16, FINE NEEDLE ASPIRATION NEEDLES
C. Beglinger17, P. Bytzer18, V. Lamy19, A. Goldis20, L.G. Cappelle21, L. Veijola22, J.Y. Bang1,*, M. Hasan1, R. Hawes1, S. Varadarajulu1
M. Caldas1, M. Ramas1, F. Megraud23, C.A. OMorain24, J.P. Gisbert1 on behalf 1
Center for Interventional Endoscopy, Florida Hospital, Orlando, United States
of On Behalf of the Hp-EuReg investigators and, the European Helicobacter Contact E-mail Address: jybang213@gmail.com
Study Group
1
H. La Princesa and IP, CIBERehd, Madrid, Spain, 2U.Sacro Cuore, Italy, Rome, INTRODUCTION: To overcome the limitations associated with cytology, a
Italy, 3AM DC Rogaska, Ljubliana, Slovenia, 4Central Hospital, stfold, Norway, ProCore biopsy platform has been developed in 19, 22 and 25G sizes.
5
Clinical Sci. Centre, Moscow, Russian Federation, 6Medical University, Kyiv, However, individual studies comparing the ProCore and FNA needles have
Ukraine, 7H. Henry Dunant, Athens, Greece, 8U. of Health Sciences, Kaunas, yielded varying conclusions.
Lithuania, 9University of Latvia, Riga, Latvia, 10Clinical Hospital, Zagreb, AIMS & METHODS: This meta-analysis was conducted to compare the perfor-
Croatia, 11IPATIMUP, Porto, Portugal, 12Medical University of Sofia, Sofia, mance of the ProCore and standard FNA needles when performing EUS-guided
Bulgaria, 13Medical C. Postgraduate Education, Warsaw, Poland, 14Dokuz Eylul tissue acquisition. All published manuscripts and presented abstracts
University, Izmir, Turkey, 15Ferencvaros Health Centre, Budapest, Hungary, (International Scientific Meetings) that compared the ProCore and FNA needles
16
University, Leeds, United Kingdom, 17U. Hospital, Basel, Switzerland, 18U. were analyzed. Excluded were non-comparative and technical feasibility studies.
Hospital, Koge, Denmark, 19CHU, Charleroi, Belgium, 20CECH, Timisoara, Main outcome measures: Compare the rates of diagnostic adequacy, diagnostic
Romania, 21Erasmus MC, Rotterdam, Netherlands, 22Hospital, Herttoniemi, accuracy, histological core tissue procurement and mean number of passes to
Finland, 23Bacteriologie-Enfants, Hopital Pellegrin, Bordeaux, France, 24Trinity diagnosis when sampling all solid organ lesions and solid pancreatic masses.
College Dublin, Dublin, Ireland RESULTS: A total of 21 studies involving 1617 patients met inclusion criteria.
Contact E-mail Address: adrian.mcn@gmail.com There was significant heterogeneity in study design and end points. Study out-
comes are shown in the Table. There was no significant difference in diagnostic
INTRODUCTION: Due to the diversity of H. pylori strains, resistances and adequacy/accuracy, histological core tissue procurement or mean number of
geographical particularities, the most efficient management strategy is still to passes to diagnosis between both cohorts. Subgroup analysis did not reveal
be found. any difference between the 19, 22/25G needles for any of the outcome measures.
AIMS & METHODS: To systematically register the clinical practice of CONCLUSION: Current data does not demonstrate a significant difference in
European gastroenterologists regarding H. pylori infection and treatment (31 performance between the ProCore and standard FNA needles for establishing a
countries and 250 recruiting investigators) diagnosis with fewer no. of passes, for yielding a better cytological aspirate or
A Local Coordinator was selected from each Country with more than 10 H. histological core tissue. Therefore, the choice of a needle should be based on
pylori REFERENCES on PubMed. Each Coordinator selected a representative endosonographer preference and needle costs.
group of recruiting investigators from its country (250 so far). An electronic Disclosure of Interest: None declared
clinical research file was created to systematically register all adult patients
infected with H. pylori. Variables included: Patients demographics, previous
eradication attempts, prescribed eradication treatment, adverse events, and out-
comes (cure rates, compliance, follow up, etc.).
RESULTS: Up to now, 5,000 patients have been included, and 3,333 have fin-
ished follow up. 58% females. 87% Caucasian. Mean age was 57 years. 4.3% had
drug allergies (77% to penicillin). 53% of indications were dyspepsia. 23% had
gastroduodenal ulcer. 70% were diagnosed using endoscopy based methods.
78% were na ve, 16% second-line, 4.8% third-line, 1.2% fourth-line, and 0.5%
fifth-line. Culture was performed in 15%, of which 57% showed antibacterial
resistance (40% to nitroimidazoles, 32% clarithromycin, 17% quinolones, 0.8%
amoxicillin and 0.9% tetracycline). 63% of prescriptions were triple regimens
(PPI 2 antibiotics), 12% non-bismuth concomitant quadruple, 14% sequential,
and 6.9% bismuth quadruple. 53% of patients had adverse events (13% metallic
taste, 12% diarrhea, and 11% nausea) although they were mostly mild (65%) and
lasted an average of 6.8 days, causing treatment discontinuation in 4.2% of cases.
Overall eradication rate was 80%, and only 64% of eradication failures were
retreated. The most common prescribed treatments for first (triple therapy with
clarithromycin and amoxicillin) and second line (triple therapy with amoxicillin
and levofloxacin) achieved suboptimal eradication rates: 76% and 78%
respectively.
United European Gastroenterology Journal 2(5S) A37
OP107 SMART ATLAS FOR SUPPORTING THE INTERPRETATION OF needles for diagnostic accuracy: first pass: EZ Shot 2 vs. EZ Shot 2 with side port:
NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE) 22/30 (73.3%) vs. 23/30 (76.7%) (p 0.766); combined 2 passes: EZ Shot 2 vs.
OF PANCREATIC CYSTS: FIRST CLASSIFICATION RESULTS OF A EZ Shot 2 with side port: 26/30 (86.7%) vs. 26/30 (86.7%) (p 1.0). When the 4
COMPUTER-AIDED DIAGNOSIS SOFTWARE BASED ON IMAGE passes for each lesion were assessed together adequate cellularity was obtained in
RECOGNITION all cases and the correct diagnosis was obtained in 24/24 cases of pancreatic
M. Kohandani Tafreshi1,*, B. Napoleon2, A.-I. Lemaistre3, M. Giovannini4, adenocarcinoma, 2/2 neuroendocrine tumor, 2/2 pseudotumor, 1/1 serous cysta-
V. Joshi5, N. Ayache1, B. Andre6 denoma and 0/1 case of cholangiocarcinoma. There were no EUSFNA related
1
INRIA, Sophia Antipolis, 2Hopital prive Jean Mermoz, 3Centre Regional Leon complications.
Berard, Lyon, 4Institut Paoli Calmette, Marseille, France, 5Ochsner Clinic CONCLUSION: For EUSFNA of pancreatic masses, there were no statistically
Foundation, New Orleans, United States, 6Mauna Kea Technologies, Paris, France significant differences in adequacy of cellularity or diagnostic accuracy between
Contact E-mail Address: marzieh.kohandani-tafreshi@inria.fr FNA needles with or without side port. After 4 passes, adequate cellularity was
obtained in all cases and the correct diagnosis was achieved in 96% of cases.
INTRODUCTION: nCLE enables microscopic imaging of pancreatic cysts, Disclosure of Interest: None declared
in vivo and in real time, during an EUS-FNA procedure. Differentiating
branch duct-type Intraductal Papillary Mucinous Neoplasm (IPMN) and
Serous Cystadenoma (SCA) of the pancreas can be difficult, especially in case OP109 CRITICAL ASSESSMENT OF THE CHOICE OF
of a solitary lesion without clear communication with the pancreatic duct. Recent ENDOPROSTHESIS FOR TRANSMURAL DRAINAGE OF
studies (Konda et al., Endoscopy 2013; Napoleon et al., DDW 2013) have iden- PANCREATIC FLUID COLLECTIONS
tified reliable nCLE descriptive features (superficial vascular network in SCA; J.Y. Bang1,*, R. Hawes1, S. Varadarajulu1
finger- like projections in IPMN), allowing endoscopists to discriminate between 1
Florida Hospital, Orlando, United States
SCA and IPMN. In parallel, a computer-aided diagnosis software called Smart Contact E-mail Address: jybang213@gmail.com
Atlas has been developed to assist endoscopists with the interpretation of nCLE
video sequences. This study aims at evaluating the performance of this software INTRODUCTION: With increased application of endoscopic techniques for the
for the differentiation of SCA and IPMN cases. management of pancreatic fluid collections (PFCs), metal stents are being used
AIMS & METHODS: Several nCLE sequences, of proven SCA or IPMN, were more frequently for transmural drainage despite the lack of data.
retrospectively collected from nCLE procedures performed in multiple clinical AIMS & METHODS: A systematic review and meta-analysis were conducted to
centers. These video sequences, along with their annotated final diagnosis, were compare the performance of metal and plastic stents when undertaking endo-
used to train a classification software that uses a content-based image retrieval scopic transmural drainage of PFCs.
algorithm to predict the diagnosis of a query video based on the diagnoses of the MEDLINE and EMBASE were searched to identify all published manuscripts
most visually similar atlas videos. All evaluations were performed using leave- that evaluated metal stents for endoscopic transmural drainage of PFCs.
one-patient-out cross-validation to avoid bias. To reduce the number of unne- Additionally, all published studies from the same period involving plastic stent
cessary surgeries with high morbidity rates, false positives were minimized on a placement for the same indication that included 450 patients were also identi-
receiver operating curve. fied. A random effects model was used. Main Outcome Measures: Compare the
RESULTS: 29 nCLE video sequences were collected from 18 patients, with one rates of treatment success, complications and recurrence between patients under-
lesion per patient (12 SCA, 6 IMPN), leading to 22 sequences annotated with going metal versus plastic stent placement for endoscopic transmural drainage of
SCA and 7 sequences annotated with IPMN. The classification results maximiz- PFCs.
ing the specificity for an acceptable sensitivity show a specificity of 95.5% for a RESULTS: A total of 12 studies consisting of 725 patients met inclusion criteria.
sensitivity of 85.7%, an accuracy of 93.1%, a PPV of 85.7% and a NPV of The overall treatment success was marginally higher for patients treated with
95.5%, with only one false positive and one false negative. In comparison, plastic than metal stents (Table) as the proportion of success for plastic stents
Napoleon et al. reported that the performance achieved by a consensus of inves- (89.7%) was more than the 95% confidence interval (CI) for metal stents (72.6-
tigators on retrospective data to differentiate SCA from all other types of lesions 88.7%). Also, subgroup analysis revealed that the treatment success rates were
reaches a specificity of 100% for a sensitivity of 62.5%. higher when pseudocysts were drained using plastic (96.3% [95% CI 91.8-
CONCLUSION: These first results demonstrate that the Smart Atlas software is 98.4%]) than metal stents (82.0% [95% CI 71.8-89.1%]) as there was no overlap
able to differentiate SCA and IPMN cases using only the image content of nCLE of 95% CI between the cohorts. There was however, no difference in the rates of
sequences, with very high specificity and rather high sensitivity. Besides, the case- treatment success for walled-off pancreatic necrosis (WOPN). Additionally, there
based reasoning software can detect relevant video content and provide diagnos- was no difference in the rates of complications or recurrence between plastic and
tic confidence levels. It could thus be used as an educational tool to train non- metal stents as evident by the considerable overlap of 95% CIs.
expert endoscopists, but also as a second-reader tool to assist any user in real-
time diagnosis of pancreatic cysts using nCLE. Future software improvements
will leverage a larger sample size, various types of cysts and clinical metadata. Metal stents (n94) Plastic stents (n631)
Disclosure of Interest: None declared
Treatment success: % (95% CI)
All PFC types 82.1 (72.6 - 88.7) 89.7 (78.9 - 95.3)
OP108 A PROSPECTIVE RANDOMIZED CROSS-OVER STUDY OF THE Pseudocysts only 82.0 (71.8 - 89.1) 96.3 (91.8 - 98.4)
DIFFERENCE IN DIAGNOSTIC YIELD BETWEEN EUSFNA
NEEDLES WITH AND WITHOUT A SIDE PORT IN PANCREATIC WOPN only 75.1 (39.2 - 93.4) 74.9 (56.9 - 87.1)
MASSES Complications: % (95% CI)
All PFC types 17.9 (10.7 - 28.3) 15.7 (9.4 - 25.1)
T.L. Ang1,*, A. Kwek1, D.W. Seo2, W.H. Paik2, H.-P. Wang3, T.-Y. Cheng3
1
Gastroenterology and Hepatology, Changi General Hospital, Singapore, Pseudocysts only 17.1 (9.6 - 28.5) 9.8 (2.9 - 27.9)
Singapore, 2Gastroenterology, Asan Medical Centre, Seoul, Korea, Republic Of, WOPN only 20.6 (6.0 - 51.3) 17.0 (12.0 - 23.6)
3
Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Recurrence: % (95% CI)
Province of China All PFC types 9.3 (4.1 - 15.9) 9.1 (5.1 15.6)
Contact E-mail Address: tiing_leong_ang@cgh.com.sg
Pseudocysts only 9.2 (3.9 - 20.5) 9.7 (3.7 - 23.0)
INTRODUCTION: Currently two needles with similar designs, apart from WOPN only 10.0 (0.6 - 67.4) 8.3 (3.3 - 19.5)
absence and presence of side port, are available from Olympus Corporation
(Tokyo, Japan) for EUS-guided fine needle aspiration (FNA). These are EZ- CONCLUSION: Current evidence does NOT support the routine placement of
Shot 2 and EZ-Shot 2 with side port. The theoretical basis for introduction of metal stents for transmural drainage of PFCs, particularly pseudocysts. Large,
the side port was to facilitate the process of FNA and increase diagnostic yield multicenter, randomized trials are needed to justify the use of metal stents for
but this advantage remained unproven. PFC drainage.
AIMS & METHODS: This pilot study aimed to determine the difference in Disclosure of Interest: None declared
diagnostic yield between EZ-Shot 2 and EZ-Shot 2 with side port in patients
with pancreatic masses. This was a pilot multicenter prospective randomized
cross-over study involving 3 referral centers in Korea, Singapore and Taiwan. OP110 LAPAROSCOPIC VERSUS OPEN DISTAL PANCREATECTOMY
Patients referred for EUSFNA of pancreatic masses were recruited. Four FOR BENIGN AND MALIGNANT DISEASE: A MULTICENTER
EUSFNA passes were performed per patient. Patients were randomized to one RETROSPECTIVE MATCHED-COHORT STUDY
needle for the first 2 passes, followed by the other needle for the next 2 passes. T. de Rooij1,*, A. Jilesen1, G. Kazemier2, D. Boerma3, B. Bonsing4, K. Bosscha5,
Rapid on-site cytopathological assessment was not performed. A pathologist R. van Dam6, C. van Eijck7, M. Gerhards8, H. van Goor9, E. van der Harst10,
blinded to the needle that was used assessed each individual needle pass for I. de Hingh11, J. Klaase12, Q. Molenaar13, E. Nieveen van Dijkum1, G. Patijn14,
cellularity and morphology. The diagnostic yield between both needles was com- H. van Santvoort13, J. Scheepers15, G. van der Schelling16, J. Vogel1, E. Sieders17,
pared. The reference standard was based on composite of cytology, histology and O. Busch1, M. Besselink1
clinical course. 1
Surgery, Academic Medical Center, 2Surgery, VU Medical Center, Amsterdam,
RESULTS: A total of 30 patients were recruited (mean age 66 year; 53% female) 3
Surgery, Antonius Hospital, Nieuwegein, 4Surgery, Leiden University Medical
with total of 120 needle passes. The sites of lesions were 15/30 at pancreatic head, Center, Leiden, 5Surgery, Jeroen Bosch Hospital, Den Bosch, 6Surgery, Maastricht
7/30 at pancreatic neck/body and 8/30 at pancreatic tail. The final diagnoses were University Medical Center, Maastricht, 7Surgery, Erasmus University Medical
pancreatic adenocarcinoma (24/30), neuroendocrine tumor (2/30), cholangiocar- Center, Rotterdam, 8Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, 9Surgery,
cinoma (1/30), pancreatitis related pseudotumour (2/30) and serous cystadenoma St Radboud University Medical Center, Nijmegen, 10Surgery, Maasstad Hospital,
(1/30). Mean size of mass was 3.5 cm (range: 1.2 6.3). Comparison of the 2 Rotterdam, 11Surgery, Catharina Hospital, Eindhoven, 12Surgery, Medisch
needles for cellularity adequacy: first pass: EZ Shot 2 vs. EZ Shot 2 with side Spectrum Twente, Enschede, 13Surgery, University Medical Center Utrecht,
port: 26/30 (86.7%) vs. 25/3 (83.3%) (p 0.718): 2nd pass: EZ Shot 2 vs. EZ Shot Utrecht, 14Surgery, Isala Clinics, Zwolle, 15Surgery, Reinier de Graaf Groep, Delft,
2 with side port: 25/30 (3.3%) vs. 26/30 (86.7%) (p 0.718). Comparison of the 2
A38 United European Gastroenterology Journal 2(5S)
16
Surgery, Amphia Hospital, Breda, 17Surgery, University Medical Center REFERENCES
Groningen, Groningen, Netherlands (1) Agarwal J et al. ERCP in the management of pancreatic diseases in children.
Contact E-mail Address: t.derooij@amc.nl Gastrointest Endosc 2014; 79: 271-278.
Disclosure of Interest: None declared
INTRODUCTION: Recent cohort studies from expert centers suggest that
laparoscopic distal pancreatectomy (LDP) is superior to open distal pancreatect-
omy (ODP). Introduction of LDP, however, has been slow, possibly because of MONDAY, OCTOBER 20, 2014 15:4517:15
unclear external validity of these data. Data on the use, outcomes and attitude CIRRHOSIS AND NON-INVASIVE DIAGNOSIS OF FIBROSIS LOUNGE
regarding LDP on a national level are lacking. 6_____________________
AIMS & METHODS: This study aimed to determine the extent of LDP in the
Netherlands and to assess the attitude of Dutch pancreatic surgeons regarding OP112 PROTON PUMP INHIBITOR INTAKE IS NEITHER
this procedure. Adults who underwent LDP or ODP in one of the 17 Dutch ASSOCIATED WITH THE DEVELOPMENT OF SPONTANEOUS
medium-high volume centers between January 2005 and September 2013 were BACTERIAL PERITONITIS OR OTHER INFECTIONS NOR WITH
analyzed retrospectively. Patients were excluded if DP was not the primary pro- MORTALITY IN PATIENTS WITH CIRRHOSIS AND ASCITES
cedure or if too little data were available. Every LDP patient was matched to an M. Mandorfer1,*, S. Bota1, P. Schwabl1, T. Bucsics1, N. Pfisterer1,
ODP patient based on sex, age, ASA score, indication for surgery and tumor size. C. Summereder1, A. Blacky2, A. Ferlitsch1, W. Sieghart1, M. Trauner1, M. Peck-
Primary endpoint were clinically relevant complications (Clavien-Dindo score Radosavljevic1, T. Reiberger1 on behalf of Vienna Hepatic Hemodynamic Lab
42). Analyses were by intention-to-treat. A questionnaire regarding attitudes 1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
towards LDP was sent to all 30 Dutch pancreatic surgeons. III, Medical University of Vienna, 2Clinical Institute of Hospital Hygiene, Vienna
RESULTS: Of 633 included patients, 64 (10%) underwent LDP and 569 (90%) General Hospital, Vienna, Austria
ODP. 128 patients were excluded, 124 because DP was not the primary procedure Contact E-mail Address: thomas.reiberger@meduniwien.ac.at
and 4 because too little data were available. 63 LDP patients were matched
adequately to 63 ODP patients, such that baseline characteristics were compar- INTRODUCTION: Conflicting results have been reported on the association
able. Clinically relevant complications occurred less after LDP than after ODP between proton pump inhibitor (PPI) intake and spontaneous bacterial perito-
(14% vs. 30%, P0.03). Conversion occurred in 33% of LDPs. LDP was asso- nitis (SBP) development in patients with cirrhosis and ascites.
ciated with 375ml less intra-operative blood loss (P0.04) and 2 days shorter AIMS & METHODS: The aim of this study was to assess the impact of PPI
postoperative stay (P0.01). No significant differences were seen regarding oper- intake on the development of SBP or other infections, as well as mortality, in a
ating time, fistula, gastroparesis, bleeding, infection, ICU admittance and total thoroughly documented cohort with a particularly high prevalence of PPI intake.
duration of hospitalization. The questionnaire (90% response) showed that 85% We performed a retrospective analysis of data from 607 consecutive patients with
of Dutch pancreatic surgeons wanted to participate in LDP-training and 96% in cirrhosis who had their first paracentesis at the Medical University of Vienna
a randomized trial. from 2006 through 2011. Cox models were calculated to investigate the effect of
CONCLUSION: LDP seems to be safe in the Netherlands in this relative small PPI intake on the incidence of SBP or other infections, as well as transplant-free
group of selected patients despite the high conversion rate. A nationwide training survival. All models were adjusted for age, hepatocellular carcinoma (HCC),
scheme for LDP (LAELAPS) has been developed. previous variceal bleeding, varices and model of end-stage liver disease
Disclosure of Interest: None declared (MELD) score.
RESULTS: PPI intake was very common (86%). At the first paracentesis, mean
age was lower (PPI:57.1 11.7 vs. no-PPI:60.2 12.1; P0.02), while median
OP111 ENDOSCOPIC TREATMENT OF CHRONIC PANCREATITIS IN MELD score was higher (PPI:18 (10.3) vs. no-PPI:15.2 (7.7); P0.037) among
CHILDREN: LONG TERM FOLLOW UP patients with PPI intake. While the proportion of patients with HCC was higher
M. Napoleone1, I. Boskoski1,*, P. Familiari1, I. Costamagna2, A. Tringali1, among patients without PPI intake (PPI:22% vs. no-PPI:37%; P0.003), pre-
V. Perri1, M. Mutignani3, G. Costamagna4 vious variceal bleeding (PPI:20% vs. no-PPI:10%; P0.038) and varices
1
DIGESTIVE ENDOSCOPY UNIT, 2Department of Anestesiology, CATHOLIC (PPI:75% vs. no-PPI:60%; P0.003) were more frequently observed in the PPI
UNIVERSITY OF ROME, Rome, 3Digestive Endoscopy, Niguarda Hospital, group. Similar differences were observed in the subgroups of patients without
Milan, 4Digestive Endoscopy, CATHOLIC UNIVERSITY OF ROME, Rome, SBP and patients without SBP or other infections at the first paracentesis.
Italy The proportion of patients with SBP at the first paracentesis was comparable
Contact E-mail Address: ivoboskoski@yahoo.com between PPI (19%) and no-PPI (17%; P0.691) patients. After adjusting for
potential confounding factors, PPI intake was not associated with SBP incidence
INTRODUCTION: Chronic pancreatitis (CP) in children is a rare disease and (HR:1.33; 95%CI:0.6-2.96; P0.486), or incidence of SBP or other infections
experience of ERCP in children with CP is limited. (HR:1.36; 95%CI:0.67-2.77; P0.389).
AIMS & METHODS: All pediatric patients (518 yrs) with CP who underwent Moreover, PPI intake had no impact on transplant-free survival, neither in the
ERCP from Oct 1992 to Feb 2013 were retrospectively identified from a pro- overall cohort (HR:0.973, 95%CI:0.719-1.317; P0.859), nor in the subgroups of
spective database at a tertiary care referral center. Indications, findings, treat- patients without SBP (HR:1.01, 95%CI:0.72-1.42; P0.971) and without SBP or
ment modalities, adverse events/outcomes were recorded. Data on long term other infections at the first paracentesis (HR:0.944, 95%CI:0.668-1.334;
follow-up were analyzed. Safety and efficacy on treatment were also evaluated. P0.742).
RESULTS: During the study period 125 children underwent ERCP for bilio- CONCLUSION: Previous studies reporting an association between PPI intake
pancreatic disorders. Of these, 35 (28%) children (16 boys, mean age 11.6 yrs and SBP incidence were based on cohorts with a substantially lower proportion
[range 2.5-17]) underwent ERCP for painful CP and were included in the study. of patients on PPI treatment, suggesting indications for PPI administration were
Indications to ERCP were recurrent bouts of pancreatitis and pain. Mean symp- followed more rigorously. In our cohort with a particularly high prevalence of
toms duration before ERCP was 2.4 yrs (range 0.1 to 14 yrs). Gene mutations for PPI intake, we observed no association between PPI intake and SBP or other
CP had 17 (48.5%) children while 8 (22.8%) had pancreatic calcifications (X-ray/ infections, as well as mortality. Thus, the underlying disease and other unknown
CT/US). Data were missing regarding the number of patients that underwent factors, rather than PPI treatment per se may predispose for complications in
MRCP before ERCP. On ERCP, normal main pancreatic duct (MPD) anatomy patients with cirrhosis and ascites.
was found in 19 (54.3%) children, while pancreas divisum and dominant dorsal Disclosure of Interest: None declared
duct anatomy had 10 (28.6%) and 6 (17.1%) respectively. On first ERCP, 21
children had major papilla pancreatic endoscopic sphincterotomy (ES), while
minor papilla ES was done in 9 (5 had both major and minor papilla ES). Of OP113 PORTAL VEIN THROMBOSIS NATURAL COURSE AND
these, 3 underwent also Extracorporeal Shock-Wave Lithotripsy on pancreatic SURVIVAL IN CIRRHOTIC PATIENTS
stones. Stones and plugs were extracted and in 17 cases. Dominant MPD stric- I. Girleanu1,*, A. Trifan1, C. Cojocariu1, A.M. Singeap1, O.C. Stoica1,
ture was found in 5 children, and plastic stents were placed. ERCP-related com- C. Stanciu1
plications during the first treatment (bleeding/pancreatitis) occurred in 2 children 1
Gastroenterology, University of Medicine and Pharmacy Iasi, Romania, Iasi,
(5.7%) and were managed conservatively. Mean follow-up of the 35 patients was Romania
8 yrs (range 0.7-21). Fourteen (40%) children had only one ERCP and were pain- Contact E-mail Address: gilda_iri25@yahoo.com
free during 7.3 yrs (range 0.7-17) of follow-up, while 21 (60%) had recurrence of
pain after a mean of 3.8 yrs (range 0.1-20.4) and underwent additional ERCPs INTRODUCTION: Portal vein thrombosis (PVT) has a high incidence in
(total of 68 re-interventions [range 1-13; 3.2/patient]). On re-interventions, 9 patients with liver cirrhosis, frequently in its advanced stages, and determines a
patients had dominant MPD stricture and were treated with plastic stents place- poor prognosis of hepatic disease.
ment. These were pain-free on last follow-up (5.8 yrs [range 0.3-14.8]) after stent AIMS & METHODS: The aim of this study was to evaluate long-term outcome
removal. Sixteen children had stricture on the site of ES and had re-ES and/or of patients with portal vein thrombosis and liver cirrhosis. We conducted a
pneumatic dilation. Plugs were extracted in 17 children during re-interventions. prospective cohort study including all adult patients referred to a tertiary
One boy had post re-ES bleeding that was managed endoscopically and there center between January 2011 and December 2013 with non-malignant PVT
were two cholecystitis managed conservatively. After the last re-intervention and liver cirrhosis. We excluded patients who received anticoagulant treatment,
these children were pain-free for mean 3.6 yrs [range 0.3-5.6]). The number of patients with malignant disease including hepatocellular carcinoma, known
re-interventions was higher in female children (p 5 0.01), and in those with less thrombofilia, those with portal cavernoma. All patients were evaluated by
than 8 yrs of age (p50.01). Pain recurrences were not related to MPD anatomy Doppler abdominal ultrasound and computed tomography. Portal vein throm-
or the presence of gene mutations (p0.2 and p0.3 respectively). bosis group was compared with a control group consisting in cirrhotic patients
CONCLUSION: ERCP in pediatric patients with chronic pancreatitis is a safe comparable in terms of liver disease severity.
and effective procedure. In more than one third of cases only one ERCP can be RESULTS: A total of 62 patients (51.6 % female) were included, with a median
resolutive. Like already described (1), our series confirms the need for repeated age at PVT-diagnosis of 59.02 years (range 2980). Study group included 32
ERCPs for pain recurrences, that can be managed endoscopically without major patients diagnosed with PVT, 22 of them with partial PVT. The control group
complications. consisted in 30 cirrhotic patients with comparable baseline characteristics as the
study group. Median follow-up was 21.69 months (range 431). There was no
United European Gastroenterology Journal 2(5S) A39
difference regarding hepatic decompensation rate at 6 and 18 months between in the duodenum where villi were imaged using a GastroFlex-UHDTM mini-
patients with PVT and control group groups (19% vs. 20%, P0.821 and 54% probe (Mauna Kea Technologies, Atlanta, GA), providing 1000x magnification,
vs. 51%, P0.755, respectively). The survival rate at 6 months was 81.3% in PVT a 20 mm optical slice thickness, 1mm lateral resolution, and a 240mm field of view.
group vs. 84.7% (P0.067) in control group, and 63.1% vs. 61.7% (P0.122) at Digital videos were then analyzed off-line in a blinded manner for vessel and
18 months, respectively. Multivariate analysis showed that total PVT was the epithelial morphometry using image processing algorithms.
independent predictor of hepatic decompensation [hazard ratio (HR) 1.56; 95% RESULTS: To date, pCLE images have been analyzed from 15 control and 16
confidence interval (CI): 1.14-6.67, P0,032] with no influence on survival rate. PHT patients. Average vessel diameter (AVD) and branching (AVB) were mea-
CONCLUSION: There was no difference regarding decompensation and survi- sured in 249 regions of interest from control vs. 301 regions from PHT subjects.
val rates between cirrhotic patients with or without PVT and similar stage of liver Average columnar cell height (ACCH) within the villus epithelial stripe was
disease. Total portal vein thrombosis negatively influence hepatic decompensa- measured in 219 control vs. 197 PHT regions. Spearman correlations of 0.87
tion rate. (95%CI, 0.74,0.93; p8.3x10-11), 0.42 (95%CI, 0.09,0.67; p0.01), and 0.71
Disclosure of Interest: None declared (95%CI, 0.48,0.85; p3.8x10-6) were obtained for AVD, AVB, and ACCH,
respectively, when compared to the severity of portal gastropathy, and of 0.88
(95%CI, 0.76,0.94; p1.99x10-11), 0.41 (95%CI, 0.07,0.66; p0.02), and of 0.66
OP114 PATIENT UNDERSTANDING OF LIVER CIRRHOSIS: (95%CI, 0.41,0.82; p3.1x10-5), respectively, when compared to the grade of
IMPROVEMENT THROUGH USE OF AN EDUCATIONAL esophageal varices. In addition, AVD, AVB, and ACCH correlated with spleen
SCREENCAST size with a Pearson correlation of 0.72 (95%CI, 0.49,0.85; p2.6x10-6), 0.20
W. Fateen1,2,*, M. Goldsworthy1, M. Aldersley2, R. Jones2 (95%CI, -0.15,0.51; p0.26), and 0.56 (95%CI, 0.27,0.76; p6.2x10-4), respec-
1
University of Leeds, 2Department of Hepatology, Leeds Teaching Hospitals NHS tively, and correlated with platelet count with a correlation of -0.69 (95%CI, -
Trust, Leeds, United Kingdom 0.84,-0.45; p8.7x10-6), -0.30 (95%CI, -0.58,0.05; p0.09), and -0.40 (95%CI, -
Contact E-mail Address: umwaf@leeds.ac.uk 0.65,-0.07; p0.02), respectively.
CONCLUSION: PHT is associated with endoscopically-inapparent microvascu-
INTRODUCTION: Working in partnership with patients and their families is lar dilatation and altered epithelial cell volume/morphology revealed in vivo by
essential in modern healthcare. For this partnership to be effective, patients must pCLE. Analysis shows that quantitative pCLE markers correlate with surrogate
have sufficient understanding of their condition. Patient understanding may be clinical markers of PHT. Additional studies will seek to define the correlation
limited due to restricted time for counselling in clinic and the variable quality of between microscopic portal hypertensive vascular patterns, epithelial cell volume,
available educational resources. To our knowledge, patient understanding of and the hepatic venous pressure gradient. Quantitative pCLE of the duodenum
cirrhosis and its complications has not been previously studied. may reveal subclinical PHT and serve as a novel and early biomarker of liver
AIMS & METHODS: We aim to assess the baseline knowledge of a cohort of disease and its complications.
patients with liver cirrhosis and to test the effectiveness of a condition-specific Disclosure of Interest: None declared
screencast. This is a narrated video that presents relevant and evidence-based
information about liver cirrhosis, supported by on-screen text, diagrams and
animations. OP116 LIVER STIFFNESS AND CONTROLLED ATTENUATION
The study has been approved by our local research and development department PARAMETER FOR ASSESSMENT OF FIBROSIS AND STEATOSIS
as a study designed for service quality improvement. Patients attending the out- IN CHILDREN WITH NON-ALCOHOLIC FATTY LIVER DISEASE
patient clinic aged 18 years or over with liver cirrhosis and on a surveillance W. Janczyk1,*, E. Jurkiewicz2, A. Wierzbicka-Rucinska3, P. Socha1
programme for hepatocellular carcinoma were eligible to participate. Those 1
Gastroenterology, Hepatology and Eating Disorders, Childrens Health Memorial
who were not aware they had liver cirrhosis and patients who had hepatic ence- Institute, 2Radiology, Childrens Health Memorial Institute, 3Biochemistry and
phalopathy were not eligible to participate. Experimental Medicine, Childrens Health Memorial Institute, Warsaw, Poland
Participants completed a baseline questionnaire assessing their knowledge of the Contact E-mail Address: w.janczyk@czd.pl
management and complications of cirrhosis. They were then invited to watch a
12-minute-long screencast, which was developed in collaboration with patient INTRODUCTION: Liver stiffness measurement (LSM) by FibroScan (FS) was
groups and liver specialists. The screen-cast describes the definition, causes, previously shown to be a valuable method in detection of liver fibrosis in adults
management and complications of cirrhosis. Patients were invited to complete with chronic liver diseases as HCV and non-alcoholic fatty liver disease
a new copy of the original questionnaire immediately after watching and once (NAFLD). The Controlled Attenuation Parameter (CAP) available on FS
again at least one month (range 1-6 months) after watching the screen-cast. allows simultaneous assessment of the degree of liver steatosis. This method
Participants completed the interval questionnaire and submitted it by post or seems especially promising for children with liver diseases in whom indications
online. to perform liver biopsy are limited.
RESULTS: Sixty-three patients were approached. Eight were not eligible to AIMS & METHODS: Aim of the study was to evaluate LSM and CAP in
participate and six declined. Forty-nine patients were assessed (M31, F 18) children with NAFLD and compare these results to healthy controls. We also
with a median age of 56 and median follow-up period of three years. Participants assessed their relationship to non-invasive parameters describing the degree of
achieved a total score of 29.1% on the baseline questionnaire. This increased to obesity, liver function and lipid metabolism.
67.9% after watching the screencast (P50.001). Thirty-four patients completed We investigated 38 overweight/obese children aged 14y (11.4-15.8) [median (Q1-
the follow-up questionnaire after an interval period. They achieved a total score Q3)] with NAFLD diagnosed by presence of liver steatosis on ultrasound and
of 64.7%, an increase of 35.6% compared to baseline (P50.001). Between base- increased ALT activity and 18 healthy controls aged 12y (6.7-15.2). NAFLD
line and interval follow-up, knowledge of the reason for having regular ultra- patients underwent detailed investigation including risk factors associated with
sounds improved by 22.2%, regular endoscopies by 41.3%, bone-density scans metabolic syndrome. In children with NAFLD we performed MRI of the lumbar
by 53.3%, being prescribed laxatives by 73.3%, risk of bleeding by 51.1%, lia- region to assess subcutaneous (SAT) and visceral adipose tissue (VAT). VAT
bility to develop encephalopathy by 66.1%, knowledge of complications (e.g. area and SAT area at the L2-L3 and L4-L5 interspaces and total VAT and SAT
muscle wasting and impaired clotting) by 12.9% and knowledge of liver functions volumes were determined by manual examination using image analysis software.
by 27.2%. Correlations were tested by Spearman rank test.
CONCLUSION: Participating patients had been seen previously in a liver clinic RESULTS: NAFLD patients had significantly increased LSM compared to con-
where information about cirrhosis is regularly delivered by healthcare profes- trols [5.35 (4.70-6.4) vs. 4.2 (3.6-4.4) kPa] and there was a marked difference in
sionals and where information leaflets are readily available. Despite this, baseline CAP [264.5 (243-304) vs 187 (112-217) dB/m]; p50.05.
understanding was poor. Delivering information by video led to a significant LSM correlated with all fat tissue compartments measured by MRI and HDL
increase in patients knowledge about their condition. This was present both cholesterol (r(-0.4)). CAP significantly correlated with waist circumference
immediately and following an interval period. We therefore present an effective (r0.51), extraperitoneal visceral adipose tissue (r0.37), subcutaneous subfas-
way to empower patients with accurate, up-to-date and retainable information, cial fat tissue (r0.38) and serum levels of ALT (r0.57), AST (r0.42) and
which could be easily translated to several other chronic disease conditions. GGTP (r0.5).
Disclosure of Interest: None declared CONCLUSION: 1. LSM and CAP using Fibroscan are easily applicable to
children with NAFLD.
2. Liver stiffness and steatosis using LSM and CAP are significantly higher in
OP115 ASSESSMENT OF PORTAL HYPERTENSION USING PROBE- NAFLD patients when compared to healthy controls.
BASED CONFOCAL LASER ENDOMICROSCOPY (P-CLE) 3. Liver fat content measured by CAP correlates significantly with liver function
S.K. Singh1,*, E. Rodriguez-Diaz1, G. Baffy2 tests and adipose visceral tissue in the extraperitoneal compartment as well as
1
Medicine, Gastroenterology / Endoscopy, Boston University / VA Boston subcutaneous adipose tissue. LSM is correlated to fat tissue in all compartments
Healthcare System, 2Medicine, Gastroenterology / Endoscopy, VA Boston but does not correlate with liver function tests.
Healthcare System, Boston, United States Disclosure of Interest: None declared
Contact E-mail Address: singhsk@bu.edu
INTRODUCTION: There has been recent increasing interest in the early detec-
tion of portal hypertension (PHT) in an attempt to prevent the morbidity of late-
stage cirrhosis, stratify disease severity and modify outcomes in potentially-rever-
sible conditions like NAFLD and alcoholic hepatitis.
AIMS & METHODS: To evaluate as a proof-of-concept the relationship of
novel quantitative endomicroscopic microvascular and morphological features
to clinical markers of PHT.
Methods: In an IRB-sanctioned study, we enrolled subjects with and without
PHT scheduled for a medically-indicated upper endoscopy at VA Boston.
Upon IV injection of 300 mg sodium fluorescein, real-time pCLE and video
microangiography were performed. The microvasculature was best visualized
A40 United European Gastroenterology Journal 2(5S)
OP117 ELASTOGRAPHIC ASSESSMENT OF LIVER STIFFNESS IN CONCLUSION: Rumination can be effectively corrected by biofeedback-guided
CHILDREN control of abdomino-thoracic muscular activity
O. Belei1,*, L. Olariu1, O. Gradinaru2, O. Marginean1 Disclosure of Interest: F. Azpiroz Financial support for research from: Danone,
1
First Pediatric Clinic, UNIVERSITY OF MEDICINE AND PHARMACY Given, Beneo, Shire, Consultancy for: Danone, E. Barba: None declared, M.
VICTOR BABES, 2Gastroenterology Department, Emergency County Hospital, Mego: None declared, A. Accarino: None declared, J. Malagelada: None
Timisoara, Romania declared
Contact E-mail Address: oana22_99@yahoo.com
INTRODUCTION: Non-invasive techniques for liver fibrosis assessment were TUESDAY, OCTOBER 21, 2014 8:3010:30
developed for adult patients and recent researches tested their accuracy in chil- UPDATE ON THE MANAGEMENT OF ACUTE PANCREATITIS HALL
dren. There is a trend towards elastography replacing liver biopsy in the evalua- B_____________________
tion of liver fibrosis among children with chronic diffuse liver diseases.
AIMS & METHODS: To investigate the feasibility of liver stiffness (LS) mea- OP119 VALIDATION AND COMPARISON OF THE NEW SEVERITY
surement in children with chronic diffuse hepatopathies by means of Acoustic CLASSIFICATION SYSTEMS FOR SEVERITY OF ACUTE
Radiation Force Impulse Elastography (ARFI) and Shear Wave Elastography PANCREATITIS WITH OLD ATLANTA CLASSIFICATION
(SWE), compared to transient elastography (TE) as reference method. 54 chil- R.B. Thandassery1,*, M. Manrai1, J. Medarapalem1, P. Siddappa1, S. Appasani 1,
dren aged 4-18 years with different chronic hepatopathies (HBV, HCV infections, S.K. Sinha1, T.D. Yadav2, R. Kochhar1
autoimmune hepatitis, nonalcoholic steato-hepatitis, Wilson disease) were 1
Gastroenterology, 2General Surgery, Postgraduate Institute of Medical Education
enrolled. All children were examined by means of TE using FibroScan.10 valid and Research, Chandigarh, India
TE measurements were performed under fasting conditions and the median value Contact E-mail Address: doc.ragesh@gail.com
was calculated. ARFI was performed with Siemens Acuson S2000 Virtual Touch
ultrasound system. We calculated the mean value of 10 valid measurements for INTRODUCTION: Two new classification systems for the severity of acute
each patient. SWE was performed with an Aixplorer ultrasound system pancreatitis (AP) have been proposed recently, the determinant based classifica-
(SuperSonic Imagine). We calculated the mean value of 5 valid measurements tion (DBC) and revised Atlanta classification (RAC). We aimed to validate and
for each patient. All measurements were performed in the right liver lobe, in the compare these classification systems with original Atlanta classification (OAC).
same session. In all patients, transaminases levels didnt overcome 3 times upper AIMS & METHODS: Our aim was to validate and compare the DBC and RAC
normal limit values. with original Atlanta classification (OAC).
RESULTS: 54 children with an average age of 8.4 years ( 2.5) were included 469 adult patients with AP admitted to a tertiary care center from January 2009-
and had a successful measurement rate of 94,4%(51/54). Valid measurements June 2013 were included in the study. The new classification systems were vali-
were defined as a median value of LS measurements with a success rate(SR) dated and compared in terms of outcomes (need for interventions, total hospital
60% and an interquartile range interval(IQR)530%. Mean values were as and intensive care unit (ICU) stay and mortality).
follows: FibroScan: 7.36 1.3 kPa; ARFI: 1.46 0.12 m/s; SWE: 6.33 2.1 RESULTS: The mean age of patients was 39.913.4 years (331 males) with the
kPa. Accuracy of ARFI for detecting F1 was 85.71%, for F2 was 90.47 %, commonest etiology being alcohol (161, 34.3%) followed by gall stones (125,
for F3 was 80.95% and for F4 was 88%. Accuracy of SWE for detecting F1 26.6%). There were 119 (25.4%) patients with mild and 250 (74.6%) patients with
was 88%, for F2 was 92.85%, for F3 was 91% and for F4 was 95.23%. We severe AP as per OAC. Pancreatic necrosis was present in 66.1% and infected
found a significant correlation between FibroScan and SWE (r0.64, p0.001). pancreatic necrosis in 23.1% patients. 126 (26.9%) patients underwent interventions
Analysis of the whole lot of patients with valid measurements didnt show sig- (endoscopic n 49, 10.4%, radiological n95, 20.2% and surgical n47, 10%). 93
nificant correlation between FibroScan and ARFI (r0.24, p0.14). SWE didnt (19.8%) patients died. As per DBC, 97(20.7%), 172 (36.7%), 152 (32.4%), and
correlate with ARFI values (r0.18, p0.28). We analyzed separately the sub- 48(10.2%) patients were determined to have mild, moderate, severe, and critical
group of patients with valid measurements but less satisfactory technical para- AP, respectively. As per RAC, 119 (25.4%), 160 (34.1%), and 190 patients
meters (SR between 60%470% and/or IQR30%). There was no significant (40.3%) were determined to have mild, moderately severe, and severe AP, respec-
correlation between LS measurements by means of FibroScan and ARFI (r- tively. Higher grades of severity were associated with worse outcomes in DBC, RAC
0.26, p0.52). However, in the same subgroup FibroScan correlated significantly and OAC.
with SWE (r 0.67, p0.05). In the subgroup of children in whom the quality Predictive accuracies were evaluated using area under the receiver operator char-
parameters for LS measurements were fulfilled with SR between 70% and 100% acteristics curve (AUROC) and Somers D co-efficient. The DBC, RAC and
and IQR530%, there was a significant correlation between FibroScan and OAC were comparable in predicting the need for interventions (AUROC 0.53,
ARFI (r0.58, p0.01) and FibroScan and SWE (r0.90, p0.01). 0.55, 0.54, p0.36) and length of hospital stay (Somers D, 0.27, 0.26, 0.23,
CONCLUSION: SWE based on supersonic share imaging is a new technique p0.41). However, both DBC and RAC had comparable but better accuracy
designed to overcome some of the disadvantages of other elastographic techni- than OAC in predicting need for ICU admission (AUROC 0.73 for both vs. 0.62
ques. Overall, it seems to correlate better with FibroScan compared to ARFI in for OAC, P50.001), length of ICU stay (Somers D, 0.35 for both vs. 0.24 for
children. Excluding patients with less satisfactory technical parameters OAC, p50.001) and mortality (AUROC 0.78 for both vs. 0.61 for OAC,
(SR60%470% and/or IQR30%), we obtained significant correlations p50.001).
between all 3 elastographic techniques. Both SWE and ARFI are non-invasive CONCLUSION: Determinant based classification and revised Atlanta classifica-
techniques feasible to perform in children along with FibroScan. tion categorize patients into subgroups that reflect clinical outcomes. Both have
Disclosure of Interest: None declared comparable and higher predictive accuracy than old Atlanta classification for
need for ICU admission, length of ICU stay and mortality.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
THERAPY UPDATE: GORD HALL D_____________________
TUESDAY, OCTOBER 21, 2014 8:3010:30
OP118 RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF COLORECTAL CANCER SCREENING: THE FUTURE HALL C_____________________
BIOFEEDBACK FOR THE TREATMENT OF RUMINATION
F. Azpiroz1,2, E. Barba3,*, M. Mego3, A. Accarino3, J.R. Malagelada4 OP120 POSITIVE PREDICTIVE VALUE OF FLEXIBLE
1
Medicina, Universitat Auto`noma Barcelona, Barcelona, 2Digestive System SIGMOIDOSCOPY SCREENING FOR PROXIMALLY LOCATED
Research Unit, University Hospital Vall dHebron, Barcelolna, 3Digestive System COLON LESIONS
Research Unit, University Hospital Vall dHebron, 4Digestive System Research S. C. Van Doorn1,*, R. Bevan2, E.J. Kuipers3, C. Rees2, E. Dekker1
1
Unit, University Hospital Vall d?Hebron, Barcelona, Spain Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
Contact E-mail Address: azpiroz.fernando@gmail.com Netherlands, 2Gastroenterology and Hepatology, South Tyneside General Hospital,
South Shields, United Kingdom, 3Gastroenterology and Hepatology, Erasmus
INTRODUCTION: In a previous study we showed that rumination is produced Medical Center, Rotterdam, Netherlands
by an unperceived, somatic response to food ingestion and developed an original Contact E-mail Address: s.c.vandoorn@amc.uva.nl
biofeedback technique for the treatment of rumination based on EMG-guided
control of abdomino-thoracic muscular activity. INTRODUCTION: In the UK flexible sigmoidoscopy screening (FSS) is offered
AIMS & METHODS: Our aim was to demonstrate the superiority of biofeed- at the age of 55. During sigmoidoscopy, if one of the following criteria is met, the
back versus placebo for the treatment of rumination. Twenty-four patients (16 participant is referred for colonoscopy: detection of a polyp in left colon
women, 8 men; 16-82 yrs age range) who fulfilled the Rome criteria for rumina- 410mm; 3 or more adenomas; adenoma with villous or tubulovillous compo-
tion were recruited and randomly allocated to biofeedback and placebo treat- nent; adenoma with high-grade neoplasia (dysplasia); or 20 or more hyperplastic
ment. Abdomino-thoracic muscle activity after a challenge meal was recorded by polyps 4 3 mm above the distal rectum. It is of importance to estimate which
EMG and the signal was displayed on a monitor and front in the patients: in the lesions in the proximal colon (proximal to the splenic flexure) are left undetected
biofeedback group, patients were instructed to control muscle activity, whereas in by FSS.
the placebo group patients were administered 120 mg symethicone. In each AIMS & METHODS: We aimed to evaluate the positive and negative predictive
patient 3 sessions were performed over a 10-day period. Physiological (muscular value (PPV & NPV) of FSS for proximally located colorectal lesions using a
activity by EMG) and clinical outcomes (number of rumination events by ques- model screening population.
tionnaires administered daily for 10 days) were measured before and after treat- In a previous Dutch screening colonoscopy trial (COCOS-trial), 1426 asympto-
ment. Data of 16 patients who already completely the study (8 per group) were matic persons between 50-75 years of age underwent primary colonoscopy. We
analyzed and mean SE calculated. evaluated which participants (based on the distally located findings that would
RESULTS: Patients on biofeedback, but not on placebo, effectively learned to have been identified during a screening sigmoidoscopy) would have met the
reduce intercostal activity (by 467 % vs 17 % on placebo; P5.001) and criteria for referral for colonoscopy. We also evaluated which participants had
anterior wall muscle activity (by 504 % vs 14 % on placebo; P5.001). relevant lesions in the proximal colon (defined as carcinoma, any adenoma, any
Biofeedback was followed by a reduction of rumination activity (738 % sessile serrated adenoma/polyp, or a hyperplastic polyp 4 10 mm). We calcu-
decrease of regurgitation episodes/day vs -218 % on placebo; P015). lated the PPV and the NPV of FSS for lesions in the proximal colon.
United European Gastroenterology Journal 2(5S) A41
RESULTS: If participants of the Dutch primary colonoscopy screening trial had intensity. The cross-validated area under the curve of a Receiver Operating
been screened by sigmoidoscopy, 117 of 1426 (8.2%) would have been referred Characteristic (ROC) curve using deamidated sequences for predicting undiag-
for colonoscopy. In 59% of the referred participants, no relevant lesions would nosed CD was 0.99. While TTg peptides sequences were not sensitive nor specific
have been detected in the proximal colon (Table 1). In 81.3% of 1309 participants to identify the undiagnosed CD, the combining peptides sequences of DGPs and
that would not have been referred, no relevant lesions would have been missed in transglutaminase were both highly sensitive (98.9 %) and highly specific (100 %).
the proximal colon. However, in 18.7% a relevant lesion would have been CONCLUSION: Combining subsequences in a specific order shows a high
missed; 1.5%advanced neoplasia, and 16.6% tubular adenomas with low-grade degree of specificity and sensitivity for celiac disease. Specially, the combination
dysplasia. The PPV of FSS for the detection of relevant lesions in the proximal of transglutaminase and deamidated gliadin seems likely to be a high-fidelity test
colon is 41% and the NPV is 81%, with an accuracy of 78%. with a high degree of accuracy. This method also may provide insight into the
Table 1.Lesions detected in the proximal colon shift in epitope recognition as patients progress from undiagnosed to sympto-
matic disease
Would not have Disclosure of Interest: None declared
been referred Would have
for colonoscopy been referred
Total number of 1309 for colonoscopy TUESDAY, OCTOBER 21, 2014 8:3010:30
colonoscopies 1426 (91.8%) 117 (8.2%) MANAGEMENT OF COMPLICATED CROHNS DISEASE HALL F2_____________________
n
due to a FC value above the cut-off level was accomplished in 28 (54.9 %) AIMS & METHODS: The aim of this study was to assess the correlation
w
patients in the intervention group. In the control group, 28 patients (70.0 %) between the concentration of fecal calprotectin and endoscopic findings one
had at least one FC value 4 300 mg/g. In all, 8 (28.6 %) and 16 (57.1%) of these
patients with a FC 4 300 mg/g experienced a relapse, in the intervention and
control groups, respectively (p 5 0.05). In all, 9 and 6 patients in the intervention
d ra
year after ileocaecal resection for Crohns Disease.
Prospective cohort study. Adult patients with CD that performed ileocaecal
i t h
resection between September 1, 2011 and December 31, 2013 were considered
group and 6 and 5 patients in the control group were treated with oral and topical
corticosteroids during a flare, respectively (NS).
CONCLUSION: In this trial with UC patients at high risk of disease relapse, we
found no significant difference in relapse rates between the patients with targeted
therapy based on FC levels and the patients in the control group. However,
W
for inclusion. Variables analyzed: age, sex, Montreal classification, smoking
habits, concentration of FC one year after surgery, ileocolonoscopy findings
one year after ileocaecal ressection according with Rutgeerts score. The sensitiv-
ity and specifity of FC was assessed using endoscopic findings as gold standard.
Endoscopic recurrence was considered if the Rutgeerts score was i2. A ROC
among the patients with active intervention due to a FC above the cut-off curve was performed to assess the best cut-off value for FC.
level, the relapse rate was significantly lower as compared to the patients in RESULTS: 22 patients were included. 48% males; 36% smokers. Endoscopic
the control group with a FC value 4 300 mg/g. Thus, our results indicate, that findings one year after ileocaecal resection according to Rutgeerts score was: i0
FC-levels might be used to identify patients with UC at risk for an imminent (n9), i1 (n4); i2 (n2); i3 (n2) and i4 (n5). Average fecal calprotectin
disease flare before symptoms develop, and that dose escalation of a 5-ASA agent concentration one year after surgery was 149.12 ug/g [minimum 10, maximum
is a therapeutic option for these patients. 562] in i0 group; 751.7 ug/g [minimum 81, maximum 1888] in the i1 group; 181
Disclosure of Interest: None declared ug/g [minimum 157, maximum 205] in the i2 group; 424 ug/g [minimum 55,
maximum 793] in the i3 group and 529.8 ug/g [minimum 33, maximum 1117]
in the i4 group. In this study the concentration of fecal calprotectin was not
OP141 STOOL TESTS CAN POTENTIALLY RULE OUT SIGNIFICANT statistically different between the group with endoscopic remission and the
BOWEL DISEASE IN SYMPTOMATIC PATIENTS IN PRIMARY group with endoscopic recurrence (p0.31). However, all patients with fecal
CARE calprotectin concentration 4 570ug/g had endoscopic recurrence. Some patients
J. Digby1,*, R. J. C. Steele2, J.A. Strachan3, C. Mowat4 (n4) with endoscopic recurrence had FC 5 200ug/g. The sensibility and speci-
1
University of Dundee, Dundee, United Kingdom, 2Medical Research Institute, ficity of FC was calculated using 5 cut-offs. The best cut- off for a 67% sensitivity
University of Dundee, 3Scottish Bowel Screening Centre, 4Department of and 81% specificity was 4 200ug/g. Thus, a value greater than 200ug/g of FC 1
Gastroenterology, Ninewells Hospital and Medical School, Dundee, United year after surgery shows a strong correlation with the presence of endoscopic
Kingdom recurrence of CD, although we have observed a high number of patients with
Contact E-mail Address: jaynedigby@nhs.net endoscopic recurrence with values below this cut -off.
CONCLUSION: Fecal calprotectin is a biomarker that, according to this study,
INTRODUCTION: Assessment of colorectal symptoms in primary care is diffi- has a high specificity but moderate sensitivity for predicting postoperative recur-
cult as they are poor predictors of underlying pathology. Patients presenting with rence in CD. All patients with FC 4 570ug/g had endoscopic recurrence. Studies
new symptoms are frequently referred for colonoscopy, which is the gold stan- with a larger number of patients are needed to better define the role of calpro-
dard for detection of significant bowel disease (SBD; colorectal cancer (CRC), tectin in this scenario.
high risk adenoma (HRA, defined as 3 or any 1 cm) and inflammatory bowel Disclosure of Interest: None declared
disease (IBD)). When symptomatic patients are brought to colonoscopy, yield of
SBD is low, with local audit revealing CRC yield of only 2%. Faecal immuno-
chemical tests for haemoglobin (FIT) are established in colorectal cancer screen- TUESDAY, OCTOBER 21, 2014 8:3010:30
ing, as faecal calprotectin (CPT) tests are in IBD clinics. We aimed to test their IMPLICATIONS OF MOLECULAR PATHOGENESIS ON ENDOSCOPIC THERAPY FOR
performance in primary care as a means to reduce unnecessary colonoscopy. BARRETTS OESOPHAGUS HALL L/M_____________________
AIMS & METHODS: Over a six-month period, general practitioners (GPs) in one
health board in Scotland were prompted when referring patients with colorectal OP143 A FISH BIOMARKER PANEL FOR THE PREDICTION OF HIGH-
symptoms to the Colorectal Service to obtain single samples of faeces for each GRADE DYSPLASIA AND ADENOCARCINOMA IN NON-
stool test (OC-Sensor FIT and BUHLMANN Calprotectin ELISA). Patients DYSPLASTIC BARRETTS ESOPHAGUS; RESULTS FROM A LONG-
referred to endoscopy were appointed within six weeks of referral. Clinical out- TERM PROSPECTIVE COHORT STUDY
comes were collected for all patients completing the tests and undergoing endo- M.R. Timmer1,*, C.T. Lau1, W. Rosmolen1, S.L. Meijer2, M.G. Dijkgraaf3,
scopy. Analysis of test performance for identification of SBD was performed. P. Fockens1, J.J. Bergman1, K.K. Krishnadath1 on behalf of On behalf of the
RESULTS: To date, 1000 patients have participated and analysis is ongoing. At North Holland, GUT club
present, a total of 569 patients (52.7% female, median age 64 years (range: 16-90, 1
Department of Gastroenterology and Hepatology, 2Department of Pathology,
IQR: 52-73) have completed both stool tests and had clinical outcomes available. 3
Clinical Research Unit, Academic Medical Center, Amsterdam, Netherlands
CRC was detected in 24 patients, 36 had HRA and 32 cases of IBD were diag- Contact E-mail Address: m.r.timmer@amc.uva.nl
nosed. FIT at the manufacturers recommended cut-off concentration of 50ng/ml
or above was present in 25.2% of referrals and at this cut-off, positive predictive INTRODUCTION: Barretts esophagus (BE) with no dysplasia is associated
value (PPV) for SBD would be 43.0%, negative predictive value (NPV) 92.9%, with a risk as low as 0.1% per year of developing esophageal adenocarcinoma
sensitivity 67.0% and specificity 82.8%; no CRC cases were below 50ng/ml but (EAC). Predictive biomarkers would be of great clinical value in facilitating more
48.6% patients with HRA and 40.6% of IBD cases were below this cut-off. The cost-effective surveillance. Due to the low progression rate of non-dysplastic BE,
CPT test at the manufacturers recommended cut-off concentration of 50mg/ml biomarker studies require long-term follow-up as well as a robust sample size and
or above was present in 60.0% of referrals and would give a PPV 19.9%, NPV are therefore scarce.
90.5%, sensitivity 75.9% and specificity 42.9%, however two cases of CRC had a AIMS & METHODS: We conducted a prospective multicenter cohort study in a
reading of below 50mg/ml along with 39.2% of HRA and 17.2% of IBD cases. community-based setting of Barrett patients with no dysplasia to determine
Further results will be available once analysis is complete. genetic predictors of progression. All patients were enrolled in an endoscopic
CONCLUSION: If we use FIT at a 50ng/ml cut-off concentration in primary surveillance program. Genetic abnormalities were detected on endoscopic cytol-
care it would potentially reduce referrals by around 75% whilst affording GPs ogy brushes by fluorescence in situ hybridization (FISH) using a probe-set
confidence that CRC in negative patients is highly unlikely, with no CRC cases including probes for P16, P53, Her-2/neu, 20q, and MYC, and the chromosomal
were present below this concentration in our cohort. The CPT test did not per- centromeric probes 7 and 17 to detect aneuploidy. All markers were dichoto-
form as well, but combining the tests is an option to reduce missed cases of HRA mized into normal/abnormal based on cut-off values determined using ROC
and IBD; however, this would produce many more referrals and false positives. If curves. Endpoints were progression to high-grade dysplasia (HGD) or EAC.
we are setting an arbitrary cut-off concentration for FIT of 50 ng/ml, we would RESULTS: A total of 428 patients were included in the study (345 males; age 59
have to accept that a number of HRA would be missed and we would have to 12 y.o.; BE length 3 cm, IQR 2-6) Median follow-up was 45 months (IQR 35
balance the risk of not referring patients with these lesions against the risks 72). There were 22 patients (5%) with histologic progression after review by 2
associated with unnecessary colonoscopy. Using FIT in primary care may help expert pathologists; 13 cases of HGD and 9 cases of EAC. Univariable analysis
target colonoscopy more appropriately when patients present with colorectal revealed that P16, and aneuploidy were significantly associated with progression,
symptoms. as well as the clinical variables age and maximum Barrett segment length (M).
Disclosure of Interest: None declared The remaining markers showed a non-significant tendency towards increased
odds of progression. Patients who tested positive for P16 and/or aneuploidy
were designated as marker-positive. Kaplan-Meier analysis revealed that there
A48 United European Gastroenterology Journal 2(5S)
was a significant difference in time to progression between the two groups (Log- TUESDAY, OCTOBER 21, 2014 8:3010:30
rank P0.009; Figure 1). The overall rate of progression to HGD/EAC was RISK FACTORS AND MANAGEMENT OF UPPER GI BLEEDING HALL
1.09% per patient-year. Marker-positive patients had a higher annual risk to N_____________________
progress to HGD/EAC (1.85%) than marker-negative patients (0.58%)
(P0.015). In a multivariate proportional hazards model, controlling for M OP145 DERIVATION AND VALIDATION OF A PROGNOSTIC SCORE
and age, a positive FISH result was a significant predictor of histological pro- IN OVER 12,000 PATIENTS WITH ACUTE UPPER
gression to HGD/EAC (HR 3.23; 95% CI 1.32-7.95). GASTROINTESTINAL BLEEDING
CONCLUSION: A FISH panel assessing aneuploidy and P16, can be used as a B. Kahan1, A. Barkun2, M. Martel2, R. Bryant3, Q. Nyguen3, V. Jairath4,*
decision making tool to stratify nondysplastic Barrett patients into low- and 1
Queen Mary University, London, United Kingdom, 2McGill University Health
high-risk disease categories to improve the efficacy of surveillance programs. Centre, Montreal, Canada, 3Royal Adelaide Hospital, Adelaide, Australia,
Disclosure of Interest: M. Timmer Other: The FISH probes used in this study 4
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
were donated by Abbott Molecular., C. T. Lau: None declared, W. Rosmolen:
None declared, S. Meijer: None declared, M. Dijkgraaf: None declared, P. INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common med-
Fockens: None declared, J. Bergman: None declared, K. Krishnadath: None ical emergency worldwide. Early risk assessment is an essential part of manage-
declared ment to help identify appropriate support and timely endoscopy for high risk
patients as well as early discharge for low risk patients. The Rockall and
Glasgow-Blatchford (GBS) scores are the most commonly utilised indices, with
OP144 PERSISTENT HUMAN PAPILLOMAVIRUS INFECTION AND the former a better prediction tool for mortality and the latter for identification
P53 OVEREXPRESSION ARE ASSOCIATED WITH TREATMENT of low risk patients.
FAILURE AFTER ENDOSCOPIC ABLATION OF BARRETTS AIMS & METHODS: We aimed to derive and validate a new risk score which
OESOPHAGUS combines features of both the Rockall and GBS scores to create a single scale
S. Rajendra1, B. Wang2, D. Pavey3, P. Sharma4, T. Yang5, C.S. Lee5, which could better identify low risk patients, as well as higher risk patients
N. Gupta6,*, R.S. Gill3, X.J. Wu5 requiring intervention (therapeutic endoscopy, surgery/embolisation) and at
1
Gastroenterology/Hepatology, Bankstown-Lidcombe Hospital, 2South Western risk of adverse outcome (mortality, rebleeding). Variables were selected for inclu-
Sydney Clinical School, University of New South Wales, 3Department of sion in the model based upon widespread association with outcomes plus clinical
Gastroenterology/Hepatology, Bankstown-Lidcombe Hospital, Sydney, Australia, judgement. The new score was derived using three large observational data-sets
4
Gastroenterology & Hepatology, Veterans Affairs Medical Center & University of (UK audit, Canadian RUGBE and REASON studies) and ranged on a scale
Kansas City, Kansas, United States, 5Anatomical Pathology, South Western Area from 0-20. The score was then validated in two independent data-sets (a UK
Pathology Service, Sydney, Australia, 6Gastroenterology & Nutrition, Loyola randomised trial and an Australian database). Receiver operating characteristics
University Medical Center, Maywood, United States were used to compare the performance of the new score with the Rockall and
Contact E-mail Address: Shan.Rajendra@sswahs.nsw.gov.au GBS scores, as well as quantifying the number of patients with events (thera-
peutic endoscopy, mortality, rebleeding, and surgery) at a score of 3 in com-
INTRODUCTION: Recently, we reported that transcriptionally active high-risk parison to the GBS.
HPV was strongly associated with Barretts dysplasia (BD) and oesophageal RESULTS: Variables in the new score were age, blood pressure, pulse, haema-
adenocarcinoma (OAC) suggesting a potential role in oesophageal carcinogen- temsesis, melaena, syncope, haemoglobin, urea, liver disease and malignancy.
esis.1 Moreover, increasing viral load and integration status was significantly The score was derived in 10639 cases of UGIB and validated in 1606 cases.
associated with disease severity along the Barretts metaplasia-BD-OAC The new score was superior to the GBS in predicting mortality (AUROC 0.77
pathway.2 vs. 0.74; P0.05), had a higher AUROC for surgery/radiological embolisation
AIMS & METHODS: Thus, HPV and p53 (a good predictor of dysplasia pro- (0.72 vs. 0.70; P0.51), and was identical for rebleeding (AUROC 0.68 vs. 0.68);
gression in Barretts oesophagus) clearance was examined in relation to treatment it performed less well than the GBS for predicting therapeutic endoscopy
outcome after endoscopic ablation of BD/OAC. Forty patients with BD/neopla- (AUROC 0.77 vs. 0.78; P0.05). The new score was superior to the Rockall
sia undergoing RFA/-EMR were included in the study. Pre/post-treatment score in predicting need for therapeutic endoscopy (AUROC 0.77 vs. 0.66;
biopsies obtained from the lesion/neo-squamous epithelium were analysed for 50.01), transfusion (AUROC 0.90 vs. 0.75; P50.01), rebleeding (AUROC
HPV DNA (nested PCR), viral transcriptional markers (E6/E7mRNA and 0.68 vs. 0.64; P0.09), surgery/embolisation (AUROC 0.72 vs. 0.72; P0.01);
p16INK4A) and p53. it had a lower AUROC than the Rockall score for mortality (0.77 vs. 0.79,
RESULTS: Post-ablation, 34/40 subjects achieved complete eradication of dys- P0.43). Using a threshold of 3 for the new score, fewer patients experienced
plasia and 24 reverted to squamous epithelium and 10 to intestinal metaplasia. all of the clinical endpoints of need for therapeutic endoscopy [2.3% (10/437) vs.
Pre-ablation, 15 patients were positive for transcriptionally active hr-HPV. 13/15 3.3% (20/600)], rebleeding [2.3% (10/436)] vs. 2.7% (16/597)], mortality [0.5%
patients cleared HPV and transcriptional markers after a median of 6.7 months (2/437) vs. 1.3% (8/600)] or surgery [0.5% (2/437) vs. 0.7% (4/600)] in compar-
(range 4 to 23.1). All but one who cleared the virus eliminated dysplasia/OAC ison to patients with a GBS score of 3.
whereas 2 who continued to have detectable HPV oncogene activity had persis- CONCLUSION: We have successfully derived and externally validated a novel
tent dysplasia (p50.05). A single patient with biologically active HPV and high- risk score for UGIB which can be used to triage both low and high risk patients
grade dysplasia at pre-ablation, cleared the virus post-treatment and subse- with UGIB. It performs better than the Rockall score for all outcomes apart
quently developed persistent p53 positivity with progression to cancer. Of thir- from mortality and better than GBS in predicting mortality and need for surgery/
teen p53 positive patients pre-ablation, 2 had non-biologically active HPV. 10/13 embolisation. It also performs more favourably than the GBS in identifying low
patients cleared p53 overexpression after a median of 6.7 months (range 3 to risk patients with a score of 3. The study was performed in a large sample size
36.4) becoming disease free, whilst 3/13 with persistent p53 mutation continued across three continents, enhancing the generalisability of the results. Further
to have detectable dysplasia at the end of the investigation (p0.004). 12/40 validation of the score is now warranted.
patients negative for both HPV & p53 at pre-ablation eradicated dysplasia/neo- Disclosure of Interest: None declared
plasia. All patients with persistent/progressive dysplasia/neoplasia at the end of
the study (6/40) had either detectable biologically active hr-HPV (n2) or over-
expression of p53 (n4). Only 1/10 patients with intestinal metaplasia (post- OP146 A MODEL TO ASSESS THE RISK FOR ASA/NSAID-RELATED
treatment) had persistent laboratory abnormality (p53 over-expression) at the ULCER BLEEDING FOR THE INDIVIDUAL PATIENT BASED ON
end of the investigation. 0/24 individuals who reverted to squamous epithelium THE NUMBER OF RISK FACTORS
had any detectable transcriptionally active hr-HPV or p53 mutation. There were J.M. Petersen1,*, J. Hallas2, M. Dall1, O.B. Scaffalitzky de Muckadell1, J. Mller
no cases of recurrence. Hansen1
CONCLUSION: Most HPV infected BD/OAC patients cleared the infection 1
Department of Medical Gastroenterology, Odense University Hospital, 2Research
with endotherapy. Persistence/progression of dysplasia/neoplasia after endo- Unit of Clinical Pharmacology, University of Southern Denmark, Odense,
scopic ablation of BO was associated with the presence of either HPV oncogenic Denmark
activity (viral persistence) or p53 overexpression. Contact E-mail Address: jmpetersen@health.sdu.dk
REFERENCES
1. Rajendra S, Wang B, Snow ET, et al. Transcriptionally active human papillo- INTRODUCTION: Aspirin/NSAID related peptic ulcer bleeding occurs in 1-3%
mavirus is strongly associated with Barretts dysplasia and esophageal adenocar- of patients and with a mortality rate of 10-15%. A number of risk factors are well
cinoma. Am J Gastroenterol 2013; 108: 1082-1093. established, but the incidence rate for the individual patient with a given set of
2. Wang B, Rajendra S, Pavey D, et al. Viral load and integration status of high- risk factors is unknown. The aim of this study was to develop a model that could
risk human papillomaviruses in the Barretts metaplasia-dysplasia-adenocarci- predict the incidence rate of UGB in users of ASA/NSAID based on the presence
noma sequence. Am J Gastroenterol 2013; 108: 1814-1816. of well-defined risk factors for the individual patient.
Disclosure of Interest: None declared AIMS & METHODS: The model was developed on data from a case-control study.
Cases were all diagnosed with upper gastrointestinal bleeding (UGB) from 1995-2006.
Controls were sampled from the source population by use of a risk-set technique. All
cases and controls were characterized in terms of factors known to affect the risk of
UGB. By use of census data, we inflated the control group, so that their composition
accurately reflected the age and gender distribution of the source population.
The incidence rate of UGB was calculated among 80-89 year old women, who
were users of NSAID, but not corticosteroids, ASA or SSRI and had no ulcer
history. This constituted the largest subgroup and could thus be used as refer-
ence. We used multivariate logistic regression and included first-order interac-
tions which could be meaningfully interpreted.
RESULTS: Number of cases was 1388. The adjusted incidence rate ratios (IRR)
for each risk factor was found with the reference: woman aged 80-89 and in
NSAID-treatment:incidence UGB: 12.1/1000 patient-year.
United European Gastroenterology Journal 2(5S) A49
OP146
An example: Male (1.23) aged 85 (1.0) in warfarin-treatment (2.56). corticoster- were 10.616.9 and 4.65.4 days respectively. The overall mortality was 10.3%
oids (1.84) and SSRI (1.80). 1.23*1.0*2.56*1.84*1.80*12.1 125.74 risk/1000 (n26).
pers /year. The mortality in those with AIMS65 scores of 0,1,2,3 and 4 were 3%, 7.8%,
CONCLUSION: This model allows an estimate of the incidence rate for UGB 20%, 36% and 40% respectively. The mortality was significantly higher in those
for each patient group based on the individual pattern of risk factors. Further with score 3 (37.1%) as compared to those with score 53 (6%), p50.001. The
studies are needed to confirm the validity of the model. predictive accuracy for mortality with a score 3 was high (area under the
Disclosure of Interest: None declared receiver operator characteristics curve 0.70, 95% CI 0.57-0.82). The mean
hospital stay (21.531.1 versus 9.012.8 days, p0.040) and ICU stay (5.1 6.1
versus 3.53.6 days, p0.042) were significantly higher in patients with scores 3
OP147 RISK FACTORS FOR EARLY AND DELAYED POST-OPERATIVE as compared to those with 53.
BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF CONCLUSION: AIMS65 is a simple, accurate, non endoscopic risk score that
GASTRIC NEOPLASMS can be applied early (within 24 hours of hospital admission) in patients with acute
T. Matsumura1,*, M. Arai1, K. Okimoto1, S. Minemura1, D. Maruoka1, upper GI bleeding. AIMS65 score 3 predicts high in-hospital mortality and
T. Nakagawa1, O. Yokosuka1 increased duration of hospital and ICU stay.
1
Department of Gastroenterology and Nephrology, Chiba University, Chiba, Japan REFERENCES
Contact E-mail Address: matsumura919@yahoo.co.jp 1. Saltzman JR, Tabak YP, Hyett BH, et al. A simple risk score accurately
predicts in-hospital mortality, length of stay, and cost in acute upper GI bleeding.
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely Gastrointest Endosc 2011; 74: 1215-24.
recongnized as the optimal treatment for gastric neoplasms. Safety of gastric Disclosure of Interest: R. Thandassery Financial support for research from: Nil,
ESD has been almost established, post-operative bleeding is sill the main concern Lecture fee(s) from: Nil, Consultancy for: Nil, Shareholder of: Nil,
affecting the safety, effectiveness, and outcome of the procedure. Directorship(s) for: Nil, Other: Nil,: Nil, M. Sharma Financial support for
AIMS & METHODS: Our aim of this study was to identify risk factors for post- research from: Nil, Lecture fee(s) from: Nil, Consultancy for: Nil, Shareholder
operative bleeding after gastric ESD, and to evaluate the relevance between such of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil, S. Mohiuddin Financial support
risk factors and the time of post-operative bleeding. for research from: Nil, Lecture fee(s) from: Nil, Consultancy for: Nil,
There were 413 patients with 425 gastric neoplasms consecutively treated by ESD Shareholder of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil, S. Al Kaabi
from June 2005 to March 2014. Demographic and clinical parameters associated Financial support for research from: Nil, Lecture fee(s) from: Nil, Consultancy
with post-operative bleeding were investigated. 83 patients (20.0%) were receiv- for: Nil, Shareholder of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil
ing antithrombotic agents, and they were assessed separately by the methods of
how to use such agents during ESD procedure. Post-operative bleeding that
occurred during the first 5 postoperative days was defined as early post-operative OP150 USE OF GASTROPROTECTIVE AGENTS AND RISK OF
bleeding, whereas subsequent bleeding was defined as delayed post-operative DABIGATRAN ASSOCIATED GASTROINTESTINAL BLEEDING: A
bleeding. POPULATION-BASED RETROSPECTIVE COHORT STUDY
RESULTS: Overall post-operative bleeding rate was 4.8%. In multivariate ana- W. Lau1, E.W. Chan1, I. C. Wong1, Y. He1, T.S. Tong2, W.-K. Leung2,*
lysis, intravenous heparin replacement (HR), chronic kidney disease (CKD) 1
Department of Pharmacology and Pharmacy, 2Department of Medicine,
undergoing hemodialysis, and a specimen size of 40 mm were predictive factors University of Hong Kong, Hong Kong, Hong Kong
for post-operative bleeding (odds ratio 5.77, 95 % CI: 1.67-19.96, odds ratio Contact E-mail Address: waikleung@hku.hk
33.86, 95 % CI: 4.72-242.74, and odds ratio 3.70, 95 % CI: 1.09-12.52, respec-
tively). A specimen size of 40 mm was a predictive factor for early post- INTRODUCTION: Dabigatran, a direct thrombin inhibitor, is the first new oral
operative bleeding (odds ratio 6.08, 95 % CI: 1.74-21.27), and HR and CKD anticoagulant available as an alternative to warfarin. Despite its convenience and
undergoing hemodialysis are risk factors for delayed one (odds ratio 12.23, 95 % superiority over warfarin in the prevention of stroke and thromboembolism,
CI: 2.63-56.77 and odds ratio 28.35, 95 % CI: 4.67-172.11, respectively). recent studies suggested an increase risk of gastrointestinal bleeding (GIB) in
CONCLUSION: Large size of specimen is a risk factor for early post-operative patients treated with dabigatran when compared to warfarin. These data were
bleeding, and intravenous HR and CKD undergoing hemodialysis are risk fac- however largely derived from clinical trials in selected patient population.
tors for delayed one. Patients with one or more risk factors should be watched AIMS & METHODS: This study determined the risk of dabigatran associated
carefully allowing for the timing of post-operative bleeding after ESD. GIB and the role of gastroprotective agents, including proton pump inhibitors
Disclosure of Interest: None declared (PPIs) and H2-receptor antagonists (H2RAs), in preventing dabigatran related
GIB in a population-based retrospective cohort study. Data were extracted from
the central database of the Hong Kong Hospital Authority, which is the provider
OP148 VALIDATION OF A NEW BEDSIDE PROGNOSTIC SCORE of all public medical services to a 7 million population. We identified all patients
(AIMS65) IN UPPER GASTROINTESTINAL BLEED who were newly prescribed with dabigatran between Jan 2010 and Dec 2013. The
R.B. Thandassery1,*, M. Sharma1, S.A. Mohiuddin1, S.R. Al Kaabi1 primary endpoint is the onset of clinical GIB. Multivariate analysis was used to
1
Gastroenterology, Hamad General hospital, Doha, Qatar characterize the risk of GIB after adjusting for baseline patients characteristics,
Contact E-mail Address: doc.ragesh@gmail.com medical illnesses and concurrent medications.
RESULTS: 5,041 patients, who were newly prescribed dabigatran, were included
INTRODUCTION: There are various risk stratification scores available for pre- in the analysis. Among them, 222 (4.4%) patients developed GIB with a median
dicting outcome in upper gastrointestinal (GI) bleed. However they are cumber- time to bleeding of 97 (IQR 262) days. Patients who were aged 75 years (OR
some and sometimes require endoscopic evaluation and therefore are rarely 1.83; 95% CI, 1.36 to 2.47), had prior ischemic stroke, transient ischemic attack
applied for early risk stratification. or systemic embolic events (OR 1.62; 1.19 to 2.2), and a prior history of peptic
AIMS & METHODS: To prospectively evaluate the newly proposed early bed- ulcer or GIB (OR 2.48; 1.81 to 3.39) were found to have higher risks of GIB.
side score, AIMS65 (A-albumin, I-INR, M-Mental status, S Systolic Blood Concurrent use of gastroprotective agents (OR 0.61; 0.44-0.84; log rank test P
pressure), in patients with acute upper GI bleed admitted to our tertiary care 0.018) or statin (OR: 0.58; 0.43-0.78) reduced the likelihood of GIB. Subcategory
hospital analysis showed that the use of either PPIs (OR 0.70; 0.51-0.98) or H2RAs (OR
251 consecutive patients presenting with acute upper GI bleed, from January 0.67; 0.50-0.90) significantly lowered the bleeding risk. The risk reduction by
2012 to December 2012, were included in the study. The AIMS65 scores were gastroprotective agents was significant only in patients with prior history of
calculated by allotting 1 points each for albumin (A) 530g/l, INR (I) 41.5, ulcers or GIB (OR 0.24; 0.14 to 0.43) but not in patients with no prior history
alteration in mental status (M), systolic blood pressure (S) 90mmHg and age (OR 0.83; 0.56 to 1.21).
65 years. The risk stratification was completed within 24 hours of hospital CONCLUSION: The risk of GIB associated with dabigatran use in real life
admission. Patients were managed as per standard protocol and outcomes were clinical settings is 4.4%. The use of gastroprotective agents significantly reduced
evaluated. the risk of dabigatran related GIB, particularly in high-risk patients with prior
RESULTS: The mean age of study group was 52.4 years with 193 males. The history of peptic ulcer or GIB.
etiology for upper GI bleed was duodenal ulcer in 74 (29.6%), gastric ulcer in 38 Disclosure of Interest: W. Lau: None declared, E. Chan: None declared, I. Wong:
(15.2%) and esophageal varices in 32 (12.8%) patients. 51 patients (20.3%) None declared, Y. He: None declared, T. Tong: None declared, W.-K. Leung
required intensive care unit (ICU) admission. The mean hospital and ICU stay Lecture fee(s) from: Takeda, Ferring, Consultancy for: Janssen.
A50 United European Gastroenterology Journal 2(5S)
OP151 ENDOSCOPIC TREATMENT OF UPPER GASTROINTESTINAL (difference -0.7; 95% CI -1.4 to 0.0; p0.05). For the restrictive policy fewer
BLEEDING WITH A NOVEL HEMOSTATIC POWDER: RESULTS patients received RBCs (difference -13%, 95% CI -35 to 11%) with on average
FROM A MULTICENTER PROSPECTIVE REGISTRY PERFORMED 08 (-19 to 03) fewer RBC units transfused. Clinical outcomes were better in the
IN ROUTINE PRACTICE (THE GRAPHE REGISTRY) restrictive policy: 28-day further bleeding, 5% restrictive vs 9% liberal (difference
S. Haddara1, S. Lecleire2, S. Leblanc3, J. Branche4, J. Jeremie5, J. Privat6, -37%, 95% CI -122 to 48%); 28-day mortality, 5% restrictive vs 7% liberal
L. Heyries7, J.-F. Bourgaux8, Y.L. Baleur9, P. Bichard10, J. Levy11, B. Godart12, (difference -1.3%, 95% CI -8.0 to 5.5%).; serious adverse events, 18% restrictive
A. Charachon13, U. Chaput14, P. Grandval15, V. Quentin16, L. Vuitton17, vs 22% liberal (difference -4.9%, 95% CI -22.6 to 12.8%). In the subgroup with
E. Coron1,* on behalf of The GRAPHE IHD, there was a large observed difference for mortality (12% restrictive arm
1
CHU Hotel Dieu, Nantes, 2Hopital Charles Nicolle, Rouen, 3Hopital Cochin, (n6) vs. 3% liberal arm (n2); interaction P0.11).
Paris, 4Centre Hospitalier Universitaire, Lille, 5Centre Hospitalier Universitaire, CONCLUSION: Adherence to both policies was high, resulting in a reduction in
Limoges, 6Centre Hospitalier, Vichy, 7Hopital Sainte Marguerite, Marseille, RBC transfusion and separation in the degree of anaemia and RBC exposure.
8
Centre Hospitalier, Nimes, 9Hopital Henri Mondor, Creteil, France, 10Centre There was a trend towards improved safety in the restrictive policy, apart from
Hospitalier Universitaire, Gene`ve, Switzerland, 11Clinique des Ce`dres, Toulouse, the increased mortality observed in patients with IHD. We have demonstrated
12
Centre Hospitalier Universitaire, Tours, 13Centre Hospitalier Princesse Grace, that a large-scale cluster randomised trial is feasible and is now warranted to
Monaco, 14Hopital La Riboisie`re, Paris, 15Hopital de La Timone, Marseille, determine the effectiveness of implementing restrictive RBC transfusion for all
16
Centre Hospitalier, Saint-Brieuc, 17Centre Hospitalier Universitaire, Besancon, patients with AUGIB.
France Disclosure of Interest: None declared
Contact E-mail Address: emmanuel.coron@chu-nantes.fr
INTRODUCTION: In recent pilot studies, the use of a hemostatic powder OP153 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
showed promising results to treat gastrointestinal bleeding. However, few data CONTROLLED TRIAL OF HIGH-DOSE REBAMIPIDE FOR LOW-
exist in routine practice with this new method. DOSE ASPIRIN-INDUCED MODERATE TO SEVERE SMALL
AIMS & METHODS: The aims of registry were to determine 1) the feasibility of INTESTINAL DAMAGE IN CHRONIC ASPIRIN USERS
the application of the hemostatic powder in routine clinical practice, and 2) its O. Handa1,*, T. Watanabe2, T. Tanigawa2, M. Shiba2, T. Takeuchi3, Y. Sakata4,
effectiveness in the short and medium term in different clinical situations. We Y. Naito1, K. Higuchi3, K. Fujimoto4, T. Yoshikawa1, T. Arakawa2
performed a prospective multicenter study in 17 centers, with 46 endoscopists. All 1
Molecular Gastroenterology and Hepatology, KYOTO PREFECTURAL
patients receiving the hemostatic powder (HemosprayTM, Cook Medical, USA) UNIVERSITY OF MEDICINE, Kyoto, 2Gastroenterology, OSAKA CITY
were included. The hemostatic powder was sprayed endoscopically onto the UNIVERSITY GRADUATE SCHOOL of MEDICINE, 32nd Department of
bleeding site using a catheter passed through the operative channel of the endo- Internal Medicine, OSAKA MEDICAL COLLEGE, Osaka, 4Internal Medicine,
scope. The quantity of powder was administered at the discretion of the endos- SAGA MEDICAL SCHOOL, Saga, Japan
copist based on clinical efficacy. The following parameters were analyzed: Contact E-mail Address: handao@koto.kpu-m.ac.jp
demographic characteristics, type of exteriorization (hematemesis, melena, hema-
tochezia), type of bleeding lesion, use of hemostatic powder as a first-line treat- INTRODUCTION: Recent studies using capsule endoscopy have shown that
ment or a rescue therapy (i.e. after failure of conventional treatment) and ease of prevalence of small intestinal damage in patients taking low-dose aspirin
use of the hemostatic powder as well as the main outcomes parameters, which (LDA) is high. Although some drugs have been shown to be effective in treating
were: firstly, the immediate efficacy defined by hemostasis achieved at the end of LDA-induced small intestinal damage, patients with mild damage which was
the endoscopic procedure, and secondly the absence of clinical recurrence eight thought to be clinically insignificant have not been excluded and not a few
days after the procedure. patients with such damage have been enrolled in most studies. Furthermore,
RESULTS: Ninety-six patients (69M/27F) aged 70 14 years were included in few randomized, double-blind, placebo-controlled trials to evaluate the efficacy
the study between June 2013 and April 2014. Patients were hospitalized for of drugs in the treatment of the LDA-induced damage have been reported.
hematemesis (n 34), melena (n 54) or hematochezia (n 11). Initial hypo- AIMS & METHODS: We conducted a multicenter, randomized, double-blind,
tension was noted in 28 patients. At endoscopy, an active bleeding was noted in placebo-controlled trial to assess the efficacy of high-dose of rebamipide, which is
88/96 (91%) cases, either pulsatile (14.6%) or oozing (85.4%). The location of a gastro-protective drug with various actions including enhancement of prosta-
bleeding was esophageal (n 14), gastric (n 31) or duodenal (n 50). The glandin synthesis, for the healing of LDA-induced moderate to severe small
bleeding lesion was identified in 89/96 (92.7%) cases. These lesions were 31 intestinal damage. Methods: Patients received 100 mg enteric-coated aspirin
tumors (32%), 43 ulcers (45%), 8 bleeding margins following endoscopic muco- daily for more than 3 months for primary or secondary prevention of cardiovas-
sal resection (8%) and 14 (15%) others bleeding lesions. The duration of the cular and cerebrovascular disease, and were found to have more than 3 mucosal
endoscopic procedure (including both the diagnostic and therapeutic steps) was breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy were
32 23 minutes. Application of the hemostatic powder was found to be very enrolled, whereas patients who had less than 3 mucosal breaks (mild damage)
easy, easy, moderately easy or difficult in respectively 39%, 50%, 5% and 6% of were excluded. Since we used inactive placebo, patients with overt gastrointest-
cases. This treatment was used as a first-line treatment in 51.6% of cases and as a inal bleeding were also excluded. Eligible patients were assigned to receive either
rescue therapy in 48.4% of cases. The immediate efficacy rate was 93.6%. No rebamipide 300 mg three times daily or placebo for 8 weeks with an allocation
recurrence of bleeding was noted in 74% of cases. ratio of 2:1. Then capsule endoscopy was performed again to investigate the
CONCLUSION: Our multicenter data obtained in routine practice conditions treatment effects on the damage. The primary endpoint was change in the num-
suggest the good feasibility and effectiveness of the hemostatic powder applied bers of mucosal breaks in 8 weeks. Secondary endpoints included complete heal-
endoscopically for gastrointestinal bleeding, even after failure of conventional ing of small intestinal mucosal breaks and improvement of the severity of the
methods. damage (from the damage of more than 3 mucosal breaks to the damage of less
Disclosure of Interest: None declared than 3 mucosal damages or complete healing).
RESULTS: A total of 43 patients were enrolled between February 2011 and
January 2014 and were randomly assigned to rebamipide group (n29) or pla-
OP152 RESTRICTIVE VERSUS LIBERAL BLOOD TRANSFUSION FOR cebo group (n14). Five patients were excluded because of cessation of LDA
ACUTE UPPER GASTROINTESTINAL BLEEDING (TRIGGER): therapy (n2), incomplete visualization at the second capsule endoscopy (n1),
PRAGMATIC, CLUSTER RANDOMISED, FEASIBILITY TRIAL patients intention to withdraw from the trial (n1), and development of overt
V. Jairath1,*, B. Kahan2, A. Gray3, C. Dore2, K. Palmer4, S. Travis5, R. Logan6, gastrointestinal bleeding (n1). Remaining 38 patients (rebamipide group; n25,
T. Walsh7, M. Murphy8 on behalf of on behalf of the TRIGGER Trial placebo group; n13) completed the study. After 8 weeks treatment, rebamipide
Investigators significantly decreased the number of mucosal breaks (p0.046), whereas pla-
1
Translational Gastroenterology Unit, Nuffield Department of Medicine, cebo did not. Although the difference was not significant (p0.13), the rate of
University of Oxford, Oxford, 2MRC Clinical Trials Unit, London, 3Emergency complete healing of mucosal breaks in rebamipide group (32%, 8 of 25) had a
Medicine, University of Edinburgh, 4Western General Infirmary, Edinburgh, tendency to be high, compared with placebo group (7.7%, 1 of 13). The rate of
5
Translational Gastroenterology Unit, Oxford, 6University of Nottingham, improvement of severity of the damage in rebamipide group (63%, 17 of 25) was
Nottingham, 7Critical Care, University of Edinburgh, Edinburgh, 8NHS Blood and significantly higher than that in placebo group (23.1%, 3 of 13, p0.016). Triple
Transplant, Oxford, United Kingdom dose of rebamipide was well-tolerated.
Contact E-mail Address: vipul.jairath@nhsbt.nhs.uk CONCLUSION: High-dose rebamipide is effective in the treatment for LDA-
induced moderate to severe enteropathy.
INTRODUCTION: Transfusion thresholds for upper gastrointestinal bleeding Disclosure of Interest: O. Handa: None declared, T. Watanabe: None declared, T.
(UGIB) are controversial. Observational studies suggest associations between Tanigawa: None declared, M. Shiba: None declared, T. Takeuchi: None
liberal red blood cell (RBC) transfusion and adverse outcome, and a recent declared, Y. Sakata: None declared, Y. Naito Financial support for research
trial reported increased mortality following liberal transfusion. from: Takeda Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co. Ltd, Eisai
AIMS & METHODS: Pragmatic cluster randomised trial to evaluate the feasi- Co. Ltd, K. Higuchi Financial support for research from: Otuka Pharmaceutical,
bility and safety of implementing a restrictive (transfusion when haemoglobin Lecture fee(s) from: Otuka Pharmaceutical, K. Fujimoto: None declared, T.
(Hb) 58gdL) versus liberal (transfusion when Hb 510g/dL) RBC transfusion Yoshikawa: None declared, T. Arakawa: None declared
policy for UGIB. Hospitals were randomised to a policy which was implemented
through a multi-faceted educational intervention targeting all staff caring for
patients with UGIB. All adult patients were eligible to participate, regardless
of co-morbidity; the only exclusion criterion was exsanguinating haemorrhage.
Feasibility and exploratory clinical outcomes were recorded up to day 28.
RESULTS: 936 patients were enrolled in six hospitals (three restrictive, three
liberal). Although there were some baseline imbalances, Rockall and Blatchford
risk scores were identical between policies. Protocol adherence was 96% in the
restrictive policy vs 83% in the liberal policy (difference 14%, 95% CI 7 to 21%).
In patients with Hb5120 g/L, Hb at discharge was lower for the restrictive policy
United European Gastroenterology Journal 2(5S) A51
TUESDAY, OCTOBER 21, 2014 8:3010:30 A multicenter follow-up study was carried-out including 649 patients, diagnosed
GASTRIC CANCER: NEW INSIGHTS INTO PATHOGENESIS AND MANAGEMENT with PL between 1995 and 2004, in 9 participating hospitals from Spain, which
LOUNGE 5_____________________ repeated the endoscopy and biopsy (following the Sidney protocol) during 2011-
2013. Fresh gastric mucosa, a sample of saliva, and a questionnaire on medical
OP154 H. PYLORI INFECTION ALTERS HUMAN GASTRIC information and habits of life were collected. DNA from paraffin blocks of
MICROBIOTA AND BACTERIAL DIVERSITY recruitment biopsy was used for analysis of H. pylori by PCR, and for the
T.H. Li1,*, Y. Qin2, P.C. Sham2, W.K. Leung1 analysis of methylation patterns by the Infinium 450 K methylation arrays.
1
Department of Medicine, 2Department of Psychiatry, The University of Hong Based on morphology, IM was sub-classified as complete (small intestinal type,
Kong, Hong Kong, Hong Kong CIM) and incomplete (colonic type, IIM). Analysis was done using Cox propor-
Contact E-mail Address: silviath@hku.hk tional hazards risk (HR) models.
RESULTS: At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34%
INTRODUCTION: H. pylori (HP) is classified by the World Health IIM, and 4% dysplasia. The mean of follow-up was 12 ys. 24 patients (3.7%)
Organization as a type I carcinogen. However, the distribution and significance developed a gastric adenocarcinoma during follow-up. The incidence rate of GC
of other bacteria in the human stomach remain poorly characterized. was 2.76 and 5.76 per 1,000 person-years, for those with CIM and IIM respec-
AIMS & METHODS: This study aims to characterize the gastric microbiota in tively. The HR of progression to CG was 6.4 (95%CI 0.8-49.6) and 2.4 (0.3-19.8)
individuals with and without HP infections; and determine the changes in micro- for those with IIM and CIM at baseline, compared with those with chronic
biota after HP eradication. Endoscopic gastric biopsies were obtained from the atrophic gastritis, after adjusting for sex, age, family history of GC and use of
antrum and corpus of informed consent patients. Patients should have no ulcer NSAIDs.
or tumor found on gastroscopy. HP infection status was determined by rapid CONCLUSION: Patients with IIM have the highest risk of progression to GC.
urease test and histology exam. Bacterial DNA was extracted and sequenced on Disclosure of Interest: None declared
next generation sequencing platform (454 pyrosequencing), targeting the V3 and
V4 regions of bacterial 16S rRNA genes. Operational taxonomic unit (OTU)
clustering, diversity indexes calculation, taxonomic classification, PCoA and sta- OP156 ZIPPER-INTERACTING PROTEIN KINASE INDUCES
tistical analyses were performed after quality control and raw sequence proces- EPITHELIAL-MESENCHYMAL TRANSITION IN GASTRIC
sing. Hierarchical clustering based on weighted UniFrac distance of samples CANCER CELL THROUGH AKT-BETA CATENIN SIGNALING
using Wards algorithm was implemented. J. Bi1,*, J. Li2, Q. Su1, L. Zhang1
RESULTS: A cohort of 27 patients was studied including 13 HP infected 1
Lab of General surgery, The first affliated hospital of Sun Yet-sen university,
patients, among which 3 had repeated endoscopic biopsy after receiving antibio- 2
State Key Laboratory of Oncology in South China, Sun Yat-Sen University
tics for HP eradication. In total, 494 non-singleton OTUs were identified from Cancer Center, guangzhou, China
165,651 high-quality sequencing reads. 27 OTUs accounted for over 90% of all Contact E-mail Address: jiongbi@gmail.com
sequencing reads, which belong to three phyla of Proteobacteria (5 OTUs),
Firmicutes (16 OTUs) and Actinobacteria (6 OTUs). Hierarchical clustering pre- INTRODUCTION: Zipper-interacting Protein Kinase (ZIPK) belongs to the
sents two cluster groups: first group contains mostly HP negative samples (n37) death-associated protein kinase family [1]. In accordance with its cell death pro-
while the second group exclusively comprises HP positive samples only (n16). moting activity, some evidences suggest that ZIPK functions as a tumor suppres-
The phylum Fusobacteria was only found in the first group of predominantly HP sor[2]. However, the DAPK family exhibits anti-apoptotic activity under certain
negative samples. The first group has markedly greater microbial species diversity conditions. ZIPK is described as a novel co-activator of the AR and provide a
with an average Shannon diversity index of 4.08 (SD 0.50) comparing to 1.95 (SD growth advantage to prostate cancer cells [3]. ZIPK induces Wnt/-catenin -
0.46) of the second group (p 5 0.01); the species richness estimator Chao 1 index mediated gene expression and cell growth in human colon carcinoma cells [4].
is also distinctly greater in the first group (SChao 1 61.71, SD 19.21) than that of In the current study, both in vitro and in vivo assays have been used to char-
the HP positive group (SChao 1 35.66, SD 14.19) (p 5 0.01). Consistent with the acterize the function of ZIPK. The possible molecular mechanism of ZIPK in
Chao 1 index, 227 and 58 OTUs specifically appeared in the first and second cancer cell growth and metastasis has been emphasized.
group, respectively. The average Shannon diversity index increases from 2.42 (SD AIMS & METHODS: ZIPK was stably expressed in BGC-823 cells using lenti-
0.97) to 4.37 (SD 0.35) (p 5 0.01) after antibiotics treatment for HP. Besides the viral vector. Foci formation and soft agar assays were performed to detect cell
increase in diversity and species richness, two genera Corynebacterium (p 0.03) growth, and cell proliferation was tested by XTT as well. Cell migration and
and Haemophilus (p 0.03) were significantly enriched in the post treatment invasion were investigated by wound healing and transwell invasion experiments.
samples. Clustering analysis however shows minimal correlation between micro- For in vivo tumorigenicity and metastatic assays, subcutaneous and intravenous
biota composition and the anatomical site of the biopsy or patients age. injections were done in the 4- to 5-week old nude mice. EMT markers and AKT-
CONCLUSION: H. pylori colonization of the stomach results in alteration in GSK3 signaling were detected by western blot. ZIPK and AKTp308 were tested
gastric microbiota and reduction in bacterial diversity. The changes in gastric by immunohistochemistry in primary gastric cancers and matched metastatic
microenvironment by HP may contribute to gastric carcinogenesis that deserves lymph nodes, the patient survival time was also analyzed.
further investigations. RESULTS: ZIPK could markedly increase BGC-832 cell proliferation, colony
Disclosure of Interest: None declared formation, migration and invasion in vitro. The nude mouse tumor growth
curves showed that tumors induced by ZIPK-transfected cells grew much more
rapidly. A significantly larger number of metastatic nodules were found at the
OP155 INCOMPLETE TYPE OF INTESTINAL METAPLASIA HAS THE surface of the lungs of mice injected with the ZIPK- BGC823 cells. Through
HIGHEST RISK TO PROGRESS TO GASTRIC CANCER: RESULTS western blot, we found that ZIPK increased expression of -catenin and vimen-
OF THE SPANISH FOLLOW-UP MULTICENTER STUDY tin, and decreased the levels of E-cadherin. In addition, the expression levels of
C.A. Gonzalez1,*, J.M. Sanz-Anquela2, O. Companioni1, C. Bonet1, Snail and Slug, were dramatically elevated by ZIPK expression. The expression
M. Berdasco3, C. Lopez4, J. Mendoza5, M. Martin-Arranz6, J.J. Pozo7, E. Rey8, of pAkt was increased when ZIPK was overexpressed. However, the phosphor-
F. Sanchez-Ceballos8, E. Poves9, L. Espinosa9, J. Barrio10, M.A. Torres11, ylation of GSK-3 was not changed. These results suggested that ZIPK plays a
M. Cuatrecasas12, I. Elizalde13, L. Bujanda14, M. Garmendia15, A. Ferrandez16, key role in regulation of EMT through AKT/-catenin. Consistent with our
G. Munoz17, M. Barenys18, M.J. Paules19, S. Lario20, M.J. Ramirez20, J. Gisbert5 finding in gastric cancer cells, co-expression of ZIPK and phosphorylated
1
Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, AKT in metastatic lymph nodes predicted unfavorable outcome in gastric
Hospitalet del Llobregat, Barcelona, 2Dept of Pathology, Hospital Principe de cancer patients.
Asturias, Alcala de Henares, 3Cancer Epigenetics and Biology Program, CONCLUSION: ZIPK promoted cell growth, migration and tumor formation in
IDIBELL, Hospitalet del Llobregat, Barcelona, 4Dept of Pathology, 5Dept of nude mice. ZIPK enhanced AKT activity, inducing EMT and promoting tumor
Gastroenterology, Hospital Universitario de la Princesa, 6Dept of invasion and metastasis.
Gastroenterology, 7Dept of Pathology, Hospital Universitario La Paz, 8Dept of REFERENCES
Gastroenterology, Hospital Clnico San Carlos, Madrid, 9Dept of 1. Kawai T, Matsumoto M, Takeda K, et al. ZIP kinase, a novel serine/threonine
Gastroenterology, Hospital Universitario Prncipe de Asturias, Alcala de Henares, kinase which mediates apoptosis. Mol Cell Biol 1998; 18: 1642-1651.
10
Dept of Gastroenterology, 11Dept of Pathology, Hospital Universitario Ro 2. Bi J, Lau SH, Hu L, et al. Downregulation of ZIP kinase is associated with
Hortega, Valladolid, 12Dept of Pathology, 13Dept of Gastroenterology, Hospital tumor invasion, metastasis and poor prognosis in gastric cancer. Int J Cancer
Universitari Clnic de Barcelona, Barcelona, 14Dept of Gastroenterology, 15Dept of 2009; 124: 1587-1593.
Pathology, Hospital Universitario Donostia, Donostia, 16Dept of Gastroenterology, 3. Leister P, Felten A, Chasan AI, et al. ZIP kinase plays a crucial role in
17
Dept of Pathology, Hospital Clnico Universitario Lozano Blesa, Zaragoza, androgen receptor-mediated transcription. Oncogene 2008; 27: 3292-3300.
18
Dept of Gastroenterology, Hospital de Viladecans, Viladecans, Barcelona, 19Dept 4. Togi S1, Ikeda O, Kamitani S, et al. Zipper-interacting protein kinase (ZIPK)
of Pathology, Hospital Universitari de Bellvitge, Barcelona, 20Dept of modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-
Gastroenterology, Corporacio Sanita`ria Universita`ria Parc Taul, Sabadell, Spain like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem 2011; 286: 19170-
Contact E-mail Address: aexposito@iconcologia.net 19177.
Disclosure of Interest: None declared
INTRODUCTION: In high or moderate risk population, periodic surveillance of
patients at risk of progression from gastric precursor lesions (PL) to gastric
cancer (GC) is recommended, as it represents the most effective strategy for
reducing the burden of GC. The incomplete type of intestinal metaplasia (IM)
may be considered as the best candidate, but more research is needed to confirm
it, and to identify other markers of progression.
AIMS & METHODS: 1)To evaluate the risk of progression to GC in patients
with PL and 2)To assess the effect of virulence factors of H. pylori infection, the
effect of polimorphisms of candidate genes, and the effect of epigenetic variants.
Results regarding the first aim are described in this presentation.
A52 United European Gastroenterology Journal 2(5S)
OP157 HELICOBACTER PYLORI-RELATED LONG NONCODING RNA OP159 EFFECTS OF ALDH2-GENOTYPE, PPI-TREATMENT AND L-
(LNCRNA) DOWN-REGULATED EXPRESSION (DREG) INHIBITS CYSTEINE ON THE LEVELS OF CARCINOGENIC
GASTRIC CANCER PROLIFERATION AND METASTASIS BY ACETALDEHYDE IN GASTRIC JUICE AND SALIVA AFTER
TARGETING MUC2 INTRAGASTRIC ALCOHOL ADMINISTRATION
X. Zhou1,*, G. Zhang1 R. Maejima1,*, K. Iijima1, P. Kaihovaara2, T. Koike1, T. Shimosegawa1,
1
Gastroenterology, the First Affiliated Hospital of Nanjing Medical University, M. Salaspuro2
1
Nanjing, China Tohoku University Hospital, Sendai, Japan, 2Research Unit on Acetaldehyde and
Contact E-mail Address: zhouxiaoying0926@sina.cn Cancer, University of Helsinki, Helsinki, Finland
Contact E-mail Address: kiijima@med.tohoku.ac.jp
INTRODUCTION: Gastric cancer is one of the most frequent malignancies in
East Asian countries [1]. Despite efforts in multiple fields, there has been little INTRODUCTION: Acetaldehyde (ACH) associated with alcoholic beverages is
success in improving the disease-free survival rate of patients [2]. H. pylori has Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase
infected more than 50% of the total population and has been recognized as type I (ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50%
carcinogen of gastric cancer [3]. A significantly association has been identified in of Eastern Asians. In alcohol drinkers ALDH2-deficiency is well known risk
the relationship between H. pylori infection and gastric cancer but the underlying factor for upper digestive tract cancers. Presence of alcohol in systemic blood
mechanism was still unclear circulation of ALDH2-deficient subjects results in significantly elevated salivary
AIMS & METHODS: Long non-coding RNAs (lncRNAs) have been shown to ACH levels. This provides strong evidence for the causal relationship between
have critical regulatory roles in cancer biology. In this study, we investigated local ethanol-derived ACH and oral, pharyngeal and esophageal cancers.
whether H. pylori infection could promote gastric cancer by regulating the Alcohol and ALDH2-deficiency are established risk factors also for stomach
expression of lncRNAs. Differentially expressed lncRNAs between H. pylori cancer. Normal human gastric mucosa expresses three alcohol dehydrogenase
positive and negative tissues were identified by microarray and validated using (ADH) isozymes and low Km ALDH2-enzyme activity. High-Km and high-
quantitative real-time polymerase chain reaction. Vmax ADH4 plays a key role in the gastric first pass metabolism of ethanol to
RESULTS: Our results indicated that H. pylori positive tissues have a specific ACH at high intragastric ethanol concentrations during the first 1 2 hours after
profile of lncRNAs. Cell biological assays in combination with small interfering alcohol intake. ADH-containing oral microbes, colonizing hypochlorhydric sto-
RNA-mediated knockdown or lentivirus vector-mediated over-expression were mach, contribute significantly to local intragastric production of ACH. However,
performed in order to probe the functional relevance of these lncRNAs. We the combined role of ALDH2-genotype, PPI-induced achlorhydria and ACH
identified an lncRNA, AF147447 (termed as Dreg), down-regulated expression eliminating L-cysteine in the regulation of ACH levels in gastric juice and
by H. pylori infection, which can inhibit gastric cancer growth and invasion saliva is not yet known.
in vitro, act as a tumor suppressor in the development of H. pylori induced gastric AIMS & METHODS: To assess the effect of ALDH2-genotype, achlorhydria
cancer. LncRNA-Dreg could combine with the oncogene MUC2 and repress its produced by PPI-treatment and slowly L-cysteine releasing capsule on the levels
expression. We also found that Dreg was regulated by transcription factor E2F1 of ACH in gastric juice and saliva following an intra-gastric infusion of ethanol.
by RNA immunoprecipatation and RNA pull down assays. These findings sup- 15. ALDH2-active and 10 ALDH2-deficient H. pylori negative healthy volun-
port a role of lncRNA- Dreg in tumor suppression. teers were included in the study. Through a nasogastric tube 15% ethanol (0.5g/
CONCLUSION: This discovery contributes to a better understanding of the impor- kg) was infused into the stomach. 5ml of gastric aspirate and 1-2 ml of saliva were
tance of the deregulated lncRNAs by H. pylori in gastric cancer and provides a collected at 30-min intervals up to 120 min. The first two samplings were done
rationale for the potential development of lncRNA-based targeted approaches for before and after 7-day administration of proton pump inhibitor (PPI, rabepra-
the treatment of H. pylori-related gastric cancer. zole 10mg b.i.d.) (experiment 1 and 2). After 3 more days on PPI, sampling of
REFERENCES gastric juice and saliva was repeated with 200mg of slowly L-cysteine releasing
1. Song JH and Meltzer SJ. MicroRNAs in pathogenesis, diagnosis, and treat- capsule administered before ethanol infusion (experiment 3).
ment of gastroesophagel cancers. Gastroenterology 2012; 143: 35-47. RESULTS: After intragastric infusion of alcohol ALDH2-deficiency resulted in
2. Ohnita K, Isomoto H, Shikuwa S, et al. Early and long-term outcomes of mean 5.6-fold increase in gastric juice ACH and mean 2.1-fold increase in sali-
endoscopic submucosal dissection for early gastric cancer in a large patient series. vary ACH compared to the subjects with normal ALDH2-enzyme (p50.0001 for
Exp Ther Med 2014; 7: 594-598. both). In ALDH2-active subjects PPI-treatment increased gastric juice ACH to
3. Kupcinskas J, Wex T, Link A, et al. Gene polymorphisms of micrornas in 3.3.-fold (p50.0001), but had no effect on salivary ACH. L-cysteine eliminated
Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS effectively gastric juice ACH both in PPI-treated ALDH2-active and ALDH2-
One 2014; 9: e87467. deficient subjects (mean 75% and 60%, p5 0.0001 and 50.0031, respectively).
4. Akhavan-Niaki H and Samadani AA. Molecular insight in gastric cancer CONCLUSION: Alcohol-induced marked increase in gastric juice ACH in
induction: an overview of cancer stemness genes. Cell Biochem Biophys 2013. ALDH2-deficient subjects provides strong evidence for the local carcinogenic
Disclosure of Interest: None declared action of ACH in gastric carcinogenesis. Nondependent changes in gastric
juice and salivary ACH levels caused by PPI-treatment and intragastric L-
cysteine indicate that gastric juice ACH level is locally regulated by gastric
OP158 MICRORNA-18A PROMOTES CELL PROLIFERATION BY mucosal ADH- and ALDH2-enzymes and by oral microbes colonizing acid
TARGETING IRF2 IN HUMAN GASTRIC CANCER AND PREDICTS free or achlorhydric stomach.
POOR SURVIVAL IN GASTRIC CANCER PATIENTS Disclosure of Interest: R. Maejima: None declared, K. Iijima Financial support
Y.-J. Chen1,*, H. Wu1, X.-Z. Shen1 on behalf of The staff of Prof. Xi-Zhong for research from: Biohit Oyj and TEKES the Finnish Funding Agency for
Shens laboratory Innovation, P. Kaihovaara: None declared, T. Koike: None declared, T.
1
Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shimosegawa: None declared, M. Salaspuro Consultancy for: Board member,
Shanghai, China medical advisor and stock owner of Biohit Oyj
Contact E-mail Address: shen.xizhong@zs-hospital.sh.cn
INTRODUCTION: MicroRNAs (miRNAs) are regulatory factors which are OP160 MIR-21, MIR-223 AND MIR-155 ARE NOVEL MUCOSAL
believed to play a crucial role in oncogenesis. Gastric carcinoma is one of the BIOMARKERS FOR HIGH-RISK GASTRITIS
most common malignancies and the second most lethal cancer worldwide. In this A. Link1,*, W. Schirrmeister1, C. Langner1, M. Varbanova1, J. Bornschein1,
study, we assessed the value of miR-18a in predicting outcome after curative T. Wex1, P. Malfertheiner1
resection in gastric cancer (GC) patients and defined the oncogenic significance 1
Gastroenterology, Hepatology and Infectious Diseases, OTTO-VON-
and function of miR-18a. GUERICKE UNIVERSITY HOSPITAL MAGDEBURG, Magdeburg, Germany
AIMS & METHODS: We analyzed miR-18a expression in 90 clinicopathologically Contact E-mail Address: alinkmail@gmail.com
characterized GC tissues by in situ hybridization, and 53 gastric juice samples (24
GC patients, 14 healthy controls, and 16 gastric ulcer patients) by quantitative RT- INTRODUCTION: Gastric carcinogenesis is a multifactorial H.pylori-triggered
PCR. The prognostic significance was assessed using Kaplan-Meier survival esti- dynamic process that goes through a cascade of preneoplastic conditions.
mates and log-rank tests. Biological roles of miR-18a were also explored in vivo. The Identification of biomarkers predictive for gastric cancer development may
interferon regulatory factor 2 (IRF2) were validated as targets of miR-18a by luci- help to improve current screening and surveillance programs.
ferase assay, quantitative RT-PCR, and western blot. The expression of IRF2 in the AIMS & METHODS: In this study, we systematically characterized expression
same 90 GC cases was also analyzed by immunohistochemistry. of miR-21, miR-155 and miR-223, microRNAs that are frequently deregulated in
RESULTS: In this study, we found that overexpressed intratumoral miR-18a gastric cancers (GC), with regard to preneoplastic precursor conditions in gastric
was associated with poor survival rate (P 5 0.001), and was an independent mucosa, H. pylori infection and gastric region. In a prospective study, 80 patients
prognostic factor for overall survival rate (P 5 0.001) in the GC patients. (normal (N), chronic gastritis (CG), atrophic gastritis intestinal metaplasia
High expression of miR-18a was also found in the gastric juice of GC patients. (AG) and GC) underwent upper GI endoscopy and H.pylori status, mucosal
Forced expression of miR-18a remarkably enhanced cell proliferation, migration, inflammation, atrophic or malignant changes were systematically evaluated
and invasion in GC cells, while inhibition of miR-18a by inhibitor caused the according to the updated Sydney classification. Biopsies were assessed from
opposite effects. Bioinformatics analysis identified the IRF2 as a potential miR- corpus, antrum and in case of gastric tumor also from the tumor (T-GC) and
18a target. Further studies confirmed the miR-18a suppressed the expression of near the tumor (NT-GC). Expression of miR-21, miR-223 and miR-155 was
IRF2 by directly binding to is 3-untranslated region. Moreover, miR-18a expres- analyzed by qRT-PCR from total RNA. Normalization was performed using
sion levels correlated inversely with IRF2 in human GC tissues. Western blot RNU6b. Potential diagnostic utility was tested using a simple miRNA expression
showed that forced expression of miR-18a in GC cells could not only down- score.
regulate the expression of IRF2, but also inhibit the expression of P53, suggesting RESULTS: All three studied miRNAs are differentially expressed in normal
that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC. gastric mucosa compared to tumor, especially for miR-21 and miR-223.
CONCLUSION: Taken together, these results demonstrated that miRNA-18a Remarkably, miRNA expression pattern was different between normal gastric
promoted cell proliferation by targeting IRF-2 in human GC and predicted poor corpus and antrum mucosa (p50.001) and therefore, further analyses were per-
survival in GC patients. formed for different localizations independently. In correlation with Correas
Disclosure of Interest: None declared cascade of mucosal alterations, we observed gradual increase in miR-155, miR-
United European Gastroenterology Journal 2(5S) A53
223 expression in corpus mucosa and increase of all 3 miRNAs in antrum from N Promotion, The Advanced Clinical Research Center, The Institute of Medical
to CG to AG (p50.001). In GC patients, adjusted non-tumorous corpus and Science, The University of Tokyo, Tokyo, Japan
antrum mucosa showed increased miRNA expression compared to subjects with
normal mucosa, although, we also observed heterogeneous and miRNA-specific INTRODUCTION: Immunohistochemistry (IHC) and fluorescence in situ
expression pattern between different regions including non-tumorous and tumor- hybridization (FISH) are the current mainstays of diagnosis of tissue HER2
ous tissues. H.pylori infection was associated with increased miR-155 and miR- status in gastric cancer. In contrast to breast cancer, however, HER2 expression
223 expression both in corpus and antrum, and slight increase of miR-21 expres- in gastric cancer occasionally demonstrates intratumoral heterogeneity, raising
sion in antrum. Lastly, using calculated summary score of three miRNAs, we concern about false-negative cases. Serum HER2, concentrations of the HER2
were able to distinguish atrophic gastritis from normal mucosa with area under extracellular domain (ECD) shed into the bloodstream, evaluates a different
the curve (AUC) 0.90 (95% CI 0.81.0) for corpus and AUC 0.98 (95% CI aspect of HER2 status but has not been well studied in gastric cancer.
0.961.01) for antrum. AIMS & METHODS: To elucidate the clinical utility of serum HER2 in gastric
CONCLUSION: Gastric cancer-associated miRNAs are differentially expressed cancer, we performed a prospective multicenter study (SHERLOCK trial, UMIN
in preneoplastic gastric mucosa and surrounding mucosa of GC patients. 000009773). Patients with gastric or gastro-oesophageal junction cancer of all
Gradual increase in miRNA expression correlates with Correas cascade of pre- stages were recruited. Pretreatment serum HER2 level was measured using che-
neoplastic alterations and H.pylori, suggesting miRNAs as diagnostic and poten- miluminescense immunoassay (CLIA), and tissue HER2 status was assessed by
tial predictive biomarkers. However, regional differences in miRNA expression IHC and FISH for IHC 2 cases at central laboratory. For stage IV cases, tissue
pattern within the stomach need to be considered in future studies. HER2 status was firstly assessed by various anti-HER2 antibodies at local
Disclosure of Interest: None declared laboratories of each hospital, then reevaluated using two antibodies (Dako
HercepTest II and SV2-61
) and FISH at central laboratory in a blinded manner.
RESULTS: From June 2011 to July 2013, a total of 224 patients were enrolled
OP161 HIGH LEVELS OF RELM-ALPHA CORRELATE WITH POOR from 14 centers. Both tissue HER2 status and serum HER2 level were success-
PROGNOSIS AND PROMOTE METASTASIS IN GASTRIC CANCER fully determined in 194 patients (stage I: 103, stage II: 11, stage III: 16, stage IV:
C. Ping1,*, Y. yaozong1 64). Tissue HER2 was positive in 42 patients (21.6%) and HER2 positive rate
1
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University was higher in an advanced stage. Serum HER2 level ranged from 4.5 to 148.0 ng/
School of Medicine, Shanghai, China ml (median 10.3 ng/ml), and significantly correlated with tissue HER2 status
Contact E-mail Address: chenping714@medmail.com.cn (p0.0058). With a cut-off level of 16.5 ng/ml determined by receiver operating
characteristics (ROC) analysis, sensitivity, specificity, positive predictive value
INTRODUCTION: Accumulating evidence indicates that Resistin-like mole- and negative predictive value of serum HER2 were 26.2%, 95.4%, 61.1% and
cule (RELM-) is involved in the angiogenesis of endothelial cells and indu- 82.4%, respectively.
cing of vascular of remodeling, while the clinical significance of RELM- in Among 64 stage IV patients, tissue HER2 results from both local and central
gastric cancer is poorly understood and the exact role of RELM- in gastric laboratories were available in 56 patients. Local laboratories initially diagnosed
cancer remains obscure. 18 cases as tissue HER2-positive and 38 as negative. Serum HER2 levels were
AIMS & METHODS: The aim of this study is to evaluate the expression of elevated (416.5ng/ml) not only in 9 of 18 tissue HER2-positive cases but also in
RELM- and its clinical significance in gastric cancer, to investigated its effective 7 of 38 tissue HER2-negative cases. Reevaluation of tissue by central laboratory
mechanism in order to the new therapeutic target. In the present study, expres- had identified 4 false-negative cases among 38 initially judged as HER2-negative.
a w n
sion levels of RELM- in 96 gastric carcinoma tissues, adjacent normal tissue,
and 2 types of gastric cancer cell lines were quantified by immunohistochemical
Of these 4 cases, 2 demonstrated extremely high serum HER2 level (61.2 and 53.3
ng/ml). Consequently, serum HER2 thus rescued 2 false-negative cases out of 4.
ithdr
staining or Western blot, and the relationship between RELM- expression and CONCLUSION: Serum HER2 level was correlated with tissue HER2 status in
cliniopathological characteristics of cancer was explored. To investigate the gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be
potential role of RELM- in gastric cancer cell biological behavior, the study useful to salvage tissue HER2 false-negative patients who will benefit from anti-
W
performed cell proliferation, migration and invasion assays in two gastric cancer
cell lines (SGC7901 and MKN45), and the study tested whether knockdown of
RELM- modulates vascular endothelial growth factor (VEGF) expression by
small interference RNA in cancer lines, and dissected the possible signaling path-
HER2 treatment.
Disclosure of Interest: None declared
ra w n
as well as the autonomic neurons located within gallbladder muscularis propria
are considered as predominant regulatory cells of gallbladder motility.
patients at the time of diagnosis. Pancreatic enzyme replacement therapy
(PERT) in the form of enteric coated pancreatin microspheres is recommended
d
AIMS & METHODS: The purpose of the current study was to determine the in pancreatic cancer patients with these symptoms to prevent weight loss and
W i t h
influence of lithogenic bile on the gallbladder autonomic neurons, in relationship
to ICLCs. Gallbladder specimens were collected from 20 patients (8 males and 12
females) who underwent elective laparoscopic cholecystectomy for symptomatic
gallstone disease. The control gallstone-free group consisted of 20 consecutive
patients (9 males and 11 females) who received elective treatment for pancreatic
malnutrition and improve quality of life. Given that the probability of pancreatic
exocrine insufficiency is high in PC, PERT is recommended without the use of
formal diagnostic tests. The optimal dose of pancreatic enzyme replacement
therapy is 40-50000 lipase units per main meal with half that dose for each snack.
AIMS & METHODS: The aim of this study was to evaluate the use of PERT in
head tumors. ICLCs were visualized in paraffin sections of gallbladders with pancreatic cancer and to ascertain if patients were being prescribed the recom-
double immunofluorescence using primary antibodies against c-Kit (anti- mended dose. A single centre retrospective analysis of patients diagnosed with PC
CD117) and anti-mast cell tryptase. The telocytes were stained with anti-CD34 in a large North London district general hospital was performed. The database of
antibody and assessed simultaneously. Autonomic neurons within the gallblad- all patients diagnosed with PC since 2010 was obtained from the local upper
der wall were visualized by immunohistochemistry using anti-PGP9.5, anti- gastrointestinal cancer multidisciplinary team records. 149 patients were identi-
ChAT and anti-NOS antibodies and assessed semi-quantitatively. Cholesterol, fied but 32 excluded from the study due to poor documentation in the records
phospholipid and bile acid concentrations were measured in bile samples leading to insufficient information surrounding enzyme supplementation and
obtained by needle aspiration from the gallbladder during surgery. dosages. Information was collected from electronic patient records on the
RESULTS: The number of ICLCs in the gallbladder wall was significantly lower patients symptoms, evidence of PERT and the dose prescribed.
in the study group than in the control group (3.2 1.5 vs. 6.6 1.8 cell/area of RESULTS: Symptoms of pancreatic enzyme insufficiency (weight loss and/or
view in the muscularis propria, P 5 0.001) and correlated with a significant steatorrhoea) were recorded in 72/117 (61.5%) of patients included in this
increase in the cholesterol saturation index, so did the telocytes count. The glyco- study. Only 14 out of the 117 (8%) patients included in this study were prescribed
cholic and taurocholic acid levels were significantly elevated in the control sub- PERT. The table below shows the enzyme formulation and dosages used.
jects compared with the study group. Numerous PGP9.5 positive neural fibers
were present, including some neuron bodies. Only sparse cholinergic (ChAT-
positive) as well as nitrergic (NOS-positive) neurons were found. The cumulative Pancreatic enzyme formulationDose (units) Number of patients
neurons count was slightly decreased in patients with gallstones.
CONCLUSION: These results suggest that bile composition plays an important Creon 50 000 three times/day (TDS)1
role in the reduction of ICLC and autonomic neurons density in the gallbladder, 40 000 TDS 1
and this might lead to the gallbladder dysmotility in patients with cholelithiasis.
Disclosure of Interest: None declared 30 000 TDS 1
25 000 TDS 4
10 000 TDS 4
OP168 SMALL FIBERS PERIPHERAL NEUROPATHY IN WILSON Not documented 2
DISEASE: AN IN VIVO DOCUMENTATION BY CORNEAL
CONFOCAL MICROSCOPY Creon Micro Not documented 1
1, 2 2 2
O. Bartolo *, D. Lazzarini , M. Berton , A. Leonardi , I. A. Fregona , 2 CONCLUSION: In our study we demonstrate that the majority of patients
E. Midena2, G.C. Sturniolo1 (92%) with PC are not prescribed PERT despite the presence of symptoms
1
Department of Gastroenterology, University of Padova, Padova, Italy, indicating pancreatic enzyme insufficiency. Of the 14 patients prescribed
2
Department of Ophthalmology, University of Padova, Padova, Italy, University of PERT, only 2 patients were treated with the recommended dose. This study
Padova, Padova, Italy, Padova, Italy highlights the missed opportunity to reduce symptoms and improve quality of
Contact E-mail Address: ottjbartolo@gmail.com life in PC patients with simple PERT. Increased awareness of the availability of
this simple treatment amongst those treating patients with PC is required.
INTRODUCTION: Wilson disease (WD) is a rare inherited autosomal recessive Disclosure of Interest: None declared
disorder of copper metabolism whose hallmarks are: liver damage, neuropsychia-
tric symptoms and Kayser-Fleischer (KF) corneal ring. The presence of KF ring
correlates with central nervous system (CNS) involvement, being detectable in OP170 FAST TRACK RECOVERY REDUCES COMPLICATIONS AND
nearly 100% of subjects with CNS involvement, and in about 50% of those with COSTS AFTER PANCREATICODUODENECTOMY
hepatic and pre-symptomatic WD. Corneal confocal microscopy (CCM) is a fast C. Williamsson1,*, R. Andersson1, G. Lindell1, B. Tingstedt1
reliable and repeatable technique to analyze the human cornea in vivo, allowing a 1
Department of Surgery, Lund University, Lund, Sweden
high magnification imaging of different corneal structures, including corneal Contact E-mail Address: bobby.tingstedt@med.lu.se
nerves.
AIMS & METHODS: We aimed to investigate central corneal changes and to INTRODUCTION: Enhanced recovery after surgery is multimodal, evidence
assess the parameters of corneal subbasal nerve plexus (CSNP) in patients based approach to optimize the patient outcome. Enhanced recovery after sur-
affected by Wilson disease (WD), using corneal confocal microscopy (CCM). gery (ERAS) or fast track programmes were developed and described by Kehlet
Twenty-four patients affected by WD and 24 healthy control subjects were et al. more than 10 years ago for colorectal surgical patients.
enrolled in this cross-sectional comparative study. One eye of each subject was Pancreaticoduodenectomy (PD) is a very complex operation with a high morbid-
examined to quantify different corneal parameters, by means of non invasive ity rate and long post-operative hospital stay.
corneal confocal microscopy. Mean cell diameter and mean cell density of the AIMS & METHODS: The aim of this study was to evaluate the safety and
epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of clinical outcome of a fast track programme after PD. 100 pancreaticoduodenec-
branchings (NBr), number of beadings (NBe) and fiber tortuosity (FT) of the tomies were prospectively followed at Skane University Hospital Lund, Sweden.
subbasal nerve plexus; mean cell density of keratocytes of the anterior, medium 50 patients were evaluated before adopting the perioperative routine changes
and posterior stroma and mean cell density, polimegatism and pleomorphism of (preFastTrack) and 50 patients after (FastTrack). The postoperative care was
the endothelium were analyzed. challenged and changes were made according to the basic ERAS concept. A
RESULTS: WD induced significant alterations in both corneal subbasal nerve programme was adopted that standardized the care and automated certain func-
plexus, and corneal epithelium. All the parameters of the subbasal nerve plexus tions. Changes made include; preoperative nutrition, secondary antibiotic pro-
were altered in WD: NFLD (P50.0001), NF (P0.001), NBe (P0.025) and NBr phylaxis, standardized withdrawal of nasogastric tubes and abdominal drains.
(P50.0001) were significantly lower, whereas FT (P50.0001) was significantly Patients were also put on a standardized pain relief scheme. Patients were thor-
higher in WD subjects compared to controls, documenting, for the first time, a oughly informed preoperatively regarding the proposed care and discharge cri-
(corneal) peripheral nerve damage in WD. The decrease of major CSNP para- teria. Data regarding demographics, symptoms, blood, operations and
meters confirms the damage (and death) of a significant number of small nerve postoperative course was prospectively and continuously registered.
fibers, whereas the increase of FT is a sign of tentative nerve regeneration. Mean RESULTS: There was no difference between the groups regarding background
epithelial cell diameter (P50.0001) and mean epithelial cell density (P50.0001) data on age, sex, symptoms, histopathological diagnosis and TNM stage. 30
resulted significantly higher and lower compared to controls, respectively. No days-mortality was zero in both groups.
significant difference in corneal stroma and endothelium were observed. Complications were decreased in the Fast Track group with delayed gastric
CONCLUSION: CCM showed significant corneal changes in subbasal nerve emptying (DGE) significantly decreased (Table 1). Patients with complications
plexus, with secondary corneal epithelium changes in WD, demonstrating the (55% vs 34%) and severity of complications according to Clavien-Dindo was
presence of small fibers peripheral neuropathy in these patients. CCM may significantly reduced (p0.013 and p0.0.001 respectively).
A56 United European Gastroenterology Journal 2(5S)
Table 1. Patients were divided into normal, moderate and high IR according to their
Table to abstract OP170 homeostatic model assessment (HOMA score).
Flow cytometry (FACS) was used to identify CD4CD25FOXP3 regulatory
Pre Fast Track Fast Track P-value lymphocytes (Tregs) and CD4IL17 (TH17) cells from both the peripheral
blood and visceral adipose tissue, which were then compared with anthropo-
Wound infection 12 (24%) 7 (14%) 0.067 metric parameters.
RESULTS: Intra-operative biopsies and blood samples were collected from 28
Seroma 3 (6%) 1 (2%) 0.096 patients. 16 patients had normal IR (HOMA score 53) and 9 patients had
Postoperative bleeding 2 (4%) 2 (4%) 1.0 moderate IR (HOMA score 3-5). 3 patients had high HOMA score and were
Pancreatic fistula 14 (28%) 11 (22%) 0.288 excluded from final analysis because of a small group size.
Serious complications * 5 (10%) 6 (12%) 1.0 Mean age and body mass index (BMI) of the normal and moderate IR groups
were 44.5 and 38.5 years (NS) and 39.5 and 41.6 kg/m2 (NS).
Delayed Gastric Emptying * 25 (48%) 11 (22%) 0.029 In patients with normal IR, Tregs positively correlated both BMI and waist
CONCLUSION: The result of this study shows it is feasible to perform an circumference [r 0.6 (p0.01) and 0.66 (p50.01), respectively). However in
enhanced recovery even after a major operation such as the pancreatodudode- patients with moderate IR, the correlation between Tregs and BMI was lost, and
nectomy without increasing mortality or morbidity. The shorter hospital stay and the correlation to waist circumference was actually reversed and became negative
less frequent use of radiology decrease the in-hospital cost significantly with [r -0.86 (p50.01)]. No significant difference was demonstrated in waist cir-
almost 25%. cumference (122 and 127.6 cm in normal and moderate IR groups).
Disclosure of Interest: None declared Similarly, a positive correlation between the adipose tissue Treg/TH17 ratio and
the BMI and waist circumference which was demonstrated in normal IR patients
[r 0.59 (p50.05) and 0.74 (pp50.01) respectively] was lost in the moderate IR
OP171 ELEVATED ALKALINE PHOSPHATASE IS AN INDEPENDENT group.
PREDICTOR OF GOOD RESPONSE DURING SOMATOSTATIN CONCLUSION: In this study we identify two opposite distribution patterns for
ANALOGUE THERAPY: A MULTI-CENTER POOLED ANALYSIS ON adipose tissue Tregs, differentiating obese patients according to their insulin
INDIVIDUAL PATIENT DATA resistance status.
T. J. G. Gevers1,*, F. Nevens2, V. E. Torres3, M.C. Hogan3, J.P. Drenth1 Combined analysis of anthropometric parameters with adipose tissue Tregs may
1
Gastroenterology and Hepatology, Radboudumc, Nijmegen, Netherlands, offer a new insight into the pathogenesis of insulin resistance in obese patients,
2
Hepatology, KU leuven, Leuven, Belgium, 3Division of Nephrology and hyper- and may mark adipose tissue Tregs as potential therapeutic targets.
tension, Mayo clinic, Rochester, United States Disclosure of Interest: T. Adar Financial support for research from: Synageva,
Contact E-mail Address: tom.gevers@radboudumc.nl Lecture fee(s) from: Shire, Consultancy for: Janssen, Other: Boston Scientific,
Immune Pharma, R. Spira: None declared, S. Shteingart: None declared, A. Ben-
INTRODUCTION: Somatostatin analogues (SA) reduce liver volumes in Yaacov: None declared, S. Shmorak: None declared, A. Jarjoui: None declared,
patients with polycystic liver disease. However, polycystic liver disease patients G. Kalak: None declared, S. Abu-Khalaf: None declared, M. Yisraeli: None
show a great variety in treatment responses, which makes it difficult to predict declared, A. Shitrit: None declared, M. Mahamid: None declared, E. Broide:
which patients will respond to SA therapy. None declared, E. Goldin Consultancy for: Immune Pharma, Bioline Rx Ltd
AIMS & METHODS: Our aim was to identify specific patient, disease or treat-
ment characteristics that predict good response to SA in polycystic liver disease.
We pooled the individual patient data of 4 trials (NCT00771888, NCT00426153, OP173 HELICOBACTER PYLORI INFECTION CAUSES INSULIN
NCT01157858, NCT01354405) that evaluated the effect of long-acting SAs (120 RESISTANCE THROUGH C-JUN/MIR-203/SOCS3 PATHWAY
mg lanreotide or 40 mg octreotide) for 6-12 months in polycystic liver disease X. Zhou1,1,*, G. Zhang1
patients and had liver volume as a primary outcome. We performed univariate 1
Gastroenterology, the First Affiliated Hospital of Nanjing Medical University,
and multivariate logistic regression analysis with preselected patient, disease and Nanjing, China
drug characteristics to identify predictors of good-response. Good-response was
defined as a reduction of 120 ml in liver volume, as this was associated with a INTRODUCTION: Epidemiological studies indicate that patients with
clinical response1. All analyses were adjusted for center and baseline liver volume. chronic Helicobacter pylori (H. pylori) infection have an increased risk of devel-
RESULTS: We included 153 polycystic liver disease patients (86% female, mean oping type 2 diabetes mellitus (1, 2), but the underlying mechanism remain
age 50 years, median liver volume 4974 ml) from 3 international centers that were largely unknown.
treated with octreotide (n70) or lanreotide (n83). Median reduction in liver AIMS & METHODS: This study aims to investigate whether H. pylori infection
volume was 4% (range -32 to 10%), and 57% patients achieved a good contributes to the development of insulin resistance, as well as the underlying
response during therapy. Multivariate logistic regression revealed that elevated mechanism both in vivo and in vitro.
alkaline phosphatase (ALP) (odds ratio 2.61, 95% confidence interval 1.17 RESULTS: We found that average fasting glucose levels were increased in
5.83, p 0.019) as a predictor of good response during SA therapy, independent patients and mice with H. pylori infection. Diabetic mice with H. pylori infection
of baseline liver volume. Renal function, elevated bilirubin, duration of therapy showed impaired glucose and insulin tolerance and hyperinsulinemia.
(6 versus 12 months) and SA type (octreotide or lanreotide) did not affect the Furthermore, H. pylori infection impairs insulin signaling in primary hepato-
probability for a response. Elevated ALP remained an independent predictor for cytes. H. pylori infection can upregulate suppressors of cytokine signaling
response when it was defined as percent change in liver volume instead of abso- (SOCS)-3, a well-known insulin signaling inhibitor by down-regulating miR-
lute change. Our model, including ALP, performed well in differentiating 203. SOCS-3 over-expression interfered with insulin signaling proteins and
patients with and without good response during SA therapy (AUC 0.72, p 5 knockdown of SOCS-3 alleviates H. pylori-induced impairment of insulin signal-
0.001). ing. We also identified c-Jun, a transcription factor which affect gene expression,
CONCLUSION: Elevated ALP is an independent predictor for good response could induced by H. pylori infection and suppress miR-203 expression.
during SA therapy in polycystic liver disease, and could possibly serve as a CONCLUSION: Our results demonstrated that H. pylori infection could induce
marker to select patients for initiating therapy. hepatic insulin resistance by c-Jun/miR-203/SOCS3 signaling pathway and pro-
REFERENCES vide possible implications toward resolving insulin resistance.
1. Temmerman F, Gevers T, Ho TA, et al. Safety and efficacy of different REFERENCES
lanreotide doses in the treatment of polycystic liver disease: pooled analysis of 1. Jeon CY, Haan MN, Cheng C, et al. Helicobacter pylori infection is associated
individual patient data. Aliment Pharmacol Ther 2013; 38: 397-406. with an increased rate of diabetes. Diabetes Care 2012; 35: 520-525.
Disclosure of Interest: None declared 2. Zhou X, Zhang C, Wu J, et al. Association between Helicobacter pylori
infection and diabetes mellitus: a meta-analysis of observational studies.
Diabetes Res Clin Pract 2013; 99: 200-208.
TUESDAY, OCTOBER 21, 2014 11:0012:30 Disclosure of Interest: None declared
INFLAMMATION AND CELL DEATH IN GI DISORDERS HALL R_____________________
OP172 ADIPOSE TISSUE REGULATORY LYMPHOCYTES MISMATCH OP174 A UBIQUITIN-MODIFYING ENZYME A20 CONTROLS THE
WITH ANTHROPOMETRIC PARAMETERS IS ASSOCIATED WITH DYNAMICS OF AUTOPHAGY
INSULIN RESISTANCE IN OBESE PATIENTS Y. Matsuzawa1,*, S. Oshima1, M. Takahara1, K. Nozaki1, M. Kobayashi1,
T. Adar1,*, R.S. Spira2, S. Shteingart1, A. Ben-Yaacov1, S. Shmorak1, Y. Nibe1, C. Maeyashiki1, Y. Nemoto1, A. Ma2, M. Watanabe1
A. Jarjoui1, G. Kalak1, S. Abu-Khalaf1, M. Yisraeli 1, A. B.-G. Shitrit1, 1
Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo,
M. Mahamid1, E. Broide3, E. Goldin1 Japan, 2Medicine, University of California, San Francisco, San Francisco, United
1
Digestive Diseases Institute, 2Department of General Surgery, 3Flow cytometry States
unit, Department of immunology, Shaare Zedek Medical Center, Jerusalem, Israel
Contact E-mail Address: adartom@szmc.org.il INTRODUCTION: Crohns disease is a chronic inflammatory disease, mainly
affecting the gastrointestinal tract. Genome wide association studies identified
INTRODUCTION: Insulin resistance is associated with obesity. The mechanism autophagy related genes as conferring susceptibility to Crohns disease. We have
for why some obese patients develop insulin resistance (IR) while others retain also reported that A20 (Tnfaip3), a ubiquitin-modifying enzyme, is a Crohns
normal IR is unknown, and may be multifactorial. Adipose tissue is recognized disease susceptibility gene. A20 is critical for preventing inflammation in vivo.
as an inflammatory active organ, harboring several types of regulatory lympho- A20 may play important roles in human autoimmune diseases and Crohns dis-
cytes, which may be involved in the development of IR. ease. However, the physiological role of A20 in T cells is not fully understood.
AIMS & METHODS: To identify different adipose tissue regulatory lympho- AIMS & METHODS: In this research, we analyze A20s potential function in T
cytes population patterns in obese patients with and without insulin resistance. cells, and demonstrate how important A20 is for autophagy regulation and
Peripheral blood samples and intra-operative visceral adipose tissue biopsies inflammation.
were taken from consenting patients undergoing elective abdominal surgery.
United European Gastroenterology Journal 2(5S) A57
To analysis the function of A20 and autophagy in vivo, we generated mice NF-B, IB and active caspase-2 levels were also measured by immunoblotting.
lacking A20 and ATG5 specifically in T cells by breeding A20FL and NF-B activation was evaluated using a specific luciferase assay and by analysing
ATG5FL mice with CD4-Cre transgenic mice. Single-cell suspensions were pre- NF-B subcellular localization. In functional studies, miR-21, PDCD4, caspase-2
pared from thymus, spleen, and peripheral lymph nodes of mice, and were ana- and NF-B were modulated using both genetic and pharmacologic modulators.
lyzed by flow cytometry and immunoblotting. To determine whether A20 Finally, reactive oxygen species (ROS) levels were determined by using the fluor-
regulates autophagy in T cells, A20 deficient na ve CD4 T cells were puriEed escent probe 2,7-dichlorodihydrofluorescein diacetate.
from spleens and lymph nodes. Cells were stimulated with anti-CD3 plus anti- RESULTS: Our results show that the miR-21/PDCD4 pathway is modulated by
CD28 in vitro. Live cells were analyzed by immunohistochemistry using LC3 DCA in a dose-dependent manner, with a concomitant decrease in cell viability
antibody (LC3 is generally considered as a marker of autophagosome). Images and an increase in cell death, apoptotic nuclei, caspase-2/-3 activation and ROS
were acquired on a confocal laser microscope. production. Importantly, miR-21 overexpression and either PDCD4 or caspase-2
RESULTS: A20 and ATG5 double deficient (DKO) mice were obtained in silencing counteracted DCA-induced apoptosis. Furthermore, NF-B activity
Mendelian numbers and developed normally. Enlarged spleen and lymph node was decreased in a similar pattern to miR-21 expression after incubation of
were observed in DKO mice. Surprisingly, the absolute number of peripheral T hepatocytes with DCA. In fact, NF-B inhibition, using a selective chemical
cells was significantly reduced in DKO mice as compared to control mice. inhibitor (BAY 11-7085), potentiated the effects of DCA impacting on the
Moreover, both B cells and myeloid cells were expanded in DKO mice. These miR-21/PDCD4 pathway, further decreasing miR-21, while increasing PDCD4
data indicate that T cell lineage deletion of A20 and ATG5 perturbs lymphoid expression levels and apoptosis. In agreement, NF-B overexpression had oppo-
homeostasis. The immunohistochemistry analysis of na ve CD4 T cells revealed site effects.
that the LC3 punctae formation was reduced in A20 deficient cells after stimula- CONCLUSION: In conclusion, the miR-21/PDCD4/apoptosis axis is modulated
tion. To understand the biochemical mechanisms by which A20 may regulate by DCA in a dose-dependent manner. Mechanistically, DCA targets miR-21 via
autophagy, we studied CD4 T cells in vitro and found the target of A20 in inhibition of NF-B activity, likely as a downstream result of caspase-2 engage-
autophagy signaling. Thus, A20 regulates induction of autophagy in na ve ment in response to DCA-induced ROS production. A better understanding of
CD4 T cells. the network of signalling mechanisms activated by toxic bile acid species may
CONCLUSION: Our studies demonstrate that A20 regulates autophagy, and allow the development of new therapeutic tools to treat bile acid-associated liver
provide new insights into how Crohns disease susceptibility genes in T cells pathologies. (Supported by PTDC/SAU-ORG/111930/2009, PTDC/BIM-MEC/
regulate inflammation. 0873/2012, SFRH/BD/88212/2012 and SFRH/BD/91119/2012 from FCT,
REFERENCES Portugal)
1. Mizushima N and Levine B. Autophagyin mammalian development and dif- Disclosure of Interest: None declared
ferentiation. Nat Cell Biol 2010; 12: 823-830.
2. Levine B, Mizushima N and Virgin HW. Autophagy in immunity and inflam-
mation. Nature 2011; 469: 323-335. OP177 ROLE OF NECROPTOSIS IN MURINE MODELS OF BILE ACID
3. Ma A and Malynn BA. A20: linking a complex regulator of ubiquitylation to TOXICITY
immunity and human disease. Nat Rev Immunol 2012; 12: 774-785. M.B. Afonso1,*, M. Caridade1, P.M. Rodrigues1, R.E. Castro1,2, C. M.
Disclosure of Interest: None declared P. Rodrigues1,2
1
Instituto de Investigacao do Medicamento (iMed.ULisboa), Faculdade de
Farmacia, Universidade de Lisboa, 2Department of Biochemistry and Human
OP175 PREVENTION OF GENOTOXICITY AND PROTUMORAL Biology, Faculdade de Farmacia, Universidade de Lisboa, Lisbon, Portugal
EFFECT MEDIATED BY COLIBACTIN-PRODUCING BACTERIA Contact E-mail Address: mbafonso@ff.ul.pt
A. Cougnoux1, J. Delmas1,2, L. Gibold1,2, T. Fa s1,2, C. Romagnoli3, F. Robin1,2,
G. Cuevas-Ramos4,5, E. Oswald4,5, A. Darfeuille-Michaud6, F. Prati7, INTRODUCTION: Cholestasis is a common pathological condition caused by
G. Dalmasso6,*, R. Bonnet2,6 disruption of bile flow, resulting in retention of bile acids in serum and in liver,
1
Medicine, Inserm U1071, 2Centre Hospitalier Universitaire, Clermont-Ferrand, with a concomitant toxic response in hepatocytes. Accumulating evidence sug-
France, 3Department of Life Sciences, University of Modena and Reggio Emilia, gests that regulated necrosis or necroptosis may be involved in hepatocyte injury
Modena, Italy, 4Inserm U1043, 5CNRS UMR5282, Toulouse, 6Inserm U1071, during cholestasis, through unclear signalling pathways.
Clermont-Ferrand, France, 7University of Modena and Reggio Emilia, Modena, AIMS & METHODS: Thus, we aimed to evaluate the role of necroptosis in
Italy hepatocytes exposed to toxic bile acids and in animal models of bile acid toxicity.
Contact E-mail Address: guillaume.dalmasso@udamail.fr Bile duct ligation (BDL) was performed in male C57BL/6 mice to induce cho-
lestasis and secondary fibrosis. Serum and livers were collected 3, 7 and 14 days
INTRODUCTION: Colorectal cancers are frequently colonized by Escherichia after BDL. To further explore the role of toxic bile acids in necroptosis activa-
coli producing the toxin called colibactin. Those bacteria induce DNA damage in tion, deoxycholic acid (DCA; 250 mg/Kg/day, oral gavage, 5 days) was adminis-
host cells, exhibit protumoral activities and increase the number of tumors in tered to male Wistar rats. Necroptotic markers were evaluated in liver tissue and
colorectal cancer mouse model. serum. HepG2 cells and primary rat hepatocytes were incubated with glycoche-
AIMS & METHODS: Our objectives were to identify drug-like molecules that nodeoxycholic acid (GCDCA; 200 mM) or DCA (400 mM), in the presence or
prevent the toxic effects mediated by colibactin-producing bacteria. Using a absence of pan-caspase inhibitor, zVAD-fmk (50 mM), and/or necroptosis inhi-
structural approach, we selected putative ligand of the ClbP enzyme, which is bitor, necrostatin-1 (100 mM), or ursodeoxycholic acid (UDCA; 100 mM).
involved in the synthesis of colibactin. The activity of compounds was evaluated RESULTS: Our results showed that BDL-operated mice displayed a strong
in vitro and in vivo using intestinal epithelial cells and a colorectal cancer mouse increase of serum transaminases, alkaline phosphatase and bilirubin.
model. Histological analysis revealed that BDL resulted in bile duct hyperplasia, multi-
RESULTS: Crystallography revealed that two drug-like molecules were able to focal necrosis and fibrosis. Moreover, BDL increased liver proinflammatory
bind the active site of ClbP. These compounds suppressed both in vitro and cytokines. Similarly, DCA induced hepatocellular necrosis and inflammatory
in vivo the genotoxic activity of colibactin-producing E. coli. In addition, they cell infiltration in rat liver, with a concomitant increase of liver proinflammatory
prevented cellular proliferation, as well as tumourigenesis mediated by those cytokines and serum transaminases. Serum markers of necroptosis, namely high
bacteria in mouse. mobility group box 1 (HMGB1) and cyclophilin A, were increased in both
CONCLUSION: These demonstrate that targeting colibactin production con- animal models. Further biochemical pathway analysis in the liver of BDL and
trols genotoxicity and protumoral effects mediated by this toxin. DCA animals, namely receptor interacting protein 3 (RIP3) expression, con-
Disclosure of Interest: None declared firmed the role of necroptosis in pathogenesis. Finally, DCA and GCDCA
were strong inducers of apoptosis in both HepG2 cells and rat hepatocytes. In
HepG2 cells, bile acid-induced cell death was completely abolished by zVAD-
OP176 DEOXYCHOLIC ACID INDUCES MIR-21/PDCD4-DEPENDENT fmk. On the contrary, DCA and GCDCA induced caspase-3-independent cell
CYTOTOXICITY BY HAMPERING NF-JB SURVIVAL SIGNALLING death, inhibited by necrostatin-1, representing necroptosis of primary rat hepa-
IN PRIMARY RAT HEPATOCYTES tocytes. UDCA was also effective at modulating necroptosis.
P.M. Rodrigues1,*, M.B. Afonso1, A.L. Simao1, P.M. Borralho1,2, C. M. CONCLUSION: In conclusion, necroptosis is involved in liver injury induced by
P. Rodrigues1,2, R.E. Castro1,2 toxic bile acids both in vitro and in vivo. As such, necroptosis may play a role in
1
Instituto de Investigacao do Medicamento (iMed.ULisboa), 2Department of the pathogenesis of cholestatic liver disease and should be regarded as a potential
Biochemistry and Human Biology, Faculdade de Farmacia, Universidade de therapeutic target. (Supported by FCT, Portugal; PTDC/SAU-ORG/119842/
Lisboa, Lisbon, Portugal 2010, HMSP-ICT/0018/2011, SFRH/BD/91119/2012 and SFRH/BD/88212/
Contact E-mail Address: pmvrsrodrigues@ff.ul.pt 2012).
Disclosure of Interest: None declared
INTRODUCTION: Toxic bile acids have been implicated in the development of
several liver diseases, including non-alcoholic fatty liver disease (NAFLD). In
particular, deoxycholic acid (DCA) is increased in the liver of NAFLD patients,
correlating with disease progression.We have recently shown that microRNA-21
(miR-21) is decreased in response to DCA in primary rat hepatocytes.
AIMS & METHODS: Our aim was to describe the mechanisms by which DCA
modulates miR-21-dependent pathways and whether these contribute to DCA-
induced cytotoxicity. Primary rat hepatocytes were treated with 25-200 mM DCA
for 24 h. Cell death, viability and caspase-3 activity were measured by the
ApoTox-GloTM Triplex Assay and the presence of apoptotic nuclei confirmed
by Hoechst staining. miR-21 expression was measured by qRT-PCR.
Programmed cell death 4 (PDCD4), a miR-21 pro-apoptotic target, was evalu-
ated by both immunoblotting and after transfecting cells with a specific luciferase
plasmid, containing the miR-21 3-UTR-binding fragment of the PDCD4 mRNA.
A58 United European Gastroenterology Journal 2(5S)
OP178 STUDY THE ROLE OF MIR-223 IN COLITIS ASSOCIATED colonic epithelial wound healing in Sdc4-/- mice was significantly impaired
CARCINOGENESIS (wound closure at day 6: 62%2.3 vs. 98.1%3.1, P50.05).
N. Bouznad1,*, L. Servais1, S. Jacques1, C. Josse1, C. Delierneux1, V. Bours1, After induction of DSS-colitis, sdc4-/- mice lost significantly more body weight
C. Oury1 compared to WT animals (day 8: 24.8%1.9 vs. 9.2%3.1; P0.008).
1
Unit of Human Genetics, GIGA Research - Laboratory of Thrombosis and Furthermore, colonic inflammatory damage in Sdc4-/- mice was dramatically
Hemostasis, Lie`ge, Belgium increased as reflected by increased colonic shortening (63.3 mm2.4 vs. 74.8
Contact E-mail Address: n.bouznad@doct.ulg.ac.be mm2.3; P0.01), increased histological damage (Dieleman Score: 16AU3.7
vs. 3.4AU0.2; P0.016) as well as enhanced mucosal infiltrate of macrophages
INTRODUCTION: MicroRNAs are short non-coding single-stranded RNAs and neutrophils. Additionally, aggravated damage of intestinal barrier function
that modulate gene expression by destabilizing mRNA and/or inhibiting transla- in Sdc4-/- animals was indicated by significantly reduced Cl-1, Cl-3 and ZO-1
tion. They are also implicated in many pathophysiological processes, including expression and increased Evans blue uptake compared to WT mice (extinction:
inflammation and cancer. Patients diagnosed with inflammatory bowel disease 4.30.03 vs. 2.70.07; P50.01). Notably, Evans Blue uptake and tight junction
(IBD) have an increased risk of developing a colorectal cancer. Inflammatory protein expression was not altered in healthy Sdc4-/- compared to WT mice.
conditions are increasingly being acknowledged to contribute to tumor forma- CONCLUSION: Loss of Syndecan-4 significantly impaired intestinal epithelial
tion; however, there is a limited understanding of the mechanisms that are wound healing in vivo and in vitro and resulted in a markedly aggravated course
involved in the transition from intestinal inflammation to cancer. Myeloid of experimental colitis. Future studies are needed to elucidate the potential ther-
derived suppressor cells (MDSC) represent immature heterogenous cells that apeutic effects of Syndecan-4 in inflammatory bowel disease.
are recruited from bone marrow under inflammatory conditions and in cancer. Disclosure of Interest: None declared
These cells have immunosuppressive properties contributing to the inhibition of
anti-tumor immunity. However, the molecular mechanisms responsible for
MDSC expansion remain elusive. Recent studies revealed that miRNA could OP180 RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS
be involved in the expansion of MDSC. (RAGE): A NEW FRONTIER IN INTESTINAL FIBROSIS
miR-223 is the main miRNA linked to myeloid development, and its role in S. Speca1,*, M. Body-Malapel1, M. Djouina2, E. Boulanger2, A.-M. Schmidt3,
myeloid cell proliferation and diGerentiation has been extensively studied both P. Desreumaux1, C. Vignal2
in vitro and in vivo. In a recent work in our laboratory, we identified miR-223 as 1
Inserm U995 Lille, 2Universite Lille-Nord, Lille, France, 3NYU Langone Medical
one of the main miRNA showing strong upregulation in mouse colons during Center, New York, United States
tumor formation. Cell sorting enabled us to confirm high expression of miR-223
in infiltrating myeloid cells (CD45 CD11b Gr-1) as compared to colono- INTRODUCTION: Intestinal fibrosis is a common and severe complication of
cytes, but also in the blood and spleen as compared to other immune cells inflammatory bowel disease (IBD) characterized by excessive deposition of extra-
(CD45 CD11b Gr-1 ). cellular matrix components (ECM) and for which efficient and well-tolerated
AIMS & METHODS: We used the well-established Azoxymethane (AOM)/ therapies are currently lacking. Inflamed colonic mucosa of patients with
Dextran Sulfate Sodium (DSS) mouse model of colitis-associated cancer in active IBD show a significant increase in expression of the receptor for advanced
order to characterize miR-223 expression in the different myeloid cell subpopula- glycation end products (RAGE), a member of the immunoglobulin superfamily
tions, during tumor development and to determine whether inhibition of miR- of cell surface receptors, able to regulate chronic inflammation by activating the
223 activity or its overexpression by means of a lentiviral vector strategy can NF-kB pathway and inducing inflammatory and oxidative stress. In addition, a
affect the recruitment of myeloid cells and carcinogenesis. growing body of evidences in kidney, liver and lung fibrosis shows how the
RESULTS: Flow cytometry and cell sorting revealed 4 myeloid subpopulations increased myofibroblast activation and numbers and the consequent ECM accu-
in spleen and blood of AOM/DSS-treated mice. Using real-time QPCR, we mulation are regulated by RAGE. All these data may place this receptor among
found that one monocytic subpopulation and the granulocytic cells are the the most innovative and promising targets for new antifibrotic therapies in IBD
main sources of miR-223 in mouse spleen and blood during periods preceding AIMS & METHODS: We propose to investigate the involvement of RAGE in
tumor development. We generated lentiviral vectors to specifically overexpress the development of the DSS-induced intestinal fibrosis in mice. Chronic colitis
miR-223 or inhibit its activity by expressing miR-223 Target sequences (miR- and fibrosis were induced in C57BL/6 wild type (WT) and RAGE null mice by
223T). We verified that intravenous injection of the miR-223 expressing lentivirus administration of 2.5% (w/v) dextran sulfate sodium (DSS) in drinking water for
in mice resulted in an increase of circulating miR-223 that persisted for at least 3 5 days followed by 7 days of water, for three cycles. Three days after the last cycle
weeks. We are currently assessing whether this lentivirus based strategy affects of treatment, the entire colon was rapidly excised and scored for the assessment
MDSC recruitment and subsequent tumor development. of macroscopic lesion, including dilation, thickness and adhesion, on a 0-3 scale
CONCLUSION: miR-223 may contribute to myeloid cell recruitment, differen- by an investigator na ve to the experimental conditions. The sum of the scores of
tiation and function during colon tumor development. Our lentiviral vectors colonic lesions was expressed as total macroscopic score. Tissue specimens, col-
represent valuable tools to investigate its role in mouse models of colorectal lected from distal colon, were subject to Hematoxylin/Eosin staining, to assess
cancer. the degree of inflammation, and Picrosirius red staining was performed to assess
Disclosure of Interest: None declared collagen deposition. Thus, a total microscopic score was calculated evaluating
presence of ulceration, inflammatory degree, depth of lesions and fibrotic degree.
mRNA expression of the main profibrotic mediator, Tgf-1, and the expression
TUESDAY, OCTOBER 21, 2014 11:0012:30 of ECM components, mainly collagen types I-III (Col1A1 gene) and fibronectin
TOWARDS BETTER UNDERSTANDING OF IBD PATHOGENESIS HALL (Fn-1 gene), were evaluated by quantitative RT-PCR
N_____________________ RESULTS: Compared to WT mice, DSS-treated C57/Bl6 RAGE null mice
showed a significant 29% decrease of the colon weight/length ratio
OP179 SYNDECAN-4 IS A KEY REGULATOR OF INTESTINAL (p50.0001), an indicator of wall thickening. A total macroscopic score of 6
EPITHELIAL REGENERATION AND INFLAMMATION 0.92 was assessed in colons recovered from DSS-treated WT mice, but in mice
D. Bettenworth1,*, M. Frohling2, M. Bruckner1, R. Mennigen3, T. Nowacki1, devoid of RAGE, the appearance of the macroscopic lesions was significantly
A. Lugering4, T. Pap2, A. Stratis2 reduced, 1.43 0.54 (p50.0001, n15). DSS-treated RAGE null mice showed
1
Medicine B, University Hospital Munster, 2Institute of Experimental also a significant 49% decrease of total microscopic score compared to WT mice.
Musculoskeletal Medicine, University of Munster, 3Department of General and mRNA Tgf-1 expression was significantly increased 3.4 fold by the DSS admin-
Visceral Surgery, University Hospital Munster, 4MVZ Portal 10, Munster, istration in WT mice colon, whereas it was unchanged in RAGE null mice
Germany compared to mice receiving only tap water. Col1A1 and Fn-1 genes were upre-
Contact E-mail Address: dominik.bettenworth@ukmuenster.de gulated in DSS-treated WT mice (5.52 folds, p 0.137 and 53 folds, p 0.0016,
respectively). Lack of RAGE decreased 3.17 folds (p 0.0341) Col1A1 expression
INTRODUCTION: Syndecan(Sdc)4 is a transmembrane protein with receptor and totally prevents the Fn-1 upregulation induced by DSS treatment
function and was found to modulate wound healing and inflammation, e.g. in the CONCLUSION: The potential profibrotic role of RAGE in IBD could both
skin. However, the role of Sdc4 in intestinal epithelial wound healing/regenera- shed light into the complex and dynamic fibrogenic processes in IBD and pave
tion and inflammation has not been investigated yet. The aim of this study was to the way for new anti-fibrotic agents and approaches in this disease.
evaluate the impact of Sdc4 deficiency on intestinal epithelial wound healing Disclosure of Interest: None declared
in vitro and in vivo as well as to evaluate its potential impact on experimental
colitis.
AIMS & METHODS: In vitro, impact of Sdc4 on intestinal epithelial wound OP181 ENHANCED NOD2-DRIVEN IMMUNITY TO ENTERIC
healing was evaluated by scratch assays in WT human T84 and murine colon-26 BACTERIAL INFECTION IN NLRP12-DEFICIENT MICE
cells as well as after blockade of Sdc4 by siRNA or anti-Sdc4 antibody admin- S. Normand1,2, N. Waldschmitt1,2,*, C. Chauvin1,2, L. Huot1, M. Delacre1,2,
istration (n6). In vivo, epithelial wounds were mechanically generated using a A. Couturier-Maillard3, D. Hot1,2, L. Poulin1,2, M. Chamaillard1,2
biopsy forceps during colonoscopy of Sdc4-/- and WT mice (n5/group). 1
Pasteur Institut, 2Inserm Lille, Lille, 3CNRS, Orleans, France
Monitoring of wound closure was performed by daily endoscopic examination. Contact E-mail Address: mathias.chamaillard@pasteur-lille.fr
To evaluate the susceptibility of Sdc4-/- mice to intestinal inflammation, experi-
mental colitis was induced by DSS (n6/group). The course of colitis was INTRODUCTION: The Nucleotide-binding oligomerization domain protein 12
assessed by weight loss, colon length, histological damage as well as immunohis- (Nlrp12) is thought to negatively regulate inflammatory response to intracellular
tochemical staining for F4/80, Gr1 and CD20. Finally, intestinal barrier function bacteria, but its role on the growth and colonization by extracellular bacteria
as reflected by mucosal permeability was determined by mucosal uptake of Evans remains largely undefined. In this study, we aim to investigate the role of Nlrp12
Blue and immunohistochemical analysis of tight junction proteins composition in bacterial-driven colitis using Citrobacter rodentium as an infection model for
including Cl-1, Cl-3, Cl-5 and ZO-1. attaching and effacing infections.
RESULTS: In vitro, administration of anti-Sdc4 antibody or siRNA targeting AIMS & METHODS: Age and sex-matched wild-type, Nlrp12 -/-, Nod2 -/-, and
Sdc4 resulted in significantly delayed wound closure compared to WT cells Nlrp12-/-Nod2-/- mice were orally inoculated with 1 109 CFU of either C.
(wound closure at day 7: 61%4,3 vs. 88%3.7; P50.05). Similarly, in vivo, rodentium strain DBS100 or kanamycin (Kn)-resistant C. rodentium strain
DBS120 for non-invasive monitoring of bacterial growth in vivo. Lamina propria
United European Gastroenterology Journal 2(5S) A59
mononuclear cell influx to the site of the infection was examined by FACS GPR84 agonist is described to mediate PMN and macrophage activation and
analysis before and one week after infection. Gene expression profiling was migration. In view of these data, we set out at developing GPR84 inhibitors to
determined in the caecum of non-infected and infected wild-type and Nlrp12-/- confirm the pro-inflammatory role of GPR84 in vitro and in vivo. Several series of
mice. Vali dation of gene expression changes was performed by qRT-PCR ana- GPR84 inhibitors were developed and shown to inhibit immune cell migration.
lysis on RNAs isolated from either the caecum, the colon, the intestinal epithelial As the infiltration of immune cells to the inflamed intestinal tissue is a hallmark
cells and the lamina propria mononuclear cells. of inflammatory bowel diseases (IBD), we further tested the capacity of these
RESULTS: An enhanced inflammatory response was found to correlate with compounds at reducing disease severity in an IBD model.
improved clearance of C. rodentium in the early phase of the infection of AIMS & METHODS: Activity of GPR84 antagonists was measured in a GTPgS
Nlrp12-deficient mice. Mechanistically, the colonic mucosa of Nlrp12-deficient assay using membranes of HEK293 cells expressing GPR84 and the di-indolyl
mice showed spontaneous signs of colitis which was improved in the absence of methane agonist of GPR84. The capacity of GPR84 antagonists to inhibit the
the major Crohns disease predisposing Nod2 gene. The protective immune GPR84 agonist (Embelin)-induced neutrophil chemotaxis was assessed in pri-
response in Nlrp12-deficient mice was primarily restricted to the intestinal epithe- mary cells using the Transwell system. This assay was also used to test the activity
lium and corroborated with enhanced recruitment of monocyte-derived dendritic on ortholog receptors using primary neutrophil from different species. In vivo
cells. efficacy was evaluated in the well-validated mouse chronic dextran sodium sul-
CONCLUSION: Overall, our results suggest that Nlrp12 repress Nod2-mediated phate (DSS)-induced colitis model for IBD using disease activity index score,
host defense against enteric bacterial infection, which may have contributed to a histology lesion score and neutrophil infiltration score as readouts.
selective advantage of Nlrp12 variants. Exploitation of the Nlrp12-coupled RESULTS: Several series of GPR84 inhibitors were developed with potencies at
inflammasome represents a novel gene-for-gene model of pathogen evolution the target in GTPgS assay down to low nM levels and clear SAR. The series
alongside host immunity. displayed strong developability properties and PK, with GLPG1205 as lead
Disclosure of Interest: None declared compound. GPR84 inhibitors were shown to inhibit GPR84 agonist-driven neu-
trophil and macrophage migration in vitro, with an IC50 matching their potency
at GPR84. GPR84 antagonism also modulated rat macrophage biology, as
OP182 STAT6 DEFICIENCY IMPAIRS M2 MACROPHAGE GPR84 antagonists specifically inhibit Embelin-induced macrophage migration.
POLARIZATION AND DELAYS WOUND HEALING IN A MURINE The impact of GPR84 inhibitors on the migration of neutrophils from different
MODEL OF COLITIS species was assessed to confirm activity at orthologs and support the proposed
J. Cosin-Roger1, D. Ortiz-Masia1,*, S. Calatayud1, C. Hernandez2, development path towards the clinic. GPR84 gene expression level was found
D. Barrachina1 increased in DSS colon versus intact colon. In the DSS model, GLPG1205 dose-
1
Pharmacology, CIBERehd-Universidad de Valencia, 2Pharmacology, FISABIO, dependently hampered the development of the disease, by reducing the disease
Valencia, Spain activity index, to a similar level as sulphasalazine and cyclosporine. The histolo-
Contact E-mail Address: mdorma@uv.es gical score for colon lesion, neutrophil influx as well as MPO content was sub-
stantially reduced by GLPG1205 oral administration, providing hints forthe
INTRODUCTION: Inflammatory Bowel Disease (IBD) is a chronic disorder of mode of action of GPR84 inhibition in IBD.
the intestinal tract caused by a deregulated mucosal immune response and epithe- CONCLUSION: GLPG1205 is characterized as a potent and selective antagonist
lial barrier disruption. These changes are mainly produced by an alteration of the of GPR84 with strong developability properties. It demonstrates good in vitro
cytokine production. STAT6 has diverse biological functions within immune activity in primary neutrophil assays, as well as pronounced in vivo activity in the
system and is a critical mediator of cytokine signalling. It has been shown that mouse chronic DSS model. These studies support GPR84 antagonism as novel
STAT6 promotes in vitro polarization towards M2 macrophages. We aim to mode-of-action for the treatment of IBD and the progression of GLPG1205
evaluate the role of STAT6 in M2 polarization in vivo and to determine its towards the clinic.
relevance on wound healing in a murine model of colitis. Disclosure of Interest: S. Dupont Other: employee, F. Labegue`re Other:
AIMS & METHODS: Peritoneal macrophages were isolated from wild type employee, R. Blanque Other: employee, S. de Vos Other: employee, P.
(WT) and STAT6-/- balb/c mice by an injection of 10ml DMEM in the peritoneal Clement-Lacroix Other: employee, L. Nelles Other: employee, A. Hagers
cavity, RNA was extracted and gene expression of M1 markers (iNOS, IL-6 and Other: employee, C. Cottereaux Other: employee, D. Merciris Other: employee,
Cd11c) and M2 markers (Arg1, Ym1, and Fizz1) was analyzed by qPCR. Colitis M.-C. Ceccotti Other: employee, C. Belleville Da Costa Other: employee, S.
was induced in WT and STAT6-/- balb/c mice by an intrarectal injection of 17.5 Fletcher Other: employee, R. Brys Other: employee
mg TNBS/100g mice dissolved in EtOH 40% (day 0). Mice were weighted diary
(results are expressed as percentage vs the weigth at day 0) and were sacrificed on
day 2, 4 and 6 after TNBS administration. The colon length was measured and OP184 SILENCING OF PROLYL HYDROXYLASE 1 IN INTESTINAL
the histology was evaluated according to Wallace Score (1-10). Vehicle mice MICROVASCULAR ENDOTHELIAL CELLS PREVENTS
received an intrarectal injection of 40% ethanol. INFLAMMATION-INDUCED ENDOTHELIAL DYSFUNCTION AND
RESULTS: Analysis of the expression of M1- and M2-markers in peritoneal DAMPENS MURINE COLITIS
macrophages reveal that macrophages isolated from knock-out mice exhibited S. Van Welden1,*, D. Laukens1, L. Devisscher1, C. Correale2, S. DAlessio2,
higher expression levels (fold induction) of iNOS (4.11.1), IL-6 (5.81.0) and S. Danese2, M. De Vos1, P. Hindryckx1
Cd11c (5.70.6) than macrophages from WT mice. In contrast, in macrophages 1
Ghent University, Ghent, Belgium, 2Clinico Humanitas, Milan, Italy
from knock-out mice the expression of Arg1 (0.420.12), Ym1 (0.320.04) and Contact E-mail Address: sophie.vanwelden@ugent.be
Fizz-1 (0.540.19) was reduced compared with WT mice. In STAT6 knockout
mice either the body weight or the histological score were similar to that observed INTRODUCTION: Active inflammatory bowel disease (IBD) is characterized by
in WT mice, and these parameters were not significantly altered at any time extensive mucosal angiogenesis. However, these newly formed blood vessels are
analyzed. TNBS administration induced, 2 days later, a peak reduction in likely dysfunctional, as they are unable to resolve the inflammation-induced
body weight in both WT mice (91.31.9%) and STAT6 knockout mucosal hypoxia. Prolyl hydroxylases (PHD1-3) are oxygen sensing enzymes
(87.71.8%). Three days after TNBS administration, the body weight started that are actively involved in tumoral vascular dysfunction. We previously
to recover in WT mice (97.61.6%) and it was completely recovered at day 4 showed that the expression of PHD1, but not PHD2 and 3, is increased in
(99.11.0%) and day 6 (101.71.8%). In contrast, in knockout mice the body inflamed biopsies of IBD patients.
weight recover was slower (87.22.7% at day 3, 90.82.2% at day 4 and AIMS & METHODS: The aim was to characterize endothelial dysfunction in
96.21.7% at day 6) and differ significantly (P50.05) than that observed in IBD patients and to investigate the role of PHD1, 2 and 3 in the vascular
WT mice. In a similar manner, TNBS administration induced intestinal endothelium during experimental colitis. The expression of endothelial dysfunc-
damage that peaked 2 days later and was similar between WT mice (6.50.6) tion markers was analyzed by qRT-PCR in inflamed and non-inflamed colonic
and knockout mice (6.40.5). However, significant differences in damage were biopsies from IBD patients and compared to samples from healthy controls and
observed at day 4 and day 6 between WT mice (4.60.5 and 3.10.4, respec- infectious colitis patients. Human colonic microvascular endothelial cells (freshly
tively) and knockout animals (6.90.5 and 4.40.7, respectively). Finally, TNBS isolated from resection specimens) and mouse endothelial cells were subjected to
induced a significant reduction at day 2 in the colon length in both WT and TNF to mimic inflammatory angiogenesis. The expression of endothelial dys-
knockout mice, compared with the respective vehicle. However, at day 4 only function markers and PHD isoforms was analyzed. We then generated endothe-
knockout animals still maintained a reduced colon length. lial specific PHD1, PHD2 and PHD3 knock-out mice and subjected these mice to
CONCLUSION: STAT6 deficiency delays wound healing in a murine model of dextran sulfate sodium (DSS)-induced colitis, after which they were assessed for
colitis which may be related to an impaired M2 macrophage polarization. histological inflammation. Colonic vascular leakage was quantified using
Disclosure of Interest: None declared dynamic contrast-enhanced T1-weighted micro-MRI.
RESULTS: Inflamed colonic biopsies from both UC and CD patients showed a
significant up-regulation of the endothelial dysfunction markers ICAM-1,
OP183 GPR84, A NOVEL TARGET FOR THE DEVELOPMENT OF VCAM-1, vWF and VEGFR-2 (all p50.0001). Moreover, these markers all
THERAPIES FOR IBD displayed a strong positive correlation with PHD1 (r0.667, r0.792, r0.731
S. Dupont1,*, F. Labegue`re1, R. Blanque1, S. de Vos2, P. Clement-Lacroix1, and r0.747 respectively) and TNF (r0.908, r0.881, r0.806 and r0.860).
L. Nelles2, A. Hagers2, C. Cottereaux1, D. Merciris1, M.-C. Ceccotti1, Endothelial cells showed a significant up-regulation of PHD1 (p50.01) in
C. Belleville Da Costa1, S. Fletcher1, R. Brys2 response to TNF. In accordance, PHD1-/- cko mice had significantly less
1
GALAPAGOS, ROMAINVILLE, France, 2GALAPAGOS, MECHELEN, weight loss (p50.0001), reduced colon shortening (p50.01) and a lower histo-
Belgium logical inflammation score (p50.001) during DSS-induced colitis, when com-
Contact E-mail Address: sonia.dupont@glpg.com pared to the littermate controls. Furthermore, the PHD1-/- cko mice showed
significantly less vascular leakage (p50.05) and a significant down-regulation
INTRODUCTION: Among the GPCRs demonstrated to be activated by FFAs, of the endothelial dysfunction markers ICAM-1, VCAM-1, vWF and VEGFR-
GPR84 is less characterized and suggested not to play a role in energy home- 2 (all p50.05) in their colonic lysates. Pharmacological hydroxylase inhibition in
ostasis. It is liganded by medium chain fatty acids, has a restricted expression mouse endothelial cells significantly reduced the expression of ICAM-1, VCAM-
profile (mainly immune cells as macrophages and polymorphonuclear leukocytes 1 and the inflammatory marker CXCL2 (all p50.05) in response to TNF.
(PMN)) and is upregulated under inflammatory conditions. In addition, a
A60 United European Gastroenterology Journal 2(5S)
Genetic inhibition of endothelial specific PHD2 and PHD3 had no effect on the Z-line was normal without macroscopically visible islands or tongues of meta-
course of DSS-colitis. plastic mucosa.
CONCLUSION: Our findings characterize a dysfunctional endothelial pheno- During the follow-up, there were 10 recurrences of IM at the level of neo-Z-line
type in IBD and show that selective silencing of PHD1 in microvascular colonic (out of 35 patients with BE with the follow-up of at least 18 months after
endothelial cells is sufficient to restore endothelial function and to dampen finishing the treatment; 28,6%). In 9 of these patients, the neo-Z-line was macro-
experimental colitis. scopically normal. LGD (within the Z-line) recurred in 2 patients (3,8%). HGD
Disclosure of Interest: None declared and/or carcinoma have not recurred. The risk factors for recurrence of IM were
male sex, younger age and diagnosis of cancer. We did not detect burried glands
beneath the new neosquamous epithelium in any patient.
TUESDAY, OCTOBER 21, 2014 11:0012:30 CONCLUSION: Treatment of BE with RFA results in CR-D and CR-IM in a
NOVEL ENDOSCOPIC INTERVENTIONS IN THE OESOPHAGUS HALL high proportion of patients with a low recurrence rate. A majority of patients
O_____________________ without CR-IM or with a recurrence of IM have macroscopically normal neo-Z-
line. CR-IM and a recurrence of IM might not be clinically relevant endpoints in
OP185 EFFICACY AND SAFETY OF HYBRID-APC FOR THE ABLATION patients with macroscopically normal neo-Z-line after RFA.
OF BARRETTS ESOPHAGUS: RESULTS OF THE PILOT SERIES Disclosure of Interest: None declared
H. Manner1,*, I. Kouti1, A. May2, O. Pech3, M. Vieth4, C. Ell2
1
HSK Wiesbaden, Wiesbaden, 2Sana Klinikum, Offenbach, 3St. John of God
Hospital, Regensburg, 4Institute of Pathology, Klinikum Bayreuth, Bayreuth, OP187 PREVENTION OF POST-ESD ESOPHAGEAL STRICTURE
Germany USING ENDOSCOPIC TRANSPLANTATION OF TISSUE-
Contact E-mail Address: HSManner@gmx.de ENGINEERED AUTOLOGOUS ORAL MUCOSAL EPITHELIAL CELL
SHEETS AT THE END OF ROUND TRIP TRANSPORTATION
INTRODUCTION: The widely used methods for the ablation of Barretts eso- BETWEEN TOKYO AND NAGASAKI
phagus (BE) are radiofrequency ablation and argon-plasma coagulation (APC). H. Isomoto1,*, N. Yamaguchi1, H. Fukuda1, K. Nakao1, S. Kobayashi1,
However, these methods lead to stricture formation in 5-15% of patients. The K. Kanetaka1, Y. Sakai1, S. Eguchi1, N. Kanai2, T. Ohki2, M. Yamato2,
question arises whether submucosal fluid injection prior to thermal ablation may T. Okano2
lower the risk of stricture formation. 1
NAGASAKI UNIVERSITY HOSPITAL, Nagasaki, 2Institute of Advanced
AIMS & METHODS: The aim of the present study was to evaluate the efficacy Biomedical Engineering and Science, Tokyo Womens Medical University, Tokyo,
and safety of the new technique of Hybrid-APC for BE ablation. Patients who Japan
had a residual Barretts segment of at least 1 cm after endoscopic resection of Contact E-mail Address: hajimei2002@yahoo.co.jp
early Barretts neoplasia underwent thermal ablation of BE by Hybrid-APC.
During Hybrid-APC, submucosal injection of sodium chloride 0.9% was carried INTRODUCTION: Endoscopic submucosal dissection (ESD) is a treatment of
out using an ErbeJet probe (Erbe Elektromedizin, Tuebingen, Germany). Check- choice for superficial esophageal neoplasms. However, largely extended esopha-
up upper GI endoscopy was carried out 3 months after macroscopically complete geal ESD requires multiple balloon dilations due to postoperative luminal stric-
ablation including biopsies from the Neo-Z-line and the former BE segment. ture. Endoscopic transplantation of tissue-engineered autologous oral mucosal
Potential stricture formation was recorded. epithelial cell sheets offers a treatment of choice for management of post-ESD
RESULTS: A total of 60 patients were included into the study during a 2-yr stricture.
interval. 55 patients were male (92%), 5 female (8%). The mean age was 629 AIMS & METHODS: We investigated the safety and efficacy of endoscopic
Jahre (42-79). The LSBE:SSBE ratio was 41:19. 10/60 patients were excluded transplantation of tissue-engineered autologous oral mucosal epithelial cell
from the study. In 5 of these 10 patients, poor mucosal healing after ablation sheets following the transportation of 1200 km between Tokyo and Nagasaki
had been observed, and the patients could not be treated according to the study in the clinical settings of large esophageal ESD. For this aim, we collected speci-
protocol. In 48 of the remaining 50 patients (96%), macroscopically complete mens of oral mucosal tissue and sufficient serum from 7 patients themselves with
Barretts ablation was achieved after a mean of 42 APC sessions (range 1-10). superficial esophageal squamous cell carcinoma in Nagasaki University Hospital,
In ITT analysis, macroscopic ablation success was 80% (48/60). The 2 other and the samples were transferred into Institute of Advanced Biomedical
patients had ablation rates of 495%. In 48/50 patients, the biopsy protocol Engineering and Science, Tokyo via air. Then, epithelial cell sheets were fabri-
was complete. Freedom from BE was histopathologically observed in 39/48 cated ex vivo by culturing isolated cells for 16 days on temperature-responsive
patients (78%). In 6% of patients, buried glands without intraepithelial neoplasia cell culture surfaces nourished using auto-sera. Again, the cell sheets were trans-
were detected in the area of the neosquamous epithelium. There was no treat- ferred into Nagasaki which is distant from Tokyo with 1200 km by airplane.
ment-related stricture. After a reduction in temperature, these sheets were endoscopically transplanted
CONCLUSION: According to this pilot series, Hybrid-APC was effective and directly onto the ulcer surfaces of patients who had just undergone esophageal
safe during BE ablation. There was no treatment-related stricture. Further stu- ESD on the day. All patients were monitored by endoscopy once a week until
dies are required to confirm the present results. epithelialization was complete. Untra-magnification endoscopy employing
Disclosure of Interest: None declared Endocyte (Olympus) was performed after 4 weeks.
RESULTS: Autologous cell sheets were successfully grown despite the transpor-
tation of 1200 km-distance in each case and were transplanted to ulcer surfaces.
OP186 IS A COMPLETE REMISSION OF INTESTINAL METAPLASIA A Complete re-epithelialization occurred within a median time of 4 weeks.
SUITABLE ENDPOINT IN PATIENTS UNDERGOING Endocytoscopic observation under approximate 400-fold magnification revealed
RADIOFREQUENCY ABLATION (RFA)? LONG-TERM RESULTS OF that almost normal squamous epithelial cells were grown over each transplanted
RFA TREATMENT IN 67 CONSECUTIVE PATIENTS area more than 4 weeks after transplantation. The nuclei of cells showed nominal
J. Krajciova1,*, M. Stefanova2, J. Maluskova3, M. Kollar3, J. Spicak1, abnormality in size and configuration. Notably, this transplantation substantially
J. Martinek1 reduced sessions of endoscopic balloon dilation or even nullified in 4 cases. There
1
Hepatogastroenterology, Institute for Clinical and Experimental Medicine were no adverse events in association with cell sheet transplantation.
Prague, 2Internal Medicine, Hospital Na Frantisku, 3Pathology, Institute for CONCLUSION: Endoscopic transplantation of autologous oral mucosal epithe-
Clinical and Experimental Medicine Prague, Prague, Czech Republic lial cell sheets promotes re-epithelialization of the esophagus after ESD, prevent-
Contact E-mail Address: kraj@ikem.cz ing post-operative luminal stricture. This study paves the way for clinical
application and dissemination of cell sheet engineering for the intractable stenosis
INTRODUCTION: Radiofrequency ablation (RFA) in combination with endo- diseases and provides new possibilities in the field of regenerative medicine.
scopic resection (ER) is a method of choice for treatment of early esophageal Disclosure of Interest: H. Isomoto: None declared, N. Yamaguchi: None
neoplasia. Complete remission of intestinal metaplasia (CR-IM) and complete declared, H. Fukuda: None declared, K. Nakao: None declared, S. Kobayashi:
remission of dysplasia (CR-D) are commonly used as the endpoints of successful None declared, K. Kanetaka: None declared, Y. Sakai: None declared, S.
treatment. The relevance of CR-IM (in patients with macroscopically normal Eguchi: None declared, N. Kanai: None declared, T. Ohki: None declared, M.
neo-Z-line) has recently been challenged. Yamato: None declared, T. Okano Financial support for research from: Teruo
AIMS & METHODS: The aim of this prospective, single center study was to Okano is a founder and director of the board of CellSeed Inc., a cell sheet
assess the long-term efficacy of RFA. Main outcome measurements were com- regenerative medicine company in Japan, licensing technologies and patents
plete remission of intestinal metaplasia (CR-IM) or dysplasia (CR-D) in patients from Tokyo Womens Medical University related to this presentation. The pre-
with/without a complete macroscopic eradication of Barretts esophagus and sentator is also a stake holder of the company listed at JASDAQ (Code: JQG
recurrence rate of IM and dysplasia. Conover one-way analysis was used to 7776).
calculate the risk factors for recurrence of IM.
RESULTS: The study involved 67 consecutive patients (mean age 62, range 20-
86; 60 males and 7 females) undergoing endoscopic treatment for esophageal OP188 EFFICACY OF PROPHYLACTIC STEROID ADMINISTRATION
neoplasia in our center during 1/2009-4/2014. Sixty-five patients were diagnosed FOR STRICTURES AFTER ENDOSCOPIC RESECTION FOR LARGE
with Barretts esophagus related neoplasia, the remaining 2 patients had squa- SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA
mous neoplasia. The median follow-up was 30 months (range 4-64). In 20 T. Kadota1,*, T. Yano1, T. Kato1, M. Imajoh1, H. Morimoto1, S. Osera1,
patients (30%), RFA was a single treatment modality while in 47 patients Y. Yoda1, T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
(70%), RFA was combined with endoscopic resection or dissection of a visible 1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
lesion. The indications for endoscopic treatment were as follows: early adeno- Hospital East, Kashiwa, Japan
carcinoma (EAC): 25 (37,3%), early squamous carcinoma (ESC): 2 (3%), high-
grade dysplasia (HGD): 22 (32,8%), low-grade dysplasia (LGD): 18 (26,9%). INTRODUCTION: Esophageal stricture is a major problem after endoscopic
A total of 125 RFA treatment sessions were performed (38x with HALO 360, 86x resection (ER) for large superficial esophageal squamous cell carcinomas
with HALO 90 and once with HALO 60). (SESCC). Steroid administration is reported as a prophylactic treatment for
CR-IM and CR-D were achieved in 66% (95% CI 36-70%) and 94,5% (95% CI strictures, however, it is uncertain regarding steroid administration technique
93-99%), respectively. In a majority of patients without CR-IM (83%), the neo- and esophageal circumference of mucosal defect after ER. We evaluated the
United European Gastroenterology Journal 2(5S) A61
efficacy of prophylactic administration of steroids in patients with large SESCC treated by emergency band ligation. No mortality was reported for all those
receiving endoscopic resection. patients over 30 days follow-up.
AIMS & METHODS: Between 2009 and 2013, 951 consecutive SESCC patients CONCLUSION: Hemospray application appears to be safe and easy technique
underwent ER in our institution. Eligibility criteria showed as follows: 1) a to control, at least temporally, AVB in this series. Further studies, preferably
mucosal defect after ER for a solitary lesion was 3/4ths or more circumference randomized controlled trials are required to determine its role and effectiveness
of the esophageal lumen, and 2) follow-up periods of 3 months or longer. In in acute variceal bleeding and its potential impact on patients outcome.
December 2009, steroid (triamcinolone acetonide 50 mg) injections into ulcer bed Disclosure of Interest: None declared
after ER were introduced for the patients with 3/4ths and larger mucosal defects.
Furthermore, from November 2012, we commenced oral steroid administration
(30 mg daily, tapered gradually for 8 weeks) in addition to the local injections in OP190 EVOLVING ENDOSCOPIC MANAGEMENT OPTIONS FOR
case of the mucosal defect of 7/8ths and larger the circumference after resection. SYMPTOMATIC STENOSIS POST-LAPAROSCOPIC SLEEVE
The mucosal defect circumference in all cases was retrospectively estimated by GASTRECTOMY FOR MORBID OBESITY: EXPERIENCE AT A
independent endoscopists in endoscopic pictures taken immediately after ER. We LARGE BARIATRIC SURGERY UNIT IN NEW ZEALAND
defined as an esophageal stricture in case the endoscope could not pass through R. Ogra1,*, P.K. geogry1
the stricture, and then endoscopic balloon dilation (EBD) was required. All 1
Gastroenterology & hepatology, Middlemore Hospital, Auckland, New Zealand
patients were classified into 3 groups according to the width of the mucosal Contact E-mail Address: rogra@xtra.co.nz
defect (group A: 3/45, 57/8; group B: 7/85, subentire circumference;
group C: completely entire circumference), and the frequency of esophageal INTRODUCTION: Symptomatic stenosis is an increasingly recognized compli-
strictures and the efficacy of individual prophylactic therapies were compared cation following laparoscopic sleeve gastrectomy (LSG) to treat obesity with a
among 3 groups. This study was approved by an institutional review board in our reported prevalence between 0.1 to 3.9%. Common findings are stricture and
institution. twisting at the incisura of the stomach remnant resulting in functional
RESULTS: Of 951 patients, 121 patients (104 men, 17 women; median age 69 obstruction.This study aimed to determine the prevalence and management
years, range 4685) were eligible. Endoscopic submucosal dissection and endo- options for symptomatic stenosis (SS) after LSG.
scopic mucosal resection were performed in 112 and 9 patients, respectively. AIMS & METHODS: All cases referred for management of symptomatic steno-
There were 49 patients in group A (no treatment: 37%, local injection of steroid: sis after LSG were recorded between May 2008 and June 2013. Patients were
55%, oral steroid: 8%); 45 in group B (13%, 64%, 22%), and 27 in group C followed up until resolution of the symptoms and up to 1 year following resolu-
(11%, 26%, 63%), respectively. The frequencies of stricture after ER of group A, tion. A total of 857 morbidly obese patients underwent LSG at Counties Health
B, and C were 22%, 53% (vs group A, p 0.0027), and 85% (vs group B, p in the study timeframe. Methods of management included Balloon dilatation
0.0098), respectively. A significant efficacy of the prophylactic steroid adminis- with CRE Balloons 12-20 mm size, Rigiflex Achalasia Balloon dilators 30-35
tration was not found in group A. However, oral steroids were effective in group mm size and use of removable fully covered self expanding metal stents. The
B, since there was a significantly lower stricture rate (no treatment: 100%, local: area of deformity at and near the stricture was noted as short (53cm) and long
59%, oral: 10% (vs local; p 0.011)). Conversely, a higher stricture rate was (43 cm). Peustow metal guidewire was used to facilitate the passage of the
found in group C regardless of prophylactic treatment (no treatment: 100%, rigiflex balloons to the area of the sleeve requiring dilatation.
local: 100%, oral: 77%). RESULTS: Symptomatic stenosis developed in 26 (3.03%) of these patients.
CONCLUSION: The stricture rate after ER for SESCC increased in the larger Eleven (42%) were males and 15 (58%) females with a mean age of 45.3 9
mucosal defect circumference. Oral steroid administration was most effective to years and a mean body mass index of 46.5 8.1 kg/m2. Four (15.4%) patients
prevent strictures when the mucosal defect was from 7/8ths to subentire circum- had SS following stent placement for sleeve leaks. The remaining 22 (84.6%)
ference. However, the efficacy of steroid treatments was limited in cases of com- patients showed fixed stenosis at the incisura angularis on barium swallow.
pletely entire circumference and stricture formation remains a major problem to Endoscopic treatment was initiated with standard CRE balloon dilators ranging
be resolved. between 12-20 mm in diameter in the majority of patients (n19, 73%). The
Disclosure of Interest: None declared mean number of dilatations was 1.6. Nine (34.6%) patients required only one
dilatation with CRE Balloon. Out of patients who required more than one dila-
tation (n11, 42.3%) only 1 (3.84%) was successfully treated with 520mm
OP189 MANAGEMENT OF ACUTE VARICEAL BLEEDING USING dilators. All of these had long (43 cm) segment of stricture and deformity.
HEMOSTATIC POWDER Seven (78%) of the Non-responders (All long segment strictures) (n9, 35%)
M. Ibrahim1,2,*, A. El-Mikkawy 2, H. Abdalla2, I. Mostafa2, J. Deviere1 were trialled with 30mm achalasia dilators and 2 (22%) with metal stents with
1
Gastroenterology & Hepato-Pancreatology, ERASME HOSPITAL, 100% success. Achalasia balloon dilatation (30 mm) was attempted as primary
UNIVERSITE LIBRE DE BRUXELLES, Brussels, Belgium, 2Gastroenterology treatment in 7(27%) patients with long segment strictures at the incisura success-
and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt fully in 5(71%) success and 2(29%) of these required metal stents. In total
Contact E-mail Address: mostafa.ibrahim@me.com 5(19.2%) patients were sucessfully treated with metal stents. No adverse events
were recorded amongst any patients treated endoscopically and none needed
INTRODUCTION: The treatment of acute variceal bleeding (AVB) includes surgical intervention.
restrictive transfusion, vaso-active drugs, antibiotics and endoscopic therapy. CONCLUSION: Endoscopic techniques of dilatation are safe and effective for
Early endoscopic treatment is recommended, however it is not always possible management of SS post LSG. The use of 30 mm achalasia balloon dilators was
in daily practice mainly due to the lack of treatment capabilities available in every also found to be safe and effective in patients who failed standard dilators.
center in an emergency setting. A hemostatic powder (Hemospray ) has recently Encouraged by our results, we now inititate dilatation therapy with 30mm acha-
been introduced for management of non variceal upper GI bleeding and was lasia balloon for those with SS post LSG
shown effective in preliminary studies for managing peptic ulcer bleeding, Disclosure of Interest: R. Ogra Other: Member Australia New Zealand Medical
cancer related bleeding or temporizing uncontrollable bleeding in severe Advisory board for Boston Scientific corporation, P. geogry: None declared
situations.
AIMS & METHODS: A bi-centric prospective trial to evaluate the effectiveness
of hemospray application for emergency control of AVB. (Clinical-Trials.gov TUESDAY, OCTOBER 21, 2014 11:0012:30
under number NCT01783899). In addition to routine medical treatment, emer- UPPER GI MOTILITY DISEASES: MECHANISMS, DIAGNOSTICS AND NEW
gency endoscopy was performed confirming acute variceal bleeding, identifica- TREATMENT OPTIONS LOUNGE 5_____________________
tion of a bleeding site was assessed; esophageal, gastric or duodenal varices, then
hemostatic powder was administered diffusely covering the mucosa over the OP191 HIGH RESOLUTION MANOMETRY IMPROVES THE
bleeding varices in order to obtain immediate endoscopic hemostasis. Clinical DIAGNOSIS OF ESOPHAGEAL MOTILITY DISORDERS IN
surveillance was performed to every patient with second endoscopy and definitive PATIENTS WITH DYSPHAGIA: RESULTS OF A RANDOMIZED
therapy the next day. MULTICENTER TRIAL
RESULTS: Thirty eight patients with suspected acute variceal bleeding were S. Roman1,2,*, L. Huot3, F. Zerbib4, S. Bruley des Varannes5, G. Gourcerol6,
included. 8 were excluded because bleeding was not variceal. Endoscopy was A. Roux7, B. Coffin8, A. Roppert9, F. Mion1
performed under sedation without endotracheal intubation, bleeding site was 1
Digestive Physiology, Hospices Civils de Lyon, 2Digestive Physiology, Lyon I
from esophageal varices in 83.4%, from gastric varices in 10% and from duode- university, 3Departement dInformation Medicale, Hospices Civlls de Lyon, Lyon,
nal varices in 6.6 % and the bleeding was active at the time of endoscopy in 43.4 4
Gastroenterology, CHU Bordeaux, Bordeaux, 5Gastroenterology, CHU Nantes,
%. Primary endoscopic hemostasis was observed in all patients after Hemospray Nantes, 6Physiology, CHU Rouen, Rouen, 7Departement dInformation Medicale,
application. Clinical hemostasis was achieved in 29/30 (96.7%) patients. One Hospices Civils de Lyon, Lyon, 8Gastroenterology, Assistance Publique Hopitaux
patient experienced hematemesis 6 hours after Hemospray application and was
OP191
Motility Disorders None Achalasia EGJ obstruction Hypertensive disorders Hypotensive disorders UES disorders Non classified
All Patients (n295) TNF Antagonist Na ve (n159) Previous TNF Antagonist Failure (n136)
GEMINI 1 Completers (VDZ Combined) Mean (SD) Score Change From Baselinea
Study Time Point n Baselinea On Study Mean (SD) 95% CI
Observed Cases
pMC score for UC 32 5.9 (1.7) 2.6 (1.6) 3.3 (1.7) 3.9, 2.7
Efficacy Population
GEMINI 1 9 6.2 (1.6) 4.3 (3.2) 1.9 (3.6) 4.6, 0.9
No. (%) of Patients n275a No. (%) of Patients n Wk 6 31 5.9 (1.7) 5.8 (1.8) 0.1 (1.6) 0.7, 0.5
Wk 26 19 5.9 (1.6) 2.4 (1.7) 3.5 (2.1) 4.5, 2.5
Clinical Remission GEMINI LTS 16 5.8 (1.6) 1.8 (1.7) 4.0 (2.4) 5.3, 2.7
Wk 52 181 (65.8) 181 (72.4) 250 Wk 0
Wk 28
Wk 80 212 (77.1) 212 (83.8) 253
Wk 52
Wk 104 200 (72.7) 200 (83.7) 239 HBI score for CD 56 11.4 (3.0) 6.4 (3.1) 5.0 (3.3) 5.9, 4.1
Clinical Response GEMINI 2 19 11.4 (2.2) 8.5 (4.1) 2.9 (4.7) 5.2, 0.6
Wk 52 216 (78.5) 216 (86.4) 250 Wk 6 57 11.5 (3.0) 10.1 (4.1) 1.4 (4.3) 2.5, 0.2
Wk 26 40 11.3 (2.7) 6.0 (3.4) 5.3 (3.7) 6.5, 4.1
Wk 80 234 (85.1) 234 (92.5) 253 GEMINI LTS 30 11.1 (2.4) 4.1 (3.0) 7.0 (3.4) 8.2, 5.7
Wk 104 219 (79.6) 219 (91.6) 239 Wk 0
Wk 28
CONCLUSION: The efficacy of VDZ observed in GEMINI 1 was maintained Wk 52
for an additional 52 weeks in GEMINI LTS, regardless of previous TNF antago-
nist exposure.
REFERENCES Consistent with the findings above, median predicted average wk 52 VDZ con-
1. Feagan BG, et al. N Engl J Med 2013; 369: 699-710. centrations in patients on VDZ Q8W were higher for those who completed the
2. Colombel JF, et al. Poster presented at: American College of Gastroenterology studies (GEM 1: 36.9 mcg/mL, n75; GEM 2: 39.5 mcg/mL, n74) than for
Annual Scientific Meeting, San Diego, CA, 11-16 October 2013. those who discontinued (GEM 1: 30.5 mcg/mL, n32; GEM 2: 32.7 mcg/mL,
Disclosure of Interest: B. Feagan Consultancy for: Abbott Laboratories, n57).
Actogenix, Albireo Pharma, AstraZeneca, Athersys, Axcan, Berlex, Bristol- CONCLUSION: Patients who lost response to VDZ Q8W had improvements in
Myers Squibb, Celgene, Centocor, Cerimon Pharma, CombinatoRx, Elan/ mean disease activity scores with an increase in VDZ dosing frequency to Q4W
Biogen, Genentech, GICare Pharma, Gilead, Given Imaging Inc, without an apparent accompanying increased risk for AEs. Although uncon-
GlaxoSmithKline, Johnson and Johnson, Napo Pharma, Nektar, Novo trolled, these data provide insight regarding possible utility of VDZ Q4W dosing.
Nordisk, Ore Pharmaceuticals, Pfizer, Procter and Gamble, Prometheus Disclosure of Interest: B. Sands Consultancy for: Abbott Immunology, Amgen,
Therapeutics and Diagnostics, Salix Pharma, Serono, Shire, Sigmoid Pharma, Astellas Pharma Global Development, Avaxia Biologics, Baxter Healthcare,
Takeda Pharmaceuticals International, Inc., Tillotts, UCB Pharma, Unity Bracco Diagnostics Inc., Bristol-Myers Squibb, Creative Educational Concepts,
Pharmaceuticals, Wyeth, Zealand Pharma, Zyngenia, A. Kaser: Nothing to dis- Curatio CME Institute/Axis Healthcare Communications, LLC, Dainippon
close., M. Smyth Other: Employee of Takeda Global Research & Development Sumitomo Pharma, Dyax Corp, Elan Pharmaceuticals, Emmi Solutions LLC,
Centre (Europe) Ltd, R. Panaccione Consultancy for: Abbott, Abbvie Amgen, GlaxoSmithKline, Glaxo Wellcome, IMEDEX, Immune Pharmaceuticals,
Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Janssen, Merck, Schering-Plough, Kyowa Hakko Kirin Pharma, Inc., Mechanisms in Medicine, Millennium/
Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Takeda, Pfizer, Prometheus Laboratories, PureTech Ventures, LLC, Sigmoid
Warmer Chilcott, Takeda, S. Sankoh Other: Employee of Takeda Pharma, Teva Pharmaceutical Industries, M. Dubinsky Consultancy for:
Pharmaceuticals International Co., B. Abhyankar Other: Employee of Takeda Abbvie, Janssen, Pfizer, Prometheus, UCB Pharma, S. Vermeire Financial sup-
Global Research & Development Centre (Europe) Ltd port for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from:
Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB
Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, S.
OP207 EFFECTS OF INCREASED VEDOLIZUMAB DOSING Sankoh Other: Employee of Takeda Pharmaceuticals International Co., M.
FREQUENCY ON DISEASE ACTIVITY IN ULCERATIVE COLITIS Rosario Other: Employee of Takeda Pharmaceuticals International Co., C.
AND CROHNS DISEASE Milch Other: Employee of Takeda Pharmaceuticals International Co.
B.E. Sands1, M.C. Dubinsky2, S. Vermeire3,*, S. Sankoh4, M. Rosario4,
C. Milch4
1
Icahn School of Medicine at Mount Sinai, New York, 2Cedars-Sinai Medical OP208 HOW LONG SHOULD GOLIMUMAB TREATMENT BE
Center, Los Angeles, United States, 3University Hospital Gasthuisberg, Leuven, CONTINUED IN PATIENTS WITH ULCERATIVE COLITIS WHO
Belgium, 4Takeda Pharmaceuticals International Co., Cambridge, United States DO NOT RESPOND TO INITIAL INDUCTION THERAPY?
Contact E-mail Address: bruce.sands@mssm.edu P. Rutgeerts1,*, W. Reinisch2, B. Feagan3, W. Sandborn4, D. Tarabar5,
Z. Hebzda6, H. Weng7, R. Yao7, H. Zhang8, C. Marano8, R. Strauss8
INTRODUCTION: Efficacy and safety of vedolizumab (VDZ) in patients with 1
University Hospital Gasthuisberg, Leuven, Belgium, 2McMaster University,
ulcerative colitis (UC) and Crohns disease (CD) were established in the Hamilton, 3U Western Ontario, London, Canada, 4University of California San
GEMINI (GEM) 1 (Feagan BG, et al. N Engl J Med.2013;369 (8):699-710) Diego, La Jolla, United States, 5Military Medical Academy, Belgrade, Serbia,
and 2 (Sandborn WJ, et al. N Engl J Med.2013;369(8):711-21) trials, respectively. 6
Wojskowy Szpital Kliniczny z Poliklinika, Krakow, Poland, 7Merck & Co., Inc.,
To investigate whether increased VDZ dosing frequency benefits patients who Whitehouse Station, 8Janssen R&D, LLC., Spring House, United States
lost response to VDZ every 8 wks (Q8W) during GEM 1 or 2, disease activity was Contact E-mail Address: paul.rutgeerts@uz.kuleuven.ac.be
assessed when these patients received VDZ every 4 wks (Q4W) in an open-label,
long-term extension study (GEM LTS; EudraCT No. 2008-002784-14). INTRODUCTION: To determine an appropriate time to discontinue golimumab
AIMS & METHODS: The randomized placebo-controlled GEM 1 and 2 studies (GLM) maintenance therapy for ulcerative colitis (UC) in patients (pts) who do
included a 6-wk induction phase and a 46-wk maintenance phase. Data from not respond to initial induction treatment.
patients who responded to VDZ 300 mg induction therapy but later discontinued AIMS & METHODS: The PURSUIT study enrolled pts with moderate to
for lack of efficacy on VDZ 300 mg Q8W maintenance therapy and who enrolled severe, active UC (Mayo scores 612 inclusive; endoscopic subscore 42) with
in GEM LTS (to receive VDZ 300 mg Q4W) were analyzed. Mean partial Mayo inadequate response or intolerance to conventional UC therapy. Pts were rando-
Clinic (pMC) scores (UC) and mean Harvey-Bradshaw Index (HBI) scores (CD) mized to receive at wk 0/2 either placebo (PBO)/PBO, GLM 200mg/100mg, or
were calculated. For patients who discontinued from GEM 1 and 2, average wk GLM 400mg/200mg. Pts who were not in clinical response (30% and 3 points
52 VDZ concentrations were predicted to standardize pharmacokinetic data at Mayo score decrease from wk 0 with a rectal bleeding subscore of 0/1 or decrease
the same time point relative to study entry (Rosario M, et al. Presented at: 9th 1) after 6-wk induction received GLM 100mg every 4 wk. Partial Mayo
Congress of the ECCO; Feb 20-22, 2014; Copenhagen). These values were com- response (improvement 3 from wk 0) and remission (score 2) without endo-
pared with predicted VDZ concentrations in those who completed GEM 1 or 2. scopy were evaluated through wk 22. There was no control group; all nonre-
RESULTS: Among those who received VDZ Q8W in GEM 1 (n122) or GEM 2 sponders received GLM. Pts who had a prohibited medication change, ostomy or
(n154), 32 patients (26%) from GEM 1 and 57 (37%) from GEM 2 discon- colectomy, dose adjustment, missing partial Mayo scores, or discontinued for
tinued for lack of efficacy. Mean disease activity scores for these patients lack of efficacy were considered nonresponders.
improved after transition to VDZ Q4W dosing in GEM LTS (Table). AE profiles RESULTS: Among GLM induction nonresponders (N398, 7 pts excluded due
were generally similar for the VDZ Q8W and Q4W regimens in GEM 1 and 2. to site misconduct), further GLM therapy resulted in additional pts achieving
response/remission (table; data from induction responders are shown for com-
parison). At wk 10 of GLM exposure, 11.8% of induction nonresponders had
achieved partial Mayo remission, and 23.1% had achieved partial Mayo
response. At wk 14, 15.6% achieved remission; 28.1% achieved response.
Although the proportion of pts who achieved remission/response increased
beyond wk 14, the incremental benefit was minimal. While adverse events
(AEs) were reported with a slightly greater frequency during the first months
of maintenance treatment, the majority of pts did not report an AE during
continued treatment.
A68 United European Gastroenterology Journal 2(5S)
Table. Partial Mayo Response/Remission With Continued GLM Treatment of controls (6.3% vs. 25.9% respectively, OR 0.19, 95%CI 0.1-0.34, p50.0001).
Table to abstract OP208 When also considering all prior colonoscopies performed over 7.74.6 years of
follow-up (mean 4.12.9 colonoscopies/patient, range 1-15, total 832 colonosco-
Induction Responders pies), the risk of ever finding an adenoma in UC patients was still significantly
Induction (50 and 100mg dose groups) lower compared to controls (14.1% vs.25.9% respectively, OR 0.47, 95%CI 0.3-
Nonresponders (N398) (N302) 0.72, p0.0005). On multi-variate analysis, the incidence of adenomas was posi-
tively associated with advanced age (OR 1.07/year, 95%CI 1.04-1.09, P50.0001)
Wk of GLM Partial Mayo Partial Mayo Partial Mayo Partial Mayo and with male gender (OR1.54, 95%CI 1.02-2.3, p0.04) and negatively asso-
exposure remission, n (%) response, n (%) remission, n (%) response, n (%) ciated with having UC (OR 0.16, 95%CI 0.09-0.30, P50.0001). Among 115
Crohns patients 450 years old, the rate of ever-adenomas in Crohns ileitis
Wk 6a 7 (1.8) 14 (3.5) 205 (67.9) 234 (77.5) patients and controls was similar (p0.8), whereas patients with Crohns disease
Wk 10 47 (11.8) 92 (23.1) 190 (62.9) 232 (76.8) involving the colon had significantly lower rate of adenomas compared to con-
trols (3.9% vs. 25.9%, p0.002).
Wk 14 62 (15.6) 112 (28.1) 186 (61.6) 206 (68.2) CONCLUSION: Patients with UC or colonic Crohns disease seldom develop
Wk 18 77 (19.4) 129 (32.4) 181 (59.9) 201 (66.6) sporadic adenomatous polyps. These data provide novel insight into possible
Wk 22 84 (21.1) 129 (32.4) 172 (57.0) 186 (61.6) mechanisms restricting the adenoma-carcinoma sequence and suggest organ-spe-
cific immune activation may confer protection against development of colonic
CONCLUSION: Among patients who were nonresponders after initial GLM adenomas.
induction, 15.6% achieved partial Mayo score remission, and 28.1% achieved Disclosure of Interest: S. Ben-Horin Consultancy for: Abbott, Janssen, Takeda &
response by wk 14. Continued therapy may not be useful in patients who show no Schering-Plough, Z. Izhaki: None declared, O. Haj-Natur: None declared, S.
evidence of therapeutic benefit after 1214 wks of GLM treatment. (Financial Segev: None declared, R. Eliakim Consultancy for: Abbott, Janssen &
support for this study was provided by Janssen Research & Development, LLC., Schering-Plough, B. Avidan: None declared
Spring House, PA, USA.)
Disclosure of Interest: P. Rutgeerts Financial support for research from: Merck
Sharp & Dohme Corp, Consultancy for: Merck Sharp & Dohme Corp, W. OP210 CHARACTERIZATION OF INCIDENT CASES OF CANCER IN
Reinisch Lecture fee(s) from: Abbott Laboratories, AbbVie, Aesca, Amgen, INFLAMMATORY BOWEL DISEASE PATIENTS: RELATION WITH
AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IMMUNOMODULATORY TREATMENTS AND DISEASE
IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, PHENOTYPE IN A PROSPECTIVE MULTICENTER MATCHED-PAIR
Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, IG-IBD STUDY
Grunenthal, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid L. Biancone1,*, G. Condino1, A. Armuzzi2, M.L. Scribano3, R. DInca`4, C. Papi5,
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, L. Spina6, L. Guidi2, A. Kohn3, E. Calabrese1, C. Petruzziello1, S. Onali1,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, F. Mocciaro7, R. Monterubbianesi3, P. Alvisi8, W. Fries9, G. Riegler10,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, F. Castiglione11, I. Frankovic4, G. Margagnoni5, G. Meucci12, F. Rogai13,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC, A. Orlando14, S. Ardizzone15, F. Pallone1
Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma, 1
Systems Medicine, Universita` Tor Vergata, Rome, 2GI, CIC, Universita`
Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Bristol- Cattolica, Roma, 33AO S. Camillo Forlanini, Roma, Rome, Rome, 4Universita`
Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria, Padova, Padova, Padova, 5UOC GE/Hep, AO S.Filippo Neri, Roma, Rome, Rome,
Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grunenthal, 6
Universita` S. Donato, Milano, Milano, Milano, 7ARNAS Civico-DI Cristina
Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Benfratelli, Palermo, Palermo, Palermo, 88Osp. Maggiore Bologna, Bologna,
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD, Bologna, 9Universita` Messina, Messina, Messina, 10SUN, Seconda Universita`,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Napoli, 11Universita` Federico II, Napoli, Napoli, Napoli, 12Ospedale S. Giuseppe,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire, Milano, Milano, Milano, 13AOU Careggi, Firenze, Firenze, Firenze, 14Ospedale
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC, B. Cervello, Palermo, Palermo, Palermo, 15Universita` "Sacco", Milano, Milano, Italy
Feagan Financial support for research from: Abbott/AbbVie, Amgen, Astra Contact E-mail Address: biancone@med.uniroma2.it
Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen,
Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB INTRODUCTION: Concern exists about cancer risk using thiopurines (IMM)
Pharma, Lecture fee(s) from: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner- and/or anti-TNFs in Inflammatory Bowel Disease (IBD).
Chilcott, UCB Pharma, Consultancy for: Abbott/AbbVie, Actogenix, Albireo AIMS & METHODS: In a prospective, multicenter, case-control study, we
Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter aimed to characterize incident cases of cancer in IBD. The role played by clinical
Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso characteristics of IBD vs IMM and/or anti-TNFs use in determining the fre-
Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, quency of cancer was also investigated. From Jan 2012 to April 2014, character-
GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, istics of all incident cases of cancer in IBD patients (pts) referring to 15 centers
Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., were recorded. In each center, each IBD pt developing cancer (IBD-K) was
Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Prometheus matched with 2 IBD pts with no cancer (IBD-C) for: IBD type (CD/UC),
Therapeutics and Diagnostics, Pfizer, Receptos, Salix Pharma, Serono, Shire, gender, age (5yrs). Data reported as median (range):chi-squared, Fisher
Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB exact, Student t test, univariate analysis as appropriate.
Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia, W. RESULTS: The study included 106 IBD-K and 212 IBD-C. Cancer occurred in
Sandborn Financial support for research from: Janssen, Consultancy for: 106 IBD-K (54M, age 59 [16-85];2 cancers in 8 pts).The frequency of cancer was
Janssen, D. Tarabar: None declared, Z. Hebzda: None declared, H. Weng higher in CD (CD-K)(n61;57%) vs UC (UC-K)(n45;43%; p0.03). IBD-C
Other: Merck Employee, R. Yao Other: Merck Employee, H. Zhang Other: included 212 pts (110M, age 57[15-83]). IBD duration was comparable between
Janssen Employee, C. Marano Other: Janssen Employee, R. Strauss Other: IBD-K and IBD-C (yrs:12[1-54] vs 12.5[10-50]. Cancers included: GI tract
Janssen Employee (n42;40%;colorectal, CCR 24%), genitourinary (n26;25%), skin (n9;8%),
lung (n9;8%), breast (n9;8%), hematologic cancers (n7;7%:5NHL/
1HL,5%;1 leukemia (0.9%), others (4%). Cancers involved: GI tract (n42; 18
TUESDAY, OCTOBER 21, 2014 14:0015:30 CD/28UC; CCR n26: 7CD/19UC; ileal carcinoma 6CD/0UC), genitourinary
IBD: DYSPLASIA AND CANCER HALL I/K_____________________ tract (n26:15CD/11UC; cervix 5CD/0UC), skin (n9; 6CD/3UC;CD:3 mela-
noma [2 noIMM/anti-TNFs;1 IMM], 3 NMSC [2IMManti-TNFs,1IMM]; UC:
OP209 RARITY OF ADENOMATOUS POLYPS IN ULCERATIVE 1 melanoma,1 Kaposi [no IMM/anti-TNFs both];lung (n9;5CD/4UC), breast
COLITIS: IMPLICATIONS FOR COLONIC CARCINOGENESIS (n9;6CD/3UC), lymphoma (n6; 5NHL/1HL, 6CD, 6M, [2 IMManti-TNFs,
S. Ben-Horin1,*, Z. Izhaki1, O. Haj-Natur1, S. Segev1, R. Eliakim1, B. Avidan1 1 IMM, 2 no IMM/anti-TNFs], others (n5). Cancer-related death: 10/106
1
SHEBA MEDICAL CENTER, Tel-Hashomer, Israel (9.4%) pts. GI cancers were more frequent in UC (53%) vs CD (29%;
Contact E-mail Address: shomron.benhorin@gmail.com p0.02), lymphoma and ileal carcinoma in CD vs UC (9.8% vs 0%;
p0.03both). The frequency of any cancer was higher in pancolitis (59%) vs
INTRODUCTION: Despite ample research on dysplasia-carcinoma risk in distal (30%; p0.01), subtotal UC (11%; p0.0001), with no differences between
ulcerative colitis (UC) there are scant data on sporadic adenomas risk in this stricturing, fistulizing, inflammatory CD (39% vs 27% vs 34%; pns). IMM and
population. anti-TNFs were used in a comparable proportion of IBD-K and IBD-C pts
AIMS & METHODS: The aim of this study was to investigate the prevalence of (IMM 39% vs 45%; Anti-TNFs 28% vs 35%;pns both).
sporadic colon adenoma in UC patients in order to gain insight of possible role of CONCLUSION: In a prospective multicenter match-pair study, incident cases of
chronic immune-driven inflammation on adenoma development. For this pur- cancer were more frequent in CD vs UC, with a high frequency of GI and
pose, the number and histology of all polyps detected at colonoscopies of UC genitourinary cancers in IBD. CCR was more frequent in UC, lymphoma and
patients during 2006-2012 were compared to controls undergoing screening colo- ileal carcinoma in CD. CD phenotype and UC extent may influence the fre-
noscopy. The analysis was deliberately restricted to patients who were over 50 quency of any cancer, while IMM and/or anti-TNFs the frequency of specific
years-old at the time of the index colonoscopy to reinforce the validity of the cancer histotypes (lymphoma, skin cancer).
comparison to screening colonoscopy controls. However, to exclude a potential Disclosure of Interest: None declared
bais, an additional analysis was performed including all prior colonoscopies
undergone by the UC group. A third group comprising of Crohns disease
patients was also evaluated to dissect the role of colonic IBD versus ileal IBD
on sporadic adenoma rate.
RESULTS: 206 UC patients and 624 controls (mean age 61.78.7 versus
60.86.1, respectively, P0.15) were included. Adenomatous polyps were
detected in only 13/206 UC colonoscopies compared to 162/624 colonoscopies
United European Gastroenterology Journal 2(5S) A69
OP211 SERRATED POLYPS IN PATIENTS WITH INFLAMMATORY Table to abstract OP212
BOWEL DISEASE (IBD): ENDOSCOPIC CHARACTERISTICS
DIFFER FROM SERRATED POLYPS IN NO-IBD POPULATION MiR-18a MiR-21 MiR-135b
D. Moussata1,*, G. Boschetti2, M. Chauvenet3, K. Stroeymeyt3, S. Boyer3,
S. Nancey3, F. Berger4, B. Flourie3 Combined Tissue Fold Fold Fold
1 Groups P Value Change P Value Change P Value Change
Lyon Sud Hospital, Pierre Benite, 2Gastroenterology, Lyon Sud Hospital, Lyon,
3
Gastroenterology, 4Pathology, Lyon Sud Hospital, Pierre Benite, France
Normal vs. UC 0.092 2.8 0.0358* 1.4 5 0.0001* 6.6
Contact E-mail Address: driffa.moussata@chu-lyon.fr
Normal vs. CAC and Dysplasia 5 0.0001* 6.4 5 0.0001* 3.9 5 0.0001* 11.4
INTRODUCTION: Serrated polyps (SP) include hyperplastic polyp (HP), sessile UC vs. CAC and Dysplasia 0.022* 3.6 0.0002* 2.4 0.0008* 4.8
serrated adenoma (SSA) and traditionnal serrated adenoma (TSA). Endoscopic
characteristics of these lesions are well-known in general population, but whether
they have specific aspect in patients with inflammatory bowel disease (IBD) is
unknown. Table 1.0: MiR expression in different tissue groups.
AIMS & METHODS: To compare endoscopic characteristics of SP between Furthermore mir-31 appeared to be increased in the acute phase of UC and
IBD and non-IBD patients. Prospectively, 229 patients were included. A chro- combining selected miRNA profiles (mir18a and 21) showed significant variance
moendoscopy with indigo carmin (0.2%) was performed (H180, Olympus, (p50.05).
Japan) under sedation. All the lesions were described according to Paris classi- CONCLUSION: Several miRNAs were increased in dysplastic and CAC tissues
fication; the size (mm), localization and histology were reported. and may contribute to pathological processes, such as dysregulation of apoptosis
RESULTS: 154 IBD patients (77 men, 53 13.5 yrs, mean SD) and 75 non- and impairment of epithelial barrier dysfunction. Further investigation of these
IBD patients (38 men, 58 15 yrs) were included. We detailed for each group the miRNAs may enable clinicians to monitor disease progression in patients with
characteristics of HP and SSA polyps which are summarized on table1. No UC and distinguish those at increased risk of developing CAC.
patient presented TSA. A total of 349 SP were detected by chromoendoscopy: Disclosure of Interest: None declared
195 in 56% (42/75) of patients in non-IBD and 154 in 13.6% (21/154) of IBD
patients. Among patients with SP, the HP polyps were more frequent in non-IBD
group (26/42, 62% vs 11/21, 52.3%, NS) and presented the same macroscopic OP213 RISK OF DYSPLASIA AND CANCER COMPLICATING
aspect (IIa) in the 2 populations. Whereas, among patients with SP, SSA tended COLONIC STRICTURES IN INFLAMMATORY BOWEL DISEASE: A
to be more frequent in IBD patients (10/21, 47.6% vs 16/42, 38%, NS) and GETAID STUDY
presented more often dysplasia than in non-IBD patients (6/21, 28.6% vs 8/42, M. Fumery1,*, G. Pineton de Chambrun2, C. Stefanescu3, A. Buisson4,
19%, p50.05). Their macroscopic aspect was different with IIb of Paris classi- A. Bressenot5, L. Beaugerie6, A. Amiot7, R. Altwegg8, G. Savoye9, V. Abitbol10,
fication in IBD patients. In IBD patients, SSA tended to be larger (10.3 /- 12.7 G. Bouguen11, M. Simon12, J.-P. Duffas13, X. Hebuterne14, S. Nancey15,
vs 4.7 /- 2.1 mm, p50.01). In IBD group, SSA were localized all along the X. Roblin16, J. Lefevre6, J.-P. Le Mouel1, J. Moreau13, Y. Bouhnik3, L. Peyrin-
colon, whereas in non-IBD the SSA were preferentially localized in the right Biroulet5 on behalf of GETAID
colon. 1
Amiens University and Hospital, Amiens, 2Lille University and Hospital, lille,
3
Beaujon Hospital, APHP, Clichy, 4Clermont-Ferrand Hospital and University,
Cmernont Ferrand, 5Nancy University and Hospital, Nancy, 6Saint Antoine
Nb of pts with SP Non-IBD (42/75, 56%)IBD (21/154, 13.6%)p Hospital, APHP, Paris, 7Creteil Hospital, APHP, Creteil, 8Montpellier University
and Hospital, Montpellier, 9Rouen Hospital and University, Rouen, 10Cochin
Total nb of SP lesions 195 154 - Hospital, APHP, Paris, 11Rennes University and Hospital, Rennes, 12Institut
Nb of pts with HP 26 (26/42, 62%) 11 (11/21, 52.4%) NS Mutualiste MontSouris, Paris, 13Toulouse University and hospital, Toulouse,
14
Nb of pts with SSA 16 (16/42, 38%) 10 (10/21, 47.6%) NS Nice University and Hospital, Nice, 15Lyon University and Hospital, Lyon, 16St
Etienne University and Hospital, St Etienne, France
Nb pts with SSA with dysplasia8 (8/42, 19%) 6 (6/21, 28.6%) 50.05
Contact E-mail Address: mathurinfumery@gmail.com
Total nb of SSA 37 (37/195, 19%) 37 (37/154, 24%) NS
Total nb of SSA with dysplasia 13 (13/37, 35%) 14 (14/37, 37.8%) NS INTRODUCTION: Management of colonic strictures complicating inflamma-
tory bowel disease (IBD) is a challenge in clinical practice and leads frequently to
Mean size of SSA 4.7 /- 2.1 10.3 /- 12.7 50.01 surgical resection because of the fear of associated dysplasia/cancer. The risk of
Paris classification of SSA 25 IIa, 12 Is 23 IIa, 10 IIb, 4 Is - intestinal dysplasia or cancer complicating colonic strictures in both ulcerative
Localization of SSA 24 RC, 13LC 20 RC, 17 LC - colitis (UC) and Crohns disease (CD) is unknown.
AIMS & METHODS: We aimed to determine the frequency of dysplasia and
CONCLUSION: In IBD patients, the size, Paris classification and localization of cancer among adult patients with IBD undergoing intestinal resection for a color-
serrated polyps differ from those of non-IBD patients. IBD patients presented ectal stricture without dysplasia or cancer known at the time of surgery. The
more often SSA with dysplasia, suggesting that SSA could be involved in cancer GETAID conducted a nationwide retrospective study. Only centers having a
pathway. This hypothesis has to be verified by following prospectively the cohort database of all consecutive IBD patients who underwent intestinal resection
of IBD patients. for IBD during a given period could participate in this study. All patients with
Disclosure of Interest: None declared preoperative evidence of dysplasia/cancer were excluded. Demographical, clini-
cal, endoscopic, surgical, and histopathological data and outcomes were
collected.
OP212 INVESTIGATION OF DIFFERENTIALLY EXPRESSED RESULTS: Among 12 013 IBD patients operated for IBD in 16 GETAID cen-
MICRORNAS IN COLITIS ASSOCIATED DYSPLASIA AND ters between August 1992 and January 2014, we identified 293 patients operated
ADENOCARCINOMA for a colonic stricture, including 248 CD, 39 UC and 6 IBD unclassified. 51%
M. Patel1,2,*, M., I. Aslam1,2, A.M. Verma1,2, K. West2, J. Jameson2, were males and the median age at stricture diagnosis was 38 years (Q125-
J.H. Pringle1, B. Singh2 Q351). All patients underwent preoperative colonoscopy. The stricture was
1
Cancer Studies & Molecular Medicine, University of Leicester, 2University not passable in 66% of cases. The median disease duration at stricture diagnosis
Hospitals of Leicester, Leicester, United Kingdom was 8 (3-14) years. Strictures presented a median length of 6 cm (4-10), and were
Contact E-mail Address: maleene@doctors.org.uk symptomatic in 73% of patients. They were located in the right colon, transverse,
or left or rectal in respectively 16%, 14%, 64% and 6% of CD patients, and
INTRODUCTION: A number of recent studies have identified microRNA respectively 6%, 13%, 62% and 19% in UC. The median stricture duration
(miRNA) expression profiles associated with Ulcerative Colitis (UC). Our before surgery was 6.3 (1.6-20) months in CD and 3 (0.6-9.6) months in UC.
study aimed to discover miRNAs related to disease progression in order to Surgical procedure was segmental, subtotal colectomy and coloprotectomy in
identify dysplasia and colitis associated cancer (CAC) in patients with UC. respectively 79%, 19% and 10% of CD patients and in respectively 18%, 28%
AIMS & METHODS: Total RNA was extracted from archived paraffin and 54% in UC. In CD, low-grade dysplasia was observed in 3 patients (1%),
embedded tissue and allocated to 4 discovery groups: UC (n4), CAC (n4), high-grade dysplasia in one patient (0.4%) and cancer in 2 patients (0.8%). In
low grade dysplasia (n4) and high grade dysplasia (n4). MiRNA expression UC, cancer was observed in 2 (5%) patients, high-grade dysplasia in 1 (2%) and
profiling was performed using Applied TaqMan human miRNA array cards low-grade dysplasia in 1 patient (2%). The median follow-up after strictures
v2.0. Quantitative RT-PCR using individual miRNA assays was subsequently resection was 4.3 years (1.4-8.1). All patients with dysplasia or cancer received
used to validate the results in a further independent cohort: normal (n21), UC a curative surgery, but one patient died of colorectal cancer.
(n 22), Dysplasia (n7) and CAC (n12). CONCLUSION: In this cohort of 293 IBD patients undergoing intestinal resec-
RESULTS: Intergroup comparison of the initial array data identified a progres- tion for colonic stricture, dysplasia or cancer were observed in 3% of cases. These
sive increase in the differential expression levels of miR-10b, 18a, and 32 from findings should be taken into account to guide decision in IBD patients with
dysplasia to CAC. colonic strictures in clinical practice.
The validation cohort showed a significant differential expression of miR-18a, 21 Disclosure of Interest: None declared
and 135b (table 1.0).
A70 United European Gastroenterology Journal 2(5S)
OP214 FORTY-YEARS OF ULCERATIVE COLITIS SURVEILLANCE a markedly reduced prevalence of the genus Ralstonia and parallel increases in
FOR COLORECTAL CANCER: PREVALENCE OF MULTIFOCAL Parabacteroides and Escherichia / Shigella. S. boulardii treatment alone did not
NEOPLASIA AND INTERVAL CANCER, TIME TREND IN CANCER substantially modify the microbiome. However, when S. boulardii was adminis-
RISK, AND THE NATURAL HISTORY OF PROGRESSION OF EACH tered in combination with Amoxicillin/Clavulanate the antibiotic-induced
GRADE OF DYSPLASIA changes in the genera Ralstonia, Parabacteroides and Escherichia / Shigella
C. H. R. Choi1,*, M. Rutter2, A. Askari1, J. Warusavitarne1, M. Moorghen1, were significantly attenuated (P50.05 for each). Diarrhea scores (measured
S. Thomas-Gibson1, B. Saunders1, T. Graham3, A.L. Hart1 using the Gastrointestinal Symptom Response Score (GSRS)) increased during
1
Academic Institute, St. Marks Hospital, London, 2Gastroenterology, University antibiotic treatment in parallel with increases in the prevalence of Escherichia /
Hospital of North Tees, Stockton on Tees, 3Tumour biology, Barts Cancer Shigella in the stool (R2 0.9993 by Linear regression, P50.001). S. boulardii
Institute, Queen Mary University of London, London, United Kingdom treatment in combination with the antibiotic prevented the increase in
Contact E-mail Address: pacoblue@gmail.com Escherichia/shigella prevalence and also prevented antibiotic associated diarrhea
(P50.05 for each).
INTRODUCTION: The prevalence of multifocal neoplasia and interval cancer CONCLUSION: The microbiomes of healthy individuals show substantial diver-
in patients with ulcerative colitis (UC) is unclear. Furthermore, there is a con- sity but remain stable over time. Antibiotic treatment is associated with marked
tinuing debate on the change in colorectal cancer (CRC) incidence over time and microbiome changes with both reductions (Ralstonia) and increases
the risk of progression from each grade of dysplasia to CRC. This study reports (Parabacteroides, Escherichia / Shigella) in different genera. S. boulardii treat-
on data collected from patients with extensive UC between 1971 and 2012 at a ment can prevent some antibiotic-induced microbiome changes and, in parallel,
large tertiary center in the UK, with an aim to answer these important questions. can reduce antibiotic associated diarrhea. Future studies are warranted to
AIMS & METHODS: A retrospective analysis of UC patients enrolled in long- explore whether the strong correlation between an increased prevalence of
term surveillance was performed. Data were obtained from medical records, Escherichia / Shigella and increased symptom scores for antibiotic associated
surgical, endoscopy and histology reports. The primary end point was defined diarrhea represent a cause and effect association that is positively influenced
as death, colectomy, withdrawal from surveillance, or the census date (January 1, by S. boulardii.
2013). Raised dysplastic lesions arising within a diseased segment were classified Disclosure of Interest: C. Kelly Financial support for research from: Biocodex
as sporadic adenoma or UC-associated dysplasia according to the clinical con- Inc, Other: Travel support, T. Kabbani Other: Travel support, K. Pallav: None
sensus made at the time of diagnosis. Cox proportional hazards models and declared, J. Villafuerte-Galvez: None declared, R. Vanga: None declared, N.
Kaplan-Meier curves were generated to assess the risk of cancer progression. Castillo: None declared
RESULTS: A total of 1,375 patients underwent 8,650 colonoscopies (median, 5
per patient; interquartile range (IQR), 3 8 per patient) during 16,037 patient-
years of follow-up (median, 11 years; IQR, 7 17 years). Colorectal cancer was OP216 GUT PERMEABILITY IN IBS IS SITE SPECIFIC, SUBTYPE
detected in 72 patients (5% of study population). The rate of interval cancer was DEPENDENT AND AFFECTED BY CONFOUNDING FACTORS
23.8%. Out of 64 CRCs where a surgical specimen was available, 24 (37.5%) had Z. Mujagic1,*, S. Ludidi1, D. Keszthelyi1, M.A. Hesselink1, J.W. Kruimel1,
synchronous cancers or a spatially distinct focus of dysplasia. The cumulative K. Lenaerts2, N.M. Hanssen3, J.M. Conchillo1, D.M. Jonkers1, A.A. Masclee1
incidence of CRC by disease duration was 0.07% at 10 years, 2.9% at 20 years, 1
Division Gastroenterology-Hepatology, Department of Internal Medicine -
6.7% at 30 years and 10% at 40 years. Linear regression revealed no significant NUTRIM School for Nutrition, Toxicology and Metabolism, 2Department of
change in the overall incidence of CRC during the four decades of the surveil- Surgery - NUTRIM School for Nutrition, Toxicology and Metabolism,
lance program (R -0.13; p0.42). However, there was a significant reduction in 3
Department of Internal Medicine - CARIM School for Cardiovascular Diseases,
incidence of colectomy performed for dysplasia or CRC over time (R -0.43; Maastricht University Medical Center, Maastricht, Netherlands
p0.007). The risk of developing CRC for each type of neoplasia compared with
patients with no neoplasia was: sporadic adenoma (hazard ratio (HR), 0.50; 95% INTRODUCTION: Altered intestinal barrier function is one of the assumed
confidence interval (CI), 0.15 1.64; p0.25), indefinite for dysplasia (HR, 6.1; pathophysiological mechanisms of irritable bowel syndrome (IBS). Intestinal
95% CI, 1.721.5; p0.005), low-grade dysplasia (HR, 7.8; 95% CI 2.425.7; permeability has previously been studied in small IBS populations, but findings
p50.001), and high-grade dysplasia (HR, 33.1; 95% CI, 9.7112.9; p50.001). were contrasting and difficult to compare due to differences in methodology.
There was no significant difference in the risk of CRC between indefinite for AIMS & METHODS: Objectives of the present study were 1) to assess intestinal
dysplasia and low-grade dysplasia group (log-rank; p0.786). permeability at different sites of the GI tract, in a large group well characterised
CONCLUSION: The overall risk of CRC was considerably lower than pre- IBS patients and healthy controls (HC) and investigate differences between sub-
viously reported. However, there was no significant change in CRC incidence types, and 2) to assess potential confounding effects of multiple patient-related
over time. Multifocal neoplasia and interval cancer was common, highlighting factors.
the importance of careful inspection with advanced imaging technologies to IBS patients (all according to ROME III criteria) and HC of a large IBS cohort
ensure lesions are not missed. High-grade dysplasia is a strong indication for underwent a validated multi-sugar test to assess intestinal permeability on four
colectomy. Indefinite for dysplasia may have a similar risk of CRC compared sites of the GI tract. Sucrose excretion and the lactulose/rhamnose (L/R) ratio in
with low-grade dysplasia and the differential patient management decisions 0-5 h urine indicated gastroduodenal and small intestinal permeability, respec-
should not be made solely on the histological finding. tively. Sucralose/erythritol (S/E) ratio in 0-24 and 5-24 h urine was used as
Disclosure of Interest: None declared indicators of whole gut and colonic permeability, respectively. Linear regression
analysis was used to assess the association between IBS and IBS subtypes and
intestinal permeability and to adjust for possible confounding factors, i.e. demo-
TUESDAY, OCTOBER 21, 2014 14:0015:30 graphics (age, sex, BMI), psychological symptoms (anxiety or depression), life-
NORMAL AND ABNORMAL CROSS-TALK AT THE MUCOSAL BORDER: RELEVANCE style factors (smoking history, (defined as current or previous smoker) and
FOR GI FUNCTION AND DYSFUNCTION HALL L/M_____________________ alcohol intake of 415 units/week), and use of medication in the 2 weeks prior
to inclusion (NSAID, PPI, SSRI and medication that affects motility).
OP215 ANTIBIOTIC INDUCED DYSBIOSIS AND CORRECTIVE RESULTS: 91 IBS patients, i.e. 37% diarrhoea predominant (IBS-D), 23%
IMPACT OF SACCHAROMYCES BOULARDII IN HEALTHY constipation predominant (IBS-C), 33% with mixed (IBS-M) and 7% with
VOLUNTEERS unspecified stool pattern (IBS-U), and 94 HC were enrolled. Sucrose excretion
C.P. Kelly1,2,*, T.A. Kabbani1, K. Pallav1, J.A. Villafuerte-Galvez 1, was significantly increased in the total IBS group versus HC (median [Q1; Q3] in
R.R. Vanga1, N. Castillo1 mmol: 5.26 [1.82; 11.03] vs. 2.44 [0.91; 5.85], p50.05), as well as in IBS-C (7.40
1
Gastroenterology, Medicine, Harvard Medical School, 2Gastroenterology, [2.37; 18.29], p50.01) and IBS-D (4.22 [2.12; 8.03], p50.05) versus HC.
Medicine, Beth Israel Deaconess Medical Center, Boston, United States However, the differences attenuated when adjusting for confounders. Factors
Contact E-mail Address: ckelly2@bidmc.harvard.edu with significant confounding effects were higher BMI, smoking history and use
of drugs that positively affect motility.
INTRODUCTION: Interactions between the microbial flora of the intestine and Furthermore, the L/R ratio was increased in IBS-D patients compared to HC
the human host play a critical role in maintaining intestinal health and in the (0.023 [0.013; 0.038] vs. 0.014 [0.008; 0.025], p50.05), which remained significant
pathophysiology of a wide variety of disorders including antibiotic associated after adjustment for confounders.
diarrhea, Clostridium difficile infection and inflammatory bowel disease. There was no significant difference between groups in 0-24 and 5-24 hour S/E
Antibiotics disrupt the normal intestinal microflora whereas probiotics, such as ratio.
Saccharomyces boulardii, have the potential to reduce these harmful effects and CONCLUSION: Small intestinal, but not gastroduodenal, colonic and whole gut
to restore a more healthy and balanced intestinal microbiota. permeability is increased in patients with IBS-D when compared to HC, irrespec-
AIMS & METHODS: The aim of this study was to evaluate the effects of an tive of possible confounding factors. Adjustment for possible confounders is
antibiotic (Amoxicillin/Clavulanate), a probiotic (Saccharomyces boulardii), necessary when studying intestinal permeability, especially in a heterogeneous
Florastor) and the combination on the microbiota of healthy adult volunteers. disorder as IBS.
Healthy subjects were randomized to one of four study groups (n12 for each): Disclosure of Interest: Z. Mujagic: None declared, S. Ludidi: None declared, D.
1) S. boulardii (SB), 500 mg twice daily for 14 days, 2) Amoxicillin/Clavulanate Keszthelyi: None declared, M. Hesselink: None declared, J. Kruimel: None
(AC), 875/125 mg twice daily for 7 days, 3) Amoxicillin/Clavulanate plus S. declared, K. Lenaerts: None declared, N. Hanssen: None declared, J.
boulardii (each dosed as above), 4) Control (no treatment). Conchillo: None declared, D. Jonkers: None declared, A. Masclee Consultancy
Seven stool samples were collected from subjects in the active groups (groups 1, 2 for: Pentax medical, Grunenthal GmbH, Ferring
& 3) and 3 stool samples from controls. Gastrointestinal symptom questionnaires
were also completed by the participants. 16S rRNA gene pyrosequencing was
used to identify the predominant bacterial genera in stool samples and to monitor
changes in the microbiota in each study group.
RESULTS: Subjects showed a complex microbiome at study entry that appeared
to segregate into groupings or enterotypes as previously described. Antibiotic
treatment (AC group) was associated with marked microbiome changes and
these persisted for some time after treatment ended. Antibiotic treatment led to
United European Gastroenterology Journal 2(5S) A71
TUESDAY, OCTOBER 21, 2014 14:0015:30 RESULTS: Between January 2011 and December 2013, 93.7% (30/32) centers
UPDATE ON CAPSULE ENDOSCOPY HALL N_____________________ accessed the registry, recording 3191 procedures. The main indications for SBCE
were: obscure gastrointestinal bleeding (OGIB) / unexplained anemia 76.1%,
OP217 THE USE OF SMALL BOWEL CAPSULE ENDOSCOPY IN THE suspected Crohns disease 4.5%, known Crohns disease 1.0%, chronic diarrhea
INVESTIGATION OF IRON DEFICIENCY ANAEMIA. ADHERENCE 3,0%, suspected small bowel tumor 1.5%, others 13.9%. Overall, SBCE was
TO BSG GUIDELINES AND IMPACT ON DIAGNOSTIC YIELD positive in 48.2 % of patients, negative in 41.8% and undefined in 10.0%. In
G.H. Bain1,*, V. F. P. Ritchie1, S.S. Salunke1, J.M. Thomson1 37.0% of the cases SBCE was performed as an inpatient procedure, 61.9% as an
1
NHS GRAMPIAN, Aberdeen, United Kingdom outpatient procedure and in 1.1% in a day hospital setting. Patients who
Contact E-mail Address: gillianbain@nhs.net performed the VCE as outpatients were younger: mean 60.217.2 vs.
65.917.3 yrs respectively (p50.001), whereas there was no difference for
INTRODUCTION: Iron deficiency anaemia (IDA) occurs in 2-5% of adult men gender, indications, results and prescriber. 86.7% of patients were evaluated
(M) and postmenopausal women (F) in the developed world1 and is a common directly by the physician at his own medical center before performing the
reason for referral to Gastroenterology2. Small bowel (SB) capsule endoscopy VCE, 10 .7% came from other hospitals and only 2.6% directly from the general
(CE) has revolutionised investigation of SB disorders. British Society of practitioner. Of 3191 patients, 27 (0.84%) experienced capsule complications; 18
Gastroenterology (BSG) guidelines suggest considering CE if the Haemoglobin (0.56%) of them required endoscopic or surgical retrieval. Acute obstruction
(Hb) cannot be restored or maintained with iron therapy3. The few studies exam- occurred in 5 (0.15%) patients. The distribution of the centers and activity of
ining diagnostic yield (DY) of CE in IDA alone have demonstrated a wide VCE is however not homogeneous in 11 district of Lombardia.
variability in positive findings (30%5-71%6). CONCLUSION: Our prospective data confirm that OGIB is still the leading
AIMS & METHODS: To determine if use of CE in IDA adhered to BSG guide- indication for SBCE. VCE is a safe outpatient procedure, usually performed
lines, and the effect of adherence to guidelines on DY. A retrospective audit of by local district hospitals. Its distribution among the regional district is however
CEs performed in our institution over 5 years from 2009-2013 was performed. All not homogeneous.
patients with the indication of IDA were identified and their CE reports exam- Disclosure of Interest: None declared
ined. Data were collected on blood indices from the laboratory system. IDA was
defined, according to local laboratory indices, as: Hb in M of 5140g/l (if
570yrs) or 5116g/l (if 70yrs) and in F of 5120g/l (570yrs) or 5108g/l OP219 IRON DEFICIENCY ANEMIA DESPITE EFFECTIVE GLUTEN-
(70yrs), along with a serum ferritin in M of 520mg/l and in F of 57mg/l FREE DIET IN CELIAC DISEASE: DIAGNOSTIC ROLE OF VIDEO-
(550yrs) or 510mg/l (50yrs). CAPSULE ENDOSCOPY
RESULTS: From 2009-2013, 391 CEs were performed. 131 (33.5%) had IDA as K. Efthymakis1,*, A. Milano1, F. Laterza1, M. Serio1, M. Neri1
the recorded indication. Following review, 22 were excluded (5 as indication was 1
Department of Medicine and Ageing Sciences, "G. DAnnunzio" University and
overt bleeding, 7 no CE report, 10 no blood results available). 10 were incomplete Foundation, Section of Internal Medicine and Center for Excellence on Ageing
(poor bowel prep): 6 were not repeated and therefore excluded, 4 were repeated (Ce.S.I.), Chieti, Italy
and the incomplete study excluded. Therefore a total of 99 patients were included Contact E-mail Address: mneri@unich.it
in the study. The capsule was retained at a stricture in 4 patients- these patients
were included. Retention was confirmed with abdominal x-ray at 2 weeks in 2 INTRODUCTION: Iron deficiency anemia (IDA) is frequently associated with
patients (2%). Combined with the incomplete studies, this gives a completion rate celiac disease (CD). Although gluten free diet (GFD) and adequate oral or
of 87.2%. parenteral iron supplementation is an efficient treatment for IDA, iron deficiency
The number of CE performed per year for IDA increased over the study period. remains a relatively frequent finding during follow-up and it is usually correlated
The mean age was 60 (17-90) of which 46.5% (n46) were M and 53.5% (n53) to both clinical and serological lack of response to GFD. Little is known on
were F. patients with persistent IDA despite effective GFD treatment, a finding observed
In 71.7% (n71) CE was performed according to BSG guidelines: 38.4% (n38) in approximately 8% of patients[1].
Hb not restored with iron therapy and 33.3% (n33) Hb restored but not main- AIMS & METHODS: To evaluate the role of video-capsule endoscopy (VCE) in
tained. In the remaining 28.3% (n28) CE was performed out with BSG guide- CD patients with IDA non-responsive to adequate GFD.
lines: 14.1% (n14) Hb restored and maintained, 7.1% (n7) Hb checked once We evaluated consecutive patients affected by CD undergoing GFD for at least
and was restored but not checked again to determine if maintained and in 8.1% 24 months with persistent concomitant IDA. All patients were assessed for IgG
(n8) no bloods were checked after initial blood tests before CE. and IgA transglutaminase (t-TG) and endomysium (EMA) antibodies and, if
46 studies had positive SB findings giving a DY of 46.5%. Findings were angio- negative, underwent complete endoscopic evaluation.
dysplasia 23.2% (n23), inflammation/ulceration/stricture 15.2% (n15), angio- RESULTS: We evaluated 32 consecutive female patients (mean age 43.18.9
dysplasia and inflammation 3% (n3), active bleeding 2% (n2), polyp/mass years) on GFD for a mean of 6.24.9 years and concomitant IDA with negative
2% (n2) and blunted villi 1% (n1). In addition to this, 12 studies had sig- antibody work-up. Six were excluded for gynecological disorders or major recent
nificant findings outside the SB giving a DY of 12.1% and an overall DY of surgery. None of the patients presented signs of overt gastrointestinal bleeding.
58.6%. Twenty six patients were eventually included in the study and underwent gastro-
Overall DY was higher when CE was performed in accordance with BSG guide- scopy, colonoscopy and VCE. Altogether, eleven patients resulted positive at
lines [64.8% (46/71) versus 42.9% (12/28) (p0.07)]. endoscopy. Gastroscopy showed mucosal lesions potentially causing anemia in
CONCLUSION: Adherence to BSG guidelines for use of CE in IDA was 71.7%. seven (27%): erosive duodenitis (n1), active CD (n3), erosive gastritis (n2),
Overall DY was high at 58.6% but improved to 64.8% when guidelines were esophagitis (n1). Colonoscopy showed only 2 potentially associated finding
adhered to. (hemorrhoids). At VCE we documented small bowel involvement in 6 cases
REFERENCES (23%): 3 erosive jejunitis (1 eventually diagnosed as refractory CD, 2 Crohns
1. WHO. 2008. disease), 2 jejunal teleangectasias, 1 diffuse jejunal lymphangectasia. Some over-
2McIntyre and Long. 1993. lap was observed between endoscopic procedures since in four subjects EGDS
3. SG. 2011. and VCE produced significant findings. However, in three cases VCE was suc-
4Koulaouzidas, et al. 2012. cessful in unraveling a more severe/extensive disease that could not have been
5Holleran, et al. 2013. picked up or correctly assessed by gastroscopy. Low albumin levels were signifi-
Disclosure of Interest: None declared cantly associated with a positive outcome at VCE in celiac disease (p50.009). No
correlation was found for vitamin B12, vitamin D, folate, or transferrin serum
levels.
OP218 SMALL BOWEL CAPSULE ENDOSCOPY IN CLINICAL CONCLUSION: VCE allows the identification of significant clinical findings in
PRACTICE: PROSPECTIVE DATA FROM A REGIONAL REGISTRY approximately 23% of CD patients with IDA despite adequate GFD. These are
2011-2013 (REGISTRO LOMBARDO DELLE COMPLICANZE) associated to hypoalbuminemia, indicating their occurrence at more severe stages
M. Soncini1, E. Rondonotti2,*, C.M. Girelli3, A. Russo4, D. Moneghini5, L. Elli6, of the disease.
R. Schalling7, M. Maino8, P. Cesari9, N. Mantovani10, D. Conte6, R. de REFERENCES
Franchis11 on behalf of AIGO, SIED and, SIGE Lombardia [1]Rubio-Tapia A, et al. Am J Gastroenterol 2013.
1
Gastroenterology, A.O. San Carlo Borromeo Milano, Milano, 2Gastroenterology, Disclosure of Interest: None declared
Valduce Hospital, Como, 3Internal Medicine, A.O. Busto Arsizio, Varese,
4
Epidemiology, ASL Milano1, Milano, 5Gastroenterology, A.O. Spedali Civili
Brescia, Brescia, 6Gastroenterology, IRCCS Policlinico Milano, Milano, 7Internal OP220 BULGES ON SMALL BOWEL CAPSULE ENDOSCOPY:
Medicine, A.O. Vimercate, Monza-Brianza, 8Gastroenterology, A.O. Sa Gerardo, INNOCENT LESIONS WE SHOULD TAKE WITH A PINCH OF SPICE
Monza, 9Gastroenterology, Congregazione Ancelle della carita`, Brescia, G. Hatem1,*, A. Buda2, R. Caccaro1, A. Ugoni1, R. DInca`1, M. De Bona2,
10
Gastroenterology, A.O. Poma, Mantova, 11Gastroenterology, A.O. L. Sacco, M. De Boni2, F. Galeazzi1, A. DOdorico1, E., V. Savarino1, G.C. Sturniolo1
1
Milano, Italy Department of Surgery, Oncology and Gastroenterology, University of Padova,
Contact E-mail Address: soncini.marco@sancarlo.mi.it Padova, 2Department of Oncology, Gastroenterology Unit, S. Maria del Prato
Hospital, Feltre, Italy
INTRODUCTION: Data on small bowel capsule endoscopy (SBCE) mostly Contact E-mail Address: giorgia.hatem@gmail.com
come from retrospective studies
AIMS & METHODS: The primary outcome was to prospectively describe the INTRODUCTION: A drawback of Small Bowel Capsule Endoscopy (SBCE) is
extent of use, indications, results, complications, and practical issues of SBCE in represented by the difficulty to distinguish submucosal masses from innocent
clinical practice. The secondary outcome was to compare the distribution of the bulges, in particular when alarm signs are lacking (e.g. bleeding, irregular surface,
VCE in the different districts of the region.All the 32 centers performing capsule polyp-like appearance). A correct interpretation of the endoscopic images is
endoscopy in Lombardia region were invited and agreed to participate in the data necessary in order to avoid patients unnecessary investigations.
collection. In January 2011 a dedicated registry has been set up to collect data on AIMS & METHODS: Aims of our study were 1. to evaluate prospectively the
diagnostic yield, practical issues and complications for each performed proce- prevalence of bulges on SBCE and 2. to discriminate innocent bulges from sub-
dure. Each center was asked to update the registry every three months. mucosal tumours with a previous validate score (SPICEa) in a large cohort of
A72 United European Gastroenterology Journal 2(5S)
patients referred to a teaching hospital. Consecutive patients undergoing SBCE Makins Lecture fee(s) from: SynMed UK, U. Kopylov: None declared, L.
from January 2010 to December 2013 were considered eligible. All SBCE data Bartzis Other: grant from the Hellenic Society of Gastroenterology, A.
were analysed by expert readers (4 200 SBCE analysed). Patients with a pro- Nemeth: None declared, G. Wurm Johansson: None declared, M. Nadler:
truding lesion as the main finding of SBCE were included and the SPICE score None declared, A. Eliakim Other: Speaker for Given Imaging Ltd, E. Seidman
applied. All these patients were either investigated by Computed Tomography Other: Speaker for Given Imaging Ltd, J. Plevris: None declared
Enterography or Magnetic Resonance Enterography and clinically followed-up
in the long period.
RESULTS: 640 consecutive patients (male/female 330/310, median age 55) OP222 ASSESSMENT OF THE PERFORMANCE OF THE COLONIC
underwent SBCE between January 2010 and December 2013. Patients had a PILLCAM PCCE-2 IN PATIENTS WITH ACTIVE COLONIC
median follow-up period of 26 monthes (range 4-48). 30 patients (4.7%) CROHNS DISEASE: A PILOT STUDY
showed at least one bulging area without alarm signs. Out of them three patients M. Lowenberg1,*, M.A. Samaan1, D. Franchimont2, C. Ponsioen1, P. Bossuyt3,
(10%) had a SPICE score 4 2 and in 2 a neoplastic lesion was diagnosed (1 L. Amininejad2, E.M. Lensink1, A. M. Van Gossum2, G.R. DHaens1
carcinoid and 1 ovarian cancer). Among the 27 patients with a SPICE score 5 2, 1
Inflammatory Bowel Disease Unit, Academic Medical Centre, Amsterdam,
seven (26%) had peritoneal adhesions whereas in 20 (74%) all investigations Amsterdam, Netherlands, 2Gastroenterology, Hospital Erasme, Brussels,
showed normal findings. 3
Gastroenterology, Imelda Ziekenhuis, Bonheiden, Belgium
CONCLUSION: Bulges represent a rare finding (4.7%) when SBCE is evaluated Contact E-mail Address: markasamaan@gmail.com
by experienced physicians. SPICE score can predict the presence of malignant
lesion and identify low risk patients in whom further invasive investigations can INTRODUCTION: Treatment goals in Crohns disease (CD) have evolved in
be avoided. Indeed, in our large cohort 2/3 of suspected lesions were eventually recent years from symptom control to mucosal healing, usually visualized by
diagnosed as innocent bulges. optical ileocolonoscopy. The Pillcam colon capsule endoscope (PCCE-2, Given
REFERENCES Imaging, Israel), an ingestible capsule equipped with a video camera at both
Girelli CM et al. Gastrointestinal Endoscopy 2011; 74: 1067-1074. ends, was designed for visualization of the colon. This multicenter pilot explora-
Disclosure of Interest: None declared tory study was designed to investigate and validate the value of the PCCE-2 in
patients with active CD.
AIMS & METHODS: A cohort of 39 patients with active CD was prospectively
OP221 CORRELATION BETWEEN FAECAL CALPROTECTIN AND studied with serial PCCE-2 and optical colonoscopy. The primary aim of the
LEWIS SCORE IN SMALL-BOWEL CAPSULE ENDOSCOPY; A study was to compare the assessment of CD activity using the PCCE-2 with
MULTICENTRE STUDY colonoscopy, which was used as the gold-standard technique.
A. Koulaouzidis1,*, T. Sipponen2, E. Toth3, R. Makins4, U. Kopylov5, Inclusion criteria: patients with a CDAI 4 200, an elevated serum CRP (4 5 mg/
L. Bartzis1, A. Nemeth3, G. Wurm Johansson3, M. Nadler 6, A. Eliakim6, L) and faecal calprotectin (FC 4 200 mg/g) in whom a colonoscopy was clinically
E.G. Seidman5, J.N. Plevris1 indicated and with prior documentation of involvement of at least 2 colonic
1
Centre for Liver & Digestive Disorders, The Royal Infirmary of Edinburgh, segments by CD. Exclusion criteria: any contraindication for optical colonoscopy
Edinburgh, United Kingdom, 2Clinic of Gastroenterology, Department of Medicine, or colon capsule examination. Evaluation: CDEIS & SES-CD, serum CRP & FC
Helsinki University Central Hospital, Helsinki, Finland, 3Department of levels, CDAI, PCCE-2 passage time and side effects. Independent investigators
Gastroenterology, Skane University Hospital, Malmo, Sweden, 4Gastroenterology reviewed recordings of colonoscopy and PCCE-2 procedures. Statistics:
Department, Cheltenham General Hospital, Gloucestershire Hospitals NHS Pearsons correlation coefficient was used to calculate correlations.
Foundation Trust, Cheltenham, United Kingdom, 5Division of Gastroenterology, RESULTS: Thirty-nine patients were enrolled with ages ranging from 18 to 60
McGill University Health Center, Montreal, Canada, 6Department of years. The mean baseline CDAI was 292 (/- 94); serum CRP 51 (/- 76) mg/L;
Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel FC 1201 (/- 725) g/g. The average capsule passage time through the entire
gastrointestinal tract was 7:11 (/- 5:52) hours. In 65% of the cases, the capsule
INTRODUCTION: Faecal calprotectin (FC) remains an invaluable, non-inva- was expelled from the rectum in less than 6 hours. No episodes of capsule reten-
sive biomarker of gut inflammation. Small-bowel capsule endoscopy (SBCE) is a tion were reported.
prime imaging modality for the small-bowel. The Lewis score (LS) has been The mean CDEIS and SES-CD were 8.0 (/- 5.6) and 10.9 (/- 7.1) for PCCE-2,
developed to standardize inflammation reporting of in SBCE. Previously, we and 11.0 (/- 7.0) and 15.9 (/- 9.5) for colonoscopy, respectively. A strong
showed that LS shows only moderate correlation with FC levels, although this correlation was found between the two techniques when assessing CDEIS
seems to improve for FC levels 5100g/g.[1] (Pearson 0.75, p 0.01) and a moderate correlation was found for SES-CD
AIMS & METHODS: To check the validity of the above observation across (Pearson 0.65, p 0.01).
other SBCE centres. Retrospective study; 6 centres (5 university hospitals and
1 district general hospital), offering SBCE, in Canada, Finland, Israel, Sweden,
and UK; 2 SBCE systems (PillCamSB; GivenImaging Ltd, Israel and PCCE-2: PCCE2: Colonoscopy: Colonoscopy:
MiroCam; IntroMedic Co, Seoul, Korea) and 2 types of FC assays (quantita- CDEIS SES-CD CDEIS SES-CD
tive and semi-quantitative). An interval of 43 months between FC measurement
and SBCE was considered exclusion criterion. Spearmans rank correlation coef- PCCE-2:CDEIS 1 .904** .749** .704**
ficient (rs) was employed as non-parametric measure of statistical dependence PCCE-2:SES-CD 1 .653** .648**
between two variables. A two-tailed P value of 50.05 was considered statistically
significant. Colonoscopy:CDEIS 1 .929**
RESULTS: In the aforementioned period, a total of 333 SBCE have been per- Colonoscopy:SES-CD 1
formed fulfilling the inclusion criteria. Of those, 283 were attached to an ELISA
quantitative estimation of FC and the remainder to semi-quantitative assays. In Table 1: Showing Pearsons correlation coefficients for the techniques used to
the former group, by convention, FC levels below the detection threshold (i.e. assess CD activity.
undetectable) were considered as 0. The mean FC, LS and the time interval When comparing the PCCE-2 scores with CDAI and CRP measurements, a poor
between FC measurement and SBCE was 100.36 190.67 g/g, 435.96 970, correlation was seen. FC measurements showed slightly better correlation with
and 28.3 39.3 days, respectively. In this subgroup, the correlation between FC PCCE-2 CDEIS but the correlation remained weak and did not reach statistical
and LS was only moderate (rs0.385), as previously showed [1]. significance (Pearson 0.27, p 0.11).
Although 2 different SBCE systems were used (PillCamSB: 132 and CONCLUSION: This pilot study comparing PCCE-2 to standard colonoscopy
MiroCam: 151), there was no statistically significant difference between FC in patients with active colonic CD has shown a strong correlation for assessing
levels (100.37 191.24 g/g vs 90.71 166.1 g/g; P0.649), time interval CDEIS and moderate correlation for SES-CD. No capsule retention was
between FC/LS (28.4 39.4 days vs 20.63 29.5 days; P0.059), prokinetic observed. The present data should encourage further large trials to confirm the
(P0.547) or bowel prep used (P0.717). Eventually, no LS/FC correlation utility of PCCE-2 in assessing colonic CD activity.
difference was recorded between the 2 SBCE systems, despite the fact that LS Disclosure of Interest: M. Lowenberg: None declared, M. Samaan: None
calculator is only available in the proprietary review software from declared, D. Franchimont: None declared, C. Ponsioen Financial support for
GivenImaging Ltd, (P0.1188). In the group of semi-quantitative FC measure- research from: Abbott Laboratories, Schering-Plough Corp., Falk Pharma,
ment (n50), the interval between SBCE and FC was 40.1 58.4 days (i.e. not Tramedico, Consultancy for: Abbott Laboratories, Glaxo Smith Kline, P.
different to the quantitative FC group; P0.07) and the rs between LS and FC Bossuyt Lecture fee(s) from: Abbott, Consultancy for: Falk pharma Belgium,
was 0.092, P0.126. L. Amininejad: None declared, E. Lensink: None declared, A. Van Gossum:
When the 2 FC thresholds of 100 g/g and 250 g/g where used, irrespective of None declared, G. DHaens Financial support for research from: Falk
FC assay, no difference in the time interval between FC and LS was noted Pharma, MSD, Lecture fee(s) from: MSD, UCB Inc., Abbott, Ferring
(P0.945), while the rs between FC and LS for the 2 threshold levels was Pharmaceuticals Inc., Consultancy for: Abbott, Jansen Biologics, TEVA,
0.247 and 0.337, respectively (P0.307). Glaxo Smith Kline, Shire Pharmaceuticals Inc., Nova Nordisk A/S, Pfizer Inc,
CONCLUSION: This multicentre study confirms that LS low to moderate cor- MSD, UCB Inc.
relation with FC levels.
Acknowledgement: We would like to thank Endoscopy nurses Pirkko Tuukkala
and Virpi Pelkonen for their invaluable help with data collection.
REFERENCES
Koulaouzidis A, et al. Lewis score correlates more closely with fecal calprotectin
than Capsule Endoscopy Crohns Disease Activity Index. Dig Dis Sci 2012; 57:
987-993.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE-GivenImaging Research grant 2011, Lecture fee(s) from: Dr
FalkPharma UK, Other: Travel support: Dr FalkPharmaUK, Almirall,
Abbott, MSD, T. Sipponen: None declared, E. Toth: None declared, R.
United European Gastroenterology Journal 2(5S) A73
TUESDAY, OCTOBER 21, 2014 14:0015:30 normal squamous epithelium HET1A cell line through ELISA analysis as well
FROM RISK STRATIFICATION TO ABLATION IN BARRETTS OESOPHAGUS HALL as Western Blotting was also undertaken.
O_____________________ Finally, the effect of Estrogen blockade through Tamoxifen treatment on the
effect on the NF-kB pathway was evaluated.
OP223 IMPACT OF SURVEILLANCE FOR BARRETTS ESOPHAGUS RESULTS: Pre-incubation with estradiol at physiological concentrations reduces
ON SURVIVAL OF PATIENTS WITH NEOPLASTIC baseline nuclear NF-kB p-65 levels (p50.05). Furthermore, this treatment abro-
PROGRESSION: RESULTS OF A LARGE MULTICENTER gated the NF-kB inducing effect of deoxycholic acid.
PROSPECTIVE COHORT STUDY Immunohistochemical staining of endoscopically retrieved biopsies of Barretts
F. Kastelein1,*, S. van Olphen1, M. Spaander1, E. Steyerberg2, M. Bruno1 on metaplasia, OA and squamous tissue adjacent to cancer revealed that female
behalf of ProBar-study group patients have higher levels of inactive cytoplasmic p-65 than men (p0.006), as
1
Gastroenterology and Hepatology, 2Public health, ERASMUS UNIVERSITY well as lower levels of activating pIKK than their male counterparts (non-
MEDICAL CENTER, Rotterdam, Netherlands significant).
Contact E-mail Address: f.kastelein@erasmusmc.nl Finally, the inhibitor of NF-kB, ikB was significantly increased in both OE33 and
HET1A cell lines exposed to Estradiol (p50.01).
INTRODUCTION: Surveillance is recommended for Barretts esophagus (BE) CONCLUSION: Given that female patients have higher cytoplasmic p65 levels
to detect esophageal adenocarcinoma (EAC) at an early stage. However, the than males, it is possible that the mechanisms underlying this could be through
value of BE surveillance is under discussion given the overall low incidence of reduced nuclear localisation following exposure to sex hormones. This is sup-
neoplastic progression, large screening base, and lack of discriminative tests for ported by the in-vitro demonstration that 17B-Estradiol reduces nuclear p65
risk stratification. levels.
AIMS & METHODS: The aim of this study was to evaluate the impact of BE It is plausible therefore that estrogen could have a role in reducing inflammation
surveillance on the survival of patients with neoplastic progression. 783 patients in the oesophageal mucosa following exposure to noxious chemicals present in
with BE of at least two centimeter were included in a multicenter prospective refluxate, and this protective effect may be through its activity on the NF-kB
cohort study and followed during surveillance according to the ACG guidelines. pathway.
Incident cases of high-grade dysplasia (HGD) and EAC were identified during Disclosure of Interest: None declared
follow-up. Patients with neoplastic progression were treated with intensive sur-
veillance or endoscopic treatment for HGD or early EAC, and esophagectomy
for advanced EAC. Survival data were collected for all patients in the study, OP225 ACTIVATED METABOLIC PATHWAYS IN BARRETTS
cross-checked using death and municipal registries and compared to survival OESOPHAGUS ACCORDING TO BODY COMPOSITION OR BMI
data from patients with EAC in the general population based on data from AND PROGRESSION TO CANCER
the Dutch cancer registry. Information on cause of death was obtained from S. Di Caro1,*, W.H. Cheung2, L. Fini3, R. Haidry1, M. Keane1, L. Lovat1,
the general practitioner or gastroenterologist and was compared to cause of R. Batterham2, M. Banks1
death in age and gender matched controls in the general population based on 1
Gastroenterology, 2Centre for Obesity Research, UNIVERSITY COLLEGE
data from the Dutch central statistical office. Cox-regression models were used to HOSPITAL, LONDON, UK, London, United Kingdom, 3Gastroenterology, Busto
calculate hazard ratios (HR) and 95% confidence intervals (CI). Arstizio Hospital, Milan, Italy
RESULTS: During follow-up 53 patients developed HGD or EAC with an Contact E-mail Address: Simona.DiCaro@uclh.nhs.uk
incidence rate of 1.2 per 100 person-years. Thirty-five patients (66%) were clas-
sified as stage 0 disease, 14 (26%) as stage 1, and 4 (8%) as stage 2. EAC was INTRODUCTION: Barretts oesophagus (BE) remains the strongest risk factor
diagnosed at a significantly earlier stage during BE surveillance than in the gen- for oesophageal adenocarcinoma (OAC). Several studies describe an association
eral population (P50.001). The survival of BE patients with neoplastic progres- between BE and obesity through mechanical and metabolic consequences.
sion during surveillance was worse than those of BE patients without neoplastic Visceral fat is a recognised endocrine organ. Adipokines and insulin resistance
progression during surveillance (HR 2.98, 95% CI 1.62-5.50), better than those of have an impact on obesity related diseases and cancer pathways.
patients with EAC in the general population (HR 0.16, 95% CI 0.09-0.29), and AIMS & METHODS: In sequential patients (pts), undergoing upper gastroin-
comparable to those of patients with stage 0 or stage 1 EAC in the general testinal endoscopy, we assessed BMI, waist-hip ratio (WHR) and presence of
population. The overall 5-year survival was 74% in BE patients with neoplastic metabolic syndrome, to evaluate the correlation between BMI and body compo-
progression during surveillance, 94% in BE patients without neoplastic progres- sition with metabolic indexes and adipokines in BE compared to controls. A
sion during surveillance and 17% in patients with EAC in the general population. blood sample was obtained to test fasting insulin, glucose, lipids, HbA1c and
The majority of BE patients died due to malignancies (36%) or cardiovascular serum adiponectin and leptin. All pts were classified to overweight, obese and
diseases (29%). Four percent of BE patients died due to EAC. The cause of death abdominally obese (by WHR). Biopsies were obtained from BE and histological
for BE patients was comparable to those of age and gender matched controls in progression to cancer was correlated with metabolic indexes. Chi square, Fisher,
the general population. t-Student test and logistic analysis were used for comparison.
CONCLUSION: BE surveillance enables the detection of EAC at an early and RESULTS: 480 patients (250 cases; F/M: 193/287; mean age: 58.0815.51) were
curable stage when endoscopic treatment is still feasible. The 5-year overall enrolled. Insulin levels (10.2 vs 7.2IU/ml; p0.001), Hba1c (5.8 vs 5.1%;
survival of patients with neoplastic progression during surveillance is 74% p50.01), metabolic syndrome (33.2 vs 20%; OR 1.95; p 0.0017), insulin resis-
which corresponds to the survival of patients with stage 0 or stage 1 EAC in tance (47 vs 27%; OR 1.54; p50.01), dyslipidaemia (72.8 vs 53.9; OR 2.3;
the general population. p50.0001) and hypertension (37.4 vs 21.3%; OR 2.4; p50.001), were higher in
Disclosure of Interest: None declared BE compared to controls.
MS was present in 39.7 vs 34.2% (OR 3.05; p50.001), 43.7 vs 21.9% (OR 5.2;
p50.001), 92.1 vs 54.9% (OR 8.08; p50.0001), in overweight, obese, abdominal
OP224 SEX HORMONES AND BARRETTS OESOPHAGUS - A FUTURE obese pts with BE and controls, respectively.
THERAPY OR JUST A HOT FLUSH? Insulin resistance was present in 39.2 vs 33.8% (OR 1.3; p50.05), 38 vs 22.3%
H.N. Haboubi1,*, E. McAdam1, P. Griffiths2, G. Jenkins1 (OR 1.7; p50.01) and in 82.5 vs 54.5% (OR 1.5; p50.001) in overweight, obese
1
Cancer Biomarker Group, Swansea University, 2Department of Histopathology, and abdominal obese pts, respectively.
ABM University NHS Board, Swansea, United Kingdom A trend was observed for decreased adiponectin levels in BE vs controls while
Contact E-mail Address: h.n.y.haboubi@swansea.ac.uk leptin showed no correlation.
In BE pts, the presence of dysplasia was associated with MS (42 vs 25%;
INTRODUCTION: The presence of Barretts Oesophagus (BO) and subsequent p0.005) and and insulin resistance (51.4 vs 34.0%; p0.005).
development of Oesophageal Adenocarcinoma (OA) is up to four-times more CONCLUSION: BE association with dyslipidaemia, insulin resistance, MS and
common in male patients compared to females. The reasons behind this gender hypertension suggests activation of specific metabolic pathways in pts with
difference remain unclear, and whilst hormones have been an attractive area for altered body composition or BMI. The strongest risk factor is abdominal obesity.
investigation, the results have been quite variable, probably owing to the multi- Progression to cancer appears modulated by metabolic dysfunction in MS and a
factorial mechanisms underlying carcinogenesis. carcinogenic insulin pathway.
The pro-inflammatory transcription factor, NF-kB has been implicated in a REFERENCES
number of infectious and malignant processes. Given that Barretts 1. Ryan AM, Healy LA, Power DG, et al. Barrett esophagus: prevalence of
Oesophagus arises in an inflammatory environment associated with the reflux central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg
of acid and bile, it has not been surprising to note increased NF-kB activity in 2008; 247: 909-915.
these tissues during the progression of Barretts metaplasia through the dysplastic 2. Kendall B, Macdonald G, Hayward N, et al. The risk of Barretts oesophagus
sequence to OA. In-vitro studies have demonstrated activation of NF-kB p65 and associated with abdominal obesity in males and females. Int J Cancer 2013; 132:
nuclear localisation following exposure to bile and acid. In other cell lines, NF- 2192-2199.
kB has also been demonstrated to be under the influence of hormonal control, 3. Rubenstain J, Kao J, Madanick R, et al. Association of adiponectin multimers
both directly as well as through the inhibition of alternate immunomodulatory with Barretts oesohagus. Gut 2009; 58: 1583-1589.
pathways. Disclosure of Interest: None declared
AIMS & METHODS: We aimed to investigate the effects on nuclear localisation
of NF-kB p65 following hormone therapy in oesophageal cell lines to attempt to
explain the observed gender differences in BO and OA.
We investigated the possible protective effects of 17B-Estradiol on OE33 cell lines
through ELISA analysis of activated NF-kB p-65 levels. We subsequently inter-
rogated members of the NF-kB pathway to better understand the mechanisms
underlying observed effects using western blotting and RT-PCR of in-vitro trea-
ted cells, as well as immunohistochemical staining of endoscopically obtained
oesophageal biopsies. Analysis of the effect of estradiol on immortalised
A74 United European Gastroenterology Journal 2(5S)
OP226 OUTCOMES OF ENDOSCOPIC SURVEILLANCE IN BARRETTS OP228 THE SURF TRIAL PRE-ASSESSMENT COHORT: SPATIAL
OESOPHAGUS: A POPULATION BASED COHORT STUDY IN THE EXTENT OF LOW-GRADE DYSPLASIA AND EXTENT OF
UK AGREEMENT BETWEEN EXPERT PATHOLOGISTS ARE
M. Solaymani-Dodaran1,2,*, J. West2, T. Card2 ASSOCIATED WITH RISK OF MALIGNANT PROGRESSION
1
Minimally Invasive Surgery Research Center, Iran University of Medical L.C. Duits1,*, K.N. Phoa1, T., V. Pham1, F.J. Ten Kate2, C.A. Seldenrijk3,
Sciences, Tehran, Iran, Islamic Republic Of, 2Division of Epidemiology and Public G.J. Offerhaus2, M. Visser1, S.L. Meijer1, K.K. Krishnadath1, R.C. Mallant-
Health, University of Nottingham, Nottingham, United Kingdom Hent4, J.G. Tijssen1, J.J. Bergman1
1
Contact E-mail Address: Masoud.Solaymani-Dodaran@nottingham.ac.uk Academic Medical Centre, Amsterdam, 2University Medical Centre, Utrecht, 3St
Antonius Hospital, Nieuwegein, 4Flevoziekenhuis, Almere, Netherlands
INTRODUCTION: The impact of endoscopic surveillance in patients having
Barretts oesophagus (BO) is not clear. We compared oesophageal cancer inci- INTRODUCTION: Low-grade dysplasia (LGD) in Barretts oesophagus (BO) is
dence and mortality in a cohort of patients with BO undergoing surveillance and an accepted risk factor for progression to high-grade dysplasia (HGD) or oeso-
another of those not being surveyed. phageal adenocarcinoma (OAC). However, the diagnosis of LGD is subjective
AIMS & METHODS: We used linked UK Clinical Practice Research Datalink, and it is unclear which additional factors can help identify LGD patients at
Hospital Episode Statistics, Office of National Statistics Death records, and increased risk of progression. For the purpose of this study, all patients screened
Cancer Registry Data. We identified cases with Barretts oesophagus and cate- for the SURF trial were separately reviewed by 3 expert pathologists. The SURF
gorized them as surveyed or not surveyed based on subsequent endoscopic exam- trial is a randomized study showing that prophylactic ablation of BO with con-
ination(s) starting at least 1 year after Barretts diagnosis. We estimated firmed LGD reduces progression to HGD/OAC.1
oesophageal cancer incidence and mortality as well as all cause mortality after AIMS & METHODS: We aim to investigate predictors of malignant progression
excluding the first year of follow-up and compared them in the two groups. Cox in BO patients diagnosed with LGD. 234 LGD patients (78% male; mean 63
proportional hazard regression models were used to estimate hazard ratios and years 10.7) underwent histology review by 3 expert pathologists, who separately
their 95% confidence intervals. evaluated each available level of biopsies from the BO segment. Confirmed LGD
RESULTS: In total 15704 subjects with Barretts oesophagus were identified of was defined as a majority diagnosis from the expert pathologists. Primary out-
which 3499 were surveyed. Mean ages were 61 and 65 in those surveyed and not come was neoplastic progression (HGD/OAC) during endoscopic follow-up
surveyed respectively. While risk of occurrence of oesophageal cancer (HR3.89 (FU). Median duration of FU was 41 months (IQR 22-61). Cox regression
95%CI 1.91-7.92) and oesophageal adenocarcinoma (HR4.04 95%CI 1.88- analysis was performed on the risk of malignant progression.
8.70) in those undergoing surveillance was four times higher compared with RESULTS: 36/61 patients (59%) with confirmed LGD at baseline developed
those not being surveyed after adjusting for age, sex, smoking, alcohol and HGD/OAC. 10/173 patients (6%) who were downstaged at baseline to non-
BMI, their risk of death due to oesophageal cancer showed only a 26% non- dysplastic BO (NDBO) demonstrated malignant progression. The hazard ratio
significant excess (HR1.26 95%CI 0.68-2.36) and their risk of death due to all (HR) for baseline confirmed LGD was 15.1 (95% CI 7.4-30.5). The number of
causes was significantly lower (HR0.81 95%CI 0.68-0.98). expert pathologists confirming the presence of LGD and the number of levels
CONCLUSION: At present less than a quarter of those with BO in the UK are within the BO segment with confirmed LGD predicted progression, as shown in
surveyed. Those who are surveyed have a lower risk of death overall, suggesting a the table below.
rational targeting of surveillance resources. If the increased incidence of carci-
noma in the surveyed is real (rather than just representing earlier diagnosis due to
surveillance) then the far lower excess of death than occurrence might suggest No of events Hazard ratio (95% CI)
surveillance is of benefit.
Disclosure of Interest: None declared Pathologists confirming LGD:None 4.1% (5/122) -
1/3 9.8% (5/51) 2.6 (0.77-9.14)
OP227 SOX2 AS A NOVEL MARKER TO PREDICT NEOPLASTIC 2/3 51.5% (17/33)17.4 (6.39-47.24)
PROGRESSION IN BARRETTS OESOPHAGUS 3/3 67.9% (19/28)28.6 (10.60-77.29)
S. H. Van Olphen1,2,*, K. Biermann2, M. Spaander1, F. Kastelein1, B. Hansen1, Extent of LGD*: No LGD 5.8% (10/173)-
H. Stoop2, L. Looijenga2 on behalf of on behalf of the ProBar-study group 1 level LGD 58.3% (21/36)13.8 (6.49-29.39)
1
Department of Gastroenterology & Hepatology, 2Department of Pathology, 2 levels LGD50% (5/10) 14.6 (4.90-43.52)
Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
3 levels LGD83.3% (5/6) 26.4 (8.84-78.98)
Contact E-mail Address: s.vanolphen@erasmusmc.nl
INTRODUCTION: The value of surveillance for patients with Barretts oeso- 15/173 patients who were downstaged to NDBO at baseline developed confirmed
phagus (BO) based on histological diagnosis of low-grade dysplasia (LGD) LGD at a subsequent FU endoscopy, of whom 5 patients had malignant pro-
remains debated given the lack of discriminative power to stratify BO patients gression. Time-dependent Cox regression yielded a HR of 20.8 (95% CI 8.80-
at high risk for neoplastic progression of those at low risk. The use of biomarkers 49.07) for occurrence of confirmed LGD at any time during follow-up.
in addition to histological assessment improves risk stratification and has the CONCLUSION: A consensus LGD diagnosis is the most important predictor of
potential to improve cost-effectiveness of BO surveillance. SOX2 plays a pivotal malignant progression. Multilevel LGD and extent of agreement between expert
role in the development of oesophageal and gastric epithelium and is down pathologists were strongly associated with risk of HGD/OAC. These character-
regulated in intestinal metaplasia and gastric cancer. istics might help select BO patients with LGD for prophylactic ablation therapy.
AIMS & METHODS: The aim of this study was to investigate the value of SOX2 REFERENCES
in BO patients to predict neoplastic progression and to combine the results with 1. Phoa et al. JAMA 2014; 311: 1209-1217.
our previously reported p53 immunohistochemical data within the same. We Disclosure of Interest: L. Duits: None declared, K. Phoa: None declared, T.
conducted a case-control study within a large prospective cohort of 720 BO Pham: None declared, F. Ten Kate: None declared, C. Seldenrijk: None declared,
patients, with a total follow-up time of more than 5600 years. In total 44 BO G. Offerhaus: None declared, M. Visser: None declared, S. Meijer: None
patients with neoplastic progression defined as development of high-grade dys- declared, K. Krishnadath: None declared, R. Mallant-Hent: None declared, J.
plasia (HGD) or oesophageal adenocarcinoma (OAC)(cases) and 44 BO patients Tijssen: None declared, J. Bergman Financial support for research from:
without neoplastic progression (controls) were selected and matched for age and Covedien GI Solutions
gender. SOX2 protein was detected by immunohistochemistry in more than 3000
biopsies and was scored independently by two investigators blinded for long-term
outcome. The results were combined with p53 immunohistochemical data. TUESDAY, OCTOBER 21, 2014 14:0015:30
Hazard ratios (HRs) were calculated by Cox-regression models adjusted for CHALLENGES IN THE TREATMENT OF PANCREATIC AND BILIARY TRACT CANCER
age, gender, BE length and esophagitis. LOUNGE 5_____________________
RESULTS: Normal BO epithelium showed homogeneous strong nuclear expres-
sion of SOX2, while expression of SOX2 was progressively lost in dysplastic OP229 CLINICOPATHOLOGICAL CHARACTERISTICS OF
epithelial cells. Loss of SOX2 expression was seen in 9% of biopsy series without PANCREATIC RESECTION SPECIMENS OF INHERITED/
dysplasia, in contrast to 37% of biopsy series with LGD and 70% of biopsy series FAMILIAL VERSUS SPORADIC PANCREATIC DUCTAL
with HGD or OAC. Multivariate analysis showed that loss of SOX2 expression ADENOCARCINOMA
(HR 2.3; 95% CI:1.1-4.6) and aberrant p53 expression (HR 3.7; 95% CI:1.8-7.8) F. Harinck1,*, F. Boersma1, I. Konings1, P. Fockens2, J. van Hooft2,
were independent predictors for neoplastic progression (multiplied HR of 8.5), M. Dijkgraaf2, W. Dinjens1, K. Biermann1, M. Bruno1 on behalf of On behalf of
whereas presence of LGD was no longer predictive. The positive predictive value the Dutch Research Group of Pancreatic Cancer Surveillance in High-Risk
for neoplastic progression increased from 47% with histological diagnosis of Individuals
LGD, to 83% with LGD and concurrent aberrant SOX2 expression, to 87% 1
ERASMUS MC UNIVERSITY MEDICAL CENTER ROTTERDAM,
with LGD and concurrent aberrant p53 expression and to 91% with aberrant Rotterdam, 2Academic Medical Center Amsterdam, Amsterdam, Netherlands
SOX2 and p53 expression. Contact E-mail Address: f.harinck@erasmusmc.nl
CONCLUSION: SOX2 is lost during transition from non-dysplastic BO to
HGD/OAC. Loss of SOX2 and aberrant p53 expression are independent pre- INTRODUCTION: There is a growing interest towards pancreatic cancer screen-
dictors for neoplastic progression in patients with BO and more powerful than ing in individuals with an increased inherited or familial risk for this disease.
the histological diagnosis of LGD. SOX2 and p53 immunohistochemistry may be When designing screening programs aiming to identify high-risk lesions for early
useful as a discriminative test to improve risk stratification of Barrett resection, knowledge of the pathology of the disease is essential. In this current
surveillance. study we focus on the clinicopathological characteristics of pancreatic resection
Disclosure of Interest: None declared specimens of patients with inherited or familial pancreatic cancer in comparison
to sporadic cases.
AIMS & METHODS: Pancreatic intraepithelial neoplasia (PanIN) and intra-
ductal papillary mucinous neoplasm (IPMN) were quantified in surgical
United European Gastroenterology Journal 2(5S) A75
resection specimens of patients with inherited/familial pancreatic cancer and evaluate the psychological burden of repeated pancreatic surveillance of indivi-
patients with sporadic pancreatic cancer. Inherited/familial pancreatic cancer duals at genetically high risk to develop PC.
was defined as patients with at least one first degree relative with pancreatic AIMS & METHODS: Individuals with a lifetime risk of developing PC410%,
cancer and/or carriers of a pancreatic cancer prone gene mutation. who are offered yearly pancreatic surveillance with MRI and endoscopic ultra-
RESULTS: Pancreatectomy specimens were evaluated from 16 patients with sound (EUS) in a Dutch ongoing prospective multicenter cohort study (FPC-
inherited/familial PDAC (mean age 63, SD 8.9) and 19 patients with sporadic study), were invited to complete a questionnaire each year to assess their experi-
PDAC (mean age 69, SD 8.9). PanIN lesions were the most common precursor ence with MRI and EUS, and their psychological distress (assessed with the
lesions for both groups, IPMNs were seldom detected. A significant difference Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale
was observed in the mean number of precursor lesions (9.3 vs. 2.7, p0.04). The (HADS)). The questionnaires were sent after intake for participation but
number of patients in whom at least two high-grade precursors were detected was before the first MRI and EUS (T1), after the first MRI and EUS (T2), and
significantly higher in the inherited/familial group. More patients within the after the MRI and EUS one (T3), two (T4) and three years (T5) after initial
inherited/familial group had PanIN-3 lesions and the number of PanIN-3 lesions intake.
found in these patients was significantly higher compared to the sporadic group. RESULTS: A total of 477 out of 512 questionnaires were returned (93%) by 141
Furthermore, in significantly more patients within this group multiple PanIN participants: 36, 69, 128, 108, 85 and 51 T0, T1, T2, T3, T4 and T5 questionnaires
lesions were detected. respectively. The mean age of participants was 52 years. An average of 90%
CONCLUSION: This study shows that the number of high-grade PanIN-lesions experienced the MRI as not or a little burdensome (86%, 92%, 90% and
in patients with inherited or familial PC are higher than in patients with sporadic 94% at T2, T3, T4 and T5 respectively) versus an average of 89% in case of
PC. These high-grade precursor lesions are an important target for screening and an EUS (91%, 94%, 95% and 94% at T2, T3, T4 and T5 respectively). Prior to
surveillance of high-risk individuals for which the most suitable test has yet to be the first MRI and EUS (T1), 34% of individuals dreaded the EUS while only 3%
identified. of individuals dreaded the MRI. However, after their first MRI and EUS, the
Disclosure of Interest: None declared percentage of individuals dreading their next EUS decreased significantly to 5-
9% (T2-T5); the percentage of individuals dreading a next MRI remained stable
(0-8%, T2-T5). The mean CWS-score (13) remained stable and low as surveil-
OP230 EXPLORING THE EFFECTS OF FACTORS ASSOCIATED WITH lance progressed. An average of 7% showed clinical relevant anxiety levels
THE OUTCOME OF PANCREATIC CANCER SCREENING IN HIGH- (HADS-A-score 11) and an average of 5% clinical relevant depression levels
RISK INDIVIDUALS (HADS-D-score 11).
I. Driesprong-de Kok1, F. Harinck1,*, I. Konings1, I. Vogelaar1, P. Fockens2, CONCLUSION: The psychological burden of repeated pancreatic surveillance
M. van Ballegooien1, M. Bruno1 seems tolerable with an average of 90% of high risk individuals experiencing no
1
ERASMUS MC UNIVERSITY MEDICAL CENTER ROTTERDAM, or little burden of the yearly MRI and EUS. Participants also have few worries
Rotterdam, 2Academic Medical Canter Amsterdam, Amsterdam, Netherlands about cancer and the percentage of individuals with clinical relevant levels of
Contact E-mail Address: f.harinck@erasmusmc.nl anxiety and depression is comparable to that of the general population.
Therefore, from a psychological point of view, yearly pancreatic surveillance of
INTRODUCTION: There are several disease-related aspects of pancreatic cancer high risk individuals seems feasible.
(PC) that indicate that screening for this cancer type among high-risk individuals Disclosure of Interest: None declared
(HRI) could be worthwhile. However, we currently lack scientific evidence to
recommend screening for PC in HRI outside research protocols. By using an
established simulation model, we aimed to analyse which parameters have the OP232 EFFICACY OF NEOADJUVANT THERAPY IN BORDERLINE
highest impact when estimating the effects of a pancreatic cancer screening RESECTABLE PANCREATIC CANCER WITH ABUTMENT OF THE
program. SUPERIOR MESENTERIC ARTERY
AIMS & METHODS: The Microsimulation Screening Analysis (MISCAN) D. Satoh1,*, Y. Shiozaki1, H. Araki1, K. Yoshida1, H. Matsukawa1,
model (Habbema JD, 1985) was used. The majority of the model assumptions M. Okajima1, M. Ninomiya1
were based on the recommendations as stated in the consensus paper of the 1
Department of Surgery, Hiroshima city hospital, Hiroshima, Japan
international Cancer of the Pancreas Screening (CAPS)-consortium (Canto
MI, 2013). By performing sensitivity analyses we explored which parameters INTRODUCTION: Neoadjuvant therapy may be beneficial for patients with
had the highest impact on the effects of screening. borderline resectable pancreatic cancer (BRPC) due to selection of the patients
RESULTS: The mortality reduction (MR) was 35% and 58% (436 and 722 cases likely to experience the most favorable surgical outcome. Such selection excludes
per 10,000 persons) for 5 yearly and annual screening, respectively. In the base patients who develop distant metastasis during treatment, precludes delayed
case situation for 5 yearly screening, the number needed to screen (NNS) was postoperative adjuvant therapy that results from surgical complication or
117.1 and number needed to treat (NNT) was 2.5 to prevent one cancer death. delayed recovery, and reduces the risk of margin-positive resection. Until now,
The NNT was lowest in case all screen positives with preinvasive stage 3 or few reports have demonstrated that the outcome of patients with BRPC treated
cancer are treated (2.4, MR 32%). If only persons are treated who are already with neoadjuvant therapy was directly comparable to that of patients with BRPC
in an (early) invasive stage of disease, the NNT was 5.3 (MR 10%). Results were who initially underwent resection without neoadjuvant therapy. In actuality,
sensitive for PDAC risk (risk doubled: NNS 64.3, NNT 2.7, MR 38%) and patients with severe superior mesenteric-portal vein (SMPV) impingement or
duration of the preclinical stage of the disease (increased to 30 years: NNS occlusion of the short segment, defined as one of the criteria of BRPC, initially
92.6, NNT 3.2, MR 46%). Results were less sensitive for test characteristics. have undergone resection with considerable frequency. The aim of this study was
CONCLUSION: By building a comprehensive microsimulation model, we iden- to compare the outcome of patients with BRPC treated with and without neoad-
tified which parameters potentially have the highest impact on the outcome of a juvant therapy.
PC screening program. FU strategy of screen positives and duration of the pre- AIMS & METHODS: We retrospectively reviewed 27 patients with BRPC,
clinical stage are important as is inclusion of patient populations that are exposed according to the National Comprehensive Cancer Network (NCCN) classifica-
to a certain risk to develop PC. To identify these risk groups and to assess their tion system, who underwent resection with or without neoadjuvant therapy, and
risk level, more epidemiological research needs to be done. The true effect of the 53 patients with locally advanced but resectable pancreatic cancer (LAPC) who
PC surveillance including the impact of various FU strategies can only be derived initially underwent resection between 2001 and 2012. We divided the patients
from clinical trials with long term follow up. The present study provides some with BRPC into three groups: 1) the patients with severe SMPV impingement or
guidance as to which choices could be made. occlusion of the short segment, pathologically confirmed as invasion, treated
Disclosure of Interest: None declared without neoadjuvant therapy (BRPC-P(-); n10); 2) the patients with superior
mesenteric artery (SMA) abutment 5180 degrees, treated without neoadjuvant
therapy (BRPC-S(-); n9); and 3) the patients with SMA abutment 5180
OP231 REPEATED PANCREATIC SURVEILLANCE IN HIGH RISK degrees, treated with neoadjuvant therapy (BRPC-S(); n8). We evaluated
INDIVIDUALS FOR PANCREATIC CANCER: THE the outcome of these three groups, and that of the LAPC patients.
PSYCHOLOGICAL BURDEN RESULTS: The R0 resection rates were 50% in the BRPC-P(-) group, 56% in
I. Konings1,*, G. Sidharta2, F. Harinck1, C. Aalfs3, J.W. Poley1, E. Smets4, the BRPC-S(-) group, and 88% in the BRPC-S() group. Although the R0
A. Wagner5, P. Fockens6, A. van Rens7, J. van Hooft6, M. Bruno1, E. Bleiker2,7 resection rate of the BRPC-S() group was higher than that of the other two
on behalf of the Dutch research group on pancreatic cancer surveillance in high groups, the difference was not statistically significant. The median overall survi-
risk individuals val in the BRPC-S() group was 52 months, which was significantly better than
1
Department of Gastroenterology and Hepatology, Erasmus MC University that of the BRPC-S(-) (27 months, P0.0345) and BRPC-P(-) (8 months,
Medical Center Rotterdam, Rotterdam, 2Division of Psychosocial Research and P0.0192) groups.
Epidemiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek The LAPC group had a significantly more favorable median overall survival
Hospital, 3Department of Clinical Genetics, 4Department of Medical Psychology, compared with the BRPC-P(-) group (29 months and 8 months, respectively,
Academic Medical Center Amsterdam, Amsterdam, 5Department of Clinical P0.0345).
Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam, CONCLUSION: BRPC patients with SMA abutment should be treated with
6
Department of Gastroenterology and Hepatology, Academic Medical Center neoadjuvant chemotherapy. When SMPV invasion is very suspicious, such as
Amsterdam, 7Family Cancer Clinic, The Netherlands Cancer Institute, Antoni van radiological findings of SMPV deformity or occlusion, initial resection may be
Leeuwenhoek Hospital, Amsterdam, Netherlands avoided.
Contact E-mail Address: i.konings@erasmusmc.nl Disclosure of Interest: None declared
INTRODUCTION: Pancreatic cancer (PC) is one of the most fatal human malig-
nancies with a median survival of 56 months. There is great interest in PC
surveillance for high risk individuals to detect PC or precursor lesions in an
earlier, potentially curable stage. Studies assessing the feasibility of such PC
surveillance programs have, however, not addressed the psychological burden
for participants. The aim of this ongoing, prospective study is therefore to
A76 United European Gastroenterology Journal 2(5S)
OP233 SECOND-LINE CHEMOTHERAPY FOR ADVANCED BILIARY improvement of palliation could be achieved (Karnofsky performance status,
TRACT CANCER AFTER FAILURE OF GEMCITABINE PLUS median 10%, range -20% - 40%). PDT was technically successful in all
PLATINUM: RESULTS OF AN AGEO MULTICENTER cases and was generally well tolerated; there was no grade 4 toxicity and no
RETROSPECTIVE STUDY treatment-associated mortality. Adverse events were phototoxic skin reactions
B. Brieau1,*, L. Dahan2, Y. De Rycke3, T. Boussaha4, P. VASSEUR5, (n9), three late phototoxic skin reactions (at T-injected vein), cholangitis
D. Tougeron5, T. LECOMTE6, R. CORIAT1, J.-B. Bachet7, P. Claudez8, (n4), and liver abscess (n1).
A. ZAANAN9, P. Soibinet10, J. Desrame11, A. Bidault12, I. Trouilloud13, CONCLUSION: T-PDT can be delivered safely to patients with biliary tract
F. Mary14, C. Locher15, L. Marthey16, W. Cacheux3, A. LIEVRE17 cancer and shows improved time to treatment patency and prolonged survival
1
Hopital Cochin, PARIS, 2Hopital La Timone, MARSEILLE, 3Institut Curie, compared to P-PDT. It is statistically not inferior to P-PDT concerning improve-
4
Hopital Saint Antoine, PARIS, 5CHU Poitiers, Poitiers, 6CHU Tours, TOURS, ment of cholestasis and palliation. It is highly tumoricidal and associated with
7
Hopital La Pitie Salpetrie`re, PARIS, 8CHU Saint Etienne, Saint Etienne, similar rates of infectious complications, but with an elevated rate of skin photo-
9
Hopital Europeen Georges Pompidou, PARIS, 10CHU Reims, Reims, 11Hopital toxicity, which could have been possibly avoided, taking specific precautions.
Jean Mermoz, Lyon, 12Hopital Kremlin Bicetre, Kremlin Bicetre, 13Hopital Disclosure of Interest: None declared
Ambroise Pare, Boulogne-Billancourt, 14Hopital Avicenne, Bobigny, 15Centre
hospitalier de Meaux, Meaux, 16Hopital Beclere, Clamart, 17Hopital Rene TUESDAY, OCTOBER 21, 2014 14:0015:30
Huguenin, Saint Cloud, France COLORECTAL CANCER: NOVEL MECHANISMS, NOVEL TARGETS LOUNGE
INTRODUCTION: First-line chemotherapy (CT1) with the combination of 6_____________________
gemcitabine platinum has become a new standard in advanced biliary tract
cancer (ABTC) but data on second-line CT (CT2) are lacking. The aim of this OP235 ZINC FINGER PROTEIN 545 IS A NOVEL TUMOR SUPPRESSOR
study was to evaluate the efficacy and tolerability of CT2 in patients with ABTC THROUGH INHIBITING RIBOSOMAL RNA TRANSCRIPTION IN
who received gemcitabine-platinum in CT1. COLON CANCER
AIMS & METHODS: We retrospectively reviewed data of consecutive patients S. Wang1,*, X. Zhang1, J. Yu2
who received CT2 for ABTC after failure to gemcitabine-platinum in 17 French 1
School of Chemistry and Biological Engineering, University of Science and
institutions from November 2002 to December 2013. Progression-free survival Technology Beijing, Beijing, China, 2Institute of Digestive Disease and Department
(PFS) and overall survival (OS) were estimated from the start of L2 CT using of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka
Kaplan Meier method. Cox models were applied for multivariate analyses. Shing Institute of Health Sciences, CUHK Shenzhen Research Insititute, The
RESULTS: Among 603 patients who were treated by gemcitabine-platinum in Chinese University of Hong Kong, Hong Kong, Hong Kong
CT1, 196 patients (median age, 63 years, range: 28-82; male, 51.5 %) received a Contact E-mail Address: wangshiyan9885@hotmail.com
CT2. CT1 included gemcitabine cisplatin (7%) or oxaliplatin (93%), with a
median PFS of 9.7 months and an ORR of 31%. Characteristics at the beginning INTRODUCTION: Zinc finger protein 545 (ZNF545) is a member of Kruppel-
of CT2 were: metastatic disease, 94%; 1-2 metastatic sites, 68%; ECOG PS 0-1, associated box containing Zinc-finger proteins.
68%. CT2 CT was 5FU-irinotecan (n62), 5FU-oxaliplatin (n17), 5FU-cispla- AIMS & METHODS: We aim to clarify its biological function as a tumor
tin (n37), 5FU/capecitabine (CAP) (n39) or other various regimens (n41). suppressor in colon cancer. ZNF545 methylation was evaluated by bisulfite
Among the 186 evaluable patients, there were 22 partial response (12%) and 70 genomic sequencing. The biological function of ZNF545 was determined by
stable disease (38%). After a median follow-up of 26.4 months, median PFS and apoptosis and autophagy assays. ZNF545 target pathway was identified by pro-
OS were 3.2 and 6.7 months respectively. There was no significant difference moter luciferase assay, immunofluorescence, electrophoretic mobility shift assay
between CT regimens in terms of PFS (5FU-irinotecan, 2.6 months; 5FU-oxali- (EMSA) and co-immunoprecipitation assays.
platin/5FU-cisplatine, 4.0 months; 5FU/CAP, 3.2 months and others, 3.7 RESULTS: ZNF545 was silenced or downregulated in all 8 colon cancer cell
months; p0,27) and OS (6.0 months, 6.3 months, 5.6 months and 9.7 months lines by promoter hypermethylation. Partial and dense promoter methylation of
respectively; p0.27). There was no significant difference between 5FU/CAP ZNF545 was detected in 41.7% (25/60) of cancer tissues. Restoring ZNF545
monotherapy and 5FU-based doublet chemotherapy (5FU-irinotecan, 5FU-cis- expression in colon cancer cell lines induced apoptosis as well as autophagy.
platin and 5FU-oxaliplatin), in terms of PFS (3,0 months and 3,3 months; These effects were attributed to inhibition of ribosomal RNA (rRNA) transcrip-
p0,91) and OS (5,6 months and 6,3 months; p0,93). In multivariate analysis, tion. To elucidate the binding sites of ZNF545 on rDNA promoter, two deletion
PS 2-3, bilirubine 4 17 mmol/L and CA19.9 4 400 UI/mL were significantly mutants in rDNA promoter were constructed based on pHrD-IRES-Luc con-
associated with a shorter PFS while PS 2-3, CA19.9 4 400 UI/mL and non- struct containing the human rDNA promoter (from -410 to 81). pHrD-IRES-
response to CT1 with a shorter OS. A grade 3-4 toxicity was observed in 32% of Luc-deletion-1 is from -268 to 81 containing far upstream control element
patients (neutropenia, 33%; diarrhea, 17%) and a toxic death occurred in 1.4% (UCE), UCE and rDNA core promoter element and pHrD-IRES-Luc-dele-
of patients. tion-2 is from -172 to 81 containing UCE and rDNA core promoter element.
CONCLUSION: CT2 is associated with a disease control in a half of patients We found that ZNF545 significantly suppressed the promoter transcriptional
with ABTC who received gem-platinum in CT1. Nevertheless, the short median activity on both rDNA promoter reporter deletion constructs, indicating that
PFS observed in this study should encourage the evaluation of new treatments in the binding site(s) of ZNF545 should be at least present within the minimal
patients with good clinical conditions and an adequate biliary drainage. rDNA promoter region. To further refine the binding site(s) of ZNF545,
Disclosure of Interest: None declared EMSA was performed using six overlapping biotinylated DNA probes spanning
minimal rDNA promoter region (60bp). Our results showed that two regions in
rDNA promoter exhibited strong binding to Flag-tagged ZNF545 proteins
OP234 TEMOPORFIN PHOTODYNAMIC THERAPY IN LOCALLY derived from nuclear extracts. One was within the linking region between UCE
ADVANCED BILIARY TRACT CARCINOMA: A MULTICENTER and core promoter element (from -97 to -62), and the other was located down-
PROSPECTIVE PHASE II STUDY stream of the transcription start site (from 41 to 78). Bioinformatic analysis
A. Wagner1,*, U.W. Denzer2, D. Neureiter3, T. Kiesslich4, F. Berr1, demonstrated that ZNF545 protein contains twelve C2H2 zinc fingers arranged
A. Puspoeck5, K. Emmanuel6, A.W. Lohse2, U. Beuers7, E.A. Rauws8, in two distinct clusters which are separated by a degenerate zinc finger motif (Z5).
N. Degenhardt9, G.W. Wolkersdorfer1 The first cluster, referred to as Hand1, contains zinc fingers 1 to 4, and the second
1
Department of Internal Medicine I, Paracelsus Medical University / Salzburger cluster, in the carboxyl terminus, referred to as Hand2, contains zinc fingers 6 to
Landeskliniken (SALK), Salzburg, Austria, Salzburg, Austria, 2I. Department of 13. To explore which part of the multiple adjacent zinc fingers participate in
Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, promoter DNA interaction, ZNF545 Hand1 and Hand2 were individually
3
Institute of Pathology, 4I. Department of Medicine, Paracelsus Medical University cloned and fused at the N-terminal end to GFP protein or its KRAB domain.
/ Salzburger Landeskliniken (SALK), Salzburg, 5Department of Internal Medicine Fluorescence microscopy imaging and EMSA assay indicated that both Hand1
IV, Medical University of Vienna, Vienna, 6Department of General and Visceral and Hand2 were capable of binding to rDNA promoter independently.
Surgery, Krankenhaus Barmherzige Schwestern, Linz, Austria, 7Department of Luciferase reporter assay demonstrated that transcriptional repression KRAB
Gastroenterology & Hepatology, 8Academic Medical Centre, Amsterdam, domain coupled Hand1 and Hand2 still exhibited significant negative influence
Netherlands, 9University Medical Center Hamburg-Eppendorf, Hamburg, on rDNA promoter activity, albeit to a lesser extent compared with the full-
Germany length ZNF545, suggesting that ZNF545 needed both Hand1 and Hand2 for
Contact E-mail Address: f.berr@salk.at firmly binding to rDNA promoter for rRNA transcription inhibition.
Moreover, KRAB domain of ZNF545 was responsible for recruiting KAP1, a
INTRODUCTION: Photodynamic therapy using porfimer (P-PDT) is estab- scaffold corepressor for recruiting other co-repressors as evidenced by co-
lished local tumor ablative therapy in non-resectable hilar bile duct cancer immunoprecipitation.
(hBDC) improving palliation and survival time. In a pilot trial, temoporfin CONCLUSION: ZNF545 acts as a functional tumor suppressor in colon cancer
PDT (T-PDT) showed improved tumoricidal penetration depth, if compared through inhibiting rRNA transcription.
with P-PDT. Disclosure of Interest: None declared
AIMS & METHODS: We investigated clinical effectiveness and safety of T-PDT
in a single-arm phase II study (NCT01016002; from 2005 to 2011). In respect of
previous publications on P-PDT, results were compared concerning OS, local OP236 SEPT9 AND SFRP1 DNA HYPERMETHYLATION IN
tumor control (TTP), and adverse events (ADE). Twenty-nine patients with COLORECTAL CANCER: RESTRICTION TO A SINGLE CPG
unresectable hBDC received median 1.0 (range 1-4) T-PDT plus stenting and ISLAND AND EXPANSION TO THE GATEKEEPER
were followed up at three-month intervals. MYOFIBROBLASTS
RESULTS: OS after treatment was median 17.3 (12.6 22.0, 95% CI) months A. Kalmar1,2,*, R. Wasserkort3,4, S. Spisak2,5, G. Valcz2, B. Wichmann1,2,
for 19 patients of category M0, and 15.4 months for all patients (M0 M1, 11.7- K. Toth1, K. Leiszter1, B. Bartak1, T. deVos6, B. Molnar1,2, Z. Tulassay1,2
19.1, 95% CI). Median time to local tumor progression was 6.5 months (3.6-9.4, 1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
95% CI). Cholestasis improved significantly in patients with initially elevated Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary,
bilirubin levels and 74% of patients with occluded segments at baseline 3
Extracorporeal Immune Modulation Unit, Fraunhofer Institute of Cell Therapy
showed local response with reopening of median 3.0 segments. A significant
United European Gastroenterology Journal 2(5S) A77
and Immunology, Rostock, 4Epigenomics AG, Berlin, Germany, 5Dana-Farber is hard to decide the baseline. Because the muscularis mucosae sometimes split up
Cancer Institute, Harvard Medical School, Boston, 6Epigenomics Inc, Seattle, and both of them or their surface can be considered as the baseline. The depth of
United States SM invasion is associated with the morphology of the lesion to some extent.
Contact E-mail Address: alexandra.kalmar@gmail.com Many of depressed-type lesions invade downward, but protruded types often
grow upward. Sometimes the depth of SM invasion becomes shorter after
INTRODUCTION: Several genes are regulated by DNA methylation and the being more massively invaded. Some lesions collapse in tumor development.
aberrant alteration of this mechanism can lead to cancer formation. Septin 9 LN metastasis was found in 4 (6.7%) out of 60 lesions with SM 51000m
(SEPT9) and secreted frizzled-related protein 1 (SFRP1) are known to play and in 50 cases (9.8%) out of 508 lesions with SM =1000m (p0.49). The
role in colorectal cancer, however, the DNA methylation pattern of these depth of SM invasion was not a statistically significant risk factor for LN
genes in the epithelial and stromal cells in colorectal cancer remains unknown. metastasis.
AIMS & METHODS: Our aim was to analyse DNA methylation patterns in CONCLUSION: There are several problems in measuring the depth of SM
DNA methylation-regulated genes in healthy and diseased colonic epithelial and invasion. The reconsideration should be needed concerning the depth of SM
stromal cells. Colonic epithelial and stromal cells were collected separately using invasion.
laser capture microdissection (LCM). Microdissected samples were subjected to Disclosure of Interest: None declared
bisulfite treatment and direct bisulfite sequencing was used to analyze the methy-
lation status of ten regions within SEPT9, SFRP1 genes in tissue samples
obtained from normal (n3), adenomatous (n3) and colorectal cancer (n3) OP239 ECTOPIC COLORECTAL FAT ACCUMULATION ASSOCIATES
samples. In addition SEPT9 and SFRP1 protein expression was assessed using WITH ABDOMINAL OBESITY AND INSULIN RESISTANCE IN
immunohistochemistry on independent healthy (n10), adenomatous (n14) JAPANESE COLORECTAL POLYP PATIENTS
and CRC (n13) samples. Stromal myofibroblast cells were detected by alpha- S. Kawata1,2,*, S. Wada1, Y. Yasunaga1, K. Oka1, N. Dan1, H. Matsumoto1,
SMA immunohistochemistry, the immunopositive cells were LCM separated and S. Yoshioka3, Y. Inui1
SFRP1 DNA methylation was assessed by high resolution melting analysis 1
Gastroenterology, Hyogo Prefectural Hospital, Nishinomiya, 2Gastroenterology,
(HRM). Yamagata University Hospital, Yamagata, 3Surgery, Hyogo Prefectural Hospital,
RESULTS: The regions analysed in SEPT9 were unmethylated in normal tissues Nishinomiya, Japan
except for a methylation boundary detected downstream of the largest CpG Contact E-mail Address: sumio_kawata@pref.hyogo. lg.jp
island within SEPT9. In adenoma and tumor samples, the epithelial cells dis-
played markedly increased methylation levels (480%, p510-4), but only within INTRODUCTION: Several lines of epidemiological evidence have suggested that
one of the CpG islands investigated. In stromal cells increased methylation (up to obesity and insulin resistance are independent risk factors for the development of
50%, p510-4) was only seen in tumor patients and in histologically normal tissue colorectal adenoma and cancer (Ref. 1, 2). Obesity is known to be associated with
close to the tumor, but not in adenoma. The analyzed region of SFRP1 also ectopic fat accumulation in the liver and skeletal muscle. However, obesity-
showed remarkable increase in the adenoma and tumor epithelial cells. Protein related accumulation of fat in the colorectal tissue has not been reported.
level of SEPT9 and SFRP1 showed significant (p50.05) decreasement in ade- AIMS & METHODS: We conducted the present study to seek evidence of
noma and tumor tissue samples compared to the healthy controls. Alpha-SMA obesity- or insulin resistance-related colorectal accumulation of fat in patients
immunopositive myofibroblast cells were identified as the main source of stromal with colorectal polyps. For the 27 patients (15 males and 12 females) with color-
SFRP1 protein, that was found to be downregulated by DNA hypermethylation ectal polyps enrolled in this study, we measured the triglyceride, total cholesterol,
only in carcinoma, but not in adenoma. and phospholipid contents of non-tumorous tissues surrounding the polyps
CONCLUSION: Hypermethylation of SEPT9 and SFRP1 could be detected in which were resected by endoscopic mucosal resection (EMR) or endoscopic
the analysed adenoma and cancer samples compared to the healthy control submucosal dissection (ESD). Non-tumorous colorectal tissues of 32 patients
samples. According to the results of the laser microdissected samples, the (13 males and 19 females) with colorectal cancer, obtained from surgical resec-
DNA methylation alterations originated in epithelial cells, while stromal cells tion, were used for immunohistochemistry examination using anti-perilipin
appear to acquire hypermethylation only subsequently via field effects. The (PLIN1) antibody to examine the location of lipid droplets. The contents of
DNA hypermethylation of the analyzed genes result in decreased protein level, lipid droplets were divided into three grades (0 to 2), and then the grades of
that can contribute to colorectal cancer formation and invasion. the lipid contents were compared with visceral fat areas assessed by CT scan.
Disclosure of Interest: A. Kalmar: None declared, R. Wasserkort Shareholder of: RESULTS: The tissue triglyceride/phospholipid value was significantly corre-
Epigenomics AG, Other: former employee of Epigenomics AG, S. Spisak: None lated with serum triglyceride, fasting plasma insulin (FPI), and HOMA-IR (P
declared, G. Valcz: None declared, B. Wichmann: None declared, K. Toth: None 5 0.01, P 5 0.01, and P 5 0.01, respectively; Spearman rank test). Tertile
declared, K. Leiszter: None declared, B. Bartak: None declared, T. deVos Other: analysis of the triglyceride/phospholipid value to assess factors associated with
employee of Epigenomics Inc., B. Molnar: None declared, Z. Tulassay: None higher triglyceride/phospholipid values showed that serum triglyceride (P
declared 0.025), FPI (P 0.041), and HOMA-IR (P 0.013) were significantly higher
in the highest tertile than in the lowest tertile. Serum adiponectin level (P 0.046)
was also significantly lower in the highest tertile. Lipid droplets were observed in
OP238 IS MEASURING THE DEPTH OF SUBMUCOSAL INVASION A the submucosal region of non-tumorous colorectal tissue in 27 of 32patients
MEANINGFUL APPROACH IN MANAGEMENT OF T1 (grade 1 in 13 and grade 2 in 5), and the grades of fat droplet correlated
COLORECTAL CARCINOMAS AFTER ENDOSCOPIC TREATMENT? with BMI, abdominal circumstance and visceral fat area (P 0.04, P 5 0.01, and
Y. Kouyama1,*, S.-E. Kudo1, H. Miyachi1, K. Ichimasa1, S. Matsudaira1, P 5 0.01, respectively; Kruskal-Wallis test).
H. Oikawa1, T. Hisayuki1, K. Wakamura1, T. Hayashi1, K. Kodama1, T. Kudo1, CONCLUSION: Triglyceride content of colorectal tissue was increased in color-
Y. Mori1, M. Misawa1, A. Katagiri1, M. Kaga1, E. Hidaka1, F. Ishida1, ectal polyp patients with insulin resistance. Ectopic colorectal fat accumulation
S. Hamatani1 was observed in the submucosal region, correlating with BMI, abdominal cir-
1
Showa University Northern Yokohama Hospital, Tsuzuki-ku Yokohama-shi, cumstance and visceral fat accumulation. Thus, the results in the present study
Japan suggest an association of the ectopic fat accumulation with abdominal obesity
Contact E-mail Address: kouyuta1101@gmail.com and insulin resistance.
REFERENCES
INTRODUCTION: According to the current Japanese guideline, additional sur- 1. Otake S, Kawata S, et al. Association of visceral fat accumulation and plasma
gical colectomy with lymph node (LN) dissection should be considered after adiponectin with colorectal adenoma: evidence for participation of insulin resis-
endoscopic treatment even for cases where the depth of SM invasion is tance. Clin Cancer Res 2005; 11: 3642-3646.
1000m or more. However, many patients who underwent additional colectomy 2. Otake S, Kawata S, et al. Decreased levels of plasma adiponectin associated
did not have LN metastasis. This over-surgery problem has become a major with increased risk of colorectal cancer. World J Gastroenterol 2010; 16: 1252-
issue. 1257.
AIMS & METHODS: The aim is to investigate the necessity of measuring the Disclosure of Interest: None declared
depth of submucosal invasion in T1 colorectal carcinomas after endoscopic
treatment.
A total of 21060 colorectal neoplasms excluding advanced cancers have been OP240 RISK OF METACHRONOUS ADVANCED COLORECTAL
resected endoscopically or surgically at our unit from April 2001 to September NEOPLASIA AFTER POLYPECTOMY OF SMALL AND
2013. Of these, 902 SM-invasive cancers were included. Initial or additional DIMINUTIVE ADENOMAS
surgical colectomy with LN dissection was performed in 568 cases, and of J.S. Koo1,*, S.Y. Kim1, J.J. Hyun1, B. Keum1, B.J. Lee1, Y.T. Jeen1, S.W. Lee1
which LN metastasis was found in 54 cases (9.5%). There are two ways to 1
Division of Gastroenterology Departmemt of Internal Medicine, Korea
measure the depth of SM invasion. One is to directly measure the vertical dis- Univiversity College of Medicine, Seoul, Korea, Republic Of
tance from the line of muscularis mucosae. The other is, when the line of mus-
cularis mucosae is not easily identified due to cancer invasion, the surface layer of INTRODUCTION: As screening colonoscopy is increasing for colorectal cancer
the lesion is used as a baseline. According to this rule, a pathologist in our unit prevention, colorectal polyps 510 mm in diameter are encountered more fre-
categorized 816 lesions and measured each depth of SM invasion. Then, we quently. Generally, surveillance colonoscopy is recommended considering the
analyzed the correlations between the depth of SM invasion and the other patho- index colonoscopy findings. However, it is not well established what factors
logical factors including LN metastasis. are related with developing advanced neoplasia after polypectomy of small and
RESULTS: Of these 568 lesions, the muscularis mucosa could be identified in diminutive polyps.
180 lesions (31.7%), and 60 lesions were invaded SM 1000m, 120 lesions AIMS & METHODS: The study was conducted to reveal the risk of advanced
showed SM =1000m. For the other 388 lesions (68.3%), the muscularis colorectal neoplasia after polypectomy in patients with small and diminutive
mucosa was recognized broken or disappeared and the depth of SM invasion adenomas. We enrolled 3,526 patients (mean age 53.9 year, 2,164 male), who
was measured from the surface layer. All the results turned out to be =1000m. underwent surveillance colonoscopy after index colonoscopy from January 2002
Once the muscularis mucosae was judged to be unclear and the surface layer was to June 2012 in Korea University Hospital. We reviewed the medical records and
applied as the baseline, all the cases would be considered =1000m. It indicates pathology reports to evaluate the risk for the development of advanced colorectal
that there is no need to measure the invasion depth in this case. In some lesions, it neoplasm in surveillance colonoscopy. According to the largest size and number
A78 United European Gastroenterology Journal 2(5S)
of adenoma in index colonoscopy, the patients were divided into the subgroups ulcerations on the apex, proximal head 25 mm in diameter and length, with
and analyzed. the ramification at the distance of 45 mm from the stalks base. EUS detected
RESULTS: Among a total 3,526 patients, 1,949 (55.3%) had colorectal adenoma the lesion originated from the submucosal layer with inhomogeneous echo-tex-
and 528 (15.0%) of them had advanced adenoma in index colonoscopy. During a ture with both hyper- and hypoechoic features with a number of vascular struc-
median follow-up period of 46.5 months, colorectal adenoma was diagnosed in tures within the stalk.
1,401 (39.7%), 115 (3.3%) of whom had advanced neoplasm. In the patients with RESULTS: Removal of the polyp was performed under general anesthesia with
polypectomy in index colonoscopy, metachronous advanced neoplasia were elective intubation, started with GIF-H180 following by GIF-2T160, using the
higher among patients with 4 or more baseline adenomas, those with an adenoma Maxim-402 electrosurgical unit and CO2 insufflation. The equipment for inter-
6 mm in diameter or greater. In subgroup analysis, the risk of metachronous vention included 4 endo-loops, grasping forceps and large electrosurgical snare.
advanced adenoma was increased with the adenoma number and size. However, At first, we applied two loops at the level of ramification, resected the first 75 mm
the risk in the group with multiple (3) diminutive adenomas was not higher fragment above the loop and removed it. Then, we placed 2 another loops at the
than the group with 1 or 2 small adenomas. In multivariate analysis, age (OR very base of the pedicle and removed the second fragment, thus performed total
1.06, 95%CI 1.03-1.08) was significantly associated with an increasing metachro- polypectomy, leaving the ligated 10 mm long stalk stump in place. Neither bleed-
nous advanced neoplasm, as were the number and size of baseline adenomas (p ing nor other complications occurred. The total length of the resected esophageal
50.01 and p 50.01, respectively). lesion measured 135 mm. Histology showed the mixture of fibrous and adipose
CONCLUSION: As risk of metachronous advanced neoplasia is associated with tissue accompanied by an abundant network of large vessels, covered by a
the number and size of prior adenomas, it will be needed to modify the surveil- normal squamous epithelium. The patient was discharged from the hospital on
lance interval considering the size and number of previous adenomas. the 4th day. A month later control EGD was performed, it revealed just tiny scar
Disclosure of Interest: None declared at the level of the upper esophageal sphincter and no other changes of the
esophageal wall.
CONCLUSION: The removal of the giant esophageal polyp using modern endo-
TUESDAY, OCTOBER 21, 2014 15:4517:15 scopic equipment can be safely performed without open surgery.
VIDEO CASE SESSION HALL A_____________________ Disclosure of Interest: None declared
DB (n36) p (Vs no DB) All patients (N881) OP263 HOW SAFE AND EFFECTIVE IS ORAL REHYDRATION
THERAPY IN CORRECTING THE METABOLIC DISTURBANCES
Size(mm 30/40 77.8/47.2 50.01/0.01 55.9/28.4 POST-COLECTOMY IN PATIENTS WITH FAMILIAL
Location Proximal transverse/proximal 63.9/72.2 50.01 39.2/49.9 ADENOMATOUS POLYPOSIS?
S. Mallappa1,*, S. Gabe2, R. Phillips1, M.D. Robertson3, S.K. Clark1
splenic flexure 1
The Polyposis Registry, 2Gastroenterology, St Marks Hospital, Harrow, 3Faculty
Age(years) 60/61-74 / 75 17.1/25.7/57.1 0.02 21.3/43.1/35.6 of Medicine, University of Surrey, Guildford, United Kingdom
ASA I/II/III/IV 8.3/36.1/52.8/2.8 0.03 15/51.3/30.6/3.1 Contact E-mail Address: s.mallappa@imperial.ac.uk
Aspirin No/ Yes (ceased)/ 66.7/22.3/11.1 0.03 83.2/13.2/3.7
7emsp;Yes (during EMR) INTRODUCTION: There is evidence that colon is an active metabolic organ, the
Clips Mucosal defect complete closure 5.6 0.06 17.3 removal of which leads to chronic activation of the renin-angiotensin-aldosterone
system (RAAS) which in turn results in sodium depletion, hyperaldosteronism
and abnormal glucose tolerance. Previous work has studied patients who have
undergone colectomy for inflammatory bowel disease (IBD)1,2. Patients with
A total of 881 EMR were performed. There were 36 (4.0%) cases of DB and 11 Familial adenomatous polyposis (FAP) undergo prophylactic colectomy with
(1.2%) perforations. Factors associated with DB were increasing lesion size, ileorectal anastomosis (IRA) or restorative proctocolectomy (RPC) or colectomy
proximal location, patients older than 75 years, higher ASA classification and with end-ileostomy in their late teens. We have established (60 FAP participants)
aspirin treatment. Only 2 of the EMR which had their mucosal defect fully that colectomy results in RAAS activation, abnormal glucose tolerance and poor
clipped underwent DB (1.3%(2/151) Vs 4.7% not closed, p0.06). Lesions that quality of life.
had been treated with APC for coagulation did not suffer DB (pNS). All DB AIMS & METHODS: To evaluate if oral rehydration therapy (ORT) is safe and
were successfully managed endoscopically with the exception of one patient who effective in restoring water and electrolyte balance post-colectomy.
required a vascular interventional radiology treatment. Two patients required Blinded placebo-controlled randomised cross-over trial. 30 patients with demon-
surgery due to perforation (0.2%). No risk factors has been associated to strated hyperaldosteronism from the on-going observational study were
perforation. recruited. Patients were randomised to receive either placebo or ORT first in a
CONCLUSION: DB rate after EMR of large colorectal lesions in our study was cross-over trial for 4 weeks with an intervening washout period of 4 weeks.
4.0 %. DB occurred most frequently in lesions 30-40 mm located in the prox- Patients attended clinical investigation day (CID) once at the end of each 4
imal colon, in older patients with comorbidities (ASA IIIIV) and in those taking weeks. CID: After fasting, urine and blood samples were collected to measure
aspirin (p50.05). Perforation rate in this study was 1.2%. No risk factors has sodium loss, hydration status and RAAS activation. Oral glucose tolerance test
been associated to this complication. was performed. Health related quality of life (HRQoL) was assessed using SF-36
Disclosure of Interest: None declared and FACIT-F questionnaires.
RESULTS: Cross-over RCT: Biochemistry results: Data acquired so far in 16
patients (n48 patient CIDs) have demonstrated fasting plasma aldosterone
OP262 EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL concentration post-ORT to be significantly lower compared to baseline [189.25
DISSECTION FOR EARLY STAGE COLORECTAL NEOPLASIA; (7.24) vs 536.25 (12.56) pmol/L; p0.05]. HRQoL results: SF 36 Post-ORT,
RESULTS FROM A NATIONWIDE REGISTRY THROUGHOUT patients reported improvement in six of the eight dimensions of health as com-
JAPAN pared to baseline. FACIT-F Post-ORT, patients reported higher scores on four
Y. Saito1,*, M. Fujishiro2, S. Tanaka3, H. Iishi4, T. Miyata5, M. Kaise6, of the five scales with higher total scores when compared to baseline.
T. Shimbo7, H. Ishikawa8, N. Uemura7, J. Yoshino9, K. Obara10, CONCLUSION: ORT forms a safe and effective intervention to correct the
M. Kaminishi11, H. Tajiri12 on behalf of, JGES Colorectal, ESD Study Group metabolic disturbances post-colectomy resulting in restoration of metabolic
1
Endoscopy Division, NATIONAL CANCER CENTER HOSPITAL, Tsukiji, homeostasis and a positive impact on quality of life.
Chuo-ku, Tokyo, 2The University of Tokyo Hospital, Tokyo, 3Hiroshima REFERENCES
University Hospital, Hiroshima, 4Osaka Medical Center for Cancer and 1. Robertson MD, Bickerton AST, Dennis AL, et al. Enhanced metabolic cycling
Cardiovascular Diseases, Osaka, 5Jichi Medical University, Tochigi, 6Toranomon in patients following colonic resection for ulcerative colitis. J Clin Endocrinol
hospital, 7National Center for Global Health and Medicine, Tokyo, 8Kyoto Metab 2005; 90: 2747-2751.
Prefectural University of Medicine, Kyoto, 9Fujita Health University, Nagoya, 2. Robertson MD. Metabolic cross talk between the colon and the periphery:
10
Fukushima Medical University Hospital, Fukishima, 11Showa General Hospital, implications for insulin sensitivity. Proc Nut
12
The Jikei University School of Medicine, Tokyo, Japan Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15 the esophagus in the isolated vagally-innervated guinea pig esophagus
VISCERAL SENSITIVITY: CLINICAL AND TRANSLATIONAL SCIENCE ASPECTS preparation.
LOUNGE 5_____________________ RESULTS: The selective adenosine A2A receptor agonist CGS21680 sensitized
mechanical response of nodose C-fibers to distention (10-60mmHg) of the eso-
OP288 CORTICOTROPHIN-RELEASING HORMONE INCREASES phagus with EC50 of 1-3nM. CGS21680 (3nM) induced (2.40.3)-fold increase
OESOPHAGEAL SENSITIVITY TO MECHANICAL DISTENTION IN in mechanical response (measured by esophageal distention with 30mmHg,
HEALTH n10, p50.01). The protein kinase A (PKA) activator forskolin mimicked the
C. Melchior1, C. Broers1,*, T. Vanuytsel1, L. Van Oudenhove1, J. Tack1, sensitizing effect of CGS21680 by causing a (1.90.3)-fold (n8) and (2.20.2)-
A. Pauwels1 fold (n7) increase in mechanical response at concentrations 1mM and 10mM,
1
Translational Research Center for Gastrointestinal Disorders, KU Leuven, respectively (p50.05). The protein-kinase A (PKA) inhibitor H-89 partially
Leuven, Belgium inhibited the CGS21680-induced increase in excitability. In the presence of H-
Contact E-mail Address: ans.pauwels@med.kuleuven.be 89 (30mM), CGS21680 (3nM) caused only insignificant (1.50.3)-fold increase in
mechanical response (n9). The TRPA1 receptor selective antagonist AP18
INTRODUCTION: Oesophageal hypersensitivity has been proposed as an inhibited the CGS21680 (3nM)-induced increase in mechanical response. In the
important pathophysiological factor in patients with gastro-oesophageal reflux presence of AP18 (30mM), CGS21680 (3nM) only caused insignificant (1.30.3)-
disease (GORD) refractory to acid suppressive therapy. Stress is well-known to fold increase in mechanical response (n8).
affect visceral sensitivity in humans. It has been shown that a real-life stressor is CONCLUSION: Our data show that the activation of adenosine A2A receptor in
able to exacerbate heartburn in GORD patients. A recent study from our group the vagal nodose C-fibers induces increase in mechanical excitability that is
showed that, in humans, an acute psychological stressor increases duodenal per- mimicked by the activation of PKA activator forskolin. Our data indicate that
meability in a mast cell dependent way and that this effect on barrier function is that the adenosine A2A receptor sensitizes vagal nodose C-fibers via protein
mimicked by IV administration of exogenous corticotrophin-releasing hormone kinase A and TRPA1. The activity of sensitized vagal C-fibers may modulate
(CRH). perceptions in patients with noncardiac chest pain. Supported by BioMed Martin
AIMS & METHODS: The aim was to investigate the effect of CRH-adminis- (ITMS: 26220220187)
tration on oesophageal sensitivity in health.This cross-over, randomized, single- Disclosure of Interest: None declared
blind study was performed in 10 HV (4m/6f, mean age 31.611.5y) with no prior
history of digestive disease. Oesophageal multimodal sensitivity was quantified
after administration of CRH (100mg IV) and placebo (0.9% NaCl IV), with 1 OP290 UP-REGULATIONS OF GASTRIC TRPV RECEPTORS AND
week interval. After an overnight fast, a multimodal oesophageal stimulation DECREASED SERUM CONCENTRATION OF BDNF IN PATIENTS
probe was positioned in the distal oesophagus. Thermal (recirculating a heated WITH FUNCTIONAL DYSPEPSIA (FD)
solution), mechanical (increasing balloon volume), electrical (2 stimulation elec- C. K. Y. Cheung1,*, L.L. Lan1, Y. Chan1, J. C. Y. Wu1
trodes) and chemical sensitivity (modified Bernstein) were tested. Perception 1
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong,
scores were assessed using Visual Analogue Scale (VAS) and stimulus intensities Hong Kong
corresponding to pain perception threshold (VAS 5) and pain toleration thresh- Contact E-mail Address: ckycyn@gmail.com
old (VAS 7) were assessed. Anxiety and angor were assessed by the State-Trait
Anxiety Inventory (STAI-state) and Profile of Mood Schedule (POMS) ques- INTRODUCTION: Immune activation has been implicated in the mechanism of
tionnaire before and after the stimulations. Thresholds were compared between post-infectious functional dyspepsia. However, the role of immune activation in
CRH and placebo, and differences in questionnaire data before and after stimu- FD patients without infection remains unclear.
lations () were analysed using paired t-tests. A p-value 50.05 was considered AIMS & METHODS: To compare the gastric mucosal and serum expression of
significant. brain-derived neurotropic factor (BDNF), transforming growth factor beta
RESULTS: After CRH administration, VAS 5 levels during mechanical stimula- (TGFB) families and transient receptor potential vanilloid type (TRPV) families
tion were significantly lower compared to placebo administration, with a large between FD patients and healthy controls.
size effect (Cohens d1.2; Table 1)). Five HV (50%) did not reach VAS 7 in the Consecutive adult FD patients (Rome III) with no recent history of gastroenter-
placebo condition at inflation to the maximal volume of the balloon (50ml), itis and age-and-sex matched asymptomatic healthy controls were recruited for
whereas this was only the case in 1 HV (10%) in the CRH condition. CRH upper endoscopy. Subjects with GERD and IBS as predominant symptoms,
had no significant influence on oesophageal sensitivity to both thermal and diabetes mellitus, current or previous H. pylori infection, psychiatric illness and
electrical stimulations compared to placebo condition (Table 1). Since both recent use of NSAID or PPI were excluded. Serum and mucosal biopsies from the
VAS 5 and VAS 7 were not reached in the majority of the HV at the endpoint gastric corpus were obtained for quantitative assay of mRNA TRPV1, TRPV2,
of the chemical stimulation, we were unable to analyse these data. The POMS- TGFB1 by RT-PCR. Serum concentrations of TGFB families and BDNF were
anxious was slightly higher (p0.06) in the CRH condition compared to placebo. analyzed using immunoassay. The gastric mucosal inflammation was evaluated
No significant effects on STAI-scores were observed. After CRH administration using Sydney classification. The associations between these assays and dyspeptic
5/10 HV had mild transient facial flushing. symptoms were evaluated.
Table 1 Results of oesophageal stimulation test (mean SD). RESULTS: 45 [M:F8:37, mean age: 35.9(9.1)] FD patients were matched with
23 healthy controls [M:F 8:15, mean age: 36.6(10.2)] respectively. FD patients
had PDS as predominant sub-type (PDS: 43, EPS:2). There was no significant
CRH Placebo p uncorrected Cohens d difference in the median inflammation score between FD patients and controls
(FD: 0 (0-1) Vs Control: 0 (0-1), p0.54). However, FD patients had significantly
Temperature ( C) higher mRNA expression of gastricTRPV1 (FD: 0.0080.002, Control: 0.003
VAS 5 43.953.15 45.424.43 0.15 0.4 0.001, p0.03), TRPV2(FD:0.0060.001, Control: 0.0020.001, p0.01)and a
trend of increased gastric TGFB1 (FD: 0.0130.003, Control:0.0050.002,
VAS 7 46.682.61 47.923.95 0.17 0.4 p0.07) compared to controls.
Mechanical (ml) The serum concentration of BDNF(FD: 240.711.0, Control: 389.622.7,
VAS 5 23.214.39 33.8311.29 0.0057* 1.2 p50.001) were significantly lower in FD patients. Serum TGFB1 and TGFB2
Electrical (mA) concentrations were significantly correlated with symptoms of
belching(R0.441, p0.01) and vomiting (R0.378, R0.04) in FD patients.
VAS 5 14.579.16 15.377.27 0.43 0.1 CONCLUSION: Despite the absence of gastric mucosal inflammation, up-reg-
CONCLUSION: CRH administration increased oesophageal sensitivity to ulations of gastric mucosal TRPV1, TRPV2, TGFB1 and down-regulation of
mechanical distention in HV and was also associated with a slightly higher serum BDNF were observed in FD patients. The immune activation is associated
anxiety level. The exact mechanisms of this CRH-induced visceral hypersensitiv- with symptoms of belching and vomiting. These findings suggest that mucosal
ity need to be further explored. immune activation also contributes to the development of FD in those without
Disclosure of Interest: None declared history of infection.
Disclosure of Interest: None declared
OP303
BCH PE DIS Neu/Eos
BI at 3 cm BI at 5 cm BI at 3 cm BI at 5 cm BI at 3 cm BI at 5 cm BI at 3 cm BI at 5 cm
Grade 0 -1 2300 (840-4225) 2100 (560-3300) 2415 (560-4225) 2282 (640-3300) 2930 (880-4225) 2850 (560-3540) 2200 (560-4225) 2080 (580-4060)
Grade 2 980 (770-4060) 890 (580-2980) 1050 (590-4060) 995 (580-2980) 1045 (830-4060) 1000 (580-3610) 980 (590-2640) 910 (600-2490)
United European Gastroenterology Journal 2(5S) A97
OP304
Size of intercellular
Hiatal Microscopic Sex IPCL size Fluorescein channels / DIS
Number PPI Hernia (n) esophagitis (n) M/F (n) (Mean /range m) leak (mean /range, mm) Reflux disease questionnaire (score)
OP305 TASTE MISPERCEPTION AND SENSITIVITY IN SUBSETS OF HLE-sphere), but well-differentiated HCC-derived HuH-7 and Hep 3B cells did
GERD PATIENTS not. SK-spheres showed increased NANOG, LIN28A, and ALDH1A1 mRNA
P. Andreozzi1,*, F.P. Zito1, A. Dalessandro1, M. Pesce1, V. Verlezza1, E. Vitale1, levels compared to parental cells. SK-sphere cells showed increased liver meta-
V. Passananti1, F. Turco1, G. Sarnelli1, R. Cuomo1 static potential compared to parental cells. As regards epithelial-mesenchymal
1
Clinical Medicina and Surgery, UNIVERSITY OF NAPLES " FEDERICO II", transition (EMT), increased expression of Vimentine and Snail were observed in
Naples, Italy SK-sphere cells compared to parental cells. The cell viability of SK-spheres was
Contact E-mail Address: paoloandre.85@gmail.com significantly higher than that of SK-HEP-1 cells in the presence of several anti-
cancer drugs except sorafenib (1.7- to 7.3-fold, each P 5 0.05). Similarly, HLE-
INTRODUCTION: Patients with gastroesophageal reflux disease (GERD) may sphere showed increased chemoresistace. Regarding drug efflux, ABCG2 expres-
experience an altered taste perception. However, no studies have explored the sion was higher in SK-sphere than in SK-HEP-1 cells. The cell cycle of SK-sphere
ability of GERD patients to discriminate primary taste. We aimed to investigate was arrested at the G0/G1 phase compared to SK-HEP-1. In addition, SK-sphere
the individual ability to recognize primary tastes in GERD patients. showed induced P21 mRNA. Furthermore, SK-sphere showed higher HIF1A
AIMS & METHODS: Sixty-four clinically diagnosed GERD patients without mRNA expression, more CD44 variant-positive cells, and lower ROS production
known nasal and oral pathologies (27 males, age range 2569 years) and fifty healthy compared to parental cells. Integrated analysis with 373 molecules showed that
subjects (HS) (21 males, age range 23-68 years) were studied. Among GERD patients HIF1A and its downstream genes were up-regulated in SK-sphere (P 5 0.001).
26 were ON therapy and 38 OFF therapy (with or without proton pump inhibitors SK-sphere cells was correlated with mitochondrial dysfunction (P 5 0.001) and
therapy, respectively). All subjects underwent a standardized taste-testing to evaluate was activated in invasion of cells (P 5 0.001).
the ability to identify sweet (acesulfame K), bitter (quinine), salty (NaCl), umami CONCLUSION: Our novel method successfully induced cancer stem-like cells,
(monopotassium glutamate inosine monophosphate) and sour taste (citric acid), which showed increased metastatic potential and chemoresistace. Moreover, it
scoring the intensity of taste perception by using a 100 mm line visual analogue scale was suggested that EMT, cell cycle dormancy, drug efflux, and decreased pro-
(VAS). In addition, GERD patients underwent pH-impedance 24h monitoring, in duction of ROS were responsible for those SK-sphere characteristics.
order to measure the pH and the extent of the refluxes. Disclosure of Interest: None declared
RESULTS: The percentage of overall taste misperception was significantly
higher in OFF and ON therapy GERD patients than in HS (22.415% and
20.418% vs 13.615%, respectively; p0.028). OFF and ON therapy GERD OP307 SOMATIC LOSS OF ALLELES FROM HEPATIC CYST
patients more frequently failed to correctly identify sweet tastant compared to EPITHELIUM ALLOW IDENTIFICATION OF CANDIDATE GENES
HS (10.520.7% and 9.624.5% vs 1000%, respectively; p0.007), whereas a IN POLYCYSTIC LIVER DISEASE
significant lower perception of salty taste was observed for GERD patients, both W.R. Cnossen1,*, A. Hoischen2, R. Woestenenk3, M. Steehouwer2, M. Leenders3,
OFF and ON therapy, compared to HS (OFF: 4819.2 and 5325 vs 66.117.2 R.H. te Morsche1, J.A. Veltman2, J.P. Drenth1 on behalf of Genomic Disorders
mm, respectively; p50.001). A negative association was found between both acid Group (GDG); Radboud Institute for Molecular LifeSciences (RIMLS)
and non-acid reflux extent and umami perception (r-0.45, p0.002; r-0.43, 1
Department of Gastroenterology and Hepatology, 2Department of Human
p0.043), whereas a positive association was found between non-acid reflux Genetics, 3Department of Hematology, Radboud university medical center,
extent and sour perception (r0.32, p0.032). Nijmegen, Netherlands
CONCLUSION: GERD patients, independently of current proton pump inhi- Contact E-mail Address: wybrich.cnossen@radboudumc.nl
bitors therapy, showed a lower ability to discriminate and perceive primary
tastes. In particular, GERD patients showed a poor ability to recognize sweet INTRODUCTION: Autosomal dominant polycystic liver disease (PCLD) is
taste and to perceive salty taste. Interestingly, we found that refluxes extent is characterized by presence of multiple fluid-filled hepatic cysts. Germline muta-
associated to taste impairment with a hypo- and hypersensitivity for humami and tions in PRKCSH or SEC63 underlie 20% of PCLD cases, but despite wide-
sour tastants, respectively. Given the absence of macroscopic ORL lesions in our spread presence of the encoded protein(s), the phenotype is restricted to the liver.
population, the impairment of gustatory function in GERD patients might be We hypothesized that the second allele of these genes is somatically deleted in
due to refluxes-induced neuro-mediated or microscopic mucosal changes, that cyst epithelium, and that this may also occur for other, as yet unknown PCLD
may affect molecular transduction pathways of gustatory signals. genes. Loss of somatic allele copies in cystic fluids, which can be detected by
Disclosure of Interest: None declared genome-wide SNP microarrays, may therefore directly point to the location of
the germline mutation (the first hit).
AIMS & METHODS: We collected 50 cyst fluid samples from patients with
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 isolated hepatic cysts. Cyst fluid samples were obtained by aspiration sclerother-
ADVANCES IN DIAGNOSIS AND MANAGEMENT OF LIVER NODULES HALL apy and subjected to centrifugation, cytokeratin-19 staining and fluorescent-acti-
C_____________________ vated cell sorting of cholangiocytes. Flow-sorted cells were lysed and DNA was
amplified using whole-genome-amplification (WGA, Repli-G single cell kit,
OP306 CANCER STEM-LIKE SPHERE CELLS INDUCED FROM DE- Qiagen). Genome-wide SNP analysis on a CytoScanHD array (Affymetrix) fol-
DIFFERENTIATED HEPATOCELLULAR CARCINOMA-DERIVED lowed to identify regions with loss of heterozygosity (LOH).
CELL LINES EXERTS LIVER METASTATIC POTENTIAL AND RESULTS: Hundreds to thousands of cytokeratin-19-positive cholangiocytes
CHEMORESISTANCE were sorted. We isolated and amplified DNA from these cells in 8 PCLD
R. Tsunedomi1,*, K. Yoshimura1, N. Hashimoto1, Y. Watanabe1, S. Hazama1, patients. Cyst fluid with a clear content was eligible to process for further ana-
M. Oka1 lysis. Genome-wide SNP analysis identified multiple somatic deletions from 0.5
1
Digestive Surgery and Surgical Oncology, YAMAGUCHI UNIVERSITY, Ube, to 12.5Mb. Therefore, genome-wide SNP microarrays of genomic DNA were
Japan simultaneously conducted.
Our experiment was confirmed in a PCLD patient with heterozygous germline
INTRODUCTION: Cancer stem cells (CSCs) are thought to play important mutation PRKCSH c.2921G4C which is present in a homozygous state in
roles in carcinogenesis, recurrence, metastasis, and therapy-resistance. hepatic cyst epithelium. In addition, a PCLD patient without a known
Recently, it was suggested that the possible existence of plasticity between PRKCSH or SEC63 germline mutation harbored the largest (12.5Mb) homozy-
CSCs and their more differentiated derivative cancer cells. We hypothesized gous region on chromosome 3 in hepatic cyst epithelium. Subsequently, whole-
that poorly-differentiated hepatocellular carcinoma (HCC) has potential that exome sequencing of genomic DNA identified candidate genes for PCLD.
convert to CSC, which would responsible for metastasis and recurrence. CONCLUSION: Cyst epithelium in PCLD is characterized by multiple somatic
AIMS & METHODS: To identify molecular tartgets for HCC treatment, we loss of genomic regions. These regions may contain genes that contribute to the
induced cancer stem-like cells from HCC cell lines using a unique medium, and phenotype.
examined their potentials. The human HCC cell lines SK-HEP-1, HLE, Hep 3B, Disclosure of Interest: None declared
and HuH-7 were used to induce cancer stem-like cells with our sphere induction
medium supplemented with neural survival factor-1. Liver metastatic potential was
examined by injection of the cells to immune-deficient mice spleen. Cell viability was OP308 PRP19 FACILITATES TWIST1-INDUCED EPITHELIAL-
measured by MTS assay. 9 anti-cancer agents (5-Fluorouracil, Cisplatin, MESENCHYMAL TRANSITION AND PROMOTES INVASION OF
Carboplatin, Docetaxel, Doxorubicin, SAHA, Irinotecan, Sorafenib, Sunitinib) HEPATOCELLULAR CARCINOMA
were used. The mRNA and protein levels were examined by real-time PCR and J. Yin1,*, J. Zhu1, X. Shen1
flow cytometry analyses. Reactive oxygen species (ROS) activity was measured with 1
Department of Gastroenterology, Zhongshan Hospital, Fudan University, shang-
the cell-permeable fluorogenic probe. Comprehensive analyses were performed by hai, China
DNA chip for mRNA and microRNA expressions and by iTRAQ-labeled 2D-LC- Contact E-mail Address: wellyoudiandian@gmail.com
MS/MS analysis for protein expressions. Integrated analysis of those comprehensive
analyses was performed using the Ingenuity Pathway Analysis software. INTRODUCTION: A large body of evidence demonstrates abnormality of ubi-
RESULTS: Poorly differentiated HCC derived SK-HEP-1 and undifferentiated quitination contributes to the development of various cancer including hepato-
HCC derived HLE cell lines efficiently formed spheres of cells (SK-sphere and cellular carcinoma (HCC). In our previous work, deubiquitinating enzyme
A98 United European Gastroenterology Journal 2(5S)
UCH37 promoted invasion and postoperative recurrence of HCC, and decreased P. Kaye: None declared, M. Novelli: None declared, B. Disep: None declared, R.
ubiquitin/proteasome-dependent degradation of pre-mRNA processing factor 19 Ostler: None declared, B. Aigret: None declared, B. North: None declared, P.
(Prp19), making Prp19 a potential downstream effector to mediate invasion of Bhandari: None declared, A. Haycock: None declared, D. Morris: None
HCC. As one member of protein-ubiquitin ligase, Prp19 participates in activation declared, S. Attwood: None declared, A. Dhar: None declared, C. Rees: None
of mRNA splicesome, DNA damage response, and ubiquitin/proteasome depen- declared, M. Rutter: None declared, P. Sasieni: None declared, R. Fitzgerald
dent degradation of proteins.Although dysfunction of aforementioned activities Other: Since this study was conducted the CytospongeTM-TFF3 technology
is closely correlated with oncogenesis, the role of Prp19 in the development of has been licensed to Covidien GI solutions by the Medical Research Council.
HCC is less understood.
AIMS & METHODS: We investigated the expression of Prp19 and underlying
mechanisms linked to its pro-invasive role in HCC. rp19 expression in tumor and WEDNESDAY, OCTOBER 22, 2014 8:3010:30
paratumor tissues from 169 HCC patients was detected by immunochemistry NOVEL APPROACHES TO RECTAL CANCER HALL G/H_____________________
staining and western blot, and its correlation with clinical features was analyzed.
Biological behaviors of HCC cell lines with ectopic Prp19 expression were then OP310 INCIDENCE OF RECTAL ADENOCARCINOMA AND IMPACT
assessed ex vivo and in vivo. OF NEOADJUVANT TREATMENTS ON PATIENTS SURVIVAL
RESULTS: Prp19 expression was up-regulated in most HCC tissues and cell BETWEEN 1990 AND 2009 IN THE DISTRICT OF FINISTERE
lines, which was positively correlated with vascular invasion, absent tumor cap- (FRANCE)
sule and poor prognosis. Prp19 knockdown significantly attenuated migratory M.C. Deniel1,*, M. Cariou2, J.-B. Nousbaum1,2, M. Robaszkiewicz1,2
and invasive capacity of HCC cells both ex vivo and in vivo, whereas Prp19 1
Gastroenterology, 2Registre des Tumeurs Digestives du Finiste`re, University
overexpression had the opposite effects. Moreover Prp19 promoted epithelial- Hospital, Brest, France
mesenchymal transition (EMT) of HCC cells via sustaining Twist1stability,
which was dependent on p38 mitogen-activated protein kinase (p38 MAPK) INTRODUCTION: During the past decades, total mesorectal excision techni-
mediated Ser68 phosphorylation within Twist1. Prp19 interacted with transform- ques and neoadjuvant treatments have been applied in order to improve the
ing growing factor- activated kinase 1 (TAK1) and facilitated k63-linked poly- prognosis of rectal cancer.
ubiquitination of TAK1 in HCC cells, leading to strengthened activation of p38 AIMS & METHODS: The aim of this study performed in the district of Finistere
mitogen-activated protein kinase (p38 MAPK). Prp19/p38 MAPK/Twist1 regu- (France) between 1990 and 2009, was to analyze the variations in incidence of
latory axis was further attested in orthotopic xenografts models of HCC in nude rectal adenocarcinoma, as well as access to neoadjuvant treatments and their
mice and human HCC specimens. impact on patients survival.
CONCLUSION: Increased Prp19 expression promotes HCC invasion by facil- All cases of rectal adenocarcinoma diagnosed between January 1, 1990 and
itating EMT via p38 MAPK/Twist1 pathway. These studies imply that gain of December 31, 2009, recorded in the datbase of the digestive cancer registry of
Prp19 is a pivotal oncogenetic event during HCC progression, rendering it a Finistere, were included in the study. Four 5-years periods were compared. The
promising therapeutic target for advanced HCC. studied variables were gender, age, cancer stage at diagnosis (UICC) and first
REFERENCES type of treatment applied. Qualitative variables were compared using the Chi 2
Fang Y, Fu D, Tang W, et al. Ubiquitin C-terminal Hydrolase 37, a novel test; survival curves were established using the Kaplan-Meier method and com-
predictor for hepatocellular carcinoma recurrence, promotes cell migration and pared with the log-rank test.
invasion via interacting and deubiquitinating PRP19. Biochim Biophys Acta 2013; RESULTS: 2838 patients were included in the study. The incidence of rectal
1833: 559-572. cancer did not change significantly during the study period (1990-1994: 7.51
Disclosure of Interest: None declared 0.33; 2005-2009: 7.97 0.32 per 100 000 inhabitants). A significant change in the
distribution of cancer stages was noted over time (p 0.04): the proportion of
stage 4 cancers increased from 16.4% to 21.6% between the first and last period.
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 The proportion of patients who received a neoadjuvant treatment with radiation
NEW FRONTIERS IN BARRETTS OESOPHAGUS HALL F2_____________________ therapy or chemoradiotherapy, increased over time for stage 2 and stage 3 can-
cers (23% between 1990 and 1994, 55% between 2005 and 2009.) The proportion
OP309 PROSPECTIVE, MULTI-CENTRE, CASE-CONTROL STUDY TO of patients with a stage 4 cancer and treated by chemotherapy increased from 17
EVALUATE A NOVEL CYTOSPONGETMTFF3 TEST FOR to 65%. Overall 5 years survival rates are presented in the table. The variation of
DIAGNOSING BARRETTS OESOPHAGUS survival was statistically significant (p 10-5). The highest variation in 5-year
C. Ross-Innes1, I. Debiram1, M. ODonovan1, E. Walker1, S. Varghese1, P. Lao- survival was noted for patients with stage 3 cancer (29.3% to 65.4%).
Sirieix1,*, L. Lovat2, M. Griffin3, K. Ragunath4, R. Haidry2, S. Sami4, P. Kaye4,
M. Novelli2, B. Disep3, R. Ostler5, B. Aigret5, B. North5, P. Bhandari6,
A. Haycock7, D. Morris8, S. Attwood9, A. Dhar10, C. Rees11, M. Rutter12, Survival
P. Sasieni5, R. Fitzgerald1 on behalf of BEST2 Study Group
1
University of Cambridge, Cambridge, 2University College London Hospital, Period 1 year 2 years 3 years 4 years 5 years Total
London, 3Royal Victoria Infirmary, Newcastle upon Tyne, 4Nottingham Queens
Medical Centre, Nottingham, 5Cancer Prevention Trials Unit, London, 6Queen 1990-1994 75% 59,9% 49,3% 41,3% 37,3% 630
Alexandra Hospital, Portsmouth, 7St Marks Hospital, London, 8QEII and Lister 1995-1999 76,3% 64,2% 54,9% 48,2% 43,8% 716
Hospitals, Hertsfordshire, 9North Tyneside General Hospital, North Tyneside, 2000-2004 77,9% 64,7% 55,7% 51,3% 45,8% 706
10
County Durham and Darlinton NHS Foundation Trust, Durham, 11South
2005-2009 81,9% 70,5% 61,5% 54,3% 49,8% 780
Tyneside NHS Foundation Trust, Tyne and Wear, 12North Tees and Hartlepool
NHS Foundation Trust, North Tees, United Kingdom
Contact E-mail Address: rcf29@mrc-cu.cam.ac.uk Table: survival (in %) at 1, 2, 3, 4 and 5 years, for each period
CONCLUSION: The incidence of rectal adenocarcinoma has not changed in the
INTRODUCTION: Barretts oesophagus (BE) is a common condition which is Finistere district between 1990 and 2009. Despite a significant increase in the
often undiagnosed and predisposes to oesophageal adenocarcinoma. A mini- proportion of advanced stages, there was a significant increase in survival rates
mally-invasive cell sampling device, the CytospongeTM, coupled with an immu- with time, to be compared with the increase in the proportion of patients who
nohistochemical marker, trefoil factor 3 (TFF3), has shown promise as a received neoadjuvant treatment or exclusive medical treatment with chemotherapy.
diagnostic tool. Disclosure of Interest: None declared
AIMS & METHODS: A multicentre, prospective study was performed to eval-
uate the safety, acceptability and accuracy of the CytospongeTM-TFF3 test in
patients with reflux and dyspepsia symptoms without BE (controls) and cases OP311 ADDITIONAL SURGICAL RESECTION AFTER ENDOSCOPIC
with BE ( 1cm circumferential BE or 3 cm tongues). The data were compared REMOVAL OF T1 COLORECTAL CARCINOMA IS ASSOCIATED
with endoscopy. WITH IMPROVED OVERALL SURVIVAL
RESULTS: 1,110 individuals took part comprising 463 controls (median age 56 T.D. Belderbos1,*, F. N. van Erning2, I. H. de Hingh3, M. G. van Oijen1,
years (interquartile range (IQR) 44-66), Male:Female ratio 1.0:1.3) and 647 cases L.M. Moons1, V. E. Lemmens2, P.D. Siersema1
(median age 66 years (IQR 58-73), Male:Female ratio 4.0:1.0). 1,042 (93.9%) 1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht,
patients successfully swallowed the CytospongeTM and no serious adverse 2
Eindhoven Cancer Registry, Comprehensive Cancer Centre The Netherlands,
events were attributed to the device. Using a visual analogue scale, the 3
Surgery, Catharina Hospital, Eindhoven, Netherlands
CytospongeTM was rated favourably compared with endoscopy (p0.0003) and Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl
patients who were not sedated for endoscopy were more likely to rate the
CytospongeTM higher than endoscopy (Mann-Whitney test, p50.001). The over- INTRODUCTION: Controversy exists on the adequate management of patients
all sensitivity of the test was 79.9% (95% confidence interval (CI) 76.4-83.0%) with pathologically confirmed T1 colorectal carcinoma (pT1 CRC) after initial
increasing to 87.2% (95%CI 83.0-90.6%) for BE segments with 3 cm of cir- endoscopic removal. It is currently not well known whether additional surgery
cumferential BE. There was no loss of sensitivity in patients with dysplasia. The following endoscopic resection of a pT1 CRC indeed improves the prognosis of
specificity for diagnosing BE was 92.4% (95%CI 89.5-94.7%). patients. Moreover, it is unknown in which subgroups of patients additional
CONCLUSION: The CytospongeTM-TFF3 test is safe, acceptable and has very surgery is actually performed in clinical practice.
good accuracy for diagnosing BE. This test warrants consideration as an alter- AIMS & METHODS: We collected data on current treatment strategies in a
native to endoscopy for diagnosing BE with potential applicability to screening in cohort of patients with pT1 CRC to compare the overall survival between
primary care. patients undergoing additional surgery versus endoscopic resection only and to
Disclosure of Interest: C. Ross-Innes: None declared, I. Debiram: None declared, identify factors associated with the decision to perform additional surgical resec-
M. ODonovan: None declared, E. Walker: None declared, S. Varghese: None tion after endoscopic resection. All patients diagnosed with pT1 CRC between
declared, P. Lao-Sirieix Other: Pierre Lao-Sirieix is now employed partly by 1995 and 2011 in the area of the Eindhoven Cancer Registry (southern part of the
Covidien GI Solutions, L. Lovat: None declared, M. Griffin: None declared, Netherlands) were included. The Cochrane-Armitage Trend test was used to
K. Ragunath: None declared, R. Haidry: None declared, S. Sami: None declared, evaluate trends over time in endoscopic resection of pT1 CRC. Multivariable
United European Gastroenterology Journal 2(5S) A99
logistic regression was used to assess patient and tumour characteristics asso- OP313 SCREENING FOR COLORECTAL CANCER: A RANDOMIZED
ciated with additional surgical resection. Crude 5-year overall survival was based TRIAL COMPARING PATIENT RESPONSE OF SIGMOIDOSCOPY
on Kaplan-Meier curves and Cox regression analysis was used to discriminate the VS. CT COLONOGRAPHY
independent effect of additional surgical resection on the risk of death after C. Senore1,*, N. Segnan1, L. Correale2, G. Iussich3, C. Hassan4, D. Regge3
adjusting for relevant patient and tumour characteristics. 1
CPO Piemonte, AOU Citta` della Salute e della Scienza, 2I-m3d S.p.a.,
RESULTS: A total number of 1965 patients with pT1 CRC were identified, of 3
Radiology, IRCC Candiolo (TO), Torino, 4Gastroenterology, Osepedale Nuovo
whom 827 (42%) were treated with endoscopic resection (with (n567, 69%) or Regina Margherita, Rome, Italy
without (n260, 31%) additional surgery) and 1138 with primary surgical resec- Contact E-mail Address: carlo.senore@cpo.it
tion. The rate of endoscopic resection in pT1 CRC patients remained stable over
time (41% in 1995 and 43% in 2011, p0.45). Patients in whom additional INTRODUCTION: CT colonograpphy has been proposed as non invasive,
surgical resection was performed were younger (mean age 65 vs. 69 years, potentially acceptable, primary screening test for colorectal cancer (CRC).
p50.01), more often had no comorbidities (34% vs. 25%, p50.01) and more Only one randomised trial (1) has been conducted in a population base program,
often had a colon than a rectum tumour (71% vs. 63%, p0.017), compared to comparing CT colonography and colonoscopy.
patients undergoing endoscopic resection only. In multivariable analysis, AIMS & METHODS: The aim of the study is to compare the participation rate
younger patients (OR for patients 550 years versus 70 years 1.95, 95%CI of people invited to perform a Flexible Sigmoidoscopy (FS) to the response rate
1.05-3.59) and patients with a tumour in the colon (OR for colon versus to the invitation to performa a CT Colonography (CTC), in the context of a
rectum tumours 1.54, 95%CI 1.11-2.15) were more likely to undergo additional population-based screening program.
surgery. Crude 5-year overall survival was higher in patients with additional A sample of 58 years olds in the general population living in Turin, Italy were
surgical resection after endoscopic resection compared to patients with endo- randomly allocated (1:1) to be invited by mail for primary screening with FS or
scopic resection only (82% versus 75%, p50.01). The association remained sig- CTC. Those with a history of CRC, adenomas, inFammatory bowel disease,
nificant after adjusting for patient and tumour characteristics (adjusted HR 0.68: recent colonoscopy, or two Erst-degree relatives with CRC were ineligible.
95% CI 0.50-0.93). Female gender, younger age, higher socioeconomic status and Non-responders to invitation for FS screening were re-invited to attend for
absence of comorbidity were all independently associated with lower mortality. screening with CTC or immunological Fecal Occult Blood Test (FOBT). The
CONCLUSION: In a large cohort of pT1 CRCs, one third of patients, particu- primary outcome was screening participation rate, defined as numbers of invitees
larly younger patients with a colon tumour, undergoing endoscopic resection, undergoing to the screening relative to the total number of invitees. Participation
underwent additional surgical resection, which was independently associated rates were also compared in a multivariate model to assess the effect of covariates
with an improved overall survival rate. (gender and screening arm). We conducted also a survey of a sample of partic-
Disclosure of Interest: None declared pants and of refusers to compare screenee experience with the two tests and to
study reasons for non-participation.
RESULTS: Of the 1984 eligible subjects included in the study, 995 and 989 were
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 randomly assigned to CTC and FS arm, respectively. After excluding 27 people
COLORECTAL CANCER SCREENING: STRATEGIES AND OUTCOMES HALL I/ who could not be traced (1.4% across intervention groups), the participation rate
K_____________________ following the first invitation and mail remainder was 27.1% (265/977) for FS and
30.5% (299/980) for CTC (P0.09).
OP312 GETTING OLD WITH LYNCH SYNDROME IN Participation in screening with CTC was significantly better than with FS (34%,
NORTHEASTERN ITALY 95% CI: 30-39% vs. 26%, 95% CI: 22-31; OR, 1.6; 95% CI: 1.1-2.3; P0.01)
M. Fornasarig1,*, M. Tabuso1, R. Talamini2, A. Viel3, E. Orzes1, V. Canzonieri4, among men, while no difference between CTC and FS screening was observed
R. Cannizzaro1 among women (OR, 0.91; 95% CI: 0.7-1.2; P0.53). Invitation for FS non-
1
Gastroenterology, 2Epidemiology, 3Experimental Oncology I, 4Pathology, Centro responders to undergo screening with CTC or FOBT increased participation
di Riferimento Oncologico, Aviano, Italy (80-100 days after invitation) by 5% (18 of 330 invitees) and 4.8% (16 of 330
Contact E-mail Address: mfornasarig@cro.it invitees), respectively.
CONCLUSION: A trend toward increased participation in CTC vs. FS screen-
INTRODUCTION: Lynch Syndrome (LS) is an inherited cancer predisposition ing was seen. Moreover, men were significantly more likely to adhere to screening
bringing about 2-3% of all new cases of ColoRectal Cancer (CRC), caused by with CTC than with FS. Additional effort may be needed to improve participa-
mutation in mismatch repair (MMR) genes. LS patients have a lifetime risk to tion of women in CRC screening.
develop a CRC up to 75% in men and 52% in women and an Endometrial REFERENCES
Carcinoma (EC) up to 71%. The cancer spectrum involves other organs 1) Stoop EM, de Haan MC, de Wijkerslooth TR, et al. Participation and yield of
(ovary, stomach, urinary tract and small bowel), but with a lower risk. colonoscopy versus non-cathartic CT colonography in population-based screen-
AIMS & METHODS: We report our experience of a hospital LS registry collect- ing for colorectal cancer: a randomised controlled trial. Lancet Oncol 2012; 13:
ing cases mainly from Northeastern Italy focusing on the clinical history of 55-64.
patients through aging. Families included in the study were registered in the Disclosure of Interest: C. Senore: None declared, N. Segnan: None declared, L.
Registro Tumori Ereditari del colon-retto, settled since 1992 at our Correale Other: Dr. Correale is employed bu I-m3d spa. The company developed
Institution. Pathogenic mutations in MSH2, MLH1 and MSH6 were identified the CAD system used for the study and it contributed to the funding of the study
in 37 unrelated families. We tested 251 members of the families including the together with the Piedmont Region Health Authrority, G. Iussich: None
probands: 113 (45%) were gene carries (44M and 69F) and 138 were wild-type. declared, C. Hassan: None declared, D. Regge: None declared
25 families displayed mutation in MSH2, 11 families in MLH1 and one in MSH6.
Surveillance program included colonoscopy from age 22 with an interval of 1-2
years, abdominal ultrasound, urine cytology every two years and upper GI endo- OP314 OUTCOMES OF THE FRENCH COLORECTAL CANCER
scopy every 4 years from age 35. For women, the gynecological work out POPULATION-BASED SCREENING PROGRAMME USING GUAIAC
included transvaginal ultrasonography and endometrial biopsy every two years FAECAL OCCULT BLOOD TEST
from 30-35 years. F. Assogba1,*, D. Jezewski-Serra1, D. Lastier1, C. Quintin1
RESULTS: The first cancer diagnosed was CRC in almost all males. EC and 1
1Department of Chronic Diseases and Injuries, INVS, Saint-Maurice, France
CRC were equally diagnosed in women. The number of CRC increased abruptly Contact E-mail Address: f.assogba@invs.sante.fr
until age 40 and decreased slowly with aging. Extra-colonic cancers (EXC),
instead, increased from age 50. 78 (69%) patients developed at least one INTRODUCTION: With more than 42 000 new cases and more than 17 000
cancer: 57 (50.4%) CRC and 32 female patients (46.4%) EC. However, cancer deaths each year, colorectal cancer is the third most common cancer and the
of any type occurred in all patients over age 60. 66 (56.4%) had multiple primary second most common cause of cancer-related death in France. Due to its large
cancers related to aging. A progressive increase of CRC and EXC was seen and and growing burden, an organized biennial population-based on a guaiac Fecal
patients with six EXC had a mean age of 74 years. The deaths registered were 11 Occult Blood Test (g-FOBT) screening programme has been launched, and gen-
(9.7%): 2 (1.7%) for pancreatic cancer and 9 (7.9%) for other diseases between eralized since 2008 in 46 French districts, and progressively spread throughout
69 and 83 of age. Colonic surveillance lasted for an average period of 10.5 years the country and now covers all (99) French districts.
(2-22 years). 5 patients (4.4%) out of 113 had CRC at stage T1 (2 pts), T2 (2 pts) AIMS & METHODS: Biennially, all average-risk men and women aged 50 to 74
and T2N1 (1 pt) and 38 (33.6%) patients had 121 advanced adenomas. years are invited to perform a g-FOBT. Individuals with positive g-FOBT were
CONCLUSION: Getting old, all LS patients displayed at least one cancer and referred to a gastroenterologist to undergo a total colonoscopy. Early perfor-
more than 50% had multiple primary cancers. Colectomy with ileo-rectum ana- mance indicators for the third round (January 1, 2012 to December 31, 2013)
stomosis is the therapy of choice at first CRC diagnosed to avoid any further were evaluated according to European guidelines, and then compared with those
surgical procedures for that disease. Surveillance of organ targets (pancreas, of the second round (2010-2011), when available. The TNM classification of
small bowel, duodenum, urinary tract and stomach) should be included in long malignant tumours, (7th edition 2009) has been used.
survivors from CRC. RESULTS: More than 18 million people were invited for this third-round and
Disclosure of Interest: None declared 5.1 million people performed a g-FOBT. Participation rate was 31% (- 3.4%
since the previous-round). It increased with age and was higher in women than
in men (33% vs 29%). Positive rate was consistent with the expected (2.2%, men
2.5% vs women 1.9%), and varied widely with age and across the districts.
Compared to the previous-round, the positive rate decreased from 2.6% to
2.2%, a decrease of 15.4%. During the period 2010-2011, follow-up colonoscopy
compliance rate was 87%, and varied across the districts from 17% to 98%.
Advanced adenoma detection rate was 4% (men: 5.9% vs women 2.5%), that
of colorectal cancer was 1.5% (men: 2.1% vs women 1.0%). A total of 3949
colorectal adenocarcinomas were detected (in situ: 27% vs invasive: 73%). Stage
I was 39.5% (resp., 38.1%), stage II 26.2% (resp., 26.3%), stage III 22.1% (resp.,
25.6%) and stage IV 12.2% (resp., 10%) for men (resp., women). As expected,
A100 United European Gastroenterology Journal 2(5S)
cancers detected at subsequent screening are more often diagnosed at earlier considered persons who were diagnosed with CRC (screen-detected or interval
stages (stage I and II) then those diagnosed during a first screening (68% vs CRC) until the end of the follow-up period and examined whether their FIT level
63%). at the inSR was beyond a certain value. We first looked at FIT11 (i.e., a CL of
CONCLUSION: Five years after the generalization of the French population- 11 ng Hb/ml, corresponding to 2 mg Hb/g faeces). This CL is - according to
based screening programme throughout the country, participation rate fail to published literature on diagnostic performance - expected to yield a similar
achieve the European minimum recommended goal (45%). More efforts number of advanced adenomas as detected in the 2 FIT50 rounds combined.
should be done to identify the profile of non-adherent to the programme for We also compared positivity rates for the different scenarios.
developing most effective communication strategies for these targeted people. RESULTS: In the 2 FIT50 rounds, 28 CRCs were detected, of which 22 (79%)
One can hope that the next implementation of fecal immunochemical tests to were at an early stage (UICC stages I-II). The cumulative positivity rate was
replace g-FOBT tests might contribute to enhanced the adherence to screening. 14%. In a hypothetical inSR with FIT11, 27 CRCs would have been detected. Of
Disclosure of Interest: None declared these, 19 (70%) would definitely have been detected at an early stage. Two of the
27 CRCs were detected at UICC stage III 9 months and 2 years after the inSR,
respectively, and thus might have been at an early stage if detected at the inSR.
OP315 COLORECTAL CANCER SCREENING PILOT IN NORWAY - The positivity rate of a hypothetical inSR with FIT11 would have been 18%. All
COMPARATIVE EFFECTIVENESS RESEARCH OF FLEXIBLE CRCs detected with FIT11 would also have tested positive with CLs up to 24ng/
SIGMOIDOSCOPY (FS) AND FECAL IMMUNOCHEMICAL TEST ml. The positivity rate of a hypothetical inSR with FIT24 would have been 12%.
(FIT) CONCLUSION: We provide first empirical evidence regarding alternative FIT
T. de Lange1,*, A. Jrgensen1, O.P. Brmer2, P. Sandvei3, C.B. Steen1, G. Ursin1, strategies using extended screening intervals in combination with a lower than
G. Hoff1 usual positivity threshold. The findings remove concerns that such strategies
1
Cancer Registry of Norway, 2Oslo University Hospital, Radiumhospitalet, Oslo, would go along with a significant increase in the rate of interval cancers or in
3
Department of Internal Medicine, stfold Hospital, Fredrikstad, Norway the overall positivity rate. Although the approach taken here to lower the posi-
Contact E-mail Address: t.d.lange@medisin.uio.no tivity threshold (i.e., CLs below 50 ng/ml) would require careful consideration
regarding test-retest reliability, the findings suggest that, in principle, such alter-
INTRODUCTION: Although several modalities are being used in colorectal native FIT strategies could be interesting options and provide the basis for
cancer (CRC) screening, only fecal occult blood testing (FOBT) and FS have planning next research steps in this direction.
been subjected to randomized trials and long-term follow-up. Both have been Disclosure of Interest: None declared
found to reduce CRC mortality compared to no screening (18% and 28%,
respectively), but a direct comparison between the two has never been done
with end-point CRC incidence and mortality. It is also not clear which modality OP317 THE 10 YEARS EVALUATION OF THE CZECH COLORECTAL
is the most cost-effective in any given population. In Norway, a country with CANCER SCREENING PROGRAM EFFICACY BASED ON THE
high colorectal cancer incidence and little prior CRC screening, the government LONG-TERM IMPACT INDICATORS
decided to start a comparative effectiveness research pilot in 2012. S. Suchanek1,*, O. Majek2, L. Dusek2, B. Seifert3, M. Zavoral1
AIMS & METHODS: The pilot aims to randomize 1x1 the entire population 1
Department of Gastroenterology, 1st Faculty of Medicine of Charles University
aged 5074 in a defined geographical area in South-East Norway (approximately and Military University Hospital, Prague, 2Institute of Biostatistics and Analyses,
140 000 individuals) to one of two screening modalities, FIT (OC-Sensor Diana, Masaryk University, Brno, 3Institute of General Medicine, 1st Faculty of Medicine,
Eiken Ltd) or once only FS. The enrollment will take six years and the pilot Charles University, Prague, Czech Republic
includes a number of sub-studies to determine how the screening is perceived in Contact E-mail Address: stepan.suchanek@uvn.cz
the target population. We report the results from the enrollment in the main trial
after the first 24 months. INTRODUCTION: In the Czech Republic, there is 3.75 million inhabitants aged
RESULTS: A total of 51500 women and men have been invited so far, 33.373 to over 50. The Czech Colorectal Cancer (CRC) Screening Program was introduced
FIT and 18.127 to FS. Participation rates have been 49% in the FS arm, and in 2000 based on guiac fecal occult blood testing (gFOBT). In the last decade, the
57% in the FIT arm, with slightly higher rates among women than men. Positive program has continuously evolved. Currently the annual immunochemical
FS was defined as advanced neoplasia or three or more adenomas. A total of FOBT (FIT) is offered at the age 50 54, followed by FOBT colonoscopy, if
10.3% of the FS patients have been referred to colonoscopy. The cut-off value positive. In age of 55, there is a choice of either FIT biannually or screening
for positive FIT was set to 75 ug/L, and 1287 patients (6.9%) have so far tested colonoscopy in 10 years interval.
positive and referred to colonoscopy. AIMS & METHODS: Three main quality control long-term impact indicators
Forty-three cases of CRC have been detected in the FS group so far, at a rate of recommended by the European Guidelines (published in 2010) have been com-
5/1000 examined, somewhat higher in men (5.7/1000) than in women (4.3/1000). pared in 10 years interval (decrease of CRC incidence and mortality and the
Forty-nine cancers have been found in the FIT group after first screening round increase of the proportion of early stage cancers) to assess the CRC screening
(2.6/1000 examined), with 3.7/1000 in men and 1.7/1000 in women. Overall the program efficacy. The data from the Czech National Cancer Registry have been
adenoma detection rate at sigmoidoscopy is 14.4 %. A total of 853 high-risk used.
adenomas (adenomas 410 mm, or with high-grade dysplasia or villous features) RESULTS: The CRC incidence in years 2000 and 2010 reached the level of 42.23
have been detected. Adenoma detection rate in the population referred for colo- and 39.19 (the world standard, ASR-W) and 7,553 and 8,265 (absolute numbers,
noscopy is 59%. One perforation has occurred due to the enema installation 712, 9.4%). The CRC mortality recorded in the same years was 23.79 and 17.20
prior to sigmoidoscopy. At colonoscopy the rate of serious adverse events need- (ASR-W) and 4,508 and 3,991 (absolute numbers, -517, -11.5%). The compar-
ing hospitalization is currently 8/1000, the main ones being reported are burned ison of CRC stages in years 2000 and 2010 is shown in the table.
serosa and bleeding, while no perforation has occurred.
CONCLUSION: Participation rates in both arms are slightly below the expected
50% for FS and 60% for FOBT. Cancer rates among those screened are higher in Stage 2000 2010 Change
the once-only FS than after first round of biennial FIT screening, but rates are
within the expected range. Stage I 16 % 23 % 7%
Disclosure of Interest: None declared Stage II 27 % 24 % -3%
Stage III 17 % 24 % 7%
OP316 IMMUNOCHEMICAL FECAL OCCULT BLOOD TESTING TO Stage IV 23 % 23 % 0%
SCREEN FOR COLORECTAL CANCER: CAN THE SCREENING Stage unknown 18 % 6% -12%
INTERVAL BE EXTENDED?
U. Haug1,*, E. Grobbee2, I. Lansdorp-Vogelaar2, M. Spaander2, E. Kuipers2 CONCLUSION: The ten years results show that the Czech CRC screening pro-
1
German Cancer Research Center, Heidelberg, Germany, 2Erasmus MC University gram is effective. All three main long-term impact indicators are fulfilled, the
Medical Center, Rotterdam, Netherlands incidence and mortality are decreasing and the ratio of stage I cancers diagnosed
Contact E-mail Address: u.haug@dkfz.de is rising.
This project has been supported by the Czech Ministry of Health grant No. NT
INTRODUCTION: Colorectal cancer (CRC) screening programs based on fecal 13673
immunochemical testing for hemoglobin (FIT) typically use a screening interval REFERENCES
of 2 years. Studies have shown that the diagnostic yield of the first re-screening von Karsa L, Patnick J and Segnan N. European guidelines for quality assurance
round (reSR) is significantly lower as compared to the initial screening round in colorectal cancer screening and diagnosis. First EditionExecutive summary.
(inSR), which raises the question whether the first reSR could be skipped. This Endoscopy 2012; 44 (Suppl. 3): SE1-SE8.
would lead to a longer screening interval that could be advantageous regarding Disclosure of Interest: None declared
adherence and organizational effort. Given the quantitative nature of FIT, the
skipped round could be compensated for by lowering the cutoff level (CL) of FIT
at the initial round (i.e., increasing sensitivity at the cost of decreasing specificity).
We aimed to explore how such alternative FIT strategies compare to conven-
tional ones in terms of CRC detection and positivity rate.
AIMS & METHODS: We analyzed longitudinal data of 4523 Dutch individuals
(5074 years) participating in the inSR of a 1-sample FIT screening program, of
which 3427 individuals also participated in the first reSR after 1-3 years. FIT50
was used in both rounds (i.e., a CL of 50 ng haemoglobin (Hb)/ml, correspond-
ing to 10 mg Hb/g faeces). The cohort was followed up until 2 years after the first
reSR. We determined the cumulative number of (screen-detected) CRCs for the 2
FIT50 rounds and compared it to the number of CRCs that would have been
detected at a hypothetical, single inSR with a lower CL. For the latter, we
United European Gastroenterology Journal 2(5S) A101
OP318 LONG-TERM IMPACT OF THE DUTCH COLORECTAL AAd and 6% CRC miss rate. The IC rate over the 2-year period after the initial
CANCER SCREENING PROGRAMME ON CANCER INCIDENCE - negative FIT was 2.5 (N10) and 7.2 (N25) x 10,000 women aged 50-59 and 60-
EXPLORATION OF THE SERRATED PATHWAY 69 respectively; the corresponding figures for men were 3.6 (N12) and 8.3
M. Greuter1, J.-B. Lew2, J. Berkhof1, K. Canfell2, E. Dekker3, G. Meijer1, (N24) x10,000; the Hb level at the preceding FIT was 0 in 39.4% of the
V. Coupe1,* cases. Among people with 2 negative FITs the IC rate was 3.9 (N19) and 3.9
1
VU University Medical Center, Amsterdam, Netherlands, 2Lowy Cancer Research (n16) x 10,000 women and men respectively; no Hb was detected in the previous
Centre, The University of New South Wales, Sydney, Australia, 3Amsterdam 2 FITs in 34.3% of these cases.
Medical Center, Amsterdam, Netherlands
Contact E-mail Address: mj.greuter@vumc.nl Age 50-59 N examined FIT TC PPV AAd PPV CRC DR AAd DR CRC NNScope
INTRODUCTION: The Netherlands has recently started with the stepwise 1 FIT 88935 4,3% 91,5% 35,3% 4,2% 1,40% 0,17% 2,5
implementation of a colorectal cancer (CRC) screening programme consisting 2 FIT 46692 3,3% 93,0% 25,0% 2,5% 0,77% 0,08% 3,6
of biennial faecal immunochemical test (FIT) screening in individuals aged 55 to 3 FIT 24009 3,0% 93,3% 22,7% 2,8% 0,64% 0,08% 3,9
75 years.
4 FIT 3569 2,9% 94,3% 33,3% 1,0% 0,92% 0,03% 2,9
AIMS & METHODS: 1) To evaluate the impact of the Dutch screening pro-
Age 60-69 N examined FIT TC PPV AAd PPV CRC DR AAd DR CRC NNScope
gramme on the long-term CRC incidence and colonoscopy demand. 2) To
explore the impact of assumptions concerning the serrated pathway on these 1 FIT 76934 6,6% 88,7% 34,6% 7,1% 2,01% 0,41% 2,4
long-term predictions. 2 FIT 61922 4,6% 91,3% 26,7% 3,5% 1,13% 0,15% 3,3
The Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model was 3 FIT 41882 4,2% 91,6% 24,0% 3,2% 0,93% 0,12% 3,7
set up to simulate the Dutch CRC screening programme between 2014 and 2044. 4 FIT 19166 4,0% 90,2% 23,3% 3,0% 0,84% 0,11% 3,8
Based on pilot studies, we assumed a participation rate of 62% for FIT testing.
We adopted an open-model approach by simulating multiple birth cohorts and
combining the results while accounting for the ageing of the population. Besides
a no screening scenario, we evaluated three screening scenarios differing in the CONCLUSION: The high DR of AAd over several screening rounds is sugges-
contribution of the serrated pathway to the CRC incidence (0%, 15% and 30%). tive for a larger impact of FIT screening on CRC incidence, as compared to
Model-predicted outcomes were CRC incidence and the colonoscopy demand guaiac-FOBT. Gender, age and stool Hb at previous tests could be used to
per year from 2014 until 2044. In addition to the contribution of the serrated modulate the cut-off at subsequent tests, to reduce TC workload. Apparently a
pathway to the CRC incidence, we assessed the impact of other natural history substantial proportion of ICs may not bleed.
assumptions regarding the serrated pathway. Disclosure of Interest: None declared
RESULTS: Due to ageing, the model-predicted CRC incidence in the no screen-
ing scenario increased from 77/100,000 in 2014 to 109/100,000 in 2044. In the
screening scenarios, the predicted CRC incidence first increased compared to no OP320 COLONPREDICT STUDY: DEVELOPMENT AND VALIDATION
screening due to the detection of asymptomatic, prevalent tumours. In 2014, the OF A PREDICTIVE MODEL FOR COLORECTAL CANCER
CRC incidence was predicted to peak between 105/100,000 (under the assump- DETECTION IN SYMPTOMATIC PATIENTS
tion that all CRCs arise from adenomas) and 109/100,000 (under the assumption J. Cubiella1,*, P. VEGA1, M. T. ALVES1, M. SALVE1, M. DIAZ-ONDINA2, P.
that 30% of CRCs arises from serrated lesions). After this peak, the predicted MACIA2, I. BLANCO2, L. BUJANDA3, J. FERNANDEZ-SEARA1,
incidence under screening gradually decreased. In 2044, the estimated CRC inci- E. SANCHEZ1
dence under screening reached a new equilibrium between 65/100,000 and 71/ 1
GASTROENTEROLOGY, 2CLINICAL ANALYSIS, COMPLEXO
100,000 under the assumption that 100% versus 70% of CRCs originate via the HOSPITALARIO UNIVERSITARIO DE OURENSE, OURENSE,
adenoma-carcinoma pathway, respectively. Due to the stepwise implementation, 3
GASTROENTEROLOGY, Hospital de Donostia, San Sebastian, Spain
the predicted number of colonoscopies required for the screening programme Contact E-mail Address: joaquin.cubiella.fernandez@sergas.es
increased gradually over time. In 2014, the expected number of colonoscopies
under screening was estimated to be around 38,000 (752,199 invitees) whereas in INTRODUCTION: Predictive models for colorectal cancer (CRC) detection in
2044, the predicted colonoscopy demand was estimated to be around 117,000 symptomatic patients are based on subjective clinical criteria and have low diag-
(2,154,875 invitees). Except for the contribution of the serrated pathway to the nostic accuracy.
CRC incidence, model predictions were robust for other assumptions regarding AIMS & METHODS: We designed a prospective blind diagnostic tests study
the natural history of the serrated pathway. aimed to develop and validate a CRC predictive model in symptomatic patients
CONCLUSION: The Dutch screening programme will markedly decrease the based on clinical and laboratory variables. We compared its diagnostic accuracy
CRC incidence. With the results of this study, decision-makers on health care with the National Institute for Health and Care Excellence (NICE) referral cri-
planning can anticipate the expected change in CRC-related health care use and teria for the detection of colorectal cancer in symptomatic patients. We included
colonoscopy demand. Although the natural history of the serrated pathway has consecutive patients with gastrointestinal symptoms referred for colonoscopy. In
not yet been fully clarified, different assumptions for these unknown parameters each patient, the symptoms were collected in a structured protocol; fecal calpro-
have limited impact on model predictions. However, the estimate of the propor- tectin (Buhl Quantum Blue ) and hemoglobin (OC-Sensor ) concentrations,
tion of CRCs arising through the serrated pathway does influence the predicted serum carcinoembryonic antigen (CEA) and hemoglobin were determined and
effectiveness of screening. the findings in anorectal examination were described. A predictive model was
Disclosure of Interest: None declared developed based on a binary logistic regression and was internally validated using
the split-sample technique. To compare COLONPREDICT model with NICE
criteria, we used ROC curves and AUC to detect differences in overall diagnostic
OP319 REPEATED FIT SCREENING: THE INFLUENCE OF SUBJECTS accuracy and McNemar test to determine differences in sensitivity and specificity
CHARACTERISTICS AND SCREENING HISTORY ON THE for CRC detection.
POSITIVE PREDICTIVE VALUE AND NEOPLASIA YIELD RESULTS: Between March 2012 and September 2013, 1572 patients were
R. Sassatelli1, S. Crotta2, C. Senore3,*, C. Campari4, L. Paterlini4, C. Cerrato2, included and were valid for analysis. We detected 215 (13.7 %) CRC. The vari-
R. Lolli2, B. Dagnes2, N. Segnan3 ables included in the predictive model were age (years) (OR 1.04, 95% CI 1.02-
1
Gastroenterology, IRCCS Ospedale S Maria Nuova, Reggio Emilia, 1.06), sex (male) (OR 2.27, 95% CI 1.5-3.44), fecal hemoglobin 100ng/ml (OR
2
Gastroenterology, Ospedale Beauregard, Aosta, 3CPO Piemonte, AOU Citta` della 17.2, 95% CI 10.18-29.03), hemoglobin (5 10g/dL) (OR 4.76, 95% CI 2.19-
Salute e della Scienza, Torino, 4Centro Screening, AUSL Reggio Emilia, Reggio 10.37) (10-12g/dL) (OR 1.8, 95% CI 1.09-2.96), CEA ( 3ng/mL) (OR 4.52,
Emilia, Italy 95% CI 3-6.9), treatment with acetylsalicylic acid41 year (yes) (OR 0.42, 95%
Contact E-mail Address: carlo.senore@cpo.it CI 0.24-0.74), colonoscopy in the last 10 years (yes) (OR 0.12, 95% CI 0.06-0.25),
mass on digital rectal examination (yes) (OR 17.19, 95% CI 10.18-29.03), benign
INTRODUCTION: There is limited experience of colorectal cancer (CRC) anorectal disease (yes) (OR 0.27, 95% CI 0.17 to 0.44), rectal bleeding (yes) (OR
screening with fecal immunochemical tests (FIT) over several screening rounds. 2.27 95% CI 1.5-3.44) and change in bowel habits (yes) (OR 1.7, 95% CI 1.14-
AIMS & METHODS: To assess FIT screening performance among people per- 2.51). The AUC of COLONPREDICT model was 0.92 (95% CI 0.91 to 0.94),
forming consecutive tests in 3 population based programs in Italy and to explore significantly higher than the AUC of NICE criteria (AUC 0.59, 95% CI 0.55-
the impact of modulating positivity cuf-off to account for screenees character- 0.63; p 5 0.001). At a COLONPREDICT model cut-off with a 90% sensitivity
istics and screening history. The participating programs target people aged 50 to for CRC detection, the predictive model is statistically more sensitive (89.3 %,
74 (Aosta), 59 to 69 (Turin) and 50 to 69 (Reggio Emilia), offering single sample 67.9 %; p 5 0.001) and specific (79.3 %, 50.3 %; p 5 0.001) than the NICE
biennial FIT, with 100 ng haemoglobin (Hb)/ml buffer (20 g/mg faeces) posi- criteria.
tivity cut-off. We measured the positive predictive value (PPV), the number CONCLUSION: COLONPREDICT is a predictive model with high diagnostic
needed to scope (NNScope) and the detection rate (DR) for advanced adenoma accuracy for the detection of CRC in symptomatic patients. External validation
(AAd) and CRC, and the interval CRC (IC) rate (ICs x 10,000 subjects with is required for widespread use in the indication and priorization of colonoscopy.
negative FIT), among people aged 50 to 69. We simulated the impact of modu- Disclosure of Interest: None declared
lated positivity thresholds, accounting for age, gender and Hb level at previous
tests, among people undergoing their third screening.
RESULTS: The PPV, the NNScope and the DR for AAd and CRC, stratified by
subjects age at screening, are presented in table 1. The PPV for advanced neo-
plasia (AAd CRC) is higher among older people at the initial (p0.047), but
not at subsequent screening (p0.076). The DR is higher among men than
among women both at the initial and at subsequent tests. Setting the positivity
cut-off at 200 ng/ml for women with 0-49 ng Hb/ml at the 2 previous FITs, and
for men with no Hb at the initial FIT and 0-49 ng Hb/ml at the second FIT,
would result in a 26% reduction in the colonoscopy (TC) workload and in a 17%
A102 United European Gastroenterology Journal 2(5S)
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 RESULTS: Pre-operative biomarker assessment from EUS acquired specimens
GENETIC INFORMATION IN UPPER GI CANCER: ALREADY CLINICALLY RELEVANT? was possible in 92% (127/138) of patients. IHC stain for the biomarkers was
HALL L/M_____________________ positive in 59 (46%) patients and co-expressed 31 (56%) patients.
Pancreatectomy was performed in 28 (22%) patients. Overall median survival
OP321 A NOVEL TUMOR SUPPRESSOR MDGA2 ACTIVATES was 11 (5-16) months with patients who had (i) S100A2/A4 -ve PDAC on EUS (8
ANTI-TUMOR DMAP1/ATM/P53 PATHWAY AND IS AN vs. 20 months, P50.0001) and (ii) pancreatic resection (18 vs. 12 months,
INDEPENDENT PROGNOSTIC FACTOR IN GASTRIC CANCER P0.002) had a significantly better median survival. Of patients who had pan-
K. Wang1,*, Q. Liang1, X. Li1, H.T. Ho Tsoi1, E.S. Chu1, J. Shen1, M. Y. GO1, createctomy, patients with S100A2/A4 expressing PDAC had shorter survival
J.J. Sung1, J. Yu1 (12.0 vs. 22.0 months; P0.02). In the non-surgical treated patients, the presence
1
Institute of Digestive Disease and Department of Medicine and Therapeutics, of S100A2/A4 was also associated with poorer survival (7 vs. 19.9 months;
State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health P50001). Amongst patients with S100A2/A4 expressing PDAC, pancreatect-
Sciences, Shenzhen Research Institute, The Chinese University of Hong Kong, omy, however, led to a small survival benefit compared with those with non-
Hong Kong, Hong Kong surgical treatment (12 vs. 7 months, P0.03). Chemotherapy was given to 86
Contact E-mail Address: junyu@cuhk.edu.hk (68%) patients (3 neo-adjuvant, 17 adjuvant and 66 palliative). Amongst patients
who received palliative chemotherapy, patients who had S100A2/A4 expressing
INTRODUCTION: By using genome-wide promoter methylation screening PDAC had significantly poorer survival (7 vs. 22 months, P50.0001), and were
assay, we identified that MDGA2 (MAM domain containing glycosylphospha- similar to those who had no treatment (vs. 7months, P0.47).
tidylinositol anchor 2) was preferentially methylated in gastric cancer (GC). CONCLUSION: Biomarker assessment from EUS guided biopsy specimens is
However, the role of MDGA2 in tumorigenesis remains unexplored. feasible and successful in over 90% of cases. In patients with PDAC, the presence
AIMS & METHODS: This study aimed to elucidate the epigenetic regulation, of S100A2 and S100A4 expression predicts both survival, and influences the
clinical significance, biological function and molecular mechanism of MDGA2 in responses to both pancreatectomy and palliative chemotherapy. These findings
GC. Promoter methylation was evaluated by bisulfite genomic sequencing and support the potentially important role of pre-operative EUS guided biopsy for
combined bisulfite restriction analysis. Gene expression was examined by RT- biomarker determination and guide clinical decision-making, particularly with
PCR, western blot and immunohistochemistry. The biological functions of regard to selection for operative resection of PDAC.
MDGA2 were examined by MTS assay, colony formation, flowcytometry, Ki- Disclosure of Interest: None declared
67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
stainings in vitro and in vivo tumorigenicity analysis. The molecular mechanism
of MDGA2 was explored by promoter-luciferase activity assay, cDNA array, etc. WEDNESDAY, OCTOBER 22, 2014 8:3010:30
RESULTS: MDGA2 was silenced in 90.9% (10/11) GC cell lines, which was DIAGNOSIS AND TREATMENT OF CONSTIPATION AND FAECAL INCONTINENCE
closely related to promoter methylation. After treatment with demethylation HALL R_____________________
agent, expression of MDGA2 was restored in silenced GC cells. MDGA2 expres-
sion was also significantly lower in gastric tumors as compared to their adjacent OP323 THE BALLOON EXPULSION TEST: REPRODUCIBILITY AND
normal tissues (P0.001). Importantly, MDGA2 methylation was detected in AGREEMENT WITH RECTAL MANOMETRY AND PELVIC FLOOR
62.4% (136/218) of primary gastric tumors. Multivariate analysis revealed that EMG
MDGA2 methylation is an independent factor for poor survival in GC patients G. Chiarioni1,2,*, S.M. Kim2, W.E. Whitehead2
[P0.005, RR1.85 (1.21-2.84)]. Kaplan-Meier survival curves showed that 1
Gastroenterology, Azienda Ospedaliera Universitaria Integrata Verona,
MDGA2 methylation was signiEcantly associated with shorter survival of GC VERONA, Italy, 2UNC Center for Functional GI and Motility Disorders and
patients (1.59y vs. 4.87y, median; P0.001). Division of Gastroenterology and Hepatology, University of North Carolina at
We further tested the biological function of MDGA2. Re-expression of MDGA2 Chapel Hill, NC, Chapel Hill, NC, United States
in GC cell lines (AGS and BGC823) significantly suppressed cell viability, Contact E-mail Address: chiarioni@tin.it
reduced cell proliferation, inhibited clonogenicity, caused cell cycle arrest at G1
phase and induced cell apoptosis. On the other hand, knockdown of MDGA2 INTRODUCTION: The balloon evacuation test (BET) measures the time
promoted cell growth by accelerating cell cycle progress and reducing apoptosis required to evacuate a 50 ml water-filled balloon. We aimed to assess reprodu-
in MKN1 GC cells. In vivo growth of BGC823 GC cells was markedly inhibited cibility of the BET, determine the upper limit of normal, and assess concordance
by MDGA2 transfection in both subcutaneous (P50.001) and orthotopic with anorectal manometry (ARM) and pelvic floor surface electromyography
(P50.001) xenograft models in nude mice. (EMG).
The molecular mechanisms of the tumor suppressive effect of MDGA2 were AIMS & METHODS: BET was tested in 286 chronically constipated patients
further characterized. We demonstrated that MDGA2 activated p53 pathway before and after 30-days of conservative treatment at a tertiary gastroenterology
by p53-luciferase reporter assay. In keeping with this, downstream mediators clinic in Italy. BET was performed with a 16 FR Foley catheter filled with 50 ml
of p53 signaling were also upregulated by MDGA2, including p63, p73, caspase of tepid water. Up to five minutes were allowed to evacuate the balloon while
9, p21 and ATM. Moreover, MDGA2 directly upregulated and binded to sitting on a conventional toilet in a private bathroom. BET was tested twice, 7-
DMAP1 (an essential regulator of ATM activity) as evidenced by mass spectro- days apart, in 40 healthy controls recruited among hospital personnel and Med
metry analysis of immunoprecipitation products and pull-down assays using students. The 238 constipated patients who did not respond to conservative
MDGA2 and DMAP1 recombinant proteins. MDGA2-DMAP1 subsequently therapy (increased fluids and fiber, laxatives no more than twice a week) received
activated ATM and p53, followed by upregulation/activation of p53 signaling an ARM, EMG, and digital rectal examination (DRE). Forty-seven patients with
mediators. Activating of DMAP1/ATM/p53 signaling pathway contributes to conflicting ARM and BET results received defecography.
the suppression of tumor growth in gastric cancer. RESULTS: Patients averaged 44 years and 91% were females; controls averaged
CONCLUSION: MDGA2 is a novel tumor suppressor inactivated by promoter 38 years and 92% were females. Balloon evacuation was achieved within 1 min
methylation in gastric cancer. MDGA2 methylation is significantly associated by 37/40 healthy controls, but 3 (8%) required 1-2 minutes. In constipated
with shorter survival of GC patients. MDGA2 exhibits tumor suppressive effect patients, 148/286 passed the balloon within 5 minutes including 110 in 1
by directly upregulating DMAP1 to stimulate ATM/p53 signaling pathway. minute, 35 in 1-2 minutes, and 3 in 2-5 minutes. BET showed perfect reprodu-
Disclosure of Interest: None declared cibility in 280/286 (98%) constipated patients when a BET interval over two
minutes is defined as abnormal. Agreement between BET and ARM for dyssy-
nergia was 78% and agreement between BET and EMG was 83%. In 32 patients,
OP322 BIOMARKER ASSESSMENT FROM EUS GUIDED BIOPSY BET was abnormal but ARM was normal, and 31 of these cases showed inade-
PREDICTS OUTCOMES AND TREATMENT IN PANCREATIC quate straining (n11) or anatomical defects which might explain failed BET
CANCER (n20).
N.Q. Nguyen1,*, A. Ruzskiewicz2, D. Chang3, C.-P. Tan4, J. Bambrick1, CONCLUSION: The optimal upper limit of normal for the BET is two minutes.
A. Biankin5 Test re-test reproducibility is excellent (98%). The BET shows good agreement
1
Department of Gastroenterology & Hepatology, 2Department of Pathology, Royal with ARM and EMG. A normal BET almost rule out a disordered defecation
Adelaide Hospital, Adelaide, 3Pancreatic Research Group, Garvan Institute, syndrome.
Darlinghurst, 4Department of Surgery, Royal Adelaide Hospital, 5Pancreatic Disclosure of Interest: None declared
Research Group, Garvan Institute, Adelaide, Australia
Contact E-mail Address: quocnam.nguyen@health.sa.gov.au
OP324 ENDOFLIP: A NEW DIAGNOSTIC MODALITY FOR
INTRODUCTION: Current methods of pre-operative predicting outcome of MEASURING ANAL CANAL FUNCTION
pancreatic cancer and related pancreatectomy are limited. Although several prog- L. Kumar1,*, F. Zaman1, A. Emmanuel1
nostic biomarkers, including S100A2 and S100A4, are associated with poor out- 1
GI Physiology Unit, UCLH, London, United Kingdom
come, currently these can only be assessed in operatively resected specimens. The
amount of tissue from EUS guided fine needle aspiration is often insufficient for INTRODUCTION: Anorectal manometry is the most well established and com-
biomarker assessment. Procore needles aim to acquire larger volumes of tissue monly used technique for investigating anorectal function but despite its wide-
that may be suitable for pre-operative biomarker assessment. spread use, it has well established limitations. Functional Lumen Imaging Probe
AIMS & METHODS: (i) To evaluated the feasibility of S100A2 and S100A4 (FLIP) is a novel technique for measuring anorectal function. Its repeatability
assessment in EUS guided biopsy specimens using the Procore needle, and (ii) to and validity of in anorectal studies has already been established. This study
evaluate the relationship of these biomarkers with outcomes. METHODS: looked at its utility in establishing dynamic properties of anal canal with and
Clinico-pathological, treatment and survival data from 138 patients (702yrs; without rectal distension, in particular to demonstrate the sampling reflex, the
70M:68F) with pancreatic ductal adenocarcinoma (PDAC) were prospectively poorly understood physiological mechanism of which remains uncertain.
acquired. All subjects had EUS guided biopsy with a 22G Procore needle and AIMS & METHODS: To establish dynamic and non-homogenous properties of
cell-block preparation was performed. Sections of cell-block material were the anal canal in healthy volunteers using EndoFLIP. Demonstrate the segmental
assessed for S100A2 and S100A4 protein expression using immunohistochemistry differences in anal canal. Methods: 19 healthy volunteers were recruited (9
(IHC). females), mean age 34 (20-75). Purpose built catheters incorporating rectal and
United European Gastroenterology Journal 2(5S) A103
anal canal balloon were used. Appropriate sized catheter anal canal balloon (2, 3 Ret9-GFP. Here, the percentage of neurons changed from 5.451.4% in miRet51
and 4cm long) corresponding to the length of subjects anal canal (based on to 17.34.4% in miRet51;Ret9 EPCs versus 21.63.5% in control EPCs; p0.06.
manometry) was used. 3 cross sectional area (CSA) readings were obtained CONCLUSION: Our results indicate that expression of both RET isoforms,
with 2cm balloon, 5 with 3cm and 10 with 4cm balloon. In order to obtain which underpins normal RET activity, is required for the migration, proliferation
meaningful results, the anal canal balloon was required to be touching the and differentiation of NCC ultimately leading to the formation of a functional
lumen wall and this was achieved by using different inflation volumes, according ENS. EPCs from miRet51 animals can be isolated and most importantly, the
to the balloon size, determined by analysing the pre-study test results. Rectoanal neuronal differentiation deficit in these cells restored by introducing the Ret9
inhibition reflex (RAIR) was recorded by inflating the rectal balloon while isoform into miRet51 cells. The isolation of EPCs and the ability to manipulate
recording the anal canal CSAs with the anal canal balloon. Participants under- and rescue key HSCR genes such as RET paves the way for generating novel
went standard water-perfused anal manometry followed by FLIP on the same therapies for gut motility disorders.
day. The anal canal was divided into distal, mid and proximal parts based on Disclosure of Interest: None declared
anatomy and preliminary data analysis. Paired t-test was done comparing CSA in
the following segments (across all the balloon volumes), distal with mid anal
canal, mid with proximal anal canal and distal with upper anal canal. The para- OP326 LIBERTAS: A MULTICENTRE, PHASE II, DOUBLE BLIND,
meters looked at included CSA at rest, squeeze and during RAIR. RANDOMISED, PLACEBO CONTROLLED INVESTIGATION TO
RESULTS: Statistically significant difference was noted in between CSAs of the EVALUATE THE EFFICACY, SAFETY AND TOLERABILITY OF
three segments both at rest and squeeze (Table 1). In all the three phases of rest, LOCALLY APPLIED NRL001 IN PATIENTS WITH FAECAL
squeeze and RAIR, distal segment had the lowest mean CSA followed by mid INCONTINENCE
and proximal segment respectively (Table 1). Analysis of RAIR revealed a sig- D.G. Walker1,*, D. Jones1, J. Pilot1, R. Ng Kwet Shing1
nificant difference in CSAs between proximal and distal segments (p 5.0001) 1
Norgine Limited, Uxbridge, United Kingdom
but not between mid and the proximal segments (p .351). Contact E-mail Address: DWalker@norgine.com
Segmental cross sectional areas INTRODUCTION: Faecal incontinence (FI) affects up to 8% of the general
population, rising to c.50% among nursing home residents. FI is under-reported
Rest Squeeze RAIR and can have devastating effects on quality of life (QoL). Although non placebo-
Mean CSA Mean CSA Mean CSA controlled studies have shown a reduction in Wexner score, FI episodes and the
Anal Canal Segment (in mm)(SD) (in mm)(SD) (in mm)(SD) FIQOL, little is available to inform appropriate management strategies as few
well-designed, placebo-controlled clinical trials of FI treatment have been
Distal 13.27 (3.19) 12.04 (2.55) 12.37 (3.38) conducted.
Mid 15.25 (3.37) 14.40 (3.14) 13.85 (3.88) AIMS & METHODS: The aim of Libertas, a robustly-designed, multicentre,
Proximal 15.44 (3.97) 15.18 (3.96) 14.03 (4.14) Phase II, double-blind, randomised, placebo-controlled, parallel-group study
p values for intra-segmental comparison of CSA was to investigate the efficacy and safety of 1-adrenoceptor agonist NRL001
Measured phase Distal - M id M id - Proximal Distal - Proximal (1R,2S-methoxamine hydrochloride) in the treatment of non-retentive FI
Resting .000 .013 .000 (ClinicalTrials.gov: NCT01656720). Patient recruitment was across 55
Squeeze .023 .000 .000 European study centres. Patients with FI were randomised into four groups
(approximately n110 each) to receive once-daily self-administered doses of
NRL001 (5mg, 7.5mg, 10mg or placebo suppositories) for 8 weeks. Libertas
primary objective was to assess the impact of NRL001 versus placebo on severity
CONCLUSION: EndoFLIP allows detailed segmental description of the anal and frequency of FI episodes (Wexner scores) at 4 weeks. Key secondary out-
canal. CSA differences in three segments of anal canal clearly reveal its dynamic comes for NRL001 versus placebo include: efficacy at 8 weeks (Wexner score and
nature. The distal-most part of anal canal has the lowest distension followed by FI episodes); safety and tolerability; quality of life (FIQoL) following 4 and 8
mid and proximal part, both at rest and squeeze. This segmental difference in the weeks therapy; and overall patient satisfaction with the treatment.
anal profile demonstrates the anatomical and physiological basis of the sampling RESULTS: Patients (n466) were randomised evenly into each of the 4 arms.
reflex. Patient demographics were broadly similar in each group: 84% female, mean age
Disclosure of Interest: None declared 62 (range 19-91) years, mean study entry score ranged from 12.9 to 13.3 points on
the Wexner score. There was a 2.4-3.0 point reduction from baseline in Wexner
score at Week 4 in all four arms with a non-significant treatment effect
OP325 EXPLORING THE POTENTIAL OF GENE THERAPY FOR (p0.6867). There was a 3.1-3.6 point reduction from baseline in Wexner score
HIRSCHSPRUNG DISEASE: STUDIES IN THE MIRET51 MOUSE at Week 8 in all four arms with a non-significant treatment effect (p0.5005).
MODEL There was a reduction in FI episodes of between 4.8-7.3 episodes per week at
D. Natarajan1,2,*, J. Dattani3, A.J. Burns1, N. Thapar1,4, V. Pachnis2 Week 8 with a non-significant treatment effect (p0.5278). NRL001 tolerability
1
UCL Institute of Child Health, 2National Institute for Medical Research, London, profile in each of the active treatment arms was comparable to placebo. A similar
3
Department of Mathematics, University of Bath, Bath, 4Great Ormond Street increase in FIQOL was seen at week 8 in each arm. Patient satisfaction was high
Hospital, London, United Kingdom in all arms; 74.7-85.6% of patients would choose to take a suppository of either
Contact E-mail Address: d.natarajan@ucl.ac.uk NRL001 or placebo again.
CONCLUSION: Although NRL001 was safe and effective with improvements in
INTRODUCTION: Hirschsprung disease (HSCR) affects 1:4500 births and is both clinical outcome scores and QoL at the end of 8 weeks treatment compared
characterized by aganglionosis of the distal bowel, caused by a failure of devel- with baseline, this improvement was also observed in the placebo arm. This
opment of the enteric nervous system (ENS) from neural crest cells (NCC). The outcome is of interest to the scientific community in that it demonstrates for
RET receptor tyrosine kinase is part of a key signalling pathway for ENS devel- the first time in a robust study design that there is a significant placebo response
opment and is implicated in the majority of HSCR cases. In mice and humans, in this patient population that should be considered in all future study designs
RET is expressed as two main isoforms, Ret51 and Ret9. Mice expressing only the investigating FI.
Ret51 isoform (monoisoformic-miRet51) have distal colon aganglionosis and are Disclosure of Interest: D. Walker Other: Employee of Norgine, D. Jones Other:
an established model of human HSCR. Employee of Norgine, J. Pilot Other: Employee of Norgine, R. Ng Kwet Shing
AIMS & METHODS: (i) Characterise ENS development in miRet51 mice in Other: Employee of Norgine
terms of NCC migration, proliferation and neuronal differentiation by lineage
tracing with YFP. (ii) Label and isolate ENS progenitor cells (EPCs) from
miRet51 and wild type animals using a GFP retroviral vector. (iii) Perform genetic OP327 PRELIMINARY SIGNIFICANT FINDINGS FROM A
rescue of miRet51 EPCs by infecting with a retrovirus carrying a Ret9-GFP RANDOMISED CONTROL TRIAL OF POSTERIOR TIBIAL NERVE
cassette. STIMULATION IN SYSTEMIC SCLEROSIS ASSOCIATED FAECAL
To label all NCC with YFP, miRet51 mice were crossed with INCONTINENCE
Rosa26YFPstopWnt1cre mice. Immunolabelling of whole guts and sections of S.K. Butt1,*, A. Alam1, A. Raeburn1, J. Liwanag1, V. H. Ong2, C.P. Denton2,
embryos from miRet51 and control littermates was performed using GFP (to C.D. Murray3, N. Zarate-Lopez1, A. Emmanuel1
identify YFP cells) plus antibodies to investigate migration, proliferation 1
Gastroenterology, UCLH, 2Rheumatology, 3Gastroenterology, Royal Free
(BrdU) and neuronal differentiation (HuC/D). To generate EPCs, cells were Hospital, London, United Kingdom
infected with a GFP retroviral vector and positive cells were isolated via fluor- Contact E-mail Address: s.butt@ucl.ac.uk
escent activated cell sorting (FACS). To rescue the miRet51 defect, cells from
miRet51 gut were infected with a Ret9-GFP retrovirus and neuronal differentia- INTRODUCTION: The gastrointestinal tract is affected in up to 90% of
tion studied. Systemic Sclerosis (SSc) patients with faecal incontinence (FI) being reported
RESULTS: Migration of NCC in miRet51 guts was impaired compared to con- in up to 38%. Passive faecal incontinence secondary to internal anal sphincter
trols at all stages in development as determined by immunolabelling of whole gut atrophy is the characteristic finding. We have shown that neuropathic changes
and embryo sections. Proliferation was reduced in miRet51 cells compared to are implicated in SSc patients with FI and sacral nerve stimulation has emerged
control littermates both in vitro and in vivo. At E10.5, 6.80.9% miRet51 cells as a potentially beneficial therapy in SSc. However this is expensive, invasive, not
divided versus 19.050.9% in controls; p50.05. At E14.5, proliferation was widely available and we have shown that medium term efficacy is poor. Posterior
13.953.51% in miRet51 cells versus 25.53.78% in controls; n6, p50.05. tibial nerve stimulation (PTNS) is a potential alternative to modulate the sacral
Neuronal differentiation and axonal outgrowth, in vivo, was reduced throughout plexus indirectly, with none of these disadvantages. This is the preliminary data
development. At E18.5, 17.94% of YFP cells were positive for HuC/D in on a randomized placebo controlled trial of PTNS versus sham PTNS to deter-
miRet51 versus 36.110% in control embryos; n4, p50.05. EPCs isolated from mine if nerve modulation is an effective treatment in SSc associated FI.
miRet51 guts also displayed reduced neuronal differentiation in vitro compared to AIMS & METHODS: We commenced a prospective randomised single-blind
controls (5.451.4% in miRet51 and 16.94.7% in controls; p50.05). This def- study of SSc patients with FI in February 2013 from a specialist Scleroderma
icit was rescued when miRet51 EPCs were infected with a retrovirus expressing unit. Baseline symptom scoring (bowel diary, Wexner), manometry and endoanal
A104 United European Gastroenterology Journal 2(5S)
ultrasound were completed prior to randomization to PTNS or sham. PTNS was OP329 COMPARISON OF THE EFFECT OF POLYETHYLENE GLYCOL
administered conventionally, by insertion of an acupuncture needle according to 3350, PRUCALOPRIDE, BISACODYL AND PLACEBO ON COLONIC
anatomical landmarks, connected to an electrical stimulator. Sham PTNS was MOTILITY ASSESSED WITH INTRALUMINAL COLONIC HIGH-
administered in identical fashion but the PTNS surface electrode was not con- RESOLUTION MANOMETRY IN HEALTHY SUBJECTS: THE
nected and instead separate TENS surface electrodes were connected to a TENS QUANTITATIVE ANALYSIS
unit. Each patient underwent blinded intervention for 30 minute periods, once a M. Corsetti1,*, G. Pagliaro1, E. Deloose1, I. Demedts1, A. Gevers1, L.
week for 12 weeks. The primary endpoints were the percentage reduction in Van Oudenhove1, J. Tack1
faecal incontinence episodes and change in Wexner incontinence scores. 1
TARGID, KULEUVEN, Leuven, Belgium
RESULTS: A total of 13 SSc patients (11 f), mean age 61 (36-72) completed the Contact E-mail Address: maura.corsetti@med.kuleuven.be
trial by October 2013. Of these 6 (5 f) underwent PTNS and 7 (6 f) patients
underwent sham stimulation. All PTNS patients showed a reduction (5-100%) INTRODUCTION: PEG, bisacodyl and prucalopride were demonstrated to be
in the number of FI episodes in comparison to 0 sham patients at 12 weeks superior to placebo for treatment of chronic constipation (Ford AC 2011).
(p50.01 (CI -81.49-14.34)). This matched an improvement in mean Wexner Impaired colonic propulsive motility is considered a major pathophysiological
scores from baseline to treatment end (14.8 to 10.8 vs 13.4 to 13.6, true vs mechanism underlying constipation. The effect of these treatments on colonic
sham respectively, p0.03. motility has never been directly compared.
CONCLUSION: This pilot data is demonstrating significant effects of PTNS in AIMS & METHODS: To compare the effect of PEG, prucalopride, bisacodyl
Scleroderma-associated FI. We present this significant initial data but anticipate and placebo on colonic motility and on number of high amplitude contractions
having at least 25 completed patients by October 2014. (HAPCs) assessed with high resolution manometry (HRM).
Disclosure of Interest: None declared In 10 volunteers (293 ys) four colonic HRM studies were performed, at least 10
days apart, after an overnight fast and tap water enema preparation. During
colonoscopy under conscious sedation the HRM catheter (40 solid state sensors,
OP328 TREATMENT OF SLOW-TRANSIT CONSTIPATION (STC) IN 2.5 cm spaced) was advanced as far as possible and clipped to the mucosa. After
CHILDREN WITH HOME-BASED TRANSCUTANEOUS 90 min of basal recording, PEG 13.8 mg, prucalopride 2 mg, bisacodyl 10 mg or
ELECTRICAL STIMULATION (TES) placebo were administered orally in a single-blind, randomized, cross-over fash-
B.R. Southwell1,2,*, Y.-I. Yik2,3, J. Jordan-Ely1, K. Dobson1, J.M. Hutson1,4 ion, and the recording continued for 180 min before and after a standardized
1
Surgical Research, Murdoch Childrens Res Inst, 2Dept Paediatrics, University of meal. During the meal, in case of PEG, a second dose (13.8 mg) was adminis-
Melbourne, Melbourne, Australia, 3Department of General Surgery Faculty of tered. Colonic motility index (MI; averaged every 15 min in the right and left
Medicine, University of Malaya, Kuala Lumpur, Malaysia, 4Dept of Urology, colon and in the rectum, and expressed as ratio of the baseline value) of four
Royal Childrens Hospital, Melbourne, Australia periods (180 minutes before meal, first, second and third hour after the meal) was
Contact E-mail Address: Bridget.southwell@mcri.edu.au compared between treatments by means of a mixed models analysis with post-
hoc t-tests and Bonferroni correction. The characteristics of HAPCs were com-
INTRODUCTION: Slow-transit constipation (STC) is generally resistant to pared by means of Students t test. Data are meanSEM.
medical treatments. We have shown that transcutaneous electrical stimulation RESULTS: The catheter was clipped to the right colon mucosa in 23/40 studies,
(TES) using interferential current given by physiotherapists, sped up colonic and at least to the splenic flexure in the remaining cases, with no difference
transit 1, reduced soiling 2 and increased defecation 3. Battery-operated machines according to treatment arm. Baseline MI did not differ between treatments in
allow stimulation at home 3. the right (2.60.36 for PEG, 3.60.72 for prucalopride, 3.60.87 for bisacodyl,
AIMS & METHODS: To determine if TES administered at home can improve 3.90.26 for placebo, NS), left colon (2.70.49, 3.60.49, 3.20.74, 3.60.41,
STC in children. We tested 2 types of treatment. Group 1) if TES added onto NS) and rectum (2.70.53, 4.10.79, 3.20.81, 3.80.50, NS). At mixed models
existing treatment and administered daily at home can improve defecation, soil- analysis, a significant treatment effect was found in each region of the colon (all
ing, abdominal pain and laxative use in STC children. Group 2) if TES combined P0.001). In the right colon, the ratio of the baseline value was significantly
with selected laxatives and bowel education was more effective than TES alone. higher after PEG (P0.01) and borderline significant after prucalopride
Children with treatmentresistant constipation with no palpable faecaloma who (P0.05) as compared to placebo for all the time points after the meal. In the
presented to a surgical unit at a tertiary childrens hospital were sent for radio- left colon, the ratio was significantly higher after PEG than placebo for all the
nuclear colonic transit study 4. Children with slow motility in the proximal colon time points after meal (P0.01). In the rectum, the ratio was significantly higher
were diagnosed with STC. Parents were trained to give TES. Four sticky electro- after PEG than placebo during the first hour after meal (P0.01). Bisacodyl
des (4cm x 4cm) were placed, 2 on the belly and 2 on the back at the umbilical induced HAPCs in a significantly higher number of subjects as compared to
level and connected so currents crossed right front to left back and left front to prucalopride (9 vs. 3, Fishers exact test P 0.01), PEG (9 vs. 1, P0.001) and
right back. A beating interferential current (4kHz carrier frequency, 80-160Hz placebo (9 vs 1, P 0.001). The amplitude of HAPCs was significantly higher
beat frequency, 30mAmps3) was given 1 hr/day. Daily continence diaries and after prucalopride than bisacodyl (29214 vs 20012 mm Hg, P 0.01) while
laxative use were recorded for 1 mth before and during TES. Defecation, soiling duration, length and velocity did not differ between treatments.
and laxative use were compared before (pre) and after 2-6 mth stimulation (post). CONCLUSION: In man, PEG, prucalopride and bisacodyl have distinct effects
In Group 1, 62 children (23 male; 2-16yrs) had TES added onto existing laxatives. on colonic phasic activity. While PEG mainly increases phasic activity, bisacodyl
In Group 2, 33 children (17 males, 4-16yrs) were educated on diet and water mainly induces HAPCs. Prucalopride has no major effect on colonic phasic
intake, best time for toileting and correct toilet posture, transferred to low doses activity but increases HAPCs amplitude.
of polyethylene glycol (PEG) and sodium picosulphate laxatives, then had TES Disclosure of Interest: None declared
for 2-3mths.
RESULTS: Gr 1: At the start, 56/62 had 5 3 bowel actions (BA)/wk. 6/62
children (10%) had no improvement. Defecation frequency increased in 54/56 OP330 ENTERIC NEUROPROTECTION IN HUMAN NEURONS:
from 1.61.6 to 3.51.9 BA/wk, meanSD, p50.05) with 32/54 (59%) patients EFFECTS MEDIATED BY PRUCALOPRIDE, A SEROTONINERGIC
increased 3 BA/wk). Soiling reduced in 56/57 (4.62.4 to 0.71.1 days soiling/ FULL 5-HT4 SELECTIVE AGONIST
wk, p50.001). Urge to defecate started as nil or weak and developed to moder- F. Bianco1,*, E. Bonora1, M. Vargiolu1, F. Giancola1, N. Thapar2,
ate/strong in half. Laxative use reduced (15/60 (25%) stopped & 30/60 (50%) D. Natarajan2, V. Stanghellini1, M. Seri1, R. De Giorgio1
reduced). Gr 2: All started with 53 BA/week. 32/33 (97%) increased to 43 BA/ 1
DIMEC, University of Bologna, BOLOGNA, Italy, 2Dept of Neurosciences &
wk with 29/33 (88%) to 7 BA/wk. Stool output improved from 1 (0-2) cups/wk to Mental Health, UCL Institute of Child Health, London, United Kingdom
7 (2-10) cups/wk (p50.001). Mean number of soiling episodes decreased from 5 Contact E-mail Address: franc.bianco19@gmail.com
to 0 episodes/wk (p50.001).
CONCLUSION: TES is a painless non invasive treatment and can be adminis- INTRODUCTION: Serotonin (5-hydroxytryptamine, 5-HT) and related trans-
tered at home. In treatment-resistant patients presenting to a surgeon, home- porters and receptors are involved in a wide array of digestive functions and
based TES added onto existing treatment increased defecation into the normal disorders. Specifically, 5-HT4 receptors play a major role in intestinal peristalsis
range in half. With the addition of selected oral laxatives and education on diet and among agonists, prucalopride (a full 5-HT4 agonist) is an effective entero-
and toileting prior to TES improvement occurred in more patients, was bigger kinetic agent in the treatment of chronic constipation. In addition, 5-HT4 recep-
improvement and was more rapid than with TES alone. tor agonists may evoke enteric neuroprotection. We tested whether prucalopride
REFERENCES exerts protective effects on enteric neuron cell cultures exposed to damaging
1. Clarke MC, et al. J Pediatr Surg 2009; 44: 408-412. factors, i.e. oxidative agents e.g. H2O2. Specifically, we aimed to: i) evaluate
2. Leong LC, et al. J Pediatr Surg 2011; 46: 2309-2312. the expression and selective identification of 5-HT4 receptors in human enteric
3. Ismail KA, et al. J Pediatr Surg 2009; 44: 2388-2392. neurons; and ii) define the 5-HT4 receptor-mediated neuroprotection in human
4. Sutcliffe JR, et al. Pediatr Surg Int 2009; 25: 465-472. cell cultures by assessing the anti-apoptotic effect exerted by different doses of
Disclosure of Interest: B. Southwell Consultancy for: GI Therapies, Other: prucalopride.
Product supplied with no restrictionsby Norgine, Inventor of new TES device AIMS & METHODS: Human enteric neurospheres were generated from human
to treat constipation in development by GI Therapies, Y.-I. Yik: none, J. Jordan- gut tissue*; cells from neurospheres were seeded onto 35-mm Petri dishes coated
Ely: none, K. Dobson: none, J. Hutson Other: Inventor of new TES device to with fibronectin (2 mg/cm2) and maintained in Dulbeccos modified Eagle
treat constipation in development by GI Therapies medium (DMEM)/F-12 medium. Western blotting (WB) analysis were per-
formed using the following primary antibodies: anti-5-HT4 receptor (Abcam,
1:200), anti-HuC/D (Invitrogen, 1:200; a paneuronal marker), anti p75_NTR
(Thermoscientific, 1:200) and anti-vinculin (Sigma-Aldrich, 1:50.000). In addi-
tion to neurosphere-derived cells, the expression of the 5HT4 receptor was also
evaluated in the following cell lines: human embryonic kidney (HEK293); mouse
neural crest-derived N2A; and human neuroblastoma cell line (SH-SY5Y).
SulfoRhodamine B (SRB) assay was used to determine the neuronal survival
of SH-SY5Y cells following H2O2 (200 mM for 30 min) exposure and the neuro-
protective effect exerted by prucalopride on these cells. GR 113808 (10 nM for 30
United European Gastroenterology Journal 2(5S) A105
min) was applied to SH-SY5Y cells to reverse the protective effect of depressed type, which has a higher potential for invasion and requires a precise
prucalopride. histological evaluation (GIE 2007;66:966). ESD is technically more demanding
RESULTS: WB analysis demonstrated that all cell lines as well as cells from and has a relatively high complication rate; EMR is limited by its inability to
human neurospheres expressed the 5HT4 receptor. SRB assay showed that SH- achieve en-bloc resection. Hybrid resection techniques (ESD with snaring, EMR
SY5Y cells previously exposed to prucalopride at different concentrations (10, after circumferential pre-cutting or small incision) have been introduced to make
100 pM; 1, 10 and 100 nM; 100 mM; 1 and 20 mM) were protected by the noxious ESD and EMR easier, safer and quicker (DDS 2013;58:1727).
effect induced by H2O2. Specifically, prucalopride at 10 pM to 1 nM concentra- AIMS & METHODS: To perform the first meta-analysis on colorectal ESD-
tions exhibited the best neuroprotective effect compared to neurons exposed to EMR to assess their impact on their safety and effectiveness in removing color-
H2O2 only (476.50.1% of neuronal survival vs. 33.30.1%, respectively) ectal LST 20 mm. Medline, PubMed, and Google searches (June 2009-October
(P50.05). Prucalopride concentrations applied alone to SH-SY5Y neurons did 2013) were considered to identify appropriate RCTs that compared ESD with
not show any toxicity and resulted in 910.1% of neuronal survival. In contrast, EMR for colorectal LST 20 mm. Keywords were: ESD, EMR, colorectal
the neuroprotective effect of prucalopride was reversed by the 5-HT4 antagonists tumors, LST. Reviews, case reports and abstracts were excluded. The existence
GR 113808 (10nM for 30 min). of noninvasive pattern, determined by magnification chromoendoscopy, was the
CONCLUSION: Prucalopride, a 5-HT4 receptor full agonist, mediated signifi- minimum requirement for all lesions candidates for ESD and EMR. Primary
cant neuroprotection against oxidative-mediated proapoptotic effects. These end-points were en bloc resection rate, curative resection rate and local recur-
results may pave the way to novel application of 5-HT4 agonists as neuroprotec- rence. Secondary end-points: rate of bleeding and perforation. Fixed or random-
tive agents in enteric neuropathies. effect models were used as appropriate based on homogeneity or heterogeneity of
REFERENCES data according to I2 statistic.
Metzger et al. Gastroenterol 2009 RESULTS: 8 studies (7 retrospective and 1 prospective) were identified. Data are
Disclosure of Interest: None declared expressed as odds ratio (OR) and 95% confidence interval (CI) [95% CI]. A total
of 4023 lesions were found: 2104 were treated by ESD, 1919 by EMR, respec-
tively. The tumor size was significantly larger in the ESD group (30.65mm vs
OP331 INTEREST IN A MORPHOLOGICAL EVALUATION OF 243.1 mm, p50.05). The ESD group had a significantly higher proportion of
INTERSTITIAL CELLS OF CAJAL (ICC) IN PATIENTS WITH NG-LST (38.0% vs 27.3%, p50.001). Adenocarcinomas-sm1 were more fre-
SEVERE COLONIC INERTIA (SCI) REQUIRING SUBTOTAL quent in the ESD group than in the EMR group (18.3% vs 9.2%, p50.001).
COLECTOMY. A CASE-CONTROL STUDY ESD was associated with a longer procedure time (8933 min vs 227 min,
M. Cohen1,*, D. Cazals Hatem2, B. Coffin3 p50.001). Meta-analysis confirmed that, compared to EMR, ESD achieved
1
Gastroenterology, AP HP Hopital Louis Mourier, Colombes, 2Pathology, Hopital higher en bloc resection OR 9.77 [7.9-12.0], curative resection OR 2.04 [1.6-
Beaujon, Clichy, 3Gastroenterology, APHP Hopital Louis Mourier, Colombes, 2.57], and lower local recurrence irrespective of lesion size OR 0.08 [0.04-0.18].
France ESD had higher number of perforations OR 3.6 [2.19-5.93]. Bleeding was similar
Contact E-mail Address: benoit.coffin@lmr.aphp.fr between the two groups: OR 1.15 [0.73-1.81].
CONCLUSION: The current meta-analysis shows that ESD has considerable
INTRODUCTION: Subtotal colectomy is the last resort treatment in patients advantages regarding en bloc resection rate, curative resection rate and absence
with SCI refractory to a well-conducted and optimized treatment. In this condi- of local recurrence, at the expense of a higher perforation rate and longer pro-
tion, some studies reported an ICC hypoplasia by using a semi-quantitative cedure time. ESD appeared to be an effective and safe procedure, at least in
analysis. The aims of this case-control study were (1) to determine the best expert hands, for lesions otherwise difficult to be radically treated with snare-
technique to quantify colonic ICC, (2) to search a relationship between the based endoscopic resection techniques. Better ESD standardization and a more
number of ICC and the severity of constipation and (3) to evaluate functional widespread and systematic implementation in Western countries are required.
results 1-year after colectomy Disclosure of Interest: None declared
AIMS & METHODS: Clinical and pathological data from patients with SCI
having colectomy with ileo-rectal anastomosis in 3 academic hospitals have been
collected. Quantification of ICC immunostained with CD117 was performed in 3 OP333 WHICH IS THE STRONGEST PREDICTOR TO MOVE FROM
colonic segments in patients and in sex and age matched controls by 2 indepen- ESD TO PIECEMEAL EMR (PEMR) WHEN EN BLOC RESECTION
dent observers using a semi-quantitative technique (muscularis propria on ten CANNOT BE COMPLETED?
high power field (HPF)) according to Wang et al, followed by a morphometric J.C. Mar n-Gabriel1,*, J. D az-Tasende1, P. Cancelas Navia1, S. Rodr guez-
quantitative technique (% of ICC/10 HPF). ICC hypoplasia was defined as 57 Munoz1, A.J. Del Pozo-Garc a1, A. Gonzalez-Blanco1, P. Hernan-Ocana1,
ICC/HPF using Wang et al method or as a mean percentage of ICC 5 1 % using M. Perez-Carreras1, M. Alonso-Riano2, F. Colina-Ruizdelgado2, A. Dom nguez-
morphometry. Functional results were evaluated 1-year after colectomy. Rodr guez1, G. Castellano-Tortajada3
RESULTS: Over a 10-year period, 20 patients (female: 85 %; mean age: 46.2 1
Department of Gastroenterology. Endoscopy Unit., 2Department of
11.6 years) had a colectomy for SCI. Constipation had been present since child- Histopathology, 3Department of Gastroenterology., Hospital Universitario 12 de
hood or adolescence in 76.4 % of patients. Mean number of stool was 0.9 0.4/ Octubre, Madrid, Spain
week with optimized treatment and 45 % of patients have been hospitalized at Contact E-mail Address: josecarlos.marin@salud.madrid.org
least once for colonic occlusion related to fecaloma. All patients were in opti-
mized treatment failure. Mean colonic transit time (CTT) was 128.2 11.6 h, INTRODUCTION: Endoscopic submucosal dissection (ESD) allows en bloc
ano-rectal manometry did not show megarectum and small bowel manometry resection of gastrointestinal tumors regardless of their size. However, a high
was normal in all patients. According to Wang et al method, 30 % of patients (n level of expertise is needed in the early learning curve to perform en bloc resection
6) display ICC hypoplasia and all controls had normal ICC. Using morpho- by ESD and piecemeal endoscopic mucosal resection (pEMR) is frequently
metry, the percentage of colonic ICC was significantly decreased in patients vs. needed to complete the resection.
controls (1.04 0.16 % vs. 1.97% 0.21 %; P 0.005) with no differences AIMS & METHODS: To analyse the factors associated with changing the initi-
between the 3 colonic segments (P 0.25) and 60 % of patients (n12) had ICC ally planned ESD to pEMR in a clinical practice setting where 5 100 procedures
hypoplasia 5 1% vs. 20 % (n 4) of controls (P 0.009). ICC hypoplasia was have been performed. We included prospectively the first 85 ESDs performed in
not significantly associated with CTT or occlusion related to fecaloma. After a our hospital, from September 2008 to April 2014. All ESD procedures were
one-year follow-up, 17 patients (85 %) were satisfied with at least 1 stool/d, and 3 performed by two teams with 2 endoscopists in each one (A-team: J.C.M.G. &
still had constipation. J.D.T.; and B-team: S.R.M. & A.P.G.) in equal numbers. We recorded charac-
CONCLUSION: In patients with severe colonic inertia requiring surgery, mor- teristics of the lesions and the procedure to predict the need for pEMR to com-
phometric analysis is more sensitive than semi-quantitative analysis to detect a plete the resection.
defect in ICC In our study, the severity of constipation seems unrelated to the RESULTS: Main characteristics of the patients and lesions are shown in table 1.
importance of this defect and ICC evaluation has little clinical interests. Clearly, ESD had to be changed to pEMR in 37 patients (43.5%) to complete the resec-
patients with SCI are satisfied after colectomy. tion of the lesion. In the univariate analysis, the factors that showed a statistically
REFERENCES significant association with moving to pEMR were: location of the lesion other
Wang et al. Am J Pathol 2008; 32: 980-985. than in the stomach (54.7% vs. 25%; p 0.007), procedure duration longer than
Disclosure of Interest: None declared 180 min (57.9% vs 31.9%; p 0.016) and a maximum diameter more than 30 mm
(63.6% vs. 28%; p 0.001). None of the following factors showed statistically
significant association with moving the therapeutic approach to pEMR:
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 depressed morphology (28.6% vs. 48.4%; p 0.11), lesions treated after the
UPDATE ON ENDOSCOPIC RESECTION OF EARLY COLORECTAL NEOPLASIA HALL first 50 ESDs were performed (48% vs. 37.1%; p 0.32), previous electrosurgery
N_____________________ of the lesion (62.5 vs. 41.6%; p 0.29), team who performed the ESD (41.2% vs.
47.1%; p 0.59) or the presence of deep submucosal invasion in the histological
OP332 ENDOSCOPIC SUBMUCOSAL DISSECTION VERSUS specimen (66.7% vs. 41.8%; p 0.39). In the logistic regression model, the size of
ENDOSCOPIC MUCOSAL RESECTION FOR LARGE the lesion with a maximum diameter 4 30 mm, was the only factor indepen-
COLORECTAL TUMORS: A META-ANALYSIS dently correlated with moving to pEMR (OR: 3.2; CI 95%: 1.1 8.3).
M. Liggi1,*, S. Cadoni1, P. Gallittu1, M. Erriu2
1
Digestive Endoscopy Unit, Santa Barbara Hospital, Iglesias, 2Department of
Surgery, University of Cagliari, Cagliari, Italy
Contact E-mail Address: macnol@tiscali.it
INTRODUCTION: Colorectal lateral spreading tumors (LST) 20 mm are best
treated by Endoscopic submucosal dissection (ESD) or Endoscopic mucosal
resection (EMR). EMR is a safe and effective treatment for most colorectal
granular-LST (G-LST) lower than 40 mm. ESD should be preferred for both
greater G-LST and non-granular type LST (NG-LST), especially the pseudo-
A106 United European Gastroenterology Journal 2(5S)
Table 1. Characteristics of the lesions, procedure and patients. OP335 KNIFE ASSISTED RESECTION (KAR) OF LARGE AND
Table to abstract OP333 REFRACTORY COLONIC POLYPS AT A WESTERN CENTRE:
FEASIBILITY, SAFETY AND EFFICACY STUDY TO GUIDE FUTURE
n 85 PRACTICE
Age (mean SD) 68 12 R. Bhattacharyya1,*, G. Longcroft-Wheaton1, P. Bhandari1 on behalf of
Male / Female n;% 48/37 (56.5 / 43.5) Portsmouth, UK
1
Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, United
Mean tumor size, mm (mean SD) 30.4 14.9 Kingdom
En bloc resections (n; %) 48 (56.5)
INTRODUCTION: ESD enables large lesions to be resected en bloc. This
Snare use (Hybrid ESD) 12 (14.1)
reduces recurrence rates, but ESD is technically challenging with high complica-
Piecemeal resections (n; %) 37 (43.5) tion rates and hence not widely practiced in the west.
R0 (n; %) 33 (38.8) We have used a novel Knife Assisted Resection (KAR) technique.
Procedure time (mean SD) 183 87 AIMS & METHODS: We aim to evaluate the outcome of KAR in the treatment
of large and refractory colonic polyps and identify polyp features that can predict
CONCLUSION: When the experience with ESD is low, with 5 100 procedures complications and recurrence after KAR.
performed, the size of the lesion, with a maximum diameter 4 30 mm, is the Cohort study of patients referred to our centre for resection of refractory polyps.
strongest predictor for the need to complete the resection with pEMR. All patients who had knife assisted resection of colonic polyps over 20mm in size
Disclosure of Interest: None declared from 2006 to Feb 2013 were included. All procedures were performed by a single
experienced endoscopist.
The technique starts with submucosal (SM) injection followed by mucosal inci-
OP334 RETROSPECTIVE COHORT STUDY TO ELUCIDATE LONG- sion using a dual knife (Olympus KD-650L). This is followed by variable degrees
TERM CLINICAL OUTCOMES OF COLORECTAL ENDOSCOPIC of SM dissection and completion of circumferential mucosal incision. Finally a
SUBMUCOSAL DISSECTION snare assisted resection is performed in an en bloc or piecemeal fashion, depend-
M. Yamada1,*, Y. Saito1, H. Takamaru1, T. Sakamoto1, Y. Otake1, ing on the polyp size and extent of SM dissection.
T. Nakajima1, T. Matsuda1 RESULTS: 127 polyps in 127 patients of mean age 71 years. Mean polyp size
1
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan 46mm (20-170mm). 27% were 450mm. 27% were scarred from previous
Contact E-mail Address: masyamad@ncc.go.jp attempted resection. 26% were in the right colon.
En bloc resection: 58/127(46%). Size of polyp 550mm was a significant
INTRODUCTION: Endoscopic submucosal dissection (ESD) is performed as a (p0.001) predictor of en bloc resection (88% vs. 12%).
curative treatment for colorectal neoplasms.1-5 Long-term clinical outcomes, The complication rate was 11/127(8.6%) with 5(3.9%) bleeds, 4(3.1%) diathermy
however, are necessary to clarify whether colorectal ESD truly has a favorable damage to muscle fibres and 1(0.78%) perforation. Complications were not
effectiveness beyond lower recurrence rates. linked to polyp size, scarring or resection site. A single patient with perforation
AIMS & METHODS: The aim of this retrospective cohort study is to elucidate required surgery. All other complications were managed endoscopically.
long-term clinical outcomes for colorectal ESD. To allow five-year follow-up data, The recurrence rate was 14/106(13%). This was significantly higher for polyps
out of 418 consecutive patients who were treated by ESD at National Cancer 450mm (p 0.009) and in scarred polyps (p 0.024).
Center Hospital, Tokyo, Japan, between February 1998 and December 2008, we On sub-analysis of the unscarred polyps, polyps 50mm with no scarring had a
conducted a survey on patients followed-up longer than three years. After exclu- very low recurrence rate of 3.2% as compared to 25% in polyps 450mm (p
sion criteria of squamous cell carcinoma, carcinoid tumor, coexistence of 0.005).
advanced cancer, familial adenomatous polyposis and ulcerative colitis, 408 Table: Factors associated with recurrence
patients were enrolled. Long-term outcome data were collected between March CONCLUSION: This is the largest reported western series demonstrating the
and September 2013. Incomplete and missing data were retrieved from the referral feasibility, safety and efficacy of KAR for large and refractory polyps, with or
hospital by asking their chief physician by letter; including last examination data, without scarring, at all colonic sites. Our data demonstrates that complications of
date of recurrence, treatment history of any recurrence and the date of death. KAR are not related to size but the recurrence rate is. Size 450mm and scarring
Finally, we had complete data of the outcome of 286 patients (70%) and the seem to be predictors of recurrence.
survival analyses were conducted. The primary endpoint was 5-year overall survi- We propose flat polyps 20 50mm in size as the ideal indication for KAR in the
val rate (OS) and the secondary endpoints were recurrence free survival rate (RFS) western setting.
and cause specific survival rate (CSS). R0 resection was defined as cancer-free Disclosure of Interest: None declared
resection margins. Curative resection was defined when the pathological findings
revealed R0, irrespective of piecemeal or en-bloc resection, with non of the follow-
ing features: deep submucosal invasion (=1,000 m, T1b), lymphovascular inva- OP336 EFFECTIVENESS AND SAFETY OF ENDOSCOPIC
sion, or poorly differentiated adenocarcinoma component. An adenoma with an SUBMUCOSAL DISSECTION USING THE BALL-TIP
unknown lateral margin also classified curative resection. BIPOLARCURRENT NEEDLE KNIFE WITH WATER-JET FUNCTION
RESULTS: The 5-year OS, RFS and CSS were 95%, 91% and 100%, respec- (JET B-KNIFE) FOR THE TREATMENT OFCOLORECTAL TUMORS
tively, after the 5.4-year (0.3-11.1) median follow-up period. In 220 curative K. Hiramatsu1,*, H. Matsuda1, M. Ohtani1, T. Nemoto1, H. Suto1,
patients, the 5-year OS, RFS and CSS were 95% 95% and 100%, while the Y. Nakamoto1
CSS was low in 66 non-curative patients as 95%, 80% and 100%, respectively. 1
Second Department of Internal Medicine, University of Fukui, Fukui, Japan
In the curative patients, three local recurrences including one intramural recur- Contact E-mail Address: hiramatz@u-fukui.ac.jp
rence were detected in two patients with multiple piecemeal resections and one
with R0 resection for recurrence lesion. Two of these patients were successfully INTRODUCTION: ESD is a technically difficult and time-consuming procedure
treated by additional ESD and no recurrence was detected in more than 5 years for the treatment of large colorectal tumors. In Japan, Ball-Tip Bipolar Current
after the second ESD, respectively, and the other patient underwent salvage Needle Knife (BB-knife) has been used as a device for safe treatment in ESD by
surgery. In the non-curative patients, 38 patients were followed without addi- minimizing the damage in deeper tissues of colorectal neoplasms. In May 2012, a
tional surgery and 10 recurrences (26%) including 4 distant metastases were BB-knife combined with Water-Jet function (Jet B-knife) was newly developed.
detected. In contrast, only one distant metastasis (3%) was detected in 28 AIMS & METHODS: The aim of this study was to examine the effectiveness and
patients who underwent additional surgery. These patients with recurrence safety of Jet B-knife, which is the Bipolar Current Needle Knife with a ball tip
received salvage surgery and/or chemotherapy. and 1.5 mm in length. The endoscope we used was Olympus H260AZI or
CONCLUSION: The present study has shown favorable long-term clinical outcomes PCF260AI. Electorosurgical unit was VIO300D(ERBE) with dry cut mode
of colorectal ESD for patients with intramucosal and submucosal superficial invasive (effect 3,60W) or spray coagulation mode (effect 2 60W). Translucent hood
cancer. Therefore, colorectal intramucosal and superficial submucosal cancer can be had been always attached to the point of the endoscope. We treated 276 lesions
well managed by endoscopic resection when it achieves curative resection. by ESD using BB-knife between March 2007 and April 2012(group A) and 101
REFERENCES lesions using Jet B-knife between May 2012 and March 2014 (group B). We
1) Lee EJ, et al. Surg Endosc 2013 retrospectively evaluated including the diameter of resected tumor, the time
2) Saito Y, et al. Surg Endosc 2010 required for resection, the rate of en-block complete resection, the rate of per-
3) Repici. A, et al. Endoscopy 2012 foration, and compare these data between two groups.
4) Probst A, et al. Endoscopy 2012 RESULTS: The median time required for the resection was 103 min. in group A
5) Niimi K, et al. Endoscopy 2010. and 61 min. in group B. The difference was statistically significant (p50.01). And
Disclosure of Interest: None declared the median diameter of tumor in group A was 23.1mm and that in group B was
OP335
SIZE RESECTION TYPE SITE SCARRED
ALL POLYP RECURRENCE 14/106 (13%) 6/78 (7.6%) 8/28 (28.5%) 1/42 (2.3%) 7/44 (15.9%) 13/83 (15.6%) 1/23 (4.3%) 6/20 (30%) 8/86 (9.3%)
P 0.009 P 0.001 P 0.15 P 0.024
UNSCARRED POLYP RECURRENCE 8/86 (9.3%) 2/62 (3.2%) 6/24 (25%) 1/42 (2.3%) 7/44 (15.9%) 8/68 (11.7%) 0/18 (0%)
P0.005 P0.058 P0.195
United European Gastroenterology Journal 2(5S) A107
26.6mm. The difference was statistically significant (p50.01). On the other hand, Most pedunculated polyps were removed using HS; this proportion was lower in
the en-block complete resection rate was 94% in group A and97% in group B. the right vs. left colon (69.6% vs. 88.3%, OR 0.30, CI 0.28-0.33, p 5 0.01).
The rate of perforation was 1.8% in group A and 2.0% in group B. These CS was most common for non-pedunculated polyps in the right colon (29.8% vs.
differences were not statistically significant. 19.0% in left, OR 1.81 CI 1.76-1.85, P 50.01); whereas most common in the left
CONCLUSION: The resection time was significantly shortened using Jet B- colon was HS (34.8 vs. 22.5% in right, OR 1.84 CI 1.79-1.88, P 50.01).
knife, although the mean size of lesions was significantly larger than the other. Surgeons were more likely than physicians to use diathermy irrespective of site or
This may be not only due to the improvement of cutting skill but also due to the morphology (65.6% vs. 56.5%, OR 1.46 CI 1.43-1.51, P 5 0.01).
efficient water jet function during the procedure of hemostasis and the enhanced In 60% of polyps removed completeness of excision was not histologically asses-
lifting effects of lesions by launching it at the submucosal layer. In conclusion, sable. 21.2% were completely excised, 5.8% incomplete and 13% not stated. For
the use of Jet B-knife may contribute to time-saving and safe procedure in ESD non-pedunculated polyps, histologically-confirmed complete excision was more
for the colorectal tumors. common after EMR (23.4% vs. 6.2%, OR 1.16, CI 1.08-1.25, p 50.01) com-
Disclosure of Interest: None declared pared to other techniques (CBF 17.7%, CS 15.1%, HBF 19.1%, HS 21.5%); for
pedunculated polyps it was more common after EMR (42.3%) and HS (42.0%)].
Sub-analysis of colonoscopies where only polyps 510mm were removed (45227),
OP337 STRATEGY TO OVERCOME A DIFFICULTY OF THE complications were rare. 12 (0.03%) bleeding episodes required transfusion; the
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR rates for single and multiple polypectomy cases were 0.01% and 0.04% respec-
COLORECTAL TUMORS ACCOMPANIED BY FIBROSIS IN tively (OR 5.01, CI 1.10-22.8, P 0.02). The HS technique was most commonly
SUBMUCOSAL LAYER used. There were 16 (0.04%) perforations; 0.02% for single vs. 0.05% for multi-
Y. Tamegai1,*, T. Kishihara1, H. Ishikawa1, K. Okamoto1, A. Chino1, ple polypectomies (OR 2.20, CI 0.77-6.34, P 0.13). No technique dominated for
J. Fujisaki1, M. Igarashi1 single compared with HS for multiple polypectomies.
1
Endoscopy Division, Cancer Institute Hospital, Tokyo, Japan Between 2010 and 2012, use of CBF, CS and EMR increased, whereas HBF and
Contact E-mail Address: yoshiro.tamegai@jfcr.or.jp HS decreased (p 5 0.01). Table 1
Table 1 Change in trends according to technique
INTRODUCTION: The safety and curability of one-piece resection of colorectal
tumor using ESD technique sometime depends on the degree of fibrosis in the
submucosal (SM) layer. ESD for the tumors accompanied by hard and tight 2010(%) 2012(%) OR, 95% CI
fibrosis are thought to be most difficult to complete. The aim of this study is
to establish the strategy to overcome a difficulty of the ESD for colorectal tumors CBF 15.2 23.0 OR 1.67, CI 1.61-1.72
accompanied by fibrosis in SM. CS 21.3 23.3 OR 1.12, CI 1.09-1.16
AIMS & METHODS: ESD was performed for 766 cases of colorectal neoplasm
in 760 patients (male: female 449:311; mean age, 65.7 years). Among these HBF 14.1 10.1 OR 0.68, CI 0.66-0.71
cases, 190 cases were accompanied by SM fibrosis. These cases were divided into HS 41.0 31.1 OR 0.65, CI 0.63-0.67
three groups, absent with fibrosis (type A), fibrosis due to benign causes (type B), EMR 8.5 12.5 OR 1.55, CI 1.48-1.62
and fibrosis due to submucosal cancer invasion (type C). And these were classi-
fied into mild (grade 1), moderate (grade 2), and severe (grade 3) degree. In this CONCLUSION: The removal of polyps 510mm within the BCSP is safe, but
study, we compared the one-piece resection rate between these three groups histological evidence of complete excision is poor with all techniques. Wide
according to the degree of SM fibrosis. variations in practice reflect the lack of evidence guiding these decisions,
RESULTS: We completed ESD procedure on 758 of 766 colorectal tumors, and although use of cold resection techniques has increased over time.
8 cases were abandoned due to severe degree fibrosis relating deep SM cancer Disclosure of Interest: None declared
invasion and screen-like fibrosis. Among the 190 cases with SM fibrosis, 59 cases
were considered related to cancer invasion (type C), and 131 cases were related to
benign cause (type B). The fibrosis of non-cancerous origin was caused by prior OP339 ENDOSCOPIC FULL THICKNESS RESECTION IN THE LOWER
inadequate endoscopic treatment, biopsy, and others. We classified the endo- GASTROINTESTINAL TRACT USING A NOVEL OVER-THE-SCOPE
scopic findings as mild degree (B-1), moderate degree (B-2), and screen-like as DEVICE
severe degree (B-3). Otherwise, a white or brown hump and rich abnormal vessels A. Schmidt1,*, M. Damm1, C. Gubler2, K. Caca1, P. Bauerfeind2
were identified in the cases with SM cancer invasion (C-1 to 3). We performed 1
Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany,
one-piece resection for 723 (94.4%) cases of 766 ESD cases. One-piece resection 2
Gastroenterology, Universitatsspital Zurich, Zurich, Switzerland
rate of type A as 97.6% (562/576) and type BC was 84.7% (161/190). And the
one-piece resection rate according to the degree of fibrosis as follows, type B-1; INTRODUCTION: Diagnostic or therapeutic endoscopic full thickness resection
68/71(95.8%), B-2:27/30(90.0%), B-3:18/30 (60.0%), type C-1;31/31(100%, aver- in the colon may be indicated for non-lifting adenomas and other indications.
age SM depth:822.6m), C-2:7/8(87.5%, average SM depth:2,067.1m), C-3:10/ However, to date there is a lack effective and safe endoscopic methods and
20(50%, average SM depth:3,078.9m). These dates of B-3, and C-3 were show- devices. The FTRD (Full Thickness Resection Device, Ovesco, Tubingen,
ing unwilling results. We experienced only one case (0.13%) of perforation in Germany) is a novel over-the-scope device developped for endoscopic full thick-
type B. Therefore, in cases accompanied by severe degree fibrosis, onepiece ness resection.
resection becomes more difficult due to the risk of perforation. We designed AIMS & METHODS: Between 07/2012 until 03/2014, 21 patients underwent
safe technique by using endo-clips to prevent perforation before dissection in 3 endoscopic full thickness resection at two tertiary referral centers. All resections
type B-3 cases, and successfully completed ESD procedure. And in other type B-3 were conducted with the FTRD mounted on a standard colonoscope. Resection
cses, we have searched a dissection line just above muscle layer carefully. Because technique: The lesion to resect was pulled into a long transparent cap, a 14 mm
of these results, type B-1, type B-2, type C-1, and type C-2 become standard Over-The-Scope Clip (OTSC) was deployed and the pseudopolyp above the clip
indication of ESD, type B-3 becomes relative indication of ESD, and type C-3 was resected with a preloaded snare.
was thought to be an indication of laparoscopic surgery. Recently, we established In this study we report our first clinical experience with this novel full thickness
the laparoscopy endoscopy cooperative surgery (LECS) procedure applied with resection technique.
ESD technique to complete an one-piece resection for the tumors accompanied RESULTS: Indications for endoscopic full thickness resection were: recurrent or
by wide and hard fibrosis(type B-3), and we performed one-piece resection for 4 incompletely resected adenoma with negative lifting sign (9); untretated adenoma
cases successfully. with high-grade dysplasia and negative lifting sign (1), adenoma involving the
CONCLUSION: Endoscopic intra-operative evaluation of the cause and degree appendix (3), flat adenoma in a patient with coagulopathy (1), diagnostic re-
of SM fibrosis is very important to complete safe and curative ESD procedure for resection after incomplete resection of a T1-carcinoma (3), adenoma involving
early colorectal cancers. a diverticulum (1), submucosal colonic tumor (2), diagnostic resection in a
Disclosure of Interest: None declared patient with suspected Hirschsprungs disease. The lesions were located as fol-
lowed: coecum (3), ascending colon (4), transverse colon (2), descending colon
(4), sigmoid (2), recosigmoid transition (3) and rectum (3). Reaching the target
OP338 POLYPECTOMY PRACTICES IN THE ENGLISH BOWEL lesion with the endoscope and the mounted FTRD was possible in 20/21 patients
CANCER SCREENING PROGRAMME (95.2%). Having reached the target lesion, macroscopically complete resection
S. Din1,*, A. Ball1, E. Lunn1, S. Riley1, M. Rutter2, S. Johal1 was achieved in 19/20 patients. Full thickness resection was confirmed histolo-
1
Gastroenterology, Sheffield Teacing Hospitals NHS Foundation Trust, Sheffield, gically in 17/20 cases (85%). Histologically complete resection was achieved in
2
Gastroenterology, University Hospital of North Tees, Newcastle upon Tyne, 17/20 cases (85%). No perforations or relevant bleeding was observed during or
United Kingdom after resection. Two patients developed a post-polypectomy syndrome which was
managed with antibiotic therapy.
INTRODUCTION: Most polyps are 510 mm in size and a range of polypect- CONCLUSION: Full thickness resection in the lower GI tract with the novel
omy techniques are available with wide variations in practice. We aimed to FTRD is feasible and effective. Prospective studies are needed to further evaluate
examine the techniques employed for removal of 510mm polyps in relation to the technique and device.
polyp characteristics, completeness of excision, safety and changes over time. Disclosure of Interest: A. Schmidt Lecture fee(s) from: Ovesco Endoscopy, M.
AIMS & METHODS: Data relating to removal of polyps 510mm between Jan Damm: None declared, C. Gubler: None declared, K. Caca: None declared, P.
2010 and Dec 2012 were retrieved from the national Bowel Cancer Screening Bauerfeind: None declared
Programme (BCSP) database. Categorical data was compared using x2.
RESULTS: 147174 polyps 510mm were removed during 62679 colonoscopies.
A range of techniques was used (cold biopsy forceps (CBF) 19.7%, cold snare
(CS) 22.1%, hot biopsy forceps (HBF) 12.2%, hot snare (HS) 35.1%, EMR
10.9%). EMR was used more frequently in the right colon compared to the
left (14.3% vs. 8.3%, OR 1.84, 95% CI 1.78-1.90, P 50.01).
A108 United European Gastroenterology Journal 2(5S)
OP340 ELRR OR TATMR BY TEM FOR TREATMENT OF LOW RECTAL was highest among smokers (40%). Patients with alcoholic etiology and current
CANCER smokers had a comparable cumulative risk for CP of about 15%. With both
E. Lezoche1,*, A.M. Paganini1, S. Quaresima1, A. Balla1, E. de Werra1, factors present the risk doubled to 30%.
F. Mattei1, G. DAmbrosio1 Table 1. Multivariable analysis of risk factors for progression to chronic
1
Sapienza University of Rome, Azienda Policlinico Umberto I, Roma, Italy pancreatitis
Contact E-mail Address: emanuele.lezoche@gmail.com
INTRODUCTION: From the beginning of the 90s, the authors have introduced CP diagnosed CP as defined by
an original technique of loco-regional resection by Transanal Endocopic clinically the M-ANNHEIM criteria
Microsurgery (TEM) named Endoluminal Loco-Regional Resection
(ELRR). In selected patients, this technique is a valid alternative to traditional odds ratio odds
surgery for early (Tis-T1) and for T2N0 rectal cancer after neoadjuvant radio- (95% confidence- ratio (95%
chemotherapy (n-RCT). Sphincter-saving procedures in patients with low rectal interval) P-value confidence-interval) P-value
cancer are largely successful, but there is no universally adopted standardized
technique. From 2008, the authors have developed a new combined technique: Etiology 1 50.001 1 0.001
Transabdominal Transanal Total Mesorectal Resection (TATMR) by TEM in - Biliary 6.48 (2.53 16.58) - 4.22 (1.83 9.73) -
patients not eligible for ELRR (T2-T3N0/N). Transanal TME is achieved with - Alcohol 4.66 (1.71 12.74) 50.001 3.98 (1.64 9.65) 0.001
a modified original TEM rectoscope. The abdominal part is performed laparos- - Idiopathic/other 0.003 0.002
copically, followed by colo-anal anastomosis and ileostomy. Current smoking 2.52 (1.19 5.31) 0.02 2.90 (1.42 5.93) 0.004
AIMS & METHODS: From 2001 to 2014, 135 patients (82 males, 53 females,
median age 65 years) with rectal cancer were selected. All patients were studied Pancreatic necrosis 3.45 (1.68 - 7.09) 0.001 6.65 (3.40 13.01) 50.001
preoperatively with tumor markers assay (CEA, Ca19.9, Ca125), digital rectal
examination, colonoscopy with macrobiopsies, vital staining, peri-tumoral tat- CONCLUSION: Five years after a first AP episode, about 1 out of 6 patients
tooing on histologically normal mucosa, total body CT scan, pelvic MRI and develop RP and 1 out of 15 patients develop CP. Smoking was the predominant
endorectal ultrasound. One hundred and nineteen patients with T1-T2N0 rectal risk factor for RP, while the combination of alcohol and smoking resulted in the
cancer underwent ELRR by TEM and sixteen patients with T2-T3N0/N under- highest cumulative risk for CP. Based on these results, pancreatic specialist
went TATMR. All T2-T3 patients underwent n-RCT. should not only advise patients to discontinue alcohol use after a first pancreatitis
RESULTS: Mean operative time for ELRR and TATMR was 138 min (range episode, but should emphasize the importance of smoking cessation as well.
40-300) and 450 (range 360-600), respectively. No intraoperative complication Disclosure of Interest: None declared
was observed. Final staging was pT0N0 (5), pTis (51), pT1 (46), pT2 (24), pT3N0
(5), pT3N1 (4). Mean hospital stay was 4 days for ELRR and 16 days for
TATMR. No late complications were observed in ELRR group. In the OP342 DISRUPTION OF FRACTALKINE/CX3CR1 SIGNALLING
TATMR group, anastomotic leakage occurred in 6 cases. Mortality was ATTENUATES PANCREATIC PAIN IN EXPERIMENTAL CHRONIC
observed in two patients for unrelated causes. PANCREATITIS
CONCLUSION: In patients with low rectal cancer, quality of life should be a J.G. DHaese1,*, T.D. DHaese1, H. Sezgin1, T. Kehl1, I. E. Demir1,
primary objective, without compromising the oncological results. TME is the F. Bergmann2, H. Friess1, G.O. Ceyhan1
gold standard, but postoperative functional sequelae are often observed. 1
Department of Surgery, KLINIKUM RECHTS DER ISAR, Munchen, 2Institute
Several surgical alternative procedures are described, but none has been univer- of Pathology, University of Heidelberg, Heidelberg, Germany
sally adopted. In selected T1 or T2 (after n-RCT) patients, ELRR by TEM is a Contact E-mail Address: jan.dhaese@med.lmu.de
valid alternative to traditional surgery. The authors described a new technique
named TATMR to treat patients with T2-T3 rectal cancer. The main advantages INTRODUCTION: Chronic pancreatitis (CP) is a chronic inflammatory condi-
are the preliminary identification of the distal margin of the tumor and dissection tion of the pancreas leading to severe pain and fibrosis. Fractalkine is a chemo-
of the intact distal mesorectal fascia, in order to detect peri-rectal tumor invasion kine that chemoattracts inflammatory cells through its highly selective receptor
and to verify the possibility to perform a sphincter-saving procedure. Adequate CX3CR1 and has been suggested to aggravate pancreatic inflammation.
experience in TEM is a pre-requisite. Fractalkine is moreover known to be expressed on spinal neurons and sensory
Disclosure of Interest: None declared afferents where it has shown major pain-modulatory effects in different experi-
mental pain states.
AIMS & METHODS: We aimed to investigate the course of experimental
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 chronic pancreatitis in CX3CR1-/- deficient mice and the potential therapeutic
PATHOPHYSIOLOGY AND MANAGEMENT OF PAIN AND FIBROSIS IN CHRONIC implications of a CX3CR1 inhibitor. CP was induced in CX3CR1-knockout and
PANCREATITIS HALL O_____________________ wild-type mice by repetitive intraperitoneal cerulein injections. Treatment groups
received an orally available small molecule CX3CR1 inhibitor. Hyperalgesia was
OP341 RISK OF RECURRENT PANCREATITIS AND PROGRESSION TO assessed by systematic behavioural observation, locomotion analysis, and mea-
CHRONIC PANCREATITIS AFTER A FIRST EPISODE OF ACUTE surement of abdominal mechanical sensitivity. Pancreatic tissue was harvested
PANCREATITIS after sacrifice for further analyses.
U. Ahmed Ali1,2,*, Y. Issa1, J.C. Hagenaars2, O.J. Bakker2, H. van Goor3, RESULTS: Both CX3CR1-knockout and CX3CR1-blocking treated mice
V. Nieuwenhuijs4, T. Bollen5, B. van Ramshorst6, B.J. Witteman7, M.A. Brink8, showed significantly less pain related behaviour (p 5 0.0001) and significantly
A.F. Schaapherder9, C.H. Dejong10, B.M. Spanier11, J. Heisterkamp12, E. van less weight loss (p 5 0.01) when compared to their wild-type controls, with a
der Harst13, C. H. van Eijck14, M.G. Besselink1, H.C. Gooszen15, H. C. clear dose-response correlation in the treated mice. This reduction in pain related
van Santvoort6, M.A. Boermeester1 on behalf of Dutch Pancreatitis Study Group behaviour was confirmed in IHC and WB analysis of pain markers.
1
Department of Surgery, Academic Medical Center Amsterdam, Amsterdam, Unexpectedly, there was no difference in inflammatory cell infiltrations, fibrosis,
2
Department of Surgery, University Medical Center Utrecht, Utrecht, 3Department Amylase/Lipase levels, and Trypsin/MPO activity.
of Surgery, Radboud university medical center, Nijmegen, 4Department of Surgery, CONCLUSION: Fractalkine/CX3CR1 signalling seems to be crucial in initiating
Isala Clinics, Zwolle, 5Department of Radiology, 6Department of Surgery, St chronic pancreatic hyperalgesia. It does however not seem to have a direct effect
Antonius Hospital, Nieuwegein, 7Department of Gastroenterology, Gelderse Vallei on inflammatory cell infiltration and fibrosis. Nevertheless, these novel findings
Hospital, Ede, 8Department of Gastroenterology, Meander Medical Center, reveal CX3CR1 as a promising new target for the treatment of chronic pancreatic
Amersfoort, 9Leiden University Medical Center, Leiden, 10Department of Surgery, pain.
University Hospital Maastricht, Maastricht, 11Department of Gastroenterology, Disclosure of Interest: None declared
Rijnstate Hospital, Arnhem, 12Department of Surgery, St Elisabeth Hospital,
Tilburg, 13Department of Surgery, Maasstad Ziekenhuis, 14Department of Surgery,
Erasmus Medical Center, Rotterdam, 15Department of Evidence Based Surgery, OP343 PATHOPHYSIOLOGIC EVENTS IN PANCREATIC ACINAR
Radboud university medical center, Nijmegen, Netherlands CELLS ASSOCIATED WITH PANCREATITIS IN RESPONSE TO
Contact E-mail Address: u.ahmedali@pancreatitis.nl TOBACCO COMPARED TO ALCOHOL
M. Luaces-Regueira1,*, M. Castineira-Alvarino1, J.E. Dominguez-Munoz2
INTRODUCTION: Recurrent pancreatitis (RP) and chronic pancreatitis (CP) 1
Gastroenterology, Foundation for Reserch in Digestive Diseases, 2University
may occur after a first episode of acute pancreatitis. Data on incidence and risk Hospital of Santiago de Compostela. Foundation for Reserch in Digestive Diseases,
factors for these events are scarce. Santiago de Compostela, Spain
AIMS & METHODS: A cross-sectional survey and retrospective review of a
prospectively collected cohort of patients with a first episode of acute pancreatitis INTRODUCTION: Pancreatitis is characterized by the development of inflam-
was performed. Primary endpoints were RP and CP. CP was defined in two way: matory process secondary to intracellular premature activation of digestive
1. based on clinical diagnosis by treating physician, and 2. based on the M- enzymes, alteration of intracellular calcium levels and enzyme secretion, reactive
ANNHEIM diagnostic criteria. Both definitions were analysed seperately. Risk oxygen species (ROS) production and death of pancreatic acinar cell. Tobacco is
factors were evaluated using regression analysis. The cumulative risk was generally recognized as a relevant risk factor for pancreatitis, but its effect on
assessed using Kaplan-Meijer analysis. acinar cells is unknown
RESULTS: 669 patients were included, with a median follow-up of 57 months. AIMS & METHODS: To evaluate the role of tobacco compared with alcohol in
RP and CP were observed in 117 (17%) and 42 (6%) patients, respectively. Rates the pathophysiologic events associated with pancreatitis in pancreatic acinar
of RP were 12%, 24% and 25% in patients with biliary, alcoholic and idiopathic/ cells.
other etiology, respectively. CP developed in 2%, 15% and 7% for these etiol- Acinar cells isolated from Swiss mice pancreas by enzymatic and mechanic degra-
ogies, respectively. Etiology, smoking and necrotizing pancreatitis were indepen- dation were stimulated with different concentrations of alcohol (10-100mM) or
dent risk factors for both RP and CP (Table 1). APACHE-II score on admission tobacco (0.001-0.4mg/ml) and with CCK (positive control). Intracellular enzyme
was independently associated with RP only. Cumulative risk for RP over 5 years activity, ROS production, necrosis and intracellular calcium were evaluated by
United European Gastroenterology Journal 2(5S) A109
fluorescence with rodhamine, DCFDA, propidium iodide and fluo-4 substrates, OP345 SMOKING CESSATION BUT NOT ALCOHOL ABSTINENCE
respectively. Amylase secretion was evaluated with p-nitrophenyl-maltohexao- REDUCES THE MORPHOLOGICAL PROGRESSION OF TOXIC
side as substrate. NFB activation was measured by Western blot. Interleukin- CHRONIC PANCREATITIS: A PROSPECTIVE, LONGITUDINAL
1 and TNF secretion was analyzed by ELISA in the supernatant. Apoptosis COHORT STUDY
was evaluated by caspase 3 activity (western blot). LDH was quantified as a J. Iglesias-Garc a1,*, M. Luaces-Regueira2, J. Larino-Noia1, M. Castineira-
marker of cytotoxicity. Statistic analysis was performed by ANOVA. Alvarino2, J.E. Dominguez-Munoz1
RESULTS: Neither alcohol nor tobacco induced a significant activation of intra- 1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
cellular enzyme. Tobacco significantly increased intracellular calcium levels Research in Digestive Diseases, 2Foundation for Research in Digestive Diseases,
[11.384.89% (0.1mg/ml) - 56.2613.14% (0.5mg/ml)] similarly to alcohol Santiago de Compostela, Spain
[14.402.06% (10mM) - 59.82.57% (75mM)]. This was associated to an
increase in amylase secretion only after tobacco (21%, 0.4mg/ml). Tobacco, INTRODUCTION: Smoking and alcohol are recognized risk factors for chronic
but not alcohol, induced activation of NFB (2.691.05 fold increase of p65 pancreatitis (CP). Smoking enhances ethanol-induced pancreatic injury and
translocation at 0.1 mg/ml over negative control). Neither tobacco nor alcohol accelerates the development and progression of CP. However, the effect of stop-
induces interleukin-1 and TNF release. Moreover, tobacco, but not alcohol, ping the consumption of tobacco and alcohol on the progression of CP has not
produced a significant citotoxicity (p50.05) and induced acinar cell necrosis at been well defined.
0.3 y 0.4 mg/ml (14.3% and 19.4%, respectively). This was associated with ROS AIMS & METHODS: We aimed at investigating the effect of cessation the
production in a dosis-dependent manner (p50.05). In addition, tobacco stimu- consumption of tobacco and alcohol on the morphological progression of CP
lated the activation of caspase 3 at 0.01 and 0.1 mg/ml (2.530.38 and 1.770.12 as evaluated by endoscopic ultrasound (EUS).
vs negative control). A prospective, longitudinal cohort study was designed. Inclusion criteria were
CONCLUSION: High concentrations of tobacco induce a significant increase of patients diagnosed of toxic non-calcific CP by EUS. All patients should be active
intracellular calcium levels, amylase secretion, ROS production and necrosis in smokers at inclusion. Minimum follow-up was 2 years. EUS was performed
pancreatic acinar cells. At lower concentrations, tobacco initiates the inflamma- under conscious sedation by the lineal Pentax echoendoscope and HITACHI
tory process through the activation of NFB and induces apoptosis in pancreatic ultrasound at inclusion and at 2-year intervals during follow up. Standard
acinar cells. Alcohol does only induce an increase of intracellular calcium levels EUS criteria for the diagnosis of CP were evaluated (5 parenchymal criteria
in the same experimental model. These results support the relevant role of and 5 ductal criteria). Progression was considered when the total number of
tobacco as an etiological factor of pancreatitis. EUS criteria of CP increased during follow-up. Data regarding smoking and
Disclosure of Interest: None declared alcohol consumption were recorded at baseline and during follow-up. Data are
shown as mean and 95%CI, and compared by the t-student test. A multivariable
logistic regression analysis was performed to determine the effect of maintained
OP344 IS TOBACCO A TRIGGER FACTOR OF PANCREATIC alcohol and tobacco consumption on the progression of CP.
FIBROGENESIS? EVIDENCE FROM THE INTERACTION RESULTS: 68 patients (61 male, 7 female, mean age 48.9 years, range 23-74
BETWEEN ALCOHOL AND TOBACCO IN PANCREATIC STELLATE years) were finally included. 44 of them (64.7%) were drinkers. Median follow-
CELLS up time was 56 months (range 24-123 months). Regarding toxic habits, 24
M. Castineira-Alvarino1,*, M. Luaces-Regueira1, J.E. Dominguez-Munoz2 (35.3%) patients stopped smoking, and 26 (59.1%) stopped alcohol consump-
1
Gastroenterology, Foundation for Research in Digestive Diseases, tion. Morphological progression of the disease was observed in 34 patients (50%)
2
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for during follow-up. Eight (8.8%) patients developed calcifications. A morphologi-
Research in Digestive Diseases, Santiago de Compostela, Spain cal progression of the disease was observed in 28 out of the 44 patients who
continued to smoke (66.6%) and in 6 out of the 24 patients who stopped smoking
INTRODUCTION: Alcohol has been associated with the activation of pancrea- (25%) (p0.005). Morphological progression of CP was observed in 61.5% of
tic stellate cells (PSC) and survival of activated PSC. The effect of ethanol is patients who stopped alcohol intake and in 50% of those who continued drinking
partly mediated by the generation of oxidative stress within the cells but other (n.s.). The only factor significantly and independently associated with the mor-
factors are required for pancreatic fibrogenesis to develop. Tobacco is recognized phological progression of the disease during follow-up was maintained tobacco
as an etiological factor of chronic pancreatitis (CP). Tobacco has been shown to consumption (OR5.25, 95%CI 1.73-15.92). Maintained alcohol consumption
activate fibrogenesis in tissues such as heart, liver and kidney, but its effect on the was not associated with the progression of CP (OR1.0, 95CI% 0.34-2.93).
pancreas is unknown. We hypothesized that tobacco alone or in combination CONCLUSION: Smoking is a major factor in the morphological progression of
with alcohol stimulates pancreatic fibrogenesis by PSC activation through the toxic CP. Smoking cessation should be strongly encouraged in these patients.
generation of oxidative stress within the cells. Maintained alcohol intake was not associated with the progression of the disease
AIMS & METHODS: Our aim was to evaluate the effect of tobacco alone and in in this study.
combination with alcohol on the activation of PSC and production of extracel- Disclosure of Interest: None declared
lular matrix (ECM) proteins, secretion of proinflammatory molecules and the
generation of oxidative stress within the cells.
PSC were isolated from rat pancreas Sprague-Dawley and exposed to tobacco OP346 POTENTIAL MECHANISMS OF THERAPEUTIC CANNABIS
(cigarette smoke condensate) alone (0.01mg/ml) or in combination of increasing USE IN CHRONIC PANCREATITIS
concentrations of ethanol (5 to 50mM). PSC activation (-SMA expression) was W.K. Utomo1,*, K. Parikh2, M. de Vries3, H. van Goor3, M.J. Bruno1,
measured in both early and primary cell culture by Western blot. Fibronectin-1 M.P. Peppelenbosch1, H. Braat1
(FNT-1) was evaluated by western blot and immunochemistry. Collagen-I was 1
Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam,
measured by western blot and Masson trichrome. As proinflammatory mole- 2
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
cules, fractalkine secretion was analyzed by Enzyme-linked immunosorbent 3
Surgery, Radboud University Medical Center, Nijmegen, Netherlands
assay. Oxidative stress was examined using 2-7-dichlorofluorescin diacetate Contact E-mail Address: w.utomo@erasmusmc.nl
(DCF-DA) and was detected by flow cytometry. Results are expressed as
meanSEM. Statistical analysis was carried out one-way ANOVA followed by INTRODUCTION: Cannabis has been a traditional medicine used for centuries
Fishers LSD post hoc test. to treat a broad range of disorders from asthma to multiple sclerosis. Several
RESULTS: Tobacco alone (-SMA 1.830.3; p0.003 versus negative control) studies using cannabinoid receptor agonists show possible anti-inflammatory and
or in combination with 50 mM ethanol (-SMA 1.530.2; p0.04 versus negative anti-carcinogenic effects in vitro and in vivo. However, the molecular pathways
control) induced PSC activation in early culture. Tobacco in combination with 50 underlying these effects remain unclear. Chronic pancreatitis is characterized by
mM ethanol increased the expression of collagen-I (3.91.2, p50.001 versus an ongoing inflammation leading to irreversible changes, and is associated with
negative control) and FNT-1 (3.60.3, p50.001 versus negative control and increased risk of developing pancreatic cancer.
ethanol alone). Tobacco also increased the expression of FNT-1 in combination AIMS & METHODS: We hope to reveal the signalling pathways that are acti-
of 10mM alcohol (2.230.1, p0.007 versus negative control). Tobacco in com- vated after ingestion of medicinal cannabis in patients suffering from chronic
bination with 50 mM ethanol induced fractalkine secretion at 48 hours (11.53.3 pancreatitis.
pg/mL vs 51.25 pg/mL negative control; p0.017). Ethanol (50mM) alone Cannabis-na ve volunteers drank a medicinal cannabis preparation
(3.060.77, p0.008 versus negative control) or in combination with tobacco (Bedrobinol). Peripheral blood was obtained before and 1 hour after ingestion.
(0.01mg/mL) (2.680.49 E50, p0.027 versus negative control) increased the Comprehensive descriptions of signal transduction were obtained in these sam-
reactive oxygen species fluorescence emission. ples employing kinome profiling on peptide chips exhibiting 960 different kinase
CONCLUSION: Tobacco alone or in combination with alcohol induces the substrates. We calculated mean phosphorylation levels for all 960 substrates
activation of PSC. Tobacco associated with alcohol increases the expression of before and after the treatment with medicinal cannabis. Additionally, we ana-
extracellular matrix proteins, fractalkine secretion and it is a potential inducer of lyzed peripheral blood from 3 patients enrolled in a phase 2 clinical trial compar-
oxidative stress. These results support for the first time the synergistic effect of ing purified 9-Tetrahydrocannabinol (Namisol) against placebo in chronic
alcohol and tobacco in the pathogenesis of chronic pancreatitis. pancreatitis patients (clinicalTrials.gov ID: NCT01551511) to confirm our find-
Disclosure of Interest: None declared ings in abovementioned kinome array.
RESULTS: As expected there is a great deal of similarity between the two
phosphoproteomes (r20.87). Phosphorylation of 106 substrates on the 960
array differs significantly between the two data sets. Of particular interest was
the strong down regulation of cell cycle kinases: Cdk2, Cdk5, and Cdk7. The
inhibition of the G1 to S phase kinase, Cdk2, is apparently mediated via a ATM/
ATR-p53-p21-dependent pathway. Furthermore, we observed a down regulation
of p38 MAP kinase, suggesting a specific anti-inflammatory effect. Finally, there
was also increased activity of the PI3K-Akt-mTOR signaling pathway, which
was confirmed in flow cytometry. Activation of the mTOR pathway is shown to
inhibit autophagy, possibly leading to enhanced cell death in tumors.
A110 United European Gastroenterology Journal 2(5S)
CONCLUSION: The observation that medicinal cannabis impairs activation of immunoreactivity was exclusively evident in acinar cells. In CP, a slight immu-
specific components of the inflammatory cellular signal transduction provides a noreactivity in acinar cells was present in 18 out of 60 tested patient samples.
mechanistic rationale for the use of medicinal cannabis in chronic pancreatitis IL1R1 mRNA expression showed a moderate but significant correlation with
patients and selected autoimmune diseases. Furthermore, the inhibition of cell neural hypertrophy.
cycle proteins leading to cell cycle arrest and upregulation of mTOR signaling The mean relative expression of IL13Ra2 did not differ between NP and CP. In
may contribute to anti-cancer properties of medicinal cannabis, justifying its use 17/32 patients with NP, a slight to moderate IL13Ra2 immunoreactivity was
in terminal cancer patients. evident in acinar cells, islets, and especially in intrapancreatic ganglia, whereas
Disclosure of Interest: None declared intrapancreatic nerves as such did not show any IL13Ra2 immunoreactivity. In
CP, a slight IL13Ra2 immunoreactivity was observed in acinar cells, tubular
complexes and islets and moderate immunoreactivity in intrapancreatic ganglia
OP347 DECREASED CFTR ACTIVITY AFTER ETHANOL in 33 out of 60 tested patient samples. IL13Ra2 mRNA expression correlated
CONSUMPTION AND IN ALCOHOLIC PANCREATITIS significantly with the presence of pain and showed a significant negative correla-
J. Maleth1,*, P. Pallagi1, L., V. Kemeny1, Z. Balla1, B. Kui1, A. Balazs1, tion with the severity of fibrosis.
L. Judak2, I. B. Nemeth3, Z. Rakonczay Jr.1, V. Venglovecz2, I. Foldesi4, CONCLUSION: Although IL1 and IL13 have been suggested to play major
A. Somoracz5, K. Borka5, D. Perdomo6, G.L. Lukacs6, M.A. Gray7, roles in the pathogenesis of CP in mice models, their receptors IL1R1 and
S. Monterisi8, M. Zaccolo8, M.M. Lerch9, M. Sahin-Toth10, P. Hegyi1 IL13Ra2 are not overexpressed in human CP. Furthermore, IL13Ra2 expression
1
First Department of Medicine, 2Department of Pharmacology and was even negatively correlated with the severity of fibrosis. These targets may
Pharmacotherapy, 3Department of Dermatology and Allergology, 4Department of therefore not be as promising as therapeutic targets in CP as initially
Laboratory Medicine, University of Szeged, Szeged, 52nd Department of hypothesized.
Pathology, Semmelweis University, Budapest, Hungary, 6Department of Disclosure of Interest: None declared
Physiology, McGill University, Montreal, Canada, 7Institute for Cell & Molecular
Biosciences, Newcastle University, Newcastle upon Tyne, 8Department of
Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom, OP349 SERUM IGG4 IN ACUTE, CHRONIC AND AUTOIMMUNE
9
Department of Medicine A, University Medicine Greifswald, Greifswald, PANCREATITIS
Germany, 10Department of Molecular and Cell Biology, Boston University Henry J. Buijs1,*, D.L. Cahen1, M. J. Van Heerde1, R.A. Hollemans2, B.E. Hansen1, H.
M. Goldman School of Dental Medicine, Boston, Hungary C. Van Santvoort2, M.G. Besselink3, H. R. Van Buuren1, M.J. Bruno1
1
Contact E-mail Address: jozsefmaleth1@gmail.com Erasmus University Medical Center, Rotterdam, 2University Medical Center,
Utrecht, 3Academic Medical Center, Amsterdam, Netherlands
INTRODUCTION: Excessive ethanol consumption is one of the most common Contact E-mail Address: j.buijs.1@erasmusmc.nl
causes of acute and chronic pancreatitis. It is also documented that genetic
defects of CFTR can lead to pancreatitis, however the effects of alcohol con- INTRODUCTION: Type 1 autoimmune pancreatitis (AIP) is the pancreatic
sumption on CFTR function in the pancreas is not known. manifestation of a systemic IgG4-related fibroinflammatory disorder (IgG4-
AIMS & METHODS: Our aim was to investigate the role of CFTR in the RD). It may be challenging to distinguish AIP from acute and chronic pancrea-
pathogenesis of alcohol-induced pancreatitis. The effects of ethanol and ethanol titis, as they share clinical and radiological features.
metabolites (fatty acids and fatty acid ethyl esters) on CFTR function and AIMS & METHODS: The aim of our study was to evaluate the diagnostic value
expression were examined in human (volunteers, patients and cell lines) and in of IgG, IgG-subclasses, and IgE, in distinguishing type 1 AIP from other forms
animal models (guinea pigs and CFTR-/- mice). of pancreatitis. Between March 2007 and May 2011, sera were obtained from
RESULTS: Sweat chloride concentration was increased in alcohol intoxicated consecutive patients presenting with AIP and chronic pancreatitis (CP) in a
patients but not in healthy volunteers, indicating impaired CFTR function. Dutch tertiary referral center. Sera from patients with acute pancreatitis (AP)
Moreover, decreased CFTR expression was found in pancreas specimens from were selected, stratified for gender and cause of pancreatitis, from a database of
patients with acute or chronic alcohol-induced pancreatitis. In functional studies, 732 patients, who participated in a Dutch multicentre trial between March 2004
we detected strong inhibitory effects of alcohol and fatty acids on CFTR activity and March 2007. Causes of acute pancreatitis were alcoholic, biliary and idio-
and HCO3- secretion in pancreatic ductal epithelial cells. The inhibition was pathic. Serum levels of IgG, IgG1-IgG4, and IgE were determined.
mediated by intracellular calcium overload, decreased cellular cAMP levels and RESULTS: A total of 174 patients were included; 32 with AIP, 90 with acute
ATP depletion. In addition, we reproduced the alcohol-induced decrease in pancreatitis, and 52 with chronic pancreatitis. Elevated IgG4 levels ( 1.4 g/L)
CFTR expression in cultured pancreatic epithelial cells and in vivo in guinea were found in 27 AIP patients (84%), but also in 7 AP (8%) and 9 CP patients
pigs, which was caused by a combination of reduced CFTR mRNA levels, (17%; p50.001). IgG4 levels 42x the upper limit of normal (ULN) were found
decreased cell surface stability and folding defect of CFTR. Finally, we in 66% of AIP patients, compared to none of the AP and 3 CP patients (6%;
showed that genetic deletion of CFTR lead to more severe pancreatitis in p50.001). Median serum IgG4 was higher in AIP than in AP and CP (Table 1).
CFTR knock-out mice induced by ethanol and fatty acids. Total IgG, IgG1, IgG3, and IgE levels were also increased in AIP patients,
CONCLUSION: The findings indicate that alcohol-induced loss of CFTR func- compared to the other types of pancreatitis. There was no difference in serum
tion is critical in the development of alcoholic pancreatitis; therefore, correcting IgG2 levels between the three groups.
CFTR function should offer therapeutic benefit. In AP and CP patients with elevated IgG4, none of the other subclasses was
Our research was supported by the Hungarian National Development Agency useful in distinguishing them from AIP patients. However, median total IgG and
grants (TAMOP-4.2.2.A-11/1/KONV-2012-0035, TAMOP-4.2.2-A-11/1/ IgE levels were lower in these patients, as compared to AIP patients (p0.02 and
KONV-2012-0052; TAMOP-4.2.2.A11/1/KONV-2012 - 0073; TAMOP- 50.001, respectively). In IgG4-negative AIP patients, serum IgE was higher than
4.2.4.A2-11-1-2012-0001, TAMOP- 4.2.4.A2-SZJO-TOK-13-0017), the in AP and CP patients (p0.013). Total IgG and the other IgG subclasses were
Hungarian ScientificResearch Fund (OTKA NF100677). comparable in IgG4-negative AIP and the other types of pancreatitis.
Disclosure of Interest: None declared Table 1 Serum IgG, IgG subclasses and IgE in patients with AIP, AP and CP.
Table to abstract OP349
OP348 EXPRESSION PATTERN OF IL1R1 AND IL13RA2 IN PATIENTS Variable AIP (n32) AP (n90) CP (n52) p-value1
WITH CHRONIC PANCREATITIS AND CLINICOPATHOLOGICAL
CORRELATIONS Total IgG 12.7 (10.5-21.7) 9.5 (7.7-11.1) 10.5 (8.9-12.6) 5 0.001*
1, 1 2 3 4
R. Poth *, J.G. DHaese , P. Brohawn , F. Bergmann , K. Tan , A. Lewis , 4
IgG1 7.7 (5.9-11.9) 5.4 (4.3-6.9) 6.2 (5.3-7.9) 5 0.001*
J. Roberts4, H. Friess1, G.O. Ceyhan1 IgG3 0.6 (0.4-1.0) 0.4 (0.3-0.7) 0.4 (0.3-0.6) 0.003*
1
Department of Surgery, KLINIKUM RECHTS DER ISAR, Munchen, Germany,
2 IgG4 4.5 (1.7-7.7) 0.4 (0.2-0.9) 0.6 (0.3-1.1) 5 0.001*
Translational Sciences, MedImmune, Gaithersburg, United States, 3Institute of
Pathology, University of Heidelberg, Heidelberg, Germany, 4Translational IgE 302 (50-978) 38 (16-104) 47 (19-102) 5 0.001*
Medicine, MedImmune, Cambridge, United Kingdom
Contact E-mail Address: jan.dhaese@med.lmu.de CONCLUSION: IgG4 levels are higher in AIP, but can be elevated in AP and
CP patients as well. Therefore, elevated serum IgG4 does not exclude a diagnosis
INTRODUCTION: Chronic pancreatitis (CP) is a major inflammatory disease of of AP and CP, and must be interpreted with caution in patients clinically sus-
the pancreas, characterized by vast inflammatory cell infiltration, pancreatic pected for AP or CP. Combined IgG4 testing with IgG or IgE, may contribute to
fibrosis and severe abdominal pain. IL1 has been shown to have an important the differentiation between AIP and other types of pancreatitis.
role in the pathogenesis of pancreatitis, where IL1b overexpression in the murine Disclosure of Interest: None declared
pancreas was associated with CP. IL13 is a major profibrogenic cytokine that has
recently been shown to promote pancreatic stellate cell proliferation suggesting
its role in pancreatic fibrogenesis. While evidence in animal models is constantly
growing, little is known on the expression status of these cytokines and their
receptors in the chronically inflamed human pancreas. In order to evaluate their
therapeutic potential, we therefore aimed to investigate the expression of the IL1
receptor IL1R1 and the IL13 receptor IL13Ra2 for the first time in human tissue
samples and correlate these with clinicopathological parameters.
AIMS & METHODS: The expression and localization of IL1R1 and IL13Ra2
was investigated in CP (n69), and normal pancreas (NP; n32) by QRT-PCR
and immunohistochemistry analyses. Results were correlated with clinicopatho-
logical parameters including the severity of fibrosis, pain, neuritis, and neural
hypertrophy.
RESULTS: There was no difference in the mean relative expression of the recep-
tor IL1R1 in NP vs. CP. In 16/32 patients with NP, a slight IL1R1
United European Gastroenterology Journal 2(5S) A111
WEDNESDAY, OCTOBER 22, 2014 8:3010:30 enrollment. Patients received subcutaneous TED 0.05 mg/kg/day for 24
HOT TOPICS IN SMALL INTESTINAL DISEASES LOUNGE 5_____________________ months (NT PBO/TED) or 30 months (TED/TED). Clinically meaningful
response was defined as 20%100% reduction from baseline in weekly PS
OP350 SAFETY AND EFFICACY OF LONG-TERM TEDUGLUTIDE volume; baseline was determined at enrollment in STEPS (TED/TED) or
TREATMENT FOR PATIENTS WITH SHORT BOWEL SYNDROME STEPS-2 (NT PBO/TED).
AND INTESTINAL FAILURE: FINAL RESULTS OF THE STEPS-3 RESULTS: Of the 88 patients enrolled (TED/TED, n37; NT PBO/TED,
STUDY n51) in STEPS-2, 65 (74%) completed the study. Among patients who com-
K. Iyer1,*, K. Fujioka2, J., I. Boullata3, T.R. Ziegler4, N.N. Youssef5, D. Seidner6 pleted the study, clinically meaningful response was achieved in 93% of TED/
1
Mount Sinai Medical Center, New York, NY, 2Scripps Clinic, La Jolla, CA, TED, 55% of PBO/TED, and 67% of NT/TED patients. PS requirement was
3
University of Pennsylvania, Philadelphia, PA, 4Emory University School of reduced by 7.6, 3.1, and 4.0 L/week in TED/TED, PBO/TED, and NT/TED
Medicine, Atlanta, GA, 5NPS Pharmaceuticals, Inc, Bedminster, NJ, 6Vanderbilt groups, respectively. 18 patients in TED/TED, 5 in PBO/TED, and 2 in NT/
University Medical Center, Nashville, TN, United States TED were able to achieve 3 days/week off PS. Responses to TED were
Contact E-mail Address: Kishore.lyer@mountsinai.org observed regardless of age, remnant anatomy, underlying disease aetiology, or
baseline PS requirements (subgroup analysis). Patients 545 years of age had a
INTRODUCTION: Patients with intestinal failure associated with short bowel 61% reduction, those between 4564 years had 65% reduction, and those 65
syndrome (SBSIF) require parenteral support (PS) because of malabsorption years of age had 76% reduction in PS from baseline. Patients with colon-in-
caused by intestinal resection or dysfunction. Chronic PS is associated with continuity had a 70% reduction and those without colon-in-continuity had a
serious complications and reduced life quality. Teduglutide (TED), a recombi- 57% reduction of PS from baseline. 21/22 patients who were responders with
nant analogue of human glucagon-like peptide 2, improves absorption by TED in STEPS and completed STEPS-2 sustained their response after 2 years of
increasing small bowel mucosal surface area.1 In a 24-week, placebo-controlled, TED treatment. 13/88 patients with varying baseline characteristics were able to
phase III study (STEPS) and its 2-year, open-label extension (STEPS-2), TED achieve independence from PS with TED treatment. TED was generally well
significantly reduced PS volume requirements and number of infusion days in tolerated. The most common gastrointestinal (GI) adverse events (AEs) were
patients with SBSIF.2,3 STEPS-3 was undertaken to further evaluate long-term abdominal pain (34%), nausea (19%), and abdominal distension (16%). The
efficacy and safety of TED in patients with SBSIF and provide prior clinical most common non-GI AEs were catheter sepsis (28%), episodes of weight
trial patients with TED access while awaiting marketing authorisation. decrease (25%), and asthenic conditions (23%). Although 64% of patients
AIMS & METHODS: STEPS-3 was a 1-year, open-label, multicentre study of reported serious AEs, only 10% were considered treatment related. The serious
subcutaneous TED (0.05 mg/kg/day) conducted in patients who enrolled in AEs included 3 cases of cancer (2 resulting in death and 1 considered treatment
STEPS and completed STEPS-2. Patients randomised to TED in STEPS related) and 1 additional death (not considered treatment related).
(TED/TED group) were exposed to TED for 42 months. Patients randomised CONCLUSION: In patients with SBSIF, long-term treatment with TED was
to placebo in STEPS (PBO/TED) and patients who qualified for STEPS but were generally well tolerated and resulted in durable and sustained response as demon-
not treated because of full enrolment (NT/TED) were exposed to TED for 36 strated by continued reductions in PS, and, in some patients, independence from
months. Baseline was considered the start of TED treatment in STEPS (TED/ PS. This effect was observed across a range of varying baseline characteristics.
TED group) or STEPS-2 (PBONT/TED group). REFERENCES
RESULTS: 14 patients enrolled (mean age, 56 years [range, 4080 years]; 12/14 1. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481.
[86%] white; 10/14 [71%] women; 8/14 [57%] with colon-in-continuity; Disclosure of Interest: P. Jeppesen Financial support for research from: NPS
meanSD prescribed PS volume at baseline, 12.98.1 L/week); 13 completed Pharmaceuticals, Inc, Consultancy for: NPS Pharmaceuticals, Inc, Other: advi-
the study. At the last dosing visit, PS was reduced from baseline by 9.8 L/week sory board member and study investigator for NPS Pharmaceuticals, Inc, K.
(50%), 3.3 L/week (35%), and 5.2 L/week (73%) in the TED/TED (n5), PBO/ Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator
TED (n6), and NT/TED (n3) groups, respectively. Compared with baseline, for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS Pharmaceuticals,
mean weekly PS infusions were reduced by 3.0 days/week in the TED/TED Inc, Other: employee of NPS Pharmaceuticals, Inc, S. OKeefe Financial support
group, 1.7 days/week in the PBO/TED group, and 2.8 days/week in the NT/ for research from: NPS Pharmaceuticals, Inc, Consultancy for: NPS
TED group. 2 patients achieved independence from PS after 126 and 130 Pharmaceuticals, Inc, Other: study investigator for NPS Pharmaceuticals, Inc
weeks of TED treatment (as of 1st visit off PS); 2 additional patients who
were weaned off PS in STEPS-2 maintained enteral autonomy throughout
STEPS-3. Treatment-emergent adverse events (AEs) occurred in all patients; OP352 INDEPENDENCE FROM PARENTERAL SUPPORT DURING
the most common were asthenic conditions and diarrhoea (both n3). No malig- TREATMENT WITH TEDUGLUTIDE AMONG PATIENTS WITH
nancies; gallbladder-, biliary-, or pancreatic-related events; episodes of gastroin- INTESTINAL FAILURE ASSOCIATED WITH SHORT BOWEL
testinal obstruction; or deaths were reported. Furthermore, no patient SYNDROME (SBSIF)
discontinued the study because of an AE. P.B. Jeppesen1,*, J., I. Boullata2, T.R. Ziegler3, U.-F. Pape4, K. Iyer5,
CONCLUSION: Long-term TED treatment for up to 42 months is associated M. Kunecki6, S.M. Schneider7, N.N. Youssef8, K. Fujioka9
with sustained efficacy in patients with SBSIF, as shown by continued reduc- 1
Department of Medical Gastroenterology CA-2121, RIGSHOSPITALET,
tions in PS requirements and achievement of PS independence in some patients. Copenhagen, Denmark, 2University of Pennsylvania, Philadelphia, PA, 3Emory
The safety profile was consistent with prior studies; no unexpected safety signals University School of Medicine, Atlanta, GA, United States, 4Charite University
were detected. Medical Center, Berlin, Germany, 5Mount Sinai Medical Center, New York, NY,
REFERENCES United States, 6M. Pirogow Hospital, Lodz, Poland, 7University of Nice-Sophia
1. Tappenden KA, et al. J Clin Gastroenterol 2013; 47: 602-607. Antipolis, Nice, France, 8NPS Pharmaceuticals, Inc, Bedminster, NJ, 9Scripps
2. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481. Clinic, La Jolla, CA, United States
3. Schwartz L, et al. Am J Gastroenterol. 2013; 108: S101. Contact E-mail Address: Bekker@dadlnet.dk
Disclosure of Interest: K. Iyer Consultancy for: NPS Pharmaceuticals, Inc, Other:
study investigator and advisory board member for NPS Pharmaceuticals, Inc, K. INTRODUCTION: The intestinotrophic agent teduglutide (TED) was asso-
Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator ciated with clinically significant reductions in parenteral support (PS) in clinical
for NPS Pharmaceuticals, Inc, J. Boullata Other: study investigator and advisory trials in patients with SBSIF.1-4
board member for NPS Pharmaceuticals, Inc, T. Ziegler Other: study investiga- AIMS & METHODS: We report the clinical characteristics of patients who
tor for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS achieved complete independence from PS while receiving TED 0.05 mg/kg/day
Pharmaceuticals, Inc, Other: employee of NPS Pharmaceuticals, Inc, D. in either of 2 phase III randomised controlled trials (RCTs)1,2 or their exten-
Seidner Financial support for research from: NPS Pharmaceuticals, Inc, sions.3,4 PS was reduced (at 4-week intervals in RCTs and 4- to 12-week intervals
Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator and advi- in extension studies) if clinical status was stable and 48-hour urine output was
sory board member for NPS Pharmaceuticals, Inc increased by 10% over baseline (target urine output: 12 L/day).
RESULTS: A total of 134 patients were treated with TED 0.05 mg/kg/day. Of
these, 16 patients achieved independence from PS after 12130 weeks of TED
OP351 SAFETY AND EFFICACY OF LONG-TERM TEDUGLUTIDE treatment (as of first visit off PS). The duration of PS dependency at baseline
TREATMENT: FINDINGS FROM A 2-YEAR, OPEN-LABEL (start of treatment with TED) ranged from 116 years in these patients. Baseline
EXTENSION TRIAL, STEPS-2 demographics and disease characteristics varied widely (Table 1). However, more
P.B. Jeppesen1,*, K. Fujioka2, N.N. Youssef3, S.J. OKeefe4 patients who achieved PS independence had colon-in-continuity (n12/16) and/
1
Department of Medical Gastroenterology CA-2121, RIGSHOSPITALET, or lower baseline PS requirements (57 L/week, n11/16). Adverse reaction
Copenhagen, Denmark, 2Scripps Clinic, La Jolla, CA, 3NPS Pharmaceuticals, Inc, profile of all treated patients was consistent with underlying cause of SBS, con-
Bedminster, NJ, 4University of Pittsburgh Medical School, Pittsburgh, PA, United comitant medication use, pharmacologic effect of TED within the gastrointest-
States inal (GI) tract, and PS requirements. The most commonly reported serious
Contact E-mail Address: bekker@dadlnet.dk adverse event (AE) in all treated patients was catheter sepsis; GI AEs were
common and were the main reason for discontinuation.
INTRODUCTION: Teduglutide (TED), a glucagon-like peptide-2 analogue,
enhances intestinal absorptive capacity and enables reduction of parenteral sup-
port (PS) requirements in patients with intestinal failure associated with short
bowel syndrome (SBSIF). In the pivotal, phase III, placebo-controlled STEPS
study, 63% of patients treated with TED had a 20%100% reduction in PS from
baseline at Weeks 20 and 24 vs 30% of patients receiving placebo (P0.002).1
STEPS-2 was a 2-year, open-label, multicentre, multinational extension study of
STEPS designed to assess the long-term safety and efficacy of TED.
AIMS & METHODS: Enrolled patients included those participating in STEPS
who completed 24 weeks of TED (TED/TED) or placebo (PBO/TED) treatment
or those who qualified but were untreated (NT/TED) owing to full study
A112 United European Gastroenterology Journal 2(5S)
Table 1. Baseline Characteristics of Patients Who Achieved Independence From
PS With TED (0.05 mg/kg/day)
Table to abstract OP335
SIZE RESECTION TYPE SITE SCARRED
ALL POLYP RECURRENCE 14/106 (13%) 6/78 (7.6%) 8/28 (28.5%) 1/42 (2.3%) 7/44 (15.9%) 13/83 (15.6%) 1/23 (4.3%) 6/20 (30%) 8/86 (9.3%)
P 0.009 P 0.001 P 0.15 P 0.024
UNSCARRED POLYP RECURRENCE 8/86 (9.3%) 2/62 (3.2%) 6/24 (25%) 1/42 (2.3%) 7/44 (15.9%) 8/68 (11.7%) 0/18 (0%)
P0.005 P0.058 P0.195
CONCLUSION: A number of patients with widely varied baseline characteris- TABLE. Analysis Results
tics were able to achieve enteral autonomy and independence from PS with TED
treatment. Ex-PN Intra-PN
REFERENCES Insulin Insulin
1. Jeppesen PB, et al. Gut 2011; 60: 902-914. Variables (n56) (n41) p-value
2. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481.
3. OKeefe SJ, et al. Clin Gastroenterol Hepatol 2013; 11: 815-823. Mean Age 65.91013.369 65.7610.178 0.949
4. Schwartz LK, et al. Am J Gastroenterol 2013; 108: S101. Male (%) 44.6% 43.9% 0.942
Disclosure of Interest: P. Jeppesen Financial support for research from: NPS Mean BMI 23.9184.556 22.5524.894 0.166
Pharmaceuticals, Inc, Consultancy for: NPS Pharmaceuticals, Inc, Other: advi- % hypoglycemia (54.0) by Population 31/1876 (1.7%) 16/1788 (0.9%) 0.042
sory board member and study investigator for NPS Pharmaceuticals, Inc, J. % hypoglycemia (54.0) by Patient-Day 21/438 (4.8%) 12/422 (2.8%) 0.182
Boullata Other: study investigator and advisory board member for NPS
% hypoglycemia (54.0) by Patient 10/56 (17.9%) 9/41 (22%) 0.462
Pharmaceuticals, Inc, T. Ziegler Other: study investigator for NPS
Pharmaceuticals, Inc, U.-F. Pape Other: study investigator and advisory board
member for NPS Pharmaceuticals, Inc, K. Iyer Consultancy for: NPS
Pharmaceuticals, Inc, Other: study investigator and advisory board member CONCLUSION: Protocolized administration of insulin inside PN bag has lower
for NPS Pharmaceuticals, Inc, M. Kunecki Other: study investigator for NPS risk of hypoglycaemia compared to Ex-PN insulin and can be safely
Pharmaceuticals, Inc, S. Schneider Other: study investigator and advisory board administered.
member for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS Disclosure of Interest: None declared
Pharmaceuticals, Inc, Other: employee of NPS Pharmaceuticals, Inc, K.
Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator
for NPS Pharmaceuticals, Inc OP354 LARGE DELETION IN THE EPCAM GENE RESPONSIBLE FOR
THE MILDER PHENOTYPE OF CONGENITAL TUFTING
ENTEROPATHY
OP353 RISK OF HYPOGLYCEMIA WAS LOWER WITH J. Gerada1, C. Saliba2,*, R. Galdies1, W. Cassar1, V. Mercieca3, J. DeGaetano1,
ADMINISTRATION OF PROTOCOLIZED INSULIN INSIDE E. Gerada1, N.J. Sebire4, S. Hill4, M. Vassallo1, C. Scerri2, G. Grech2,
PARENTERAL NUTRITION (PN) BAG COMPARED TO T.M. Attard1
CONVENTIONAL INSULIN ADMINISTERED SEPARATELY 1
Mater Dei Hospital, 2University of Malta, Msida, 3Gozo General Hospital, Gozo,
DURING TOTAL PARENTERAL NUTRITION (TPN) Malta, 4Great Ormond Street Hospital, London, United Kingdom
J.L. Hartono1,*, S.N. Teoh2, M.Y. Sim3, T.M. Foo3, C.Y. Tong4, L.L. Lim1
1
Gastroenterology and Hepatology, 2Pharmacy, National University Hospital INTRODUCTION: A number of point mutations within the EPCAM gene have
Singapore, 3Yong Loo Lin School of Medicine, National University of Singapore, been found to be responsible for congenital tufting enteropathy (CTE). We pre-
4
Dietetics, National University Hospital Singapore, Singapore, Singapore viously described a milder phenotype of CTE in a cohort of Maltese patients1.
Contact E-mail Address: juanda_leohartono@yahoo.com EpCAM staining was negative in the whole cohort1, suggesting a defective
EPCAM gene in the milder phenotype.
INTRODUCTION: Insulin dose adjustment for diabetic patients with inpatient AIMS & METHODS: To identify the underlying genetic abnormality within the
parenteral nutrition (PN) is required to achieve glycemic control. Route of EPCAM gene responsible for the milder CTE. In the period 1985 2012, eight
administration with concomitant protocolized insulin inside the PN bag is per- Maltese patients with CTE from six unrelated families were retrospectively iden-
ceived to have a higher risk of hypoglycaemia compared to conventional ad-hoc tified. Genomic DNA was extracted from peripheral blood. Primers for all nine
insulin administered separately. exons within the EPCAM gene were designed and optimized. PCR products were
AIMS & METHODS: We aim to compare the rate of hypolycemia between amplified and sequenced. To sequence exon 4 exon 6 region, the PCR product
those who received protocolized intra-PN bag insulin and ex-PN bag ad-hoc was purified from the gel and ligated in a TA Vector. The ligated products were
(sliding scale) insulin (administered separately) among diabetic patients who transformed into DH5 bacteria and cultured on ampicillin-containing agar
received inpatient TPN. plates. The cultured DNA was extracted and sequenced. All DNA sequences
Retrospective analysis was conducted for all inpatient diabetic patients who were compared with controls. Unaffected family members (parents) and healthy
received TPN between April 2008 to August 2012 in National University controls were screened for the deletion.
Hospital Singapore. Demographic data such as age, gender, and body mass RESULTS: Genetic analysis of the EPCAM gene in Maltese CTE patients
index (BMI) as well as glycemic reading was recorded. Hypoglycemia was defined revealed a novel homozygous 1773bp deletion in seven patients, starting from
as blood glucose level of 54.0 mmol/L based on ASPEN guidelines. Besides the 1170bp downstream of exon 4, up to 721bp upstream of exon 6, resulting in
conventional model of using the total number of glucose readings from all complete deletion of exon 5. The remaining patient was a heterozygote for the
patients between the 2 groups (by population), we also analysed other gluco- deletion. The mutant homozygous variant resulted in a frameshift, introducing
metrics using other analytic models by patient-day and by (individual) patient 23 novel amino acids, formation of a premature stop codon, p.Ala164Metfs*24.
as previously proposed (Goldberg PA et al. 2006) in order to have a more loss of the transmembrane domain and complete lack of EpCAM protein within
comprehensive result. By patient-day model was done by grouping the glucose the intestinal epithelium. Three sets of parents of 3 affected patients were all
readings into per single day readings per patient as denominator. By patient heterozygous for this deletion. 98 out of 100 healthy controls tested were homo-
model was done by grouping glucose readings of the entire stay using each zygous wild type and two (2%) were heterozygous for the deletion.
individual patient as denominator. CONCLUSION: This novel large deletion within the EPCAM gene was found to
RESULTS: Total of 97 patients were analysed (56 ex-PN insulin; 41 intra-PN be responsible for the milder phenotype of Maltese CTE patients. The hetero-
insulin) with total 3664 glucose readings. Results were summarised in Table. zygous mutation of the patients parents confirms the autosomal recessive pat-
Demographic characteristics (age, gender, and BMI) were similar between the tern of inheritance of CTE. This genetic deletion present in all patients implies a
2 groups. The hypoglycaemic rate for Intra-PN insulin group was not higher than founder effect and we propose this as the first genotype-phenotype correlation in
Ex-PN insulin group. The rate of hypoglycaemia was not significantly different isolated intestinal TE patients.
between Ex-PN insulin and Intra-PN insulin group using analysis model by REFERENCES
patient (10/56[17.9%] vs. 9/41[22%], respectively; p0.462) and by patient- 1. Gerada J, Scerri C, DeGaetano J, et al. Epithelial EpCAM expression does not
day (21/438 [4.8%] vs. 12/422 [2.8%], respectively; p0.182). In fact, the correlate with intestinal absorptive function in the milder phenotype of tufting
number of glucose reading with hypoglycaemia was significantly higher in Ex- enteropathy Gut 2012; 61(Suppl. 3): A75.
PN insulin group using analysis model by population (31/1876 [1.7%] vs. 16/ Disclosure of Interest: None declared
1788 [0.9%]; p0.042).
United European Gastroenterology Journal 2(5S) A113
OP355 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS INJURE Ferrara JL, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha is
THE SMALL INTESTINE THROUGH NLRP3 INFLAMMASOME a biomarker of gastrointestinal graft-versus-host disease. Blood 2011; 15; 118:
ACTIVATION 6702-6708.
T. Watanabe1,*, A. Higashimori1, Y. Nadatani1, T. Tanigawa1, K. Tominaga1, Disclosure of Interest: None declared
Y. Fujiwara1, T. Arakawa1
1
Department of Gastroenterology, Osaka City University Graduate School of
Medicine, Osaka, Japan OP357 THE DIAGNOSTIC YIELD OF THE 75SEHCAT TEST IN
Contact E-mail Address: watanabet@med.osaka-cu.ac.jp PATIENTS WITH CHRONIC DIARRHOEA
N. Mottacki1,*, M. Simren1, K.-A. Ung2, A. Bajor1
INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) induce 1
Dept. of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy, University
intestinal overexpression of tumor necrosis factor (TNF)- in a Toll-like receptor of Gothenburg, Gothenburg, 2Department of Gastroenterology, Institute of
4 (TLR4)-dependent manner, causing small intestinal damage (Watanabe et al, Medicine, Skovde, Sweden
Gut, 2008). Although like TNF-, interleukin (IL)-1 is a potent proinflamma- Contact E-mail Address: nima.mottacki@vgregion.se
tory cytokine, its role in this damage remains unknown. The inflammasome
consists of one of several NOD-like receptors (NLRs) including NLRP3, INTRODUCTION: The 75SeHCAT test mirrors the turnover rate of bile acids
NLRP6, and NLRC4, the adaptor protein apoptosis-associated speck-like pro- and is used to diagnose bile acid diarrhoea (BAD). Retention 510% on day 7 is
tein containing CARD (ASC), and pro-caspase-1. The inflammasome is a large considered abnormal. Where this is not due to ileal disease (type 1), or associated
multiprotein complex whose assembly leads to pro-caspase-1 processing into with other pathologies (type 3) it is termed idiopathic bile acid diarrhoea (type 2).
cleaved caspase-1, which promotes the processing of pro-IL-1 into its mature AIMS & METHODS: We aimed to study the distribution of the 75SeHCAT test
active form. values in different conditions with chronic diarrhoea, and to determine if there
AIMS & METHODS: The aim of this study was to investigate the role of are diagnostic groups where the test is unnecessary. The prevalence of idiopathic
inflammasomes and IL-1. Indomethacin (10 mg/kg) was administered orally BAD was also evaluated. 2112 consecutive 75SeHCAT tests performed at our
to wild-type, NLRP3 knockout (KO), caspase-1 KO, or TLR4 KO mice. The university hospital were reviewed. Medical records from the referring clinic were
small intestines were removed 3, 6, 12, and 24 h after administration. Intestinal also investigated. Patients were included if referred for the investigation of diar-
damage was assessed by measuring the ulcerated area in the intestinal mucosa; rhoea and excluded if there was insufficient data to establish a cause of referral.
mRNA expression of inflammatory mediators was assessed using RT-PCR. Results in each diagnostic group were then compared to 29 previously published
Protein levels of pro-IL-1 and IL-1 in the small intestine were measured healthy controls using non-parametric tests. Patients were considered to have
using a specific ELISA. NLRP3, cleaved caspase-1, and IL-1 localization was BAD if 75SeHCAT on day 7 (S7) was less than 10%.
determined by immunohistochemistry. Further, to clarify the role of IL-1 in the RESULTS: Median S7 was significantly lower compared to controls in all diag-
damage, wild-type mice were intraperitoneally administered mouse recombinant noses except coeliac disease. The relative risk (RR) for a positive 75SeHCAT test
IL-1 (rIL-1), anti-IL-1-neutralizing antibodies, or vehicles after indomethacin in these patients was 7.2 compared to healthy controls. In those with ileocaecal
administration. Crohns disease and ileocaecal resection in particular RR was 13.5/12.0. Female
RESULTS: Small intestinal damage developed 3 h after indomethacin adminis- gender was more prevalent in all groups referred for testing, except patients with
tration and was accompanied by increases in IL-1B mRNA expression and UC. Though there were more female patients in those witout a predisposing
proIL-1 and IL-1 protein levels in the small intestine. IL-1 immunoneutrali- condition, there was a higher proportion of males testing positive for BAD in
zation attenuated small intestinal damage by 53%, while rIL-1 aggravated the this group of patients (54% vs. 42%, p50.005).
damage. NLRP3 mRNA expression increased after indomethacin administra-
tion, whereas that of other NLRs such as NLRP6 and NLRC4 did not. SeHCAT Median S7 Relative risk
Compared to the wild-type mice, the NLRP3 KO and caspase-1 KO mice Clinical feature (n) retention 510 (perc. 10, 90) %female (95% CI)
showed intestinal damage inhibition by 58% and 87%, respectively, with IL-1
protein level reduction, although pro-IL-1 levels were similar between the wild- All patients (n1602) 49.7% (n796) 10.7* (1.00, 36.0) 66.3 7.2 (1.9-27.3)
type and two types of KO mice. Genetic depletion of TLR4 prevented indo- No predisposing condition (n700) 46.4% (n325) 12.0* (1.86, 34.0) 61.4 6.8 (1.8-25.9)
methacin-induced overexpression of NLRP3 mRNA and IL-1 protein in the Cholecystectomy (n231) 67.5% (n156) 6.50* (1.00, 24.0) 85.3 9.8 (2.6-37.3)
small intestine and inhibited intestinal damage by 78%. Immunoreactivity for Collagenous colitis (n171) 35.1% (n60) 16.0* (3.03, 36.0) 79.5 5.0 (1.3-19.5)
cleaved caspase-1 and IL-1 was mainly observed in inflammatory cells such as
Crohns disease (n58) 93.1% (n54) 1.40* (0.01, 9.12) 56.9 13.5 (3.5-51.5)
macrophage, while NLRP3 was diffusely expressed on many types of cells includ-
Ileocecal resection (n58) 82.8% (n48) 2.40* (0.01, 13.2) 63.8 12.0 (3.1-45.9)
ing inflammatory and epithelial cells.
CONCLUSION: Our results suggest that the NLRP3 inflammasome plays a Lymphocytic colitis (n53) 34.0% (n18) 15.0* (1.2, 39.8) 66.0 4.9 (1.2-19.7)
crucial role in NSAID-induced small intestinal damage, and the TLR4 signaling Coeliac disease (n53) 20.8% (n11) 27.0 (3.86, 64.2) 77.4 3.0 (0.71-12.7)
pathway may trigger NLRP3 inflammasome activation. Ulcerative colitis (n38) 28.9% (n11) 20.0* (4.80, 49.7) 28.9 4.2 (1.01-17.5)
Disclosure of Interest: None declared
OP360 CLINICOPATHOLOGICAL FEATURE AND RISK FACTOR OF Overall (n39) 65.64 62.84-68.36 73.93 71.3-76.42 0.0002
INTERVAL CANCER with CLE experience (n7) 64.29 57.4-70.76 75.71 69.34-81.35 0.0195
K. Matsumoto1,*, A. Nagahara1, E. Sagawa1, Y. Nakagawa1, K. Matsumoto1, without CLE experience (n32) 65.94 62.84-68.93 73.54 70.63-76.31 0.0028
H. Ueyama1, N. Sakamoto1, T. Terai1, S. Watanabe1 GI physians and surgeons (GI) (n33) 66.87 63.84-69.80 75.66 72.86-78.30 50.01
1
gastroenterology, JUNTENDO UNIVERSITY SCHOOL OF MEDICINE, Pathologists (n6) 51.32 51.32-66.15 64.44 56.9-71.42 0.63
Tokyo, Japan German (n7) 55.71 48.72-62.55 64.9 57.40-70.76 NS
Contact E-mail Address: kmatumo@juntendo.ac.jp
Japanese (n32) 67.81 64.75-70.76 73.21 73.21-78.71 50.01
INTRODUCTION: Colorectal cancers diagnosed with a few years after index Expert w pathological training (n14) 67.38 62.66-71.84 73.33 68.83-77.50 p0.002
colonoscopy can arise from missed lesions or development of a new tumor and Expert w/o pathological training (n17) 67.64 63.39-71.69 77.25 73.37-80.82 p0.002
recently such cancers are reported as interval cancer.
AIMS & METHODS: We analyzed 59125 cases out of 43210 patients who
underwent colonoscopy. Patients were defined as having an interval cancer
(IC) if they detected colorectal submucosal invasive or deeper invasive cancer CONCLUSION: The results of this study demonstrated that reviewers clinical
within 36 months from index colonoscopy. Another cancer was defined as a non- backgrounds influenced CLE diagnosis for superficial gastric lesions and the
interval cancer (NIC). We investigated the clinical difference between IC and disease-specific expertise of standard endoscopic observation might benefit the
NIC. And investigated to clarify clinicopathological features and risk factors CLE diagnosis accuracy. The interpretation of unstable en face fluorescein
of IC. assisted CLE image might be more similar to real-time endoscopic diagnosis
RESULTS: We identified 35 cases of IC and 1030 cases of NIC. IC/NIC were than histological analysis of sliced fixed tissues.
male; 82.9%/65.3% (p0.03), diameter (T1stage); 15.9mm/21.1mm (p0.002), Disclosure of Interest: None declared
diameter (T2stage); 30.6mm/51.0mm (p0.002), respectively. Average interval
from index colonoscopy of IC was 18.1month. At the index colonoscopy,
patients which co-exist three or more lesions were 57.1%/36.7% in IC/NIC
United European Gastroenterology Journal 2(5S) A115
OP362 QUANTITATIVE ANALYSIS OF VOLUMETRIC LASER CONCLUSION: Maternal and neonatal ATA levels were inversely correlated
ENDOMICROSCOPY IMAGES WITH HISTOLOGICAL with the duration since last exposure. Cord blood ATA levels were strongly
CORRELATION OF EX-VIVO ENDOSCOPIC RESECTION correlated with maternal level at delivery. Maternal cessation of ATA prior to
SPECIMENS OF BARRETTS OESOPHAGUS WITH AND WITHOUT week 30 successfully reduced fetal exposure to drug in the vast majority of cases.
EARLY NEOPLASIA Follow up will determine whether high neonatal levels have any negative
A.-F. Swager1,*, D. M. de Bruin2, D.J. Faber2, B.L. Weusten1, S.L. Meijer3, consequences.
J.J. Bergman1, T. G. van Leeuwen2, W.L. Curvers1 Disclosure of Interest: M. Julsgaard: None declared, L. Christensen Lecture fee(s)
1
Gastroenterology and hepatology, 2Biomedical Engineering, 3Pathology, from: Ferring, MSD, AbbVie, Other: Member of the advisory board for MSD A/
Academic Medical Center, Amsterdam, Netherlands S, P. Gibson Financial support for research from: Janssen, AbbVie, Ferring,
Lecture fee(s) from: Janssen, AbbVie, Abbott, Fresenius Kabi, Astrazeneca,
INTRODUCTION: Early neoplastic lesions in Barretts oesophagus (BO) are Consultancy for: AbbVie, Janssen, Ferring, Takeda, Nestle, Danone, J.
difficult to detect with white-light endoscopy. Volumetric laser endomicroscopy Fallingborg Financial support for research from: Centocor, Abbvie, MSD,
(VLE) is a new optical coherence tomography (OCT)-based imaging technique UCB, Other: Advisory board member for Abbvie and MSD, R. Gearry
that provides large circumferential sub-surface maps of the superficial oesopha- Financial support for research from: AbbVie, Ferring, Lecture fee(s) from:
geal wall layers at a resolution of low-power microscopy. VLE data can be AbbVie, Janssen, MSD, Consultancy for: AbbVie, Janssen, MSD, A. Walsh
quantified by measuring the attenuation coefficient (mOCT), the decay of detected Consultancy for: Janssen, AbbVie, J. Kjeldsen: None declared, W. Connell
backscattered light versus depth. mOCT has the potential of providing quantitative Lecture fee(s) from: Janssen, Abbvie, M. Sparrow Financial support for research
optical diagnosis of interrogated mucosa because it relates to the organization of from: Ferring, Lecture fee(s) from: Janssen, Abbvie, Ferring, Other: Advisory
tissue. Board: Janssen, G. Radford-Smith: None declared, J. Andrews Financial sup-
AIMS & METHODS: To investigate the feasibility of mOCT for identification of port for research from: Janssen, AbbVie, Abbott, MSD, Ferring, Orphan,
early neoplasia in BO. Fresenius Kabi, Shire, Astrazeneca, Nycomed, Lecture fee(s) from: Janssen,
Endoscopic resection (ER) specimens from BO patients with and without neo- AbbVie, Abbott, MSD, Ferring, Orphan, Fresenius Kabi, Shire, Astrazeneca,
plasia were scanned ex-vivo with VLE. Histopathology slides from the specimens Nycomed, S. Connor Financial support for research from: Abbvie, Ferring,
were correlated one-to-one with VLE scans based on in-vivo and ex-vivo placed Orphan/Aspen, Shire, Lecture fee(s) from: Abbvie, Janssen, Shire, Ferring,
electrocoagulation markers. Quantification of VLE signal attenuation (mOCT) was Consultancy for: Abbvie, Janssen, Vifor, I. Lawrence: None declared, S. Wildt:
performed on areas of interest (AoIs) from VLE scans that were matched with None declared, G. Moore: None declared, L. Svenningsen: None declared, O.
histology in order to differentiate non-dysplastic (NDBO) and dysplastic BO Rosella: None declared, A. Grosen: None declared, S. Bell: None declared
mucosa.
RESULTS: In this pilot study, 14 endoscopic resection (ER) specimens yielded
14 histology-VLE matches with 25 AoIs consisting of 21 NDBO and 4 dysplastic OP364 CROSS-IMMUNOGENICITY: ANTIBODIES TO INFLIXIMAB IN
BO AoIs (LGD n1, HGD n3). Median mOCT values (mm-1) of the different REMICADE-TREATED IBD PATIENTS SIMILARLY RECOGNIZE
mucosa types were compared: NDBO 0.41 (IQR 0.17-1.82) and dysplastic BO THE BIO-SIMILAR REMSIMA
3.31 (IQR 1.43-5.49). A statistically significant difference was observed between S. Ben-Horin1,*, M. Yavzori1, E. Fudim1, O. Picard1, B. Ungar1, S. Lee2,
these groups (p 0.04). S. Kim2, Y. Chowers3
CONCLUSION: Quantitative VLE by means of mOCT may potentially differenti- 1
SHEBA MEDICAL CENTER, Tel-Hashomer, Israel, 2CELLTRION, Incheon,
ate between NDBO and dysplastic BO. Further research in larger sample size is Korea, Republic Of, 3Rambam Health Care Campus & Bruce Rappaport School of
needed to validate mOCT for the distinction between dysplastic and non-dysplastic Medicine, Technion Institute of Technology, Haifa, Israel
BO. Contact E-mail Address: shomron.benhorin@gmail.com
Disclosure of Interest: None declared
INTRODUCTION: Remsima, an infliximab bio-similar, recently received
European approval for use in IBD. However, the cross-immunogenicity of
WEDNESDAY, OCTOBER 22, 2014 11:0012:30 Remsima with the originator drug Remicade in IBD patients is unknown.
THERAPEUTIC DRUG MONITORING IN IBD HALL R_____________________ AIMS & METHODS: Sera of Remicade-treated IBD patients with measurable
antibodies to Remicade were tested by anti-lambda ELISA for their cross-reac-
OP363 TIME SINCE LAST DRUG EXPOSURE IN PREGNANCY tivity to two batches of Remsima. Sera negative for anti-Remicade antibodies
DETERMINES ADALIMUMAB AND INFLIXIMAB LEVELS IN were tested in parallel as controls. Anti-Remicade antibodies were tested for their
NEONATES (ERA STUDY) functional inhibition of TNFalpha-binding by either Remsima or Remicade
M. Julsgaard1,2,*, L.A. Christensen1, P.R. Gibson3, J. Fallingborg4, R. Gearry5, using a competition assay. Cross-reactivity of anti-adalimumab antibodies with
A. Walsh6, J. Kjeldsen7, W. Connell2, M.P. Sparrow3, G. Radford-Smith8, Remicade and Remsima was also investigated.
J.M. Andrews9, S.J. Connor10, I. Lawrence11, S. Wildt12, G.T. Moore13, RESULTS: In total, 124 sera were tested. All 68 positive anti-Remicade IBD sera
L. Svenningsen14, O. Rosella3, A. Grosen1, S.J. Bell2 were cross-reactive with Remsima. In negative controls (16 healthy individuals,
1
Aarhus University Hospital, Aarhus, Denmark, 2St Vincents Hospital, 3Alfred 40 IBD patients), there was a slightly higher background signal in the ELISA
Hospital, Monash University, Melbourne, Australia, 4Aalborg University Hospital, assay for Remsima compared to Remicade, but all 56 control sera which were
Aalborg, Denmark, 5Christchurch University hospital, Christchurch, New Zealand, anti-Remicade negative also tested negative for anti-Remsima antibodies.
6
St Vincents Hospital, Sydney, Australia, 7Odense University Hospital, Odense, Moreover, the measured titers of anti-drug antibodies were very similar when
Denmark, 8Royal Brisbane & Womens Hospital, Brisbane, 9Royal Adelaide reacted against Remicade or Remsima (rho values between 0.92 to 0.99, p50.001
Hospital, Adelaide, 10Liverpool Hospital, Sydney, 11Fremantle Hospital, for all experiments, Spearman correlation test). Anti-Remicade antibodies of
Fremantle, Australia, 12Koege Hospital, Koege, Denmark, 13Monash University, IBD patients (n10) exerted a similar functional inhibition on Remsima and
Monash Health, Melbourne, Australia, 14Herning Hospital, Herning, Denmark Remicade TNFalpha-binding capacity (PNS for all points on the inhibition
Contact E-mail Address: mjn@ki.au.dk curves). Antibodies to adalimumab in adalimumab-treated IBD patients (n7)
did not cross-react with neither Remicade nor Remsima.
INTRODUCTION: Recent studies suggest no adverse pregnancy outcomes in CONCLUSION: Antibodies-to-Remicade in Remicade-treated IBD patients
babies exposed to anti TNF antibodies (ATA). However, the long term implica- recognize Remsima to a similar extent, suggesting shared immuno-dominant
tions are unknown. This study aimed to examine drug levels of ATA in cord epitopes on these two infliximab agents. In contrast, there is no cross-reactivity
blood of newborns exposed to ATA in pregnancy, and to correlate these with of anti-adalimumab antibodies to Remsima or Remicade.
maternal levels, the duration of therapy during pregnancy, and time to clearance Disclosure of Interest: S. Ben-Horin Financial support for research from:
of ATA in infants. CELLTRION, Consultancy for: Abbott, Janssen, Takeda & Schering-Plough,
AIMS & METHODS: Women with IBD exposed to infliximab (IFX) or adali- M. Yavzori: None declared, E. Fudim: None declared, O. Picard: None declared,
mumab (ADA) during pregnancy were included from 2012-present at 14 hospi- B. Ungar: None declared, S. Lee Other: CELLTRION employee, S. Kim Other:
tals in Denmark, Australia and New Zealand. ATA levels were measured using CELLTRION employee, Y. Chowers Consultancy for: Abbott, Janssen, Takeda
an ELISA in cord and maternal blood at delivery (Matriks Biotek). If positive at & Schering-Plough
birth, the infants were tested every third month until ATA were undetectable.
Demographics, disease phenotype, disease activity in pregnancy, duration of
ATA use in pregnancy, medication and pregnancy outcomes were prospectively OP365 EARLY APPEARANCE OF ANTIBODIES TO INFLIXIMAB
collected by questionnaire and from the treating doctor. PREDICTS LACK OF RESPONSE TO INFLIXIMAB INDUCTION
RESULTS: 53 mother-baby pairs have been tested (27 IFX and 26 ADA). An TREATMENT IN PATIENTS WITH MODERATE-SEVERE
inverse correlation between duration since last exposure and cord ATA levels at ULCERATIVE COLITIS
birth was found (IFX: r 0.58, p 0.002; ADA: r 0.42, p 0.047). This was J.F. Brandse1,*, G. R. van den Brink1, J.M. Jansen2, M. Lowenberg1,
also the case for maternal levels at birth (IFX: r 0.59, p 0.002; ADA: C. Ponsioen1, G.R. DHaens1
r 0.52, p 0.01). There was a strong correlation between cord blood and 1
Department of Gastroenterology & Hepatology, Academic Medical Center,
maternal levels at delivery (IFX: Pearsons r 0.80, p 5 0.0001; ADA: r 0.80, 2
Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis,
p 5 0.0001). Drug was ceased prior to gestational week (GW) 30 in 15 (28%) Amsterdam, Netherlands
women. In them, mean serum concentrations were 0.81 mg/ml (IFX) and 0.08 mg/ Contact E-mail Address: j.f.brandse@amc.uva.nl
ml (ADA), and the cord blood level at delivery was 53 mg/ml in 11/15 (73%). So
far 30 babies have completed testing for detectable ATA levels, and testing is INTRODUCTION: Antibodies to infliximab (ATI) and low serum concentra-
ongoing in the remaining 23 babies. Complete clearance of ATA was seen in 7, 5, tions of infliximab (IFX) have been suggested as a cause of lack of response to
12 and 6 babies at birth, by 3, 6 and 9 months, respectively. To date there has this treatment in Ulcerative Colitis (UC). However, the measurement of antibo-
been one detectable ATA level at 9 months. Three women (5.7%) gave birth dies with conventional assays is limited in the presence of circulating drug.
preterm (GW 33-35). No congenital malformations were detected and all babies Therefore early development of ATI during IFX induction therapy and its rela-
are developing normally. tion to IFX concentrations and response have not been studied to date.
A116 United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We aimed to determine serum concentrations of IFX and OP367 IMPACT OF POSTINDUCTION INFLIXIMAB TROUGH LEVEL
ATI during induction therapy in patients with moderate-to-severe UC (endo- AND DISEASE ACTIVITY ON PRIMARY RESPONSE IN CROHNS
scopic Mayo 2/3) in a multicenter prospective study. Serum samples were col- DISEASE
lected at 10 serial time points during the first 6 weeks of therapy. IFX serum A. Echarri1,*, R. Ferreiro2, R. Fraga1, J. Cid3, M. Barreiro2, D. Carpio4,
concentrations and ATI were measured with a homogeneous mobility shift assay S. Pereira5, L. De Castro5, S. Soto6, A. Fernandez-Villaverde7, B. Gonzalez8,
(Prometheus Laboratories, San Diego, CA). Endoscopic response was defined as E. Santos9
improvement by at least 1 Mayo point at week 6-8. 1
Gastroenterology, Complejo Hospitalario de Ferrol, Ferrol, 2Gastroenterology,
RESULTS: Twenty patients were included, all but one receiving IFX according Hospital Universitario de Santiago, Santiago, 3Inmunology, Complejo Hospitalario
to standard induction regime (5mg/kg at week 0,2,6). 8/19 patients were endo- de A Coruna, Coruna, 4Gastroenterology, Complejo Hospitalario de Pontevedra,
scopic non-responders. ATI were detected in 7/20 patients, as early as on day 18 Pontevedra, 5Gastroenterology, Complejo Hospitalario de Vigo, Vigo,
from baseline (4 days after second infusion). In ATI positive patients week 6 6
Gastroenterology, Complejo Hospitalario de Orense, Orense, 7Gastroenterology,
median IFX trough level was 0 (0-11) ug/ml compared to 12 (8-15) ug/ml in ATI Povisa, Vigo, 8Gastroenterology, Complejo Hospitalario de A Coruna, Coruna,
negative patients (P50.01). During the induction phase 6/8 endoscopic non- 9
Gastroenterology, Complejo Hospitalario de Lugo, Lugo, Spain
responders tested ATI positive compared to 1/11 endoscopic responders Contact E-mail Address: ana.echarri.piudo@sergas.es
(P50.01, OR:30, 95%CI:2.2-406.2). 3/12 patients that used concomitant immu-
nomodulatory treatment developed ATI versus 4/8 without co-immunomodula- INTRODUCTION: Primary non-response to infliximab (IFX) induction therapy
tory treatment (ns). occurs in 10-20% of cases in clinical series. Few data have been reported on the
CONCLUSION: Early development of anti-IFX antibodies impairs IFX drug clinical impact of low serum IFX trough levels after the induction treatment and
concentrations and predicts non-response in patients with Ulcerative Colitis. their relation with clinical response, disease activity or the development of
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie and Takeda, immunogenicity.
G. van den Brink: None declared, J. Jansen: None declared, M. Lowenberg: AIMS & METHODS: There are two primary aims of this study: 1. To assess the
None declared, C. Ponsioen: None declared, G. DHaens Financial support for clinical relevance of a low serum IFX level during induction therapy. 2. To
research from: Abbott Inc, Jansen Biologics, Given Imaging, MSD, DrFalk identify possible risk factors associated with reduced serum levels of IFX.
Pharma, Photopill, Lecture fee(s) from: Abbott Inc, Tillotts, Tramedico, We included 36 Crohns disease patients with moderate to severe disease under
Ferring, MSD, UCB, Norgine, Shire, Consultancy for: Abbott Laboratories, infliximab induction treatment. Patients were treated with IFX 5mg/kg at 0, 2
Actogenix, Centocor, Cosmo, Engene, Ferring Pharmaceuticals, and 6 weeks as induction dose, followed by 5mg/kg every 8w.
GlaxoSmithKline, Jansen Biologics, Millenium Pharmaceuticals, MSD, Blood samples were drawn at standardized time points before and after induction
Novonordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB therapy (at 0, 6, 14 and 30w) just before IFX treatment. Serum IFX trough levels
and anti-Infliximab antibodies (ATI) were measured using an enzyme-linked
immunosorbent assay (ELISA). Disease activity was assessed at the same time
OP366 PERSISTENCE OF ANTIBODIES TO INFLIXIMAB FOR MORE points by means of the Harvey-Bradshaw Index (HBI; remission53, mild-mod-
THAN TWO MONTHS STRONGLY PREDICTS LOSS OF erate disease 4-14, and severe disease 415) and CRP/calprotectin levels.
RESPONSE TO INFLIXIMAB IN INFLAMMATORY BOWEL RESULTS: After IFX induction therapy, the median serum IFX trough level
DISEASES was significantly higher in patients in clinical remission (IFX: 7.62ug/ml) than in
M. leclerc1, S. Paul1, H. marotte1, E. deltedesco1, L. peyrin biroulet2, X. Roblin1,* patients with active disease (IFX 0.032 ug/ml P50.01).
1
CHU Saint Etienne, saint etienne, 2CHU Nancy, Nancy, France Receiver operating characteristic curve analysis indicated a cut-off value of 3ug/
ml at week 6. The positive predictive value of high postinduction IFX trough
INTRODUCTION: Antibodies to infliximab (ATI) are frequent and may be level (IFX43 ug/ml at 6w) for prediciting good response and sustained remission
associated with worse outcomes in Inflammatory Bowel Disease (IBD). The after IFX induction was 490%.
value of ATI (ATI threshold value, duration and kinetics) in predicting loss of ATI levels were detected in 26% of IFX treated patients and were significantly
response (LOR) is unknown. related to low trough levels and infusional IFX reactions. Low postinduction
AIMS & METHODS: We have studied, from a prospective cohort, all consecu- IFX trough levels were related to primary failure in 80% of patients. The cumu-
tive IBD patients treated with infliximab (IFX) who had at least 2 blood samples lative number of patients with low IFX trough levels were significantly higher in
for ATI measurement. Non primary responders to IFX were excluded. Loss of patients with severe disease activity and ATI detection
clinical response was defined by an increase in clinical symptoms requiring a CONCLUSION: 1. Low post-induction IFX trough levesl are associated with
therapeutic change (IFX dose intensification, initiation of another IBD-related primary failure.
medication, or surgery). 2. Optimal predictors of postinduction clinical remission to IFX were week 6
RESULTS: 93 patients (mean age 30 years, sex ratio 1.2, 59 Crohns disease, trough level43ug/ml and a low disease activity before treatment.
mean duration of follow up 17.2 months) were included in the study representing Disclosure of Interest: None declared
481 blood samples. 32 patients (34.4%) lost clinical response during follow-up: 34
patients (38%) had normal C-reactive protein (CRP), 27 patients (30%) had
positive ATI levels (14/27 only once and 13/27 more than 50% of their samples). OP368 DEVELOPMENT OF AN ALGORITHM INCORPORATING
A significant correlation was found between positive ATI level and LOR (p PHARMACOKINETICS OF ADALIMUMAB IN INFLAMMATORY
0.011) and between positive CRP level and LOR (p 0.0003). At time of first BOWEL DISEASES
sample, an ATI threshold 4 20 ng/mL predicted LOR with 94% specificity and X. Roblin1,*, M. Rinaudo1, E. Deltedesco1, L. Peyrin Biroulet2, S. Paul1
22% sensitivity (likelihood ratio 3.39, AUROC 0.59). Presence of positive ATI in 1
CHU Saint Etienne, saint etienne, 2CHU Nancy, Nancy, France
more than 50% of one patients samples was associated with more than 50% of
LOR to IFX during follow up, and with systematic clinical relapse in case of INTRODUCTION: Several decision algorithms based on the measurement of
permanent ATI (p 0.0044). The rate of LOR increased in parallel with the infliximab (IFX) trough levels and antibodies to infliximab (ATI) have been
number of consecutive samples positive for ATI (66.7% of LOR when at least 2 proposed (1). Whether such algorithms can be extrapolated to the pharmacoki-
positive samples), whereas transient ATI were not associated with LOR (p netics of adalimumab (ADA) has yet to be determined.
0.01). Concomitant thiopurines, duration and dose of IFX were not associated AIMS & METHODS: A prospective study included all consecutive patients with
with LOR neither with detectable ATI (permanent or transient) (p NS). IBD having a disease flare while being on ADA 40 mg every two weeks mono-
Independent predictive factors of LOR were ATI 4 20 ng/mL (p 0.0071) therapy were included. All patients were primary responders to ADA and anti-
and CRP 4 5 mg/L (p 0.0046). Their association was a better predictor of TNF naive. ADA trough levels and antibodies to adalimumab (AAA) were
treatment relapse than each one separately: relative risk of maintaining clinical measured in blindly to clinical data (Elisa LISA-Tracker, Theradiag). All patients
remission was 0.21 [CI 95%, 0.08-0.55] for CRP 4 5 g/L in association with ATI were optimized with ADA 40 mg weekly. Four months later, in the absence of
4 20 ng/mL, 0.64 [CI 95%, 0.46-0.9] for ATI 4 20 ng/mL alone, and 0.65 [CI clinical remission (CDAI 5 150 for Crohns disease (CD), and Mayo score 5 2
95%, 0.43-0.9] for CRP 4 5mg/mL alone. There was a significant inverse corre- for ulcerative colitis (UC)), patients were treated with IFX therapy. Patients were
lation between IFX and ATI levels; the highest association was found between y divided into three groups based on ADA trough levels based on previous
IFX trough levels at time 0 and ATI levels at time 1 (e.g. next infusion), studies:
indicating that IFX trough level decreases before ATI induction. Group A: ADA44.9 g/mL
CONCLUSION: ATI kinetics has a strong value to predict LOR to IFX therapy. Group B: ADA5 4.9 g/mL and undetectable levels of AAA (5 10 ng/mL)
The presence of more than 50% of samples positive for ATI (4 20 ng/mL) for a Group C: ADA54.9 mg/mL and AAA 4 10 mg/mL
given patient is associated with more than 50% of LOR. Permanent ATI levels RESULTS: 82 patients were included (55% CD, mean age 43 years, disease
are always associated with treatment relapse. Only one sample positive for ATI duration 7.4 years, duration of ADA therapy 17 months). After optimization
does not predict LOR. Two consecutive samples positive for ATI are associated of ADA treatment, 29.2% of patients achieved clinical remission in the group A
with 66.7% of LOR whereas transient ATI were not associated with LOR. ATI (N 41), 67% in the group B (N 24), and 12% in the group C (N 17) (p 5
and CRP levels are predictors of LOR. Preventing ATI formation is crucial to 0.01 between groups A/B and B/C). CRP level at the time of relapsee, disease
reduce LOR to IFX in clinical practice. duration, duration of ADA therapy and type of IBD were not predictive of
Disclosure of Interest: None declared clinical remission after optimization by univariate analysis. The response to
ADA optimization was significantly more durable in the group B (15 months)
than in groups A and C (respectively 4 and 5 months). Fifty seven patients who
failed following ADA optimization (69%) were treated with IFX and 31.6% of
them achieved clinical remission. Clinical remission rates following IFX initiation
were 12 %, 25% and 80% in groups A, B and C (p 5 0.01 between groups C/A
and C/B), respectively. Duration of response to IFX was significantly higher in
the group C than in groups A and B (14 vs. 3 and 5 months, respectively, p
50.01).
CONCLUSION: The presence of low ADA trough levels in serum without AAA
is strongly predictive of a favorable clinical response after ADA optimization
United European Gastroenterology Journal 2(5S) A117
(67%). Conversely low ADA levels with detectable AAA are associated with group. We found early stent dislodgement in 5 patients (2 stents without internal
failure of ADA optimization and a switch to IFX should be considered. ADA flaps, 3 FTSs), who all developed mild PEP. Of the 3 patients who received FTS 1
trough levels 4 4.9 mg/mL are associated with clinical response to two anti- TNF had severe postpapillotomy bleeding one day after the ERCP, while the other 2
(optimisation and switch) in only 10% of cases and must provide an other had papillary balloon dilation which might have contributed to early stent dis-
treatment than anti-TNF (class change). lodgement. Proximal stent migration into the pancreatic duct occurred in 3
Disclosure of Interest: None declared patients, all inserted stents were straight with internal flaps. Stent extraction
was possible in 2 patients, while it was unsuccessful twice in 1 patient, who finally
underwent distal pancreatectomy. We did not observe this complication since the
WEDNESDAY, OCTOBER 22, 2014 11:0012:30 introduction of FTSs into our practice. Although it has been described earlier we
IMPROVING SAFETY OF ERCP HALL N_____________________ have not observed pancreatitis due to stent removal.
CONCLUSION: PPS insertion is a safe method however complications may
OP369 NOVEL ERCP PHANTOM WITH X-RAY SIMULATION occur. The most severe is proximal stent migration, which may lead to surgery
OPTIMIZED AND SAFE TRAINING WITHOUT RADIATION in minority of cases when endoscopic removal remains unsuccessful. The use of
EXPOSURE FTS might prevent this complication. Other complications are mild and can be
R. Ingenpa1, A. Zipfel1, U. Schweizer1, M. Vietz2, V. Aurich2, K.E. Grund1,* managed conservatively.
1
Experimental Surgical Endoscopy, Visceral and Transplant Surgery, University Disclosure of Interest: None declared
Hospital Tubingen, Tubingen, 2Institute for Informatics, Heinrich Heine University
Dusseldorf, Dusseldorf, Germany
Contact E-mail Address: chir.endo@uni-tuebingen.de OP371 PROPHYLACTIC PANCREATIC STENT PLACEMENT AFTER
DUODENAL ENDOSCOPIC SNARE PAPILLECTOMY;
INTRODUCTION: ERCP is a challenging endoscopic procedure which requires PROSPECTIVE, RANDOMIZED STUDY
profound knowledge of anatomy and pathology as well as optimal diagnostic Y.D. Cho1,*, S.W. Cha1, P. Ahn1, T.H. Lee,1, H.J. Choi1, S.-H. Park1, S.J. Kim1
and therapeutic experience in handling of the equipment as well as a good 1
Internal Medicine, Digestive Research, Digestive Disease Center, Soonchunhyang
manual dexterity. University, College of Medicine, seoul, Korea, Republic Of
In the meantime simulator training becomes more and more relevant for learning Contact E-mail Address: ydcho@schmc.ac.kr
how to perform ERCP since MRCP has replaced diagnostic ERCP procedures.
But until now all training concepts neglect the important role of X-ray in differ- INTRODUCTION: Endoscopic snare papillectomy (ESP) is an efficient treat-
ent aspects (diagnostic yield, adjustment of the equipment and especially expo- ment for benign tumors of the duodenal major papilla. However, acute pancrea-
sure to radiation). Measurements, calculations and literature REFERENCES titis is the most common and serious complication following an ESP.
show high X-ray exposure already in clinical routine in training situations X- AIMS & METHODS: The aim of this study was to compare the rate of post-ESP
ray doses far exceed all legal levels. This is especially for female trainees and pancreatitis in patients who did or did not receive prophylactic pancreatic stent
tutors intolerable and inacceptable. placement.
To summarize, a good training setting should include an anatomically correct From March 2010 to March 2014, consecutive patients who were to undergo ESP
phantom and a possibility for optimal hands-on training as well as training of X- were randomized to pancreatic stent placement group (stent group) after ESP or
ray adjustment and learning without X-ray exposure. to no pancreatic stent placement group (no stent group). The overall outcomes
AIMS & METHODS: Our established hands-on ERCP phantom ("Tubingen after ESP including complications were compared between two groups.
Biliphant") has been additionally supplemented with a virtual reality module RESULTS: The 37 patients who received ESP for the treatment of major duo-
to eliminate the need of real X-ray exposure. This VR module consists of an denal papillary tumors were enrolled. 19 patients were assigned to the stent group
X-ray simulation system which generates the radiologic image virtually, based on and 18 patients to the no stent group. Post-ESP pancreatitis developed in 8
a complex sensor system inside the phantom. The reality-like virtual radiologic patients (21.6 %, 8/37), 5 cases occurred in the stent group and 3 cases occurred
image is depicted simulanteously with the endoscopic pictures on an external "X- in the no stent group. One case in the stent group was considered moderate grade
ray monitor". With this system the movements of guidewires and instruments can pancreatitis and the others were considered mild grade pancreatitis. The overall
be recorded by incorporated sensors, processed as a X-ray image and visualised incidence of post-ESP pancreatitis were 26.3% (5/19) in the stent group and
realistically and synchronously with the hands-on manoeuvres. The adjustment 16.7% (3/18) in the no stent group (p0.693). Although there was no statistic
of the X-ray system with all its features, e.g. widefield, zoom, pulsed mode, significance, post-ESP pancreatitis was higher in the stent group.
scatters etc. is controlled on a virtually generated panel displayed on a touch CONCLUSION: The development of post-ESP pancreatitis were not signifi-
screen; the virtual X-ray picture changes according to the adjustments. cantly different in patients with prophylactic pancreatic stent placement com-
RESULTS: The Tuebingen training phantom "Biliphant" meets the high require- pared to those without it. Our data suggest that the effectiveness of prophylactic
ments for a realistic hands-on training of ERCP and in combination with the pancreatic stent placement after ESP may be doubtful. Therefore, more large
virtual reality module for X-ray simulation opens the possibility for an unlimited scaled prospective, randomized controlled studies regarding the effectiveness of
training time and repetition rate for all interventional procedures without any X- pancreatic duct stent placement to reduce incidence of post-ESP pancreatitis are
ray exposure. needed.
This is an important factor especially for female trainees. This universal ERCP Disclosure of Interest: None declared
training system with its reality-like X-ray modules overcomes the disadvantages
of traditional ERCP training phantoms. For the first time both endoscopy and
radiology can be trained in a reality-like clinical setting but without X-ray OP372 PANCREATIC STENTS WITH A DIAMETER EXCEEDING FIVE
exposure. Due to the modular construction of the model individual training FRENCH SEEM TO HAVE A PROTECTIVE EFFECT ON POST ERCP
situations can be simulated and each training step in the full range of all diag- PANCREATITIS - A NATIONWIDE, REGISTER-BASED STUDY
nostic and therapeutical interventions can safely be repeated as often as desired. L. Enochsson1,2,*, G. Olsson2,3, F. Swahn1,2, M. Lohr1,2, U. Arnelo1,2
CONCLUSION: In conclusion, the virtual X-ray simulation system allows 1
Department of Gastroenterology, Karolinska University Hospital, 2Department of
hands-on ERCP training without X-ray exposure for a safe training session in Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm,
a realistic hospital-like setting. 3
Department of Surgery, Ryhov County Hospital, Jonkoping, Sweden
Disclosure of Interest: None declared Contact E-mail Address: lars.enochsson@ki.se
INTRODUCTION: The role of pancreatic stenting as a prophylactic measure to
OP370 COMPLICATIONS OF PROPHYLACTIC PANCREATIC reduce post ERCP pancreatitis (PEP) has yet to be determined. In the literature
STENTING USED FOR THE PREVENTION OF POST-ERCP there are conflicting views as of the beneficial effects of pancreatic stenting where
PANCREATITIS WITH REGARDS TO STENT TYPES: RESULTS OF A some studies advocate that temporary small-caliber pancreatic stenting reduce
PROSPECTIVE, CONTROLLED STUDY the risk of PEP(1) whereas other studies indicate the opposite(2). However, most
Z. Dubravcsik1,*, L. Madacsy1, I. Hritz1, A. Szepes1 studies are either single institution studies(1) or small in numbers(2).
1
Gastroenterology and Endoscopy, BACS-KISKUN COUNTY HOSPITAL, AIMS & METHODS: The present report aims to address the use of pancreatic
Kecskemet, Hungary stenting in a wider clinical perspective as well as analyzing its effect on the risk of
Contact E-mail Address: dubravcsikzs@gmail.com developing PEP.
We performed a nationwide study of ERCP procedures, with or without pan-
INTRODUCTION: Post-ERCP pancreatitis (PEP) is the most common compli- creatic stenting, registered in the Swedish Registry for Gallstone Surgery and
cation of ERCP, which can be severe and life threatening especially in high risk ERCP (GallRiks), between 2005 and 2013. Data were collected from the web-
patients. Prophylactic pancreatic stent (PPS) insertion is suggested to prevent based registry where ERCP procedures are registered prospectively. The primary
PEP. Although it is a safe procedure a few complications have been described. outcomes were pancreatitis and postoperative adverse events.
The aim of the study was to analyze these in terms of stent types in our pro- RESULTS: Data from 47,486 ERCP procedures were analyzed (1163 with pan-
spectively collected database. creatic stenting). In this unselected study population pancreatitis (OR 3.03; 95%
AIMS & METHODS: 317 patients with high risk of PEP were considered for CI 2.48-3.67) and postoperative adverse events (OR 1.45; 95% CI 1.25-1.69) were
PPS placement over the past 5 years. PEP was categorized as mild, moderate and significantly increased in the group that received pancreatic stents. However, the
severe according to the Cotton consensus criteria. Three different types of 5 Fr, 3- main indications for the group that received pancreatic stents significantly dif-
5 cm long PPSs were used (straight with or without internal flap, and Freeman fered from those without pancreatic stenting. One single factor of importance for
type stent (FTS) with internal flap and outer pigtail end). Complications such as the risk of adverse events in ERCP is cannulation of the pancreatic duct. The
unsuccessful PPS insertion, early stent dislodgement and proximal migration risks of pancreatitis (OR 3.37; 95% CI 3.06-3.70) and postoperative adverse
were identified. events (OR 1.36; 95% CI 1.28-1.44) were significantly increased when the pan-
RESULTS: PPS insertion was unsuccessful in 29 patients (9.15%). PEP devel- creatic duct was cannulated. In order to get a better estimation of the protective
oped in 41.38% of these patients (n12; 7 mild, 4 moderate, 1 severe) compared effect of pancreatic stenting we did a subgroup analysis of the ERCP procedures
to 10.07% of the 288 successfully stented patients (n29; 24 mild, 4 moderate, 1 mainly directed towards cannulating the bile duct and where the pancreatic duct
severe). The complications rate was 2.78% (n8) in the successfully stented was accidentally cannulated. In this group the risk of pancreatitis (OR 1.17; 95%
A118 United European Gastroenterology Journal 2(5S)
CI 0.73-1.81) and postoperative adverse events (OR 0.98; 95% CI 0.79-1.35) was received a biliary stent, 16 a NBD, 3 patients both. Cholangiography through
not affected by pancreatic stent placement. However, we noted a significantly the NBD showed an intraductal fibrin clot in 2 cases (5.7%) easily removed with
increased risk for pancreatitis if the diameter of the pancreatic stent was 5 Fr as a Dormia basket. No cases of pancreatitis were reported after fibrin glue
compared to if the diameter was 45Fr (OR 4.08; 95% CI 1.31-18.02). injection.
CONCLUSION: Pancreatic stents with a diameter exceeding 5Fr seems to have a CONCLUSION: Endoscopic fibrin glue injection for refractory post-sphincter-
protective effect on the risk of pancreatitis. otomy and post-papillectomy bleeding could represent a safe and effective treat-
REFERENCES ment. Main limitation of this series is the lack of a control group.
1. Cotton PB, Garrow DA, Gallagher J, et al. Risk factors for complications REFERENCES
after ERCP: a multivariate analysis of 11,497 procedures over 12 years. 1) Boujaoude J, Pelletier G, Fritsch J, et al. Management of clinically relevant
Gastrointest Endosc 2009; 70: 8088. bleeding following endoscopic sphincterotomy. Endoscopy 1994; 26: 217-221.
2. Cheng C-L, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pan- 2) Ferreira LE and Baron TH. Post-sphincterotomy bleeding: who, what, when,
creatitis: a prospective multicenter study. Am J Gastroenterol 2006; 101: 139147. and how. Am J Gastroenterol 2007; 102: 2850-2858.
Disclosure of Interest: None declared 3) Mutignani M, Seerden T, Tringali A, et al. Endoscopic hemostasis with fibrin
glue for refractory postsphincterotomy
Disclosure of Interest: None declared
OP373 THE ROUTINE USE OF RECTAL NSAIDS FOR PREVENTION OF
POST-ERCP PANCREATITIS: A META-ANALYSIS
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
T. Otsuka1,*, S. Kamachi1, S. Nakashita1, T. Akiyama2, S. Kawazoe2, T. Noda3, SHEDDING NEW LIGHT ON MICROBIOTA IN IBD HALL O_____________________
Y. Eguchi1, K. Anzai1
1
Internal Medicine, Saga University Hospital, 2Hepatobiliary and Pancreatology,
Saga-Ken Medical Centre Koseikan, Saga, 3Internal Medicine, Karatsu Red Cross OP375 ACTIVATION OF THE GCN2/EIF2ALPHA/ATF4 PATHWAY
Hospital, Karatsu, Japan TRIGGERS AUTOPHAGY RESPONSE TO INFECTION WITH
CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE
INTRODUCTION: Acute pancreatitis is a common complication of endoscopic ESCHERICHIA COLI
retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflam- H. T. T. Nguyen1,*, A. Bretin1, J. Carriere1, G. Dalmasso1, A.-C. Maurin2,
matory drugs (NSAIDs) prevent post-ERCP pancreatitis (PEP); however, it is A. Bruhat2, A. Darfeuille-Michaud1
not clear whether rectal NSAIDs should be used to prevent PEP prior to routine 1
UMR 1071 Inserm, University of Auvergne, 2Human nutrition unit (UNH),
ERCP. INRA Theix, Clermont-Ferrand, France
AIMS & METHODS: PubMed and Embase were searched to identify rando-
mized controlled trials (RCT), published in English, that assessed the effective- INTRODUCTION: A high prevalence of the adherent-invasive E. coli (AIEC) in
ness of rectal NSAIDs to prevent PEP. These RCTs were included in a meta- the intestinal mucosa of Crohns disease patients has been shown. We previously
analysis to evaluate the efficacy of routine rectal NSAIDs for the prevention of showed that upon AIEC infection, autophagy is induced in host cells to restrain
PEP. AIEC intracellular replication. The underlying mechanism, however, remains
RESULTS: Our search identified 6 RCTs (Murray et al., 2003; Sotoudehmanesh largely unknown.
et al., 2007; Montano Loza et al., 2007; Khoshbaten et al., 2008; Otsuka et al., AIMS & METHODS: Here, we investigated the role of the GCN2/eIF2/ATF4
2012; Elmunzer et al., 2012), enrolling 1,666 patients, that assessed rectal pathway in autophagy response to AIEC infection. Autophagic activity was
NSAIDs in the prevention of PEP. Three trials (Murray et al., Khoshbaten assessed by Western blot and immunofluorescent labelling of LC3.
et al., and Elmunzer et al.) enrolled high-risk patients; the other three exam- Intracellular bacterial number was determined by bacterial invasion assay and
ined all patients undergoing ERCP. A fixed-effects meta-analysis of the six RCTs confocal microscopy. Binding of ATF4 to autophagy gene promoters was
showed a pooled odds ratio [OR] for PEP of 0.380 (95% confidence interval [CI] assessed by Chromatin immunoprecipitation (ChIP) assay. Wild type (WT)
0.268 to 0.539; P 5 0.001) without heterogeneity (P 0.450; I2 0). The pooled and GCN2 knockout (KO) mice were infected with an AIEC reference strain
number needed to treat (NNT) with rectal NSAIDs to prevent one episode of LF82 by gavage.
PEP is 7. A fixed-effects meta-analysis of the three RCTs that enrolled all RESULTS: Infection of human intestinal epithelial T84 cells with AIEC LF82
patients (Sotoudehmanesh et al., Montano Loza et al., and Otsuka et al.), total- strain activated the GCN2/eIF2/ATF4 pathway as shown by increased phos-
ing 744 patients, found that the routine use of rectal NSAIDs was associated with pho-GCN2 and phospho-eIF2 levels, enhanced ATF4 protein expression, and
a significant risk reduction, with a pooled OR for PEP of 0.328 (95% CI 0.171 to upregulated mRNA expression levels of ATF4 target genes. To explore the role
0.628; P 5 0.001) without heterogeneity (P 0.578; I2 0). The NNT with the of this pathway in host responses to AIEC infection, we used GCN2-deficient
routine use of rectal NSAIDs to prevent one episode of PEP is 16. There were no mouse embryonic fibroblasts (GCN2-/- MEF). GCN2 depletion suppressed
adverse events related to the routine use of rectal NSAIDs. eIF2 activation and inhibited the increase in ATF4 protein level induced by
CONCLUSION: Routine use of rectal NSAIDs prevents PEP. LF82 infection. mRNA expression levels of the autophagy genes p62, MAP1lc3,
Disclosure of Interest: None declared Beclin1, atg3 and atg7 were significantly increased in WT MEF upon LF82
infection, and this was blocked in GCN2-/- MEF. ChIP assay showed that
GCN2 depletion inhibited the LF82-induced binding of ATF4 to the promoters
OP374 ENDOSCOPIC FIBRIN GLUE INJECTION AS A RESCUE of these autophagy genes. Consequently, autophagy induction upon LF82 infec-
THERAPY FOR REFRACTORY POST-SPHINCTEROTOMY AND tion was suppressed in GCN2-/- MEF, leading to increased LF82 intracellular
POST-PAPILLECTOMY BLEEDING replication and elevated pro-inflammatory cytokine production, compared to
S. Greco1,*, M. Napoleone1, M. Pizzicannella1, A. Tringali1, P. Familiari1, WT MEF. In vivo study consistently showed that LF82 infection activated the
I. Costamagna1, I. Bos koski1, V. Perri1, G. Vitale1, G. Costamagna1 GCN2/eIF2/ATF4 pathway in enterocytes from WT mice, but not GCN2 KO
1
Digestive Endoscopy Unit, Catholic University of Rome, Rome, Italy mice. In response to AIEC infection, autophagy was induced in WT mouse-
Contact E-mail Address: santi.greco@rm.unicatt.it derived enterocytes, and this was not observed in KO mice. LF82 persistence
in the gut was increased in KO mice, leading to aggravated intestinal inflamma-
INTRODUCTION: Bleeding is the second most common complication after tion, compared to that in WT mice.
therapeutic ERCP. Endoscopic hemostasis can be achieved by epinephrine, CONCLUSION: The GCN2/eIF2/ATF4 pathway is activated in host cells
hemoclip, thermal coagulation or combining these options1,2. In case of failure, upon AIEC infection, which is served as a defense mechanism to induce a func-
the last options were radiological or surgical treatment1. Fibrin glue injection has tional autophagy to control the intracellular replication of AIEC.
been proposed for endoscopic hemostasis in this subgroup of patients3. Results of Disclosure of Interest: None declared
endoscopic injection of fibrin glue, for refractory post-sphincterotomy and post-
papillectomy bleeding, were analyzed in a large series.
AIMS & METHODS: Between October 2007 and April 2014, all patients with OP376 CHANGE OF INTESTINAL FUNGAL COMMUNITY
intraoperative or delayed bleeding following endoscopic sphincterotomy or COMPOSITION IN THE CHEMICALLY INDUCED INFLAMED GUT
papillectomy were collected from a prospective database. Bleeding was initially AND THEIR PROTECTIVE ROLE IN THE COLON
treated by diluted ephinephrine injection, hemoclips or thermal coagulation; X. Qiu1, N. Wu2, W. Jiang1, F. Zhang1, X. Yang3, Y. Liu1,*
when these methods failed, fibrin glue (Tissucol, Baxter, frozen storage; 1
Department of Gastroenterology, Peking University Peoples Hospital, 2Institute
Beriplast P, CSL Behring, refrigerator storage) was injected using 2 separate of Clinical Molecular Biology & Central Laboratory, Peking University Peoples
23G needles to avoid lumen clogging. After fibrin glue injection the bile duct Hospital, 3CAS Key Laboratory of Pathogenic Microbiology and Immunology,
was always drained with a stent or a naso-biliary drain (NBD) to avoid cholan- Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
gitis due to possible biliary obstruction from clot or glue migration3. Contact E-mail Address: qiuxinyun2819@126.com
RESULTS: Over a 6 year period, 3224 sphincterotomies (2928 biliary, 154 pan-
creatic major papilla, 50 minor papilla, 12 both major and minor pancreatic INTRODUCTION: Increasing studies have reported the important relationships
papilla, 80 both biliary and pancreatic) and 80 papillectomies were performed between gut microbes and the intestinal diseases. However, previous studies paid
at our Unit. Bleeding occurred in 256 (7.9%) cases, 208 intraoperative (6.4%) much attention on the intestinal bacteria, while neglected the role of many other
and 48 delayed (1.5%). Hemostasis was successful in 221 (86.3%) cases by microbes (such as fungi, virus and parasites, etc).
diluted ephinephrine injection, hemoclips or thermal coagulation. In 35 AIMS & METHODS: The aim of our study was to investigate the eukaryotic
(13.7%) cases (mean age 59.4 range 19-96) with refractory bleeding, 22 post- fungal community distribution in the normal and chemical induced-inflamed gut
sphincterotomy and 13 post-papillectomy, fibrin glue injection was used as as well as the relationship between fungi and colitis. C57B/L6 mice were given
rescue therapy. Stable hemostasis was reached in 33 (94.3%) patients after one drinking water containing 2.5% (w/v) Dextran sulphate sodium (DSS) ad libitum
session. A mean of 3.8 ml of fibrin glue was injected. One patient had re-bleeding for 7 days and water for two additional days, then the mucosa and feces in
after 48 hours and was successfully retreated by fibrin glue injection. In one case different part of the gut (ileum, cecum and colon) were collected when the
hemostasis failed after fibrin glue injection and also after fully covered metal mice were sacrificed on the day 9 to isolate the total DNA. The ITS1-2
stent insertion; emergency arteriography diagnosed and successfully treated a domain of fungal DNA were amplified and detected by Illumina HiSeq 2000
gastroduodenal artery pseudoaneurism. After fibrin glue injection 16 patients platform. Bioinformatic analysis was performed with the Quantitative Insight
United European Gastroenterology Journal 2(5S) A119
Into Microbial Ecology (QIIME) software and a previously described fungal ITS OP378 FAECAL MICROBIOTA IN INFLAMMATORY BOWEL DISEASE
reference database was used to classify the fungi. Shannon-Weiner biodiversity PATIENTS WITH AND WITHOUT ARTHROPATHY
index was calculated to represent the diversity of fungi. Quantitation of 18S J. Kabeerdoss1,* on behalf of, S Pugazhendhi, A Balekuderu, D Prabavathi,
rDNA in the mucosa and stool samples were used to represent the amount of Ruchika Goel, Debashish Danda and BS Ramakrishna
fungi. To compare the role of bacteria and fungi in the intestinal inflammation, 1
Department of Clinical Immunology and Rheumatology, Christian Medical
we depleted the intestinal bacteria or fungi by giving mice an antibiotic cocktail College, vellore, India
(AB) containing four different antibiotics or fluconazole in drinking water Contact E-mail Address: jayakanthan@cmcvellore.ac.in
respectively for 23 days. Sixty mice were randomly divided into six groups:
Normal diet group, DSS group, AB group, fluconazole group, ABDSS INTRODUCTION: Inflammatory bowel disease (IBD) is considered to result
group and fluconazoleDSS group. The AB and fluconazole were provided to from an abnormal innate immune response elicited by components of the gut
the mice from day 1 to day 23 if these anti-microbial drugs were used. In the DSS, microbiota in genetically predisposed individuals. The gut microbiota shows
ABDSS and fluconazoleDSS group, DSS was added into the drinking water alterations (dysbiosis) in IBD. Joint disease or arthropathy occurs in IBD. We
only from the day 15 to day 21 at a concentration of 2.5% (w/v). The body hypothesized that the gut microbial alterations in IBD patients would be differ-
weight change, colon length and colonic inflammation scoring of the colonic ent in those with arthropathy compared to those without arthropathy.
haematoxylin / eosin-staining paraffin sections were calculated. AIMS & METHODS: To compare gut microbial phylotypes in IBD patients
RESULTS: Fungi distribution varied and increased from ileum to colon, the with and without arthropathy.
diversity and richness of fungi both decreased in the gut of DSS-treated mice
compared with the Normal control. In the colon of DSS-treated group,
a n
IBD patients were recruited from outpatient departments of Christian Medical
w
College from January 2007 to March 2009. Clinical details, laboratory results,
r
Ascomycota was increased while Basidiomycota was decreased at the phylum
level and the Asperigillus, penicillium and Candida were augmented while the
Cladosporium and Cryptococcus were reduced at the genus level. Although
depleting the intestinal bacteria cannot prevent the happening of colitis, it can
dampen the colitis by a reduced weight loss, colon shortening and colonic inflam-
i t h d
and severity of joint involvement (by rheumatologist, RG & DD) were entered
into structured forms. Patients who had received antibiotics in the 60 days prior
W
to study were excluded. This study was approved by Institutional research board.
Fresh samples of stool were collected, DNA extracted and DNA libraries pre-
pared using primers targeting hypervariable regions (HVR) 3 and 4 of the 16S
mation scoring in comparison with the DSS group. On the contrary, depleting rRNA gene using multiplex identifier sequence tags. The DNA libraries were
the intestinal fungi caused aggravated intestinal colitis by an increased weight sequenced in a 454 sequencing platform. The metagenomic diversity and phylo-
loss, colon shortening and colonic inflammation scoring. genetic analysis was assessed using the MG-RAST pipeline. Taxonomic compar-
CONCLUSION: Intestinal fungi are part of the normal enteric microbiota, ison of bacteria between the groups was performed using Kruskal-Wallis test and
which could play a protective role in alleviating the intestinal inflammation. pairwise Wilcoxon test in linear discriminate analysis effect size (LEfSe) program.
The fungal community changed in different locations and conditions of the RESULTS: Twenty four IBD patients (12 with and 12 without arthropathy) were
gut, whereas it remains to be answered which fungi participate in protecting recruited for study. Arthropathy patients included five each with isolated axial
the gut and whether the fungal community interplay with the bacterial flora in and peripheral and 2 with mixed type of joint involvement. A total of 800,968
the intestinal canal or not. reads were generated for the current study. The median read count of the samples
Disclosure of Interest: None declared was 24,884 (range 17,774-48,477). Alpha (Shannon) diversity index was signifi-
cantly different between the groups (21.74.4 Vs 38.414.1; p50.05) with sig-
nificantly higher diversity in IBD with arthropathy. The taxonomic comparison
OP377 CAUSATIVE ROLE OF THE INTESTINAL MICROBIOTA IN between the groups revealed that statistically significant differences in the micro-
CROHNS DISEASE-LIKE ILEITIS USING GERM-FREE AND bial phylotypes were noted from Class to Strain levels. The important observa-
ANTIBIOTIC-TREATED TNFARE MICE tion noted in the study that Enterococcaceae, Enterococcus and Enterococcus
M. Schaubeck1,*, T. Clavel2, D. Haller1, J. Walter3, I. Martinez3, M. Roulis4, faecium were increased in IBD with arthropathy compared to IBD without
G. Kollias4 arthropathy.
1
Nutrition and Immunology, TU Munich, 2ZIEL Research Center for Nutrition CONCLUSION: An increase in the abundance of Enterococcus and its species in
and Food Sciences, Freising, Germany, 3University of Nebraska, Food Science and the faeces differentiated IBD patients with arthropathy from those without
Technology, Lincoln, United States, 4Biomedical Sciences Research Center arthropathy. Enterococcus may be relevant to the pathogenesis of arthropathy
Alexander Fleming, Vari, Greece in IBD.
Contact E-mail Address: monika.schaubeck@tum.de Disclosure of Interest: None declared
OP380 RISK OF INVASIVE PNEUMOCOCCAL INFECTION IN OP382 THE IMPLICATION OF ULCER IN EARLY GASTRIC CANCER:
PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A CAN WE PREDICT THE CLINICAL BEHAVIOR OF EARLY GASTRIC
NATIONWIDE DANISH COHORT STUDY CANCER?
B. Kants1, J. Simonsen2, S. Hoffmann3, P. Valentiner-Branth4, A.M. Petersen5, Y.J. Lee1,2,*, J.-H. Kim1,2, J.J. Park1,2, Y.H. Youn1,2, H. Park1,2, J.W. Kim1,3,
T. Jess2,* S.H. Choi1,3, S.H. Noh1,4
1
Microbiological Diagnostics & Virology, 2Department of Epidemiology Research, 1
Yonsei University College of Medicine, 2Internal Medicine, 3Surgery, Gangnam
3
Neisseria and Streptococcus Reference Laboratory, 4Department of Infectious Severance Hospital, 4Surgery, Severance Hospital, Seoul, Korea, Republic Of
Disease Epidemiology, Statens Serum Institut, Copenhagen, 5Department of
Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark INTRODUCTION: Although the presence of ulcer in early gastric cancer (EGC)
Contact E-mail Address: bjk@ssi.dk is important for the feasibility of endoscopic resection, only a few studies have
examined the implication of ulcer on clinicopathologic factors in EGC.
INTRODUCTION: Inflammatory bowel diseases (IBD) such as Crohns disease AIMS & METHODS: This study aimed to determine the role of ulcer as a
(CD) and ulcerative colitis (UC) are a result of an inappropriate immune predictor of clinical behavior in EGC. Medical records of patients with EGC
response. Therefore, the main purpose of the medical treatment is to moderate who underwent surgery between January 2005 and December 2012 were reviewed
the immune response thus reducing disease activity, leading to a theoretically retrospectively. The clinicopathologic characteristics were analyzed according to
increased risk of invasive pneumococcal infection (IPI). the presence and stage of ulcer in EGC. The stage of gastric ulcer was categorized
The objective of this study was to examine the impact of IBD on the risk of IPI. into active (A1, A2), healing (H1, H2) and scar (S1, S2) based on the endoscopic
AIMS & METHODS: Patients diagnosed with IBD from 1977 to 2013 were findings.
identified from the Danish National Patient Register. For each IBD patient, RESULTS: Of the 3249 patients who included in this study, the presence of ulcer
20 individuals matched according to sex, age, and municipalities were selected was observed in 2317 (71.3%) patients. The proportions of ulcer according to the
from the Danish Civil Registration System. The IBD and control group data stage were 6.9% (A1), 21.4% (A2), 28.9% (H1), 30.0% (H2), 9.8% (S1) and
were linked with IPI data from the national laboratory surveillance. 3.0% (S2). Submucosal invasion, lymphovascular invasion (LVI), perineural
Using Cox regression with time since onset of IBD/date of matching as under- invasion, and undifferentiated-type histology such as poorly differentiated ade-
lying time axis we calculated hazard rate ratios (HRRs) for IPI after IBD. nocarcinoma or signet ring cell carcinoma were significantly higher in ulcerative
RESULTS: Among 83,358 IBD cases we found 316 IPI cases giving an incidence EGC than non-ulcerative EGC. When compared according to the stages of ulcer,
of 38 per 10,000, whereas the controls had an incidence of 26 per 10,000. The submucosal invasion, LVI, and undifferentiated-type histology were significantly
HRRs for CD and UC within the first 6 months after IBD diagnosis were high associated with active ulcer stages (A1 and A2). These features were significantly
(43) and then decreased to a constant level which for CD was significantly common in order from active, healing and scar stage in EGC. However, lymph
higher (approximately twofold) than for the controls and for UC non-signifi- node metastasis was not significantly different according to the presence of ulcer
cantly just above 1. and ulcer stages.
CONCLUSION: We found an increased risk of IPI infections among patients CONCLUSION: Ulcerative EGC showed more aggressive behavior than non-
with IBD, which was most pronounced in the first years after diagnosis but ulcerative EGC. In addition, the stage of ulcer may predict the clinicopathologic
remained increased over time, especially in CD. behavior of EGC. Therefore, endoscopic appearance of ulcer should be carefully
Disclosure of Interest: None declared examined for an adequate management strategy in EGC.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
CLINICAL PERSPECTIVES ON GASTRIC MALIGNANT TUMOURS LOUNGE OP383 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL
5_____________________ DISSECTION FOR SUBMUCOSAL SUPERFICIAL EARLY GASTRIC
CANCER
OP381 THE INCIDENCE AND SEVERITY OF GASTRIC S. Nonaka1,*, I. Oda1, H. Suzuki1, S. Abe1, S. Yoshinaga1, T. Nakajima1,
PRENEOPLASTIC LESIONS ASSOCIATED WITH GASTRIC Y. Saito1
CANCER 1
Endoscopy Division, NATIONAL CANCER CENTER HOSPITAL, Tokyo,
D. Lazar1,*, S. Taban2, A. Dema2, M. Cornianu2, I. Ratiu1, I. Sporea1, Japan
A. Goldis1 Contact E-mail Address: snonaka@ncc.go.jp
1
Gastroenterology, 2Pathology, UNIVERSITY OF MEDICINE AND
PHARMACY TIMISOARA, Timisoara, Romania INTRODUCTION: Endoscopic submucosal dissection (ESD) for early gastric
Contact E-mail Address: lazar_daniela@yahoo.com cancer (EGC) is now widely accepted in Japan based on the absolute and
expanded histopathological criteria for curative endoscopic resection (Table)
INTRODUCTION: Gastric cancers are the result of a cascade of histological [1]. Although EGC with submucosal superficial invasion (5500m; SM1) is
changes or precancerous lesions, such as atrophic gastritis, intestinal metaplasia included the curative resection criteria, it is very difficult to diagnose the depth
and dysplasia. of invasion of SM1 before ESD and almost SM1 EGCs are evaluated histopatho-
AIMS & METHODS: Our batch consisted of 61 consecutive patients diagnosed logically in the resected specimen. There are a few reports of recurrence of such
with gastric cancer that underwent surgery. As witness group we used antral cases [2-3], so our aim is to investigate clinical outcomes for ESD of differentiated
biopsies taken from 96 patients admitted with dyspeptic syndrome. We followed type SM1 EGC.
the incidence and severity of precancerous lesions and infection with H. pylori in AIMS & METHODS: Patient/lesion characteristics and short-/long-term out-
both the gastric cancer group and the witness group. comes evaluated for 160 patients/163 EGCs diagnosed histopathologically as
RESULTS: There were 43 males and 18 females included (average age 59.34 curative resection of SM1 in the resected specimens among 2,429 patients/
years). According to the Lauren classification, gastric carcinomas studied were 2,767 lesions treated by ESD with curative intent from 1999 to 2008. Excluded
divided in three categories: intestinal type (62.3%), diffuse type (27.9%) and cases involved EGCs in remnant stomach/gastric tube; residual/recurrent lesions;
mixed carcinomas (9.8%). Intestinal type gastric carcinomas develop most fre- patients with follow-up periods 51 year.
quently on the background of chronic atrophic gastritis (65.8%), with moderate RESULTS: Male/female, 139/21; mean age SD, 67.18.4; location: U/M/L,
(28.9%) or severe (23.7%) atrophy of gastric mucosa, accompanied by intestinal 53/60/50; macroscopic type: 0-IIa/IIc/IIaIIc/others, 36/105/17/5; median tumor
metaplasia. Chronic atrophic gastritis is observed significantly more often in size, 15mm (range, 4-30); positive ulcer finding, 37 (22.7%); median procedure
intestinal type carcinomas, compared with the diffuse ones (p0.012). Diffuse time, 60 minutes (10-300); and perforation/delayed bleeding rates, 0% (0)/1.3%
type carcinoma is associated significantly more often with chronic superficial (2). Curative patients included 1 with local recurrence/regional lymph-node
gastritis (41.2%) compared with intestinal type carcinoma (p0.009) and with metastasis (LNM)/distant metastasis detected after ESD at 86 months and died
the witness group (p0.003). Intestinal metaplasia was observed significantly at 108 months; 1 with regional LNM detected after ESD at 50 months who
more often in intestinal type (68.4%), with moderate and severe extension and underwent surgery and is alive without further recurrence. Metachronous gastric
in mixed type (66.7%) compared with diffuse type carcinomas (23.5%) cancer (MGC) was detected in 11 patients including 7 underwent curative ESDs
(p50.001). Type III intestinal metaplasia is much more frequent in carcinomas for 10 MGCs and 4 received surgeries with 2 resulting non-curative ESDs, and 2
in comparison with benign lesions studied (p0.00006). Dysplastic lesions are surgical patients died from MGC. The median interval between ESD for SM1
noted significantly more often in gastric carcinomas of mixed type (66.7%) and EGC and treatments for first MGC was 74 months (12-142). As a result, there
intestinal type (60.5%) in comparison with the diffuse type (23.5%) (p0.001). were 20 deaths including 1 from SM1 EGC, 2 from MGC and 17 from other
High-grade dysplasia is much more frequent in mixed type (50%) and intestinal causes. Five- and ten-year overall/disease-specific survival rates for curative
type carcinomas (23.7%) in comparison with the witness group (2.1%). The patients were 91.1%/99.3% and 77.5%/94.0% (median follow-up period, 74.1
incidence of bacterial colonization is significantly greater in patients with intest- months [13-160]), respectively.
inal type (73.7%) and diffuse type carcinomas (64.7%) in comparison with the
witness group (p0.007).
CONCLUSION: Our observations sustain the different histogenesis of cancers
divided after Lauren classification, the incidence of chronic atrophic gastritis and
United European Gastroenterology Journal 2(5S) A121
Table: The absolute and expanded histopathological criteria for curative endo- Nanjing Drum Tower Hospital in China. The average number of lymph node
scopic resection retrieved and reviewed was 17 ( 10) per case. LNM was detected in 49 (12.9%)
Table to abstract OP383 cases. The patient mean age in the LNM group was significantly younger (54.2
12.8 years) than that in the non-LNM group (60.7 11.4, p50.05). The M/F
En-bloc resection ratio was also significantly higher in the former (1.33) than in the latter (2.28,
Negative horizontal and vertical margin p50.05). Univariate analysis of clinicopathologic risk factors showed a signifi-
No lymphovascular infiltration cantly positive correlation with LNM for the followings: distal gastric cancer
Absolute indication (DGC), tumor size larger than 3.1 cm, ulcerated pattern, invasion into submu-
- Differentiated type intramucosal cancer 20mm in size without ulceration cosa (SM1, SM2), undifferentiated cancer, poorly cohesive carcinoma, micro-
Expanded indications papillary carcinoma, poor differentiation, and lymphovascular invasion.
- Differentiated type intramucosal cancer 420mm in size without ulceration Multivariate analysis revealed that lymphovascular invasion (OR 25.891, CI
- Differentiated type intramucosal cancer 30mm in size with ulceration 9.077 73.849, P50.001) and DGC (OR 6.735, CI 1.438 31.532,
- Differentiated type submucosal superficial cancer (SM1) 30mm in size P50.05) were significant independent risk factors for LNM.
- Undifferentiated type intramucosal cancer 20mm in size without ulceration CONCLUSION: DGC and lymphovascular invasion are the independent risk
factors for LNM include. Therefore, EGC in the proximal stomach appears to be
CONCLUSION: Clinical outcomes of ESD for differentiated type SM1 EGC more suitable than DGC for endoscopic resection.
30mm were favourable, but one patient resulting curative ESD died from SM1 Disclosure of Interest: None declared
EGC. The careful attention must be taken for possible metachronous GC and
regional LNM even if more than 5 years passes from ESD for SM1 EGC.
REFERENCES OP386 GASTRIC MALT LYMPHOMA: ANALYSIS OF A SERIES OF
1. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guide- CONSECUTIVE PATIENTS OVER 20 YEARS
lines 2010 (ver. 3). Gastric Cancer 2011; 14: 113-123. J. Moleiro1,*, S. Ferreira1, P. Lage1, D. Pereira1
2. Oya H, et al. Gastric Cancer 2012; 15: 221-225. [Please provide 2nd and 3rd 1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil,
authors names and article title for ref. 2.] E.P.E., Lisboa, Portugal
3. Abe S, et al. Gastric Cancer. Epub ahead of print 31 January 2014. Contact E-mail Address: joana_moleiro@hotmail.com
Disclosure of Interest: None declared
INTRODUCTION: Gastric extranodal marginal zone lymphoma of mucosal
associated lymphoid tissue, gastric MALT lymphoma (GML), is associated
OP384 CHARACTERISTICS OF SYNCHRONOUS AND with Helicobacter pylori (HP) infection and characterized by an indolent course.
METACHRONOUS GASTRIC NEOPLASMS AFTER ENDOSCOPIC AIMS & METHODS: To evaluate demographic, clinical and endoscopic char-
SUBMUCOSAL DISSECTION acteristics, status HP, stage, response to therapeutic and long-term prognosis of
T. Yamaguchi1,*, T. Kuwai1, S. Iio1, A. Tsuboi1, T. Mori1, K. Boda1, patients followed in our institution. Data of consecutive patients with GML
K. Yamashita1, A. Yamaguchi1, H. Kouno1, H. Kohno1 (1993-2013) staged by Ann Arbor classification / Musshoff were analyzed.
1
Department of Gastroenterology, National Hospital Organization Kure Medical Statistics: chi2, Kaplan-Meier (SPSS 20).
Center, Kure, Japan RESULTS: 144 patients (76 men; 68 women), mean age: 56 years (13-83), 67%
Contact E-mail Address: toshiki4662@yahoo.co.jp presented with dyspepsia. Most frequent endoscopic appearance and location
were erosions / ulcers (46%) in antrum or antrum-body transitional zone
INTRODUCTION: Endoscopic submucosal dissection (ESD) has become (57%), respectively. HP infection was detected in 71.5%. 127 patients (88%)
accepted as a minimally invasive treatment for gastric neoplasms such as early were diagnosed at stage IE/IIE (103/24). Stage IE: 94/103 patients (92%) received
gastric cancers (EGC) and gastric adenomas. However, gastric neoplasms found HP eradication regimens, 78 (83%) achieved remission after a mean period of 7
after initial ESD have become a major problem. months (1-63) and 67 (86%) were in remission after a mean follow-up time of 105
AIMS & METHODS: The aim of this study was to evaluate the clinicopatho- months. Diffuse and antrum plus body lymphomas were significantly (p0.007)
logical features of synchronous and metachronous gastric neoplasms after ESD. associated with lower remission rate. Relapse occurred in 11/78 (14%) patients
We studied 345 consecutive EGCs or gastric adenomas from 265 patients who after a mean period of 21 months. Patients that needed 2 eradication regimens
had undergone ESD between June 2007 and December 2012. They were periodi- had higher recurrence rate (p0.008). Stage IIE: eradication was performed in
cally followed up with endoscopic examination after 1 year or more. Patients 17/24 patients but only 5 experienced remission (30%). There were no patients
with remnant stomach or additional surgery were excluded from this study. We diagnosed at stage III and among 16 patients diagnosed at stage IV, 9 achieved
defined a second neoplasm found within 1 year after ESD as synchronous and remission after chemotherapy surgery and 3/7 without remission died due to
a second neoplasm found after more than 1 year as metachronous. In this disease progression. After a mean follow-up time of 109 months (4-246), 112
study, we investigated the incidence, clinical features and endoscopic findings patients are still alive (99 without disease) and 32 died (5 due to disease). 5, 10
associated with synchronous or metachronous gastric neoplasms. In cases with and 15-year overall survival rates were 91.8%, 82.8%, 66.9%, respectively.
metachronous lesions, data for the initial lesion were analyzed. In cases with CONCLUSION: Most patients were diagnosed at stage IE and among them HP
synchronous lesions, data for the initial or largest lesion were analyzed. eradication was an effective strategy. The diagnosis at an early stage avoided the
RESULTS: The median period of endoscopic follow up was 34 months (range 12 to need for aggressive therapies. The overall prognosis is favorable with high long-
77 months). In total, 199 patients (75.1%) had solitary lesions and 66 patients term survival rates.
(24.9%) had multiple lesions. In patients with multiple lesions, 49 patients had Disclosure of Interest: None declared
synchronous multiple lesions, 25 patients had metachronous multiple lesions, and
8 patients had both. No difference existed between age or gender among patients
with solitary, synchronous, and metachronous lesions. Additionally, no significant WEDNESDAY, OCTOBER 22, 2014 14:0015:30
differences existed between the three groups in terms of lesion location, macroscopic TARGETING NEW PATHWAYS IN IBD HALL L/M_____________________
type, or tumor size. However, marked atrophy (grading O2-3 according to Kimura
and Takemotos criteria) was significantly more frequent in patients with solitary OP387 DOWN REGULATION OF THE MICRORNA 200 FAMILY IN
lesions than in patients with synchronous or metachronous lesions. Concerning STRICTURED INTESTINAL RESECTION SPECIMENS FROM
metachronous lesions, all 28 lesions (25 second and 3 third lesions) in the 25 patients CROHNS DISEASE PATIENTS INDICATES A ROLE FOR
were underwent re-ESD. Of 28 lesions, 7 adenomas, and 20 mucosal carcinoma were EPITHELIAL TO MESENCHYMAL TRANSITION
treated curatively with re-ESD; only one lesion underwent additional surgery S. Mehta1,*, A. Lewis1, A. Nijhuis1, P. Biancheri2, C.L. Bishop3, J.O. Lindsay1,
because it invaded the submucosa to a depath into 500m less with ulceration. A. Silver1
CONCLUSION: To detect metachronous gastric neoplasms at a stage early 1
Digestive Diseases, 2Centre for Immunology and Infectious Disease, 3Centre for
enough for a curative re-ESD, an annual endoscopic examination is effective Cutaneous Research, Blizard Institute, London, London, United Kingdom
surveillance after initial ESD, especially for patients with marked atrophy of Contact E-mail Address: a.r.silver@qmul.ac.uk
gastric mucosa.
Disclosure of Interest: None declared INTRODUCTION: The development of intestinal fibrosis in patients with
Crohns disease (CD) results in complications which represent a major clinical
challenge for professionals, a significant cause of morbidity for patients and a
OP385 CLINICOPATHOLOGICAL RISK FACTORS FOR LYMPH NODE considerable cost to healthcare services. Understanding the processes that initiate
METASTASIS IN EARLY GASTRIC CARCINOMA DIAGNOSED and regulate intestinal fibrosis will facilitate the development of effective preven-
WITH THE WHO CRITERIA IN 380 CHINESE PATIENTS tative and therapeutic strategies. Specific microRNAs (miRNAs) have been
X. Zou1,*, C. Fang1, Q. Sun2, J. Shi2, Y. Zhang2, Q. Huang2,3 shown to have defined roles in fibrogenesis in several organ models. The miR-
1
Gastroenterology, 2Pathology, Nanjing Drum Tower Hospital, Nanjing, China, 200 family has been implicated in the development of murine intestinal fibrosis,
3
Pathology, Veterans Affairs Boston Healthcare System, Boston, United States possibly via a process termed epithelial to mesenchymal transition, although
human studies are lacking.
INTRODUCTION: Endoscopic resection is the preferred strategy for patients AIMS & METHODS: Our aim was to analyse the expression profiles of
with early gastric carcinoma (EGC) because of a minimal risk for lymph node miRNAs in surgical resection specimens from patients with CD between areas
metastasis (LNM), based on the clinical research results primarily from Japan. of stricture and non-stricture. From each patient, mucosal and submucosal sam-
However, it remains unclear as to LNM risk factors in Chinese patients with ples were harvested from within a stricture as well as the normal surgical resec-
EGC diagnosed with the updated WHO criteria. tion margins in order for every patient to serve as their own internal control.
AIMS & METHODS: We followed the 2010 WHO criteria to diagnose EGC in Formal histology reports were checked to ensure that fibrosis was present in the
resection specimens with nodal dissection and investigated clinicopathologic risk strictured areas used. Matched paired samples were selected (n4) and sent for
factors for LNM with the Cox logistic regression analysis. microarray analysis using the miRCURY LNATM microRNA Array platform
RESULTS: Over an 8-year period from January 2005 to December 2012, we (7th Gen, Exiqon, Denmark). The expression of differentially expressed miRNAs
identified 380 EGC gastrectomies with lymph node dissection performed at the was subsequently validated on eight new paired resection samples (stricture and
A122 United European Gastroenterology Journal 2(5S)
non-stricture). Total RNA including miRNA was extracted from the mucosa and mainly regulated by adhesion molecules which are interesting targets for IBD
submucosa of resection specimens and validation performed by qRT-PCR. therapy. Vedolizumab (VDZ) is an antibody to the adhesion molecule 47-
RESULTS: The microarray data revealed 32 distinct miRNAs significantly dif- integrin which is uniquely expressed on gut-homing lymphocytes, and thereby
ferentially expressed (p value 50.05) between the strictured and non-strictured selectively blocks the lymphocyte trafficking to the gut.
samples. These included members of the miR-200 family, all of which were down AIMS & METHODS: This study investigated the effect of VDZ therapy on
regulated in strictured specimens: miR-141 (p0.013), miR-200b-3p (p0.045) colonic mucosal gene expression in ulcerative colitis (UC). In total 120 endosco-
and miR-200c-3p (p0.009). The remaining members were also downregulated, pically-derived colonic biopsies from 44 UC patients were collected at protocol-
but not significantly so: miR-200a (p0.135) and miR-429 (p0.053). specified time points [week (W) 0, W6, W12 and W52] during 2 randomized-
QRT-PCR validation confirmed these findings. MiR-200 family members were controlled studies of VDZ1 (Millenium C13006 and C13008). Biopsies were com-
downregulated in the strictured samples compared to the non-strictured samples: pared with 12 normal colonic non-IBD biopsies and colonic biopsies before and
miR-141 (fold change 0.361, p0.002), miR-200a (fold change 0.432, p0.001), 4-6 weeks after first infliximab therapy from 23 UC patients. Mucosal healing
miR-200b-3p (fold change 0.721, p0.117) and miR-200c-3p (fold change 0.401, (Mayo endoscopic subscore 0 or 1) was assessed at W6, W12 and W52. Total
p0.002). RNA from biopsies was used to analyze whole genome gene expression via
CONCLUSION: These findings demonstrate for the first time that members of Affymetrix GeneChip Human Gene 1.0 ST arrays. Data were analyzed using
the miR-200 family are significantly downregulated in strictured fibrotic regions Bioconductor and Ingenuity Pathway Analysis software.
of intestine compared to non-strictured regions in patients with fibrostenosing RESULTS: In VDZ responders showing mucosal healing, no gene expression
CD. This mirrors findings in other organ systems, where the miR-200 family has differences at W6 and only 5 significant (false discovery rate55% and 42-fold)
been implicated in the development of fibrosis via epithelial to mesenchymal gene probe sets (down: IDO1, REG3A, KLK6, SAA2 and up: PCK1) at W12 were
transition. Further well-phenotyped human studies are warranted. found when compared to W0, while many differences in gene expression were
Disclosure of Interest: None declared found at W52. A total of 593 (462 down and 131 up) gene probe sets were
significant in VDZ responders with mucosal healing at W52 vs. W0, and 375
(63%) of these probe sets overlapped with the significant probe sets identified in
OP388 CIRCULATING MICROVESICLES IN CROHNS DISEASE: infliximab responders at W4-6 vs. W0. The common probe sets encoded genes
NOVEL MEDIATORS OF ANGIOGENESIS mainly involved in immune cell trafficking, cellular movement and inflammatory
E. Gaetani1,*, F. Del Zompo1, L. Laterza1, F. Scaldaferri1, R. Landi1, response. Interestingly, even in VDZ responders showing mucosal healing at W6,
A. Gasbarrini1 W12 and W52, many gene probe sets remained significantly dysregulated (266,
1
Internal Medicine and Gastroenterology, A. Gemelli University Hospital, Catholic 566 and 99 probe sets respectively for W6, W12 and W52) when compared with
University School of Medicine, Rome, Italy controls, and a great overlap of these significant genes was observed with the
Contact E-mail Address: eleonora.gaetani@rm.unicatt.it ones identified in infliximab responders vs. controls. Further, we found only few
genes with significantly increased expression (IGJ, IGK, IGKC, TNFRSF17) in
INTRODUCTION: Circulating microvesicles (cMVs) are small membrane VDZ responders with mucosal healing vs. infliximab responders.
bound fragments released by a number of cell types, including endothelial cells In contrast with the predictive mucosal gene signature identified for response to
(ECs), platelets, leukocytes, macrophages, and smooth muscle cells. Though infliximab2, we could not identify genes predictive of response to VDZ by com-
initially dismissed as cellular debris, cMVs are instead important mediators of paring the pre-VDZ treatment gene expression array profiles of responders show-
cell signaling and molecular communication between cells. Indeed, cMVs are ing mucosal healing with non-responders.
enriched with nucleic acids and proteins, shuttle specific mRNAs and CONCLUSION: VDZ influenced colonic mucosal expression of many genes
miRNAs, and transfer biological information between cells. MVs form through involved in immune-related functions at W52, but not yet at W6 or W12. The
exocytosis from multivesicular bodies, which leads to the formation of exosomes, observed changes were similar with those seen at W4-6 after first infliximab
or budding of MVs directly from a cytoplasmatic membrane, which results in the therapy, suggesting similar mechanisms of action for both therapies. As also
formation of so-called microparticles (MPs). In recent years, there has been observed in infliximab responders, the expression of many genes remained abnor-
increasing appreciation of the role played by cMVs in the regulation of angio- mal in VDZ responders with mucosal healing, indicating that maintenance ther-
genesis. For instance, platelet-derived MPs (PMPs) induce angiogenesis both apy is necessary to control the intestinal inflammation.
in vitro and in vivo and injection of MVs into the ischemic myocardium improves REFERENCES
revascularization after chronic ischemia. The aim of our study was to assess Feagan, et al. New Eng J Med 2013.
number, immunophenotype, and angiogenic content and activity of cMVs in Arijs, et al. Gut 2009.
subjects with active Crohns disease (CD). Disclosure of Interest: I. Arijs: None declared, G. De Hertogh Consultancy for:
AIMS & METHODS: We studied 10 subjects with active CD and 10 healthy Novartis, Genentech, Galapagos, L. Van Lommel: None declared, J. Van der
controls (HC). Clinical disease activity was determined by the CD Activity Goten: None declared, M. Ferrante Financial support for research from: Janssen
Index (CDAI). Disease was considered active for CDAI index 4220. Platelet- Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy for:
free plasma was used for fluorescence activated cell sorting (FACS) studies, to Abbvie, Merck, Janssen Biologics, F. Schuit: None declared, G. Van Assche
determine the cellular origin of circulating MPs, in particular whether they were Financial support for research from: Abbvie, Ferring, Lecture fee(s) from:
derived from ECs (EMPs), platelets (PMPs), monocytes (MMPs), or apoptotic Janssen-Cilag, Merck, Abbvie, Consultancy for: PDL BioPharma, UCB
cells (AMPs). Next, we analyzed the angiogenic content of cMVs, in terms of both Pharma, Sanofi-Aventis, Abbvie, Ferring; Novartis, Biogen Idec, Janssen
mRNAs and proteins, using specific profiler PCR arrays for angiogenic pathways Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire,
and specific angiogenic antibody arrays. Finally, we determined the functional Novartis, BMS, P. Rutgeerts Financial support for research from: UCB
activity of the angiogenic message carried by cMVs, by stimulating human umbi- Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Bristol-Meyers
lical ECs (HUVECs) with proteins extracted from cMVs isolated from the periph- Squibb, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck,
eral blood of either subjects with active CD or control individuals. UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs,
RESULTS: Activated PMPs, AMPs and MMPs were significantly higher in CD Actogenics, Prometheus, Pfizer, Falk Pharma, Tillotts, S. Vermeire Financial
when compared to HC. The presence of 84 angiogenesis-related mRNAs was support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from:
investigated in CD and HC. Data analysis of PCR arrays showed 16 significantly Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB
modulated genes, in particular 14 up-regulated and 2 down-regulated. To deter- Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, MSD
mine whether, in CD subjects, cMVs have the ability to induce neovessel gen-
eration in vitro, we used a tube formation matrigel assay. We found that the
number of branching points was significantly greater when HUVECs were incu- OP390 AMELIORATION OF ACTIVE ULCERATIVE COLITIS USING
bated with proteins derived from cMVs of CD patients, compared with HC. AN ORALLY AVAILABLE TOLL-LIKE RECEPTOR-9 MODULATOR
CONCLUSION: In CD, angiogenesis is a hallmark of active disease. Our find- (BL-7040): A PROSPECTIVE OPEN-LABEL, MULTI-CENTER PHASE
ings demonstrate that, in active CD, cMVs carry a potent and functionally active II TRIAL
angiogenic message. This novel finding increases our understanding of the I. Dotan1,*, E. Levy-Nissenbaum2, Y. Chowers3, A. Fich4, E. Israeli5, T. Adar6,
mechanisms that underlie development and progression of the disease, with S. Shteingart6, H. Soreq7, E. Goldin6
potentially important biological, clinical, and therapeutic implications. 1
IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv
REFERENCES Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv,
Danese et al. Gastroenterology 2006; 130: 2060-2073. 2
BioLineRx Ltd., Jerusalem, 3Department of Gastroenterology, Rambam Health
Hatoum et al. Gastroenterology 2003; 125: 5869. Care Campus Bat Galim, Haifa, 4Department of Gastroenterology, Soroka
Leonetti et al. PLoS One 2013; 8: e73088. Medical Center, Beer Sheva, 5IBD Unit, Institute of Gastroenterology and Liver
Chamouard et al. Dig Dis Sci 2005; 50: 574580. Diseases, Hadassah-Hebrew University Medical Center, 6Digestive Diseases
Andoh et al. Am J Gastroenterol 2005; 100: 20422048. Institute, Shaare Zedek Medical Center, 7Department of Biological Chemistry, The
Disclosure of Interest: None declared Hebrew University of Jerusalem, Jerusalem, Israel
Contact E-mail Address: irisd@tasmc.health.gov.il
OP389 THE EFFECT OF VEDOLIZUMAB THERAPY ON COLONIC INTRODUCTION: Current treatment of active ulcerative colitis (UC) may be
MUCOSAL GENE EXPRESSION IN PATIENTS WITH ULCERATIVE associated with significant adverse events and loss of response. Toll-like receptor
COLITIS (TLR)-9 mediates innate and adaptive immune response towards intestinal
I. Arijs1,*, G. De Hertogh2, L. Van Lommel3, J. Van der Goten1, M. Ferrante1, microorganisms. BL-7040 is a novel orally available synthetic oligonucleotide,
F. Schuit3, G. Van Assche1, P. Rutgeerts1, S. Vermeire1 which directly modulates TLR-9. BL-7040 has an anti-inflammatory effect in
1
Clinical and Experimental Medicine, 2Imaging & Pathology, 3Cellular and murine models of colitis as well as in patients with auto immune diseases such
Molecular Medicine, KU Leuven, Leuven, Belgium as myasthenia gravis, with a good safety profile.
Contact E-mail Address: ingrid.arijs@med.kuleuven.be AIMS & METHODS: We performed a prospective multi-center, open-label
phase IIa, proof-of-concept trial to evaluate the efficacy, safety and tolerability
INTRODUCTION: Inflammatory bowel disease (IBD) is characterized by con- of BL-7040 in patients with moderately active UC, defined by a Mayo score of
tinuous recruitment of leukocytes towards the inflamed gut. This migration is 5 and 9, and having an endoscopic sub-score 2 and rectal bleeding sub-score
United European Gastroenterology Journal 2(5S) A123
1. Concomitant mesalamine and steroids ( 10 mg prednisone/day) were Table to abstract OP391
allowed. Patients received BL-7040 12mg/day for 3 weeks, followed by BL-
7040 40 mg/day for 2 weeks. Effect was evaluated using the Mayo score, histol- Median concentration (g/ml)
ogy, and mucosal cytokines levels. Side effects were registered. Exposure (n) Weeks 04 Mean (SE) CDAI Week 4
RESULTS: Sixteen of the 22 enrolled patients completed a full five-week treat-
ment course and two-week follow-up. The primary endpoint, i.e. a 3 point Placebo (14) 0 96 (21)
decrease and 30% reduction from baseline in the Mayo score, and a 1 point Low (6) 5.9 96 (38)
reduction in rectal bleeding sub-score, or absolute 1 rectal bleeding sub-score, Medium (5) 7.8 129 (26)
was met in 8 (50%) patients. The other 8 patients remained stable. Furthermore, High (6) 10.5 174 (37)
mucosal healing evaluated by endoscopy sub-score improved. Neutrophil levels
and mucosal interleukin-6 (IL-6) levels were significantly reduced in responders, Adverse event frequencies were comparable between NNC0142-0002 and pla-
and correlated with clinical improvement (p0.002 and p0.046 compared to cebo. Most events were mild (49%) or moderate (43%) and were primarily
non-responders, respectively). BL-7040 was well tolerated with one serious gastrointestinal disorders, pyrexia, anemia, arthralgia and nasopharyngitis.
adverse event (hemoglobin decrease to 5.7gr%) considered unrelated to study CONCLUSION: A single s.c. dose of 2 mg/kg NNC0142-0002 (anti-NKG2D
drug, and 29 mild-to-moderate adverse events, mainly UC exacerbation (n4, mAb) did not reduce disease activity at Week 4 (primary outcome) compared
18.2%), influenza-like symptoms (n3, 13.6%), and dry mouth, fatigue, and with placebo, but significantly reduced disease activity at Week 12, and was well
headache (for each n2, 9.1%). tolerated. Exposure-response analysis in patients with baseline CDAI 330 pro-
CONCLUSION: In this prospective, open label phase IIa trial, oral administra- vides supportive evidence for a treatment effect of NNC0142-0002 and suggests
tion of the TLR-9 agonist BL-7040 was associated with clinical response and that higher doses and repeated dosing may further optimise the effect of
mucosal healing in 50% of UC patients with moderately active disease. The NNC0142-0002 in Crohns disease.
decrease in mucosal inflammation was reflected by significantly lower neutrophil Disclosure of Interest: M. Allez Financial support for research from: Novo
counts and decreased IL-6 levels. BL-7040 was safe and well tolerated. The Nordisk, Consultancy for: Novo Nordisk, R. Petryka: None declared, B.
efficacy and safety of BL-7040 for the treatment of active UC should be further Skolnick Other: Full-time employee of Novo Nordisk at the time of data analy-
evaluated. sis, M. Wisniewska-Jarosinska: None declared, R. Overgaard Other: Employee
Disclosure of Interest: I. Dotan Lecture fee(s) from: BioLineRx, Ferring, Falk and stock holder of Novo Nordisk A/S
Pharma, Janssen, Abbvie, Consultancy for: BioLineRx, Genentech, Pfizer,
Janssen, Abbvie, E. Levy-Nissenbaum: None declared, Y. Chowers Lecture
fee(s) from: Abbvie, Janssen, Consultancy for: Abbvie, Janssen, Takeda, OP392 EFFICACY AND SAFETY OF TRICHURIS SUIS OVA FOR
Pharmacosmos, Vecta, A. Fich: None declared, E. Israeli: None declared, T. TREATMENT OF MILDLY-TO-MODERATELY ACTIVE CROHNS
Adar: None declared, S. Shteingart: None declared, H. Soreq: None declared, DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-
E. Goldin Consultancy for: BioLineRx, Immune Pharmaceutical CONTROLLED, PHASE II STUDY
J. Scholmerich1,*, K. Fellermann2, F.W. Seibold3, G. Rogler4, J. Langhorst5,
S. Howaldt6, G. Novacek7, A.M. Petersen8, O. Bachmann9, H. Matthes10,
OP391 RANDOMISED, DOUBLE-BLIND, SINGLE-DOSE, PHASE 2 N. Hesselbarth11, T. Klugmann12, J. Wehkamp13, J. Klaus14, C. Ott15,
TRIAL ASSESSING EFFICACY AND SAFETY OF THE NOVEL K. Dilger16, R. Greinwald16, R. Mueller16 on behalf of the International, TSU-
ANTI-NKG2D MONOCLONAL ANTIBODY NNC0142-0002 IN 2 Study Group
CROHNS DISEASE: INSIGHTS FROM AN EXPOSURE-RESPONSE 1
Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt a.M, Frankfurt
ANALYSIS a.M., 2Abt. Gastroenterologie, UK-SH Campus Lubeck, Lubeck, Germany, 3Abt.
M. Allez1,*, R. Petryka2, B.E. Skolnick3, M. Wisniewska-Jarosinska4, R., Gastroenterologie, Spital Netz Bern Tiefenau, Bern, 4Div. of Gastroenterology and
V. Overgaard5 Hepatology, University of Zurich, Zurich, Switzerland, 5Integrative
1
Hopital Saint-Louis, APHP, Universite Denis Diderot, Paris, France, 2NZOZ Gastroenterologie, Internal and Integrative Medicine, Kliniken Essen-Mitte, Essen,
Vivamed, Warsaw, Poland, 3Novo Nordisk Inc., Princeton, NJ, United States, 6
Hamburgisches Forschungsinstitut fur CED, HaFCED GmbH&Co.KG,
4
Department of Gastroenterology, Medical University of Lodz, Lodz, Poland, Hamburg, Germany, 7Universitatsklinik fur Innere Medizin III, Medizinische
5
Novo Nordisk A/S, Sborg, Denmark Universitat Wien, Vienna, Austria, 8Dept. of Gastroenterology, Hvidovre
Contact E-mail Address: matthieu.allez@sls.aphp.fr University Hospital, Hvidovre, Denmark, 9Medizinische Hochschule Hannover,
Hannover, 10Abt. Gastroenterologie, Gemeinschaftskrankenhaus Havelhohe,
INTRODUCTION: NNC0142-0002 (anti-NKG2D mAb) is an antagonising Berlin, 11Arztehaus am Klinikum, Schwalmstadt, 12Gastroenterologische
human IgG4 monoclonal antibody that binds to NKG2D receptors. These recep- Gemeinschaftspraxis, Leipzig, 13Abt. Innere Medizin I, Robert-Bosch-
tors are located on T- and natural killer cells, which exhibit inflammatory and Krankenhaus, Stuttgart, 14Klinik fur Innere Medizin I, Universitatsklinikum Ulm,
cytotoxic properties, and may be linked to mucosal damage. Ulm, 15Dept. of Internal Medicine I, University Hospital of Regensburg,
AIMS & METHODS: A total of 78 patients (aged 18 and 75 years) with Regensburg, 16Dr. Falk Pharma GmbH, Freiburg, Germany
Crohns disease for 3 months, a Crohns disease activity index [CDAI] 220 Contact E-mail Address: aed@kgu.de
and 450, and either C-reactive protein 10 mg/L or endoscopic evidence of
inflammation, were randomised 1:1 to a single subcutaneous (s.c.) dose of 2 mg/ INTRODUCTION: Until now only open-label data have been available showing
kg NNC0142-0002 or placebo. Primary outcome was change in CDAI (CDAI) that a dosing of 2.500 embryonated viable eggs of Trichuris suis (TSO) every 3
from baseline to Week 4. Secondary outcomes included CDAI through Week weeks for 12 weeks led to clinical remission (CDAI5150) in 19 of 29 patients
12, NKG2D receptor occupancy, pharmacokinetics and safety. Exposure- (65.5%) with active Crohns disease (CD) refractory to standard CD-therapy
response analysis of CDAI from baseline to Week 4, based on mean before enrolment (Summers et al., Gut. 2005;54(1):87-90).
NNC0142-0002 concentrations over Weeks 1, 2 and 4 was performed. Four- AIMS & METHODS: This is the first double-blind, randomised, multicentre
level stratification based on two binary factors was implemented: failure to bio- POC study to evaluate the efficacy and safety of different TSO dosages vs pla-
logic therapy (yes/no) and baseline CDAI (5330 or 330). Pre-specified signifi- cebo for the treatment of mildly-to-moderately active, ileo-/colonic, uncompli-
cance level was 10% (p0.10; two-sided test). Primary efficacy outcome was cated CD. Patients being neither steroid-dependent/-refractory nor on
analysed via a mixed-effect model, whereas the exposure-response analysis was immunosuppressants with a CDAI of 220-350 and biochemical signs of inflam-
based on observed means. Due to slow recruitment a futility analysis was insti- mation were eligible for this study. Patients received either 250, 2.500, or 7.500
tuted, resulting in discontinuation of recruitment. TSO, or placebo at fortnightly intervals for 10 weeks. Primary endpoint was the
RESULTS: Mean CDAI from baseline to Week 4 (primary outcome) was not rate of clinical remission (CDAI5150) at week 12 (last observation carried for-
significantly different between NNC0142-0002 and placebo (CDAI 16); ward [LOCF]).
however, there was a significant difference by Week 12 (CDAI 55; RESULTS: 252 patients (154 females; mean age: 37 yrs; mean CDAI: 269) were
p0.10). Significant improvements were noted in the non-failure to biologics randomised. Efficacy is presented below. Administration of TSO did not result in
group (treated with NNC0142-0002 [n28]) from Week 1 onwards. NNC0142- any serious adverse drug reaction (ADR). Review of non-serious suspect ADRs
0002 resulted in a median NKG2D occupancy of 480% for 8 weeks. When following intake of TSO did not reveal a safety concern.
patients with high baseline CDAI (330) were partitioned into placebo or tertiles CONCLUSION: Administration of 250 7.500 TSO fortnightly over 12 weeks
based on exposure, larger magnitude CDAI changes were observed with higher was safe and showed a dose-dependent immunological response, but none of the
concentrations (see table). No signs of exposure-response at Week 4 were TSO dosages could show a clinically relevant effect over placebo for the induc-
observed for patients with baseline CDAI 5330. tion of clinical remission or response in mildly-to-moderately active, ileo-/colonic
CD.
Disclosure of Interest: J. Scholmerich Lecture fee(s) from: Falk Foundation, K.
Fellermann Lecture fee(s) from: Abbvie, Falk Foundation, F. Seibold: None
declared, G. Rogler Financial support for research from: Dr Falk Pharma
GmbH, Lecture fee(s) from: Falk Foundation, J. Langhorst Financial support
INTRODUCTION: Irritable bowel syndrome is a heterogeneous condition with Year N % Year N/N GERS % N/N non-GERS %
multiple factors leading to the symptoms of IBS such as stress, infection and diet.
Recent demonstration of immune activation in the gut has prompted trials of 5- 1988 86 17.7 (14.5-21.4) 1988-1989 31/86 36.1 36/404 8.9
aminosalicylates; however identifying the phenotype of who will respond remains 1989 91 18.6 (15.2-22.3) 1989-1995 29/91 31.9 36/399 9.0
elusive.
AIMS & METHODS: Our previous multicentre study1 showed Mesalazine (M) 1995 98 20.0 (16.5-23.8) 1995-2011 53/98 54.1 59/392 15.1
was not effective in unselected IBS-D patients. Here we report the value of a 2011 104 21.2 (17.7-25.1)
number of biomarkers collected in this same trial in an attempt to identify
responders. Stool samples and sigmoid biopsies were collected at baseline CONCLUSION: In this 23 year prospective longitudinal study on an adult
and 12 weeks later at the end of study from IBS-D patients and were randomised population, the odds of GERS has increased by 35% per decade. On an indivi-
into either M or placebo(P) to be taken for 12 weeks in Nottingham. Group 1:53 dual basis, there is a large symptom turnover both within a year and over longer
pairs of stool samples were obtained. Stool calprotectin (SCal) was analysed by periods, reflecting the natural history of GERS.
using a commercial Elisa kit. High level of SCal level is defined as 100 ug/ml. Disclosure of Interest: None declared
Group 2:43 pairs of sigmoid biopsies obtained. These samples were compared
with biopsies obtained from 21 healthy volunteers(HV). Gene expressions were
analysed by mRNA quantification via 2 step reverse transcription quantitative OP398 DISCREPANCIES BETWEEN UPPER GI SYMPTOMS
polymerase chain reaction technique. Relative expression levels for each mRNA DESCRIBED BY THOSE WHO HAVE THEM AND THEIR
were calculated using mean Ct values of 4 mRNA endogenous genes. IDENTIFICATION BY CONVENTIONAL MEDICAL TERMINOLOGY:
RESULTS: [Mean (SD)] Group 1: SCal levels did not improve with M[mean A SURVEY IN FOUR COUNTRIES
difference(md)-12.16 (82.69);p0.43] when compared to P[md0.10 (87.05); R. Heading1,*, E. Thomas2, P. Sandy3, G. Smith2, R. Fass4, P. Hungin1
p0.73]. Baseline SCal negatively correlated with anxiety score (Spearman r- 1
School of Medicine, Pharmacy and Health, Durham University, Durham,
0.28;p0.04). There was no correlation between baseline SCal with clinical symp- 2
Category Development Organisation, Reckitt Benckiser plc, Slough, United
toms such as abdominal pain severity, urgency, bloating, stool frequency or stool Kingdom, 3Winkle, Amsterdam, Netherlands, 4Gastroenterology, Case Western
consistency. When Scal were divided into 2 subgroups of high and low levels, the Reserve University, Cleveland, Ohio, United States
total hospital and anxiety (HAD) scores in the high SCal group [5.7(3.5)] were
significantly lower than the low SCal group [8.6 (4.4)];p0.03 however there were INTRODUCTION: Modern self-administered questionnaires assessing upper GI
no significant differences in abdominal pain severity, average stool frequency or symptoms are usually designed by reconciling the descriptive vocabulary used by
stool consistency. Group 2: Toll-like receptor 4(TLR-4) and myeloid differentia- symptomatic individuals with conventional medical terminology for symptoms
tion primary response 88(MYD88) mRNA were both elevated compared to HV. (e.g. heartburn, regurgitation, epigastric discomfort etc.). It is often assumed that
Quantity mRNA (mRNAq) for TLR-4 in HV vs IBS-D were 0.75(0.42) and the conventional medical vocabulary is able to identify the symptoms adequately.
1.96(0.86);p50.01. When treated with M, TLR-4 levels showed significant AIMS & METHODS: We aimed to develop a self-administered questionnaire for
reduction [md-0.29(0.68) compared to P group [md0.22(0.78)];p0.03. upper GI symptoms based on lay vocabulary without imposition of medical
There was no correlation between TLR-4 and SCal (Spearman r0.17; concepts or terminology for use in a large survey of symptom occurrence
p0.26). mRNAq for MYD88 was significantly higher in IBS-D vs HV being among sufferers in 4 countries.
1.12(0.42) vs 0.63(0.25); p50.01. Treatment with M did not alter MYD88 levels The questionnaire was designed by integrating symptom descriptions used by 38
[md0.03(0.37)] compared to placebo [md0.12(0.39)]; p0.43. symptomatic adults in Brazil, Russia, UK and USA. The resulting questionnaire,
CONCLUSION: A small cohort of IBS-D patients demonstrated patients with low in the appropriate language, was distributed on-line daily for 6 weeks to indivi-
SCal are more anxious and depressed that those with high SCal suggesting their duals experiencing upper GI symptoms in the 4 countries. Detailed information
symptoms may be centrally rather than driven by changes in the gastrointestinal was sought on up to 7 symptom episodes occurring on different days, identifying
tract. Elevated gene expression in TLR-4 and MYD88 could be a feature in a small the nature, severity, timing and duration of the predominant symptom on each
subgroup of IBS-D patients where symptoms are driven peripherally by mucosal/ occasion together with other symptoms experienced concurrently. They were also
microbiome interactions. Further larger studies are needed to confirm this. asked what term they would use to describe their symptoms to a friend or a
REFERENCES doctor.
1. Lam, et al. DDW 2014 A multi-centre, parallel group, randomised placebo RESULTS: The questionnaire development identified and described 9 symptoms
controlled trial of mesalazine for treatment of diarrhoea-predominant irritable using non-medical vocabulary. They occurred with a frequency of 24 61 % in
bowel syndrome (IBS-D). 2665 survey respondents who reported on 10,659 symptom episodes. One of the
Disclosure of Interest: C. Lam: None declared, M. Lingaya: None declared, Y. symptoms appeared to correspond with regurgitation while two distinct symp-
Falcone: None declared, A. Bennett: None declared, R. Spiller Financial support toms (experienced by 28% and 34% of subjects) possibly corresponded with
for research from: Grants from Lesaffre and Ironwoom, Consultancy for: heartburn. However, 58% of individuals who reported these two concurrently
Almirall, Astellas, Danone, Sanofi, Other: Free drug from Norgine on some occasions reported one being present without the other on other
A126 United European Gastroenterology Journal 2(5S)
occasions. Five stomach or abdominal symptoms were recognised and distin- patient received a stent for malignant biliary obstruction for the first time. We
guished and there was one chest symptom, reported by about 30% of subjects in then collected data on (i) tumour size and presence of metastases on computed
all 4 countries, for which a corresponding medical term was uncertain. tomography (CT) at diagnosis, (ii) subsequent ERCPs, (iii) subsequent hospital
Statistically significant differences in occurrence and severity of some symptoms admissions for biliary problems and (iv) survival. Using costings provided by the
were evident between countries, between genders and between age groups. Both hospital finance department, we assessed the total cost of failure of plastic stents.
the predominant symptom and the pattern of concurrent symptoms often varied Using costings provided by our supplier of metal stents we then performed a
from one symptom episode to another. Respondents use of the terms heartburn, comparison of the cost implications of metal and plastic stents for different
reflux, regurgitation, burning stomach and indigestion to describe their symp- patient groups. This analysis was based on the prediction derived from meta-
toms to a friend or doctor varied considerably between countries. analysis that the metal stent failure rate is 52% of the plastic stent failure rate2.
CONCLUSION: Discrepancies between the symptoms described by those who RESULTS: 111 patients received a 1st plastic stent, of which 11 later had surgery,
suffer them and the way in which they can be described by conventional medical leaving 100 cases where plastic stents were used for palliation alone. All these
terminology were evident in all four countries. These discrepancies deserve more patients have now died. 82 had successful relief of jaundice but the success rate
attention with a view to identifying the limitations of current upper GI symptom for Klatskin tumours was only 5/11. In 77 cases no further biliary intervention
enquiry and developing validated questionnaires, possibly derived solely from the was required. The remaining 23 patients had 38 subsequent biliary problems,
vocabulary of individuals suffering the symptoms, which will improve symptom requiring 27 admissions (totalling 403 days) and 33 further ERCPs. In the
identification and assessment. table actual costs after plastic stenting per patient are compared with predicted
Disclosure of Interest: None declared costs had a metal stent been used instead.
INTRODUCTION: Swallowed topical corticosteroids have been shown effective CONCLUSION: MCTC subtype was the predominant in the inflammatory infil-
in the treatment of Eosinophilic Esophagitis (EoE), but so far no approved trate of EoE patients. MC densities correlated with eosinophil counts and symp-
therapy with an esophageal-adjusted formulation including an optimal dosing toms. Dietary treatment significantly reduced gene expression of MC-related
is available. proteases and chemotactic factors.
AIMS & METHODS: To evaluate the efficacy and safety of two different bude- Disclosure of Interest: None declared
sonide formulations (effervescent tablet [BET] and viscous suspension [BVS]) and
two different doses for short-term treatment of EoE.
Adults with active EoE (n76) randomly received 14-days treatment with either OP408 EMPIRIC FOUR-FOOD ELIMINATION DIET FOLLOWED BY
BET 2x1mg/d (BET1, n19) or BET 2x2mg/d (BET2, n19), or BVS 2x2mg/d RESCUE SIX-FOOD ELIMINATION DIET FOR ADULT
(BVS, n19) or placebo (n19) in a double-blind, double-dummy fashion, with a EOSINOPHILIC ESOPHAGITIS: A PROSPECTIVE MULTICENTER
2-week follow-up. Primary endpoint was histological remission (mean of 516 STUDY
eos/mm2 hpf). Secondary endpoints included endoscopy score, dysphagia score, J. Molina- Infante1,*, A. Arias2, J. Barrio3, J. Rodriguez-Sanchez4, M. Sanchez-
and preference of drug formulation. Cazalilla5, A.J. Lucendo5
RESULTS: Histological remission occurred in 100%, 93.8%, and 93.3% of 1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 2Research Support
budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients Unit, Hospital General Mancha Centro, Alcazar de San Juan, 3Gastroenterology,
(p50.0001). The improvement in total endoscopic intensity score was signifi- Hospital Rio Hortega, Valladolid, 4Gastroenterology, Hospital General
cantly higher in the 3 budesonide groups compared with placebo. Dysphagia Universitario, Ciudad Real, 5Gastroenterology, Hospital General, Tomelloso, Spain
improved in all groups at the end of treatment. The improvement persisted
during the 2-weeks follow-up only in those treated with BET1 and BET2, with INTRODUCTION: Eosinophilic oesophagitis (EoE) is an esophageal disorder
BET1 showing a significant difference to placebo (p0.0196). There was sus- predominantly triggered by food antigens. A six-food elimination diet (SFED)
pected local fungal infection in 3 patients in each of the three budesonide achieves remission in over 70% of adult EoE patients. After individual food
groups. However, in a post-hoc histopathology analysis hyphae were only reintroduction, just one or two food triggers for EoE can be identified in
found in 2 patients in each of the budesonide groups. Neither serious adverse 65%485% of patients, so some dietary restrictions and endoscopies after food
events nor clinically relevant changes in plasma cortisol were observed. 80% of challenge may be unnecessary.
patients preferred the effervescent tablet. AIMS & METHODS: We aimed to evaluate the efficacy of a four-food elimina-
CONCLUSION: Budesonide administered as effervescent tablet or as viscous tion diet (FFED) (dairy products, wheat, egg and legumes) for adult EoE
suspension was highly effective and safe for short-term treatment of EoE. The patients. Prospective multicenter study. All patients were re-evaluated after 6
1mg BID dose was equally effective as the 2mg BID dose. The majority of weeks on a FFED. Response to FFED was defined by clinical and histological
patients preferred the effervescent tablet formulation. (515 eos/HPF) remission. Responders underwent reintroduction of each indivi-
The first two authors contributed equally to the first authorship dual food over 6 weeks followed by endoscopy and esophageal biopsies.
Disclosure of Interest: P. Hruz: None declared, S. Miehlke Lecture fee(s) from: Dr Nonresponders were offered a rescue SFED.
Falk Pharma GmbH, U. von Arnim: None declared, A. Madisch Lecture fee(s) RESULTS: 52 adult patients were included, of whom 12 patients (23%) had previous
from: Falk Foundation, M. Vieth Lecture fee(s) from: Falk Foundation, C. failure to topical steroid therapy. 28/52 patients (54%) achieved clinicopathological
Bussmann: None declared, M. Bajbouj: None declared, C. Fibbe: None declared, remission on FFED and 6/19 (31%) nonresponders to FFED were successfully
H. Wittenburg Lecture fee(s) from: Falk Foundation, H. Allescher: None rescued with SFED. 22/28 responders to FFED (78%) finished the individual food
declared, M. Reinshagen Lecture fee(s) from: Falk Foundation, S. Schubert reintroduction challenge. Milk was identified as an EoE trigger in 11 patients (50%),
Lecture fee(s) from: Abbvie, Falk Foundation, MSD, J. Tack: None declared, egg in 8 (36%), wheat in 7 (31%) and legumes in 4 (18%). All patients had just 1 or 2
M. Muller: None declared, A. Eckardt: None declared, P. Krummenerl: None food triggers, being milk the only causative food in 27% of patients.
declared, J. Arts: None declared, K. Dilger Other: Employee of Dr Falk Pharma, CONCLUSION: A FFED achieved clinico-pathologic remission in 54% of adult
R. Greinwald Other: Employee of Dr Falk Pharma, R. Mueller Other: Employee EoE patients. SFED was effective in almost a third of FFED nonresponders,
of Dr Falk Pharma, A. Straumann Consultancy for: Dr Falk Pharma coming to a combined efficacy of both strategies of 72%.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A129
OP409 TRANSGLUTAMINASE EXPRESSION AND COELIAC 4. Grozinsky-Glasberg S, Thomas D, Strosberg JR, et al. Metastatic type 1
AUTOANTIBODY BINDING TO THE PANCREAS IN DIABETES gastric carcinoid: a real threat or just a myth? World J Gastroenterol 2013; 19:
MELLITUS 8687-8695.
I. R. Korponay-Szabo1,2,*, M. Oikarinen3, J.E. Laiho3, K. Laurila1, M. Maki1, 5. Fykse V, Sandvik AK, Qvigstad G, et al. Treatment of ECL cell carcinoids
H. Hyoty3 on behalf of The nPOD Study Group with octreotide LAR. Scand J Gastroenterol 2004; 39: 621-628.
1
Tampere Center for Child Health Research, University of Tampere Medical Disclosure of Interest: None declared
School, Tampere, Finland, 2Paediatrics, University of Debrecen, Debrecen,
Hungary, 3Virology, University of Tampere Medical School, Tampere, Finland WEDNESDAY, OCTOBER 22, 2014 14:0015:30
Contact E-mail Address: loilko@uta.fi VIRAL HEPATITIS, CYTOKINES AND LIVER REGENERATION LOUNGE
INTRODUCTION: Coeliac disease and type-1 diabetes (T1DM) are often co- 5_____________________
existing and share common genetic background. However, it is still a question
whether coeliac disease can directly induce damage of the pancreas leading to OP411 HBX DIRECTLY MEDIATES DEREGULATION OF SEVERAL
beta cell loss and endocrine insufficiency. The aim of this study was to investigate LNCRNAS IDENTIFIED BY CHIP-SEQ EXPERIMENT
if pancreas tissue is an autoantigenic target for coeliac anti-transglutaminase F. Guerrieri1,2,* on behalf of, F. Guerrieri, S. Jeddari, L. Belloni, D. DAndrea,
(TG2) antibodies in vivo. A. Tramontano, M. Levrero
AIMS & METHODS: Frozen pancreas and full thickness duodenum tissue spe- 1
Dept Internal Medicine, 2Sapienza Life NanoScience Laboratory, SAPIENZA
cimens from cadaveric organ donors with T1DM (n22), diabetes antibody UNIVERSITY OF ROME, rome, Italy
positive subjects (n11) and non-diabetic controls (n21) were kindly provided Contact E-mail Address: fraguerrieri@gmail.com
by the Network of Pancreatic Organ Donors with Diabetes (nPOD). None of
these subjects had a coeliac disease diagnosis during lifetime. The tissues were INTRODUCTION: HBx regulatory protein is required for HBV cccDNA tran-
investigated for transglutaminase and glucagon expression, in vivo- bound celiac scription/viral replication and contributes to HBV oncogenicity. HBx affects the
disease-related IgA antibodies, CD3 and gamma-delta T cell counts by immu- epigenetic control of HBV viral chromatin, by preventing HDACs recruitment
nohistochemistry in a blinded fashion without knowledge of the clinical details. onto the cccDNA, as well as of cellular chromatin, by favouring the recruitment
RESULTS: Pancreas specimens expressed abundantly TG2 around the islets and of acetyl-transferase on activated target genes and of DNMT3a on repressed
acinar structures corresponding to the reticulin network of the pancreas. genes. (Guerrieri et al. 2013). LncRNAs are broadly defined as endogenous
Furthermore, TG2 was also present in vessel walls of islet capillaries. IgA class cellular RNAs molecules longer than 200 nt capable to regulate gene expression
coeliac autoantibodies bound to TG2 were detected on the surface of TG2 in 5 of at various levels, including chromatin modification, transcription and post-tran-
the diabetic pancreas specimens and in the corresponding duodenum samples scriptional processing. DLEU2 encodes a putative lncRNA, with one exon
within the mucosa and in the gut wall muscular layer endomysium. The presence directly overlapping the first exon of the TRIM13 gene in the opposite orienta-
of villous atrophy consistent with untreated coeliac disease was confirmed from tion (Skoblov et al. 2006). Upregulation of specific DLEU2 splicing variants
H&E sections from the same subjects in 4 of these cases, all adults (one specimen correlates with HCC (Garding et al. 2013). TRIM13 induces autophagy and
being inadequately orientated). All control pancreas samples were negative for increase ectopic levels of p53 (Tomar D et al, .2012).
IgA deposition. One non-diabetic donor had slight endomysial positivity in the AIMS & METHODS: Aim of this study was to indentify HBx role in the
gut without villous antrophy and had no IgA in the pancreas. lncRNA regulation.
CONCLUSION: Pancreas tissues express the transglutaminase 2 autoantigen High-throughput sequencing of anti-HBx ChIP-enriched DNA fragments
important for coeliac disease pathology. Celiac antibodies bound to the pancreas (ChIPSeq) was performed in HepG2 cells. Chromatin immunoprecipitated
may initiate inflammation and tissue damage leading to diabetes. A fraction of from mock, wt and HBx-mt monomeric linear full length HBV DNA cells was
T1DM cases may be preventable by screening and treatment for coeliac disease at analysed by TaqMan real-time PCR using lncRNA specific primers. HBx target
an early age. lncRNAs levels were assessed both by PCR and real-time RT-PCR.
REFERENCES RESULTS: ChIPSeq analysis of HBx chromatin recruitment revealed a specific
Acknowledgments: Network of Pancreatic Organ Donors with Diabetes, binding to a large number of new and known target sequences. In particular HBx
Juvenile Diabetes Research Foundation, TAMOP 4.2.2.A-11/1/KONV-2012- binds to 39 long non coding RNAs. Focusing on DLEU2 lncRNA, we demon-
0023, OTKA K101788. strated that HBx is able to deregulate its expression and the neighboring genes.
Disclosure of Interest: None declared We show that HBx can bind DLEU2 promoter and modifies its epigenetic status.
Therefore, HBx occupancy results in a different DLEU2 splicing profile leading
to down-regulation of hsa-mir-15 and hsa-mir-16, as previously published, but
OP410 TREATMENT WITH SOMATOSTATIN ANALOGUES OF also to up-regulation of the antisense autophagic gene TRIM13. Selective degra-
RECURRENT TYPE I GASTRIC CARCINOID IN PATIENTS WITH dation of DLEU2 RNA resulted in a reduced H4 acetylation on TRIM13 pro-
AUTOIMMUNE CHRONIC ATROPHIC GASTRITIS moter and a 50% reduction of TRIM13 expression in HBV replicating HepG2
S. Massironi1, A. Zilli2,*, R.E. Rossi2, D. Conte2, I. Fanetti3, C. Ciafardini4, cells. These results directly link DLEU2 RNA species with TRIM13 transcrip-
M. Peracchi3 tional regulation in the presence of HBx. In silico analysis indicates that DLEU2
1
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda - Ospedale RNA potentially binds HBx and using a RIP (RNA Immune Precipitation)
Maggiore Policlinico, 2Gastroenterology and Endoscopy Unit, 3Department of approach we confirmed HBx-DLEU2 interaction. Finally we found that
Medical, Surgical and Transplant Pathophysiology, University of Milan, DLEU2 inactivation has a profound impact on pgRNA transcription, thus sug-
4
Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico, Milan, Italy gesting a functional relevance of the DLEU2-HBx interaction of HBV
Contact E-mail Address: alessandra.zilli86@gmail.com replication.
CONCLUSION: HBx is recruited to 39 lncRNA promoters. HBx binds to the
INTRODUCTION: The treatment of type 1 gastric carcinoids (GC1) is still DLEU2 promoter region and affects its epigenetic status and expression by
debated, in view of their usual benign behaviour. inducing a different DLEU2 splicing profile. HBx also directly binds DLEU2
AIMS & METHODS: To evaluate the outcome of patients with recurrent GC1 and affects HBV replication.
treated with somatostatin analogues (SSA). REFERENCES
From January 2000 to September 2013, among 111 patients with chronic auto- Guerrieri F, Belloni L, Pediconi N, et al. Molecular mechanisms of HBV-asso-
immune atrophic gastritis, 23 patients were diagnosed with GC1. After they had ciated hepatocarcinogenesis. Semin Liver Dis 2013.
the GC endoscopically removed, they underwent regular clinical and endoscopic Tomar D, Singh R, Singh AK, et al. TRIM13 regulates ER stress induced
follow-up. Plasma chromogranin A (CgA) and gastrin levels were measured in all autophagy and clonogenic ability of the cells. Biochim Biophys Acta 2012.
patients. Patients showing recurrent GC1 were treated with SSA until gastrin fell Garding A, et al. Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is
below 400 pg/mL and there was no endoscopic and histological evidence of GC1 linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS
anymore. Genet 2013.
RESULTS: 12 patients (52%) showed GC1 recurrence and were treated with Disclosure of Interest: None declared
SSA for a median time of 13 months. At baseline, median gastrin and CgA levels
were 719 pg/mL and 33 U/L, respectively and they decreased to 389 pg/mL
(p0.001) and 14 U/L (p0.005), respectively, after a six-month period of treat- OP412 MAPPING OF ACCURATE LOCATION FOR COMBINATION OF
ment. In all but one patient, GC1 disappeared after a median treatment of 12 HEPATITIS B VIRUS X PROTEIN AND CYTOCHROME C OXIDASE
months. In one case it was necessary to extend the therapy for 32 months to get III
the carcinoid disappearance. After SSA discontinuation, 4 patients (36%) D. Li1,*, X. Wang1
showed GC1 recurrence after a median of 19.5 months and they were successfully 1
Gastroenterology, digestion, Fuzhou, China
retreated with a schedule of 12 months on treatment alternated to 6 months off Contact E-mail Address: doctorlidan@163.com
treatment.
CONCLUSION: This cohort study confirms that GC1 tend to recur. SSA, INTRODUCTION: Human hepatitis B virus (HBV) infection has been strongly
administered in cycles of 12 months, represent an effective treatment. associated with development of hepatocellular carcinoma(HCC). The mechan-
REFERENCES isms whereby HBV causes malignant transformation remain uncertain. Much of
1. Solcia E, Fiocca R, Villani L, et al. Hyperplastic, dysplastic, and neoplastic the evidence available supports a pathogenetic role for the product of the HBV x
enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and gene, the HBx. However, the molecular mechanisms underlying effects of HBx
histogenesis. Am J Surg Pathol 1995; 19(Suppl. 1): S1S7. protein on transcription, cellular proliferation and transformation are only par-
2. Campana D, Nori F, Pezzilli R, et al. Gastric endocrine tumors type I: treat- tially deEned. As HBx has no ability to bind dsDNA, proteinprotein interaction
ment with long-acting somatostatin analogs. Endocr Relat Cancer 2008; 15: 337- seems to be crucial for HBx function. IdentiEcation of cellular HBx -interactive
342. proteins would provide insight into the mechanism of HBV cellular effects.
3. Grozinsky-Glasberg S, Kaltsas G, Gur C, et al. Long-acting somatostatin AIMS & METHODS: In previous study, we have screened a new HBx-interact-
analogues are an effective treatment for type 1 gastric carcinoid tumours. Eur ing protein, cytochrome C oxidase subunit III(COXIII). The aim of this study is
J Endocrinol 2008; 159: 475-482. to map an accurate binding site in HBx protein with COXIII. Two fragments of
A130 United European Gastroenterology Journal 2(5S)
HBx mutants (X1 aa1-72; X2 aa1-117) were amplified by polymerase chain (VEHDMSO). Hemodynamic measurements were performed after 7 days of
reaction (PCR) and inserted into pAS2-1 to reconstruct the mutant plasmids. treatment including mean arterial pressure (MAP), heart rate (HR), portal pres-
PCR and gene sequencing were used to confirm the mutants fragments expressed sure (PP) and superior mesenteric artery blood flow (SMABF). Genes involved in
in the plasmids. PCR showed the mutants fragments expressed in yeast cells and inflammatory response, antibacterial response, and innate immunity were
western blot testified the fusion proteins were translated correctly in yeast cells. assessed by RT-PCR RNA-array from ileum. Bacterial translocation was
Hybrid in solid medium and gal activity detection mapped the key domain for assessed by mesenteric lymph node culture and LBP-ELISA.
combination of HBx and COXIII. Coimmunoprecipitation was performed to RESULTS: In the PPVL group, both portal hypertension (PP: 10.53.2 vs.
confirmed specific interaction between HBx mutant proteins with COXIII. 8.82.4mmHg, p0.059) and splanchnic blood flow (SMABF: 0.1770.031 vs.
RESULTS: Two mutant plasmids which contain HBx aa1-72 and aa1-117 were 0.1100.003 mL/min/g; p0.024) were reduced by PX treatment. HR and MAP
successfully constructed respectively. PCR and gene sequencing confirmed the were not affected by PX treatment in SO or PPVL animals. Positive lymph node
two mutant fragments were inserted in the plasmids. PCR and Western blot cultures were observed in 60% of PPVL-VEH mice but reduced to 30% in PPVL-
proved the mutant genes expressed the mutant proteins correctly in yeast cells. PX mice. LBP serum levels were non-significantly decreased in PPVL-PX vs.
Hybrid in solid medium and gal activity detection indicated the binding site of PPVL-VEH mice (20.36.9 vs. 27.312.1mg/mL; p0.067). PPVL upregulated
HBx with COXIII is located between aa72 to aa117. The specific interaction proinflammatory gene expression, while PX treatment suppressed selective pro-
between HBxX2 protein and COXIII was verified by coimmunoprecipitation. inflammatory genes (TLR2, TNF, IL-1, IL-6). However, genes involved in anti-
CONCLUSION: For the first time, it is reported aa72-117 of HBx are key bacterial defense (iNOS) were not suppressed upon FXR activation.
binding peptides for combination of HBx with COXIII. CONCLUSION: The FXR ligand PX20606 reduced splanchnic blood flow and
REFERENCES portal pressure in PPVL mice. A reduction of bacterial translocation and a
Hakami A, Ali A and Hakami A. Effects of hepatitis B virus mutations on its modified intestinal expression of proinflammatory and immunoregulatory med-
replication and liver disease severity. Open Virol J 2013; 7: 12-18. iators indicate beneficial non-hepatic/non-hemodynamic mechanisms of FXR
Wang XZ, Li D, Tao QM, et al. A novel hepatitis B virus X-interactive protein: agonism in portal hypertension.
cytochrome C oxidase III. J Gastroenterol Hepatol 2006; 21: 711-715. Disclosure of Interest: None declared
Pelicano H, Lu W, Zhou Y, et al. Mitochondrial dysfunction and reactive oxygen
species imbalance promote breast cancer cell motility through a CXCL14-
mediated mechanism. Cancer Res 2009; 69: 2375-2383. OP415 LYMPHOCYTE SUBSETS AND CYTOKINES IN ASCITIC FLUID
McClain SL, Clippinger AJ, Lizzano R, et al. Hepatitis B virus replication is OF DECOMPENSATED CIRRHOTIC PATIENTS WITH AND
associated with an HBx-dependent mitochondrion-regulated increase in cytosolic WITHOUT SPONTANEOUS ASCITES INFECTION
calcium levels. J Virol 2007; 81: 12061-12065. Z.A. Sayed1,*, E.A. Alkareemy1, N.F. Ameen1, A.M. Sabry1
Kumar V, Jayasuryan N and Kumar R. A truncated mutant (residues 58-140) of 1
Internal Medicine Department, Gastroenterology Unit., Asssiut University
the hepatitis B virus X protein retains transactivation function. Proc Natl Acad Hospital, Assiut. Egypt., Assiut, Egypt
Sci U S A 1996; 93: 5647-5652. Contact E-mail Address: zain4373@yahoo.com
Disclosure of Interest: None declared
INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a frequently
encountered and important complication of decompensated liver cirrhosis. The
OP413 HEPATITIS C NONSTRUCTURAL PROTEIN 3/4A DAMPENS immune system plays an important role in the development or eradication of this
INFLAMMATION AND CONTRIBUTES TO SLOW FIBROSIS infection. A number of compositional and functional alterations in immune
PROGRESSION DURING CHRONIC LIVER INJURY IN MICE system cells have been demonstrated in cirrhotic patients; however, there is a
R. Bansal1,*, L. Frelin2, E. Brenndorfer 2, J. Prakash1, M. Sallberg2 lack of knowledge about this issue in ascitic infections.
1
MIRA institute for Biomedical Technology and Technical Medicine, University of AIMS & METHODS: The aim of the present study was to evaluate lymphocyte
Twente, Enschede, Netherlands, 2Laboratory Medicine, Division of Clinical subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in
Microbiology, Karolinska Institute, Stockholm, Sweden decompensated cirrhotic patients with or without spontaneous bacterial perito-
Contact E-mail Address: r.bansal@utwente.nl nitis. This case-control study included 50 decompensated cirrhotic patients.
Patients with ascitic polymorphonuclear leukocyte count 250/mm3 and/or posi-
INTRODUCTION: Hepatitis C virus (HCV) primarily infects hepatocytes and tive ascitic bacterial cultures were classified as the patients group (n25,
the infected hepatocytes with ongoing inflammation appear to promote fibrogen- meanSD of age was 57.84 6.66 years). Patients with ascitic polymorpho-
esis. To date, the underlying mechanism of HCV-induced fibrogenesis remains nuclear leukocyte count 5250/mm3 and/or negative ascitic bacterial cultures
unclear. The aim is therefore to understand the role of HCV non-structural were classified as the controls group (n25, meanSD of age was 60.36
protein (NS3/4A) in the disease progression. 6.51years). Comparison was made between the patients and controls groups
AIMS & METHODS: We used HCV non-structural NS3/4A expressing trans- for the following parameters: ascites leukocyte counts and differentiations; ascitic
genic mice (NS3/4A-Tg) to accomplish the aims of the study. Hepatic fibrosis fluid protein; albumin levels and serum-ascites albumin gradients; flow cyto-
was induced in wild-type and NS3/4A-Tg mice either by single injection of metric detection of ascitic lymphocyte subsets (CD3, CD4, CD8, CD4/CD8
carbon tetrachloride (acute) or multiple injections for 4 or 8 weeks. Fibrotic ratio, CD19, CD45) and ascitic cytokine TNF-alpha.
parameters (collagen and HSC markers), inflammatory response (macrophages) RESULTS: Ascitic total protein and albumin levels were significantly decreased
and hepatocyte turnover (proliferation and apoptosis) were examined. in patients group. The CD4, CD19, CD45 and CD4/CD8 ratio were significantly
RESULTS: Hepatic expression of NS3/4A did not induce spontaneous liver decreased in the patients group. Furthermore, ascites CD3, CD8 and TNF-
damage. During acute liver injury and intermediate fibrosis (4 weeks), NS3/ levels were significantly elevated in this group. The incidence of renal impair-
4A-Tg mice exhibited enhanced liver fibrogenesis. Surprisingly, reduced fibrosis ment, gastrointestinal bleeding and hepatic encephalopathy was higher in
was observed in NS3/4A-Tg during chronic liver fibrosis (8 weeks). No difference patients group and there was a significant correlation between TNF-alpha and
in inflammation and hepatocyte turnover was observed in 4 weeks fibrosis model, renal impairment in this group.
while decreased inflammation was observed in NS3/4A-Tg during chronic liver CONCLUSION: These results suggest that a cytotoxic, especially Th1, immune
fibrosis. Interestingly, increase in M2 macrophages and increased hepatocyte response predominates in ascites infections. It also demonstrates that TNF-
proliferation (and decreased apoptosis) was found in NS3/4A transgenics might be involved in the pathogenesis of ascites infections.
during chronic liver fibrosis. REFERENCES
CONCLUSION: During early fibrogenesis, HCV induces liver damage. While 1. Bonnel AR, Bunchorntavakul C, Reddyel KR. Immune dysfunction and infec-
during chronic liver fibrosis, HCV (or HCV NS3/4A) dampens inflammation and tions in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9: 727738.
induces hepatocyte proliferation thereby contributing to slow fibrosis progres- 2. Blaise M, Pateron D, Trinchet JC, et al. Systemic antibiotic therapy prevents
sion to promote its survival or persistence. bacterial infections in cirrhotic patients with gastrointestinal hemorrhage.
Disclosure of Interest: None declared Hepatology 1994; 20: 34-33.
3. Borzio M, Salerno F, Piantoni L, et al. Bacterial infection in patients with
advanced cirrhosis: a multicentre prospective study. Dig Liver Dis 2001; 33: 41
OP414 THE SYNTHETIC FXR AGONIST PX20606 ATTENUATES 48.
BACTERIAL TRANSLOCATION, INTESTINAL INFLAMMATION, 4. Caly W and Strauss E. A prospective study of bacterial infections in patients
AND REDUCES SPLANCHNIC BLOOD FLOW IN PORTAL with cirrhosis. J Hepatol 1993; 18: 353-358.
HYPERTENSIVE MICE Disclosure of Interest: None declared
P. Schwabl1,*, M. Wagner1, L. Garnys1, F. Riedl1, T.L. Schubert1, B.A. Payer1,
D. Mitteregger2, C. Kremoser3, M. Trauner1, M. Peck-Radosavljevic1,
T. Reiberger1 on behalf of Hepatic Experimental Hemodynamic Laboratory of OP416 LGR5 LIVER ORGANOIDS AS A MODEL TO STUDY
Vienna POLYCYSTIC LIVER DISEASE
1
Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Dept. of E.S. Wills1,2,*, R. te Morsche3, R. Roepman1,4, J. H. de Wilt5, M. Huch6,
Laboratory Medicine, Div. of Clinical Microbiology, Medical University of Vienna, H. Clevers7, J.P. Drenth2
Vienna, Austria, 3PheneX Pharmaceuticals AG, Ludwigshafen, Germany 1
Department of Human Genetics, 2Department of Medicine, Division of
Contact E-mail Address: philipp.schwabl@meduniwien.ac.at Gastroenterology and Hepatology, 3Laboratory Gastroenterology & Hepatology,
4
Nijmegen Center for Molecular Life Sciences, 5Department of Surgery,
INTRODUCTION: The farnesoid X receptor (FXR) is expressed in liver and Radboudumc, Nijmegen, Netherlands, 6The Gurdon Institute, University of
gut, and affects bile acid and lipid homeostasis. In addtion, FXR agonists have Cambridge, Cambridge, United Kingdom, 7Hubrecht Institute for Developmental
been shown to be antifibrotic and enteroprotective. Biology and Stem Cell Research, University Medical Center Utrecht, Utrecht,
AIMS & METHODS: The aim of our study was to assess the effects of the non- Netherlands
steroidal FXR agonist PX20606 (PX) on hemodynamics, intestinal barrier and Contact E-mail Address: edgar.wills@radboudumc.nl
bacterial translocation in a portal hypertensive mouse model. Male C56/Bl6 mice
underwent partial portal vein ligation (PPVL) or sham-operation (SO) and were INTRODUCTION: Liver stem cells are capable of expanding into LGR5
treated with FXR agonist PX20606 (PX,10mg/kg/day, gavage) or vehicle organoids constituted of cholangiocytes. Important features of polycystic liver
United European Gastroenterology Journal 2(5S) A131
disease (PLD) are increased cholangiocyte proliferation and fluid secretion, as PLD-associated genes PRKCSH, SEC63, LRP5 and PKD2. Lanreotide sig-
which can be suppressed by somatostatin analogues such as lanreotide. PLD is nificantly decreases expansion of liver organoids in comparison to control (197%
caused by mutations in genes such as PRKCSH, SEC63, LRP5 and PKD2. There 46% versus 547% 28%; p: 0.038).
is no human in vitro model available that truly recapitulates polycystic liver CONCLUSION: LGR5 liver organoids are an appropriate in vitro model to
disease. We hypothesize that PLD cholangiocytes can form LGR5 liver orga- study PLD. Organoids respond to lanreotide by decreased expansion. Our model
noids with aforementioned features of cyst development. has potential to be used for large scale drug screening.
AIMS & METHODS: We aim: 1.) To isolate cholangiocytes from human cyst REFERENCES
biliary epithelium and cyst fluid and expand these into LGR5 liver organoids. 1. Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5 liver stem
2.) To characterize stem cell, cholangiocyte and PLD-associated gene expression cells induced by Wnt-driven regeneration. Nature 2013; 494: 247-250.
and polarization of liver organoids. 3.) To determine the effect of lanreotide on 2. Masyuk TV, Masyuk AI, Torres VE, et al. Octreotide inhibits hepatic cysto-
liver organoids. genesis in a rodent model of polycystic liver disease by reducing cholangiocyte
Cholangiocytes from patient cyst biliary epithelium and cyst fluid were isolated adenosine 3,5-cyclic monophosphate. Gastroenterology 2007; 132: 1104-1116.
and placed under conditions suitable for expansion of adult liver stem cells. Disclosure of Interest: E. Wills: None declared, R. te Morsche: None declared, R.
Following organoid development, LGR5, SOX9, KRT7, KRT19, PRKCSH, Roepman: None declared, J. de Wilt: None declared, M. Huch Other: MH is
SEC63, LRP5 and PKD2 expression were determined by quantitative real-time inventor on several patent applications related to organoid culture, H. Clevers
polymerase chain reaction. Confocal microscopy staining for -catenin was per- Other: HC is inventor on several patent applications related to organoid culture,
formed to determine organoid polarization. In three independent experiments, J. Drenth Financial support for research from: MLDS, Axcan Pharma, BBMRI,
control (0.1 M acetic acid) or lanreotide (107M in 0.1M acetic acid) was added PIDON, IPSEN, Novartis and the Dutch Kidney Foundation.
twice a day, at 12-hour intervals for seven days. Organoid development was
followed by light microscopy and circumferential areas were quantified by
Image J software (NIH). Data were expressed by percentage change in circum-
ferential area (mean SEM) on day 7 in comparison to day 1. Statistical analysis
was performed by Students t-test.
RESULTS: We successfully isolated cholangiocytes from cyst biliary epithelium
and cyst fluid that were expanded as liver organoids. Organoids form cysts with
monolayered walls, which display predominant basolateral membranous -cate-
nin staining. In addition, they express LGR5, SOX9, KRT7 and KRT19, as well
UEG Week 2014 Poster Presentations
United European Gastroenterology Journal
2(5S) A132A605
MONDAY, OCTOBER 20, 2014 9:0017:00 ! Author(s) 2014
POSTER PLUS VIDEO I POSTER EXHIBITION HALL XL_____________________ Reprints and permissions:
P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN; sagepub.co.uk/journalsPermissions.nav
COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE DOI: 10.1177/2050640614548980
WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE ueg.sagepub.com
PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY
N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1,
S. Date1, J. Bapaye3
1
Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath
Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY
Medical College, Pune, India GASTRIC CANCERS USING THE CLUTCH CUTTER
Contact E-mail Address: amolbapaye@gmail.com K. Akahoshi1,*, Y. Motomura1, M. Kubokawa1, J. Gibo1, N. Kinoshita1,
INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis. S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1,
The best approach for drainage of these collections is still controversial. We N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1
1
present our retrospective data comparing the two endoscopic methods for drai- Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan
nage of WOPN. Contact E-mail Address: kakahoshi2@aol.com
AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural
drainage (EUTMD) using a newly designed fully covered large-bore wide-flare INTRODUCTION: To reduce the risk of complications related to ESD using
metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who conventional knives, we developed the Clutch Cutter (CC), which can grasp and
underwent placement of multiple plastic stents (Gr II). The pre-op CECT con- incise the targeted tissue using electrosurgical current.
firmed suitability of endoscopic drainage based on location, wall thickness & AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients
contents. Visual quantification of necrosis (450% solid debris) by EUS excluded (228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intra-
8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by mucosal or superficial submucosal gastric cancer without lymph node involve-
standard technique by a single endoscopist. The difference between the two ment, that had been confirmed by preliminary endoscopy, EUS, and endoscopic
groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of biopsies, were enrolled into this prospective study. The CC was used for all steps
NCT and subsequent necrosectomy was done whenever necessary. Follow-up of ESD (marking, circumferential marginal incision, submucosal dissection, and
imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes hemostatic treatment). The therapeutic efficacy and safety were assessed.
were compared in terms of clinical success, need for surgery, complications, RESULTS: The mean size of the early gastric cancers and resected specimens was
hospital stay and mortality. 17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes.
RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with
demographics, etiology of pancreatitis, cyst location, size and amount of debris. tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respec-
Placement of NCT, need of necrosectomy and no of sessions required were also tively. The R0 resection rates according to tumor size and location were 97.4%
not different between the two groups. Clinical success defined as resolution of (229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9%
symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p 0.048). None (127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/
of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II 95) in upper portion. The mean operating time according to tumor size and
(p 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p 0.016) location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9
Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p 0.012). min in lower portion, 108.8 min in middle portion, and 117.2 min in upper
Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p 0.22) portion. Perforation during ESD occurred in one case (0.3%), which was man-
CONCLUSION: The Nagi stentTM is effective and safe for EUTMD of WOPN. aged with conservative medical treatment after endoscopic closure of the perfora-
It permits rapid clinical resolution with 100% technical and clinical success rates. tion. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully
It offers distinct advantage over plastic stents although further prospective stu- treated by endoscopic hemostatic treatment.
dies are warranted. CONCLUSION: ESD using CC is a safe and technically efficient method for
Disclosure of Interest: None declared resecting early gastric cancers.
REFERENCES
1) Akahoshi K, Akahane H, Murata A, et al. Endoscopic submucosal dissection
P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.
TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF 2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic
THE ESOPHAGUS USING A RENDEZ-VOUS TECHNIQUE submucosal dissection using the clutch cutter for early stage digestive tract
J.-M. Gonzalez1,*, G. Vanbiervliet2, M. Barthet1 tumors. Digestion 2012: 85: 80-84.
1
Gastroenterology, Aix-Marseille University, North Hospital, Marseille, Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM
2
Gastroenterology, Nice Hospital, Nice, France have applied for the patent in Japan, Europe, and USA for the Clutch Cutter
described in this article. China has already granted the patent., Y. Motomura:
INTRODUCTION: Complete esophageal obstruction leads to definitive fasting. None declared, M. Kubokawa: None declared, J. Gibo: None declared, N.
The rendez-vous endoscopic approach had already been described for complex Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None
stenoses as an alternative to surgery that has high morbid-mortality. declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T.
AIMS & METHODS: This is a case series report about six patients referred for Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya:
complete esophageal disruption classified in two groups: 1/ Long disruption (4 None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M.
5cm), one after caustic ingestion and two due to an esophageal stripping during Oya: None declared
SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (5
5cm), consecutive to radiation therapy for a neck neoplasia. They had been
fasting for 3 to 18 months. All the procedures were performed according the P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A
anterograde retrograde approach, under anesthesia and with CO2 insufflation COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK
and X-rays guidance. KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS
RESULTS: There were 3 men and women between 25 and 71 years old. All the M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T. Ponchon5
reconstructions have been successful in one to three endoscopic sessions, using 1
Gastroenterology and endoscopy, Hopital Edouard Herriot, 2Inserm U1032,
the non hydrophilic tip of a guide wire passed through a straight catheter in 5 3
Functional disorders unit, Hopital Edouard Herriot, Lyon, France,
cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created, 4
Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania,
by transillumination (n 1) or head and neck surgery (n 1). In order to guide 5
Gastroenterology and endoscopy unit, Hopital Edouard Herriot, Lyon, France
the reconstruction, SEMS was used in one case, NGT in one case, and both were Contact E-mail Address: mathieupioche@free.fr
used in one patient. The first dilation was performed with a CRE balloon
(12-15mm). All the patients could eat mixed after 2 POD. There was no intra- INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising
operative or post-operative complication. Then, the patients underwent 3 to 18 method for the treatment of the esophageal achalasia. But the precise technique
dilations sessions during 1.5 to 15 months; two are still undergoing dilations and can be refined. We developed a combined technique of water jet system for
all eat normally. tunnelling and hook knife section for myotomy and we evaluated its results in
CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe a prospective study.
and effective in case of esophageal disruption even with loss of SES, avoiding AIMS & METHODS: The patients presented with an achalasia without any
surgery. prior instrumental treatment. The submucosal tunnel was created 12 cm over
Disclosure of Interest: None declared the cardia and 3 cm below, and then the endoscopic myotomy was performed
using the Olympus Hook Knife by a single operator with CO2 insufflation,
beginning 8 cms over the cardia and finishing 2 cms below. The clinical evalua-
tion was realized before and then after the procedure at 1, 3, 6 and 12 months
(score of Eckardt, score of quality of life GIQLI). A high-resolution manometry
was realized before POEM and 3 months later to classify the achalasia (classifi-
cation of Chicago) and to measure basal pressure and pressure of relaxation
integrated (PRI) of the lower esophageal sphincter. Then an esophageal
pHmetry of 24 hours was performed at 3 months to diagnose GERD. The
United European Gastroenterology Journal 2(5S) A133
data are expressed in median (extremes) and compared before and later myoto-
P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL
mie by paired t-test.
FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE
RESULTS: 21 patients (13 men, average age 61 years) were included. 18 proce-
GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS
dures were complete, 1 was not realized because of a large esophageal diverticu-
CONDITIONS AND LESIONS OF THE STOMACH
lum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the
tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3
1
occurred but did not prevent to continue the procedure after mucosal closure by Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration,
clips. Dual Knife (n 7) or the water jet Nestis Enki 2 (n 11) were used for Polyclinic 1 of the Business Administration for the President of the Russian
the tunnel. No mucosal injuries were observed with the water-jet system. Hook Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl,
Knife was used for all myotomies. The average time of procedure was 94.2 min Russian Federation
with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated Contact E-mail Address: kuvaev_roman@mail.ru
with a needle during the procedure in 13 cases without any visible perforation.
CT scan at day 1 showed a pneumomediastinum (n 14/18), a pneumoperito- INTRODUCTION: Endoscopic mapping of the entire stomach with advanced
neum (n 14/18) and/or a peumothorax (n 3/18). No sepsis was observed. techniques has been recommended as an important step of surveillance of pre-
Feeding was always possible with liquids at day 1. All patients noted a clinical malignant gastric conditions/lesions [1]. Although current imaging technologies,
improvement. At 3 months, the basal pressure of the SIO was decreased for all such as narrow-band imaging (NBI) and high-magnification endoscopy, allow
patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p50.01) as well as the enhanced visualization of gastric mucosa, their application is still limited due to
PRI (8 mmHg (0-16) against 23 mmHg (9-28), p50.01). pH metry showed a low contrast and brightness of endoscopic view and complexity of usage. Newly
pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases. developed NBI system with dual focus (DF) magnification might be a promising
tool to overcome this challenge.
Inclusion 1 month 3 months 6 months 1 year AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy
of new NBI-DF system in detection, characterization of gastric lesions in patients
n 21 17 14 10 3 with extensive atrophy and/or intestinal metaplasia. A total of 43 patients (mean
Eckardt 6 (3-11) 1 (0-3)* 1 (0-3)* 0 (1-4)* 0 (0-0)* age 51.3 years, SD 12.1) were initially examined by conventional white light
GIQLI 82 (50-114) 115 (66-135)* 115 (82-140)* 131 (94-143)* 140 (130-142) endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy
(CE) with indigocarmine was performed as the gold standard for detection
of lesions. Any suspicious areas detected by NBI or CE were subsequently further
assessed with NBI with DF (Olympus Exera III GIF H190) and characterized
CONCLUSION: Water-jet injection allows rapid and safe tunneling of the sub- accordingly. Biopsies were taken from all lesions for histological assessment.
mucosa and myotomy with hook knife is very precise. Safety and effectiveness of RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic
mytomy is reinforced using these technical refinements. (chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 high-
Disclosure of Interest: None declared grade dysplasia/early gastric cancer. All lesions (100%) detected by CE were
found with NBI observation. Endoscopic histology prediction was successful in
88 cases (94.6%) Endoscopic misdiagnosis was found in 5 cases (5.4%): over-
P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGH- estimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive
MAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY predictive value and negative predictive value were 80%, 97.4%, 85.7% and
FOR DIFFERENTIATION OF GASTRIC LESIONS 96.2% respectively for early gastric cancer/high-grade dysplasia.
R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3, CONCLUSION: Observation of gastric mucosa with a novel NBI system was at
E. Nikonov4, V. Kapranov5, A. Rusakov6 least as effective as CE with indigocarmine in detection of suspicious gastric
1
Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation, lesions in patients with precancerous conditions and lesions of the stomach.
2
Institute of Science and Technology Austria (IST Austria), Klosterneuburg, Dual focus magnification provides sufficient assessment of microvascular and
Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G. microsurface patterns in order to differentiate gastric lesions. Further rando-
Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic 1 of mized controlled studies are needed to be performed for clarifying the role of
the Business Administration for the President of Russian Federation, Moscow, novel endoscopic system in diagnosis of gastric pathology.
5
Internet Center, 6Administration, P. G. Demidov Yaroslavl State University, REFERENCES
Yaroslavl, Russian Federation 1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous
Contact E-mail Address: kuvaev_roman@mail.ru conditions and lesions in the stomach (MAPS): guideline from the European
Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study
INTRODUCTION: High-magnification endoscopy with narrow-band imaging Group (EHSG), European Society of Pathology (ESP), and the Sociedade
(HME-NBI) has been used for diagnosis of gastric pathology because of its high Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.
accuracy. Nevertheless, the application of these advanced techniques in clinical Disclosure of Interest: None declared
practice is difficult due to the presence of various histological changes of gastric
mucosa with different modifications of microvascular and microsurface patterns.
Newly developed computer-aided decision support systems are designed to detect P0007 DEVELOPMENT OF A PROTOTYPE OF VIDEO
and/or classify abnormalities and thus assist a medical expert in improving the SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES
accuracy of medical diagnosis. However, there is lack of data for computer-aided DURING ENDOSCOPIC EVALUATION OF BARRETTS
devices for classification of gastric lesions with HME-NBI. OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL
AIMS & METHODS: The aim of this study was to evaluate the effectiveness of STUDY
computer-aided classifier of endoscopic magnification images of gastric lesions. S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1
We analyzed our database contains 78 endoscopy NBI magnification images of 1
CHU Strasbourg, 2IRCAD, Strasbourg, France
gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images Contact E-mail Address: adrien.sportes@free.fr
were classified into three classes: oval (13 images), tubular (31 images), and
destroyed with vessel network (34 images). Initially we divided images of every INTRODUCTION: The prevalence of Barretts oesophagus (BE) is 5 to 6% in
class into two sets training set and test set. Then we selected uniformly dis- the general population, with a progression from dysplasia to adenocarcinoma 0.6
tributed random points with fixed density (one random point for every 300 to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early
pixels) at every picture, which were analyzed by extracting topological features lesions accessible to endoscopic treatment. However, the relocalisation of lesions
for building the classifier. Training set images were used for classifier training detected by biopsies may be difficult during follow-up endoscopies. The purpose
with Adaboost algorithm and testing set images of each group were utilized for of this study was to evaluate the prototype of a magnetic probe for accurate
testing with previously trained classifier. We repeated the procedure described location of the position of the endoscope, allowing the relocalisation of this
above for the estimation of classifier quality. position in a subsequent endoscopy. We report the results of a feasibility study
RESULTS: From 78 database images there were 50 images (66.6%) with the in pigs and the use of this device in two patients with BE.
success rate of correct classification exceeding 80%. In 14 images (17.9%) all AIMS & METHODS: The system consists of an electromagnetic (EM) field
points (100%) were recognized correctly. The mean percentage of points with the transmitter and an EM probe constituting the electromagnetic tracking system
correct classification was 79%. (EMS) (NDI, Aurora). The EM probe is inserted through the operating channel
CONCLUSION: Topological features were successfully used for description of of a double channel gastroscope. The EM field generator is positioned on the
endoscopic magnification images. The combination of topological features ana- patients chest wall. The system also includes new software developed at IHU/
lyzed with Adaboost algorithm allowed for creating and effective training of IRCAD, which performs simultaneous recording of the video from the endo-
computer-aided classifier of endoscopic magnification images of gastric lesions. scope alongwith its corresponding position, as measured by the EMS. During a
Disclosure of Interest: None declared second endoscopy, this software allows automatic synchronisation of the
recorded video to provide relocalisation of the endoscope in front of previous
biopsy sites in the oesophagus.
The system was tested in 5 anesthetised pigs. During the first endoscopy, ten
markings were performed by argon plasma electrocoagulation (ERBE Tubingen,
Germany) in the distal oesophagus. The position of each marking was recorded
by the system. A second operator to then performed a blind endoscopy on the
same pigs and was asked to follow the system implicitly as a guide to relocate the
markings.
In 2 patients with BE, the system was then tested to facilitate relocalisation of the
biopsy sites.
RESULTS: Ten markings were made in the distal oeosphagus of 5. After with-
drawal of the endoscope the second operator found 48 of the 50 markings (96%)
A134 United European Gastroenterology Journal 2(5S)
using the guidance provided by the system. The positioning of the endoscope p50.05). Furthermore, depleting CD4 T-cells in MCD-fed immunized mice
provided by the EMS system was within a 2mm range from the initial position- by using an anti-CD4 monoclonal IgG did not affected B220 expression, but
ning. In the evaluation of BE patients, the system relocalised the biospy sites significantly lowered the hepatic mRNAs IFN-, iNOS and IL-12p40 and ame-
within a range of 3mm. liorated lobular inflammation and focal necrosis.
CONCLUSION: This preliminary study shows the feasibility of the EMS pro- CONCLUSION: These results indicate that B-cell responses triggered by oxida-
totype to relocalise the endoscope in the oesophagus within an acceptable range. tive stress can contribute to inflammation in NASH by stimulating T-cellular
The clinical usefulness of this system should be evaluated further during the responses.
follow-up of patients with BE. Disclosure of Interest: None declared
Disclosure of Interest: None declared
P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER
FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER CELLS IN AN ANIMAL MODEL OF NAFLD
REGENERATION IN A RABBIT MODEL V. Lembo1,*, G. Mazzone1, G. DArgenio1, M. DArmiento2, F. Morisco1,
F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van Gulik1 N. Caporaso1
1
Surgery, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam, 1
Department of Clinical Medicine and Surgery, 2Department of Advanced
Netherlands Biomedical Science, University of Naples Federico II, Naples, Italy
Contact E-mail Address: f.huisman@amc.nl
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most
INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase common liver disease in Western countries, is pathogenetically related to a seden-
future remnant liver volume in patients requiring extended resections. Reversible tary lifestyle as well as to poor quality diet characterized by an excessive energy
PVE is of interest when generating sufficient hypertrophy while preserving the intake including high fatty foods and high amounts of fructose, the so-called
embolized liver lobe. The concept of reversible PVE requires an absorbable Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of trigly-
embolization material. cerides. Vitamin D in addition to the effects on lipid metabolism, plays other
AIMS & METHODS: The aim of this study is to modulate lysis time of a fibrin- biological functions, among which a trophic effect on human cultured cells.
glue based embolization material while using different concentrations of AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by
Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG. Western Diet, the relationship between body weight, liver weight and grade of
PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5 steatosis; and if these parameters are modified by vitamin D supplementation.
groups: Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats.
Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), n 4) The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD);
Fibrin glue with Aprotinin (FG700KIU, n 5) WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment
Fibrin glue with Aprotinin (FG500KIU, n 5) was conducted for 6 months. Weekly, the rats, body weight was recorded. At
Fibrin glue with Aprotinin (FG300KIU, n 5) sacrifice, livers were excised and weighed and samples were stored at -80 C. Liver
Fibrin glue without Aprotinin (FG-Aprot, n 5) histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis
The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of was numerically scored following semi-quantitative pathological standard.
non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight RESULTS: During the experiment the increase of body weight was similar in the
ratio of NEL were evaluated. three groups. In the two groups fed with WD liver weight was significantly higher
RESULTS: Data were compared with a previous series using a permanent embo- than SD group (p50.01). A positive correlation between body weight and liver
lization material, i.e. polyvinyl alcohol coils (PVAc), showing complete and weight was observed in WD groups (p50.0001). The liver/body weight ratio was
permanent occlusion of the embolized portal vein branch in all rabbits after 7 significantly higher in WD and WDVitD groups than SD: 2.90.05, 2.80.07
days. and 2.00.04, respectively; p50.001). Steatosis was present in 61% and 21% of
FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy hepatocytes in WD group and WDVitD group, respectively, and absent in SD
response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of group. No correlation was found between the grade of steatosis and liver or body
the FG1000KIU Aprotinin group was still occluded and showed a hypertrophy weight nor between the grade of steatosis and liver/body weight ratio. Although
response comparable to the PVAc group. The group of FG 700KIU Aprotinin vitamin D supplementation reduced the degree of steatosis, liver/body weight
survived 14 days and in two of the five rabbits, the embolized portal vein was ratio in WDVitD group was similar to WD group.
recanalized at sacrifice. The hypertrophy response in these rabbits was not dif- CONCLUSION: In a rat model of NAFLD induced by WD the presence and
ferent from the PVAc group. The rabbits with FG 500KIU and 300KIU extent of steatosis are independent from body weight. Interestingly and unex-
Aprotinin were sacrificed at day 49. In the group with FG 500KIU Aprotinin, pectedly, in WD groups the supplementation with vitamin D reduces liver stea-
4 out of 5 showed recanalization of the cranial portal branches. In the group with tosis but not liver weight: this sustains the hypothesis of a trophic effect of
FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups vitamin D on liver cells.
showed hypertrophy response rates not different compared to the PVAc group. Disclosure of Interest: None declared
CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU
Aprotinin resulted in 70% reversible embolization with a hypertrophy response
comparable to the PVAc group. P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT
Disclosure of Interest: None declared MODEL OF NAFL
G. Mazzone1,*, V. Lembo1, G. DArgenio1, M. Guarino1, M. DArmiento2,
F. Morisco1, N. Caporaso1
P0024 TRANSPLANTATION OF HUMAN AMNION-DERIVED 1
Department of Clinical Medicine and Surgery, 2Department of Advanced
MESENCHYMAL STEM CELLS AMELIORATES CARBON Biomedical Science, University of Naples Federico II, Napoli, Italy
TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS Contact E-mail Address: giovanna.mazzone@gmail.com
K. Kubo1,*, S. Ohnishi1, N. Sakamoto1
1
Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp (NAFLD) rise to become the most common cause of chronic liver disease in
Western countries. It is known that insulin resistance and type 2 diabetes mellitus
INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease (T2DM) have an important role in the pathogenesis of obesity and NAFLD. A
caused by a variety of factors, such as viral infections, alcohol, drugs and che- growing body of evidence points to a linked and potentially causative relation-
mical toxicity. The only effective available treatment for end stage liver fibrosis is ship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.
transplantation; however, due to the lack of donors, complications and trans- AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin
plant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs) D3 supplementation is able to modulate the liver effects and glucose homeostasis
have been reported to be a valuable cell source in cell therapy. Recently, bone of a westernized diet, high in fat and fructose, in an animal model of NAFL
marrow- or adipose tissue-derived MSCs have been reported to be effective in the without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided
treatment of liver fibrosis. In addition, several studies have shown that MSCs can into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western
be easily isolated from human amnion, and a large amount of cells can be Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23
obtained. Therefore, we examined the effects of transplantation of human IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6
amnion-derived MSCs (hAMSCs) in rats with liver fibrosis. months. Liver histology was examined by haematoxylin/eosin and Oil Red-O
AIMS & METHODS: All pregnant women gave written informed consent, and staining. Insulin resistance was determined according to the Homeostasis
amnion was obtained at Cesarean delivery. hAMSCs were isolated by collage- Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evalu-
nase treatment, and expanded with culture medium containing fetal bovine ated according to Brunt EM et al.
serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in
intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while
week for 7 weeks. At 3 weeks, hAMSCs (1106 cells) were transplanted intrave- in WDVitD group only 27% of hepatocytes contained fat. In WD group
nously. Rats were sacrificed at 7 weeks, and histological analyses and quantita- HOMA-IR was significantly higher than in SD (41.98.9 vs 6.171.3, p50.01)
tive RT-PCR were performed. and it was reduced by vitamin D supplementation in WDVitD group (41.98.9
RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area vs 19.45.2, p50.05). Interestingly SD and WDVitD rats were not diabetic
and deposition of type I collagen. In addition, hAMSC transplantation signifi- (98.78.0 and 103.26.1, respectively) while all rats in WD group were diabetic
cantly decreased the number of -SMA-positive hepatic stellite cells and and (1399.6) with glycemic values significantly higher than SD (p50.01) and
CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expres- WDVitD (p50.05).
sion of -SMA was significantly decreased in the liver of hAMSC-treated rats, CONCLUSION: These results suggest that a daily supplementation of vitamin
and mRNA expression of type I collagen, TGF- and IL-1 tended to be D3 is able to improve insulin sensitivity and to prevent the development of
decreased by hAMSC transplantation. diabetes and hepatic steatosis in WD rats.
CONCLUSION: Transplantation of hAMSCs provided significant improvement Disclosure of Interest: None declared
in a rat model of liver fibrosis, possibly through inhibition of inflammatory
reaction. hAMSC would be considered as a new cell source for the treatment
of liver fibrosis.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A139
P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL
DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI)
S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3, AND ULTRASOUND
H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1 S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, A. Carvalho3, H. Cortez-
1
Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research Pinto1,2,*
Center for Post-genome Science and Technology, 4Pathophysiology and 1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA,
Japan Lisbon, Portugal
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp
INTRODUCTION: The fatty liver index (FLI) derived from an Italian popula-
INTRODUCTION: Sphingomyelin (SM) is a major component in lipid micro- tion includes serum triglycerides, serum gamma-glutamyltransferase, body mass
domains, and SM is synthesized from ceramide by the action of SM synthase index (BMI) and waist circumference. It has been used as a noninvasive measure
(SMS). We have recently reported that mice deficient for SMS2 are resistant to of hepatic steatosis (HS), but has not been widely validated and not examined in
high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem the Portuguese population.
2011:286;28544). In this study, we examined the relationship between SM and AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult
ceramide molecular species and the development of NAFLD and insulin resis- population by fatty liver index (FLI) and correlate with the ultrasound findings;
tance in human. validate FLI for prediction of fatty liver in the Portuguese population.
AIMS & METHODS: Non-alcoholic students of our university with body mass Methods: Recruitment from a prospective epidemiological study of the general
index (BMI) 35 kg/m2 at the regular physical checkup in 2013 were enrolled, Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI.
and volunteer students with BMI of 20-22 kg/m2 were set as a control group. Performance of FLI for diagnosing steatosis compared with US was assessed
Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0, using AUROC.
C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circum-
C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver ference and BMIs were 50.518.4 years, 94.412.7 cm and 26.94.7 kg/m2,
enzymes, lipids and insulin resistance were measured by blood examination. respectively; 43% were overweight and 22% were obese. The median of FLI
Abdominal ultrasound was performed to confirm the existence of fatty liver, was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.
and body composition including percent body fat (PBF) was measured by bioim- Using the FLI, 27.6% of subjects had HS (FLI 4 60), 41.8% had no HS (FLI 5
pedance analysis. 30) and 30.6% were not classifiable (FLI 30-60). However, these cut-offs pro-
RESULTS: The levels of total SM and ceramide were not altered in obese group posed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI
(19-28 y.o., n 12), compared with control group (18-27 y.o., n 11). The con- 530 exhibited HS on ultrasound and 13.4% of subjects with FLI 4 60 showed
centrations of SM C18:0 and C24:0 in the obesity group were significantly higher no steatosis. For the FLI, the area under the ROC curve was 0.88 for the
than in the control group. Moreover, in the obese group, SM C20:0 and C22:0 diagnosis of HS.
tended to be higher than in the control group. In the analysis of total 23 cases, the There was a significant correlation (p 5 0.01) between the FLI and the following
serum levels of SM containing saturated fatty acids positively correlated with variables: weight ( 0.80), waist circumference ( 0.74), presence of steatosis
PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing ( 0.65), triglycerides ( 0.58), BMI ( 0.51), ALT ( 0.43), GGT
unsaturated acyl chain and almost all ceramide species did not correlate with ( 0.39), HDL ( -0.36), age ( 0.33), female sex ( -0.33), insulin
those items. ( 0.29), AST ( 0.28), LDL ( 0.24) and total cholesterol ( 0.22). No
CONCLUSION: The present study demonstrated that the serum levels of SM correlation was found with physical activity.
species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are CONCLUSION: FLI could accurately identify hepatic steatosis in the general
correlated with liver function and insulin resistance, suggesting that distinct Portuguese population. The calculation of FLI may be useful to suggest the
SM species are involved in the development of NAFLD and insulin resistance. possibility of the presence of steatosis and indicate the need for an abdominal
Disclosure of Interest: None declared ultrasound.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18
AND CONTROLLED ATTENUATION PARAMETER (CAP) IN
HEALTHY POPULATION P0030 NORMAL CONTROLLED ATTENUATION PARAMETER (CAP)
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,* VALUES: A POPULATION-BASED STUDY OF HEALTHY SUBJECTS
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*
metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon, 1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Portugal Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA,
Contact E-mail Address: sofiacarvalhana@msn.com Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: Liver steatosis measurement by controlled attenuation para-
meter (CAP) is a non-invasive method for diagnosing steatosis, based on tran- INTRODUCTION: Liver steatosis measurement by controlled attenuation para-
sient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18) meter (CAP) is a non-invasive method for diagnosing steatosis, based on tran-
have been proposed as a non-invasive alternative for the diagnosis of NAFLD, sient elastography. The normal range of controlled CAP values needs to be
especially NASH. explored in clinical and anthropometrically diverse healthy subjects. A recent
AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy study has shown an association of CAP with BMI and the number of metabolic
individuals with and without steatosis. Methods: Recruitment from a prospective syndrome criteria.
epidemiological study of the general Portuguese adult population. Steatosis eval- AIMS & METHODS: Aim: define the normal range of CAP values in healthy
uated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis subjects and evaluate the associated factors.
compared with US and CAP was assessed using AUROC. Methods: Recruitment from a prospective epidemiological study of the general
RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass Portuguese adult population. CAP was performed using Fibroscan in 134 healthy
index) were 52.617.1 years and 28.24.9 kg/m2, respectively; 25% had a subjects, without fatty liver on ultrasonography or positivity serology for
normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.
on ultrasound was 52.1%. RESULTS: From 134 consecutive individuals studied (66 males), 4 were
The mean (SD), median (minimum-maximum), and 5th and 95th percentile excluded due to failure/unreliable liver stiffness measurements (LSM). The
values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respec- mean age and BMIs (body mass index) were 46.918.0 years and 24.93.5 kg/
tively. Median CK-18 were elevated in patients with vs. without hepatic steatosis m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were
by ultrasound: 33.4 [IQR: 25151] vs. 73.7 [IQR: 25508] U/L, p 50.0001. obese. The mean (SD), median (minimum-maximum), and 5th and 95th percen-
CK-18 significantly correlated with steatosis ( 0.40), ALT ( 0.40), CAP tile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3
( 0.38), triglyceride ( 0.32), waist circumference ( 0.30), HDL ( - dB/m, respectively. Men had a higher mean CAP value than women (meanSD:
0.28), AST ( 0.27), LDL ( 0.26), total cholesterol ( 0.21) and the 213.147.1 dB/m versus 191.847.8 dB/m, respectively; p 0.012).
number of metabolic syndrome criteria ( 0.29), but not with LSM or BMI. CAP significantly correlated with gender ( 0.22), age ( 0.22), waist circum-
The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of ference ( 0.33), BMI ( 0.22), alcohol consumption ( 0.25), systolic blood
243 dB/m) were 0.78 (95% CI 0.710.86) and 0.74 (95% CI 0.650.82), pressure ( 0.27), ALT ( 0.27), fasting glucose ( 0.24) and the number of
respectively. metabolic syndrome criteria.
CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151, After allowance for potential confounders, CAP was not independently asso-
with a very large range. It showed a good discriminating capacity for diagnosing ciated with BMI or other risk factors for nonalcoholic fatty liver disease.
steatosis. CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences subjects and is not associated with BMI or the number of metabolic syndrome
Disclosure of Interest: None declared criteria.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
A140 United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We explored the composition of gut bacterial commu-
P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND
nities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina next-
KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT
generation sequencing.
POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL
RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that
T.J. G. Gevers1,*, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4, most of the microbiota samples were clustered by disease status. Differences were
J.P. Drenth1 abundant at phylum, family, and genus levels between NAFLD and healthy
1
Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology, subjects. Lentisphaerae at phylum level was significant higher in NAFLD micro-
4
Nephrology, RadboudUMC, Nijmegen, Netherlands biota. Among those taxa with greater than 0.1% average representation in all
Contact E-mail Address: tom.gevers@radboudumc.nl samples, five genera including Alistipes and Prevotella were the genus types
exhibiting significant higher level in healthy microbiota, while genera
INTRODUCTION: Several trials have demonstrated that somatostatin analo- Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in
gues decrease liver volume in mixed populations of patients with autosomal NAFLD microbiota. In addition, lymphocyte profiles (CD4T cell and
dominant polycystic kidney disease (ADPKD) and isolated polycystic liver dis- CD8T cell) and proinflammatory cytokines (TNF-, IL-6 and IFN-) in gut
ease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of biopsies of patients and healthy controls was analyzed to monitor the inflamma-
lanreotide and possibly enhances risk for adverse events. tion caused by dysbiosis microbiota. The levels of CD4 T cells and CD8 T cells
AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial) were lower in NAFLD patients compared with healthy subjects, and the proin-
was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously flammation cytokine TNF-, IL-6 and IFN- showed high level in NAFLD
every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We patients. What was more, irregular arrangements of microvilli and widening of
excluded patients with an estimated glomerular filtration rate (eGFR) 5 30 ml/ the tight junction were observed in gut mucosa of the NAFLD patients by
min/1.73m2. Primary outcome was change in liver volume, secondary outcomes transmission electron microscope.
were changes in kidney volume, eGFR, symptom relief and health-related quality CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD
of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided microbiota, decreased numbers of CD4T cells and CD8T cells, and increased
t-test to analyze within-group differences. levels of TNF-, IL-6 and IFN- in gut mucosa of NAFLD patients suggest a
RESULTS: We included 43 ADPKD patients with polycystic liver disease (84% role for gut microbiota in the gut inflammation and the dysregulated gut immu-
female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver nity, which promote pathogenesis of NAFLD. We postulate that the distinct
volume decreased from 4,859 ml to 4.595 ml (-3.1%;p50.001), and median composition of the gut microbiome among NAFLD and healthy controls
kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p 0.006). eGFR could offer a target for intervention or a marker for disease.
declined 3.5% after the first injection and remained stable up to study end. REFERENCES
Lanreotide significantly relieved postprandial fullness, shortness of breath and 1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiota-
abdominal distension, but had no effect on any of the EuroQol-5D dimensions. driven disease. Trends Endocrinol Metab 2013; 24: 537-545.
Three participants had a suspected episode of hepatic or renal cyst infection 2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver
during the study. disease. Hepatology 2013; 58: 120-127.
CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and Disclosure of Interest: None declared
decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely
after starting lanreotide, but stabilized thereafter.
Disclosure of Interest: None declared P0034 ASCITIC FLUID LACTOFERRIN FOR DIAGNOSIS OF
SPONTANEOUS BACTERIAL PERITONITIS
A.A. Ghweil1,*
P0032 THE EFFECTS OF POLY-UNSATURATED FATTY ACIDS 1
TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY
(PUFAS) IN A RODENT NUTRITIONAL MODEL OF NON- OF MEDICINE EGYPT, Qena, Egypt
ALCOHOLIC STEATOHEPATITIS (NASH) Contact E-mail Address: alimena1@yahoo.com
V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1
1
4th Department of Internal Medicine, General University Hospital and 1st Faculty INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is
of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics, based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This
General University Hospital and 1st Faculty of Medicine, Charles University in procedure is operator-dependent and lysis of PMNs during transport to the
Prague, Prague, Czech Republic laboratory may lead to false-negative results. Furthermore, ascitic fluid culture
is insensitive and leads to delays in diagnosis. The aim of this study was to assess
INTRODUCTION: NAFLD and subsequent NASH are probably the most the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to
common chronic liver diseases in western countries and have a high risk of identify a cut-off level that can be used for future development of a rapid bedside
development of liver cirrhosis associated with high morbidity and mortality. test.
AIMS & METHODS: The aim of the study was to determine effects of admin- AIMS & METHODS: Sixty ascites samples from cirrhotic patients were exam-
istration of PUFAs in the MCD dietary model of NASH and to assess the ined for PMN count, bedside culture, and lactoferrin concentration. AFLAC
potential anti-inflammatory role of PUFAs in the pathogenesis of NASH. concentrations were determined using a polyclonal antibody-based enzyme-
For 6 weeks were male mice fed either with MCD or with chow. There were 4 linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or
groups of animals. Both experimental and control groups received from the greater with or without a positive culture was used for diagnosis of SBP.
beginning either PUFAs or saline. Detailed liver histology, serum biochemistry, RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples
total lipid and fatty acids compound, adiponectin and leptin levels were deter- with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/
mined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were mL; compared with non-SBP samples (median, 39 ng/mL P 5 .001). The sensi-
measured. tivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%,
RESULTS: Feeding with MCD resulted in histopathological changes of respectively. The area under the receiver operating characteristic curve was 0.98.
NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP). Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis
Administration of PUFAs led to significant decreases of total animal and liver CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis
weight in MP. PUFAs also decreased cholesterol levels (P50.001), ALT of SBP. Qualitative bedside assays for the measurement of AFLAC can be devel-
(P50.01) and AST levels (P50.01). MP developed significantly less pro-inflam- oped easily and may serve as a rapid and reliable screening tool for SBP in
matory cytokine profile, had lower leptin (P50.01) and higher adiponectin levels patients with cirrhosis.
(P50.01) than controls. Administration of PUFA led also to lower serum con- Disclosure of Interest: None declared
centrations of saturated and monounsaturated FA and to higher serum concen-
trations of polyunsaturated FA in MP. Total lipid content of liver was
significantly lower in MP. P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION
CONCLUSION: We conclude that PUFAs may play a causal role in the patho- SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN
physiology of NASH. In summary, PUFAs have favorable effects on histopatho- CIRRHOTIC PATIENTS
logical changes, serum markers of liver damage, fatty acid compound and show C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D.
anti-inflammatory properties. We expect that PUFAs may represent a promising I. Gheonea1, I. Rogoveanu1
way in prevention and treatment of this increasingly common disorder. 1
Gastroenterology, UMF CRAIOVA, Craiova, Romania
Disclosure of Interest: None declared Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex
P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS treatable malignancies as its management is dependent on the stage of the under-
WITH NON-ALCOHOLIC FATTY LIVER DISEASE lying condition liver cirrhosis. An early diagnosis assures best curative chances,
W. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1, as liver resection or transplantation have good survival rates in the general
Y. Liu1,* population. Computer aided diagnostic and prognosis (CADP) models are cur-
1
Department of Gastroenterology, 2Institute of Clinical Molecular Biology & rently being developed for a number of malignancies to help clinicians manage
Central Laboratory, Peking University Peoples Hospital, Beijing, China cases based on individual needs of the patients rather than general statistics.
Contact E-mail Address: liuyulan@pkuph.edu.cn, wuna1030@163.com AIMS & METHODS: Our aim was to develop a CADP based on our previous
work involving artificial neural networks (ANN) [1] for successfully diagnosing
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized early HCC cases and better prognosticate their evolution, based on a set of
by a broad spectrum of hepatic pathology that is closely linked to obesity and criteria in accordance with current guidelines.
ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and Ethical clearance was obtained from the local board and 107 consecutive patients
even cirrhosis. NAFLD is recently believed to be under the influence of the gut with previously diagnosed liver cirrhosis signed informed consents for entering
microbiota, which may have toxic effects on the human host after intestinal the study, between January 2009 and February 2010. Clinical and demographic
absorption and delivery to the liver via the portal vein. parameters (age, sex, body mass index, waist circumference, type of viral
United European Gastroenterology Journal 2(5S) A141
infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory INTRODUCTION: There is a quest for biomarker discovery in liver disease
data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte especially to detect cirrhosis at an early stage. Current methods are invasive,
count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein throm- more often requiring a liver biopsy to confirm the diagnosis. For patients with
bosis, size and number of possible tumors), elastography data (strain ratio, com- Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst gener-
plexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular ally helpful, is unable to confirm the presence of fibrosis particularly in the
second moment, correlation) and stiffness value (FibroScan) were collected and presence of fat within the liver which is inevitable in most cases with NASH.
imputed in the CADP. For patients with clear liver tumors contrast-enhanced The gut microbiome is altered in several gastrointestinal disorders, resulting in
ultrasound was performed and time-intensity curve parameters were calculated altered gut fermentation patterns, which we (and others) have been able to
and fed to the ANN system: peak enhancement, time to peak, rise time, fall time, recognise by analysis of volatile organic compounds (VOC) in urine, breath
mean transit time, area under the curve. We have followed the 4-year incidence of and faeces1. The altered structure of the small intestinal mucosa and increased
HCC patients in tumor-free cases and assessed the evolution when any forma- gut permeability (noted in liver disease), we hypothesised, would also change the
tion, either regeneration nodule or early HCC was found. microbiome, hence recognisable by its unique fermentome pattern, making
RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules NASH distinguishable from controls.
[median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm AIMS & METHODS: To determine if NASH results in an altered VOC pattern
(min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguish-
patient: 1 (min: 1, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The able from cirrhotics vs non-cirrhotics.
CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration 33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8
nodules based on clinical, laboratory and imaging data. A total of 28 patients with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and
also developed HCC in the four-year follow-up period; the system correctly 12 controls (normal synthetic liver function). Urine was collected and 10 ml
predicted high possibility for HCC occurrence in 26 of these patients (92.85%), aliquots were stored frozen in universal containers. For assay, the containers
while giving high estimates for HCC in another 16 patients that remained cancer- were first heated to 40 0.1oC. The headspace (the air above the sample) was
free until now. then pumped from the containers and analysed by Field Asymmetric Ion
CONCLUSION: We could successfully predict the rate of malignancy in cirrho- Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used
tic patients by using a novel CADP system. We believe that such tools may for initial statistical evaluation, with a re-classification using a leave one out
become worthy aids to clinical management of patients with various types of for calculating sensitivity and specificity.
digestive pathologies. RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in
REFERENCES these different groups of liver disease. The control group was significantly dif-
1. Streba CT, et al. Using contrast-enhanced ultrasonography time-intensity ferent to all of the other groups with a sensitivity of 100%. Of the disease groups,
curves as classifiers in neural network diagnosis of focal liver lesions. World J NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively
Gastroenterol 2012; 18: 44274434. with specificity of 80%. NAFLD however had sensitivity of 50% but specificity
Disclosure of Interest: None declared of 80%.
CONCLUSION: This pilot study suggests the IMS (FAIMS technology) offers
a novel non-invasive approach to separate not only NASH from controls but
P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL also those with established cirrhosis using urine. It offers the potential for early
AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD non-invasive tracking of NASH and its complications.
SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE REFERENCES
COHORT STUDY 1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diag-
F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4, nostic modalities in gastroenterology gas phase volatile compound biomarker
B. Sean2 detection. Aliment Pharmacol Ther 2014; 39: 780-789.
1
Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora, Disclosure of Interest: None declared
Portugal, 2Intensive Care, 3Transplantation, University of Alberta, Edmonton,
Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora,
Portugal P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN
Contact E-mail Address: desousac@ualberta.ca ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES
N. Ding1,*
INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease 1
Gastroenterology, St Vincents Hospital, Melbourne, Australia
(MELD) score 40 have high risk of death without liver transplant (LT). This Contact E-mail Address: dingnik@gmail.com
study aimed to evaluate these patients outcomes after transplant.
AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic INTRODUCTION: Endoscopic screening for gastro-oesophageal varices (GOV)
patients who underwent LT at one Canadian center between 2002 and 2012. is currently recommended for all cirrhotic patients. Noninvasive methods for
Primary exposure was severity of end-stage liver disease measured by MELD liver fibrosis assessment are identifying increasing numbers of patients with cir-
score at transplant (40 vs. 540). Primary outcome was duration of first inten- rhosis-range liver stiffness measurements (LSM), increasing the number of
sive care unit (ICU) stay after LT. Secondary outcomes were duration of first referrals for screening endoscopy. The identification of simple non-invasive mar-
hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival kers for the presence/absence of large gastroesophageal varices (GOV) would be
rates. clinically useful. We evaluated the performance of liver stiffness measurement
RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score 40. (LSM) platelet count to identify the presence of large GOV in patients with
These patients had longer first ICU stay after LT (14 vs. 2 days; p 50.001). Child Pugh (CP) A cirrhosis.
MELD score 40 at transplant was independently associated with first ICU stay AIMS & METHODS: Data were collected retrospectively. The presence of cir-
after transplant 10 days (OR, 3.21). These patients had longer first hospital stay rhosis was defined by LSM 4 13.6 kPa using elastography. We performed a
after LT (45 vs. 18 days; p 50.001); however, there was no significant difference database search for patients with LSM 4 13.6 kPa who underwent screening
in the rate of ICU readmission (18% vs. 22%; p 0.58) or re-transplant rate (4% gastroscopy (2010 2013). Only patients with compensated liver disease were
vs. 4%; p 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and included. Large GOV were defined by diameter 4 5mm or the presence of high
5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no sig- risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the com-
nificant difference in cumulative survival stratified by MELD score 40 vs. 540 bination of these factors to identify patients with large GOV. A training set of 71
at transplant (p 0.59). patients was used, and results were validated using a second cohort of 201
CONCLUSION: Cirrhotic patients with MELD score 40 at transplant utilize patients from two independent centres.
greater postoperative health resources; however, derive similar long-term survival RESULTS: The combination of LSM and Pl was more accurate for identifying
benefit with LT. CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs.
REFERENCES 0.78 [0.66 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk
Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in score was 0.11 (Sens 0.88, Spec 0.77, PPV 0.33, NPV 0.98,
cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062. accuracy 78%). Results in the validation cohort confirmed the discriminatory
Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically rele-
in patients achieving a model for end-stage liver disease score of 40 or higher. vant cut-offs to improve the negative predictive value (NPV) for large GOV. The
Transplantation 2013; 95: 507-512. NPV for the combination of LSM 5 25 kPa and Pl 100 and was 100% in both
Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease the training cohort and validation cohort. 82 (42%) of patients overall met this
(MELD) score greater than 23 predicts length of stay in the ICU but not mor- criteria.
tality in liver transplant recipients. Crit Care 2010; 14: R117. CONCLUSION: The combination of LSM 5 25 kPa and Pl 100 can be used
Disclosure of Interest: None declared to identify patients with compensated cirrhosis who do not have large GOV.
These patients do not benefit from endoscopic screening, but could be followed
with annual LSM and full blood count.
P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS REFERENCES
BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT 1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to
STUDY portal hypertension. American College of Gastroenterology Practice Parameters
J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2, Committee. Am J Gastroenterol 1997.
N. OConnell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4 2. de Franchis R. Revising consensus in portal hypertension: report of the
1
Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust, Baveno V consensus workshop on methodology of diagnosis and therapy in
Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI, portal hypertension. J Hepatol 2010; 53: 762768.
University of Warwick, Coventry, United Kingdom 3. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet
Contact E-mail Address: r.arasaradnam@warwick.ac.uk count identify portal hypertension in patients with compensated cirrhosis.
Gastroenterology 2013; 144, 102111.e1.
A142 United European Gastroenterology Journal 2(5S)
4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement
P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED
using Fibroscan for the noninvasive assessment of esophageal varices in liver
TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE
cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164170.
AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR
Disclosure of Interest: None declared
OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL
ENDOSCOPY
P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernandez-Sordo1,
ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1,
EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN I. N. Guha1
1
LABEL STUDY DATA Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham,
C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1, UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical
E. Berni3, C.J. Currie1 Catholic University of Chile, Santiago, Chile
1
Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff,
2
Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD)
Kingdom remains the gold standard test to screen for oesophageal varices (OV) in patients
Contact E-mail Address: PConway@norgine.com with liver cirrhosis. However, it has many limitations in terms of costs, accessi-
bility and tolerability. Hence, there is a need for less invasive and simple techni-
INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of ques to replace C-OGD in this setting.
cirrhosis. In recurrent, overt, episodic HE, which is the most common subcate- AIMS & METHODS: We aimed to compare the accuracy and acceptability of a
gory, its seriousness is due to the chronic debilitating effects of the recurrent portable, disposable, office-based, unsedated transnasal video endoscope (EG
episodes. ScanTM II) with C-OGD for the detection of OV.
AIMS & METHODS: The aim of this study was to characterise the impact of the This was a prospective diagnostic study. Consecutive adult patients with con-
number of prior HE episodes on the risk of future HE episodes. A post-hoc firmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited
analysis was carried out using data from 322 patients with a history of HE to participate in this study. We excluded patients with recurrent epistaxis (more
from a phase 3, open-label study evaluating the long-term safety and tolerability than once a week); nasal obstruction; disease of the nasal cavity; history of
of rifaximin- 550mg BID. All eligible patients had a Conn score of 02 at variceal bleeding or band ligation therapy in the past 12 weeks. All subjects
enrolment, and had either successfully participated in a previous HE study underwent two procedures on the same day (EG Scan followed by C-OGD),
with rifaximin- (RFHE3001), or they were new patients enrolled with 1 ver- performed by two different operators blinded to the findings of the other test.
ifiable episode of HE within the preceding 12 months. Patients completed validated tolerability (10-point visual analogue scale (VAS))
RESULTS: 319 of 322 patients (647 observations) aged 18 years had all the and adverse events questionnaires on day 0 and day 14.
information required for analysis. Median duration of follow-up was 17 months The primary outcome measure was diagnostic accuracy of EG scan (performed
(IQR 8.925.4). Stratifying patient observations by number of prior HE episodes by one operator) against C-OGD (reference standard). In addition, interobserver
and using the Kaplan Meier method the probability of being event free at year agreement of the EG scan was calculated using the kappa (k) statistic, by nine
one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.
0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539 RESULTS: 50 patients were recruited to the study (mean age 59 years /-11,
(0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for one, two, three 70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%)
and four or more prior HE episodes, respectively. Plotting the Kaplan Meier completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%),
curves of time to next HE episode, stratified by the number of prior HE episodes, p 0.882). OV prevalence was 48.9%.
a clear association between decreased time to next HE episode and increased Sensitivity, specificity and area under the receiver operating characteristic curve
number of prior episodes was seen. Using log-rank tests, there was no significant (AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95%
difference between the survival curves of one prior and two prior HE episodes confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI
(2 0 on 1 degree of freedom (d.f.), p 0.899), however there were significant 0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large
differences between survival curves of one prior or two prior episodes and greater varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI
numbers of prior episodes (2 72 on 3 d.f., p50.001). 0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis
CONCLUSION: This study supports the current understanding of the natural of any size OV (K 0.45, 95%CI 0.40-0.49) and medium/large OV (K 0.47,
history of end-stage encephalopathy; as the number of prior HE episodes 95%CI 0.42-0.52).
increased, the risk of subsequent HE episodes increased. Patients reported better experience (mean VAS/-standard deviation (SD)) and
Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other: higher preference (percentage) with EG Scan compared to C-OGD at day 0
Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa (7.8/-2.2 vs. 6.8/-3.0, p 0.058; 76.5% vs. 23.5%, p50.001, respectively)
Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni and day 14 (7.0/-2.3 vs. 5.5/-3.2, p 0.0013; 77.8% vs. 22.2%, p50.001,
Consultancy for: Norgine, C. Currie Consultancy for: Norgine respectively). There was no association between procedure preference and seda-
tion use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p 0.106;
day 14: OR 0.24, 95%CI 0.02-2.56, p 0.238). 4 patients (8.5%) experienced
P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY minor self-limiting epistaxis. No serious adverse events occurred.
CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS CONCLUSION: EG Scan was accurate for the diagnosis of any varices and
WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS clinically significant OV. Interobserver agreement was modest. More impor-
AND PORTAL HYPERTENSION tantly, patients experience and preference remained significantly higher for EG
P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1, Scan 14 days after procedures independent of sedation use.
J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on Disclosure of Interest: S. Sami Financial support for research from: Intromedic
behalf of Vienna Hepatic Hemodynamic Lab Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared,
1
Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical R. Mansilla-Vivar: None declared, J. Fernandez-Sordo: None declared, J.
Institute of Pathology, Medical University of Vienna, Vienna, Austria White: None declared, A. Khanna: None declared, M. Coletta: None declared,
Contact E-mail Address: philipp.schwabl@meduniwien.ac.at S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial
support for research from: Intromedic Ltd, Seoul, South Korea and Olympus
INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repea- Keymed UK., I. N. Guha: None declared
table tool to assess liver fibrosis and portal hypertension (HVPG). Recently, new
quality criteria for TE measurements have been proposed (Boursier et al.
Hepatology 2013): very reliable: IQR/M 50.1; reliable: IQR 0.10.3, or IQR/ P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF
M 40.3 if TE 57.1 kPa; poor reliable: IQR/M 40.3 if TE 47.1 kPa. HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER
AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE
measurements according to these new quality criteria (accurate very reliable S.H. Shin1,*, B.K. Kim1
reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal 1
Department of Internal Medicine, Institue of Gastroenterology, Yonsei University
hypertension. Therefore we retrospectively identified patients undergoing TE, College of Medicine, Seoul, Korea, Republic Of
HVPG measurement and liver biopsy within 3 months at our tertiary care center. Contact E-mail Address: earth-peace@yuhs.ac
RESULTS: Among 278 patients (48.713.1 years, 74.7% male, 75.7% viral
etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs)
measurements, while new criteria yielded in 83.2% accurate LS measurements and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs
(23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional and (2) small EVs with red sign or decompensated cirrhosis) are currently recom-
or new criteria were all significantly and similarly strong correlated with fibrosis mended for all cirrhotic patients. Recently, two new liver stiffness measurement
stage (R 0.648 vs. R 0.636) and HVPG (R 0.836 vs. R 0.846). The accu- (LSM)-based statistical equation models (PH risk score and Varices risk score)
racy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0% were introduced as a noninvasive, simple, accurate models for identifying pre-
for traditional and new TE criteria, respectively. The positive (PPV) and negative sence of EVs and clinically significant portal hypertension [1].
(NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For AIMS & METHODS: We aimed to validate predictive value of the two models for
predicting HVPG 10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet
89.8% using traditional or new criteria, respectively. Both criteria resulted in ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.
AUCs for diagnosis of HVPG 10mmHg of over 0.95 with a PPV and NPV Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis
of 76% and 97%, respectively. patients. All underwent laboratory workups, endoscopy, LSM, and ultrasono-
CONCLUSION: Applying new quality criteria for TE measurements signifi- graphy. LSM was measured by transient elastography; endoscopy was used as
cantly increases the number of valid TE measurements without affecting accu- the standard for detection of EVs. PH risk score, Varices risk score and LSPS
racy of TE for diagnosis of liver cirrhosis and portal hypertension. were calculated in all cases as follows: PH risk score -5.953 0.188 x LSM
Disclosure of Interest: None declared 1.583 x sex (1: male; 0: female) 26.705 x spleen diameter/platelet count ratio,
United European Gastroenterology Journal 2(5S) A143
Varices risk score -4.364 0.538 x spleen diameter 0.049 x platelet count of carvedilol versus non-specific betablockers (NSBB) on mortality on patients
0.044 x LSM 0.001 x (LSM x platelet count). with cirrhosis remains to be evaluated.
RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172 AIMS & METHODS: We wanted to compare the impact on mortality of carve-
(25.5%) had HEVs. The area under the receiver-operating characteristic curve dilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic
(AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950 cirrhosis from the Danish National Patient Register during the period 1995
(95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other through 2010. We used the anatomical therapeutic chemical (ATC) classification
factors: Varices risk score (0.907, 95% CI 0.876-0.939, p50.001), LSM alone to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk
(0.873, 95% CI 0.842-0.904, p50.001). At PH risk score 5 4.0, 94.6% negative time as the time from the first prescription of either carvedilol or NSBB until
predictive value (NPV) was provided (481 patients), whereas 94.3% positive death or end of follow-up (December 31, 2010). We adjusted for gender, age,
predictive value (PPV) was achieved (70 patients) at PH risk score 4 10.0. In heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of
the same way, at Varices risk score 5 -2.5, 95.6% NPV was provided (413 diuretics. We used univariate and multivariate Cox proportional hazard models
patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score to assess the HR. Persons with missing data were excluded from the analyses
4 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients (0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC,
(81.6%) and 485 patients (71.9%), respectively. USA).
CONCLUSION: The PH risk score is a reliable, noninvasive predictive model RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol
for detection of HEVs. Furthermore, the LSPS is considered as more simply and NSBB, respectively. Three patients had received both carvedilol and NSBB
applicable model having similar predictive value. Patients with PH risk score and were excluded. Patients from the carvedilol group were mainly classified with
5 4.0 may avoid endoscopy safely, whereas those with 4 10.0 should be con- uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we
sidered for appropriate prophylactic treatments. only included patients with uncomplicated cirrhosis in our mortality analysis (80
REFERENCES versus 1.857 patients). Significantly fewer patients in the carvedilol group died
1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square
count identify portal hypertension in patients with compensated cirrhosis. p50.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45
Gastroenterology 2013; 144: 102-111.e101. (95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7).
2. Kim BK, Han KH, Park JY, et al. A liver stiffness measurement-based, non- The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs.
invasive prediction model for high-risk esophageal varices in B-viral liver cirrho- 14%) prior to cohort entry were un-evenly distributed between users of carvedilol
sis. Am J Gastroenterol 2010; 105(6): 1382-1390. and NSBB. We did a sub-analysis where we matched patients on the presence of
Disclosure of Interest: None declared heart disease and variceal prior to cohort entry. In this sub-analysis we compared
80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found
an adjusted HR of 0.38 (95% CI 0.2-0.7).
P0044 PLALA SCORE PREDICT CIRRHOSIS PATIENT IN CONCLUSION: The use of carvedilol compared with NSBB in patients with
NONALCOHOLIC FATTY LIVER DISEASE cirrhosis was associated with lower mortality in this retrospective study.
T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on REFERENCES
behalf of JSG-NAFLD 1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propra-
1
gastroenterology and hepatology, Yokohama city university, yokohama, Japan nolol on circulatory regulation and oxygenation in cirrhosis: a randomised study.
Contact E-mail Address: takaomo-kesso@hotmail.co.jp Dig Liver Dis 2014; 46: 251-256.
2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of long-
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important term carvedilol and propranolol administration in the treatment of portal hyper-
cause of chronic and progressive liver injury in many countries1). NAFLD tension in cirrhosis. Hepatology 2002; 36: 1367-1373.
includes a wide spectrum of liver diseases that range from simple steatosis, Disclosure of Interest: None declared
which is generally a nonprogressive condition, to nonalcoholic steatohepatitis
(NASH), which can progress to liver cirrhosis and hepatocellular carcinoma
(HCC), despite the absence of significant alcohol consumption. If NAFLD P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD
patients have liver cirrhosis, they need to be kept under surveillance for early COMPONENT USE IN CIRRHOSIS
detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2,
is the gold standard for diagnosis and staging of fibrosis in patients with A. Burroughs3
NAFLD2). However, ad the number of NAFLD patients has reached 80100 1
Nuffield Department of Medicine, University of Oxford, 2NHS Blood and
million in the United States and about 10 million NAFLD patients are estimated Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom
in Japan, it is virtually impossible to enforce in all patients.
AIMS & METHODS: To develop a mass screening system for general physi- INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with
cians, which can be used for predicting liver cirrhosis in NAFLD patients, using a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombo-
routine laboratory parameters. tic disorder. It is a frequent indication for transfusion of blood components, both
A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from for prophylaxis and for treatment of bleeding, although indications and patterns
nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3, of blood use are poorly characterised.
190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0. AIMS & METHODS: All NHS trusts with representation on the British Society
Continuous variables were expressed as mean SD. of Gastroenterology membership list were invited to take part in a national audit.
RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransfer- Data were collected prospectively on consecutive admissions with a confirmed
ase/alanine aminotransferase (AST/ALT) ratio were selected as independent vari- diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/
ables associated with cirrhosis in NAFLD patients by multiple logistic regression death/day 28. Specific information was requested on use of blood components,
analysis. The optimal cutoff value of platelet count, serum albumin, and AST/ including indication, type of component and laboratory indices prior to transfu-
ALT ratio was set at 515.3 104/l (sensitivity; 81.6% specificity; 88.6%), 54.0 sion. Standards were defined against guidelines on the use of red blood cells
g/dl (sensitivity; 84.2% specificity; 84.6%), and 40.9 (sensitivity; 78.9%, speci- (RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate.
ficity; 82.0%), respectively, by the receiver operating characteristic curve. These RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years,
three variables were combined in an unweighted sum (platelet count 1 point, 65% male) were collected from 85 hospitals. The predominant aetiology was
serum albumin 1 point, AST/ALT ratio 1 point) to form an easily calculated alcohol (70%; 921/1313); 74% of admissions were for features of decompensa-
composite score for predicting cirrhosis in NAFLD patients, called the PLALA tion; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all
(platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA 2 had admissions were transfused a blood component; in 61% (238/391) this was for
sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sen- treatment of bleeding and in 39% (153/391) for prophylaxis. In patients trans-
sitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive pre- fused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238)
dictive value). received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238)
CONCLUSION: The PLALA score may be an ideal scoring system for detecting cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold
cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be con- was 48g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis
sidered for clinical use. the majority (61%, 94/153) received transfusion in the absence of a planned
REFERENCES procedure. In patients transfused for prophylaxis prior to a procedure (59/
1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221- 153): 19% (3/16) received FFP at an INR 1.5 for high risk procedures and
1231. 33% (6/18) received FFP at an INR2 for low risk procedures; 36% (9/25)
2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in received platelet transfusion at a platelet count450 prior to a procedure. The
patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362. most frequent procedures resulting in prophylactic transfusion were paracentesis
Disclosure of Interest: None declared (18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboem-
bolism was documented in 2% (29/1313) cases. Case fatality during follow up
was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the
P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND most frequent cause of death.
MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE CONCLUSION: Patients with cirrhosis are frequently transfused during hospi-
RETROSPECTIVE STUDY talisation. This audit highlights areas where greater scrutiny of blood component
U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1 use is required, particularly in the group transfused for prophylaxis of bleeding.
1
Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre, Further work is needed to improve patterns of blood use in cirrhosis to ensure
Denmark patients are not exposed to unnecessary transfusion and its attendant harms.
Contact E-mail Address: ulrichbangbang@gmail.com Disclosure of Interest: None declared
P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS
ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND
RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS
M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4, INDEPENDENT OF PATIENT SUBGROUPS
F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J. M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5,
V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10 E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7
1
Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro 1
Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital,
Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel,
Germans TrasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San
School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic Diego Digestive Diseases, San Diego, 6Texas Liver Institute, University of Texas
Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and Health Science Center, San Antonio, 7AbbVie, North Chicago, United States
Southern California Research Center, Coronado, 7University of Pennsylvania, Contact E-mail Address: brunetto@med-club.com, laurinda.cooker@abbvie.com
Philadelphia, 8The Queens Medical Center Liver Center, Honolulu, 9AbbVie
Inc., North Chicago, United States, 10University of Milan, Milan, Italy INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhi-
bitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta;
INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a non-
can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor nucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral
ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition. (3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected
We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients patients, 96.3% of treatment-na ve patients (SAPPHIRE-I trial) and 96.2% of
treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV
ABT-333) (3D regimen) with or without RBV. RNA 525 IU/mL at post-treatment week 12).
AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were rando-
(PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of mized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir
RBV to the safety and efficacy of the 3D regimen, were used to evaluate the (150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV
incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia, (1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the
jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were two trials were pooled, and SVR12 rates were calculated overall and according to
assessed at baseline and every 1-2 weeks per protocol. race, ethnicity, and region.
RESULTS: Total bilirubin elevations of 43X ULN occurred in 23/401 (5.7%) RESULTS: 770 patients assigned to the 3DRBV regimen received 1 dose of
3DRBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regi- study drug. The overall SVR12 rate in the combined studies was 96.2%; high
men. The majority of patients in each group (490%) had normal total bilirubin SVR rates were achieved regardless of race, ethnicity, or region (Table).
levels at the end of treatment. Mean total bilirubin levels were significantly higher Tolerability was similar across populations. Most adverse events were mild or
at each treatment visit in the RBV-containing treatment groups. Mean total moderate; the 3 most common adverse events were headache (34.3%), fatigue
bilirubin peaked at week 1 in both treatment groups (predominantly indirect), (34.2%) and nausea (22.3%). Few patients discontinued due to adverse events (6/
and declined to baseline by week 2 in the RBV-free group. Events of hyperbilir- 770, 0.8%).
ubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of
treatment and did not result in study drug discontinuation. One patient under- 3DRBV
went RBV dose modification and one interrupted study drug due to hyperbilir- % with SVR12 (n/N)
ubinaemia; both patients achieved sustained virologic response 12 weeks post-
treatment. Two patients receiving 3DRBV experienced ALT 3X ULN and Overall SAPPHIRE-I and SAPPHIRE-II 96.2 (741/770)
total bilirubin 2X ULN, however, the timing and predominance of indirect
bilirubin were not consistent with drug induced liver injury. No serious adverse Race Black 96.0 (48/50)
events related to hyperbilirubinaemia were reported. Non-black 96.3 (693/720)
Ethnicity Hispanic/Latino 93.9 (46/49)
Bilirubin-related events, n (%) 3DRBV (N 401) 3D (N 509) Non-Hispanic/Latino 96.4 (695/721)
Region Australia/New Zealand 95.5 (42/44)
Any bilirubin-related event 21 (5.2) 4 (0.8)
Europe 95.8 (346/361)
Hyperbilirubinaemia 13 (3.2) 3 (0.6)
North America 96.7 (353/365)
Jaundice 11 (2.7) 1 (0.2)
Total bilirubin 43X ULN 23 (5.7) 2 (0.4)
INTRODUCTION: Currently only liver biopsy can accurately establish the diag- P0066 LONG-TERM OUTCOMES AFTER TREATMENT OF SINGLE
nosis and severity of hepatic steatosis. Few studies to date have addressed the SMALL HEPATOCELLULAR CARCINOMA IN ELDERLY
feasibility of the Controlled Attenuation Parameter (CAP) measured by transient PATIENTS WITH WELL-PRESERVED LIVER FUNCTION AND
elastography for measuring hepatic fat content. However, the effects of hepatic GOOD PERFORMANCE STATUS
fibrosis and disease etiology on the accuracy of CAP values for grading the G. Lee1, M.S. Choi1,*, D.H. Sinn1, G.-Y. Gwak1, Y.H. Paik1, J.H. Lee1,
severity of liver steatosis are still unclear. K.C. Koh1, S.W. Paik1, B.C. Yoo1
AIMS & METHODS: The aims of this study were (1) to determine whether CAP 1
Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of
values can discriminate grades of steatosis in a sample of consecutive patients Medicine, Seoul, Korea, Republic Of
with a spectrum of liver disease etiology and steatosis severity, and (2) to evaluate Contact E-mail Address: iamann81@gmail.com
the effect of hepatic fibrosis and disease etiology on the quantification of steatosis
by CAP measurements. The study involved 50 sequential patients (64% males; INTRODUCTION: Aging of general population and advances in diagnostic
mean age, 47.4 years; range, 19-70 years) who had undergone a percutaneous imaging have led to more frequent detection of small hepatocellular carcinoma
liver biopsy and CAP measurements. The causes of liver disease were nonalco- (HCC) in elderly adults. However, long-term outcome and its predictive factors
holic fatty liver disease (n 20), chronic viral hepatitis (n 23), autoimmune after treatment of small HCC in these patients have not been established.
hepatitis (n 3), and others (n 4). A pathologist scored the specimens in a AIMS & METHODS: Between 2006 and 2009, 897 patients who had Eastern
four-graded scale as follows: 55% steatosis S0, 5-33% S1, 33-66% S2, Cooperative Oncology Group (ECOG) score 0-1 and Child-Pugh class A liver
and 466% S3. All liver biopsy specimens were at least 20 mm long and/or function were diagnosed with single small HCC (size3 cm) at Samsung Medical
contained more than 11 complete portal tracts. Center. They were divided into elderly group (age65 years, n 186) and young
RESULTS: The pathology results showed that 16 (32%) patients had S0, 12 group (age565 years, n 711). We compared baseline characteristics, initial
(24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. Overall a close relationship treatment modality, and treatment outcomes between the two groups.
was observed between the CAP values and histology steatosis scores (r 0.709, P RESULTS: At baseline, male patients were less common, and HCV infections
5 0.001). There was a stepwise increase in CAP with increasing stages of hepatic and alcoholic liver disease were more common in elderly group. Elderly group
steatosis: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. underwent surgical resections less frequently but TACE more frequently com-
Regression analysis, that included a number of potential confounders, was per- pared to young group (21.5% vs. 38.8% for surgery and 26.9% vs. 12.9% for
formed to determine the influence of hepatic fibrosis and disease etiology on the TACE, p50.001). One-, 3-, and 5-year overall survival (OS) rates (OSR) of
relationship between CAP values and the histological assessment of steatosis. elderly group were lower than those of young group (96.7%, 81.4%, and
However, neither liver fibrosis (p 0.58) nor disease etiology (p 0.96) were 60.5% vs. 97.3%, 87.9%, and 82.4%, respectively, p50.001).
found to have an interaction between CAP and the stage of steatosis. One-, 3-, and 5-year OS rates were after surgery, RFA, and TACE were 94.9%,
CONCLUSION: Liver fibrosis or disease etiology does not impact on the accu- 89.7%, and 86.6% vs. 97.9%, 79.6%, and 56.7% vs. 96.0%, 80.0%, and 50.6%,
racy of CAP for the assessment of steatosis. The results of this study strengthen respectively in elderly group (p 0.014); 98.2%, 91.8%, and 89.5% vs. 98.2%,
the role of CAP measured by transient elastography as a non-invasive alternative 87.6%, and 80.3% vs. 92.3%, 79.0% and 70.5%, respectively in young group
to liver biopsy for the evaluation of liver fat content in subjects with liver disease. (p50.001). Although OS rates after surgery and TACE were comparable
Given its accuracy and lack of confounding by fibrosis and disease etiology, CAP between the two groups, elderly group showed lower 1-, 3-, and 5-year OS
assessment is an attractive method to evaluate the presence and severity of stea- rates than young group after RFA. In addition, 1-, 3-, and 5-year recurrence-
tosis in clinical practice and may also be a useful tool to monitor change in free survival (RFS) rates of elderly subgroup were lower than those of young
steatosis in subjects undergoing an intervention. group (63.2%, 30.5%, and 23.0% vs. 75.7%, 48.0%, and 36.6%, respectively,
Disclosure of Interest: None declared p50.001).
One-, 3-, and 5-year RFS rates after surgery, RFA, and TACE were 74.4%,
61.5%, and 52.5% vs. 70.2%, 23.5% and 13.8% vs. 40.8%, 18.4%, and
P0065 FOCAL LIVER LESIONS CLASSIFICATION BY ARTIFICIAL 16.3%, respectively in elderly group (p50.001); 81.4%, 63.5%, and 51.5% vs.
NEURAL NETWORKS AND SUPPORT VECTOR MACHINES 75.1%, 41.4%, and 29.9% vs. 59.2%, 23.6%, and 11.7%, respectively in young
EMPLOYING DYNAMIC IMAGING DATA group (p50.001). RFS rates after surgery and TACE were comparable between
C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, D. I. Gheonea1, the two groups, whereas elderly group showed lower 1-, 3-, and 5-year RFS rates
L. Streba1, I. Rogoveanu1 than young group after RFA. Multivariate analysis showed that sex and initial
1
Gastroenterology, UMF CRAIOVA, Craiova, Romania treatment modality were the significant predictive factor for OS and RFS.
Contact E-mail Address: costinstreba@gmail.com CONCLUSION: Although long-term outcomes after treatment of single small
HCC in elderly group were lower than those in young group, adoption of cura-
INTRODUCTION: Early diagnostic of liver malignancies is essential for therapy tive treatment modality was an independent predictive factor for the better out-
efficiency; differentiating hepatocellular carcinoma (HCC) from intrahepatic comes irrespective of age. Therefore, in elderly patients with well-preserved liver
cholangyocarcinoma, liver metastases or benign lesions is therefore essential function and good performance status, curative treatment including surgery
even in early phases. Successful classification of liver lesions by computerized should be more positively considered for single small HCC.
methods is currently possible and artificial neural networks emerged as optimal REFERENCES
tools for independent diagnostic. Arii S, et al. Results of surgical and nonsurgical treatment for small-sized hepa-
AIMS & METHODS: Our aim was to test the validity of two separate decision tocellular carcinomas. The Liver Cancer Study Group of Japan. Hepatology
making systems an artificial neural network (ANN) and a support vector 2000; 32: 1224-1229.
machine (SVM) in classifying focal liver lesions (FLLs) by using dynamic ima- Mirici-Cappa F, et al. Treatments for hepatocellular carcinoma in elderly
ging data. patients are as effective as in younger patients. Gut. Mar 2010; 59: 387-396.
Expanding on our previous work involving ANN use in interpreting imaging Disclosure of Interest: None declared
data for HCC [1], we now proposed a comparative approach between two dif-
ferent machine learning systems, one based on ANNs and contrast-enhanced
ultrasound (CEUS) quantitative data and one employing a SVM and spiral P0067 EFFICACY OF SORAFENIB ACCORDING TO THE NUMBER OF
computed tomography (CT). After obtaining ethical clearance and signing indi- PRIOR TACE PROCEDURES IN HCC PATIENTS
vidual consent forms, we prospectively included 191 patients who underwent R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
both spiral CT and CEUS as part of their clinical work-up at the University G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf
County Hospital of Craiova between January 2009 September 2013. Final of ITA.LiCA Group
diagnosis was based on post-treatment evaluation, follow-up and pathology, 1
Gastroenterology, Pisa University Hospital, Pisa, Italy
when available. Imaging data from CEUS was obtained through time-intensity Contact E-mail Address: r.sacco@ao-pisa.toscana.it
curve (TIC) analysis and the main parameters (time to peak, rise time, fall time,
mean transit time, area under the curve) were fed to an ANN. Spiral CT data was INTRODUCTION: It has been recently suggested that sorafenib should be
obtained through manually segmenting the tumor and a tumor-free parenchyma initiated as early as possible in patients with hepatocellular carcinoma (HCC)
portion in distinctive images and obtaining Gray Level Co-occurrence Matrix who failed transarterial chemoembolization (TACE); however, the correlation
A150 United European Gastroenterology Journal 2(5S)
between the efficacy of sorafenib and the number of prior TACE procedures has
P0070 SAFETY AND EFFICACY OF SORAFENIB IN ELDERLY
not been documented. We analyze here the correlation between the efficacy of
PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
sorafenib and the number of prior TACE procedures in HCC patients included in
the Nation-wide Italian database ITA. LI. CA. S. Nakashita1,*, T. Otsuka1, Y. Eguchi2, S. Kawazoe3, K. Yanagita4, K. Ario5,
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC K. Kitahara6, S. Iwane7, H. Kato8, T. Mizuta1 on behalf of the Saga Liver
patients treated at 18 Italian Centers. All patients treated with sorafenib were Cancer Study Group
1
included in this analysis. The following endpoints were considered: overall sur- Internal Medicine, 2Liver Disease Control and Assistance Task Force, Saga
vival (OS), time to progression (TTP) and disease control rate (DCR). These University Hospital, 3Hepato-Biliary and Pancreatology, Saga-Ken Medical
endpoints were compared in patients with no TACE, one and 2 prior TACE Centre Koseikan, Saga, 4Internal Medicine, Saiseikai Karatsu Hospital, Karatsu,
5
procedures. Internal Medicine, NHO Ureshino Medical Center, Ureshino, 6Surgery, Saga
RESULTS: In total, 321 patients had received sorafenib (271 males; age 6511 University Hospital, Saga, 7Internal Medicine, Karatsu Red Cross Hospital,
years; 225 in BCLC-C stage). Of these, 201 received no TACE (187 were in Karatsu, 8Internal Medicine, NHO Saga Hospital, Saga, Japan
BCLC-C stage), 60 one TACE and 60 2 TACE procedures. Median OS was
significantly longer in patients who received one single TACE procedure, with INTRODUCTION: The average age of patients with hepatitis and hepatocellular
respect to those with no or 2 TACE procedure(s) (19 months with one TACE carcinoma (HCC) in Japan is increasing. Sorafenib is approved for the treatment
versus 11 months with no TACE and 12 months for 2 TACE; p50.05). No of advanced HCC; however, its safety and efficacy for elderly patients is not
differences among groups were observed in TTP (one TACE: 4 months; no established by published studies. Therefore, we aimed to evaluate the safety
TACE: 4 months; 2 TACE: 5 months; p not significant), but patients with and efficacy of sorafenib for elderly patients (80 years of age) included in the
only one TACE prior to sorafenib treatment had an improved DCR (one TACE: Saga Liver Cancer Study Group.
34%; no TACE: 24%; 2 TACE: 28%; p50.05). AIMS & METHODS: We conducted a retrospective study between July 2008
CONCLUSION: Although with all the limitations of any observational study, and August 2013 that included 134 patients with advanced HCC who received
this analysis, conducted in a large field-practice database, suggests that HCC sorafenib in Saga, Japan until disease progression or treatment intolerance. We
patients who start sorafenib after one single TACE procedure present improved divided the patients into two groups comprising 36 patients 80 years of age or
OS and DC with respect to those who received TACE 2 TACE procedures. greater (80 group) and 98 patients less than 80 years of age (580 group). We
Disclosure of Interest: None declared compared antitumour effect [objective response rate (ORR), disease control rate
(DCR), time to tumour progression (TTP)], overall survival (OS), and adverse
events (AEs) of the two groups.
P0068 CORRELATION BETWEEN LDH LEVELS AND RESPONSE TO RESULTS: Baseline characteristics were not significantly different between the
SORAFENIB IN HCC PATIENTS two groups. The median ORRs were 6.9% and 8.3%, and the median DCRs
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1, were 37.9% and 46.4% in the 80 and 580 groups, respectively. These values
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf were not significantly different between the two groups (p 0.81, p 0.43). The
of ITA.LiCA Group median TTPs were 2.9 months for both groups, and the median OSs were 14.7
1
Gastroenterology, Pisa University Hospital, Pisa, Italy and 9.2 months for the 80 and 580 groups, respectively, which were not sig-
Contact E-mail Address: r.sacco@ao-pisa.toscana.it nificantly different. The frequencies of AEs were 97.2% and 96.6% in the 80
and 580 groups. The frequencies of grade 3 AEs between the 80 and 580
INTRODUCTION: Lactate dehydrogenase (LDH) is a predictor of clinical out- groups were significantly different (69.4% and 49.0% respectively, p 0.036).
come in hepatocellular carcinoma (HCC) patients. However, the predictive role CONCLUSION: Sorafenib treatment is equally effective for elderly and non
of LDH on the clinical outcomes of sorafenib treatment has been poorly docu- elderly patients with advanced HCC. However, the high frequency of AEs in
mented. The correlation between LDH levels and clinical outcomes in HCC elderly patients is problematic and requires close attention.
patients treated with sorafenib included in the Nation-wide Italian database Disclosure of Interest: None declared
ITA. LI. CA is investigated here.
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC
patients treated at 18 Italian Centers. All patients treated with sorafenib treat- P0071 HEPATOCELLULAR CARCINOMA INCIDENCE IN CHRONIC
ment and with available LDH values were considered. A ROC analysis was HEPATITIS C PATIENTS ACCORDING TO SUSTAINED
performed to find a suitable threshold for baseline LDH levels. Overall VIROLOGIC RESPONSE (SVR) AND FLUCTUATION OF ALFA
Survival (OS) and time to progression (TTP) were compared in patients with FETO-PROTEIN LEVELS DURING ANTIVIRAL TREATMENT
LDH above and below the identified threshold. Study endpoints were also eval- T. Purevsambuu1,*, S. Bota1, H. Florian1, H. Hofer1, P. Ferenci1, W. Sieghart1,
uated according to different patterns of LDH levels during treatment. M. Peck-Radosavljevic1
RESULTS: Baseline LDH levels were available for 97 patients (85 males, 61 in 1
Gastroenterology and Hepatology, Internal Medicine III, Medical University of
BCLC-C stage); data on LDH levels during sorafenib were reported for 10 Vienna, Vienna, Austria
patients. Mean baseline LDH concentration was 324141 U/L. The most accu- Contact E-mail Address: tuulaigirl@yahoo.com
rate cut-off value for LDH concentration was 297 U/L. Both study endpoints
were equal in patients with LDH values 297 U/L (n 47) and in those with INTRODUCTION: Chronic hepatitis C (CHC) is an important risk factor for
lower LDH concentrations (n 52) (OS: 12.0 months in each population; TTP: progression of liver disease to advanced fibrosis and hepatocellular carcinoma
4.0 months in each group). During treatment, LDH values decreased in three (HCC) and the published studies showed that the kinetics of alfa feto-protein
patients (mean difference -219 U/L). Patients with decreased LDH concentra- (AFP) levels in cirrhotic patients are more valuable than single AFP values for
tions have a prolonged OS versus those with unmodified/increased values predicting the HCC.
(p 0.0083; all patients with decreasing LDH are alive, median OS for patients AIMS & METHODS: Our aim was to assess the HCC incidence in relation to
with increasing LDH was 8.0 months). Median TTP was 19.0 months in patients antiviral treatment response and fluctuation of AFP levels during antiviral treatment
with decreasing LDH and 3.0 months in those with increasing values (p 0.008). in a large number of patients from a single institution. We retrospectively collected
CONCLUSION: The clinical benefits of sorafenib do not seem influenced by data of HCV patients, who were diagnosed and treated between 1989-2011. We
baseline LDH. However, a decreased LDH concentration during sorafenib might analyzed the HCC incidence according to AFP fluctuation (baseline vs. end of
be associated with improved clinical outcomes. treatment-EOT) in the entire Cohort of patients and in SVR and non-SVR patients.
Disclosure of Interest: None declared RESULTS: We identified 2627 patients diagnosed with chronic hepatitis C. We
excluded 975 patients because they did not receive antiviral therapy, 5 because
they were diagnosed simultaneously with HCV/HCC and 321 patients due to lack
P0108 CLINICAL SIGNIFICANCE OF PREGNANE X RECEPTOR (PXR) P0110 PARTIAL COVERED BILIARY METALLIC STENT WITH/
AND RETINOID X RECEPTORS (RXRS) EXPRESSION IN HUMAN WITHOUT DUODENUM METAL STENT AND NEOADJUVANT
PANCREATIC ADENOCARCINOMA: AN CHEMORADIATION THERAPY PROVIDES SYMPTOMATIC
IMMUNOHISTOCHEMICAL STUDY BORDERLINE RESECTABLE PANCREATIC HEAD CANCER WITH A
I. Koutsounas1,*, K. Giaginis2, A. Zizi3, G. Kouraklis4, E. Patsouris1, CHANCE FOR R0 SURGERY
S. Theocharis1 Y. Sekino1, K. Kubota1, K. Hosono1, A. Nakajima1, Y. Fujita1,*
1 1
First Department of Pathology, Medical School, National and Kapodistrian Gastroenterology, Yokohama City University, Yokohama, Japan
University of Athens, Athens, 2Department of Food Science and Nutrition, School Contact E-mail Address: kubotak@yokohama-cu.ac.jp
of the Environment, University of the Aegean, Myrina, Lemnos, 3Department of
Pathology, Tzanion General Hospital, Piraeus, 42nd Department of Propedeutic INTRODUCTION: Neoadjuvant chemradiationtherapy (NACRT) may lead to
Surgery, Laikon General Hospital, National and Kapodistrian University of successful margin-negative resection (R0) in pts with borderline resectable pan-
Athens, Athens, Greece creatic head cancer (BRPHC). NACRT using a covered metallic biliary stent has
Contact E-mail Address: john_koutsounas@yahoo.gr been attempted in pts with BRPHC, however, the efficacy of this therapy with/
without metallic duodenal stent (MDS) and the influence of using partially cov-
INTRODUCTION: Pregnane X Receptor (PXR) is a member of the nuclear ered metallic stent (PCMS) for its delivery in the treatment of BRPHC has not
receptor (NR) superfamily, expressed mainly in the liver and intestine, exerting been evaluated.
its transcriptional regulation by binding to DNA response elements as an hetero- AIMS & METHODS: To evaluate the efficacy of and complications associated
dimer with Retinoid X Receptor (RXR). PXR is involved in the homeostasis of with the use of PCMS with/without MDS during NACRT and the surgical
numerous endobiotics, as well as in inflammatory bowel disease, bone home- period.
ostasis, liver steatosis and antifibrogenesis. Additionally, PXR has a multifactor- We reviewed the outcomes of consecutive pts with BRPHC had histopathologi-
ial impact on cancer, either by directly affecting cell proliferation and apoptosis cally proven pancreatic adenocarcinoma, who presented with symptomatic bili-
or by inducing chemotherapy resistance. Even though many studies have inves- ary obstruction, and divided the patients chronologically, in terms of the period
tigated PXR implication in various types of cancer, data on the clinical signifi- of stent placement into two groups: group A; plastic stent (PS) deployment plus
cance of this receptor in pancreatic cancer are still very limited. NACRT between August 2009 and October 2010; group B; prospectively PCMS
AIMS & METHODS: The expression levels of PXR and its heterodimeric part- deployment with/without MDS plus NACRT between November 2010 and
ners RXR-, - and - were assessed immunohistochemically on histopatholo- December 2013. The pts were categorized as having borderline resectable
gical samples obtained from pancreatic adenocarcinoma patients, and associated cancer based on the NCCN clinical practice guideline established in 2013.
with various clinicopathological parameters, tumor proliferative capacity (Ki-67 Data on the pts demographics, complications, non re-intervention rate (NRR),
labeling index), and patients survival. surgical time, operative blood loss, length of hospital stay, complications after
RESULTS: Moderate/strong PXR expression was noted in 24 (43.6%) out of 55 resection, the rate of R0 and prognosis were studied. Safe R0 surgery was defined
pancreatic adenocarcinoma cases, being positively correlated with tumour histo- as R0 surgery without the need for re-intervention or postoperative
pathological grade of differentiation (p 0.023). Moderate/strong PXR/RXR- complications.
and PXR/RXR- expression was significantly correlated with smaller tumor size RESULTS: There were a total of 57 pts with LAPHC (group A and B: 29 and 28
(p 0.005, p 0.012, respectively) and earlier histopathological stage (p 0.003, pts, respectively). The median time from stent placement to surgery in the overall
p 0.014, respectively). Additionally, pancreatic adenocarcinoma patients pre- subject population were 130.5 Days in group A and 130.7 days in group B. MDS
senting moderate/strong PXR/RXR- or PXR/RXR- expression showed longer was deployed in one pts with group A and three pts with group B. NPR for the 1st
survival times compared to those with negative/weak, at non significant levels 30 days in group A (PS) and B (PCMS) were 48% and 96%, respectively. NPR
though (log-rank test, p 0.278, p 0.053, respectively). for the 2nd 30 days in group A and B were 23% and 92%, respectively. NPR for
CONCLUSION: In our study, PXR and PXR/RXRs expression was for the first the 3rd 30 days in group A and B were 15% and 92%, respectively. Regarding
time examined in human pancreatic cancer cases, being correlated with favour- NPR, PCMS is superior to group using PS (p50.05). No severe complications
able histopathological parameters and associated with longer patients survival. including gastrointestinal bleeding after irradiation were noted in any pts. There
Disclosure of Interest: None declared were no significant differences between groups regarding surgical time, operative
blood loss, length of hospital stay. The rates of achievement of R0 surgery in
groups A and B were 68.9% (20/29) and 89.3% (25/28), respectively. The PCMS
P0109 UROKINASE-TYPE PLASMINOGEN ACTIVATOR (UPA)- and MDS did not interfere with the conduct of the NACRT and pancreatico-
POSSIBLE PANCREATIC CANCER DIAGNOSTIC AND duodenectomy in any patients. The rates of achievement of safe R0 surgery in
PROGNOSTIC MARKER? groups A and B were 10.3% (3/29) and 70.4% (20/28), respectively (p50.05).
K. Winter1,*, M. Pawlowski2, P. Szczes niak3, A. Ga siorowska1, D. Orszulak- Multivariate analysis showed that odds ratio for safe R0 surgery was 18.426
Michalak3, E. Malecka-Panas1 (p50.0001) for PCMS placement.
1
Department of Digestive Tract Diseases, 2Department of Diabetes and Internal CONCLUSION: Insertion of PCMS should be considered for the relief of biliary
Diseases, 3Biopharmacy Institution, Medical University of Lodz, Lodz, Poland and/or duodenum obstruction in pts with BRPHC scheduled to receive NACRT,
Contact E-mail Address: katarzyna.winter@vp.pl in view of the minimize need for re-intervention for recurrent biliary obstruction,
and a potentially high rate of achievement of safe R0 surgery, as compared to the
INTRODUCTION: Urokinase-Type Plasminogen Activator (uPA) is a serine results obtained with PS deployment.
proteinase, which transforms inactive plasminogen to the active plasmin. UPA Disclosure of Interest: None declared
is involved in cancer progression, growth and metastasis through degradation of
extracellular matrix (ECM), growth factors FGF, IGF, VEGF release and cel-
lular migration activation. UPA overexpression was confirmed in many human P0111 BRANCH DUCT INTRADUCTAL PAPILLARY NEOPLASMS
cancers including pancreatic cancer and was connected to the poor survival. UPA WITH CYSTS LARGER THAN 3 CM WITHOUT HIGH-RISK
expression was found in the vessels of tumor stroma, which suggests that it can be STIGMATA: SHOULD WE RESECT THESE NEOPLASMS OR NOT?
detected in serum. K.T. Lee1,*, M.J. Lee1, Y.J. Lee1, J.K. Lee1, K.H. Lee1
AIMS & METHODS: The aim of this study was to evaluate the uPA serum 1
Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic Of
concentration in patients with pancreatic cancer (PC) and chronic pancreatitis Contact E-mail Address: happymap@skku.edu
(CP) in order to determinate its possible diagnostic and prognostic value.
The study group included 90 patients: 40 with pancreatic cancer, 30 with chronic INTRODUCTION: In 2012, revised international consensus guidelines were
pancreatitis and 20 healthy individuals (control group). Serum level of uPA was published, and they suggested a more conservative approach for the management
analyzed using an enzyme-linked immunosorbent assay (ELISA). Pancreatic of BD-IPMN with cysts larger than 3 cm without other high-risk stigmata.
cancers were classified according to the TNM classification. Criteria for resect- But, several recent studies have challenged the safety of this guideline. The aim of
ability included: absence of distant metastases, lack of evidence of tumor invol- this study is to compare the prognosis in patients who underwent surgical resec-
vement of major arteries, and (if there is venous invasion) a suitable segment of tion because of the cyst size and the prognosis in patients who chose close
portal vein (above) and superior mesenteric vein (below) the site of venous observation.
involvement to allow for venous reconstruction. AIMS & METHODS: We retrospectively reviewed the data of 48 BD-IPMN
RESULTS: We revealed threefold increase in uPA serum level in patients with patients with a cyst size 3cm, without any other suspicious features, between
pancreatic cancer (3.23ng/ml) and twofold increase in patients with chronic pan- March 1995 and October 2013. We divided the patients into 2 groups (21 patients
creatitis (2.18ng/ml), with was significant higher than in control group (1.01ng/ underwent surgery, and 27 patients chose close observation), and compared the
ml) (p50.05 PC vs CP; PC vs control; CP vs control). We observed significantly patients characteristics and prognosis.
higher level of uPA in patients with pancreatic cancer and CA19-94 500 IU/l RESULTS: The patients in the observation group were older than the patients in
compared to patients with CA19-9 5500 IU/l 3.98 ng/ml vs 2.8 ng/ml the surgery group and they had severe co-morbidities (2 ACE-27 co-morbidity
(p50.03). We noticed lower level of uPA in patients with resectable pancreatic score (moderate)). None of the patients developed new worrisome features or
cancer: 2.28 ng/ml vs 3.4 ng/ml in patients with unresectable pancreatic cancer high-risk stigmata during the follow-up period, and the causes of death were
but difference was not significant (p 0.14). In addition there was no correlation not related to IPMN. Among the 21 patients who underwent resection; 4 patients
between uPA level and pancreatic cancer stage. We found the significant correla- (19%) were diagnosed with invasive carcinoma, and 1 patient (4.8%) was diag-
tion between high serum uPA concentration and shorter survival (p50.05); mean nosed with intestinal type of invasive carcinoma. No surgery-related death and
survival in patients with uPA 4 2 was 181 days 155.11 and in patients with major postoperative complications were noted.
uPA 5 2 ng/ml- 335 days 313.75 (p 0.04). CONCLUSION: While making a decision regarding the management of BD-
CONCLUSION: The results suggest the possible use of serum uPA in pancreatic IPMN with a cyst size 3cm in the absence of high-risk stigmata, we should
cancer diagnosis and differentiation from chronic pancreatitis. Significant corre- consider the risk of surgery in patients, but we should not hesitate to perform
lation between serum uPA concentration and decreased survival, may indicate on resection in surgically fit patients especially in high-volume centers with experi-
the role of uPA as a prognostic marker in pancreatic cancer. enced surgeons.
Disclosure of Interest: None declared Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A161
attention for improved patient stratification and be considered much more inten-
P0112 FOLLOW UP HIGH-RISK INDIVIDUALS FOR EARLY
sively in the development of novel therapeutic algorithms in PDAC.
DETECTION OF PANCREATIC CANCER
Disclosure of Interest: None declared
R. Ashida1,*, T. Ioka1, N. Ishida1, H. Sueyoshi2, R. Takada2, N. Fukutake2,
H. Uehara2, K. Katayama1
1
Departments of Cancer Survey and Gastrointestinal Oncology, 2Department of P0114 OBESITY IS A RISK FACTOR FOR PANCREATIC
Hepato-Biliary and Pancreato Oncology, Osaka Medical Center For Cancer And PRECANCEROUS LESIONS
Cardiovascular Disease, Osaka, Japan V. Rebours1,*, S. Gaujoux2, G. dAssignies3, A. Sauvanet2, P. Levy1,
Contact E-mail Address: rashida@goo.jp P. Ruszniewski1, A. Couvelard4
1
Pancreatology Unit, 2Surgery Unit, 3Radiology Unit, Beaujon Hospital, Clichy,
INTRODUCTION: For the detection of pancreatic cancer in early stage, it is 4
Pathology Unit, Bichat Hospital, Paris, France
important to identify high-risk individuals and follow up those patients periodi- Contact E-mail Address: vinciane.rebours@bjn.aphp.fr
cally. We have started an early detection system for pancreatic cancer since 1998,
and revealed that individual with either pancreatic cyst (45mm) or dilated main INTRODUCTION: Obesity was described as a risk factor of pancreatic cancer in
pancreatic duct (42.5mm) is high-risk for pancreatic cancer. Follow up of high- combination with metabolic abnormalities. The respective roles of intravisceral
risk individuals (HRIs) with imaging tests, such as trans abdominal ultrasound and subcutaneous fat are unknown and the prevalence of precancerous lesions in
which is specialized to pancreato-billiary area (pancreatic US: pUS), endoscopic obese patients was never evaluated.
ultrasound (EUS) and computed tomography (CT) or magnetic resonance ima- AIMS & METHODS: To characterize the frequency and severity of pancreatic
ging (MRI), can lead to the detection and treatment within asymptomatic intraepithelial neoplasia (PanIN) in patients with fatty pancreas, to correlate
patients, however usefulness of the optimal imaging approach is not known. pathological findings with metabolic abnormalities, tobacco intake and type of
AIMS & METHODS: Between June 2007 and January 2014, 535 asymptomatic fat. Consecutive pancreatic specimens of patients operated on for benign neu-
HRIs were examined periodically at single center, using pUS (every 3 or 6 month) roendocrine tumors were analyzed. The pancreatic parenchyma was analyzed at
and CT or MRI (once a year). EUS was performed when any changes such as least 2 cm apart from the tumor. Fatty infiltration and fibrosis of the parench-
hypoechoic mass, new nodule or rapid change in cyst size were detected by pUS. yma in intra- and extralobular locations were assessed. Dysplastic lesions were
ERCP was recommended for cytology when the size of cyst become bigger than described according to the PanIN classification. General characteristics of the
3cm or main pancreatic duct was dilated bigger than 3mm or a newly narrowed patients were collected, including body mass index (BMI), diabetes and tobacco
part appeared, or the size of cyst or main pancreatic duct changed rapidly. EUS- intake. Liver steatosis was assessed by CT scan (mean of 3 regions of interest,
FNA was performed when an invasive nodule or hypoechoic mass was detected. threshold 458UH). The subcutaneous and intravisceral fat (% of the total area)
Contrast harmonic pUS/EUS was also performed if necessary. was estimated on CTscan by the ImageJ software (1.47, NIH, USA).
RESULTS: Sixteen patients with pancreatic cancer have been confirmed as RESULTS: 110 patients (males: 57%) were included (median surface of pancrea-
malignancy during follow up (2.99% incidence rate), 8 males and 8 females tic specimen: 7.5 cm2). Median age at surgery was 53.8 [17-85] years. Arterial
(mean age 69.1 yrs). Eight patients had an intraductal papillary mucinous hypertension, diabetes, tobacco intake were found in 19, 9 and 23%, respectively.
neoplasms (IPMNs) with an associated carcinoma (2: invasive, 6: non-invasive), Median BMI was 24 [16-37], (BMI525: 45%, 25-530: 24%, 430: 11%).
six had an invasive ductal adenocarcinoma, and two had ductal carcinoma in situ Overall, PanIN lesions were found in 65% of the patients, Type 1, 2 and 3
(PanIN3). Mean total follow up period until the detection of cancer was 34.8 PanIN were observed in 62, 38 and 1% of the cases, respectively. Fibrosis and
months (range 6.6 - 64 mo). Fourteen patients were asymptomatic. The number fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and
of patients with cancer stage of 0, IA, IIA, IIB, III, was 7, 4, 2, 1 and 2, respec- in 30% and 51%, respectively. Liver steatosis was observed in 27%. A correla-
tively. Ten cases were brought to further examination by the findings detected by tion was observed between the presence of PanIN lesions on one hand and fatty
pUS, two with symptoms such as abdominal pain, one with tumor marker eleva- pancreas [extra- (0.01) and intralobular (50.0001)], intralobular fibrosis (0.003),
tion, one with MRI finding, one with CT finding and one with EUS finding high BMI (p 0.02), liver steatosis (p 0.03) and subcutaneous (p 0.02) and
which was found by chance during further examination for another lesion. All intravisceral fat (p 0.02) on the other. Presence of PanIN was not influenced by
invasive pancreatic cancers (smaller than 10mm) were detected only by either tobacco intake or diabetes. The number of PanIN lesions was correlated with the
pUS or EUS but not by CT nor MRI. Invasive cancer showed hypo-vascularity severity of liver steatosis (r -0.25, p 0.02), the percentage of intravisceral fat
in pUS/ CE-EUS. Three cases were comfirmed as malignant by EUS-FNA and (r 0.22, p 0.04) but not with the percentage of subcutaneous fat (r 0.14,
twelve cases by ERCP. Thirteen cases had surgical resection and three cases had p 0.22) or patient age at surgery.
chemotherapy. CONCLUSION: Obesity -and especially android obesity with increased intra-
CONCLUSION: Periodical examination of asymptomatic HRIs frequently visceral fat- is a risk factor for precancerous lesions of the pancreas. These results
detects small pancreatic cancer with early stage. EUS and pUS could detect suggest that fatty infiltration per se plays a specific role in pancreatic oncogenesis.
invasive pancreatic cancer in early stage better than CT or MRI and are thought Disclosure of Interest: None declared
to be important modalities in surveillance.
Disclosure of Interest: None declared
P0115 MUCIN PHENOTYPE PREDICTS THE SITE OF METASTASIS
AFTER RESECTION OF PANCREATIC DUCTAL
P0113 THE INFLUENCE OF NEURAL INVASION ON SURVIVAL AND ADENOCARCINOMA
TUMOR RECURRENCE IN PATIENTS WITH PANCREATIC DUCTAL Y. Hamada1,*, K. Maeshiro2, Y. Nakayama3
ADENOCARCINOMA A SYSTEMATIC REVIEW AND META- 1
Pathology, FUKUOKA UNIVERSITY, Fukuoka, 2Surgery, St. Maria Hospital,
ANALYSES Kurume, 3Laboratory Medicine, National Medical Center, Fukuoka, Japan
S. Schorn1,*, I.E. Demir1, B. Haller2, H. Friess1, G.O. Ceyhan1 on behalf of Contact E-mail Address: yhamada@fukuoka-u.ac.jp
Pancreatic Neuropathy and Pain
1
Department of Surgery, 2Institute of Statistics and Epidemiology, Klinikum INTRODUCTION: Prognosis after surgical resection of pancreatic ductal ade-
Rechts der Isar der TU Munchen, Munchen, Germany nocarcinoma remains poor because of the high incidence of recurrence. Some
Contact E-mail Address: Stephan. Schorn@tum.de studies have described the sites of metastasis after resection of pancreatic ductal
adenocarcinoma, but little is known about the relationship between clinicopatho-
INTRODUCTION: The aim of this study is to assess the true impact of peri- logical features of the primary carcinoma and site of recurrence. Both normal
neural invasion/Pn on survival and tumor recurrence in pancreatic ductal ade- and malignant epithelial cells of a variety of organs contain mucous substances
nocarcinoma/PDAC. that are rich in very high molecular weight glycoproteins called mucins, which
Pn is a histopathological hallmark of PDAC, which affects overall survival/OS contain many serine- and threonine-linked carbohydrate chains. However, few
and tumor recurrence. Until now, recent studies could demonstrate that Pn studies examine the relationship between mucin phenotype of primary pancreatic
influences disease-free-survival-time/DFS and progression-free-survival-time/ ductal adenocarcinoma and the site of metastasis.
PFS. However, at this time point, there is still no consensus on the real impact AIMS & METHODS: The current study focused on clinicopathological features,
of Pn in PDAC. including mucin phenotype, in primary pancreatic ductal adenocarcinoma and
AIMS & METHODS: Pubmed, Cochrane library, Ovid and Google Scholar their relationship to sites of metastasis after surgical resection. A total of 323
were scanned for the terms pancreatic ductal adenocarcinoma, pancreatic patients underwent pancreatic resection in our hospital from 1982 to 2003.
cancer, survival, tumor recurrence and perineural invasion. Using the Seventy-four patients died from a known cause. Patients with intraductal papil-
Preferred Reporting Items for Systematic review and Meta-Analysis/PRISMA lary mucinous neoplasm were excluded. The follow-up period was 61 to 288
guidelines, a systematic review/SR and meta-analyses was performed. All articles months. Clinical data were obtained from patients charts, and pathological
meeting the predefined criteria were critically analyzed on relevance and meta- factors were assessed according to the WHO classification. A control group
analyses were performed by pooling univariate and multivariate hazard ratios/ comprised 13 patients who had survived more than 10 years after surgery for
HR. carcinoma of the pancreas (10 group). Sections were stained with hematoxylin
RESULTS: 23 studies for the influence of Pn on tumor recurrence and a total of and eosin and high iron diamine blue stain for detection of sulfomucin and
101 studies analyzing the influence of Pn on survival were identified by the SR. sialomucin. The staining pattern was classified into three groups: pure sialomucin
The performed analyses revealed the prognostic influence of Pn on PDAC type (Si type), pure sulfomucin type (Su type), and mixed type. With regard to
patients. The pooled HR of the univariate (1.86; CI 1.67-2.08; p50.00001) and immunohistochemical staining for MUC1, MUC2, MUC5AC and MUC6, stain-
multivariate analyses (1.50; CI 1.36-1.65; p50.00001) showed a strong negative ing of more than 10% of the carcinoma was defined as positive. Neurovascular
impact of Pn on OS in PDAC. Interestingly, Pn was also closely linked to invasion was deemed to be present if involvement of more than five sites on a
decreased DFS (HR: 2.23, CI 1.13-4.41; p50.05) and PFS (HR: 2.82; CI 1.97- typical section was seen.
4.04; p50.00001) in the pooled multivariate analyses. RESULTS: Of the 74 patients with an obvious cause of death, 45 died of peri-
CONCLUSION: This is the first systematic review and meta-analyses focusing tonitis carcinomatosa following local recurrence (P group), 25 died of liver metas-
on the prognostic impact of Pn on OS, DFS and PFS in PDAC. Here we could tasis (L group), 2 died of lung metastasis, and 2 died of bone metastasis. We
demonstrate that Pn is an independent prognostic factor among PDAC patients, compared the clinicopathologic features between the L group, P group, and 10
which decreases OS, PFS and DFS. Therefore, Pn should receive increased group. Clinicopathologic features of each group are as follow: L group: frequent
A162 United European Gastroenterology Journal 2(5S)
Si type of carcinoma (vs. P group, p 5 0.0001; vs. 10 group, p 0.0002), high 19, 20-29, 30mm or bigger, the incidence of mixed type was 0% (0/15), 8% (2/24)
rate of venous invasion (vs. P group, p 5 0.0001; vs. 10 group, p 5 0.0001), and and 0% (0/15), 15% (2/13), respectively.
shorter prognosis (334 months, vs. P group, p 0.0257). P group: advanced pT 4. 0-IIb type: All of seven lesions were pure well differentiated type.
factor (vs. 10 group, p 0.0015) and high rate of R1 status (vs. L group, 5. 0-IIc type: 80, 17 and 2 of 99 lesions was pure well, mixed and pure poorly
p 0.0370; vs. 10 group, p 0.0243). 10 group: lower grade of pT factor (vs. L differentiated type, respectively. And when the size was subclassified into four
group, p 0.0086; vs. 10 group, p 0.0015) and lower stage (vs. P group, groups 2-9, 10-19, 20-29, 30mm or bigger, 0% (0/30), 25% (12/48), 27% (4/15)
p 0.0037). and 50% (3/6) were mixed type.
CONCLUSION: We might be able to predict the occurrence of liver metastasis 6. The surface pattern of well differentiated adenocarcinoma observed by mag-
by preoperative histochemical mucin staining of carcinoma cells that were clas- nified endoscopy showed irregular villous or pit pattern. However, the surface
sified as Si type preoperatively using EUS-FNA or biopsy. pattern of mixed type was unclear in some cases. However, sometimes the surface
Disclosure of Interest: None declared was covered by thick mucus, and magnified endoscopic observation was
impossible.
CONCLUSION: The incidence of mixed type depends on the size and macro-
MONDAY, OCTOBER 20, 2014 9:0017:00 scopic type of the superficial gastric cancer. Magnified endoscopy was sometimes
ENDOSCOPY AND IMAGING I POSTER EXHIBITION HALL useful to detect mixed type from the surface pattern.
XL_____________________ REFERENCES
NONE
P0116 EUS-FNA FOR SMALL GASTROINTESTINAL SUBMUCOSAL Disclosure of Interest: None declared
LESIONS: USEFULNESS OF FORWARD-VIEWING
ECHOENDOSCOPE ATTACHED WITH CAP DEVICE
P0118 SUBMUCOSAL FIBROSIS AFFECTS THE OUTCOME OF
A. Yamabe1,*, A. Irisawa1, G. Shibukawa1, Y. Abe1, K. Imbe1, K. Hoshi1,
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR GASTRIC
R. Igarashi1
1 NEOPLASMS
Gastroenterology, Fukushima Medical University Aizu Medical Center,
Aizuwakamatsu, Japan A. Shimozato1,*, N. Ogasawara1, Y. Kondo1, Y. Ito1, H. Noda1, K. Yanamoto1,
Contact E-mail Address: akaneko@fmu.ac.jp M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University, Nagakute City Aichi, Japan
INTRODUCTION: Previous reports demonstrated endoscopic ultrasound-
guided fine-needle aspiration biopsy (EUS-FNA) for gastrointestinal submucosal INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective
lesion (SML) is feasible and safe with high diagnostic yield. On the other hand, treatment for gastric neoplasms. However, because of its technical difficulty, it
since it is difficult to perform EUS-FNA for small SML especially less than takes longer, and there is a greater risk of complications such as bleeding and
15mm, almost small SMLs are observed without EUS-FNA. However, because perforation. The success of ESD depends on the technical proficiency of the
SMLs include malignant lesions even though a tumor is small, it is desirable to endoscopist and the condition of the gastric tumor. Even for a skilled endosco-
perform EUS-FNA when possible. pist, however, submucosal fibrosis can be an obstacle to success of ESD.
AIMS & METHODS: The aim of this study is to evaluate feasibility and safety Submucosal fibrosis, which usually results from inflammation or tumor invasion,
of EUS-FNA using forward-viewing echoendoscope attached with a cap device makes it harder to lift the tumor tissue from the muscle layer. This in turn
to the tip of scope for the small SML. Eight patients who had small SML less lengthens the procedure time, creates risk of complications such as perforations,
than 15mm I upper GI were enrolled in this study. EUS-FNA was done using and reduces the success rate of complete en bloc resection. Despite its impor-
forward-viewing EUS scope (XGIF-UCT160J-AL5; Olympus, Tokyo, Japan) tance, there has been little investigation of the relationship between the degree of
and needle devices (22G, 25G), with rapid on-site evaluation. To fix the SML submucosal fibrosis and outcomes of ESD in early gastric tumors. Accordingly,
at the needling, a cap device was attached to the tip of scope. We evaluated the the aims of this study were 1), to examine the association between endoscopic and
rate of sampling, accuracy, and complication. pathologic findings and submucosal fibrosis in gastric neoplasms; 2), to examine
RESULTS: Mean diameter of SMLs was 10.6 mm2.94mm (meanSD, range the association between degree of submucosal fibrosis and outcomes of ESD.
8-15mm). The puncture could be done in all 8 cases, and mean number of FNA AIMS & METHODS: Two hundred forty six patients with gastric neoplasms (52
passes was 4.61.59 (meanSD, range 3-7). The adequate materials were cases of adenomas and 194 cases of early gastric cancers) were treated by ESD
obtained in 6 (87.5%) for cytology, in 4 (50%) for histological examination from November 2008 to September 2013. Endoscopically, the degree of submu-
with immunostaining. In 1 (12.5%) patient, adequate sample for both cytology cosal fibrosis was classified as follows, based on the findings obtained after a
and histology was not obtained. As final diagnosis, 6 patients were gastrointest- solution including indigo carmine was injected under the submucosal layer: F0,
inal stromal tumor (2 in definition, 3 in suspicion), 2 patients were leiomyoma. no fibrosis, which appeared as a blue transparent layer; F1, mild fibrosis, which
No complication was noted. appeared as a white web-like structure in the blue submucosal layer; and F2,
CONCLUSION: Although the rate of definitive diagnosis was 50%, EUS-FNA severe fibrosis, which appeared as a white muscle-like structure without a blue
using forward-viewing echoendoscope attached with a cap device for small SML transparent layer.
was feasible and safe. RESULTS: The presence of endoscopic submucosal fibrosis was not significantly
Disclosure of Interest: None declared related to tumor size, ulceration, histological findings, submucosal invasion, and
en bloc resection rates in univariate analysis. However, posterior walls of the
stomach harbored higher frequency of submucosal fibrosis compared with ante-
P0117 ENDOSCOPIC CHARACTERISTICS OF EARLY GASTRIC rior wall regardless of upper, middle or lower portion of the stomach (p50.05).
CANCERS MIXED WITH WELL AND POORLY DIFFERENTIATED The procedure time according to the degree of endoscopic submucosal fibrosis
ADENOCARCINOMA were as follows (mean SD): F0, 82.142.1 minutes; F1, 146.681.6 minutes,
A. Takahashi1,*, T. Oyama1 and F2, 171.4106.7 minutes, showing significant difference between groups (p
1
Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan 50.01). The severity of endoscopic submucosal fibrosis was associated with
Contact E-mail Address: aurevoireurope@yahoo.co.jp abundant immediate bleeding which required hemostasis using hemoclips
during ESD procedure (p50.05). However, delayed bleeding was not signifi-
INTRODUCTION: The risk of lymph node metastasis of superficial gastric cantly related to the degree of submucosal fibrosis.
cancer depends on histological type, invasion depth and the size. Sometimes, CONCLUSION: Submucosal fibrosis of gastric neoplasms is closely related to
well differentiated gastric adenocarcinoma has poorly differentiated component tumor location, procedure time, and severe bleeding during ESD. Moreover, the
partially. And, the incidence of lymph node metastasis is higher than that of the more advanced the endoscopic submucosal fibrosis, the longer the time required
well differentiated type. Therefore, endoscopic diagnosis of histological type is for ESD and the higher the frequency of immediate bleeding. Further develop-
important. However, the endoscopic characteristics of such a histologically ment of endoscopic devices and peripheral equipments are needed for safe and
mixed gastric adenocarcinoma are unknown. complete resection of lesions with severe fibrosis.
AIMS & METHODS: The aim of this study is to investigate the endoscopic Disclosure of Interest: None declared
characteristics of early gastric cancers partially with poorly differentiated type.
One hundred eighty-two gastric adenocarcinomas from 172 patients treated by
ESD from January to December 2012 were enrolled in this study. All of the P0119 NEW ENDOSCOPIC TECHNIQUE FOR SECONDARY
examination was performed by Olympus H260Z with Lucera. And, narrow PLACEMENT OF VOICE PROSTHESIS
band imaging (NBI) magnified observation was performed after white light ima- A.M. Seraphim , A. Pelosof , L. Kowalski , J. Vartanian , C.Z. Sztokfisz1
1,* 1 2 2
ging (WLI) observation. Magnified endoscopic findings were divided into surface 1
endoscopy, 2head and neck surgery, AC Camargo Cancer Center, Sao Paulo,
and vascular pattern. Surface pattern was divided into villous, pit and unclear. Brazil
The gross type was classified into 0-I, 0-IIa, 0-IIb and 0-IIc type, and the number Contact E-mail Address: alvaroseraphim@yahoo.com.br
was 9, 67, 7, and 99, respectively. The histology was classified into well and
poorly differentiated type. When the cancer had only well differentiated type, INTRODUCTION: The functional speech rehabilitation in laryngectomized
it was classified as pure well differentiated type. And, when the well differentiated patients after total laringectomy remains as one of the most challenging matters
adenocarcinoma had a poorly differentiated component, it was classified as for head and neck surgeons and speech therapists.
mixed type. And when the cancer was composed of only poorly differentiated The use of voice prostheses has been considered the gold standard in voice
adenocarcinoma, it was classified as pure poorly differentiated type. rehabilitation for the last 25 years. Insertion can be performed either as a primary
RESULTS: 1. The numbers of pure well differentiated type, mixed type and pure procedure during laryngectomy or as a secondary procedure with rigid esopha-
poorly differentiated type were 157, 23 and 2, respectively. goscope or trocar. In some patients these procedure became technically impos-
2. 0-I type: Seven of 9 lesions were pure well differentiated type, and two of 9 sible due to some post treatment cervical abnormalities such as necks reduced
lesions were mixed type. The size of these two lesions was more than 20mm. hyperextension (post surgery or radiotherapy) anastomotic reduced diameter
3. 0-IIa type: Sixty three and 4 of 67 lesions were well differentiated and mixed (post surgery), trismus and other impairments situations.
type, respectively. The incidence of mixed type has relationship with the size. AIMS & METHODS: Objective: To present an endoscopic technique for sec-
When the lesions were divided three groups depends on the size such as 1-9, 10- ondary placement of Provox prosthesis using the flexible endoscope, a plastic
United European Gastroenterology Journal 2(5S) A163
pliable overtube (to keep the virtual esophageal lumen open so the traqueoeso- 12% but was not directly related to the SEMS insertion. The 7-day readmission
phageal puncture could be performed safely, avoiding unexpected lesions on the rate following SEMS placement was 5% as result of symptoms caused by SEMS
posterior esophageal wall), a 14 gauge intravenous catheter to perfomed the including pain & vomiting. The median survival was 125 (range 4-910) days. 26
puncture, and a flexible guidewire. Furthermore, using the flexible endoscope (35%) of the patients needed re-intervention due to recurrence of dysphagia due
instead of the rigid esophagoscope we can avoid some of the major complications SEMS migration or tumour overgrowth. The SEMS migration rate was 18%
of the classical technique i.e.: mediastinitis, cervical cellulitis, fracture of cervical (n 14/96) occurring after a median of 120 (range 10-365) days. 87% of the
vertebra, and esophageal perforation migrated SEMS were from tumours of the lower oesophagus and GOJ.
Methods: 7 patients referred to voice rehabilitation with Provox II vocal pros- Tumour overgrowth occurred in 16% (n 15/96) at a median of 120 (range
thesis in a secondary placement, in which the classic technique could not be 28-210) days. In 19/26 (73%) cases palliation was successfully achieved with
performed, underwent a new surgical technique, performed with a flexible endo- re-intervention; further SEMS placement in 17 & APC in 2. Interestingly, the
scope, a plastic pliable overtube, a 14 gauge intravenous catheter and a flexible patients with recurrence of dysphagia had significantly (p00.5) prolonged sur-
guidewire, vival (median 156 (range 30-790) days) compared to patients who did not need
RESULTS: The procedure was successfully performed in all seven patients. any intervention (median 125 (range 4-910) days).
There were no complications related to the surgical technique. CONCLUSION: Fully covered SEMS are safe and offer extremely effective
CONCLUSION: In patients where the classic technique for secondary insertion palliation of malignant dysphagia for up to 3-4 months. Re-intervention
of the Provox prosthesis is technically impossible, this new technique could be a beyond this point is for recurrence of dysphagia due to SEMS migration and/
good alternative or tumour overgrowth that may be due to increased patient survival. The major-
Disclosure of Interest: None declared ity of patients can be re-palliated successfully with further endotherapy.
Disclosure of Interest: None declared
INTRODUCTION: Oesophageal stenting with fully covered self-expanding P0123 PENTAX I-SCANTM WITH MAGNIFICATION FOR THE
metal stents (SEMS) has transformed the care of patients with malignant dys- IDENTIFICATION OF UNDERDIAGNOSIS ORGANIC
phagia. SEMS are easily removable and have fewer reported long-term compli- ESOPHAGEAL LESIONS (BARRET ESOPHAGUS AND
cations of tumour ingrowth although possibly more migration. However, ESOPHAGITIS) IN PATIENTS WITH FUNCTIONAL DYSPEPSIA: A
predictive factors for favourable outcomes are yet to be fully defined for those PROSPECTIVE STUDY
with malignant dysphagia. C. Robles-Medranda1,*, R. Del Valle1, M. Soria1, G. Bravo1, H. Lukashok1,
AIMS & METHODS: The aim of this retrospective study was to evaluate the C. Robles-Jara1
complications, the re-intervention rate and the survival after insertion of fully 1
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
covered SEMS for malignant dysphagia and to identify any predictive factors for DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
outcomes other than tumour stage. All SEMS procedure data were retrieved UNIVERSITY, Guayaquil, Ecuador
from Royal Liverpool University Hospital patient database retrospectively in a Contact E-mail Address: carlosoakm@yahoo.es
2-year inclusion period and analysed regarding SEMS characteristics, procedural
events, re-interventions and survival on a standard proforma. INTRODUCTION: Functional dyspepsia (FD) is a highly prevalent gastroin-
RESULTS: A total of 96 fully covered SEMS were inserted in 74 patients (47 testinal disorder characterized by symptoms originating from the gastroduodenal
males) with a median age of 73 (range 36-89) years. Technical success was 99% region in the absence of underlying organic disease as defined by Roma III
(95/96), with no complications of perforation or bleeding. Minor (n 6) compli- criteria. Upper endoscopy (UE) associated to digital chromoendoscopy (DC),
cations included chest pain, vomiting & severe GORD. The 30-day mortality was magnification (M) and high definition (HD) had shown excellent results for
A164 United European Gastroenterology Journal 2(5S)
the diagnosis of Barret esophagus (BE) and esophagitis. However, not all patients University School of Medicine, Gyeongju, Korea, Republic Of
are investigated with this kind of technology, where UE results are considered as Contact E-mail Address: sentiwalk@naver.com
absence of organic lesions, thus diagnosed as FD.
AIMS & METHODS: Based on the hypothesis that HD UE associated to DC INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
and M can detect more mucosal details than standard UE, we evaluate the performed for the treatment of early gastric cancer (EGC).
effectiveness of i-ScanTM (HD UEDCM) in patients with functional dyspep- AIMS & METHODS: The aim of this study is to confirm the effectiveness of
sia for the identification of organic esophageal lesions. After approval by the ESD in submucosal invasive gastric cancers (SM-GC), with a special focus on
ethics committee and signing of an informed consent, a prospective study was patients who underwent non-curative resection.
performed in consecutive patients undergoing for UE from Nov 2012 to June Data for 1,246 patients who underwent ESD for treatment of EGC at six medical
2013. Inclusion criteria: Criteria of FD in accordance to ROMA III criteria, centers in Daegu-Gyeongbuk, Korea, between February 2003 and May 2010
normal standard UE in the last 3 months previous to the inclusion in this were collected. After retrospective analysis of ESD databases, 118 patients
study. Exclusion criteria: age 518, pregnancy, history of: gastritis, GERD, gas- were enrolled in the study. The corresponding EGC lesions were classified into
trointestinal cancer, H pylori infection, pancreatic disease, choledocolitiasis, three groups based on the results of pathological examination: 1) gastric cancers
alcohol or smoke abuse, use of medications (IBP, NSAIDs, Antibiotics). HD with submucosal invasion less than 500mm (SM1-GC) that met the expanded
UEDC and M was performed using the EPK-i processors with i-ScanTM from criteria (EC) (SM1 EC group, n 42); 2) SM1-GC that did not meet the EC
Pentax. Under sedation patients underwent HD UE, analyzing all the mucosa (SM1 non-EC group, n 38); and 3) gastric cancers with submucosal invasion
aspects using initially white light (WL), with especial regard in the Z-line at the greater than 500mm (SM2-GC group, n 38).
level of the cardia. Then DC was performed using i-Scan. Any alteration in the RESULTS: The en bloc resection rate (SM1 EC group/SM1 non-EC group/
mucosa pattern (color, pitt or vascular pattern) was analyzed and then classified SM2-GC group: 85.7%/94.7%/97.4%, respectively) and complete resection
as inflammation or BE using Los Angeles and Prague classifications respectively. rate (SM1 EC group/SM1 non-EC group/SM2-GC group: 81.0%/81.6%/
Finally acetic acid was performed and a target biopsy was done as the gold 71.1%, respectively) did not differ significantly among the three groups.
standard method to confirm i-Scan findings. However, the curative resection rate was significantly better in the SM1 EC
RESULTS: 491 patients were included. 48% were men with a mean age of 47 group (69.0%) compared to that in SM1 non-EC and SM2-GC groups (0% in
(ranges: 18-87). 151/491 patients (30.7%) had an organic esophageal lesion both cases). Out of a total of 118 patients, 89 (75.4%) underwent non-curative
detected at i-Scan. 45/151 patients were detected initially by HD-UE-WL. resection. Cancer recurrence was observed in 9 patients (9/89, 10.1%) during the
Biopsy confirm the esophageal lesions in 125 cases. i-Scan detect 94 cases of median follow-up period of 40 months (range: 3-99). We analyzed the overall
short BE (C51,M51), 25 cases of esophagitis (Grade A), and 6 cases where survival and disease-free survival in non-curative patients that underwent or did
considered to have a mixed disease (BE and esophagitis). The accuracy to predict not undergo additional surgery. The overall survival and disease-free survival did
BE for i-Scan was 95% and 100% for esophagitis. not differ significantly between patients that were treated with additional surgical
CONCLUSION: HD UEMDC (i-ScanTM) could detect an important resection and those that were simply followed up after ESD.
number of organic esophageal lesions as BE and esophagitis in patients initially CONCLUSION: Non-curative resection in SM-GC does not always lead to
overdiagnosed as a functional disease. cancer recurrence. Thus, if additional surgery cannot be performed because of
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical, the patients unsuitable condition (due to age, underlying disease, etc.) or refusal,
MaunaKea technologies, R. Del Valle: None declared, M. Soria: None declared, a close follow-up with endoscopy can be considered as an alternative for carefully
G. Bravo: None declared, H. Lukashok: None declared, C. Robles-Jara: None selected patients. Moreover, as the ESD technology continues to evolve, it might
declared be possible to expand the criteria for curative ESD in patients with SM-GC.
Disclosure of Interest: None declared
P0149 ENDOSCOPIC SUBMUCOSAL RESECTION FOR P0151 ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE
METACHRONOUS TUMOR IN THE REMNANT STOMACH AFTER TREATMENT OF GASTROINTESTINAL NEOPLASIAS: INITIAL
SUBTOTAL GASTRECTOMY RESULTS IN 31 PATIENTS
J. Lee1,*, B.-H. Min1, J.H. Lee1, J.J. Kim1, P.-L. Rhee1, K.-M. Kim2 A. Herreros de Tejada1,2,*, M. Hernandez Conde1, J.L. Calleja1,2, A. Sanchez
1
Department of Internal Medicine, 2Department of Pathology, Samsung Medical Movilla1, C. Salas1, P. Matallanos1, E. Blazquez1, J.C. Fernandez-Rial1,
Center, Seoul, Korea, Republic Of S. Gonzalez2, J.F. Garc a2, L. Abreu1,2
1
Hospital Universitario Puerta de Hierro Majadahonda, 2M. D. Anderson Cancer
INTRODUCTION: Subtotal gastrectomy is one of the most common procedures Center, Madrid, Spain
to resect gastric cancer curatively. However, if the patients have a remnant Contact E-mail Address: marta.hernandez.conde@gmail.com
stomach after the surgery, the risk of metachronous gastric tumor remains.
Because early gastric cancer (EGC) patients have a good prognosis after curative INTRODUCTION: Endoscopic submucosal dissection (ESD) is an advanced
surgery, the incidence of metachronous tumor in the remnant stomach is now technique used for en-bloc curative resection of early neoplasms of the gastro-
problematic. When the metachronous gastric tumor is detected, endoscopic sub- intestinal tract. Main advantages are high rate of curative resection and low
mucosal dissection (ESD) can be considered as an alternative treatment option recurrence rate, avoiding in most cases the need of surgery.
than an additional operation. AIMS & METHODS: Initial training on Animal Research facilities was carried
AIMS & METHODS: Little information exists concerning the optimal treatment out for 2 years before starting ESD in humans. Prospective analysis of ESD
of metachronous tumor in the remnant stomach. The aim of this study was to performed for suspected early neoplasia of GI tract. The interventions were
assess the clinical outcomes and safety of ESD for this lesion. We retrospectively performed mostly in the endoscopy suite, full equipped to provide general anaes-
enrolled patients who had undergone ESD for metachronous tumor in the rem- thesia in selected cases (all cases on the oesophagus and stomach, as selected
nant stomach after subtotal gastrectomy from December 2007 to January 2013 at colorectal cases). Flush knife BT (Fujifilm Co. Japan) was the main knife used,
the Samsung Medical Center in Seoul, Korea. A total of 18 lesions in 12 patients both in versions BT 1.5mm (oesophagus, colon and rectum) and 2.0mm (sto-
with EGC and 6 patients with high grade dysplasia (HGD) were treated by ESD. mach); occasionally other knifes were applied, such as Hook-knifeand Dual-
The patient characteristics, endoscopic findings and histopathological features Knife (Olympus Co, Japan)
and technical outcomes of ESD were investigated. RESULTS: From January 2012 to February 2014 ESD was completed in 31
RESULTS: A total of 18 patients had previously undergone 17 Billoth-I (94%), 1 patients. The mean age was 64.4 years (SD12), with a male proportion of
Billoth-II (6%) gastrectomies. The median period from the previous gastrectomy 55%. Over 60% of the cases were performed in colorectal location (colon 12
to the subsequent ESD for metachronous tumor in the remnant stomach was (39%); rectum 7 (22%)); other locations were stomach (9 (29%)) and oesophagus
71months (range 13-207 months), the median tumor size was 13mm (range (3 (10%)). Initial success of ESD was 93.5%, with 2 cases requiring surgery due
4-22mm). En block resection with curative resections achieved for 16 lesions to failure or severe complication (both colonic cases). The en-bloc resection rate
(88.9%). Adverse events showed 1 case of perforation (5.6%) and there was was 96.5%, the average specimen size 18.1 cm2 (max. length on average 46.4mm),
neither case of requiring emergent surgery nor treatment-related mortality with a median of 114 minutes (34-256) to complete the procedure. Regarding the
during this study period. The patients who requiring additional surgery for cura- morphology, 16 cases were 0-IIa, 5 cases 0-Is, 3 cases 0-IIa/0-IIc, 2 cases 0-IIb, 2
tive treatment due to deep submucosal invasion were 2 (11.2%). cases 0-Is/IIa 1 case 0-IIa/0-IIb and 1 case 0-IIb/0-IIc. Lateral spreading tumors
CONCLUSION: ESD for the metachronous tumor in a remnant stomach after (LSTs) distribution was: LST granular mixed type 5 cases, LST granular homo-
subtotal gastrectomy showed a high en bloc resection rate and very low compli- geneous type 7 cases, and 1 case of LST non-granular type. The R0 resection rate
cation rate. Therefore, we suggest that ESD is an effective and safe treatment for successful ESD was 90% (26 cases). There were 12 cases (39%) with perfora-
method for metachronous tumor in the remnant stomach if it is performed by tion (38%), of which 10 (80%) were managed successfully with local endoscopic
highly qualified experts. It is less invasive than additional surgery. Therefore, it treatment (closure with clips). There were 2 cases of late complications (splenic
can give a better quality of life to the patients, and the treatment outcome is rupture and mild lower gastrointestinal bleeding), with no mortality associated.
excellent, with no treatment-related mortality in this study. We analyzed the population according to chronological inclusion and divided
Disclosure of Interest: None declared into 3 similar periods. The average dissection speed during the initial phase was
0.36mm/min, compared to 0.49mm/min and 0.44mm/min during the intermedi-
ate and the final phase respectively, with no statistically significant differences
P0150 EFFICACY OF REBAMIPIDE IN THE HEALING OF IATROGENIC (p 0.2) due to the small sample size.
ULCERS POST ENDOSCOPIC SUBMUCOSAL DISSECTION: A CONCLUSION: ESD is an effective technique in the treatment of early neoplas-
META-ANALYSIS tic lesions in the digestive tract, particularly in cases of flat-depressed morphol-
J.-A. V. Bisnar1,*, I.H. Cua1 ogy, with a size greater than 20mm and/or the presence of submucosal fibrosis.
1
Institute of Digestive and Liver Disease, St. Lukes Medical Center, Quezon City, The technical difficulty, along with the prolonged time of endoscopy and the risk
Philippines of serious complications (essentially perforation) are the main constraints of
Contact E-mail Address: joannebisnar@gmail.com ESD. However, in our own experience, high en-bloc and R0 resection rate can
be achieved, along with remarkable technical progress during the learning curve
INTRODUCTION: Endoscopic submucosal dissection (ESD) is a treatment and successful endoscopic management of perforation. Our results demonstrate
option for early gastric cancer (EGC). It is less invasive, however, it is associated the possibility of successful adoption of ESD in Europe after completing proper
with larger, deeper ulcers post-procedure. Combined use of mucosal protective training.
anti-ulcer drugs such as rebamipide and proton pump inhibitors (PPI) was Disclosure of Interest: None declared
reported to promote ulcer healing.
AIMS & METHODS: The study aims to determine the efficacy of rebamipide in
the healing of post ESD associated ulcers. P0152 ENTONOX DURING COLONOSCOPY; HOW SHOULD IT
PubMed, Cochrane Database and bibliographies of retrieved articles were BE USED?
searched for eligible articles. Randomized controlled trials involving patients A. Ball1,*, S. Din1, M. Donnelly1, K. Smith1, S.A. Riley1
with EGC who underwent ESD and were given rebamipide monotherapy or as 1
Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield,
adjunct to PPI were included in this meta-analysis. 2 reviewers extracted the data United Kingdom
and assessed the quality of the studies included. Review Manager 5 software was Contact E-mail Address: alex.ball@sth.nhs.uk
used to analyze data from the studies included. Random effects model was used
for combining quantitative data. INTRODUCTION: Entonox can be used to ease the discomfort associated with
RESULTS: 6 studies with a total population of 758 were included in the review. colonoscopy but the optimal mode of administration is unknown. We have
356 patients were randomized to the treatment group (rebamipide alone or as an compared continuous and as required Entonox use during screening colonoscopy
adjunct to PPI). 354 patients were randomized to the control group (PPI or H2- examinations.
RA). Rebamipide monotherapy or as an adjunct to a PPI compared to placebo AIMS & METHODS: Patients attending for screening colonoscopy were invited
(PPI or H2-RA) significantly improved healing with a p value of 0.0002 (RR to participate. Eligible patients were randomised to using Entonox as required or
1.50, 95% CI 1.21-1.87). continuously. Procedural and demographic details including HADS score were
CONCLUSION: Rebamipide improves the healing of post ESD associated collected. Examinations were performed by three experienced colonoscopists.
ulcers especially when administered with PPI for 4 weeks. Patients rated pain on a 10 point numerical ratings scale (0 no pain and
REFERENCES 10 extreme pain) every 2 minutes during colonoscopy, prior to discharge and
Rembackes BJ, et al. Endoscopic mucosal resection. Endoscopy 2001; 33: 709-718. 1-3 days following colonoscopy. The colonoscopist and specialist screening prac-
Uedo N, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on titioner (SSP) also rated the patients overall pain severity and the technical
prevention of bleeding from ulcer after endoscopic submucosal dissection of early difficulty of colonoscopy.
gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol Continuous and categorical data were compared using a t test and chi-squared
2007; 102: 1610-1616. test respectively. Correlations were assessed using Pearsons correlation coeffi-
Terano A, et al. Rebamipide, a gastro-protective and anti-inflammatory durg, cient and the agreement between observers was assessed using the intra-class
promotes gastric ulcer healing following eradication therapy for Helicobacter correlation coefficient (ICC).
pylori in Japanese population: a randomized, double-blind, placebo-controlled RESULTS: 157 patients were screened and 49 were excluded (34 opted for intra-
trial. J Gastroenterol 2007; 42: 690-693. venous sedation, 13 declined and 2 had a cardiac pacemaker). 108 patients were
Park SH, et al. Comparison of prevention of NSAID-induced gastrointestinal randomised and 8 patients were withdrawn (7 had a cancer and 1 was unable to
complications by rebamipide and misoprostol: a randomized, multicenter, con- activate Entonox). Study participants had a mean age of 67 years and 75% were
trolled trial STORM STUDY. J Clin Biochem Nutr 2007; 40: 148-155. male. 46 patients were randomised to continuous and 54 to as required use.
Kato, et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton 15/54 (27.7%) patients in the as required group did not use Entonox and 7/46
pump inhibitor after endoscopic submucosal dissection a randomized con- (15.2%) of patients in the continuous group reverted to as required use due to side
trolled study. J Gastroenterol 2010; 45: 285-290. effects. The number of patients requiring additional analgesia was not significantly
Disclosure of Interest: None declared different between continuous use and as required use (4/46 vs 3/54, p 0.54).
A172 United European Gastroenterology Journal 2(5S)
There was no significant difference in the overall pain scores given by patients
P0154 MACROSCOPIC COLONOSCOPY FINDINGS OF
who used Entonox continuously and as required (mean score 2.4 vs 3.2,
COLLAGENOUS COLITIS; A THREE-CENTRE EXPERIENCE
p 0.08 and peak score 4.2 vs 4.8, p 0.26). Overall patient satisfaction was
high with the continuous and as required methods (mean 9.9 vs 9.7, p 0.23) as A. Koulaouzidis1,*, K. Sjoberg2, L. Bartzis1, M. MacNeill3, A. Nemeth2,
was willingness to undergo a repeat examination (mean 9.2 vs. 9.7, p 0.09). G. Wurm Johansson2, P. Finneron3, A.J. Lucendo4, E. Toth2
1
A HADS anxiety score of 7 was associated with higher overall pain scores Endoscopy Unit, Centre for Liver & Digestive Disorders, The Royal Infirmary of
(mean score 2.1 vs 3.6, p 0.004 and peak scores 3.7 vs 5.6, p 0.003). Edinburgh, Edinburgh, United Kingdom, 2Endoscopy Unit, Department of
Patient with a HADS anxiety score 57 who were allocated to continuous Gastroenterology, Skane University Hospital, Malmo, Sweden, 3Pathology
rather than as required use had lower pain scores (mean 1.4 vs 2.5, Department, Western General Hospital, Edinburgh, United Kingdom, 4Endoscopy
p 0.045) but there were no significant differences between strategies in the Unit, Hospital General de Tomelloso, Tomelloso, Spain
patients with a HADS score 7 (3.3 vs 3.8, p 0.6) There was no significant
difference in the pain ratings according to gender. INTRODUCTION: Microscopic colitis (MC) encompasses 2 entities, collage-
Patients overall rating of pain prior to discharge correlated highly with the mean nous colitis (CC) and lymphocytic colitis (LC).1 Although (by definition) a his-
intra-procedural pain score (r 0.84) and peak rating of pain (r 0.84). There topathological diagnosis, there are occasions when colonoscopy reveals findings
was also a very high correlation between the patients overall pain rating prior to such as alteration of the vascular mucosal pattern/innominate grooves, mucosal
discharge and 1-3 days later (r 0.94). There was good agreement between the nodularity and a sequence of mucosal changes from defects/lacerations to cica-
patients and the SSPs (ICC 0.79) and endoscopists (ICC 0.76) overall pain tricial lesions that are thought to be characteristic of MC, and especially CC.1,2
rating. The aim of this study was to evaluate the frequency and type of endoscopic
CONCLUSION: Overall, the method of Entonox administration did not influ- findings in patients diagnosed with CC in two University Hospitals.
ence pain ratings. However, continuous Entonox use was more effective in AIMS & METHODS: Retrospective study. The database of the Pathology
patients with a low anxiety level. Department of 2 university hospitals in Edinburgh (Scotland) and Malmo
Disclosure of Interest: None declared (Sweden), and a district general hospital in Spain (general Hospital de
Tomelloso) were searched for patients who have been diagnosed with CC
between May 2008 and August 2013. Endoscopy reports & endoscopic images
P0153 NON-ANAESTHESIOLOGIST ADMINISTERED PROPOFOL IN were retrieved and reviewed; data on lesions, sedation, bowel preparation (type
COLONOSCOPY INTERIM ANALYSIS OF A RANDOMIZED and effect) and endoscopists experience were abstracted. Categorical data are
CONTROLLED TRIAL reported as mean SD. The Fischers exact, the chi-square and the t (unpaired)
A.O. Ferreira1,2,*, J. Torres1, S. Pereira1, S. Dias1, M. Rocha1, R. Pinto3, tests were used to compare datasets. A two-tailed P value of 50.05 was consid-
V. Schuler3, M. Neves3, C. Castanheira3, A.A. Santos3, F. Silva3, M. Cravo1 ered statistically significant.
1
Department of Gastroenterology, Hospital Beatriz Angelo, Loures, 2Department RESULTS: A total of 416 patients (96M/320F; mean age: 67.112.1 years) case
of Gastroenterology, Centro Hospitalar do Algarve, Portimao, 3Department of notes, who were diagnosed with CC, were collected and reviewed.
Anesthesiology, Hospital Beatriz Angelo, Loures, Portugal The colonoscopies had been carried out by senior medical/surgical staff (consul-
Contact E-mail Address: alex.gastrohep@gmail.com tants or associate specialists) in 331 (79.6%). A total of 81 (19.5%) patients had a
mix of findings, previously described as being suggestive of CC in endoscopy,
INTRODUCTION: Propofol allows the best sedation in colonoscopy. There is such as mucosal erythema/oedema (mosaic pattern): 65, colonic mucosa linear
only one Randomized Controlled Trial (RCT) comparing Non-Anaesthesiologist defects (lacerations, tears, ulcers/fractures, mucosal furrows): 10, cat-scratch
Administered Propofol (NAAP) with sedation by an anaesthesiologist. mucosa: 4, and cicatricial lesions: 3.
AIMS & METHODS: Our goal was to compare the incidence of sedation-related Although the use of polyethylene glycol (PEG) offer superior quality of bowel
adverse events (AE), colonoscopy quality, and patient satisfaction between prep effect (as compared to other pre-colonoscopy preparations; P50.0001), this
NAAP and anaesthesiologist sedation. We performed a single blinded RCT was not associated with higher detection rate of (all types) macroscopic findings
with two parallel intervention groups (group A NAAP; group B anaesthe- and/or colonic mucosal defects in specific (P 1.0). Furthermore, mucosal colo-
siologist sedation). In group A, a 40-60 mg propofol bolus was administered nic defects had no association with either the experience of the colonoscopist
followed by 10-20 mg bolus as needed. In group B propofol was administered (P 0.812), or the use of general anaesthesia/propofol (P 0.53), and/or the use
under the anesthesiologist indication. The primary endpoint was the incidence of spasmolytic (hyoscine butylbromide/glucagon), P 0.568.
AE as defined by the World SIVA International Task Force on Sedation. CONCLUSION: A substantial minority of patients with CC (19.5%) had endo-
Secondary endpoints were propofol dose, patient satisfaction, and pain assessed scopic findings indicative of CC. The presence of these findings is not associated
by a 10-point visual analogue scale, procedure and recovery time, and colono- with procedural factors such as endoscopists experience, quality of bowel prep,
scopy quality indicators (cecal intubation rate, withdrawal time, adenoma detec- and/or use of spasmolytic during colonoscopy.
tion rate). A sample size of 330 (1:1) cases was calculated for a power of 90% at a REFERENCES
5% level of significance, and based on the AE incidence in our preliminary 1. Koulaouzidis A and Saeed AA. Distinct colonoscopy findings of microscopic
experience. Patients aged 18-80 with low anaesthetic risk (ASA I-II) were colitis: not so microscopic after all? World J Gastroenterol 2011; 17: 4157-4165.
included (patients characteristics presented in table 1). Herein we present the 2. Suzuki et al. Usefulness of colonoscopic examination with indigo carmine in
interim analysis of the first 100 cases. Statistical analysis was performed with diagnosing microscopic colitis. Endoscopy 2011; 43: 1100-1104.
SPSS version 21. Chi-square, Fischers exact, t-tests and logistic regression were Disclosure of Interest: A. Koulaouzidis Financial support for research from:
used as appropriated. Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
RESULTS: The incidence of AE was 34.3% on group A and 42.4% on group B FalkPharmaUK, Other: Travel support: Dr FalkPharma, Abbott, MSD, K.
(odds ratio 0.709; 95% CI 0.302-1.668; p 0.43). There were no severe (sentinel) Sjoberg: None declared, L. Bartzis Other: Grant from the Hellenic Society of
AE events. The following interventions were necessary: atropine administration Gastroenterology, M. MacNeill: None declared, A. Nemeth: None declared, G.
(0% vs 6.1%); airway repositioning (14.9% vs 9.1%); increase in O2 adminis- Wurm Johansson: None declared, P. Finneron: None declared, A. Lucendo:
tration (8.9% vs 6.1%); increase in fluids rate (4.5% vs 0%). Mean propofol None declared, E. Toth: None declared
dose: group A 222 84 mg vs group B 245 118mg (p 0.276). Procedure times
were 22.24 13.12 and 21.39 10.78 min (p 0.75), withdrawal time was 11.97
10.36 vs 11.84 6.15 min (p 0.949) and recovery time was 62 44 vs 61 22 P0155 A TAILORED SEDATION FOR COLONOSCOPY BY NON-
min (p 0.856) in group A and group B respectively. Patients had no pain (0) in ANESTHESIOLOGISTS: USE OF PROPOFOL TARGET
84.5% vs 88.5% (p 0.946) and reported complete satisfaction with the sedation CONTROLLED INFUSION FOR SAFELY ERASE PATIENTS PAIN
in 84.8% vs 81.2% (p 0.58). Procedural amnesia was reported in 88 vs 93.8% A. Della Rocca1,*, A. Scatto2, P. Tresin3, S. Gallo1, E. Rosa-Rizzotto1,
(p 0.49). All the patients were willing to repeat the colonoscopy under propofol L. Peraro1, E. Guido1, D. Caroli1, B. Licata3, F. De Lazzari1
sedation. Cecal intubation rates were 95.5% vs 93.9% (p 1.0), adenoma detec- 1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
tion rates were 30.4% vs 31.3% (p 0.93). 2
Anesthesiology, Azienda Ospedaliera, 3Anesthesiology, St Anthony Hospital,
Padua, Italy
Patient characteristics Group A(n 67) Group B(n 33) p
INTRODUCTION: Pharmacokinetics and pharmacodinamic of both
Male sex, n (%) 24(35.8) 14(42.5) n.s. Midazolam(M) and Pethidine(P) (the most common drugs for procedural seda-
tion) dont allow during colonoscopy to rapidly adjust dosage according to
Mean age, years (sd) 57(14) 51(18) n.s. patient response and to the complexity and length of the procedure. As result
ASA I/II, n 6/61 7/26 n.s. patients may be too much or not enough sedated. Propofol sedation overcomes
Cardiovascular disease, n (%) 10(14.9) 5(15.2) n.s. these limitations but may expose the patient to dangerous side effetcs such as
Smoking, n (%) 15(22.4) 5(15.2) n.s. hypotension and respiratory depression.
AIMS & METHODS: Demonstrate that Propofol Target Controlled Infusion
Snoring history, n (%) 4(8.0) 2(6.0) n.s. (PTCI) enables properly modified infusion rate (ie total drug dose) in order to
perform a zero pain colonoscopy and without affecting safety. 3 types of sedation
were utilized in this trial: PTCI, MP, Propofol titration (PT). Propofol infusion
CONCLUSION: In the interim analysis NAAP was equivalent to anaesthesiol- was controlled by a TCI pump set on Schnider protocol. Propofol administration
ogist sedation in the rate of adverse events in a low risk population. and monitoring was performed by a nurse trained on recognizing adverse effects
Clinicaltrials.gov (NCT02067065). and on basic resuscitation maneuvers; an anesthesiologist was always on call.
Disclosure of Interest: None declared Colonoscopy started 1 min after infusion was begun. Initial Effect Site Target
Concentration was 2.5 mg/ml, increments of 0.5 mg/ml/min were allowed until
total pain relief. We monitored pts ETCO2, SpO2, NIBP, ECG. At the end of the
procedure pts were transferred to recovery room only when Observers
Assessment of Altertness/Sedation (OAA/S) scale was 4 3 and then discharged
when ALDRETE score was 4 8. Satisfaction was established by Numeric Visual
United European Gastroenterology Journal 2(5S) A173
Scale (NVS, pain evaluation from 1 to 10). A control group (treated with MP)
P0157 SHORT MESSAGE SERVICE (SMS) IN COLONOSCOPY
followed the same protocol.
PREPARATION - PERICLES-I -A FEASIBILITY STUDY
RESULTS: 721 consecutive pts undergoing both diagnostic and operative colo-
noscopy were included. No exclusion critheria were stipulated. 345 pts PTCI at B.M. Walter1,*, P. Klare1, B. Neu1, R.M. Schmid1, S.von Delius1
1
an average drug dosage (ADD) of 156.869.6 mg; 376 pts MP at an ADD, II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munchen,
respectively, of 4.181.3 mg and 47.55.5 mg; The 2 groups were clinically Germany
homogeneus (M 55.4%; F 44.6%; ASA 1-2 90%, ASA 3 10%) Adverse Contact E-mail Address: benjamin.walter@lrz.tum.de
events: Hypoxemia (So2590%): PTCI 0.Mp 8 (p50.05); Apnea:
PTCI 3, Mp 26 (p50.001); Hypotension (SBP590mmHg): PTCI 44, INTRODUCTION: High quality preparation is essential for colonoscopy. A
Mp 36 (p ns); Bradycardia (540 bpm) PTCI 5, Mp 11 (p ns). sufficient colon cleaning improves adenoma detection rate and reduces rates of
Apnea was treated successfully with neck extension. Outcome and satisfaction: necessary re-colonoscopies due to invalid preparation. Several studies showed
mean NVS (all procedures) PTCI 0.361.2 vs 1.072.1 MP (p50.001); mean importance of patients education and correct pre-colonoscopy diet. Only few
NVS (only difficult proceures) PTCI 0.241 vs 1.972.8 MP (p50.001); mean studies have evaluated feasibility of using new media such as SMS in high quality
cecal intubation time (intubation rate was 98.4%) PTCI 6.143.6 min vs MP preparation. The PERICLES-project (prospective studies for improvement of
7.524.8 min (p50.01), mean time for the entire procedure (colonoscopy colonscopy preparation by optimized visualisation) aims to optimize patient gui-
recovery time): PTCI 38.7615.1 min vs MP 53.9514.6 min (p50.001). dance by reminding the most important steps during colonoscopy preparation.
PTCI total mean dosage was compared with the mean dosage of 50 colonosco- AIMS & METHODS: Objective: To assess the feasibility of colonoscopy pre-
pies in propofol titration, at the univariate analysis less total propofol (adjusted paration using SMS (short message service) starting 4 days prior colonoscopy
for BMI, Sex, Age, Endoscopist, Abdominal surgery) was administered using appointment and to assess sufficient colonoscopy preparation.
PTCI than the titration method: 156.8569.63 vs 212.5085.70 (p50.0001). Design: A feasibility study Setting: Tertiary care center, university hospital.
CONCLUSION: Propofol TCI provide a extremely flexible technique which Subjects: Patients scheduled for out-patient colonoscopy at a university hospital.
ensures a sedation tailored to the individual patient and gives the possibility to Interventions: Patients enrolled in the SMS study group get SMS information at
guarantee an effective sedation for long lasting procedures without affecting different timepoints according to the next step of colonoscopy preparation and
recovery time. The final results are the opportunity to totally relieve pain, high diet information. Data of out-patient colonoscopies with regular preparation
performance (time length and quality of recovery) and less operator-dependent procedure were collected as control group during time of SMS study.
process. RESULTS: Colonoscopy could be performed in all patients included in the study.
Disclosure of Interest: None declared Overall patient satification receiving SMS based information was high. Asked if
the SMS reminder system was helpful to get the colonoscopy preparation done (1
not helpful to 10 very helpful) an average score of 7.8 was counted (n 18). On the
P0156 HOW WELL DOES RADIOLOGY PREDICT COLITIS? contrary asked if the SMS reminder system was inhibitory (1 not inhibitory to 10
CORRELATING IMAGING WITH ENDOSCOPY; A very inhibitory) an average of 1.1 was counted (n 19). The average total BBPS
RETROSPECTIVE STUDY was significantly higher than in the control group (MeanSEM 7.316 0.2967
A. Sinha1, J. Gulliver1,*, M. Shaw2, R. Makins1 (SMS-group), MeanSEM 6.269 0.1925 (control group); good bowel prepara-
1
Gastroenterology, 2Radiology, Gloucestershire Hospitals NHS Trust, tion for colonoscopy 5). BBPS calculated for the different colon regions.
Cheltenham, United Kingdom LC Left colon (MeanSEM 2.5000.1357 (SMS group) MeanSEM
Contact E-mail Address: ashish.sinha@glos.nhs.uk 2.1380.06530 (control group)), TC transverse colon (MeanSEM
2.4000.1124 (SMS group) MeanSEM 2.1150.06875 (control group)),
INTRODUCTION: A common indication for endoscopic assessment of the large RC right colon (MeanSEM 2.4000.1124 (SMS group) MeanSEM
intestine is to clarify an abnormal finding on either cross sectional or contrast 2.0150.07325 (control group)) were higher than in the control group.
radiological imaging. Our aim was to assess how often a positive diagnosis of CONCLUSION: A SMS (short message service) system in colonoscopy prepara-
colitis of any form was made following either CT scanning or barium enema. We tion works is stable and effective. Quality of colonoscopy preparation was higher
then aimed to correlate these radiological findings with those seen at a subse- than in regular preparation procedure. Patients were highly satisfied by using the
quent endoscopy. SMS system during colonoscopy preparation.
AIMS & METHODS: The endoscopy database at Gloucestershire Hospitals Disclosure of Interest: None declared
NHS Foundation Trust was reviewed for procedures performed between
January 2008 and June 2013. Cases where endoscopy was performed for the
indication of abnormal radiological findings were selected. The patients radi- P0158 WHY DONT WE RETRIEVE ALL THE ENDOSCOPIC RESECTED
ology reports were reviewed and the cases where colitis or inflammation was POLYPS?
described as possible differentials were selected. We then compared these radi- C. Fernandes1,*, R. Pinho1, S. Leite1, L. Proenca1, A. Rodrigues1, L. Alberto1,
ological findings with those seen on endoscopy for positive correlation. The I. Ribeiro1, T. Pinto-Pais1, A. Ponte1, J. Silva1, J. Fraga1, J. Carvalho1
endoscopic finding of diverticular disease was taken as a positive correlation 1
Gastroenterology, C. HOSPITALAR VILA NOVA GAIA, V N Gaia, Portugal
where relevant. Histology reports from the biopsies taken during the endoscopic
procedures were also reviewed to confirm the endoscopic findings. INTRODUCTION: Colonoscopy is able to diagnose, resect and retrieve colonic
RESULTS: Between January 2008 and June 2013, 562 colonoscopies or flexible polyps. The latter is of major importance to allow an accurate histological eva-
sigmoidoscopies were performed as a result of an abnormality seen on radiolo- luation. Factors associated with failed polyp retrieval are not yet clear.
gical imaging. In 168 (30%) a positive diagnosis of colitis was mentioned on the AIMS & METHODS: To evaluate the prevalence of failed polyp retrieval; to
radiology report. Demographics showed a fairly even sex distribution with 53% define factors associated with polyp retrieval failure.
of patients female, 47% male. The ages ranged from 22-98 with a mean age of A single center retrospective study that considered all the resected polyps by
60.9 years. A total of 5 cases were excluded, with the colonoscopy failing to reach snare in consecutive colonoscopies performed between September 2011 and
the region of interest in 4 cases. December 2012. Eleven gastroenterology specialists and 3 residents were consid-
Endoscopy confirmed mucosal inflammation in 60 of the 163 cases (37%) ered as endoscopists. Demographic and endoscopic data obtained through the
whereas the endoscopy was reported as normal in the remaining 103 cases (63%). colonoscopy report.
In patients with positive endoscopic correlation, biopsies were taken in 34 (57%) Statistical analysis (SPSS v.19): Chi-square, t-student.
of cases. Biopsies were not taken in cases where diverticular disease was identified RESULTS: 496 colonoscopies were evaluated, corresponding to 484 patients
and considered a positive diagnosis. (male gender 66.1%, mean age 63.4 years [10.2]). Considering a total of 1111
In those with histological specimens 28 of the 34 (82%) showed histology con- resected polyps, 52 (4.7%) were not retrieved. A deficient bowel preparation
sistent with an inflammatory process. Of these the majority (57%) showed (p 0.0006), a coloretal surgery history (p 0.008), a higher number of resected
Crohns disease. 6 specimens showed no inflammatory change on histology polyps (p50.0001), a smaller size of resected polyps (p50.0001), a right-side
despite a macroscopic impression of inflammation. location (p 0.0006) and a cold snare resection versus current snare resection
Interestingly 2 biopsy series were taken despite negative endoscopic correlation, (p 0.0007) were factors associated with failed polyp retrieval. Colonoscopy
of which 1 was confirmed as lymphocytic colitis on histology. Another showed performed by a resident (p 0.81), under deep sedation (p 0.94) or with diver-
features of Crohns on histology (this patient had known Crohns). ticulum (p 0.44) were not related with failed polyp retrieval.
CONCLUSION: 37% of the cases in our series referred for endoscopic evalua- CONCLUSION: In our study the polyp retrieval failure prevalence was 4.9%. A
tion after the finding of colitis on radiological imaging were confirmed to have 1) deficient bowel preparation, 2) a colorectal surgery history, 3) a greater number
colonic inflammation at endoscopy. This suggests that there is a limited correla- of resected polyps, 4) a smaller size of the resected polyps, 5) a righ-side location
tion between radiological and endoscopic imaging when a diagnosis of colitis is and 6) a cold snare resection were associated with polyp retrieval failure.
being considered. Disclosure of Interest: None declared
Further studies are required to determine whether a number of parameters con-
sidered together to create a scoring system would increase the likelihood of a
positive pick up at endoscopy following colitis identified on radiological imaging, P0159 FUSE COLONOSCOPY YIELDS HIGHER DETECTION OF
thereby improving diagnostic yield and reducing the number of unnecessary ADVANCED AND MULTIPLE ADENOMAS AS COMPARED TO
procedures. Interestingly, with one diagnosis of lymphocytic colitis made on STANDARD FORWARD VIEWING COLONOSCOPY: A POST-HOC
samples from endoscopically normal colon, an argument could be made for PER PATIENT ANALYSIS FROM A RANDOMIZED COMPARATIVE
taking biopsy series in all cases to exclude microscopic colitis. TRIAL
Disclosure of Interest: None declared C. Hassan1,*, I. Gralnek2
1
ONRM Hospital, Rome, Italy, 2Rambam Health Care Campus, Haifa, Israel
Contact E-mail Address: cesareh@hotmail.com
INTRODUCTION: As compared with Standard Forward Viewing (SFV) colo-
noscopy, Full Spectrum Endoscopy (Fuse) colonoscopy has been shown to sig-
nificantly increase the yield of adenomas detected (per lesion analysis) [1].
A174 United European Gastroenterology Journal 2(5S)
However, the accuracy of FUSE based upon a per-patient analysis has not fully Table to abstract P0160
been addressed.
AIMS & METHODS: We performed a post-hoc analysis of the data from a Patient demographics
recently completed international, multicentre, randomized trial (NCT01549535)
in which 197 patients underwent same-day, back-to-back tandem colonoscopy Sex (%)
with SFV- and FUSE-colonoscopes. The per-patient detection rate of polyp/
advanced adenoma was calculated for each of the two colonoscopy techniques Male 66 (66%)
according to polyp size and multiplicity (3 polyps). The relative detection rate Female 34 (34%)
was defined as the ratio between the number of patients classified by either SFV Disease extent (%)
or FUSE colonoscopy in each lesion category and the cumulative detection with Extensive 87 (87%)
both of the colonoscopy techniques (SFVor FUSE) for the same lesion category.
Statistical analysis was performed by Chi-square test. Left-sided 13 (13%)
RESULTS: We found 111, 23 and 9 patients presenting with at least one 5mm, Disease duration (years) (Median, 24 (13 33)
6-9mm, or 10mm polyp respectively, while 22 and 27 additional patients had as interquartile range)
their most severe lesion an advanced adenoma or multiple adenomas, respec- Age at the time of dysplasia diagnosis 61 (54 69)
tively. The relative sensitivity of SFV and FUSE for each type of lesion is (years) (Median, interquartile range)
shown in Table 1. In detail, the sensitivity of FUSE was statistically significantly
superior to SFV for all categories except for polyps 10mm. As compared to
SFV colonoscopy, FUSE detected an additional 9 patients with multiple adeno-
mas, resulting in a relative per-patient sensitivity of 94%, as compared with 27% CONCLUSION: Patients with endoscopically resectable, well-circumscribed
for SFV colonoscopy. dysplastic lesions within the segment of colitis may be appropriately managed
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears with endoscopic resection. However, close surveillance is necessary given the
to be more effective in identifying patients with multiple polyps and polyps up to relatively high rate of recurrence.
9 mm in size, including 6-9mm advanced adenomas. These data appear to further Disclosure of Interest: None declared
demonstrate the clinical relevance of the additional adenoma detection of FUSE
as previously shown at a per lesion level [1].
REFERENCES P0161 LOW-GRADE DYSPLASIA IN ULCERATIVE COLITIS: IMPACT
[1] Gralnek IM, et al. Standard forward-viewing colonoscopy versus full-spec- OF LESION SHAPE AND SIZE ON PROGRESSION TO HIGH-
trum endoscopy: an international, multicentre, randomised, tandem colonoscopy GRADE DYSPLASIA OR COLORECTAL CANCER
trial. Lancet Oncol 2014; 15: 353-360. C.H. R. Choi1,*, A. Askari1, A. Ignatovic-Wilson1, J. Warusavitarne1,
Disclosure of Interest: None declared M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, T. Graham2, A.L. Hart1
1
Academic Institute, St. Marks Hospital, 2Tumour biology, Barts Cancer Institute,
Queen Mary University of London, London, United Kingdom
P0160 DISCRETE DYSPLASTIC LESIONS IN ULCERATIVE COLITIS Contact E-mail Address: pacoblue@gmail.com
MAY BE ADEQUATELY MANAGED ENDOSCOPICALLY: A LONG
TERM FOLLOW-UP STUDY INTRODUCTION: One of the most challenging aspects of managing low-grade
C.H. R. Choi1,*, A. Ignatovic-Wilson1, A. Askari1, J. Warusavitarne1, dysplasia (LGD) in ulcerative colitis (UC) is the identification of patients who
M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, A.L. Hart1 will progress to high-grade dysplasia (CRC) or colorectal cancer (CRC). The aim
1
Academic Institute, St. Marks Hospital, London, United Kingdom of this study was to identify risk factors associated with progression to HGD or
Contact E-mail Address: pacoblue@gmail.com CRC in UC patients diagnosed with LGD.
AIMS & METHODS: Patients with UC who were diagnosed with LGD between
INTRODUCTION: While there is evidence to support endoscopic resection of 1990 and 2012 were identified from the UC surveillance database of a large
adenoma-like mass (ALM) occurring in patients with ulcerative colitis (UC), its tertiary centre in the UK and followed up to 1st January 2013. Data on patient
long-term follow up data is currently limited. The aim of this study is to evaluate demographics, endoscopic and histological variables at the time of the first LGD
the long-term outcomes of patients with UC who have had an endoscopic resec- episode were collected and correlated with progression to HGD or CRC, our
tion of dysplasia within segment of bowel affected by colitis. primary outcome measure. Time to event analysis was performed using Cox
AIMS & METHODS: All patients who had their dysplastic lesions resected proportional hazards methods with a Bonferroni adjusted significance level
endoscopically between 1998 and 2008 were retrospectively identified from the (p 0.0022).
endoscopic and histology databases. Patients who were immediately referred to RESULTS: A total of 189 patients were evaluated during 1,100 patient-years of
colectomy were excluded. Medical records, endoscopy and histology reports were follow up from the date of the first LGD diagnosis (median, 53 months; inter-
reviewed to determine the primary study outcome, which was defined as no quartile range, 19 92 months). Overall, 38 (20.1% of study population) had
further dysplasia episode, recurrence of dysplasia, or development of colorectal progressed to HGD (16 patients) or CRC (22 patients). Table 1 shows the variables
cancer (CRC). significantly associated with progression to HGD or CRC on univariate analysis.
RESULTS: A total of 100 patients underwent endoscopic resection for 121 dis- A statistically non-significant trend towards the progression to HGD or CRC was
crete dysplastic lesions during the study period (table 1). The median follow-up observed in those patients with history of primary sclerosing cholangitis (hazard
duration from the time of dysplasia resection was 70 months (interquartile range ratio (HR), 3.54; p 0.018), a shortened colon (HR, 2.75; p 0.024), multiple
(IQR), 53 89 months). The Paris classifications of the resected lesions were: Ip episodes of dysplasia (HR, 2.59; p 0.005), and histological active inflammation
(60 lesions, 50.4% of 121 lesions), Is (36, 29.8%), IIa (3, 2.5%), IIb (4, 3.3%), in the segment of LGD (HR, 2.20; p 0.025). At the multivariate level, only non-
IIa/c (1, 0.8%), and lateral spreading tumour (1, 0.8%). Remaining 16 lesions polypoid shape (HR, 7.3; 95% confidence interval (CI), 2.4 21.8; p50.001),
(13.2%) were described as appearance suspicious for dysplasia associated lesion lesion size one centimeter (cm) or bigger (HR, 4.2; 95% CI, 1.3 13.3;
or mass (DALM), where Paris classification was not recorded. Median size of p 0.015) remained significant variables contributing to HGD or CRC.
the resected lesions was eight millimetres (IQR, 4 15 millimetres). Lesions were
removed using snare polypectomy (66 lesions, 54.5% of 121 lesions), EMR (30, Hazards 95% confidence
24.8%), hot biopsy (21, 17.4%) or ESD (4, 3.3%) techniques. Histology showed Variables Categories ratio (HR) interval (CI) P
low-grade dysplasia (LGD) in 111 (91.7% of 121 lesions) and high-grade dyspla-
sia (HGD) in 10 lesions (8.3%). Pathologists interpretations on the lesions were Lesion shape Polypoid x 1 10.0 58.1 50.001
as follows: histological features favour DALM (36 of 121 lesions, 29.8%) favour Non-polypoid 24.1 1.5 22.6
sporadic adenoma (56, 46.3%), or distinction not possible on histological Invisible] 5.8
grounds alone (29, 23.9%). Overall, 23 patients (23% of study population) Lesion size 51cm 1 4.8 41.3 50.001
had developed recurrent episode of dysplasia in median of 41 months since the 1cm 14.1
time of resection (IQR, 16 55 months). Seven of these patients underwent Stricture No 1 2.4 21.1 50.001
colectomy: cancer was detected in two patients (Dukes A and C), but no Yes 7.1
other patients had HGD or CRC in surgical specimen. The patient who devel- Previous indefinite No 1 1.9 8.4 50.001
oped Dukes C cancer did not have surveillance colonoscopy for five years prior dysplasia Yes 4.0
to the cancer diagnosis. The cumulative incidence of recurrent episode of dyspla- Pathologists interpretation Adenoma more likely 1 1.4 109.4 50.001
sia following endoscopic resection was 3.1% in 1 year, 7.4% in 2 years, 11.9% in on histological features Distinction not 12.2 5.1 273.6
clear 37.2
3 years, 16.7% in 4 years and 22.0% in 5 years.
UC associated dys-
plasia more likely
Multifocal dysplasia No 1 1.6 6.0 .001
Yes 3.1
INTRODUCTION: New endoscopic technologies improve visibility of early col- P0164 ANALYSIS OF THE BLEEDING AFTER THE ENDOSCOPIC
orectal cancers. However, flat lesions especially in lateral spreading tumor of the SUBMUCOSAL DISSECTION (ESD) AND THE ENDOSCOPIC
non-granular type (LST-NG) are sometimes hard to detect even with such mod- MUCOSAL RESECTION (EMR) OF COLORECTAL NEOPLASMS
alities. -glutamyl-transpeptidase (GGT) is poorly expressed in normal tissue, FOR THE PATIENTS TAKING ANTI-THROMBOTIC AGENTS
but overexpressed on the cell membrane of various cancer cells in vivo. The D. Okamoto1,*, M. Tosa1, D. Komazawa1, H. Ito1, N. Dairaku1, T. Ikeda1, S.-
use of -glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been I. Ikeya1, H. Nakayama1, N. Hiwatashi1, S. Takahashi1
reported to show specific and immediate fluorescence activity with overexpressed 1
Gastroenterology, Iwaki Kyoritsu General Hospital, Iwaki city, Fukushima, Japan
GGT in tumor. This fluorescence active probe is expected to be applied to a new Contact E-mail Address: oka1572@gmail.com
modality for cancer-selective fluorescence imaging1).
AIMS & METHODS: This pilot study aimed to evaluate ex-vivo fluorescent INTRODUCTION: Recently, EMR and ESD for the patients with many com-
imaging of colorectal tumor using the GGT fluorescence activity probe. 30 plication has been increasing. Anti-thrombotic therapy is usually provided to
endoscopically resected colorectal tumors from March 2013 to March 2014 prevent cerebro-cardiovascular events. In 2012, the endoscopic treatment guide-
were included in this study. 1000l of gGlu-HMRG in a concentration of lines for the patients taking anti-thrombotic agents were published from Japan
either 50M or 500M was sprayed on the freshly resected specimen fixed on Gastroenterological Endoscopy Society. Thereafter, in our institution, we per-
a black board. Fluorescent images of the resected specimen were taken after form endoscopic treatment in accordance with the guidelines. Delayed bleeding is
spraying gGlu-HMRG every 30 seconds for 15 minutes using a dedicated ima- one of the major complications of EMR and ESD, but little is known about the
ging machine providing 550nm of blue excitation light (Discovery; INDEC Inc.). influence of anti-thrombotic therapy.
The fluorescence image 7 minutes after spraying (when fluorescence activity had AIMS & METHODS: In this study, we analyzed the delayed bleeding rate after
almost reached equilibrium) was evaluated by 3 endoscopists. The fluorescence colorectal EMR and ESD for the patients taking anti-thrombotic agents. This is
activity was judged positive or negative. Lesions showing partial fluorescence a retrospective study for the consecutive patients treated in our center from
activity were considered positive. This pilot study assessed the proportion of February 2014 to January 2013. Furthermore, we divided the patients taking
lesions positive for fluorescence and correlation with their clinicopathological anti-thrombotic agents into three groups, and compared the bleeding rate and
characteristics. the clinical background with control group. [A]: anti-coagulant continuation
RESULTS: The clinicopathological features were; mean age was 687, male/ group, [B]: heparin or anti-coagulant single agent replacement group, [C]:anti-
female 15 /15, mean tumor size: 3913mm, macroscopic type: lateral spreading coagulant discontinuation group. Statistical analysis was made by Chi-squared
tumor of the granular type (LST-G)/LST-NG 20/10, adenoma/ carcinoma in test (significance: p50.01).
adenoma 13/17. 20 (67%) of images after 7 minutes were positive for fluores- RESULTS: We treated 328 patients with 633 colorectal neoplasms by EMR, and
cence activity and 10 (33%) were negative. The mean tumor size of lesions the delayed bleeding rate was 1.9% (12/633). Male/Female ratio was 237:91 and
positive for fluorescence activity was 42mm and that of negative was 32mm. the mean age was 64.5 years. 63 patients (19.2%) with 129 neoplasms (20.4%)
Of 13 adenoma, 7 (54%) lesions were positive and 6 (46%) were negative. Of received anti-thrombotic therapy and divided into three groups, [A]:16/28, [B]:21/
17 carcinoma in adenoma, 13 (76%) lesions showed positive and 4 (24%) were 45, [C]:26/56 (patients/neoplasms). Patients taking the anti-coagulant agents were
negative. 16 LST-G lesions (80%) and 4 LST-NG lesions (40%) revealed posi- significantly older than control group (P50.01). The delayed bleeding rate was 1/
tive. 18 (75%) of 24 lesions in 50M gGlu-HMRG and 2 (33%) of 6 lesions in 28(3.6%) in group A, 2/45(4.4%) in group B and none (0/56) in group C. We
500M revealed positive. found no significant differences about the delayed bleeding rate when we com-
CONCLUSION: Topically spraying gGlu-HMRG to identify GGT activity in ex pared each group with the control group (9/504; 1.9%). On the other hand, we
vivo colorectal tumors provides rapid and selective fluorescent imaging. treated 47 patients with 47 neoplasms by ESD. Male/Female ratio was 32:15 and
REFERENCES the average age was 68.7 years. 11 patients (23.4%) received anti-thrombotic
1) Urano Y et al. Sci Transl Med 2011. agent and divided into three groups, [A]:4, [B]:2, [C]:5. In ESD, patients taking
Disclosure of Interest: None declared anti-thrombotic agents were significant older (P50.01), and the delayed bleeding
was not recognized in all cases. In addition, cerebro-cardiovascular events did not
occur in all cases during the clinical course of EMR and ESD.
P0163 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GIANT CONCLUSION: We found no significant differences about the delayed bleeding
COLORECTAL LATERAL SPREADING TUMORS LARGER THAN rate between patients taking anti-thrombotic agents and control group. Although
10 CM: IS IT FEASIBLE? this is a single institutional study, we thought that EMR and ESD for the patients
D.H. Jung1,*, Y.H. Youn1, J.-H.K. 1, J.J. Park1, H. Park1 taking anti-thrombotic agents could be performed without increased risk of
1
Yonsei University College Of Medicine, Seoul, Korea, Republic Of delayed bleeding in accordance with the guidelines.
Contact E-mail Address: leah1004@yuhs.ac Disclosure of Interest: None declared
INTRODUCTION: The efficacy of colorectal endoscopic submucosal dissection INTRODUCTION: Bowel cancer is the third most common cancer in the United
(ESD) has been reported mainly from Japanese referral centers. However, it is Kingdom forming up to 13.6% of all newly diagnosed cancers(1). Bowel cancer
technically difficult and is associated with a higher risk of adverse events than screening colonoscopy allows early polyp detection at a curable stage. Complete
endoscopic mucosal resection (EMR), especially for novices in colorectal ESD resection and follow-up of large polyps is crucial to prevent malignant
with little experience in gastric ESD. progression.
AIMS & METHODS: We aimed to evaluate the results of colorectal ESD during AIMS & METHODS: The aim of this study was to review the management of
the clinical learning curve. Colorectal ESD was performed by 2 endoscopists who polyps with diameters 2 cm, particularly of sessile polyps, to assess the enbloc
had expertise in colonoscopy and colonic EMR but had experience of fewer than resection rates, completeness of resection using endoscopic mucosal resection
5 cases of gastric ESD. A total of 120 cases consisting of the first 60 cases of each (EMR) vs surgery and the incidence of malignant polyps.
endoscopist were retrospectively investigated. The main outcome measurements Patients were identified retrospectively from a regional bowel screening pro-
were procedural time, en bloc resection rate with tumor-free margins (R0 resec- gramme database. Details of index colonoscopy including polyp characteristics,
tion rate) and adverse events rate. From among the clinical characteristics method of resection and complications were recorded. Histology results were
obtained before the ESD procedure, factors that affected the main outcome reviewed for all polyps. Outcomes from follow-up endoscopic surveillance were
measurements were identified. analysed.
RESULTS: (Clinical characteristics) Tumors were located at the rectum, left RESULTS: One hundred and fifty-eight patients (102 males, 56 females, mean
colon, right colon and junction (dentate line, SD junction, hepatic flexure, splenic age 66.2 years) with polyps 2 cm were identified from 2182 screening colonos-
flexure, ileocecal valve) in 22, 19, 51 and 28 cases, respectively. With regard to the copies from January 2010 to August 2013. Caecal intubation rate was 96.8% in
macroscopic type, 44, 23, 5 and 8 cases were granular-type laterally spreading this group.
tumor (LST), nongranular-type LST, depressed and protruding type, respec- Largest polyp size for each patient ranged from 20 to 60 mm (mean 26.6 mm).
tively. Of the 120 cases, 20 cases had factors which reflected fibrosis of the The incidence of adenocarcinoma was 11.9% (n 19), all located within the left
submucosal layer (sporadic localized lesions with ulcerative colitis, local residual colon, with 12 requiring surgical resection.
tumors after EMR, etc.). The mean tumor diameter was 38.518.3 mm. The One hundred thirty nine patients (n 139) had 155 non-malignant large polyps,
histological analysis showed 59 adenocarcinomas and 61 adenomas. mostly tubulovillous or villous histology (n 110, 79%).
(Outcomes) The mean procedural time was 101.765.9 min. A total of 113 Thirty-six patients had 37 sessile polyps which underwent primary resection by
cases (94.2%) were resected en bloc, and the R0 resection rate was 80.0% (96/ EMR (n 26) or surgery (n 11).
120). Perforation and postoperative hemorrhage occurred in 8 (6.7%) and 2 Polyp diameter was larger in the surgery group with mean polyp diameter of 40.4
(1.7%) cases, respectively. Multivariate analyses revealed that lesions in junction mm vs 28.0 mm (p50.05).
and lesions with factors reflecting fibrosis were significantly associated with EMR enbloc resection rate was 11.5% (n 3 out of 26). Completeness of excision
longer procedural time (90 min) and a lower en bloc resection rate. Larger was 38.4% (n 10) at 3 months and 92.3% (n 24) at 1 year. EMR complica-
lesions (40 mm) and lesions resected in the first half (up to 60 cases) were tions included 1 perforation, 1 post polypectomy syndrome and 1 bleed.
also associated with longer procedural time. Surgical resection included: anterior resection in 2, TEMS excision in 7 and right
CONCLUSION: Colorectal ESD is feasible and safe when performed by experts hemicolectomy in 3.
in colonoscopy with little experience of gastric ESD. For novices in colorectal CONCLUSION: Sessile polyps 2 cm are relatively uncommon in an asympto-
ESD, beginning with lesions in junction and lesions with factors reflecting fibro- matic bowel cancer screening programme (37 in 2182 colonoscopies). They can
sis may not be advisable. be successfully resected by EMR without recurrence in 92.3% at 1 year providing
Disclosure of Interest: None declared a 3 month site check is performed in all piecemeal polypectomies.
REFERENCES
(1) Cancer for National Statistics. Office for national statistics, http://www.ons.-
P0186 A VALIDATION STUDY OF 4 TYPE BOWEL CLEANSING SCALE: gov.uk/ons/dcp171778_263537.pdf (2010).of InterestDisclosure: None declared
ARONCHICK, BOSTON BOWEL PREPARATION, OTTAWA,
HAREFIELD SCALE
S.H. Kim1,1, I.K. Yoo1, J.M. Lee1, S.J. Nam1, H.S. Choi1, E.S. Kim1, B. Keum1, P0188 ARE THERE ANY PARAMETERS TO PREDICT BILE DUCT
Y.T. Jeen1, H.S. Lee1,*, H.J. Chun1, C.D. Kim1 STONES IN BILIARY PANCREATITIS BEFORE ERCP
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology, A. Sayilir1,*, B. Odemis1, E. Parlak1, S. Disibeyaz1, Y. Beyazit1, N. Sasmaz1
1
Korea University Anam Hospital, Seoul, Korea, Republic Of Gastroenterology, TURKIYE YUKSEK IHTISAS TEACHING AND
Contact E-mail Address: kimseunghan09@gmail.com RESEARCH HOSPI, ANKARA, Turkey
Contact E-mail Address: drabdurrahim@gmail.com
INTRODUCTION: Total colonoscopy is a potent tool for assessing the large
bowel. There are various bowel preparation scale, but few bowel preparation INTRODUCTION: The role of endoscopic retrograde cholangiopancreaticogra-
scale have been validated. Diversity in bowel preperation scales can cause a lot phy (ERCP) for the management of acute biliary pancreatitis (ABP) remains a
of confusion on decisions in the clinical environment and much confounding of controversial topic. Pre-ERCP detection of biliary stones in patients with ABP
results within clinical studies. However there have been no clinical trials that may strengthen the indication for a subsequent ERCP.
compared 4 types of bowel preparation scales. The aim of this study is to AIMS & METHODS: The aim of this study was to determine the value of
assess the compatibility and reliability of 4 different types of bowel preparation several clinical and laboratory parameters as non-invasive pre-ERCP indicators
scales. _
of bile duct stones. Patients presenting to Turkiye Yuksek Ihtisas Teaching and
AIMS & METHODS: This study compared 4 types of bowel preparation scales: Research Hospital (TYIH) between 1 January 2010 and 31 August 2011 with
Aronchick scale (AC), Boston bowel preparation scale (BBPS), Ottawa scale ABP, who underwent ERCP within 72 hours of the onset of symptoms were
(OS), Harefield cleansing scale (HCS). 5 trainees read 20 total colonoscopy stu- screened, and eligible patients were enrolled in the study. Receiver operating
dies twice, with an interval of 1 month. We used Intraclass correlation coefficient characteristic (ROC) curve analysis was used to determine the optimal cut-off
(ICC) to evaluate Intra-observer (test-retest) consistency and inter-observer relia- value of several parameters, such as AST, ALT, GGT, ALP, bilirubin, common
bility of the BBPS and the OS. The unweighted kappa statistic was used to assess bile duct (CBD) width on USG and duration of syptoms, with the highest sensi-
the reliability of the AC and the HCS. tivity and specificity for predicting the presence of CBD stones.
RESULTS: Total 400 ratings were completed in this study. Inter-observer and RESULTS: A total of 59 patients [20 (33.89%) males and 39 (66.1%) females]
intra-observer reliability were assessed by ICC and kappa statistic. ICC for OS were included in the final analysis. Areas under the curve for CBD width, timing
was 0.73 (95% CI, 0.52-0.87, p 5 0.0001), BBPS 0.76 (95% CI, 0.59-0.88, p 5 of ERCP, AST, ALT, GGT, ALP and bilirubin were 0.753, 0.630, 0.548, 0.370,
0.0001), inter-observer kappa for AC was 0.29 (95% CI, 0.19-0.42, p 5 0.0001), 0.577, 0.568 and 0.495, respectively. As a predictor of the presence of a biliary
HCS 0.27 (95% CI, 0.15-0.41, p 5 0.0001). Intra-observer scores for OS, ICC stone(s), CBD width was found to have the highest sensitivity, specificity,
A182 United European Gastroenterology Journal 2(5S)
negative predictive value (NPV), positive predictive value (PPV) and general
P0190 VALIDATION OF A RISK SCORE FOR PREDICTING POST-ERCP
accuracy. With a cut-off value of 8.55 mm for CBD width, sensitivity and spe-
PANCREATITIS BASED ON THE EUROPEAN GUIDELINE
cificity were 75% with a NPV of 47.4%, PPV of 90.9% and general accuracy of
75. A summary of ROC analyses for the other parameters is provided in table 1. A. Mariani1,*, M. Di Leo1, A. Ambrosi2, M.L. Grazie1, A. Giussani1,
Table 1. ROC analysis for the value of several labortory and clinical parameters P.A. Testoni1
1
as pre-ERCP indicators of the presence of bile duct stones. Division of Gastroenterology and Gastrointestinal Endoscopy Vita-Salute San
Raffaele University Scientific Institute San Raffaele, Milan, Italy, 2Vita-Salute
San Raffaele University Scientific Institute San Raffaele, Milan, Italy, Milan,
Sensitivity Specificity NPV PPV
Italy
Cut-off AUC (%) (%) (%) (%) Accuracy
Contact E-mail Address: mariani.alberto@hsr.it
CBD width (mm) 8.55 0.753 75 75 47.4 90.9 75
INTRODUCTION: Post-ERCP pancreatitis (PEP) is an important complication
Duration (hours) 25.5 0.630 60.9 61.5 30.8 84.8 61 in biliopancreatic endoscopy, associated with morbidity and mortality. While
AST (u/L) 224.5 0.548 56.5 53.8 25.9 81.3 55.9 clinical and technical risk factors for PEP have been elucidated, the identification
ALT (u/L) 156.2 0.370 43.2 40.0 13.8 76 42.6 of a simple and valid risk score to predict PEP remains a challenge.
GGT (u/L) 263 0.577 69.8 70 35 90.9 69.8 AIMS & METHODS: To develop a model to predict the risk of PEP in patients
undergoing endoscopic retrograde cholangiopancreatography (ERCP).
ALP (u/L) 153 0.568 56.8 60 24 86.2 57.4 Methods: A risk score was created based on the prognostic factors for PEP
Bilirubin (mg/dl) 1.54 0.495 54.8 50 20.8 82.1 53.8 identified on the basis of the ESGE Guideline (1) and validated on 1823
ERCPs from an independent, prospectively assembled database (validation
cohort). The predictive performance of the models was tested by ROC analysis
CBD, common bile duct; AST, Aspartat Aminotransferase; ALT, Alanin to identify patients at low and high risk of PEP.
Aminotransferase; GGT, Gama-Glutamyl Transferase; ALP, Alkaline phospha- RESULTS: A score proportional to its regression coefficient was assigned to
tase; AUC, area under the curve; NPV, negative predictive value; PPV: positive each independent prognostic factor: suspected sphincter of Oddi dysfunction
predictive value (SOD) (4.1 points), female sex (2.2 points), previous pancreatitis (2.5 points),
CONCLUSION: Determination of CBD width on ultrasonography and serum young age (2 points), no chronic pancreatitis (1.9 points), normal serum bilirubin
GGT levels are important parameters that may help predict the presence of (1.9 points), precut sphincterotomy (2.7 points), pancreatic injection (2.2 points),
biliary stones prior to endoscopic intervention. large number of cannulation attempts (2.9 points), pancreatic sphincterotomy
Disclosure of Interest: None declared (3.1 points), biliary balloon sphincter dilation (4.5 points), failure to clear bile
duct stones (3.4 points). The AUC of the ROC curve showed a predictive score
performance of 0.9268 (95% C. I. 0.90-0.95 p50.0001). We identified 9.5 as the
P0189 PROCEDURAL DESCRIPTION AND CLINICAL OUTCOMES OF cut-off between low- and high-risk classes, with 88.5% specificity, 81.6% sensi-
A NOVEL COMBINED RETROGRADE-ANTEGRADE ENDOSCOPIC tivity. Considering only severe PEP (n 12), there was a significant difference
APPROACH USING ERCP AND EUS FOR THE MANAGEMENT OF between the two risk classes (p 0.001).
POSTOPERATIVE BILE-DUCT TRANSECTIONS CONCLUSION: We developed and validated a simple risk score to predict PEP.
A.L. Vargas1,*, N. Aleman1, I. Penas Herrero1, C. De la Serna-Higuera1, It could be useful to clinicians for predicting the individual risk of PEP and
C. Almohalla1, F. Garc a-Pajares1, G. Sanchez-Antolin1, M. Perez-Miranda1 directing prophylactic measures, to researchers for designing and interpreting
1
Gastroenterology & Hepatology, Hospital Universitario Ro Hortega, Valladolid, clinical trials, and to policy-makers for saving healthcare resources.
Spain REFERENCES
Contact E-mail Address: mpmiranda5@hotmail.com 1. Dumonceau JM, Andriulli A, Deviere J, et al. European Society of
Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pan-
INTRODUCTION: Postoperative Bile-duct Transections (POBT) are not amen- creatitis. Endoscopy 2010; 42: 503-515.
able to endoscopic therapy. Preliminary data from combined percutaneous-endo- Disclosure of Interest: None declared
scopic approaches are encouraging. Isolated reports of successful retrograde
canalization are intriguing. We hypothesized that aggressive retrograde
(ERCP) and/or antegrade (EUS) attempts at recanalization may salvage P0191 MONITORING RADIATION EXPOSURE IN HEALTH
POBTs for endotherapy, and subsequent serial stenting would induce remodeling PROFESSIONALS DURING ENDOSCOPIC RETROGRADE
and durable resolution as seen in partial strictures. CHOLANGIOPANCREATOGRAPHY
AIMS & METHODS: To assess the feasibility, safety and efficacy of an endo- A.R. Alves1,*, D. Gomes1, P. Mendes2, T. Laranjeiro2, G. Paulo2, J. Santos2,
scopic treatment algorithm of POBTs and to characterize the heterogeneous N. Almeida1, S. Mendes1, R. Mesquita1, E. Camacho1, F. Portela1, C. Sofia1
techniques used to attempt recanalization. 1
Gastroenterology Department, Coimbra Hospital and University Centre,
Since September 2010, 248 consecutive ERCPs were performed at a tertiary Unit 2
Coimbra College of Health Technology, Polytechnic Institute of Coimbra,
for postoperative complications (strictures/leaks) in 150 patients (69 Liver Coimbra, Portugal
Transplant, 81 Other). POBTs were identified in 17 patients (9 Female; Contact E-mail Address: alvess.anarita@gmail.com
age 59.6 [43-79] years) following liver transplant (LT) /cholecystectomy
(CCx) /Other in 7/7/3. Clinical records were retrospectively reviewed for proce- INTRODUCTION: Use of radiation in endoscopic procedures has been increas-
dural data (success, antegrade Vs retrograde, technique) and clinical outcome ing in Gastroenterology, particularly during endoscopic retrograde cholangio-
(immediate POBT remodeling and mid-term clinical resolution). pancreatography (ERCP). Safety radiation limits have been defined for
RESULTS: Recanalization was achieved in 12/17 POBT (70%), by means of persons with occupational exposure to ionizing radiation. Monitoring the effi-
ERCP alone in 5 (4 LT, 1CCx), of ERCP combined with EUS-guided antegrade cacy of protection measures and quality of x-ray systems are recommended.
approach in 6 (2 LT, 3CCx, 1 Other), and EUS alone in 1. Lack of upstream AIMS & METHODS: The objectives of this study were to measure occupational
biliary dilation precluded EUS attempts in 4, and recanalization failed in 1 radiation doses during ERCP in a Gastroenterology department and evaluate the
despite EUS-hepaticogastrostomy (EUS-HG). 5 initial failures underwent surgi- impact of a real time individual dosimeter system in staff behavior. A prospective
cal repair with/without interval external PTBD. 10/12 recanalizations required study was performed, during three phases, in which radiation doses were mea-
forced antegrade/retrograde techniques: using the hard end of a stiff guidewire, sured with individual dosimeters in health professionals: gastroenterologist,
needle-knife, puncture with intraductal hollow needles, transhepatic peritoneo- endoscopy and circulating nurses, radiology technician and anesthesiologist.
scopy or magnetic compression anastomosis. A mean (range) of 1.5 (1-5) ERCPs Phase 1 25 procedures, dosimeter placed under the protection apron, at thor-
were needed to achieve recanalization. Coincidental bilomas were drained in 2 acic level. Phase 2 18 procedures, dosimeter placed outside the protection
POBTS (one transpapillary by ERCP and one transmural by EUS each). 11 apron, at cervical level, simulating absence of radiation protection. Phase 3
Patients have completed 12 treatment courses of serial stenting (2 plastic alone 12 procedures, dosimeter placed in second phase position, but with real time
& 10 covered metal with/without plastic) after 323(180-503) days of stents in exposure levels displayed in a monitor and staff being able to adapt their
place. After a mean follow-up of 353(30-900) days, there were 3 recurrences (1 position.
surgery, 1 currently undergoing stenting, 1 successfully remodeled endoscopi- RESULTS: In phase 2, the following doses were registered: gastroenterologist
cally). Post-procedural or stent related mild cholangitis ensued in 4, and moder- 6.785.99 Sv, endoscopy nurse 7.6312.88Sv, radiology technician
ate post-sphincterotomy bleeding in 1. 6.866.27Sv, anesthesiologist 6.5811.75Sv and circulating nurse
CONCLUSION: 70% of POBTs can successfully be recanalized endoscopically 4.565.45Sv. In phase 1, protection equipment allowed a significant reduction
by means of forced mechanical (guidewires, needles), thermal or magnetic tech- in exposure doses: gastroenterologist 3.374.00 Sv, endoscopy nurse
niques. Antegrade EUS approaches allow salvage of 60% of ERCP failures. Mid- 0.090.16Sv, radiology technician 0.701.55Sv, anesthesiologist
term treatment ouctomes using this algorithm for POBTs appear comparable to 0.430.95Sv and circulating nurse 1.153.03Sv (p50.05). In phase 3, with
those seen with partial postoperative strictures. the change of health professionals position, according to real time values, there
Disclosure of Interest: None declared was a reduction of 44-71% in radiation levels, except for the gastroenterologist
whose change of position was limited by his role in ERCP.
CONCLUSION: The present study showed occupational exposure doses within
the recommendations, proving the efficacy of radiation protective equipments.
Real time knowledge of radiation doses may have a positive impact in profes-
sionals behavior.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A183
P0192 PALLIATIVE BILIARY DRAINAGE FOR KLATSKIN TUMORS: P0194 DOUBLE-BALLOON OVERTUBE-ASSISTED ENTEROSCOPY
ENDOSCOPIC OR PERCUTANEOUS? ERCP IN PATIENTS WITH BILLROTH II GASTRECTOMY: A
A.T. Oliveira1,1,*, S. Campos1, S. Giestas1, N. Almeida1, S. Mendes1, LARGE SERIES REPORT
E. Camacho1, R. Mesquita1, D. Gomes1, A.G. Agostinho2, V. Carvalheiro2, C.-L. Cheng1,*, C.-H. Lin1, J.-H. Tang1, M.-C. Yu2, Y.-N. Tsui1, N.-J. Liu1
C. Sofia1 1
Gastroenterology, 2General Surgery, Chang Gung Memorial Hospital, Taoyuan
1
Gastroenterology, 2Radiology, Centro Hospitalar e Universitario de Coimbra, County, Taiwan, Province of China
Coimbra, Portugal Contact E-mail Address: chiliang.cheng@gmail.com
INTRODUCTION: At the time of the diagnosis only 20% of patients with INTRODUCTION: Data on double-balloon overtube-assisted enteroscopy to
Klatskin Tumors have resectability criteria. Thus, the majority will require pal- facilitate ERCP (DBE-ERCP) in patients with Billroth II gastrectomy is limited.
liative procedures for maintenance of biliary drainage. AIMS & METHODS: The primary aim was to evaluate DBE-ERCP success in
AIMS & METHODS: The aim of this study is to compare two palliative non- patients with Billroth II gastrectomy and suspected pancreaticobiliary disease.
surgical methods (endoscopic and percutaneous approach) in terms of therapeu- The seconday aim was to examine the safety and efficacy of DBE-ERCP.
tic efficacy and complications. Patients with Billroth II gastrectomy in whom standard ERCP techniques had
We performed a retrospective study of patients newly diagnosed with Klatskin failed underwent ERCP by using DBE with initial therapeutic intent were iden-
Tumors, in the period betwen 2010-2012, undergoing endoscopic biliary drainage tified retrospectively. DBE success was defined as visualizing the papilla, while
(EBD) and/or percutaneous transhepatic biliary drainage (PTHBD). We ana- ERCP success as completing the intended pancreaticobiliary intervention.
lyzed the patient characteristics, technical success (insertion of drain/stent Clinical success was delineated as a greater than 50% reduction in abdominal
through the stenosis), therapeutic success (total bilirubin 4mg/dL after the pain or level of hepatic enzyme elevations or resolution of cholangitis or complete
procedure), duration of patency, complications and need for reintervention. extraction of bile duct stone.
RESULTS: We included 70 patients with a mean age of 7111 years and a male RESULTS: From April 2006 through December 2011, 77 patients (59-male,
predominance (67.1%), of which 32 were submitted exclusively to PTHBD, 30 to mean age 73.5 years, range 50-95 years) had 92 DBE-assisted ERCPs. Overall
EBD and 8 at both. These eight were initially submitted to EBD, but by impos- DBE-ERCP success was 69 of 77 (90%). DBE success was 73 of 77 (95%), of
sibility of access to the biliary tract they needed PTHBD, so we considerer 40 whom 69 of 73 (95%) achieved ERCP success. Reasons for DBE- ERCP failure
patients in the PTHBD group and 30 in the EBD group. The two groups differed (n 8): tumor obstruction within afferent limb (n 2), peritoneal adhesion
regarding the mean age (PTHBD 68 years; EBD 74 years; p 0.006). No differ- (n 2), cannulation failure (n 3), and bowel perforation (n 1). Diagnosis in
ence was found in the Bismuth Classification (Type III/IV: PTHBD 82.5%, EBD patients with DBE-assisted ERCP success (n 69): choledocholithiasis (n 50),
70.0%) and technical success rate (PTHBD 75%; EBD 79%). The rate of ther- biliary dilatation (n 9), malignant biliary stricture (n 9), normal study (n 1).
apeutic success was PTHBD 57.5%; ERCP 79.3% (p 0.07). The terapheutic Selective interventions included biliary sphincteroplasty (dilation cautery,
failure was more common in Bismuth III/IV types, in both groups (PTHBD n 76), stone extraction (n 57), stenting (n 20), nasobiliary drainage
48.5%; EBD 30.0%). The complication rate was in the PTHBD group 47.5% (n 6), and rendezvous (n 3). Complications occurred in 5 of 77 (6.5%). In
(cholangitis in eleven patients and hemorrhage in 8 patients) and in the EBD those patients who underwent therapeutic ERCP (n 68), 66 patients (97%)
group 23.3% (cholangitis in four, pancreatitis in two and perfuration in one) achieved clinical success.
p 0.038. The patency time was similar: PTHBD 136 days; EBD 133 days. The CONCLUSION: DBE permits diagnostic and therapeutic ERCP in patients with
reintervention rate was 32.4% in the PTHBD group and 48.3% in the EBD Billroth II gastrectomy with a high success and acceptable complication rates.
group (p 0.191). DBE-assisted ERCP should be considered as an effective alternate when stan-
CONCLUSION: Palliative biliary drainage is possible by endoscopic or percu- dard ERCP failed in such patients.
taneous route, although the success rate is limited, especially in patients with REFERENCES
Bismuth types III/IV. Endoscopic biliary drainage seems to show a trend 1. Lin CH, Tang JH, Cheng CL, et al. Double balloon endoscopy increases the
toward greater treatment success, and it is associated with fewer complications. ERCP success rate in patients with a history of Billroth II gastrecotmy. World J
Disclosure of Interest: None declared Gastroenterol 2010; 16: 4594-4598.
2. Shah RJ, Smolkin M, Yen R, et al. A multicenter US experience of single-
balloon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in
P0193 ERCP CANNULATION; EVALUATION OF A WIRE-LED patients with surgically altered pancreaticobiliary anatomy (with video).
TECHNIQUE FOR BILIARY ACCESS IN A TRAINING CENTRE Gastrointest Endosc 2013; 77: 593-600.
C. Shekhar1,*, S. Shetty1, N.C. Fisher1 Disclosure of Interest: None declared
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
P0195 OUTCOMES OF THE ENDOSCOPIC DRAINAGE OF
INTRODUCTION: A range of techniques have been described to achieve suc- PANCREATIC COLLECTIONS ACCORDING TO THE NEW
cessful cannulation at ERCP, and when training in ERCP it is often difficult to ATLANTA CLASSIFICATION
select the optimum approach 1. There are potential advantages to a wire-led D. Ruiz-Clavijo 1,*, B. Gonzalez de la Higuera1, C. Prieto1, E. Sainza1, M. Casi1,
approach and we have evaluated this in our unit in a training setting. F. Bolado1, J. Urman1, I. Fernandez Urien1, F.J. Jimenez1, J.J. Vila1
AIMS & METHODS: To evaluate cannulation success rates for trainers and 1
Complejo Hospitalario de Navarra, Pamplona, Spain
trainees using a wire-led technique as the default approach. Contact E-mail Address: davidruizcla@gmail.com
A prospective evaluation was done with 2 experienced trainers and 2 trainees
(previous experience of 50-100 ERCPs each). The sphincterotome was pre-loaded INTRODUCTION: Endoscopic drainage is considered a minimally invasive
with a hydrophilic wire (in limited cases loop tip wire was used) and cannulation first-line treatment of pancreatic collections (PC). A revision of the Atlanta
started with the wire extending 3-5mm out of cannula. Attempts were then made classification has been recently published but outcomes of endoscopic therapy
to advance the wire deep into the bile duct before injecting any contrast or according to this new classification are scarce.
pushing the cannula through the ampulla. Trainees were allowed 6 minutes for AIMS & METHODS: Our objective was to evaluate the outcomes of the endo-
cannulation attempts. If the wire-led approach failed then other techniques were scopic drainage procedures of PC performed in our center during the last 5 years,
used. Wire-led cannulation was considered successful only if no other techniques assessing results with regard to morphological characteristics of the PC, techni-
were required. Only cases with a virgin ampulla were including in this study. que used, and type of stent placed. A retrospective review of all endoscopically
RESULTS: 100 cases were included over a 5 month period. Trainees were present drained PC at our center from January 2009 to December 2013 was made.
in 62 (62%) cases. Overall biliary cannulation success was 93 (93%). Success rate Indications for endoscopic drainage were symptomatic or complicated PC. PC
was 54/62 (87%) if a trainee was present and 37/38 (97%), if no trainee was were retrospectively classified according to the new Atlanta 2012 classification.
present. Independent success for trainees was 34/62 (55%), mostly using the wire- Variables analyzed: 1) general variables: sex, underlying pancreatic pathology,
led technique 29/34 (85%). In cases where a trainer took over from a trainee, the PC type, 2) endoscopic technique: endoscopic intervention, type of stent, techni-
wire-led approach was still successful in 14/28 (50%). Overall success with the cal success (successful placement of draining stents), number of endoscopic inter-
wire-led approach alone was 31 (69%); other approaches used in remaining cases ventions (including the session to retrieve the stents after PC resolution),
included pre-cut sphincterotomy, locked PD wire, and PD stent. A peri-ampul- complications, and 3) other variables: clinical success (symptom resolution),
lary diverticulum was the most common cause for failure of wire-led technique; morphological success (resolution of the PC on computed tomography), and
other common causes included stricture, floppy ampulla, or an impacted stone. need for subsequent surgery. All drainage procedures were performed under
Median cannulation time was 6.5 minutes (IQR 4-10min) overall and 5 minutes endoscopic ultrasound guidance. Chi-squared and Fishers exact test were used
(IQR 3-10min) for consultant-only cases. Immediate complications included false for analysis.
passage of wire (1 case, no further clinical events) and late complications: post RESULTS: Endoscopic drainage was performed in 39 PC in 37 patients (33
ERCP pancreatitis (1 case, hospital stay 3 days, no further clinical events). men). 46.2% of PC developed in the setting of acute pancreatitis, 38.5% in
CONCLUSION: Wire-led biliary cannulation, with selective usage of additional chronic pancreatitis, and 12.5% after pancreatic surgery. PC included 17 pseu-
techniques, may allow a cannulation rate of 490% in cases with a virgin docysts (2 infected) and 19 walled-off necrosis (15 infected). We were unable to
ampulla. The technique appears to be a useful training tool and has a low retrospectively classify 3 PC according to Atlanta 2012. The endoscopic
complication rate. approach was transgastric in 61%, transpapillary in 28%, and mixed in 7.7%.
REFERENCES In 50% of transgrastric drainages a covered biliary metallic stent was deployed
1.Gastrointest Endosc Clin N Am 2012; 22: 417-434. while the others underwent pigtail stents placement. The treatment approach and
Disclosure of Interest: None declared stent used were associated with the type of PC since walled-off necrotic PC were
preferentially drained via a transgastric approach (17 of 19) and with metallic
stents (13 of 19) (p50.05). Nasocystic lavage was performed in 38.5% of drai-
nages (13 infected walled-off necrotic PC and 2 infected pseudocysts).
Endoscopic necrosectomy was required in 2 patients. Technical, clinical and
morphological success was achieved in 94.9%, 76.9% and 66.7% of cases per
A184 United European Gastroenterology Journal 2(5S)
intention to treat analysis. Type, location, or etiology of PC, drainage technique
P0198 THE RESULTS OF ERCP IN PATIENTS WITH A HISTORY OF
and type of stent did not show a significant influence on technical, clinical, or
FAILED CANNULATION
morphological success. The median number of endoscopic sessions performed
were 2 (range:1-6). There were 30% of complications after the endoscopic drai- E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, B. Cicek3, H. Yildiz2,
nage including migration of the stents in 7 patients, infection in 2, and perfora- N. Sasmaz2, B. Sahin2
1
tion in 1 case. 3 stent migrations and the perforation required surgery while the Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, Turkiye
infections resolved after new endoscopic drainage procedure. _
Yuksek Ihtisas Hospital, Ankara, 3Gastroenterology, Acbadem University,
CONCLUSION: In our series, endoscopic treatment of PC achieved 95% tech- _
Istanbul, Turkey
nical success, 76.9% clinical success per intention to treat, and 66.7% morpho- Contact E-mail Address: koksalas@yahoo.com
logic success. The type of PC according to Atlanta classification determined the
treatment approach and stent placed. INTRODUCTION: Cannulation of common bile or pancreatic ducts is a pre-
REFERENCES requisite for biliopancreatic interventions.
Disclosure of Interest: None declared AIMS & METHODS: To determine the reasons of failed cannulations and
suggest ways to increase the success rate.
We reviewed the data of the patients who were referred to our ERCP unit after
P0196 CAN INITIAL PRECUT FISTULOTOMY IMPLEMENTATION failed cannulation at another center.
REDUCE ENDOSCOPIC RETROGRADE CHOLANGIO- RESULTS: The study group included 71 patients (40 male, mean age:57.2 years).
PANCREATOGRAPHYRELATED COMPLICATION RISK? Sixty-nine patients had biliary and 2 pancreatic pathologies. On admission, 2
D. Kim1,1,*, G. Song1, B. Lee1, D. Baek1, J. Seo1, S. Lee1, T. Kim1, K. Lee1, J. Lee patients had retroperitoneal perforation, 1 patient had pancreatitis and cholan-
1 gitis, each due to the previous ERCP attempt. The reasons of failed cannulation
1
Department of Internal Medicine, Pusan National University School of Medicine, were unsuccessfull pre-cut in 31 (43.6%), failure to reach papilla due to apical
Busan, Korea, Republic Of stenosis in 8, presence of a peripapillary diverticula in 6, altered anatomy in 6 (3
with Billroth II), distal location of the papilla in 2, and failure to identify papilla
INTRODUCTION: Precut fistulotomy allows biliary access when standard can- in 1 patient. Fifteen patients had no reasons to explain failed cannulation.
nulation methods fail. Precut fistulotomy is considered a risk factor for endo- Cannulation was not attempted in the patient with retroperitoneal perforation.
scopic retrograde cholangiopancreatography (ERCP)related complications; Of the remaining 70 patients, cannulation could be achieved in all of them (68/70,
however whether the complication risk is due to precut fistulotomy itself or to 97.1%) other than 2 with Billroth II gastroenterostomy. Cannulation could be
the prior prolonged attempts is still debated. We aimed at assessing success of achieved selectively in 50, after pre-cut in 14, dilation of the apical stenosis in 4,
cannulation and complications of an initial precut fistulotomy vs. a classic strat- and by using either one channel two accessory method or leaving a guidewire in
egy of precut fistulotomy after a difficult biliary cannulation. the pancreatic channel in 2 (2.9%) patients with peripapillary diverticula.
AIMS & METHODS: We conducted a retrospective study from January 2011 to CONCLUSION: Performing pre-cut in the appropriate direction, realising the
December 2012. A total of 152 patients without prior sphincterotomy were anatomic alterations and anomalies in the location of papilla, and applying
enrolled. The patients were classified into two groups: an initial precut fistulot- advanced cannulation techniques are required to increase the success rate of
omy (Group A, n 72) or a late precut fistulotomy only after a failed difficult cannulation.
biliary cannulation (precut fistulotomy after 4 10 cannulation attempts, 4 10 Disclosure of Interest: None declared
minutes, and 4 3 accidental pancreatic duct cannulations, Group B, n 80).
RESULTS: During the study period, total of 1412 ERCPs were performed. Of
these, 152 cases (10.7%) underwent precut fistulotomy. Both groups were com- P0199 PREVENTION OF POST-ERCP PANCREATITIS: A
parable, with no differences for age, gender or indications and findings. The RANDOMIZED CLINICAL TRIAL USING RECTAL DICLOFENAC
overall success of cannulation for Group A and Group B was 95.9% vs 95%; G.W. Lua1,*, R. Muthukaruppan1, J. Menon1
mean cannulation time: 5.7 vs. 13.0 minutes (p50.001). The overall frequency of 1
Medical Department, Ministry of Health Malaysia, Kota Kinabalu, Sabah,
postERCP pancreatitis was 3 patients in Group A vs. 11 patients in Group B Malaysia
(p 0.041). Other complications developed with 1 perforation and 2 bleeding Contact E-mail Address: guanway@hotmail.com
presenting in the Group A and Group B, respectively. All resolved conserva-
tively. Finally, the overall complication rates for Group A and Group B were INTRODUCTION: Pancreatitis is one of the commonest post ERCP complica-
8.3% (6 cases out of 72 patients) and 17.5% (14 cases out of 80 patients), tions. Preliminary research has evaluated several pharmacologic agents for pre-
respectively. vention of post-ERCP pancreatitis (PEP) but none has been proven to be
CONCLUSION: Initial precut fistulotomy provides a higher cannulation success effective. Non steroidal anti-inflammatory drugs (NSAIDs) have been shown
with significantly less time than late precut fistoltomy, although final overall to reduce the incidence of PEP via inhibition of phospholipase A2. There were
success is similar. Initial precut fistulotomy implementation reduces post various trials using different routes and dosages of NSAIDs. Meta analysis of
ERCP pancreatitis risk but not the overall complication rate. these trials was carried out but the results were inconsistent. Hence, we conducted
Disclosure of Interest: None declared a clinical trial to evaluate the efficacy of prophylactic rectal diclofenac for the
prevention of PEP in high-risk patients.
AIMS & METHODS: This was a randomized, open-label, two-arm, prospective
P0197 ENDOSCOPIC TREATMENT OF PANCREATIC FISTULAS DUE clinical trial.
TO ETIOLOGIES OTHER THAN PANCREATITIS Only patients at high risk of developing PEP were selected. This was determined
E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, S. Okten3, O. Aydinli2, by validated patient- and procedure-related risk factors. All procedures were
N. Sasmaz2, B. Sahin2 performed by gastroenterology trainees under the supervision of senior consul-
1
Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, 3Radiology, tants. They were then assigned to either receive 100mg rectal diclofenac or no
_
Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey intervention immediately after ERCP. After the procedure, the patients were
Contact E-mail Address: koksalas@yahoo.com admitted to the ward for further observation.
The primary outcome of the trial was the development of PEP, which consisted
INTRODUCTION: Endoscopy is effective in the treatment of pancreatic fistulas of new onset of upper abdominal pain, an increase in pancreatic enzymes to at
due to pancreatitis. least three times the upper limit of the normal range after the procedure, and
AIMS & METHODS: We aimed to determine the effectivity of endoscopic requiring at least 2 nights of hospital stay. The patients were also reviewed 1
treatment in patients with pancreatic fistulas due to etiologies other than month after discharge to exclude the occurrence of any adverse event related to
pancreatitis. the study drug and ERCP procedure. The difference in incidence of post-ERCP
RESULTS: The study group consisted of 44 patients (28 male, 6-80 years). pancreatitis between the 2 study groups was analysed using Fisher exact test
Etiologies were surgery in 30 and trauma in 14 patients. Thirty-seven patients (2-tailed), with P 50.05 indicating a significant difference.
were presented with drainage through the drain, 5 with pancreatic ascites, and 2 RESULTS: Among 107 patients who were enrolled and completed follow-up, 62
with pseudocyst. Pancreatic fistulas were located in the blind end in 22 (50%)and (57.9%) received diclofenac and 45 (42.1%) were in the control group. Among all
lateral side of the pancreas in 9 (20.5%) patients. Pancreatic fistula could not be the patients, 4 (3.7%) developed PEP, in which 3 were in the diclofenac group (a
visualized during pancreatography in 6 (13.6%) patients. Six patients had dis- pancreatic stent was deployed for 1 of the patient in this group) and 1 was in the
connected pancreatic duct syndrome. Endoscopic treatments were pancreatic control (p 0.31). Every cases of PEP was mild. After ERCP, 5 (4.7%) devel-
sphincterotomy (PES) stenting in 35, PES alone in 6, and PES nasopancrea- oped cholangitis and 1 (0.9%) had a perforation in which they were treated
tic drain insertion in 2 patients. The success of endoscopic treatment could not be conservatively. No drug related complications or adverse event were noted for
determined in 9 patients due to lost to follow up in 6 and exitus in 1 patient. both groups of patients.
Endoscopic treatment was unsuccessfull in 7 patients due to disconnection in 6 CONCLUSION: Among patients at high risk for developing PEP, rectal diclo-
and failure of cannulation in 1 patient. Endoscopic treatment was successfull in fenac did not significantly decrease the incidence of PEP.
29 patients (65%) and surgically placed drains were withdrawn after a mean time REFERENCES
of 27.3 days (5-90) in fistulas located in the blind end, 11.9 (3-28) days in fistulas 1. Elmunzer BJ, Scheiman JM, LehmanGA, et al. Arandomized trial of rectal
located in the lateral side, and 9.7 (3-18) days in fistulas with undefined location. indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 1414-
CONCLUSION: Endoscopy is effective in the treatment of pancreatic fistulas 1422.
due to etiologies other than pancreatitis if the pancreatic duct is not 2. Ding XW. Nonsteroidal anti-inflammatory drugs for prevention of post-
disconnected. ERCP pancreatitis: a meta-analysis. Gastrointest Endosc 2012; 76: 1152-1159.
Disclosure of Interest: None declared Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A185
Tokyo, Japan). Pancreatic interventions were successful in 9 patients (75%).
P0200 EUS AND ERCP COMBINED WITH IDUS IN THE DIAGNOSIS OF
Three of 6 patients with anastomotic stricture were treated successfully with
BILE DUCT STRICTURE
balloon dilation, and the remaining 3 patients required repeated balloon dilation
H. Jiang1,*, S.-Y. QIN1, L. TAO1, W. LUO1, S.-B. SU1, X.L.1, H.-J. NING1, and long-term pancreatic stent placement. Two patients with pancreatic fistula
X.-P. LU1, R.-E. LEI1 were treated successfully with endoscopic nasopancreatic drainage. Pancreatic
1
The First Affiliated Hospital of Guangxi Medical University, Nanning, China duct stones were successfully removed in 4 patients. Complications occurred in
Contact E-mail Address: lihuan@erbechina.com 3 (25%) patients, including retroperitoneal air (n 1) and hyperamylasemia
(n 2), but all were asymptomatic.
INTRODUCTION: A variety of cholongioscopes have been emerged as a new CONCLUSION: Endoscopic pancreatic interventions using short DBE,
tools for diagnosis of different biliary strictures. But these new techniques are not although technically demanding, are effective and safe in patients with surgically
widely applied clinically because of high price and too easy to damage. altered anatomy.
AIMS & METHODS: We evaluated the value of endoscopic ultrasonography Disclosure of Interest: None declared
(EUS) and endoscopic retrograde cholangiopancreatography (ERCP) combined
with intraductal ultrasonography (IDUS) in the diagnosis of bile duct stricture.
36 patients with bile duct stenosis were recruited. The findings by endoscopic P0202 SHORT SINGLE-BALLOON VERSUS DOUBLE-BALLOON
ultrasonography and endoscopic retrograde cholangiopancreatography com- ENDOSCOPE FOR PANCREATICOBILIARY INTERVENTIONS IN
bined with intraductal ultrasonography and the results of bile duct brushing PATIENTS WITH SURGICALLY ALTERED ANATOMY
cytology and liquid-based cytology of these patients were analyzed. The final H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1,
diagnosis was based on clinical data, histopathology and follow-up results (6 T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1,
months). N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1
RESULTS: All of the 36 patients, in whom 21 were diagnosed malignant biliary 1
Department of Gastroenterology, Graduate School of Medicine, The University of
diseases, including 9 biliary tract carcinomas, 4 duodenal papilla carcinomas, 4 Tokyo, Tokyo, Japan
pancreatic cancers infiltrating common bile duct and 4 liver cancers infiltrating Contact E-mail Address: kogureh-tky@umin.ac.jp
common bile duct; 15 were diagnosed as benign biliary diseases, including 9 bile
duct stones, 4 liver fluke diseases, 1 cholangitic stenosis and 1 external compres- INTRODUCTION: With the advent of short double-balloon endoscope (DBE),
sion, were shown to have bile duct stricture. The accuracy rate of EUS, ERCP, therapeutic pancreaticobiliary interventions are possible with surgically altered
IDUS and EUSERCPIDUS in the differential diagnosis of bile duct stricture anatomy. However, because the channel diameter of short DBE is 2.8 mm, only
disease were 77.8%, 88.9%, 91.7% and 94.4%, respectively. The accuracy rates limited ERCP devices are available and the exchange of devices is both time-
of differential diagnosis of bile duct stricture disease between EUS and ERCP consuming and cumbersome. Recently, a prototype short single-balloon endo-
were similar; while the accuracy rate of EUS and ERCP combined with IDUS scope (SBE) with passive bending and high force transmission, which has a 3.2
was significantly higher than both EUS and ERCP (P50.05). The sensitivity, mm working channel and a 152 cm in length, was specifically developed for
specificity, positive predictive value (PPV) and negative predictive value (NPV) of ERCP (SIF-Y0004-V01; Olympus Medical Systems, Tokyo, Japan).
EUSERCPIDUS were 95.2%, 93.3%, 95.2%, 93.3%, respectively; the sensi- AIMS & METHODS: The aim of this study was to compare the insertability and
tivity, PPV, NPV in EUS ERCP IDUS were higher than that of EUS, ERCP procedural efficiency of short SBE and short DBE for pancreaticobiliary inter-
and IDUS. All of the 36 patients received bile duct brushing cytology and the ventions in patients with surgically altered anatomy. Between March 2013 and
liquid-based cytology tests, 19 of which were diagnosed as malignant biliary Jan 2014, we performed endoscopic pancreaticobiliary interventions using a short
diseases, while 17 were diagnosed as benign biliary diseases. The sensitivity, SBE in 20 patients who have successfully undergone short DBE-assisted ERCP.
specificity and accuracy of differential diagnosis of bile duct stricture disease Previous surgeries included Roux-en-Y (R-Y) gastrectomy (n 7), hepaticojeju-
were 90.5%, 100% and 94.4%, respectively. nostomy (n 5), pancreaticoduodenectomy with R-Y reconstruction (n 3),
Table. Comparison of ERCP and EUS in the diagnosis of bile duct stricture Billroth II (B-II) gastrectomy with Brauns anastomosis (n 2), pancreaticoduo-
denectomy with B-II reconstruction and Brauns anastomosis (n 2), and liver
EUS ERCP IDUS EUSERCPIDUS transplantation with hepaticojejunostomy (n 1).
RESULTS: Access to the papilla or anastomosis with SBE failed in 3/20 patients
sensitivity 71.4%(15/21) 85.7%(18/21) 90.5%(19/21) 95.2%(20/21) (15%). Among successful patients, the median time (IQR) required to reach the
specificity 86.7%(13/15) 93.3%(14/15) 93.3%(14/15) 93.3%(14/15) target orifice was 26 min (1132.5 min) with SBE and 16 min (1121 min) with
PPV 88.2%(15/17) 94.7%(18/19) 95%(19/20) 95.2%(20/21) DBE (P 0.10). Pancreaticobiliary interventions with SBE were successful in 17/
17 patients (100%). Therapeutic procedures using SBE included stone extraction
NPV 68.4%(13/19) 82.4%(14/17) 87.5%(14/16) 93.3%(14/15)
(n 11), biliary plastic stenting (n 5), papillary large balloon dilation (n 3),
diagnosis 28 32 33 34
balloon dilation of anastomotic stricture (n 3), pancreatic stenting (n 3), bili-
misdiagnosis 8 4 3 2 ary metallic stenting (n 1), balloon dilation of biliary stricture (n 1), and
Accuracy rate (%) 77.8 88.9 91.7 94.4 endoscopic naso-pancreatic drainage (n 1). Although almost the same proce-
dures with prior DBE, the median ERCP procedure time (IQR) was shorter with
SBE than with DBE [29 min (2355.5 min) vs 63 min (46.593.5 min), P 0.03].
CONCLUSION: EUS and ERCP combined with IDUS can improve the diag- Aspiration pneumonia as procedure-related complication occurred in 1 patient.
nostic accuracy of bile duct disorders. IDUS is carried out under the guidance of CONCLUSION: Insertability of a short SBE is slightly inferior to that of a short
a guide wire, and the operation is simple. It can also make up for the inadequacy DBE. However, a short SBE with a 3.2 mm working channel allows most con-
of EUS. With the help of ERCP and IDUS, the bile duct could be directedly ventional ERCP devices to be used and reduces ERCP procedure time compared
brushed, which could improve the diagnostic positive rate. to a short DBE with an only 2.8 mm working channel.
Disclosure of Interest: None declared Disclosure of Interest: None declared
P0201 ENDOSCOPIC PANCREATIC INTERVENTIONS USING SHORT P0203 INTER-OBSERVER AGREEMENT AND ACCURACY OF
DOUBLE-BALLOON ENDOSCOPE IN PATIENTS WITH PREOPERATIVE EUS-GUIDED BIOPSY FOR HISTOLOGIC
SURGICALLY ALTERED ANATOMY GRADING OF PANCREATIC CANCER
H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1, A. Larghi1,*, R. Ricci2, I. Abdulkader3, G. Monges4, J. Iglesias-Garcia 5,
T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1, M. Giovannini6, F. Attili1, G. Vitale 1, C. Hassan1, G. Rindi2, G. Costamagna1
N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1 1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome,
1
Department of Gastroenterology, Graduate School of Medicine, The University of Italy, 3Department of Pathology, University Hospital of Santiago de Compostela,
Tokyo, Tokyo, Japan Santiago de Compostela, Spain, 4Department of Pathology, Paoli-Calmettes
Contact E-mail Address: kogureh-tky@umin.ac.jp Institute, Marseille, France, 5Gastroenterology Department, University Hospital of
Santiago de Compostela, Santiago de Compostela, Spain, 6Endoscopic Unit, Paoli-
INTRODUCTION: In patients with surgically altered anatomy, endoscopic Calmettes Institute, Marseille, France
treatment of pancreatic disease such as pancreaticojejunostomy stricture, pan- Contact E-mail Address: albertolarghi@yahoo.it
creatic fistula, and pancreatic duct stones can be challenging.
AIMS & METHODS: We evaluated the efficacy and safety of endoscopic pan- INTRODUCTION: Post-surgical poor differentiation/high grade of pancreatic
creatic interventions using short double-balloon endoscope (DBE) for the treat- cancer (PADC) appears to accurately predict an early unfavourable outcome,
ment of pancreatic disease in patients with surgically altered anatomy. these patients possibly deserving neo-adjuvant treatment. EUS-guided pancreatic
Between October 2009 and April 2014, we performed endoscopic pancreatic tissue core biopsy (EUS-PTCB) may in theory allow a pre-operative assessment
interventions in 12 patients using a short DBE (152 cm in length with a 2.8 of PADC-grading. To assess inter-observer pathological agreement and accuracy
mm working channel; EC-450BI5/EI-530B, Fujifilm Medical, Tokyo, Japan), of preoperative PADC-grading based on EUS-PTCB.
enabling conventional ERCP accessories. Previous surgeries included pancreati- AIMS & METHODS: 42 post-surgical PADC-cases with preoperative EUS-
coduodenectomy with Billroth II reconstruction (n 7), pancreaticoduodenect- PTCB were chosen. Four expert pathologists independently reviewed the EUS-
omy with Roux-en-Y reconstruction (n 3), and Roux-en-Y gastrectomy (n 2). PTCB slides, reporting tumour grading (well-/moderate-/poor-degree of differ-
Indication for pancreatic interventions were anastomotic stricture (n 8; with entiation). Agreement among pathologists for reporting PADC-grading on pre-
pancreatic duct stones [n 5]), pancreatic fistula (n 3), and pancreatic duct operative EUS-PTCB material was expressed by using Cohens/Fleiss kappa
stones (n 1). statistic, as appropriate. Post-surgical PADC-grading was used as gold-standard
RESULTS: Access to the papilla or the end of afferent loop successful in all 12 to assess the cumulative accuracy of EUS-PTCB in preoperatively predicting
patients, but anastomosis site could not be identified in 3 patients. Pancreatic PADG grade.
duct cannulation was achieved using a straight cannula (0.025-inch ERCP-cathe- RESULTS: The k values for PADC-grading on EUS-PTCB material ranged
ter, MTW Endoskopie, Wesel, Germany) and a 0.035-inch hydrophilic guidewire from 0.09 to 0.41. The total agreement among the four pathologists was only
(Radifocus, Terumo, Tokyo, Japan), or a metal tip cannula (PR-132Q, Olympus, fair (k 0.27; 95% CI: 0.14-0.38). When tumor grades were grouped as well-/
A186 United European Gastroenterology Journal 2(5S)
moderately differentiated versus poorly differentiated, kappa values ranged from lesions fine needle aspiration was performed initially from the esophagus under
0.19 to 0.50, with only a fair overall agreement (k 0.27; 95% CI: 0.21-0.49). local anesthesia. Cytology examination of the fine needles aspirates was made on
Preoperative EUS-PTCB-based accuracy of preoperative staging was 56% (75/ site. If EUS-FNA (8pts) gives a negative result (8pts) in the on-site cytological
134 readings; 95% CI: 40-65%), with mean sensitivity and specificity to detect a analysis, EBUS-TBNA was performed once.
high grade poorly differentiated tumor of 41% (95% CI: 19-54%) and 78% (53/ RESULTS: Diagnosis was proved in 87.3% of cases in EBUS-TBNA group and
68 readings; 95% CI: 60-99%), respectively. in 85.7% of cases in EUS-FNA group. Definitive morphology diagnosis was
CONCLUSION: Preoperative EUS-PTCB-based pathological grading of PADC made in 96.4% by the combined approach with rapid on-site evaluation of the
is unreliable, arguing against the use of this information in clinical practice. This fine needles aspirates.
appears to be related with both a suboptimal inter-observer agreement among CONCLUSION: Two procedures can be performed with single ultrasound
pathologists and an overall low accuracy in predicting post-surgical staging. bronchoscope and the combined approach with cytology examination on site
Disclosure of Interest: None declared has better diagnostic value than either alone. But EUS-FNA with ultrasound
bronchoscope is easy, safe and doesnt request moderate sedation. Therefore it
can be performed for patients for tissue diagnosis from enlarge 7 and 4L group
P0204 PERFORMANCE OF THE PROCORE 25 GAUGE NEEDLE IN lymph nodes as the first step of examination.
OBTAINING SAMPLES FOR HISTOLOGICAL EXAMINATION IN A Disclosure of Interest: None declared
LARGE AND HETEROGENOUS COHORT OF PATIENTS: A TWO
CENTERS STUDY
A. Larghi1,*, F. Attili1, G. Petrone2, I. Abdulkader3, F. Inzani 2, J. Iglesias- P0206 RESULTS AND LEARNING FROM A THERAPEUTIC
Garcia 4, C. Hassan1, G. Rindi2, G. Costamagna1 ENDOSCOPIC ULTRASOUND PRACTICAL WORKSHOP ON A
1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome, SWINE LIVING MODEL
Italy, 3Department of Pathology, 4Gastroenterology Department, University A. Teran Lantaron1,2,*, B. Castro Senosiain1,2, P. Iruzubieta Coz1,2, G. De las
Hospital of Santiago de Compostela, Santiago de Compostela, Spain Heras Castano1,2, J.C. Manuel-Palazuelos2, J.B. Gornals Soler3, J.J. Vila Costa4,
Contact E-mail Address: albertolarghi@yahoo.it M. Perez-Miranda5, J. De la Pena Garcia1,2
1
GASTROENTEROLOGY AND HEPATOLOGY, HOSPITAL
INTRODUCTION: A new 25-gauge Procore biopsy needle has become UNIVERSITARIO MARQUES DE VALDECILLA, 2HOSPITAL VIRTUAL
recently available. Scanty data on its performance are available. We evaluate VALDECILLA, SANTANDER, 3GASTROENTEROLOGY AND
the yield of this needle in obtaining samples for histologic evaluation (EUS- HEPATOLOGY, HOSPITAL UNIVERSITARI BELLVITGE, BARCELONA,
FNB), its diagnostic accuracy and inter-observer agreement between three 4
GASTROENTEROLOGY AND HEPATOLOGY, COMPLEJO
pathologists in a large cohort of patients with heterogenous indication. HOSPITALARIO DE NAVARRA, PAMPLONA, 5GASTROENTEROLOGY
AIMS & METHODS: Consecutive patients who underwent EUS-FNB using the AND HEPATOLOGY, HOSPITAL UNIVERSITARIO RIO HORTEGA,
Procore 25G were retrospectively retrieved. The collected material was placed VALLADOLID, Spain
directly in formalin or in cytolit and sent for histologic evaluation. All samples Contact E-mail Address: altelan@hotmail.com
were independently reviewed by three pathologists and scored for: (i) presence of
an histologic, cytologic specimen or no specimen; (ii) presence or absence of INTRODUCTION: Therapeutic endoscopic ultrasound (T-EUS) has been
neoplasia; (iii) diagnostic or not diagnostic. Diagnostic accuracy and inter- undergoing extensive development in recent years. Although previous experience
rater concordance among pathologists in the evaluation of the above mentioned on EUS-FNA and ERCP is considered to be needed, data on learning curves and
parameters were calculated. the potential benefit of animal models training are lacking.
RESULTS: 94 patients (median age 71 years; 55 male) underwent EUS-FNB of AIMS & METHODS: To train some different T-EUS techniques and to estimate
101 sites. Mass lesions were located in the pancreas (49 patients), abdomen (6), their difficulties and the potential benefit of the swine model in this context.
liver (8), common bile duct (3 masses and 3 wall thickening), stomach (1 sub- Prospective data analysis from a T-EUS practical workshop on a biliary obstruc-
epithelial lesion and 2 wall thickening), mediastinum (2), lung (1), and adjacent to tion porcine model by OTSC clip, addressed to endoscopists with previous
the rectum (1). All the remaining 25 sampled lesions were mediastinal (14) and EUS-FNA and ERCP experience. There were four different T-EUS procedures
abdominal (11) lymph nodes. The median lesion size was 30 mm (range, 15-67 trained: common bile duct drainage (CBDD), cholecysto-gastrostomy (CGS),
mm) and a mean of 2.5 FNA passes (range, 1-6; median, 3; IQR, 2-3) per lesion transrectal urinary bladder drainage (TUBD), simulating a fluid collection drai-
was done. A total of 41 (40.6%) lesions were classified as having a histologic nage, and gastro-jejunostomy (GJS). All animals were sacrificed after T-EUS
specimen either by at least two of the three pathologists. A presence of a cytologic procedures and necropsy studies were performed. Local Ethics Committee
specimen was found by at least two of the three pathologists in 29 (28.7%) cases. approval was obtained.
In the remaining 31 lesions no specimen was present according to all three RESULTS: Thirty three procedures were analyzed (11 CBDD, 5 CGS, 7 TUBD,
pathologists. There was good agreement among pathologists in determining if 10 GJS), performed by 12 endoscopists in 10 pigs (2.83 0.58 proc./endoscopist;
EUS-FNB provided cytologic vs. histologic samples (kappa index, 0.82; 95% 3.3 1.42 proc./animal). Main results are shown in Table 1. Together TUBD
CI:0.74-0.90). When considering non-diagnostic samples as false negative, the and GJS were the procedures more frequently and successfully completed versus
pooled sensitivity of the EUS-FNB for neoplasia was 65% (154 of 237 readings; CBDD and CGS (100% vs. 62.5%, p 0.007 and 82.4% vs. 37.5%, p 0.011).
95% CI: 54.8-75.1%), whereas specificity was 98% (50 of 51 readings; 95% CI: Among the different procedural steps, guidewire management (31.8%), stent
89-100%). The pooled accuracy of the procedure was 70.8 (204 of 288 readings; insertion (25%) and cystotome use (20%) were the most troublesome ones.
95% CI: 62.1-79.6%). In the per-protocol analysis, the overall sensitivity and Table 1. Results by procedure
accuracy of the procedure for malignancy was 93.8 (150 of 160 readings; 95% CI:
88.8-96.9) and 93.9% (170 of 181 reading; 95% CI: 89.3-96.9%), respectively. CBDD CGS TUBD GJS Total *p
Substantial agreement on the presence (or absence) of neoplasia resulted (kappa
index, 0.94; 95% CI: 0.83-1.00). Substantial agreement was seen across the three N 11 5 7 10 33
reviewers in describing diagnostic accuracy, with an overall kappa value of 0.95
(95% CI: 0.85-1.00). At multivariate analysis, histologic samples were more likely Mean time duration (min.) 51.3 48 31.3 21.2 34.7 0.000
than cytologic one to lead to a correct diagnosis (OR, 4.1; 95% CI: 1.2, 15.0; 14.5 7.6 5.9 17.2 18.5
p 0.027). Completed 63.6% 60% 100% 100% 81.8% 0.007
CONCLUSION: EUS-guided FNB with the Procore 25G needle provided sam- Final succes 45.5% 20% 85.7% 80% 60.6% 0.011
ples for histologic examination in about 40% of the cases and showed excellent Trainer intervention needed 18.8% 20% 14.3% 20% 18,8% 0.608
results in term of interobserver variability.
Disclosure of Interest: None declared Inmediate complications 10% 40% 14.3% 10% 15.6% 0.437
P0205 COMBINED ENDOBRONCHIAL AND TRANSESOPHAGEAL CONCLUSION: Our model appears to mirror the challenges of T-EUS even for
APPROACH OF AN ULTRASOUND BRONCHOSCOPE FOR TISSUE endoscopists experienced in EUS-FNA and ERCP.
DIAGNOSIS OF MEDIASTINAL LYMPHADENOPATHY Ethical and cost concerns can be minimized by optimizing the number of T-EUS
A. Strunina1,*, R. Kuvaev1, S. Kashin1, A. Levina2, V. Chernyaeva2, drainage procedures, up to 4 per animal.
N. Akhapkin3 CGS and CBDD, both longer and with higher number of steps and instrument
1
Endoscopy, 2Cytology, 3Administration, Yaroslavl Regional Cancer Hospital, requirements, are more challenging than TUBD or GJS, which suggests more
Yaroslavl, Russian Federation demanding training is needed.
Contact E-mail Address: kuvaev_roman@mail.ru This kind of training based on animal model simulation may allow a safer and
probably quicker learning curve on T-EUS.
INTRODUCTION: Morphological evaluation of mediastinal masses is essential Disclosure of Interest: A. Teran Lantaron Financial support for research from:
for diagnostic confirmation and treatment planning of patients (pts) with med- The workshop reported in this abstract was sponsorized by Boston Scientific, B.
iastinal abnormalities. EBUS-TBNA and EUS-FNA is a safe and efficacy Castro Senosiain: None declared, P. Iruzubieta Coz: None declared, G. De las
method to obtain tissue for morphological diagnosis. The combined approach Heras Castano: None declared, J. Manuel-Palazuelos: None declared, J. Gornals
reduces the need for additional equipment, the operating costs, and the duration Soler: None declared, J. Vila Costa: None declared, M. Perez-Miranda: None
of the procedure. However it could be difficult to select the order of preference if declared, J. De la Pena Garcia: None declared
both of the techniques are available.
AIMS & METHODS: The aim was to determine the diagnostic value of EBUS-
EUS combined approach by using single ultrasound bronchoscope for evaluation
mediastinal lymphadenopathy. EUS FNA and EBUS TBNA (Olympus Exera
II BF-UC160F, Olympus 21g needles) were compared in 166 patients for tissue
diagnosis from enlarge (40.9cm) 7 and 4L group lymph nodes. 110 lesions were
sampled from the respiratory tract under moderate sedation as first step. For 56
United European Gastroenterology Journal 2(5S) A187
INTRODUCTION: Treating pancreatic cancer represents a major objective in INTRODUCTION: Liver abscesses and bilomas are conventionally managed by
research, as it still remains the fourth leading cause of cancer deaths among men means of percutaneous drainage or surgical approach. However, both procedures
and women, with approximately 6% of all cancer-related deaths. Radiofrequency have been reported on high morbi-mortality rates. Transgastric EUS-guided drai-
ablation uses electromagnetic energy deposition causing thermal lesions and nage of both entities with plastic stents or nasocystic catheters have been excep-
overheating tissue which leads in a final stage to necrosis. tionally performed. We describe our experience using self expandable metal stents
AIMS & METHODS: We studied the assessment of an EUS-guided RFA probe (SEMS) tubular and lumenapposing metal stents (LAMS) in this setting.
through a 19-gauge needle, in order to achieve a desirable necrosis area in the AIMS & METHODS: The aim of the study was to assess the technical feasibility
pancreas. Radiofrequency ablation of the head of the pancreas was performed and clinical outcomes of EUS-guided drainage of liver abscesses and bilomas
using a RITA Medical System device on 10 Yorkshire pigs with a weight between using SEMS under mixed fluoroscopic, endoscopic and ultrasonographic
25 to 35 kg. Using an EUS-guided RFA experimental probe we ablated an area guidance.
of 2 to 3 cm wide at 5-10-15-20 watts for one minute a time. Retrospective analysis involving eight consecutive patients (March12 to Oct 13)
RESULTS: No major complications were noted. High levels of amylase, lipase, with liver abscesses/bilomas not accesible to percutaneous approach and/or dis-
aspartate transaminase and alanine transaminase were found within 3 days from carded for surgery by means of age or comorbidities (Table 1). Procedures were
the ablation. Necropsy pointed out a very well limited area with minimal inva- performed by using linear echoendoscopes, 19G needles under EUS & fluoro-
sion and inflammatory tissue at about 2 cm surrounding the lesion. No nearby scopic control, 0.035 guidewires, 8.5F cystotome and tract dilation with 4 mm
fibrosis or adhesions were found and no major vessel injuries or adjacent organ biliary balloon. Aspiration of fluid was routinelly performed for culture. Finally,
damage was produced. The pathology examination revealed coagulative necrosis, cSEMS were placed, either tubular or lumen-apposing metal stents (LAMS:
a local acute inflamatory reaction with structured necrosis of the glandular par- AXIOSTM- Xlumena Inc).
enchyma, steatonecrosis, and recent thrombosis of blood vessels. RESULTS: Six patients with liver abscesses and 2 bylomas were included (Table
CONCLUSION: EUS-Guided RFA of the pancreas may be a feasible procedure, 1) EUS-guided transgastric approach was performed in 6/8 cases (75%) in cor-
however more studies are necessary. respondence with abscesses located on the left hepatic lobe. 6 patients were
Disclosure of Interest: None declared managed with LAMS (5 abscesses, 1 biloma). Median diameter of abscesses
was 80.05 mm (range 52.70 - 99). Drainages were successful in all cases and
there were no procedure-related complications. Stents were removed after a
P0208 ROLE OF ENDOSCOPIC ULTRASONOGRAPHY IN THE mean of 7 weeks (range 4-12). There were no relapses after a mean follow-up
SELECTION FOR NEOADJUVANT TREATMENT OF GASTRIC of 7.5 months (range 1-18)
ADENOCARCINOMA CONCLUSION: EUS-guided drainage of hepatic abscesses and bilomas by
B.M. Goncalves1,*, P. Bastos1, J.-B. Soares1, D. Fernandes1, E. Couto2, means of SEMS appears to be a safe, effective and useful procedure in patients
J. Cunha2, C. Rolanda1, R. Goncalves1 not suitable for radiologic drainage or surgery. However, larger, prospective and
1
Gastroenterology, 2Oncology, Hospital de Braga, Braga, Portugal multicenter studies are needed.
Contact E-mail Address: brunommgoncalves@gmail.com Disclosure of Interest: None declared
P0209
Collection Size Stent Retrieval Follow-Up
type Age/ Sex (mm) Approach type Complications (weeks) (months) Outcome
P0230 DOES CHEMOTHERAPY PROLONG THE STENT PATENCY IN P0232 COMPARISON OF OUTCOMES BETWEEN INTERNAL STENT
MALIGNANT DISTAL BILIARY STRICTURE? PLACEMENT AND PTBD IN PATIENTS WITH PLANNED CRT FOR
M. Kida1,*, S. Miyazawa1, S. Tokunaga1, H. Yamauchi1, K. Okuwaki1, T. Iwai1, PERIHILAR CHOLANGIOCARCINOMA
M. Takezawa1, M. Watanabe1, H. Imaizumi1, W. Koizumi2 S.W. Yi1,*, J.H. Cho2, J.B. Chung3, S.W. Park3, S.Y. Song3, S. Bang3
1
Endoscopy Center, 2Gastroenterology, KITASATO University Hospital, 1
Internal medicine, Division of Gastroenterology, International St. Marys
Sagamihara, Japan Hospital, 2Internal medicine, Gachon University Gil Medical Center, Incheon,
3
Contact E-mail Address: m-kida@kitasato-u.ac.jp Internal medicine, Division of Gastroenterology, Yonsei University College of
Medicine, Seoul, Korea, Republic Of
INTRODUCTION: Metallic stents for malignant distal biliary stricture have Contact E-mail Address: sinbbori97@naver.com
become one of the best palliative treatments in inoperative cases who were gen-
erally treated by chemotherapy; however its influence in stent patency has not INTRODUCTION: The optimal biliary decompression method in resectable
been investigated and consensus is not established. perihilar-cholangiocarcinoma has been authorized as percutaneous transhepatic
AIMS & METHODS: From 2002 to 2013, we have inserted metallic stents in biliary drainage (PTBD). In case of locally advanced perihilar-cholangiocarci-
totally 259 cases with malignant distal biliary stricture, and treated 164(63%) noma, malignant biliary obstruction is judged to have palliation of jaundice by
caes with chemotherapy and remaining 95(37%) cases with best supportive care placement of an internal stents or PTBD. We aimed to investigate the efficacy of
(BSC). We investigated the efficacy of chemotherapy in its stent patency etc. internal placement of biliary stent compared with PTBD for patients planned
retrospectively. CRT in locally advanced perihilar-cholangiocarcinoma.
RESULTS: Subjects in this study were consisted of 206 (80%) pancreas cancers, AIMS & METHODS: The patients who are histologically proven locally
45(14%) biliary cancers, and 8(3%) papillary cancers. Metallic stents we used advanced perihilar-cholangiocarcinoma between Jan. 1995 and Dec. 2013 at
were 152(59%) partially covered Wallstents (P-WS), 54(21%) partially covered single tertiary medical center in Korea, analyzed as prospective observational
Wallflexs (P-WF), 34(13%) fully covered Wallflexs (F-WF), and 19(7%) fully study. The perihilar cholangiocarcinoma was defined as disease occurring above
covered Bonastents (F-BS). There was no significant difference on base line the junction of the cystic duct up to the secondary branches of the hepatic duct.
characteristics between chemotherapy group and BSC group except for age (68 RESULTS: Among one hundred seventy six locally advanced perihilar-cholan-
vs 74 years olds). Chemotherapy we employed was Gemcitabine (GEM) alone, giocarcinoma patients, CRT was performed in 79 patients; endoscopic biliary
GEM TS-1, and GEMTS-1CDDP etc. The median stent patency was 328 decompression was forty six patients (26.14%), and PTBD was thirty three
days in total, and the median stent patency of chemotherapy group was signifi- patients (18.75%). The mean period of internal stent indwelling is 152 days
cantly longer (354 days vs188 days in BSC, p 0.001). The median stent patency whereas 222 days in PTBD group (p 0.675). The R0 operative rate after the
of biliary cancer in chemotherapy group was significantly longer (341 days vs 119 CRT was 23.9% in endoscopic stenting group, and 12.1% in PTBD group
days in BSC, p 50.001), whereas the median stent patency of pancreas cancer (p 0.174). The median overall survivals were 463 days at endoscopic stenting
in chemotherapy group was not significant. group and 439 days in PTBD group, respectively (p 0.874). Repeated biliary
CONCLUSION: We concluded that chemotherapy prolong the stent patency in decompression procedure was performed at endoscopic decompression group 26
malignant distal biliary stricture, especially biliary cancers. patients (56.5%), 12 patients in PTBD group (36.4%) (p 0.077).
Disclosure of Interest: None declared In the subgroup analysis of endoscopic stenting group, there were 25 cases of
SEMS, and 21 cases of biliary drainage using the plastic stent. The stent dysfunc-
tion was found in 20 patients (80.0%) with plastic stent and 6 patients (28.6%) in
P0231 ENDOSCOPIC DOUBLE SELF-EXPANDING METAL STENT SEMS group (p 0.001). Median stent patency time was 111 days and 402 days
PLACEMENT FOR THE TREATMENT OF MALIGNANT BILIARY in the plastic stent and SEMS, respectively (p 0.002). Post-operative major
AND GASTRODUODENAL OBSTRUCTION: A LARGE SERIES OF complications were not seen in both cases.
TREATED PATIENTS FROM A REFERRAL HOSPITAL FOR CONCLUSION: The endoscopic placement of internal stent might be useful
PALLIATIVE CARE method for biliary decompression in patients with planed CRT for locally
R. Di Mitri1,*, F. Mocciaro1, G.M. Pecoraro1 advanced perihilar-cholangiocarcinoma, compared to PTBD. In case of biliary
1
Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli endoscopic drainage, the pre-CRT SEMS had lower rate for repeated endoscopic
Hospital, Palermo, Italy procedure than plastic stent in perihilar-cholangiocarcinoma.
Contact E-mail Address: fmocciaro@gmail.com Disclosure of Interest: None declared
a n
rate ratio of 1.32 (1.11-1.57). The median (range) age at diagnosis increased from
w
28 (379) years to 37 (587) years (p 0.0002). Similarly, the point prevalence
r
d
increased from 178/105 (157-199) on 31 December 1987 to 267/105 (244 291) on
Marys Hospital, London, United Kingdom
W
increased from 12.5% in 1963-1965 to 82.3% in 2005-2010.
CONCLUSION: The incidence of Crohns disease during the last two decades
increased. A striking increase in non-stricturing, non-penetrating disease at diag-
respectively. Dizygotic concordance rates are 0-3.6% (CD) and 0-6.3% (UC) (1). nosis was observed, suggesting earlier diagnosis or phenotypic change. The
The UK IBD Twin and Mutliplex Registry is a research database established in observed point prevalence in 2010 is among the highest reported.
October 2013; this study reviews disease patterns and environmental risk factors REFERENCES
of twin pairs recruited. 1. Lindberg E and Jarnerot G. The incidence of Crohns disease is not decreasing
AIMS & METHODS: Data subjects were recruited via clinician referral, IBD in Sweden. Scand J Gastroenterol 1991; 26: 495-500.
charities and retracing members of a database dormant since 1996. Adult twin Disclosure of Interest: None declared
pairs discordant and concordant for IBD were recruited. Data subjects com-
pleted a questionnaire regarding demographics, disease history and environmen-
tal exposure. Medical records were reviewed when available. P0280 INTERLEUKIN 6 GEN POLYMORPHISM IN PATIENTS WITH
RESULTS: Demographics, Concordance and Zygosity: 100 twin pairs were INFLAMMATORY BOWEL DISEASES
recruited. Mean age 57 years 5 months, range 21-83 years. 31 monozygotic:69 D. Cibor1,*, D. Owczarek1, M. Glowacki1, K. Jablonski2, A. Jurczyszyn3,
dizygotic. Ratio CD:UC 48:52. Concordance of twin pairs classified by zygos- A. Ciesla1, T. Mach1
ity and disease type is as follows: 1
Gastroenterology, Hepatology & Infectious Diseases, 2Medical Education,
3
Hematology, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE,
Crohns Disease Ulcerative Colitis Krakow, Poland
Contact E-mail Address: dorota.cibor@gmail.com
Monozygotic 53.3% 25%
INTRODUCTION: Interleukin 6 (Il-6) plays an important role in the develop-
Dizygotic 10% 19.4% ment of inflammatory process in IBD patients. The 174 G/C IL-6 promoter
polymorphism affects IL-6 transcription. The GG genotype seems to induce
higher IL-6 levels while the C allele (GC or CC) seems to be associated with
Early Environment: Higher rates of exclusive breastfeeding were reported in decreased transcription and secretion of IL-6.
concordant compared with discordant pairs (27.3% n 22 pairs vs 16.7% AIMS & METHODS: Our study aimed to evaluate the effect of single nucleotide
n 78 pairs). Self reports of perceived childhood illness did not show any differ- polymorphism of IL-6 (174 G/C) on the disease course in patients with UC and
ence between IBD and healthy twins of discordant pairs (16.7%, 13/78 vs 19.2%, CD.
15/78). However, the IBD twin more often recalled frequent gastrointestinal Material and methods: 105 patients (aged 18-75 years) with diagnosed IBD: 50
infection prior to IBD onset in comparison with their healthy twin (10.3%, 8/ with CD and 55 with UC were involved in the study. The controls consisted of
78 vs 3.8%, 3/78). 124 healthy individuals. In all patients were evaluated following parameters:
Diet: IBD twins from discordant pairs reported higher rates of consuming "ready disease duration, disease location, presence of complications, present pharma-
made" meals at least weekly before disease incidence (12.8%, 10/78 vs 5.1%, 4/ cotherapy, past surgical procedures, BMI, cigarette smoking. In all subjects
78). morphology, biochemical parameters, CRP, fibrinogen, IL-6 level and IL-6 poly-
Smoking: On review of discordant twin pairs (n 72), there was no significant morphism were assessed.
difference in numbers of current, ex and non smokers between subjects with UC RESULTS: No statistically significant differences in IL-6 polymorphism were
(n 41), CD (n 32) and their healthy twin at time of symptom onset. observed between patients with UC, CD and controls. Patients with GG geno-
Medication and Stress: On review of all IBD sufferers, 7.1% (8/112) and 13.4% type were significantly younger at the disease onset. In IBD patients with GG
(15/112) used NSAIDS and antibiotics within 3 months preceding onset. 48.2% genotype higher mean IL-6 level was noticed as compared to other genotypes
(54/112) reported significant stress within the year preceding onset. (4.685 /- 5.9 vs 2.715 /- 5.1 in GC and 3.186 /- 3.6 in CC). In both UC and
Time of onset in concordant pairs: The mean lag between diagnosis of concor- CD patients with GG and GC genotype a positive correlation between IL-6 and
dant pairs was 7 years 5 months. fibrinogen level as well CRP was found. In IBD patients with CC genotype no
CONCLUSION: Concordance of twin pairs with CD is in keeping with previous correlation between IL-6 and fibrinogen was found (p 0.48).
studies. However UC concordance is greater than expected; in particular 19.4% CONCLUSION: The risk of developing IBD is not connected with IL-6 poly-
dizygotic twin pairs with UC are concordant. This is 4 fold expected rates of non- morphism. However, IL-6 variation might have an influence on the course of the
twin sibling concordance(2), suggesting early environment to be important in disease in IBD patients.
pathogenesis. This study supports an associaton between diet, stress and gastro- Disclosure of Interest: None declared
intestinal infection with IBD onset. The lack of associatoin with smoking at
incidence may reflect sample size.
REFERENCES P0281 THE TPMT AND ABCB1 POLYMORPHISMS IN IBD PATIENTS
1. Brant S. Update on the heritability of inflammatory bowel disease: The impor- IN CRETE: IMPACT ON DISEASE AND RESPONSE TO TREATMENT
tance of Twin Studies. Inflamm Bowel Dis 2012. C. Coucoutsi1, A. Voumvouraki1, O. Sfakianaki1, G. Emmanuel1, E. Digenakis1,
2. Bodger, et al. Concordance for IBD among twins compared to ordinary sib- I. Koutroubakis1, E. Kouroumalis1,*
lings a Nowegian population based study. J Crohns Colitis 2010. 1
Gastroenterology, University of Crete Medical School, Heraklion Crete,
Disclosure of Interest: None declared Heraklion, Greece
Contact E-mail Address: kouroum@med.uoc.gr
P0279 TEMPORAL TRENDS IN NON-STRICTURING, NON- INTRODUCTION: It is well known that polymorphisms of the TPMT gene
PENETRATING BEHAVIOUR AT DIAGNOSIS OF CROHNS (coding for thiopourine methyl-transferase), influence response to treatment
DISEASE IN OREBRO, SWEDEN: A POPULATION-BASED with azathioprine. Polymorphisms of the ABCB1 gene (coding for p-glycoprotein
RETROSPECTIVE STUDY UPDATED FOR 1988-2010 170) has been associated with IBD and resistance to treatment but results are
Y. Zhulina1, R. Udumyan2, I. Henriksson3, C. Tysk1,3, S. Montgomery2, conflicting.
J. Halfvarson1,3,* AIMS & METHODS: The aim of this study was to determine the frequencies of
1
School of Health and Medical Sciences, Orebro University, 2Clinical TPMT and ABCB1 gene polymorphisms in IBD patients from Crete, a popula-
Epidemiology and Biostatistics Unit, Orebro University Hospital, 3Dep of Internal tion genetically homogeneous, and how these polymorphisms might influence
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden response to treatment and disease behaviour. A total of 222 IBD patients, records
Contact E-mail Address: jonas.halfvarson@orebroll.se were reviewed for intake of azathioprine, possible adverse reactions, response to
treatment and need for colectomy. All patients were genotyped for TPMT gene
n
INTRODUCTION: The incidence of Crohns disease is continuing to rise in polymorphisms, that have been related to intolerance to azathioprine (G238C,
w
several countries and in others it appears to have already levelled off. We updated G460A and A719C) as well as ABCB1 gene polymorphisms (G2677T/A and
h d ra
our previous population based study,1 by re-extraction of all information on
patients diagnosed with Crohns disease between 1963 and 1987, and included
i t
patients diagnosed with Crohns disease up to 2010.
C3435T), using a PCR-RFLP method. The same polymorphisms were also deter-
mined in 119 age and sex healthy controls.
RESULTS: Allele frequencies of TPMT gene in our study population were found
W
AIMS & METHODS: Our aim was to assess temporal trends in incidence, pre-
valence and disease phenotype at diagnosis. Patients of all ages with a potential
diagnosis of Crohns disease were identified retrospectively by evaluation of
medical notes of all current and previous patients at the Colitis clinic, Orebro
University Hospital amended by computerised search in the inpatient, outpati-
to be in concordance with those reported in other Caucasian populations. 76 IBD
patients were identified receiving azathioprine, of whom 16 were discontinued (10
CD, 6 UC) due to adverse reaction. 2 of them were found to carry the G460A and
A719G alleles (TPMT 3A genotype) (12.5%). For the ABCB1 gene, G2677T/A
allele frequencies were found to be similar to those reported in the literature. There
ents, primary care and histopatological records. The medical notes were reviewed was no association of G2677T/A or C3435T with clinical phenotype, or resistance
and patients were included if they lived within the catchment area at any time to treatment. However, 77.3% of 22/222 patients who did not respond to therapy
during their disease course, were diagnosed between 1963-2010 and fulfilled the and required surgery, were found to carry both the C3434T and the G2677T
Lennard-Jones criteria for Crohns disease. Disease phenotype was defined mutation
according to the Montreal classification. CONCLUSION: Our study was conducted in a genetically homogenous popula-
tion in the island of Crete. No correlation of any single SNP was found with
United European Gastroenterology Journal 2(5S) A207
either clinical activity or response to treatment. However, most patients who risk factors for CD or UC could be shown to be significantly associated with
carried both the G2677T and C3435T mutations were refractory to treatment, differences in anti-TNF response in CD (full vs. non-response) and UC (full vs.
a finding which implies that resistance to treatment in IBD patients is a more non-response), respectively.
complex issue, which requires the presence of a genetic locus rather than a single CONCLUSION: This is the first GWAS of anti-TNF treatment response in IBD.
SNP. Power for detecting associated markers was limited. Collaboration between
Disclosure of Interest: None declared owners of anti-TNF treated cohorts e.g. in the regi of the International
Inflammatory Bowel Disease Genetic Consortium (IIBDGC) may increase the
power for identifying SNPs associated with treatment response.
P0282 FC RECEPTOR TYPE IIIA POLYMORPHISMS AND THEIR Disclosure of Interest: M. Hubenthal: None declared, A. Franke: None declared,
CORRELATION WITH CLINICAL OUTCOME IN PATIENTS WITH V. Andersen Consultancy for: MSD & Janssen
INFLAMMATORY BOWEL DISEASE DURING A LONG TERM
FOLLOW UP
G. Bodini1,*, V. savarino1, P. dulbecco1, I. baldissarro1, E. Savarino1 P0284 RARE VARIANTS IN XIAP IN MALE PEDIATRIC-ONSET
1
IRCCS San Martino DIMI, genova, Italy CROHNS DISEASE
Contact E-mail Address: bodini.giorgia@gmail.com Y. Zeissig1,2,*, B. Petersen3, S. Milutinovic4, J. Hartwig1, G. Mayr3, E. Bosse1,
K. Peuker1, M. Kohl2, M. Laass5, S. Billmann-Born3, C. Rocken6, M. Schrappe2,
INTRODUCTION: A total of 20-30% of patients with active Crohns disease P. Rosenstiel3, J.C. Reed4, S. Schreiber1, A. Franke3, S. Zeissig1
(CD) do not respond to anti-TNF- treatments and up to 40% of patients in 1
Internal Medicine I, 2Department of Pediatrics, 3Institute of Clinical Molecular
chronic therapy experience a loss of response. Furthermore about 50% of Biology, Kiel University, Kiel, Germany, 4Sanford-Burnham Medical Research
patients with ulcerative colitis (UC) experience a loss of response to anti- Institute, La Jolla, United States, 5Childrens Hospital, Medical Faculty Carl
TNF therapy after one year. The cause of this limited efficacy is unclear, but Gustav Carus, Technische Universitat Dresden, Dresden, 6Institute of Pathology,
past studies hypothesized that the individual variation of drug metabolism may Kiel University, Kiel, Germany
play an important role. Thus, given the limited data available, the role of Fc Contact E-mail Address: szeissig@1med.uni-kiel.de
IIIa receptor (i.e. one of the four receptors involved in the catabolic pathway of
anti-TNF- drugs) polymorphisms should be further explored. INTRODUCTION: The genetic basis of inflammatory bowel disease (IBD) is
AIMS & METHODS: The aim of this prospective, long-term follow up study incompletely understood and it has been suggested that rare genetic variants
was to evaluate the correlation between Fc IIIa receptor polymorphisms and contribute to the heritability of IBD.
clinical outcome in IBD patients undergoing biologic therapy. AIMS & METHODS: Here, we aimed to study rare variants involved in the
We enrolled consecutive IBD patients who achieved clinical remission by anti- pathogenesis of IBD. We performed exome sequencing and detailed immunolo-
TNF- therapy. Blood samples were collected at the beginning of biological gical profiling in a patient with early onset Crohns disease (CD). The coding
therapy. The assessment of IBD activity was based on the Harvey-Bradshaw region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was
Index score (HBI, remission 55, mild disease 5-7, moderate disease 8-16, sequenced in samples of 275 paediatric IBD patients and 1047 adult-onset CD
severe disease 416) for CD patients and on the Mayo score (Mayo52 remission, patients. XIAP genotyping was performed in samples of 2680 IBD patients and
mild disease 2-5, moderate/severe disease 6-12) for UC patients. Biochemical 2864 healthy controls. Functional effects of the identified variants were investi-
evaluation and clinical score were assessed every 8 weeks. For the genotyping gated in primary peripheral blood mononuclear cells (PBMCs) and cultured cell
analysis we used a Light Snips (Tib-Molbiol, Genova, Italy) and the Real-Time lines.
PCR Technique developed by Light Cycler 480 Instrument (Roche, Mannheim, RESULTS: A novel, de novo, nonsense mutation in the gene encoding XIAP, a
Germany). gene previously linked to primary immunodeficiency, was identified in a male
RESULTS: We prospectively included 39 patients (12UC/27 CD, 16F/23M) with patient with early-onset CD. Sanger sequencing of XIAP in large cohorts of
a median follow-up of 66.8 weeks (10-112). A total of 25 (64.1%) (10UC/15CD) paediatric IBD and adult-onset CD revealed several additional XIAP variants.
patients kept in remission during the whole follow up period, while 14 (35.9%) XIAP variants were detected in four percent of male patients with paediatric-
(2UC/12CD) experienced disease relapse. As shown in the Table, four out of 14 onset CD and were confined to this subset of IBD patients without detection of
(28.6%) (1UC/3CD) patients who experienced disease relapse, had FcIIIa-158 XIAP variants in either UC or adult-onset CD. CD in patients harbouring XIAP
V/V receptor polymorphism, while the remaining 10 (71.4%) (9CD/1UC) had variants was characterized by small and large intestinal involvement, perianal
FcIIIa-158 F/V or F/F receptor polymorphisms. Out of 25 patients who kept in disease, and stricturing behaviour. Functional studies in primary PBMCs and
remission, 3 (12%) (1CD/2UC) had FcIIIa-158 V/V receptor polymorphism, cultured cell lines revealed that the majority of identified XIAP variants were
whereas the remaining 22 (88%) (14CD/8UC) showed FcIIIa-158 F/V or F/F associated with selective defects in NOD1 and NOD2 signalling. NOD1/2 defects
receptor polymorphisms. Patients in remission tended to have more often occurred as a consequence of impaired association of mutant XIAP with RIPK2
FcIIIa-158 V/V receptor polymorphism compared to patients who relapsed, and/or altered XIAP-dependent ubiquitylation of RIPK2 thus uncoupling
but statistical significance was not reached. NOD1/2 from its downstream mediator NF-B.
CONCLUSION: Our studies reveal the frequent occurrence of XIAP variants in
Patients in Remission Relapsers male, pediatric onset CD. Moreover, our data provide a mechanistic basis to the
(n 25) (n 14) p value previously unexplained observation of functional NOD2 defects in the absence of
genetic variants in NOD2. Finally, given the known association of XIAP muta-
Polymorphism V/V 3 (12%) 4 (28.6%) 0.2251 tions with primary immunodeficiency and the observed defect in NOD1/2 signal-
ing, our data lend further support to the concept of primary immunodeficiency in
Polymorphism V/F F/F 22 (88%) 10 (71.4%) a subset of CD patients.
Disclosure of Interest: None declared
INTRODUCTION: Around 50% of IBD patients do not respond to the HBV P0319 THE ONE-YEAR EFFICACY OF INFLIXIMAB DOES NOT
vaccine. To increase the success rate, different vaccination protocols have been DEPEND ON THE TIMING OF BIOLOGICAL THERAPY IN
proposed although no study has been able to establish the optimal strategy for ULCERATIVE COLITIS
IBD patients. A. Balint1,*, T. Nyari2, Z. Szepes1, F. Nagy1, P. Miheller3, G. Horvath4,
AIMS & METHODS: Aims: To compare the success rate between two HBV P.L. Lakatos5, K. Palatka6, K. Farkas1, R. Bor1, T. Wittmann1, T. Molnar1
vaccines in IBD patients: traditional (Engerix) and a new vaccine with adjuvant 1
First Department of Medicine, 2Department of Medical Physics and Informatics,
(Fendrix). Secondary aim was to identify predictor factors of response to the University of Szeged, Szeged, 32nd Department of Medicine, Semmelweis
vaccine. University, Budapest, 4Department of Gastroenterology, Semmelweis Health
Methods: IBD patients with negative HBV serology and without previous vacci- Center, Miskolc, 51st Department of Medicine, Semmelweis University, Budapest,
nation against HBV were randomized to receive Fendrix or double doses of 6
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
Engerix at months 0, 1, 2 and 6. Anti-HBs concentration was measured 2 Contact E-mail Address: molnar.tamas@med.u-szeged.hu
months after the 3rd and 4th doses (EUDRA CT number:2010-023947-14).
RESULTS: 170 patients had been included: 55% male, 52% with Crohns dis- INTRODUCTION: Infliximab is an effective therapeutic option in patients with
ease, 30% under immunosuppressants and 37% under anti-TNF treatment. 54% refractory ulcerative colitis (UC). The optimal timing of infliximab therapy is still
of patients received Engerix and 46% Fendrix; the main characteristics of one of the outstanding questions in the therapy of UC.
patients (age, gender, type of IBD and treatment) were similar between the 2 AIMS & METHODS: The aim of our study was to assess whether there is an
groups. Overall, 44% of patients had response (anti-HBs3 100 IU/l) after the first association between the one-year remission rates and the elapsed time between
3 doses (161 patients have already received 3 doses), and 71% after the comple- the diagnosis and the start of infliximab therapy. 116 UC patients treated with
tion of the vaccination (134 have completed the vaccination). The response rate infliximab were enrolled in this retrospective study. The time elapsed between the
after the 4 doses was 67% with Engerix vs. 76% with Fendrix (p 0.2); con- diagnosis and the first biological therapy was assessed in every patient, who was
sidering anti-HBs310 IU/l (the standard threshold), the response rate was higher then categorized to groups according to the elapsed time (45 years and 55
with Fendrix than with Engerix (87 vs. 73.6%, p 0.04). In patients under years; 0-2 years, 2-5 years, 5-10 years etc).
immunosuppressants or anti-TNF drugs, the response (anti-HBs3100 IU/l) after RESULTS: The mean elapsed time between the diagnosis and the start of bio-
the 4 doses was 55% with Engerix vs. 69% with Fendrix (p 0.12). In the logical therapy was 7 years (0-38 years). 50.4% of patients started infliximab
multivariate analysis, older age (odds ratio [OR] 0.9, p50.0001) and immuno- therapy within 5 years after diagnosis. After induction with infliximab 65.6%
suppressants or anti-TNF concomitant treatment (OR 0.04, p50.0001), but of the enrolled patients achieved remission and 34.4% achieved response. After
not the type of vaccine (OR 1.9, p 0.1), were associated with the response one-year treatment period, the remission and response rates remained 67.7% and
rate to the vaccination. 7.7% of patients flared up during the study period, and 21.8%. 10.6% of patients showed loss of efficacy at one year infliximab therapy.
13% suffered adverse events (only 41% related with the vaccine, and all of them Complete mucosal healing was detected in 31.2% and deep remission in 13.9% of
mild). The frequencies of flaring up and adverse events were similar between the 2 the patients at week 52. Response rates to infliximab therapy at one year were
groups. significantly lower compared to rates at week 14 (p 0.029). The rate of remis-
CONCLUSION: A statistically significant different response rate to Fendrix sion and loss of efficacy did not depend on the elapsed time between the diagnosis
(single dose) or Engerix (double dose) has not been demonstrated in IBD and the start of biological therapy. However, response rates were higher in longer
patients yet (although the trial is still ongoing). A 4-dose schedule increases the elapsed time (p 0.036).
response rate around 30% compared with a 3-dose regimen. The older age and CONCLUSION: Infliximab is effective for drug-refractory UC to induce and
the immunosuppressive and anti-TNF treatment decrease the success rate of the maintain clinical remission. Our results did not reveal an association between the
vaccine. Both vaccines seem to be safe in IBD patients. remission rates and the elapsed time between the diagnosis and the first biological
Disclosure of Interest: M. Chaparro Other: Dra. M Chaparro has served as a therapy in UC.
speaker and has received research funding from MSD and Abbvie, J. Gordillo: Disclosure of Interest: None declared
None declared, E. Dome`nech: None declared, M. Esteve: None declared, M.
Barreiro de-Acosta: None declared, A. Villoria: None declared, E. Iglesias-
Flores: None declared, E. Alvarado: None declared, J. Naves: None declared, P0320 HEAD-TO-HEAD COMPARISON OF 5 FECAL MARKERS TO
O. Ben tez: None declared, L. Nieto: None declared, X. Calvet: None declared, PREDICT RESPONSE TO INDUCTION AND MAINTENANCE
V. Garc a-Sanchez: None declared, J. R. Villagrasa: None declared, A. Mar n: THERAPY WITH INFLIXIMAB IN ULCERATIVE COLITIS
None declared, M. Ramas: None declared, I. Moreno: None declared, J. Mate: PATIENTS; A PROSPECTIVE STUDY
None declared, J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker, a A.C. Frin1,*, S. Nancey2, J. Filippi1, G. Boschetti2, B. Flourie2, J. Drai3,
consultant and advisory member for, and has received research funding from P. Ferrari4, X. Hebuterne1
MSD and Abbvie. 1
Gastro enterology, CHU Archet 2, Nice cedex 3, 2Gastro enterology,
3
Biochemistry, CHU Lyon sud, Hospices civils de Lyon, Pierre Benite, Lyon,
4
Biochemistry, CHU Pasteur, Nice cedex 3, France
P0318 EFFICACY OF A SECOND ANTI-TNF IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE WHOSE PREVIOUS ANTI- INTRODUCTION: The role of faecal markers in monitoring anti TNF alpha
TNF TREATMENT HAS FAILED: A META-ANALYSIS therapies has been insufficiently explored. This study aimed to determine the
J.P. Gisbert 1,2,* 1,2 1,2
, A.C. Mar n , A.G. McNicholl , M. Chaparro 1,2 usefulness of five faecal proteins in the prediction of clinical response to
1
Gasttroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid, Infliximab (IFX) in Ulcerative Colitis (UC): calprotectin (fCal), Lactoferrin
Spain (fLac), M2PK (fM2PK), neopterin (fNeo), and zonulin (fZo).
Contact E-mail Address: javier.p.gisbert@gmail.com AIMS & METHODS: Thirty-one consecutive patients with an active UC, requir-
ing IFX [5 mg/kg at week 0 (W0), 2, 6 and every 8 W] were prospectively studied.
INTRODUCTION: One-third of patients with Crohns disease (CD) or ulcera- At W0, W2, W6 and W14, clinical activity was recorded and a stool sample
tive colitis (UC) receiving anti-TNF therapy do not respond to treatment (pri- collected. Clinical response to induction therapy was defined at W14 as a reduc-
mary failure), and a relevant proportion experience a loss of response (secondary tion of at least 3 points and 30% of the Mayo score. In 25 patients, endoscopies
failure) or intolerance. were performed at W0 and W12; an endoscopic Mayo subscore of 0 or 1 defined
AIMS & METHODS: To investigate the efficacy of a second anti-TNF agent endoscopic remission. Clinical response to maintenance therapy was evaluated at
after failure or intolerance to a first drug. W52 and optimization or discontinuation of IFX were considered as a failure.
METHODS: Inclusion criteria: Studies evaluating the efficacy of infliximab RESULTS: At W0 the median partial Mayo Score, the endoscopic Mayo and the
(IFX), adalimumab (ADA), and certolizumab pegol (CZP) as the second anti- UCEIS scores were 7/9 (2-9), 3/3 (2-3) and 8/11 (6-11) respectively. At W14, 19
TNF drug in CD or UC. Search strategy: Bibliographical searches in PubMed. patients (61%) were clinical responders and 13 (52%) experienced an endoscopic
Data synthesis: Percentage of response/remission; the meta-analysis was per- response. The median levels of fCal drop dramatically from W0 to W14 in
formed using the inverse variance method. responders [from 4260 mg/g (96-25051) to 128 mg/g (11-3782); p 0.0001]. In
RESULTS: We included 42 studies (35 CD, 6 UC, 1 pouchitis). The CD studies contrast, it did not differ significantly in non-responders [from 9077 mg/g (215-
comprised 30 switching IFX!ADA, 4 IFX!CZP, and 1 ADA!IFX. Overall, 50000) to 2781 mg/g (203-14149); p 0.287]. Same trends were observed for fLac
A218 United European Gastroenterology Journal 2(5S)
and fM2PK levels. At W2, fLac and fM2PK predicted accurately clinical CRP 55 mg/L), surgery, clinical remission (CDAI 5150) or clinical response
response to IFX induction (area under the curve (AUC) 0.82, 0.84 and 0.88 (CDAI70) after induction regimen of anti-TNF (week 12).
respectively): cuts-offs of 800 mg/g for fCal, 20000 ng/g for fLac and 50 UI/mL Overall, 28 consecutive CD patients were prospectively included during 1 year.
for fM2PK determined by ROC curves allowed to discriminate clinical respon- All the patients underwent a DW-MREC1,2 within 4 weeks before starting anti-
ders from non responders to induction therapy, with good sensitivities (Se) (82%, TNF. Adalimumab (ADA) was administered as 160mg at W0, 80mg at W2 and
81% and 88%, respectively), and specificities (Sp) (69%, 70% and 80%, respec- 40mg e.o.w. Infliximab (IFX) was administered as 5mg/kg at W0, W2 and W6.
tively). FLac measured at W2 were the more valuable marker to predict endo- The collected MRI parameters were: Clermont score1,2, apparent diffusion coef-
scopic remission at W12 [(AUC 0.80, Se and Sp 72% with a cut-off of 32891 ficient (ADC), Magnetic Resonance Index of Activity (MaRIA), presence of
ng/g). At W14, the three previous markers were also reliable to predict clinical stenosis, fistula, abscess, sclerolipomatosis or mesenteric lymph nodes.
response at W52 (AUC 0.82, 0.86 and 0.75 respectively) with best cut-offs of RESULTS: Median age and disease duration at inclusion were 37 years (17-71)
146 mg/g for fCal, 3457 ng/g for fLac and 2.25 UI/mL for fM2-PK. FCal, fLac and 34 months (0-456) respectively. Overall, 14 (50%) were smokers, 7 (25%)
and fM2PK were well correlated with both the endoscopic Mayo subscore and underwent previous intestinal resection and 7 (25%) had ano-perineal lesions. 13
the UCEIS. FNeo and fZo did not show any relevant result. patients (46.4%) had ileal CD (L1), 3 (10.7%) colonic CD (L2), 12 (42.8%)
CONCLUSION: FCal, flac and fM2-PK predicted with a good accuracy the ileocolonic CD (L3). CD phenotypes were non-stricturing non-fistulizing (B1),
clinical response to induction and maintenance IFX therapy in UC. The mea- stricturing (B2) and fistulizing (B3) in 9 (32.1%),12 (42.9%), and 7 (25.0%)
surement of one of these markers at W0 and at the end of induction might patients, respectively. While 13 patients were treated with IFX (44.4%), 15
distinguish responders from non responders to IFX maintenance therapy were treated with ADA (55.6%). Among them, 10 (35.7%) patients received
within one year. concomitant thiopurines. At inclusion, median CDAI was 225 (170-393) and
Disclosure of Interest: None declared median C-reactive protein value was 17.1 mg/L (2.9-148). 13 patients (46.4%)
experienced advanced remission at W12.
Mean ADC seemed lower (1.912 vs 2.162, p 0.07) and mean MaRIA seemed
P0321 ALTERATIONS OF FECAL MICROBIOTA AND METABOLIC higher (47.0 vs 41.9, p 0.13) in the patients treated with anti-TNF therapy
LANDSCAPE IN RESPONSE TO ORAL OR INTRAVENOUS IRON which experienced advanced remission at W12.
REPLACEMENT THERAPY IN PATIENTS WITH INFLAMMATORY Presence of mesenteric lymph nodes was predictive of no need for surgery at W12
BOWEL DISEASES in the patients treated with anti-TNF therapy (p 0.01). Sclerolipomatosis
T. Lee1, A. Schmidt2,*, I. Lagkouvardos2, T. Clavel2, A. Walter3, M. Lucio3, seemed also predictive of no requirement for surgery at W12 in the patients
K. Smirnov3, P. Schmitt-Kopplin3, R. Fedorak1, D. Haller2 treated with anti-TNF therapy (p 0.13). Presence of mesenteric lymph nodes
1
University of Alberta, Edmonton, Canada, 2Technical University of Munich, was predictive of response to anti-TNF therapy at W12 (p 0.05).
Freising, 3Helmholtzzentrum Munchen, Munchen, Germany CONCLUSION: MRI parameters reflecting inflammatory activity (presence of
Contact E-mail Address: annemarie.schmidt@tum.de mesenteric lymph nodes, sclerolipomatosis, low ADC) seemed predictors of
advanced remission or response to anti-TNF agents in CD. Despite the lack
INTRODUCTION: Iron deficiency is a common complication in patients with of power due to small sample size, the intermediary results of our study show that
inflammatory bowel diseases (IBD) and oral iron replacement therapy is sug- DW-MREC could be a useful and promising tool to predict effectiveness of anti-
gested to exacerbate IBD symptoms. We hypothesized that oral iron may impact TNF therapy in CD.
the composition of the gut microbiota and thereby affect the disease status. REFERENCES
AIMS & METHODS: An open-labelled clinical trial including patients with Buisson A et al. Aliment Pharmacol Ther 2013; 37: 537-545.
Crohns disease (CD; N 29) or ulcerative colitis (UC; N 19) as well as control Buisson A, Hordonneau C, et al. Am J Gastroenterol 2014; 109: 89-98.
patients with iron deficiency (iron saturation 5 16% and ferritin 5 100) Disclosure of Interest: A. Buisson Lecture fee(s) from: Abbvie, MSD, C.
(N 20) was performed to compare the effects of oral (PO; ferrous sulfate) vs. Hordonneau: None declared, J. Scanzi: None declared, F. Goutorbe: None
intravenous (IV; iron sucrose) iron replacement therapy over a period of three declared, M. Goutte: None declared, B. Pereira: None declared, G.
months. The health status was assed via quality of life (EQ 5D and SIBDQ) and Bommelaer: None declared
disease activity (HBI and PMS) questionnaires. Stool and sigmoid mucosal biop-
sies were collected before and after treatment. Gut bacterial diversity and com-
position were assessed by high-throughput sequencing of 16S rRNA genes (V4 P0323 PREDICTIVE FACTORS OF EARLY INFLIXIMAB INFUSION
region). Fecal metabolites were analyzed by ESI-FT-ICR-MS. REACTIONS IN INFLAMMATORY BOWEL DISEASE
RESULTS: PO and IV treatments were comparable regarding amelioration of C. Duron1, A. Buisson1,2,*, M. Goutte1, B. Pereira3, G. Bommelaer1
iron deficiency, with superior but not significant levels of ferritin and iron satura- 1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2 Microbes,
tion in the IV group. Worsening or improvement of disease activity and quality Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/
of life were independent of iron treatments (no difference between PO and IV). Universite dAuvergne; USC-INRA 2018, 3Biostatistics unit, DRCI, CHU
Fecal bacterial diversity was significantly different between control, UC and CD Clermont-ferrand, Clermont-ferrand, France
patients before and after iron treatment. Samples from IBD patients were char-
acterized by marked inter-individual differences as well as lower phylotype rich- INTRODUCTION: Anti-TNF agents including infliximab (IFX), a chimeric
ness and proportions of unknown Clostridiales. We identified the presence of 18 antibody, are the most effective therapies in inflammatory bowel diseases
CD-specific molecular species (OTUs), many of which matched sequences of (IBD). Early IFX Infusion Reaction (EIIR) is rare, but is a serious complication
facultative anaerobic bacteria. Major shifts in bacterial diversity occurred in in IBD patients, and could lead to drug withdrawal and consequently impact the
approximately half of the participants after treatment, independently of disease. therapeutic strategy. The role of premedication remains uncertain.
In those samples where bacterial profiles shifted, changes in diversity were sig- AIMS & METHODS: We aimed to establish predictors of EIIR in IBD patients
nificantly higher in IBD patients. However, no consistent changes in the occur- and to assess the impact of premedication.
rence of specific OTUs relative to iron treatment could be identified, suggesting Patients, disease and infusions characteristics, collected for all IFX infusions
individual-specific responses to treatment. Metabolite analysis using OSC-PLC performed in our IBD Unit, were retrieved from electronic charts from 2008 to
classification showed a clear separation of both UC and CD from control 2013. The EIIR were defined as events related to IFX infusions occurring within
patients before the iron treatment. After therapy, metabolite profiles were only two hours of the infusion. Univariate and multivariate analysis were performed
different in UC patients indicating a possible convergence of CD patients with taking into account the inter-patients and intra-patients variability and interac-
control subjects in response to the iron treatment. Separation into IV- and PO- tion test.
specific metabolite profiles appeared in the control and CD group but not in the RESULTS: Among the 80 included IBD patients, 51 (63.8%) had Crohns dis-
UC group. ease (CD). The mean age and disease duration were 38.8 years (14.1) and 7.4
CONCLUSION: Shifts in bacterial diversity associated with iron treatment are years (7.0) respectively.
independent of the route of administration and are more pronounced in IBD Overall, 23 IBD patients (28.8%) experienced EIIR. Age, prior history of intest-
patients. Efficiency and clinical outcome of both iron therapies are comparable in inal resection, atopy or allergy, familial history of IBD, type of IBD, disease
both IBD patient cohorts. location, disease extent or disease duration were not predictive of EIIR. In uni-
Disclosure of Interest: None declared variate analysis, non-stricturing non fistulising CD was predictive of EIIR
(26.4% vs 52.2%, p 0.03). This result was confirmed by multivariate analysis.
Of 1107 infusions, we observed 38 EIIR (3.4%). In univariate analysis, the first
P0322 DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING four infusions (26.4% vs 52.6%, p 0.002) and the resumption of IFX after drug
PARAMETERS AS PREDICTORS OF REMISSION IN CROHNS holiday (17.2% vs 29.0%, p 0.001) were predictive of EIIR. Multivariate ana-
DISEASE PATIENTS TREATED WITH ANTI-TNF THERAPY lysis confirmed that the resumption of IFX after drug holiday was a major risk
A. Buisson1,2,*, C. Hordonneau3, J. Scanzi1, F. Goutorbe1, M. Goutte1, factor of EIIR (OR 24, p50.001) but not the first four infusions. Surprisingly,
B. Pereira4, G. Bommelaer1,2 a premedication (anti-histaminic or hydrocortisone) seemed to be a risk factor
1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2Microbes, for EIIR in univariate and multivariate analysis while concomitant therapies did
Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/ not prevent EIIR. As resumption of IFX after drug holiday was a major risk
Universite dAuvergne; USC-INRA 2018, 3Radiology department, CHU Estaing factor for EIIR, interaction test was performed and showed that the increased
Clermont-ferrand, 4Biostatistics unit, DRCI, CHU Clermont-ferrand, Clermont- risk induced by the premedication was related to resumption of IFX after drug
ferrand, France holiday.
The patients who experienced EIIR and those who did not experience EIIR have
INTRODUCTION: Anti-TNF agents are the most effective therapy in Crohns had to discontinue IFX therapy in 69.6% (16/23) and 50.9% (29/57) of cases,
disease (CD). However, almost one-third of the patients experience primary fail- respectively (NS).
ure to anti-TNF therapy. Diffusion-Weighted Magnetic Resonance Entero- CONCLUSION: EIIR is a major event in the history of IBD patients treated by
Colonography (DW-MREC) has shown good accuracy to detect and assess IFX as it leads to drug discontinuation and thus limits considerably the available
inflammatory activity in CD1,2. therapeutic armamentarium. The resumption of IFX after drug holiday is the
AIMS & METHODS: We aimed to study the DW-MREC parameters as pre- major risk of EIIR and could be predicted in part by the measurement of anti-
dictors of advanced remission (clinical remission defined as CDAI 5150 AND drug antibodies. Non stricturing non penetrating CD could be also a risk factor.
United European Gastroenterology Journal 2(5S) A219
The efficacy of premedication remains questionable and could be limited to the signals were observed, confirming the safety profile of GMA apheresis even in a
high risk patients. difficult-to-treat UC patients group.
Disclosure of Interest: C. Duron: None declared, A. Buisson Lecture fee(s) from: REFERENCES
Abbvie, MSD, M. Goutte: None declared, B. Pereira: None declared, G. Habermalz B and Sauerland S. Clinical effectiveness of selective granulocyte,
Bommelaer: None declared monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis.
Dig Dis Sci 2010; 55: 14211428.
Disclosure of Interest: A. Dignass Financial support for research from: ART trial:
P0324 COMPARISON BETWEEN INFLIXIMAB AND ADALIMUMAB Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka, B. Bonaz
FOR THE TREATMENT OF PERIANAL FISTULISING CROHNS Financial support for research from: ART trial: Investigator, Lecture fee(s) from:
DISEASE Otsuka, Consultancy for: Otsuka, A. Akbar Financial support for research from:
A. Tursi1, W. Elisei2, M. Picchio3, R. Faggiani4, C. Zampaletta4, G. Pelecca4, ART trial: Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka,
G. Brandimarte5,* R. Gruber Other: Employee of Otsuka Pharmaceutical Europe Ltd.
1
Gastroenterology Service, ASL BAT, Andria, 2Division of Gastroenterology, ASL
Roma H, Albano Laziale (Roma), 3Division of Surgery, "P. colombo" Hospital,
ASL Roma H, Velletri (Roma), 4Division of Gastroenterology, "Belcolle" P0326 MID-AND LONG-TERM OUTCOMES AND REMISSION
Hospital, Viterbo, 5Division of Internal Medicine and Gastroenterology, "Cristo MAINTENANCE RATE BY PROLONGED TREATMENT WITH
Re" Hospital, Rome, Italy TACROLIMUS FOR REFRACTORY ULCERATIVE COLITIS
A. Ito1,*, K. Shiratori1, O. Teppei1, M. Tanishima1, K. Tomoko1, I. Bunnei1
INTRODUCTION: Infliximab (IFX) and Adalimumab (ADA) have improved 1
Departoment of Medicine, Institute of Gastroenterology, Tokyo Womens Medical
the management of perianal Crohns disease (CD). However, comparative studies Unvercity, Tokyo, Japan
have not been reported previously. Contact E-mail Address: itoayumi@ige.twmu.ac.jp
AIMS & METHODS: Our aim was to compare the outcomes of CD patients
with perianal fistulising disease treated with IFX or ADA. INTRODUCTION: Efficacy of tacrolimus (TAC) as remission induction therapy
A retrospective medical record review of CD patients, who received IFX or ADA for refractory ulcerative colitis (UC) has been reported. However, hitherto mid-
for perianal fistulising disease, was conducted. Fistulas were assessed using and long-term outcomes and remission maintenance rates following a prolonged
Magnetic Resonance Imaging (MRI), and seton placement was performed treatment with TAC have not been evaluated.
when appropriate. A 36-month follow-up was performed. AIMS & METHODS: In this study, we were interested to evaluate the clinical
RESULTS: Twenty CD patients (9 males and 11 females; median age 31.5 years, remission maintenance rate for TAC in patients with UC. For this study, we
range 18-39) were treated (9 with IFX and 11 with ADA). Seton placement was included 29 patients (15 male and 14 female) who had received a TAC-based
performed in 18 patients (8 in IFX and 10 in ADA group). induction therapy between April 2009 and December 2013 (mean observation
The baseline Harvey-Bradshaw index (HBI) and perianal disease activity index period 728 311 days). In 10 patients, TAC was administered for 90 days
(PDAI) significantly decreased after 6 weeks and remained at similar levels for including the period of remission induction, followed by switch to an immuno-
the entire follow-up in both groups. modulator (azathioprine) to maintain remission (group 1). In 19 patients, TAC
The complete response rate of fistulas was 75% of patients at 36 months (78% in was continued beyond the period of remission induction to maintain remission
IFX and 73% in ADA group), with no significant difference between the two (group 2). The patients in groups 1 and 2 were matched with respect to gender,
study groups. disease duration, pre-TAC haemoglobin (Hb), C-reactive protein (CRP), clinical
Setons were withdrawn from twelve patients (5 in IFX and 7 in ADA group), activity index (CAI, according to Lichtiger), and endoscopic index (EI) at one
who experienced complete response and showed no radiological evidence of dis- month after TAC administration. The total dose of prednisolone administered up
ease at 12-month follow-up. to the time when clinical remission was achieved, duration of hospital stay, and
Two patients with complex fistulas failed to obtain fistula closure under anti- the time to recurrence between the two groups were factored into analyses.
TNF (one in each groups). Changing the anti-TNF was useless and both Remission was defined as a CAI score of 4 or less at week 4 or later after
patients underwent to permanent colostomy. TAC administration. Likewise, recurrence was defined as a case in whom the
CONCLUSION: Efficacy of IFX and ADA was similar in treating perianal blood trough level was increased (10 ng/dl or above) by means of intense intra-
fistulising CD patients. venous regimen of prednisolone, switch to a biological preparation, repeat or
Disclosure of Interest: None declared dose-escalating TAC administration required to induce remission.
RESULTS: There was no significant difference in gender, disease duration, pre-
TAC Hb, CRP, CAI, total dose of prednisolone administered until remission,
P0325 EFFICACY AND SAFETY OF GRANULOCYTE, MONOCYTE/ duration of hospital stay, and the time to recurrence between the two groups. The
MACROPHAGE ADSORPTIVE APHERESIS IN STEROID- mean TAC administration period in group 2 was 235 122 days vs 86 13 days
DEPENDENT ACTIVE UC WITH INSUFFICIENT RESPONSE OR for group 1. Further, the EI scores at one month after TAC administration were
INTOLERANCE TO IMMUNOSUPPRESSANTS AND/OR 5.8 1.6 and 7.8 2.1 for group 1 and group 2, respectively; the difference was
BIOLOGICAL THERAPIES (THE ART TRIAL): SAFETY RESULTS AT significant (P 5 0.012). Regarding the treatment safety, finger tremor was
12 WEEKS observed in 2 patients in group 1 and 5 patients in group 2, renal dysfunction
A. Dignass1,*, B. Bonaz2, A. Akbar3, R. Gruber4 on behalf of The ART trial was observed in none of the group 1 patients, but in 3 of group 2 patients.
working group CONCLUSION: In this study, although no significant difference was found in
1
Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany, 2CHU the time to recurrence, the EI score at one month after TAC treatment was
Grenoble, Grenoble, France, 3St. Marks Hospital, London, United Kingdom, significantly higher in group 2 compared with group 1. This finding suggests
4
Otsuka Pharmaceutical Europe Ltd., Frankfurt, Germany that a maintenance dose of TAC is likely to maintain remission even in patients
Contact E-mail Address: axel.dignass@fdk.info with delayed mucosal healing. However, longer TAC therapy may carry higher
risk of adverse side effects.
INTRODUCTION: Current medical treatment options for patients with steroid- Disclosure of Interest: None declared
dependent, active ulcerative colitis (UC) with insufficient response or intolerance
to immunosuppressants (IS) and/or biologicals are limited and not evidence-
based. In addition, the recognised related safety profiles are considerable. The P0327 STRESS AND NONSTEROIDAL-ANTIINFLAMMATORY DRUGS
clinical use of Granulocyte, Monocyte/Macrophage Adsorptive (GMA) apher- (NSAID)-INDUCED EXACERBATION OF EXPERIMENTAL COLITIS
esis with Adacolumn has previously demonstrated a safe and efficacious use in IS ATTENUATED BY ANTIBIOTIC RIFAXIMIN AND PROBIOTIC
this subgroup of UC patients. SACCHAROMYCES BOULARDII
AIMS & METHODS: This study was an uncontrolled, open-label, multicenter B. Brzozowski 1,*, M. Zwolinska-Wcislo 1, E. Karczewska 2, A. Ptak-Belowska3,
trial conducted in the UK, France and Germany (ART, NCT01481142). K. Urbanczyk 4, G. Krzysiek-Maczka3, M. Strzalka3, T. Brzozowski 3
Consecutive eligible patients (18-75 years, steroid-dependent active UC with a 1
Gastroenterology, Hepatology and Infectious Diseases Clinic, 2Department of
Rachmilewitz (CAI) index 6 and an Endoscopic Activity Index (EAI) 4, and Microbiology, Faculty of Pharmacy, 3Department of Physiology, 4Department of
insufficient response or intolerance to IS and/or biologicals) were included. Pathomorphology, Jagiellonian University Medical College, Cracow, Poland
Patients received at least 5 weekly GMA apheresis. Evaluation visits were
planned at Week 12, 24 and 48. The primary endpoint was the remission rate INTRODUCTION: Clinical and experimental studies have indicated that stress
(CAI 4) at Week 12 in the Intention-to-treat (ITT) population. We report safety plays an important role in the initiation and perpetuation of inflammatory bowel
results observed along with the earlier communicated 12 weeks interim efficacy disease (IBD), however, the mechanism of stress-induced alterations in the sever-
results of 55.9% response and 39.3% remission. ity of the inflammatory process of colonic mucosa remains unclear. Colonic
RESULTS: The safety population comprised 85 subjects having received at least microbiota is important component of IBD pathogenesis but its influence on
one apheresis treatment. 14 out of 85 patients (16.5%) discontinued up to Week the colonic mucosal barrier under stress conditions as well as the efficacy of
12. 61/85 patients (71.8%) experienced any AE; in 54 patients (63.5%) these were treatment with antibiotics or probiotics on experimental colitis have not been
of mild or moderate intensity, all transient, mainly consisting of headaches and fully explained.
problems related to venous access difficulties. Six (7.1%) patients experienced AIMS & METHODS: We studied the effect of cold stress on healing of experi-
serious adverse events (SAEs), all unrelated to the study treatment. SAEs or AEs mental colitis induced in rats by intrarectal administration of 2,4,6- trinitroben-
that led to discontinuation or withdrawal from the study were either related to zenosulfonic acid (TNBS) and we assessed the involvement of colonic microflora
the indication being studied (ulcerative colitis), or to poor venous access/ vascular in healing of TNBS colitis in rats exposed to stress and stress combined with
access. There were no clinically significant changes in vital signs. There were few aspirin (ASA) treatment. The efficacy of antimicrobial therapy by antibiotic
shifts from baseline to week 12 among clinically significant values in safety- rifaximin or probiotic Saccharomyces boulardii on stress-induced impairment of
relevant laboratory parameters. the healing of experimental colitis in the absence or presence of ASA treatment
CONCLUSION: GMA apheresis with Adacolumn has shown benefit in more was investigated. Animals with TNBS-induced colitis and exposed to cold stress
than 50% of patients with moderate to severe, active, steroid-dependent UC and for 20 min every second day were treated i.g. daily with 1) vehicle (saline), 2)
insufficient response or intolerance to IS and/or biological agents. No new safety Saccharomyces boulardii (108CFU/rat), 3) rifaximin (100 mg/kg), 4) ASA (20mg/
A220 United European Gastroenterology Journal 2(5S)
kg) alone or 5) ASA (20 mg/kg) combined with Saccharomyces boulardii (108CF/ declared, S. Nikolaus: None declared, D. Huppe: None declared, S. Schreiber:
rat) or rifaximin (100 mg/kg). At day 10 upon colitis induction, the colonic blood None declared
flow (CBF) was determined by H2-gas clearance technique, the blood was with-
drawn for measurement of plasma MPO, IL-1 and TNF- levels and the expres-
sion of proinflammatory markers IL-1, TNF-, iNOS, COX-2 and HIF- were P0329 PREDICTORS OF HOSPITALIZATION IN PATIENTS WITH
analyzed in colonic mucosa of stressed rats. MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
RESULTS: Exposure to stress significantly increased the area of TNBS damage FROM ULTRA 1 AND ULTRA 2
and the concomitant administration of ASA further augmented the area of these B. Feagan1,*, W.J. Sandborn2, W. Reinisch3, S. Ghosh4, A.M. Robinson5,
lesions. This delay in mucosal healing caused by cold stress was accompanied by A. Lazar6, Q. Zhou5, M. Skup5, R.B. Thakkar5
a significant fall in the CBF, the significant rise in tissue weight, a 4-fold increase 1
Robarts Research Institute and University of Western Ontario, London, Canada,
in MPO activity and the mucosal overexpression of IL-1, TNF-, iNOS, COX-2 2
UCSD, La Jolla, United States, 3McMaster University, Hamilton, 4University of
and HIF1. In stressed animals, the significant increase of E. coli counts in feces Calgary, Calgary, Canada, 5AbbVie Inc, North Chicago, United States, 6AbbVie
and the spleen were observed and this effect was significantly attenuated by both Deutschland GmbH & Co. KG, Ludwigshafen, Germany
rifaximin and Saccharomyces boulardii. Treatment with rifaximin and to lesser
extent with probiotic Saccharomyces boulardii significantly decreased the area of INTRODUCTION: Patients with moderately to severely active ulcerative colitis
colonic lesions while increasing CBF and significantly reducing the plasma IL-1 (UC) are frequently hospitalized due to disease deterioration. The factors asso-
and TNF- levels and the colonic expression of proinflammatory markers. ciated with hospitalization risk in patients treated with non-biologic therapy for
CONCLUSION: 1/ Stress exacerbates experimental colitis due to increase of UC are analyzed in patients randomized to placebo (PBO) in ULTRA 11 and
intestinal pathogenic E. coli and this pathogenic bacteria translocation to the ULTRA 22.
extra-intestinal organs such as spleen, and 2/ Modifying of the intestinal micro- AIMS & METHODS: ULTRA 1 had an 8 to 12 week double-blind (DB) phase
biota through probiotics or selected antibiotics could be of clinical importance in followed by an open-label (OL) all adalimumab (ADA) phase to week 52.
the limitation of the consequences of environmental factors such as stress and ULTRA 2 was a 52-week DB trial in which patients with inadequate response
adverse effects of NSAID therapy in patients with lower GI-tract disorders. could receive OL ADA 40 mg beginning at week 12. Patients with loss of
Disclosure of Interest: None declared response or intolerance to prior anti-TNF use could enrol in ULTRA 2.
Logistic regression was used to determine predictors of all-cause and UC-related
hospitalization in PBO randomized patients from ULTRA 1 and ULTRA 2.
P0328 TNF-ALPHA AS INDUCTION AND MAINTENANCE THERAPY Baseline variables assessed were age, sex, disease duration, pancolitis, prior
FOR CROHNS DISEASE: A PROSPECTIVE OBSERVATIONAL anti-TNF use, CRP, albumin, Mayo score, aminosalicylate use, immunomodu-
STUDY IN GERMANY lator use, corticosteroid use, alcohol use, smoking status, and weight. Model 1
B. Bokemeyer1,2,*, U. Helwig3, N. Teich4, C. Schmidt5, T. Krummenerl6, A.- also included baseline endoscopy subscore (2 vs 3) and Model 2 also included
K. Rupf7, H. Hartmann8, M. Blaker9, A. Krummenerl10, M. Duffelmeyer11, stool frequency (SFS, 0-1 vs 2-3), rectal bleeding (RBS, 0-1 vs 2-3), and PGA (0-2
R. Hinrichs12, P. Hartmann2, S. Nikolaus1, D. Huppe8, S. Schreiber1 vs 3) subscores. Patients were censored 70 days after moving to OL ADA.
1
Clinic of General Medicine I, University Hospital Schleswig-Holstein, Campus RESULTS: Selected odds ratios for the association of baseline variables with
Kiel, Kiel, 2Gastroenterology Practice Minden, Minden, 3Gastroenterology hospitalization for PBO randomized patients from ULTRA 1 and 2 are shown in
Practice Oldenburg, Oldenburg, 4Gastroenterology Practice Leipzig, Leipzig, the table. In both regression models, male sex was a significant predictor for
5
Gastroenterology Clinic IV, University Hospital Jena, Jena, 6Gastroenterology lower risk of all-cause and UC-related hospitalization, whereas lower baseline
Practice, Munster, 7Medical Department, Clinic of Friedrichshafen, albumin and higher baseline CRP concentration were significant predictors for
Friedrichshafen, 8Gastroenterology Practice Herne, Herne, 9Gastroenterology higher risk of all-cause and UC-related hospitalization. Alcohol use was asso-
Practice Eppendorfer Baum, Hamburg, 10Department of Internal Medicine I, ciated with UC-related hospitalization in both models. Disease activity at base-
Martha-Maria Hospital Halle Dolau, Halle (Saale), 11IOMTech GmbH, Berlin, line, as measured by Mayo score or individual subscores, disease duration, prior
12
Competence Network IBD, Kiel, Germany anti-TNF use, pancolitis, or use of aminosalicylates, immunomodulators, or
Contact E-mail Address: bernd.bokemeyer@t-online.de corticosteroids were not associated with hospitalization risk in either model.
Table. Logistic regression odds ratios for hospitalization in PBO-randomized
INTRODUCTION: The nationwide BioCrohn Registry (Biological Registry with patients from ULTRA 1 and 2
Crohns Disease Patients in Germany) of the German Competence-Network IBD
is a five-year prospective registry of about 1,500 patients with Crohns disease Model 1 Model 2
(CD) in Germany. This is a sub-study of the BioCrohn Registry reporting the
anti TNF-alpha antibody (TNF) steroid-free remission rates of induction and All-cause UC-related All-cause UC-related
maintenance therapy in 391 anti-TNF-na ve CD-patients with adalimumab
(ADA) or infliximab (IFX) up to 12-months follow-up. Sex (male) 0.37** 0.41* 0.35** 0.38*
AIMS & METHODS: Within the framework of this non-interventional prospec-
tive online documentation, data in respect to the course of disease, psychosocial Baseline CRP (mg/L) 1.01* 1.02** 1.01* 1.02**
burden of disease, health economics and the genetic profile were examined. End Albumin (540 g/L) 2.39* 2.82** 2.50* 3.00**
of 2012 the recruitment was stopped having 1,525 CD-patients included by 59 Current alcohol use 1.82 2.11* 1.82 2.12*
different gastroenterology practices and hospitals with IBD experience. All
patients have a 5 year follow-up period. The databank for baseline and 12-
months data has been closed in 03/2013 and after databank cleansing now we
have the finalized data including the 6- and 12-months visits. CONCLUSION: In this analysis, factors associated with hospitalization in
RESULTS: 391 TNF-naive CD-patients (ADA: n 264; IFX: n 127) have patients receiving non-biologic therapy for UC were sex, increased inflammation
been analysed (average age: 36 years; female: 52%; smokers 34%; disease dura- (as measured by CRP) and low baseline albumin. These factors may be useful
tion: 9.3 years; bowel resection: 33%; prior immunosuppressive therapy: 75%). when evaluating future therapeutic interventions in patients with UC failing
Baseline characteristics were similar in the two groups. The IBD-therapy fol- conventional therapy.
lowed an accelerated step-up management. Immunosuppressants were used in REFERENCES
19% at 6 and in 21% after 12 months. Accordingly to the TNF therapy, the use 1. Reinisch, et al. Gut 2011; 60: 780.
of systemic glucocorticoids dropped over time (baseline until 6 and 12 months) 2. Sandborn, et al. Gastroenterol 2012; 142: 257.
from 22.0% to 6.3% and 8.3%, respectively (p50.001). The remission rate Disclosure of Interest: B. Feagan Financial support for research from:
(PGA) at 6 months was 70.9% and 72.1% after 12 months. In spite of the Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis,
TNF-induced clinical remission (4 70%) the psychosocial impairments with Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech,
anxiety/depression (EQ-5D) showed only minor improvement and remained on ActoGenix, Wyeth, Lecture fee(s) from: AbbVie, UCB, and Janssen,
a relatively high level (baseline: 37%, 6 months: 31%, 12 months: 28%). In the Consultancy for: Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho,
induction therapy with TNF we found a steroid-free remission (HBI5 5) in Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie,
67.1% at 6 months and in 68.9% at 12 months in the maintenance therapy. Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals,
Evaluating the efficacy of ADA vs. IFX we did not find any difference in ster- Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK,
oid-free remission rates as an induction therapy at month 6 (ADA: 68.2%; IFX: Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan,
64.6%; p n.s.) or as a maintenance therapy at month 12 (ADA: 68.1%; IFX: Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc,
70.6%; p n.s.). In the per protocol TNF-group with regular visits at 6 and 12 Sigmoid Pharma, W. Sandborn Financial support for research from: AbbVie,
months (n 264) 91.7% of these patients were still on TNF after 12 months. Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium,
Additionally 5.7% of the ADA-patients switched to IFX and 9.2% of the IFX- Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals,
patients switched to ADA. This means that 76.8% of the patients starting with and UCB Pharma., Lecture fee(s) from: AbbVie, Bristol-Myers Squibb, and
TNF were on the same TNF therapy after 12 months. Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI Therapeutics, Inc.,
CONCLUSION: In this real life setting anti-TNF therapy could induce steroid- Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-
free remission in about 70% with the relatively early escalation of therapy in Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic Healthcare Limited,
IBD-experienced centres. In comparison there is no difference in steroid-free Aptalis, BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol-Myers
remission rates between ADA vs. IFX. Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon
Disclosure of Interest: B. Bokemeyer Financial support for research from: Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado
Abbvie, Ferring; UCB, Lecture fee(s) from: Abbvie, MSD, Ferring, Falk, Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical
Takeda, Consultancy for: Abbvie, MSD, Ferring, Takeda, U. Helwig: None Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics,
declared, N. Teich: None declared, C. Schmidt: None declared, T. Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc.,
Krummenerl: None declared, A.-K. Rupf: None declared, H. Hartmann: None Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead
declared, M. Blaker: None declared, A. Krummenerl: None declared, M. Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences,
Duffelmeyer: None declared, R. Hinrichs: None declared, P. Hartmann: None Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon
United European Gastroenterology Journal 2(5S) A221
Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research
P0331 PHARMACOLOGY OF ETROLIZUMAB IN A PHASE 2 STUDY IN
Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin
MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer
Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter C. Looney1, F. Fuh1, M.T. Tang1, X. Wei1, M.E. Keir1, G.W. Tew1, J. Eastham-
and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Anderson1, L. Diehl1, A. Salas2, G. De Hertogh3, S. Francom1, H. Gilbert1,
Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix D. Luca1, J.G. Egan1, S. Vermeire3, J.C. Mansfield4, C. Lamb4, B. Feagan5,
Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma J. Panes2, D. Baumgart6, S. Schreiber7, I. Dotan8, W. Sandborn9, P. Rutgeerts3,
Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. A. Pharma T.T. Lu1,*, S. OByrne1, M. Williams1
1
(UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma Genentech, Inc., South San Francisco, United States, 2Hospital Clinic de
AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Barcelona, Barcelona, Spain, 3University of Leuven, Leuven, Belgium, 4University
Limited (VBL), Warner Chilcott UK Limited, W. Reinisch Consultancy for: of Newcastle, Newcastle upon Tyne, United Kingdom, 5University of Western
AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Ontario, London, Canada, 6Humboldt-University of Berlin, Berlin, 7Christian
Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Albrechts University, Kiel, Germany, 8Tel Aviv University, Tel Aviv, Israel,
9
Ferring, Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin University of California San Diego, La Jolla, United States
Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Contact E-mail Address: bishop.caroline@gene.com
Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer,
Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough, INTRODUCTION: Etrolizumab, a humanized antibody to the integrin 7,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, blocks 47:MAdCAM-1 and E7:E-cadherin interactions, and has been
Zyngenia, Austria and 4SC, S. Ghosh Financial support for research from: shown in a Phase 2 study to be effective at inducing clinical remission in patients
AbbVie, Consultancy for: AbbVie, Shire, Pfizer, Bristol-Myers Squibb, Janssen with moderate-to-severely active ulcerative colitis (UC).1 Maximal occupancy of
and Merck & Co, Other: advisory committee or review panel for AbbVie and 7 receptors was observed on lymphocyte subsets in peripheral blood and colonic
Merck & Co., A. Robinson Shareholder of: AbbVie, Other: Employee: AbbVie, tissue in both dose cohorts (monthly subcutaneous doses of 100mg [low] or
A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, Q. Zhou 300mgloading dose [high]), with a corresponding increase in B and T intestinal
Shareholder of: AbbVie, Other: Employee: AbbVie, M. Skup Shareholder of: homing lymphocytes in peripheral blood.2 Here we present the pharmacody-
AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of: AbbVie, namic (PD) effects of etrolizumab in colonic tissue and the serum pharmacoki-
Other: Employee: AbbVie netics (PK) from the Phase 2 study.
AIMS & METHODS: Changes from baseline were assessed in colonic tissue gene
expression at weeks 6 and 10 (qPCR, n 96) and in E cells at week 10 (immu-
P0330 DEEP REMISSION IMPROVES CLINICAL OUTCOMES AFTER nohistochemistry [IHC], n 55 & 73 in epithelium and lamina propria, respec-
INFLIXIMAB DISCONTINUATION IN INFLAMMATORY BOWEL tively). Serum drug levels were measured at multiple time points following
DISEASES etrolizumab administration.
C. Felice1,*, D. Pugliese1, M. Marzo1, G. Andrisani1, O.M. Nardone1, A. Papa1, RESULTS: Etrolizumab displayed linear kinetics, with 4.4 fold exposure
I. De Vitis1, G.L. Rapaccini1, L. Guidi1, A. Armuzzi1 separation between the two dose cohorts. The average serum concentration of
1
IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato etrolizumab at week 10 was 8.5mg/mL and 37.8mg/mL for the low and high dose
Columbus, Catholic University, Rome, Italy cohorts, respectively. There were no differences in 7 gene expression in colonic
Contact E-mail Address: carla.felice@virgilio.it tissue between the etrolizumab and placebo treated groups. E cells were
decreased in the intestinal crypt epithelium, but not in the lamina propria, in
INTRODUCTION: Recent studies underlined the importance to treat inflam- etrolizumab-treated patients compared with placebo. Reduction in multiple mar-
matory bowel diseases (IBD) looking beyond symptoms and considering also kers associated with proinflammatory infiltration and active disease was
tangible indicators of disease remission, such as mucosal healing and normal- observed in etrolizumab-treated patients who achieved clinical remission com-
ization of biomarkers. A clear definition of deep remission has not been validated pared to those who did not, including decreases in expression of proinflamma-
yet. However, the achievement of clinical remission associated to mucosal healing tory cytokines, lymphocyte subset markers (CD3, CD19), MAdCAM-1, and
has been demonstrated to improve clinical outcomes during biological treat- epithelial cell-associated E cells. Although maximal occupancy of 7 receptors
ments. Some studies also showed that high C-reactive protein (CRP) levels at was observed in both low and high dose groups, there were no apparent differ-
the time of infliximab (IFX) discontinuation may represent a risk factor for ences in PD effects between the two etrolizumab-treated cohorts. Furthermore,
clinical relapse. No data are available so far about clinical outcomes of IBD within the etrolizumab-treated cohorts, there were no observed drug exposure/
patients who discontinue IFX being in deep remission defined as the combination clinical remission relationships.
of clinical remission, mucosal healing and normal CRP. CONCLUSION: In this Phase 2 study, we confirmed etrolizumab target engage-
AIMS & METHODS: This single-centre study included IBD patients who dis- ment and subsequent biological effects, both in peripheral blood and at the site of
continued maintenance treatment with IFX because of sustained steroid-free disease pathobiology. PD effects were consistent with decreased inflammation in
clinical remission (HBI4 for Crohns disease -CD- and partial Mayo score2 the colonic mucosa, particularly in patients who attained clinical remission.
for ulcerative colitis UC-, with no intake of systemic steroids during the last 12 These findings contribute to the understanding of the mechanism of action of
months before discontinuation). Deep remission was defined as sustained steroid- etrolizumab: blockade of leukocyte homing to, and decreased inflammation in,
free clinical remission associated to normal CRP (5 mg/l) and mucosal healing the colon.
(defined as absence of ulcers in CD, or endoscopic Mayo score of 0-1 in UC). REFERENCES
Primary endpoint was the comparison of clinical relapse between two groups of Vermeire S, et al. DDW, oral presentation, 18 May 2013.
patients who were in deep remission (group 1) or not (group 2) at the time of IFX Williams M, et al. UEGW, poster presentation, 15 October 2013.
discontinuation. Secondary endpoints were endoscopic recurrence, hospitaliza- Disclosure of Interest: C. Looney Other: Genentech, employee, F. Fuh Other:
tions, surgeries and retreatment with anti-TNF between the two groups. Genentech, employee, M. Tang Other: Genentech, employee, X. Wei Other:
RESULTS: Sixty-one patients (40 CD, 21 UC) were included in the study (group Genentech, employee, M. Keir Other: Genentech, employee, G. Tew Other:
1 n 34, group 2 n 27). Median follow-up after IFX discontinuation was 36 Genentech, employee, J. Eastham-Anderson Other: Genentech, employee, L.
months (IQR 23-60). No significant differences were found among baseline char- Diehl Other: Genentech, employee, A. Salas Financial support for research
acteristics. The rate of clinical relapse resulted significantly different between from: Palau Pharma, Roche Pharma AG, Boehringer Ingelheim, Lecture fee(s)
groups: 14/34 (41%) in group 1 relapsed in comparison with 21/27 (78%) in from: Pfizer, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
group 2 (p 0.009). Mucosal healing was the only other variable associated to Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, S.
a lower incidence of clinical relapse (p 0.03). Median values of CRP at the time Francom Other: Genentech, employee, H. Gilbert Other: Genentech, employee,
of IFX discontinuation were not associated to a different clinical outcome. Time D. Luca Other: Genentech, employee, J. Egan Other: Genentech/Roche,
to clinical relapse was significantly shorter in group 2: patients not in deep employee, S. Vermeire Financial support for research from: Merck, Abbvie,
remission at the time of IFX discontinuation relapsed after a median of 12 UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire, Ferring,
months (IQR 8,25-19.5) in comparison with 36 months (IQR 23-57) of group 1 J. Mansfield Financial support for research from: Genentech, Inc.,
(p50.001). No differences were found considering rates of endoscopic recur- Consultancy for: Genentech, Inc., Tillotts Pharmaceuticals, C. Lamb Financial
rence, hospitalization, surgery and need for anti-TNF retreatment. However, support for research from: Genentech, Immundiagnostik, Roche Diagnostics
patients in group 2 required hospitalization and retreatment with anti-TNF UK, B. Feagan Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra
significantly earlier in comparison with group 1 (p 0.02 and p 0.03, Zeneca, Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer-
respectively). Ingelheim, Bristol-Myers Squibb, Celgene, Elan/Biogen, EnGene, Ferring,
CONCLUSION: IBD patients who discontinue IFX because of sustained ster- Roche/Genentech, GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood
oid-free clinical remission may relapse over time. However, the presence of deep Pharma, Janssen Biotech, Kyowa Hakko Kirin Co, Lexicon, Lilly, Merck,
remission (clinical remission associated to mucosal healing and normal CRP) at Millennium Pharma, J. Panes Consultancy for: Abbvie, BMS, Genentech,
the time of IFX discontinuation seems to guarantee better clinical outcomes. MSD, Roche, Tygenics, Boehringer Ingelheim, Pfizer, Nutrition Science
Disclosure of Interest: C. Felice: None declared, D. Pugliese: None declared, M. Partners, Topivert, Novo Nordisk, D. Baumgart Financial support for research
Marzo: None declared, G. Andrisani: None declared, O. Nardone: None from: Abbott, Shire, Hitachi, Lecture fee(s) from: medac, Shire, Ferring
declared, A. Papa: None declared, I. De Vitis: None declared, G. L. Pharmaceuticals, MSD, Falk Foundation, Consultancy for: Abbott, MSD,
Rapaccini: None declared, L. Guidi Other: MSD, AbbVie, A. Armuzzi Roche, Genentech, Pfizer, S. Schreiber Financial support for research from:
Financial support for research from: MSD, Lecture fee(s) from: MSD, AstraZeneca Pharmaceuticals, UCB Pharma, Shire Pharmaceuticals Group,
AbbVie, Chiesi, Ferring, Nycomed, Otsuka, Consultancy for: AbbVie, MSD, Lecture fee(s) from: Falk Foundation, Consultancy for: Abbott, AstraZeneca
Other: MSD, AbbVie, Ferring, Nycomed Pharmaceuticals, Bayer AG, Berlex Laboratories, Bristol-Myers Squibb,
Centocor, Chemocentryx, Ferring Pharmaceuticals, Otsuka Pharma.,
Progenika Biopharma, Genentech, Schering-Plough, Shire Pharmaceuticals
Group, UCB Pharma, Novartis Pharmaceuticals, Pfizer Inc, NovoNordisk, hos-
pira, Takeda, I. Dotan Lecture fee(s) from: Abbott Laboratories, Falk Pharma,
Ferring Pharmaceuticals, J. C. healthcare, Consultancy for: Centocor, Inc.,
A222 United European Gastroenterology Journal 2(5S)
Genentech, Atlantic Healthcare Ltd, Pfizer, Bioline Rx, W. Sandborn in total Mayo score of 3 points and 30%, and a decrease in rectal bleeding
Consultancy for: ActoGeniX NV, Amgen, AM-Pharma BV, Boehringer- subscore of 1 point or an absolute subscore of 0 or 1.
Ingelheim Inc, Bristol Meyers Squibb, Celgene, Cosmo Technologies, RESULTS: A time-dependent increase in total IL-13 serum levels was observed
Coronado Biosciences, Eisai Medical Research Inc., Elan Pharmaceuticals, Eli with tralokinumab but not with placebo. Free IL-13 was detectable in homoge-
Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Glaxo Smith Kline, nates of inflamed colonic mucosa; however, there was no consistent trend regard-
Ironwood Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Millennium ing changes from baseline after 8 weeks treatment with tralokinumab. At
Pharmaceuticals, Nisshin Kyorin Pharmaceuticals Co., Ltd, Novo Nordisk A/ baseline, in situ claudin-2 mRNA expression was higher in inflamed versus
S, Orexigen Therapeutics, Inc., Pfizer, Prometheus Laboratories, Receptos, P. normal colonic mucosa. Claudin-2 mRNA expression decreased from baseline
Rutgeerts Financial support for research from: UCB Pharma, Abbott, J&J, in clinical responders. There were numerical increases from baseline in colonic
Merck & Co, Lecture fee(s) from: Abbott, Merck & Co, Consultancy for: mucosal mRNA levels for IL-6, IL-8 and S100 calcium binding protein A8 (a
UCB Pharma, Merck, Bristol-Myers Squibb, Genentech Inc., Abbott, subunit of calprotectin) in clinical responders in the tralokinumab group com-
Centocor - J&J, Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen, pared with clinical responders in the placebo group. A numerical decrease from
Pfizer, Falk Pharma, Tillotts, T. Lu Other: Genentech, employee, S. OByrne baseline in mRNA for tumour necrosis factor receptor superfamily member 12A
Other: Genentech, employee, M. Williams Other: Gilead Sciences, employee was seen in the tralokinumab group compared with placebo. However, gene
expression changes were small and would not remain significant after correcting
for multiple statistical comparisons.
P0332 CLINICAL OUTCOME OF PERIANAL CROHNS DIESEASE AND CONCLUSION: Claudin-2 may be a useful prognostic biomarker for UC. Total
IMPACT OF TREATMENT STRATEGIES OVER THE TIME IL-13 in serum increased with tralokinumab treatment, supporting systemic
C. Reenaers1,*, A. Natalis1, E. Louis2 target engagement. In colonic mucosa, small expression changes in IL-13-regu-
1
CHU Sart Tilman, Liege, Belgium, Liege, Belgium, 2Hepato-Gastroenterology, lated genes were associated with tralokinumab treatment, though measurement
CHU Sart Tilman, Liege, Belgium, Liege, Belgium of free IL-13 could not confirm target engagement by tralokinumab in colonic
Contact E-mail Address: catherinereenaers@hotmail.com mucosa.
Disclosure of Interest: C. Balendran Other: Employee of AstraZeneca, Molndal,
INTRODUCTION: Perianal Crohns disease (pCD) is associated with complica- Sweden, J. Kilhamn Other: Employee of AstraZeneca, Molndal, Sweden, S.
tions leading to recurrent surgery and tissue damage. Immunosuppressive drugs Pierrou Other: Employee of AstraZeneca, Molndal, Sweden, E. Rehnstrom
(IS) including anti-TNF have changed the management of pCD. Other: Employee of AstraZeneca, Molndal, Sweden, N. Henderson Other:
AIMS & METHODS: Our aim was to describe the management and the natural Employee of AstraZeneca, Molndal, Sweden, K. Randall Other: Employee of
history of a cohort of patients with active pCD and to identify predictive factors AstraZeneca, Alderley Park, United Kingdom, G. Hughes Other: Employee of
of poor evolution. AstraZeneca, Alderley Park, United Kingdom, M. Knutsson Other: Employee of
Methods: A retrospective study of pCD patients registred in the database of the AstraZeneca, Molndal, Sweden, F. Erlandsson Other: Employee of AstraZeneca,
university hospital of Lie`ge, Belgium. Perianal lesions included abscess, fistulae, Molndal, Sweden, M. Hansen Other: Employee of AstraZeneca, Molndal,
anal fissure, anal strictures. pCD treatments included antibiotics, surgical drai- Sweden, S. Danese Lecture fee(s) from: Schering-Plough, Abbott Laboratories,
nage (with or without seton), stoma. Medical treatments including IS and anti- Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda,
TNF were recorded at pCD diagnosis and over follow-up. pCD relapse was Nycomed, Pharmacosmos, Actelion, Alpha Wasserman, Genentech,
defined as antibiotherapy for recurrent abscess, the need for surgical drainage Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals,
or stoma. The subroups of patients followed before (old cohort) and after (young TiGenix, Vifor and Johnson & Johnson, Consultancy for: Schering-Plough,
cohort) the year 2000 were compared in a subanalysis. Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion,
RESULTS: 181 patients with pCD were included. Mean follow-up was 7.9 years Millenium, Takeda, Nycomed, Pharmacosmos, Actelion, Alpha Wasserman,
Mean time between CD and pCD diagnosis was 6.3 years. Lesions at pCD Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo
diagnosis were abscess in 93/181 (51%), fistula in 91/181 (50%; 77/93 of complex Pharmaceuticals, TiGenix, Vifor and Johnson & Johnson, Other: Advisory
fistulae), anal fissure in 28/181 (15%), anal stricture in 18/181 (10%). At diag- board member for Schering-Plough, Abbott Laboratories, Merck & Co, UCB
nosis abscess drainage was performed in 31/181 (17%), drainage seton in 44/ Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda, Nycomed,
181 (24%), stoma in 18/181 (10%). 132/181 (74%) and 83/181 (47%) had IS and Pharmacosmos, Actelion, Alpha Wasserman, Genentech, Grunenthal, Pfizer,
anti-TNF respectively at pCD diagnosis. Relapse rate was 51% within a mean AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, TiGenix, Vifor and
time of 33 months. During follow-up 15% required a stoma. Predictive factors of Johnson & Johnson
relapse were perianal abscess (p50.0001, HR 4.4), fistula (p50.0001,
HR 4.5) or surgical drainage at diagnosis (p50.0001, HR 4.5), young age
at pCD diagnosis (28 versus 31 yo, p 0.02), short time between CD and pCD P0334 THREE-YEAR STEROID FREE REMISSION AND SAFETY OF
diagnosis (5.7 versus 7 years, p 0.01), IS (p 0.04, HR 1.8) and anti-TNF AZATHIOPRINE TREATMENT IN INFLAMMATORY BOWEL
(p 0.01, HR 1.5) at pCD diagnosis. Anti-TNF during follow-up, time to DISEASE PATIENTS
introduce them and duration of anti-TNF treatment were not predictive of C. Cassieri1,*, R. Pica1, E. V. Avallone1, M. Zippi1, C. Corrado1, P. Vernia1,
relapse. The young and old cohort had the same characteristics at pCD diagnosis P. Paoluzi1, E.S. Corazziari1
except a higher use of IS (87% vs 48%, p50.0001) and anti-TNF (3% vs 68%, 1
Internal Medicine and Medical Specialties, Sapienza "University", Rome, Italy
p50.0001) in the young cohort. Clinical outcome including the time to relapse, Contact E-mail Address: claudio.cassieri@libero.it
type of relapse, need for surgery and stoma was similar in both cohorts.
CONCLUSION: In our cohort of pCD patients half of them had a perianal INTRODUCTION: Purine analogue azathioprine (AZA) is widely used for
relapse over the time requiring surgery in more than 2/3 of them. At pCD induction and maintenance of remission in steroid dependent patients with
diagnosis perianal abscess, fistula, surgical drainage, young age, treatment with inflammatory bowel disease (IBD).
IS or anti-TNF were associated with a higher risk of relapse. Although higher AIMS & METHODS: We investigated its efficacy and safety in maintaining
prescription of anti-TNF and IS in the last years new treatment strategies have steroid-free remission in steroid dependent IBD patients three years after the
not impacted the outcome of pCD. institution of treatment. Data from consecutive IBD outpatients referred in
Disclosure of Interest: None declared our Institution, between 1985-2012, were reviewed and all patients treated with
AZA were included in this retrospective study. AZA was administered at the
recommended dose of 22.5 mg/kg. Blood chemistry was analysed before admin-
P0333 BIOMARKER ANALYSES FROM A PHASE 2 STUDY istration of the drug, every 10-15 days for the first 3 months and then every 1-2
EVALUATING THE ANTI-INTERLEUKIN-13 ANTIBODY months following the institution of treatment.
TRALOKINUMAB IN PATIENTS WITH ULCERATIVE COLITIS RESULTS: Out of 2472 consecutive IBD outpatients visited in the index period,
C. Balendran1,*, J. Kilhamn1, S. Pierrou1, E. Rehnstrom1, N. Henderson1, AZA was prescribed to 360 patients, 189 (52.5%) were affected by Crohns
K. Randall2, G. Hughes2, M. Knutsson1, F. Erlandsson1, M.B. Hansen1, disease (CD) and 171 (47.5%) by ulcerative colitis (UC). Seventy-eight patients
S. Danese3 with a follow-up 536 months were excluded from the study. Two hundred and
1
AstraZeneca, Molndal, Sweden, 2AstraZeneca, Alderley Park, United Kingdom, eighty-two patients were evaluated, 152 (53.9%) with CD and 130 (46.1%) with
3
Istituto Clinico Humanitas, Milan, Italy UC. One hundred and fifty-four (54.6%) were male and 128 (45.4%) female
(average age of 33.7513.82 SD years, range 14-76 y.). Three years after the
INTRODUCTION: Interleukin-13 (IL-13) is a central cytokine effector in the T- institution of treatment, 170 (60.3%) patients still were in steroid-free remission
helper 2 immune response that has been proposed to be a key driver of ulcerative (101 CD vs 69 UC, 66.4% and 53.1%, respectively, p 0.0279), 62 (22%) had a
colitis (UC) pathogenesis. Tralokinumab (CAT-354) is a human immunoglobulin relapse requiring retreatment with steroids (38 UC vs 24 CD, 29.2% and 15.8%,
G4 antibody that inhibits binding of IL-13 both to IL-13 receptor (IL-13R) alpha respectively, p 0.0091), 50 (17.7%) discontinued the treatment due to side
1 and IL-13R alpha 2. effects (27 CD vs 23 UC, 17.8% and 17.7%, respectively). Loss of response
AIMS & METHODS: The aim of these analyses was to gain insight into the from 1st to 3rd year of follow-up was low, about 12%.
mechanistic action of tralokinumab in a phase 2 study in patients with UC. CONCLUSION: Three years after the onset of treatment 60% of patients did
Overall, 111 patients with moderate-to-severe UC were randomised in a 1:1 not require further steroid courses. After the first year loss of response was low in
ratio to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks two subsequent years. In the present series the maintenance of steroid-free remis-
during a 12-week treatment phase. Serum samples were obtained at baseline and sion was significantly higher in CD than in UC patients. The occurrence of side
at 2-week intervals throughout the treatment phase. Biopsies were taken during effects leading to the withdrawal of AZA treatment has been low.
colonoscopy at baseline and after 8 weeks of treatment from mucosal areas Disclosure of Interest: None declared
judged by the endoscopist to represent inflamed and normal colonic mucosa.
IL-13 levels were assessed in serum and biopsy homogenates at baseline and
following treatment. Changes from baseline to week 8 in colonic mRNA expres-
sion were assessed by in situ hybridisation for the tight junction protein claudin-2
and by quantitative PCR for selected IL-13-regulated genes. Data were analysed
by treatment and treatment response, with clinical response defined as a decrease
United European Gastroenterology Journal 2(5S) A223
P0335 EFFICACY OF AN MMP9-SPECIFIC MONOCLONAL ANTIBODY P0337 BODY MASS INDEX VARIATION IN INFLIXIMAB-TREATED IBD
IN A DSS-INDUCED COLITIS MODEL OF ULCERATIVE COLITIS PATIENTS
D. Marshall1, R. Spangler1, C. OSullivan1, J. Adamkewicz1, V. Smith1,* D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
1 1
Gilead Sciences, Inc., Foster City, United States Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
INTRODUCTION: Ulcerative colitis (UC) remains a high unmet medical need
with no current curative therapies; the majority of patients with UC require life- INTRODUCTION: A significant number of patients with IBD present with
long treatment to prevent disease progression. UC is characterized by disease- nutritional deficiencies and malnutrition is relatively common. There are several
specific upregulation of matrix metalloproteinase 9 (MMP9). MMP9 can exert ways of describing response to Infliximab (IFX). However, nutritional status is
pathogenic effects both by degrading extracellular matrix (ECM) proteins and rarely used as a tool to evaluate the efficacy of this anti-TNF agent.
participating in tissue destruction and by activating or releasing growth factors AIMS & METHODS: To establish a relation between BMI changes and clinical
and cytokines from the ECM or cell surface. Previous attempts to target MMPs response in patients treated with IFX.
with broad-spectrum or semi-selective inhibitors in oncology and inflammatory Patients with IBD treated with IFX for at least a year were included. Their BMI
diseases have been unsuccessful, partly due to their lack of specificity. was measured before starting IFX, after remission induction therapy, and then
AIMS & METHODS: Here we used immunohistochemistry to confirm MMP9 after 1 and 3 years of maintenance therapy. Response to IFX was evaluated
induction at colitic foci in both human and DSS-exposed mice and evaluated through clinical and laboratorial data.
efficacy of a therapeutically-dosed MMP9-specific monoclonal antibody RESULTS: A total of 62 patients were included (average age 37.3 13.8 years
(AB0046) in a DSS-induced colitis model of UC. old; 71% females; Crohns Disease 45, Ulcerative Colitis 19). Their initial
RESULTS: MMP9 immunoreactivity was limited in the healthy colon, but was average BMI was 21.43.07 (10 patients with BMI518.5 16.1%; 8 patients
strongly induced and had a similar pattern of expression at active disease sites in with BMI425 12.9%). After induction, no significant change was noted in
human UC and mouse DSS-colitis tissue. In disease, MMP9 was expressed in BMI, but one year later, a meaningful increase was noted (21.4 to 22.7;
abscessed and necrotic crypts and regions of cryptitis containing neutrophilic p 0.049). After three years of therapy, this tendency was more evident (21.4
infiltrates as well as by macrophages within the lamina propria. Extracellular to 22.8; p 0.026), as only 2 patients still had BMI518,5, whilst 16 had weight
MMP9 staining colocalized with regions of destruction in the epithelial crypt excess (26%).
basement membrane. Inhibiting MMP9 in established DSS-induced colitis with There was a significant increase in BMI in patients who responded to therapy, in
AB0046 resulted in a significant protection (50%) against body weight loss and contrast to those who maintained clinical activity. The average BMI actually
endoscopically assessed disease, and a 45% reduction in the incidence of diar- decreased in the latter group (1,81 vs. -0,96; p 0.012). This increase was
rhea. Colons from AB0046-treated animals exhibited less crypt destruction, less noted particularly in patients who had initial BMI518.5 (p 0.032), as well as
inflammatory cell infiltration, and a reduction in MMP9 expression. In concor- in male patients and with small bowel involvement. Factors such as age, disease
dance with the IHC analysis, AB0046 treatment resulted in a decrease in histo- duration, smoking or other medication did not show significant association with
pathologic disease scores. Interestingly, AB0046 treatment resulted in reduction BMI.
of serum markers of inflammation including IL-6, CXCL2, KC/GRO, MPO, CONCLUSION: Nutritional deficits are common clinical issues in IBD patients.
LIF, MCP-1/2/5, MIP-3, and TIMP-1. Therapy with Infliximab is clearly associated with improved nutritional status in
CONCLUSION: MMP9 is highly expressed in human UC and in mouse DSS- patients who are responders, unlike those who mantained disease activity. This
exposed colons. The ability of MMP9 to degrade basement membrane and to association is more clearly noted in the group with lower initial BMI.
activate or release pro-inflammatory factors from the ECM make this protein a Disclosure of Interest: None declared
compelling therapeutic target in colitis. Treatment of established DSS-induced
colitis with an MMP9-specific monoclonal antibody resulted in improvement in
clinical measures of disease, histopathology, as well as in systemic markers of P0338 MONITORING VITAL SIGNS DURING INFLIXIMAB INFUSION
inflammation. These data suggest that an MMP9 specific monoclonal antibody is IS IT REALLY USEFUL?
a promising therapeutic strategy for treatment of UC. Gilead Sciences has devel- D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
oped a humanized MMP9-specific monoclonal antibody that is currently in a 1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Phase 1b clinical trial in UC. Contact E-mail Address: diogofbranquinho@yahoo.com
Disclosure of Interest: D. Marshall Other: Is an employee of Gilead Sciences, Inc.,
R. Spangler Other: Is an employee of Gilead Sciences, Inc., C. OSullivan Other: INTRODUCTION: Monitoring vital signs is part of the surveillance protocol
Is an employee of Gilead Sciences, Inc., J. Adamkewicz Other: Is an employee of during Infliximab infusions in most IBD reference centers. Despite being innoc-
Gilead Sciences, Inc., V. Smith Other: Is an employee of Gilead Sciences, Inc. uous, it is a time consuming task, representing another burden to already strained
healthcare professionals. In this era of increasing medical care costs, and with the
growing number of IBD patients treated with biological agents, it becomes essen-
P0336 INFLIXIMAB ONE HOUR INFUSIONS A GOOD CHOICE FOR tial to analyze if this practice is able to predict or identify adverse reactions to
IBD PATIENTS? Infliximab.
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1 AIMS & METHODS: To evalute the usefulness of monitoring vital signs during
1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal Infliximab infusions.
Contact E-mail Address: diogofbranquinho@yahoo.com From January 2013 to December 2013, each patients pulse (HR), systolic blood
pressure (SBP), temperature (Temp) and pulse oximetry (SpO2) were registered
INTRODUCTION: The use of anti-TNF agents as maintenance therapy in IBD during Infliximab infusions. Acute adverse reactions were also recorded.
patients is well documented. However, administration of Infliximab (IFX) RESULTS: A total of 593 Infliximab infusions were administered to 95 patients
implies long hours at the hospital, with significant costs and inconvenience. A (average of 6.2 1.3 infusions per patient; median age: 38.8 14.2 years old;
shorter infusion protocol would minimize such drawbacks, maintaining the same 59% females; Crohns Disease 66, Ulcerative Colitis 29). The overall inci-
safety and efficacy. dence of acute infusion reaction was 2.2% (13 of 593 infusions), affecting 6
AIMS & METHODS: To evaluate the safety and efficacy profile of one hour patients (6.3%). Two of them were serious, with bronchospasm and angioedema.
IFX infusion. Comparing baseline vital signs between groups with and without acute reactions,
Between November 2012 and December 2013, the occurrence of acute adverse no relevant differences were noted (HR: 78 vs. 81/min, p 0.23; SBP: 106 vs. 109
reactions to IFX was prospectively documented. Patients under maintenance mmHg, p 0.12; Temp: 35.9 vs. 36.1 C, p 0.68; SpO2: 98% vs. 99%, p 0.42).
therapy, with at least 4 infusions with no history of reactions, received one Vital signs measured immediately before and during acute reactions were also
hour infusions. This was followed by 1-hour surveillance in the next 5 infusions, compared. No significant change was noted in most cases, except during the two
and 30 minutes from then on. serious reactions, in which there was an increase in heart rate (67 to 110 beats/
RESULTS: From a total of 95 patients under IFX therapy (Average age: 38.8 min and 86 to 112/min) and a fall in one of the patients SpO2 (97 to 85%),
14.2 years old; Female - 58%; Crohns Disease 66, Ulcerative Colitis 25, maintaining stable blood pressure and temperature.
Unclassified IBD 4), about 68% (65/95) started receiving one hour infusions CONCLUSION: Scheduled monitoring of vital signs during Infliximab infusions
(average of 6 per patient, total of 390 infusions), while 31.6% (30/95) were kept was unable to predict acute reactions or to identify patients with increased risk of
under the usual two hour protocol, with two hour infusions followed by one or such reactions, though it can help to assess its severity. Such conclusions do not
two hours of surveillance. suggest a more distant surveillance, but emphasize that clinical symptoms should
In the one hour infusion group, 38.4% were under combined therapy with immu- be the main focus.
nosuppressive agents and 23% received hydrocortisone and/or clemastine as Disclosure of Interest: None declared
prophylactic medication. There was no adverse reaction noted in this group. In
92.3% of the patients, the therapeutic regimen remained the same, but in the
remaining 7.7%, an increase in dosage or interval shortening was needed. One
patient had to change to Adalimumab (ADA) due to poor response to IFX.
In the 2-hour infusion group, 56.7% were under combined therapy with immu-
nosuppressants and 43.3% received prophylactic medication. A total of 5 reac-
tions were described (2.46%), 2 of which were severe (0.98%), leading to IFX
definitive suspension. Initial regimen was maintained in 93.3% (28/30) of these
patients, while 6.7% (2/30) had to increase IFX dosage or shorter intervals
between infusions.
CONCLUSION: During maintenance therapy, 1 hour infusions are safe and
effective, minimizing costs associated with IFX therapy, and allowing shorter
hospital stays and better quality of life to IBD patients.
Disclosure of Interest: None declared
A224 United European Gastroenterology Journal 2(5S)
p40.05), LDL (anti-TNF: 95.8 28.7 vs Aza/Mes: 90.7 24.4 mg/dl,
P0339 HISTOLOGICAL AND ENDOSCOPIC REMISSION INDUCED BY
p40.05), triglycerides (anti-TNF: 75.8 37.6 vs Aza/Mes: 90.8 61.3 mg/dl,
INFLIXIMAB IN MODERATE TO SEVERELY ACTIVE ULCERATIVE
p40.05), CRP (anti-TNF: 3 5.4 vs Aza/Mes: 4.9 6.1, p40.05) and in the
COLITIS PATIENTS HERICA STUDY
HOMA-IR index (anti-TNF: 2.77 2 vs Aza/Mes: 3.1 1.9, p40.05). In
F. Magro1,*, S. Lopes2, J. Lopes2, E. Rodrigues-Pinto2, F. Portela3, M. Silva3, patients who were treated for 6 months with anti-TNF, a statistically significant
J. Cotter4, M. Joao Moreira4, P. Lago5, C. Lopes5, C. Caetano5, P. Peixe6, decrease in insulin (before: 15.4 5.8 vs after: 10.2 2.7 mIU/ml, p 0.049) and
C. Chagas6, L. Carvalho6, S. Lopes3, B. Rosa4, A. Albuquerque7, C. Camila- c-peptide (before: 2.4 1.2 vs after: 1.4 0.4 ng/ml, p 0.038) levels as well as
Dias8, J. Afonso9, K. Geboes10, F. Carneiro7 on behalf of Working group the HOMA-IR index (before: 4.1 2.1 vs after: 2.3 0.7, p 0.047) was
1
Gastroenterology, 2Centro Hospitalar Sao Joao, Porto, 3Centro Hospitalar de observed, without any statistically significant changes in weight, BMI, glucose,
Coimbra, Coimbra, 4Centro Hospitalar do Alto Ave, Guimaraes, 5Centro HbA1c, lipids and CRP levels (in all comparisons p40.05).
Hospitalar do Porto, Porto, 6Centro Hospitalar de Lisboa Ocidental, Lisboa, CONCLUSION: These preliminary data indicate that anti-TNF therapy may
7
Centro Hospitalar de Sao Joao, 8CINTESIS - Center for research in health have a favorable effect on insulin sensitivity in non-diabetic, non-obese patients
technologies and information systems, 9Department of Pharmacology and with inflammatory bowel disease.
Therapeutics, Porto, Portugal, 10University Hospital KU, Leuven, Belgium Disclosure of Interest: None declared
Contact E-mail Address: fm@med.up.pt
INTRODUCTION: Correlation between histological activity, endoscopic find- P0341 HUMAN SAFETY, PHARMACOKINETICS AND
ings, levels of calprotectin and lactoferrin in ulcerative colitis (UC) are not well PHARMACODYNAMICS OF THE GPR84 ANTAGONIST GLPG1205,
established. Infliximab can induce remission. Residual microscopic active inflam- A POTENTIAL NEW APPROACH TO TREAT IBD
mation may predict relapse. Non-invasive methods such as calprotectin may be F. Vanhoutte1,*, S. Dupont2, T.Van Kaem1, M.-H. Gouy2, L. Gheyle3,
appropriate for this purpose. R. Blanque2, R. Brys1, N. Vandeghinste1, W. Haazen3, G.van t Klooster1,
AIMS & METHODS: The primary aim was to evaluate the histological remis- J. Beetens1
sion induced by infliximab at week 8 (Geboes 53.0); secondary aims were to 1
GALAPAGOS NV, Mechelen, Belgium, 2GALAPAGOS SASU, Romainville,
evaluate the association between histological remission, mucosal healing, faecal France, 3SGS Life Science Services, CPU, Antwerp, Belgium
calprotectin and faecal lactoferrin. 20 patients with moderate to severe UC Contact E-mail Address: johan.beetens@glpg.com
(Mayo score 6-12) with inadequate response to corticosteroids or corticosteroid
dependence, all of them anti-TNF na ve, started infliximab in a prospective, INTRODUCTION: Free fatty acids (FFAs) are nutritional components and
open-label, multi-centre study, with 1 year of follow-up, 4 visits assessments metabolic intermediates that play important roles in a wide range of cellular
(baseline, week 8, week 30, and week 52). Topical treatment was not allowed. functions (energy source, membrane structure, signalling). Recently, FFAs
In each visit, Mayo score, faecal calprotectin and lactoferrin were evaluated, and have been reported to activate a family of G protein-coupled receptors, which
sigmoidoscopy with biopsies was performed. The worst sample was used for are involved in the pathophysiology of a variety of diseases, including metabolic
histological score (Geboes index GI) and the patients were considered in and inflammatory disorders. GPR84 is activated by medium chain FFA (carbon
deep remission when in clinical remission (Mayo score 52) and GI 3 and length C9-C14). The receptor is primarily expressed on white blood cells (PMN,
calprotectin levels 5100mg/L and lactoferrin 7.25mg/L and mucosal healing monocyte/macrophage) consistent with a reported role for GPR84 in
at endoscopy (0 or 1). inflammation.
RESULTS: Out of the 20 patients, 13 had left-sided colitis (E2) and 7 had We identified GLPG1205 as a potent and selective antagonist of GPR84, inhibit-
pancolitis (E3). At weeks 8, 30 and 52, 15%, 30% and 35% of the patients, ing GPR84 activation in HEK cells, as well as GPR84-induced neutrophil migra-
respectively, were on histological remission. At the same intervals, 10%, 20% tion. In a mouse IBD model (DSS), GLPG1205 dose-dependently decreased the
and 10% of the patients, respectively, were in deep remission. Sixty-six percent of disease activity index, to a similar level as sulphasalazine and cyclosporine. The
those on histological remission at week 8 had persistent remission at week 30 and histological score for colon lesions, neutrophil influx as well as colonic MPO
52, and 100% of those on histological remission at 30 week persisted thereafter. content was substantially reduced.
Calprotectin 4100mg/L at week 8 predicted histological activity (sensitivity: AIMS & METHODS: To evaluate the safety, tolerability, pharmacokinetics
76%; specificity: 100%), with a positive predictive value (PPV) of 100% and a (PK) and pharmacodynamics (PD) of GLPG1205 in healthy volunteers, and
negative predictive value (NPV) of 42%. Lactoferrin levels higher than 7.25 mg/L identify a dose for subsequent Proof of Concept studies in inflammatory bowel
at week 8 predicted histological activity (sensitivity: 94%; specificity: 66%), with disease.
a PPV of 94% and a NPV of 66%. The probability of being in histological GLPG1205 was administered as a liquid suspension, providing maximal dose
remission once achieving mucosal healing (PPV) was 55% (weeks 30 and 52) flexibility, as single doses (10 up to 800 mg) or multiple doses (50, 100 and 200
and the probability of endoscopic mucosal healing with calprotectin 100mg/L mg once daily (QD) for 14 days). Each dose level was evaluated in panels of 8
was 100% and 75%, respectively, at weeks 30 and 52. male healthy volunteers, with 6 receiving GLPG1205 and 2 placebo. In order to
CONCLUSION: Infliximab is able to induce and maintain histological remission evaluate target engagement, PD was assessed by a competitive radiolabeled bind-
in ulcerative colitis patients. High levels of calprotectin and lactoferrin predict ing assay in whole blood, using a tritiated GPR84 antagonist chemically closely
persistent histological activity. related to GLPG1205.
Disclosure of Interest: None declared RESULTS: In healthy volunteers, GLPG1205 was generally safe and well toler-
ated up to 100 mg QD for 14 days, with no adverse effects on ECG, vital signs or
laboratory parameters. The most relevant adverse event was headache. The PK
P0340 ANTI-TNF HAS A FAVORABLE EFFECT ON INSULIN of the compound showed a good oral bioavailability with a long half-life (4 one
SENSITIVITY IN NON-DIABETIC, NON-OBESE PATIENTS WITH day) and a dose-proportional increase in exposure. Steady state was reached after
INFLAMMATORY BOWEL DISEASE 8 to 10 days. GLPG1205 showed concentration-dependent target engagement in
F. Kothonas1,*, S.A. Paschou2, A. Myroforidis1, V. Loi2, T. Terzi 2, whole blood (ex vivo), showing similar potency as in in vitro assays. The single-
O. Karagianni2, A. Poulou1, A. Vryonidou2, K. Goumas1 dose PK/PD data demonstrated a clear relationship between drug exposure and
1
Gastroenterology Department, 2Endocrinology Department, Hellenic Red Cross PD effect. Complete target occupancy for 24 hours after once daily dosing in
Hospital, Athens, Greece volunteers was observed at doses of 100 and 200 mg QD.
Contact E-mail Address: fotiskothonas@gmail.com CONCLUSION: GLPG1205, a potent and selective inhibitor of GPR84, is safe
and generally well tolerated in healthy volunteers. It shows a favorable PK/PD
INTRODUCTION: Insulin resistance is very common in autoimmune systemic profile, clearly demonstrating the ability of the compound to antagonize GPR84,
diseases and recently it was also found in children and adults with inflammatory a target which might be implicated in several neutrophil- and macrophage-driven
bowel disease (IBD). Inflammation and insulin resistance are closely linked, and inflammatory conditions. At 100 mg once-daily, full 24-hour inhibition was
inflammatory cytokines such as tumor necrosis factor alpha (TNFa) may inhibit obtained. This dose will be studied in Proof of Concept studies to evaluate the
insulin signaling and promote insulin resistance. The aim of this study was to efficacy and safety of GLPG1205 in patients with Crohns disease and ulcerative
investigate the effect of anti-TNF therapy on glucose and lipid metabolism in colitis.
non-diabetic, non-obese patients with IBD. Disclosure of Interest: F. Vanhoutte Other: employee, S. Dupont Other:
AIMS & METHODS: We studied 41 patients with IBD (25M/16F, 36.4 11 employee, T. Van Kaem Other: employee, M.-H. Gouy Other: employee, L.
(19-64) years old, 28 with Crohns disease and 13 with ulcerative colitis), without Gheyle: None declared, R. Blanque Other: employee, R. Brys Other: employee,
known history of diabetes. Eighteen patients (9M/9F, 33.6 8.8 years) were on N. Vandeghinste Other: employee, W. Haazen: None declared, G. van t
anti-TNF therapy for more than 1 year, while the other 23 patients (16M/7F, Klooster Other: employee, J. Beetens Other: employee
38.7 12.5 years) were treated with azathioprine and mesalazine (Aza/Mes).
Nine of the patients from the second group were then treated with anti-TNF
and studied again 6 months after. Fasting glucose, insulin, c-peptide, HbA1c, P0342 EFFECTS OF A FODMAP- RESTRICTED DIET ON IRRITABLE
lipids, and CRP levels were determined and HOMA-IR index was calculated, in BOWEL SYMPTOMS IN PATIENTS WITH INFLAMMATORY
all patients. Statistical analysis of the data was performed using SPSS 16.00. BOWEL DISEASE
RESULTS: Three of the patients were diagnosed with overt diabetes and were F.van Megen1,*, G.E. Kahrs1, J.G. Hatlebakk1
excluded from the analysis. Patients from the two therapy groups were matched 1
1Department of Clinical Nutrition and Section of Gastroenterology, Department
for age (anti-TNF: 33.6 8.8 years vs Aza/Mes: 38.7 12.5 years, p40.05) and of Medicine, Clinical Institute 1, BERGEN, Norway
BMI (anti-TNF: 23.3 3.4 vs Aza/Mes: 23.1 1.7, p40.05), and were not Contact E-mail Address: frida_van_megen@hotmail.com
obese. We did not find any statistical differences between the patients from the
two therapy groups in the levels of fasting glucose (anti-TNF: 88 10.7 vs Aza/ INTRODUCTION: The FODMAP (fermentable oligo- di- and monosacchar-
Mes: 93.4 14.9 mg/dl, p40.05), insulin (anti-TNF: 10.9 7.9 vs Aza/Mes: 12.1 ides, and polyols) -restricted diet has previously been proven effective to improve
6.6 mIU/ml, p40.05), c-peptide (anti-TNF: 1.9 0.9 vs Aza/Mes: 2.2 1.4 symptoms in patients with irritable bowel syndrome (IBS). FODMAPs are small
ng/ml, p40.05), HbA1c (anti-TNF: 5.2 0.3 vs Aza/Mes: 5.3 0.4%, p40.05), osmotic active and poorly absorbed short-chain carbohydrates, and include fruc-
total cholesterol (anti-TNF: 168.6 32.7 vs Aza/Mes: 162.8 34.3 mg/dl, tose (found in fruit), lactose (found in milk products), fructans (found in grain
p40.05), HDL (anti-TNF: 57.5 15.7 vs Aza/Mes: 53.8 20.3 mg/dl, and vegetables), galacto-oligosaccharides (found in legumes) and polyols (found
United European Gastroenterology Journal 2(5S) A225
in sweetened products). FODMAPs are rapidly fermented by bacteria in the Genentech, Cerimon Pharmaceuticals, C. Lamb Financial support for research
colon and can cause bloating, increased gas production, abdominal pain and from: Genentech, Immundiagnostik, Roche Diagnostics UK, D. Luca Other:
altered bowel movements. FODMAPs do not cause IBS, but a FODMAP- Genentech, employee, J. Egen Shareholder of: Genentech/Roche, Other:
restricted diet may improve the symptoms. Patients with inflammatory bowel Genentech/Roche, S. Vermeire Financial support for research from: Merck,
disease (IBD) often suffer from persistent symptoms even though the inflamma- Abbvie, UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire,
tory activity is in remission. This study aimed to investigate the FODMAP- Ferring, J. Mansfield Financial support for research from: Genentech Inc.,
restricted diet in patients with IBD in remission with persistent symptoms con- Consultancy for: Genentech Inc.; Tillotts Pharmaceuticals, B. Feagan
sistent with IBS. Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra Zeneca, Avaxia
AIMS & METHODS: A 6 week intervention was undertaken in 12 IBD-patients Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Bristol-
(10 ulcerative colitis and 2 Crohns disease, 3M/9W, age 23-57 years) in remission Myers Squibb, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech,
with CRP55mg/L and faecal calprotectin 5100mg/kg, and fulfilling the GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharma, Janssen
ROME-III criteria for IBS. FODMAP intake was determined by 4 days pro- Biotech, Kyowa Kakko Kirin Co, Lexicon, Lilly, Merck, Millennium Pharma,
spective dietary registrations at 0 and 6 weeks. Instructions and follow-up were J. Panes Consultancy for: Abbvie, BMS, Genentech, MSD, Roche, Tygenics,
given by a clinical dietician. IBS-symptoms and quality of life (QoL) were Boehringer Ingelheim, Pfizer, Nutrition Science Partners, Topivert, Novo
assessed with questionnaires (IBS-SSS and SF-36). Compliance was assessed by Nordisk, D. Baumgart Financial support for research from: Abbott, Shire,
VAS-scales. Colonic fermentation was measured by breath tests with sampling Hitachi; Speaking and Teaching: medac, Shire, Ferring Pharmaceuticals, MSD,
for 180min after intake of 10g lactulose. Statistics: T-tests and ANOVA Falk Foundation, Consultancy for: Abbott, MSD, Roche, Genentech, Pfizer, S.
(p50.05). Schreiber Financial support for research from: AstraZeneca Pharmaceuticals,
RESULTS: FODMAP intake was significantly reduced from median 6.3g/d to UCB Pharma, Shire Pharmaceuticals Group, Lecture fee(s) from: Falk
1.5g/d (p 0.0005). IBS symptoms were significantly reduced from median IBS- Foundation, Consultancy for: Abbott, AstraZeneca Pharmaceuticals, Bayer
SSS score 265.0 to 67.6 (p50.0001), and resolved in 58% of patients (remission AG, Berlex Laboratories, Bristol-Myers Squibb, Centocor, Chemocentryx,
classified as score 575). Symptoms were reduced in the first 3 weeks and Ferring Pharmaceuticals, Otsuka Pharma., Progenika Biopharma, Genentech,
remained stable from 3 to 6 weeks. Mental-related QoL significantly improved Schering-Plough, Shire Pharmaceuticals Group, UCB Pharma, Novartis
from median score 43.8 to 53.3 (p 0.039). There was a positive trend for phy- Pharmaceuticals, Pfizer Inc, NovoNordisk, Hospira, Takeda, I. Dotan Lecture
sical-related QoL with mean score 41.0 vs. 47.1 (p 0.05). QoL improved over fee(s) from: Ferring Pharmaceuticals Inc, Abbott Laboratories, J. C. healthcare,
the whole 6 weeks of the intervention. The scores for the SF-36 health domains Falk Pharma, Consultancy for: Centocor, Inc., Genentech, Atlantic Healthcare
bodily pain (53.3) and vitality (52.1) improved most, with p-values 0.004 Ltd, Pfizer; Bioline Rx, W. Sandborn Consultancy for: ActoGeniX NV, Amgen,
and 0.017, respectively. Gas production did not change (AUC 3488 vs. 3390 ppm AM-Pharma BV, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene,
x min, p 0.8). Mean compliance with the diet was 93%, and 73% continued the Cosmo Technologies, Coronado Biosciences, Eisai Medical Research Inc., Elan
diet one month after the intervention. Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences,
CONCLUSION: The FODMAP-restricted diet resolved or improved IBS symp- Glaxo Smith Kline, Ironwood Pharmaceuticals, Janssen, Lexicon
toms and QoL, and should be considered an effective treatment for patients Pharmaceuticals, Millennium Pharmaceuticals, Nisshin Kyorin
experiencing symptoms in spite of remission from IBD. Pharmaceuticals Co., Ltd, Novo Nordisk A/S, Orexigen Therapeutics, Inc.,
Disclosure of Interest: None declared Pfizer, Prometheus Laboratories, Receptos, J. Kirby: None declared, P. Irving:
None declared, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, G.
P0343 INCREASED EXPRESSION OF T-CELL-ASSOCIATED GENES IN Van Assche Financial support for research from: Abbvie, MSD, Lecture fee(s)
BASELINE BIOPSIES FROM TNF ANTAGONIST NAIVE PATIENTS from: Abbvie, Janssen, Aptalis, Ferring, Warner Chillcott, Consultancy for:
WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE Abbvie, Takeda, MSD, Janssen, BMS, Robarts Clinical Trials, P. Rutgeerts
COLITIS WHO UNDERGO REMISSION IN RESPONSE TO Financial support for research from: UCB Pharma, Abbott, J&J, Merck & Co,
ETROLIZUMAB IN A PHASE II TRIAL Lecture fee(s) from: Abbott, Merck & Co, Consultancy for: UCB Pharma,
G.W. Tew1, J. Hackney2, D. Gibbons3, C. Lamb4, D. Luca1, J. Egen1, Merck, Bristol-Myers Squibb, Genentech Inc., Abbott, Centocor - J&J,
S. Vermeire5, J. Mansfield4, B. Feagan6, J. Panes7, D. Baumgart8, S. Schreiber9, Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen, Pfizer, Falk
I. Dotan10, W. Sandborn11, J. Kirby4, P. Irving3, G. De Hertogh5, Pharma, Tillotts, S. OByrne Other: Genentech, employee, A. Hayday
G.Van Assche5, P. Rutgeerts5, S. OByrne1,*, A. Hayday3, M. Keir1 Financial support for research from: Genentech, ImmunoQure, Lecture fee(s)
1
Genentech Research and Early Development, South San Francisco, 2Genentech from: MedImmune., Consultancy for: HS-Lifesciences, ImmunoQure, M. Keir
Research and Early Development, San Francisco, CA, United States, 3Kings Other: Genentech, employee
College London, London, 4University of Newcastle, Newcastle upon Tyne, United
Kingdom, 5University of Leuven, Leuven, Belgium, 6University of Western Ontario,
Ontario, Canada, 7Hospital Clinic Barcelona, Barcelona, Spain, 8Humboldt- P0344 QAX576, AN ANTIINTERLEUKIN (IL)-13 MONOCLONAL
University of Berlin, Berlin, 9Christian Albrechts University, Kiel, Germany, 10Tel ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH
Aviv University, Tel Aviv, Israel, 11University of California, San Diego, United FISTULISING CROHNS DISEASE (CD): RESULTS OF A PROOF-OF-
States CONCEPT STUDY
Contact E-mail Address: keir.mary@gene.com G. Rogler1,*, A. Stallmach2, S. Fichtner-Feigl3, S. Schreiber4, A. Sturm5,
E. Ramsden6, P. Moulin6, D. Lee6, A. Christ6
INTRODUCTION: Etrolizumab is a humanized antibody to the integrin 7 1
Division of Gastroenterology and Hepatology, University Hospital, Zurich,
subunit that blocks 47 and E7 binding to MAdCAM-1 and E-cadherin, Switzerland, 2Department of Internal Medicine IV, Jena University Hospital, Jena,
respectively. In a recent phase II randomized double-blind placebo-controlled 3
Department of Surgery, University Medical Center Regensburg, Regensburg,
trial (EUCALYPTUS), induction therapy with etrolizumab showed clinically 4
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel,
meaningful efficacy compared to placebo at week 10 in patients with moderate 5
Charite Campus Virchow Klinikum, Medical Department, Berlin, Germany,
to severely active ulcerative colitis. 6
Novartis Institutes for BioMedical Research, Basel, Switzerland
AIMS & METHODS: RNA sequencing of inflamed colonic biopsies from TNF
antagonist na ve etrolizumab-treated patients who took part in EUCALYPTUS INTRODUCTION: Recent studies have identified IL-13 as a key cytokine driv-
was used as a hypothesis-free approach to identify gene expression patterns ing the tissue remodelling that accompanies fistula formation in CD. This study
associated with clinical remission in response to etrolizumab. Gene set enrich- assessed the effect of QAX576, an antiIL-13 monoclonal antibody on fistula
ment analysis of pre-defined immune cell gene sets was performed. Following healing in patients with fistulising CD.
this, differentially expressed genes of interest were evaluated in sorted CD4 or AIMS & METHODS: In this 52 weeks (6 weeks treatment, 46 weeks observa-
CD8 E7-positive and -negative T cells from colonic biopsies of non- tion), multi-centre, parallel group, double-blind, active controlled study, 23
EUCALYPTUS UC patients and control subjects. patients (18 years) were planned to be included. Enrolment was stopped after
RESULTS: TNF antagonist na ve patients that underwent remission in response 10 patients due to slow recruitment. Eligible patients (CD 6 months, 1
to etrolizumab had higher baseline expression of T cell-associated genes in muco- perianal fistula, 1 ineffective fistula treatment but no previous anti-TNF
sal biopsies, while high baseline expression of neutrophil-associated genes was treatment failure) were randomized to receive intravenously either QAX576 10
associated with etrolizumab non-response. Patients with higher than median gene mg/kg (at baseline, Weeks 3 and 6; placebo at Week 2; n 6) or infliximab (IFX)
expression levels of the T cell associated genes ITGAE (E integrin), granzyme A 5 mg/kg (at baseline, Weeks 2 and 6; placebo at Week 3; n 4). The primary
and TMEM200A were enriched for remission in response to etrolizumab. As variable was the number of patients (responders) achieving complete closure of
increased E gene expression was associated with remission, sort purified all perianal fistulas for 4 weeks (compared to historical placebo rate of 13%).
E7-positive T cells from biopsies of UC patients were used to test for increased Secondary variables included clinical assessments of the fistulas and MRI-based
expression of other remission-associated T cell genes. Gene expression of gran- activity scores of the fistula tracts.
zyme A in CD4 and CD8 T cells (p50.01) and TMEM200A in CD8 T cells RESULTS: Nine patients were included in the pharmacodynamic analysis set
(p50.05), along with other effector molecules such as granzyme B and perforin (QAX576 6; IFX 3 [one patient excluded due to protocol deviation]). The
in CD4 T cells (p50.05), were found to be increased in E7-positive T cells primary endpoint was achieved by two patients (33.3%; 90% CI: 0.114, 0.656)
relative to E7-negative T cells from UC patients but not healthy subjects. in the QAX576 group. One patient stopped treatment due to abscess formation
Finally, gene expression of the effector molecules granzyme A and B were (Week 3), one due to lack of efficacy (Week 14). In the QAX576 group, patients
decreased following etrolizumab treatment in patients achieving remission. had 1-4 secreting fistulas at baseline. Both responders had complete closure with
CONCLUSION: Enrichment of T cell associated genes, including E and gran- absence of any secretion within 3 weeks, although the MRI activity score
zyme A, was observed in baseline colonic biopsies from TNF antagonist na ve remained stable or even increased in these two patients. Fistula secretion
patients that achieved clinical remission in response to etrolizumab. These can- remained stable in three patients and fluctuated in one. All patients in the IFX
didate biomarkers may identify patients whose disease pathobiology is predomi- group were responders.
nantly T cell-mediated and may benefit from etrolizumab treatment. Immunohistochemistry of fistula tissue at baseline confirmed epithelial expres-
Disclosure of Interest: G. Tew Other: Genentech, employee, J. Hackney Other: sion of IL-13R2 (but not IL-13R1) and de-differentiation of distorted,
Genentech, employee, D. Gibbons Financial support for research from: entrapped crypts; SNAIL expression as marker of invasiveness was not found.
A226 United European Gastroenterology Journal 2(5S)
Overall, 35 AEs were reported in four patients (66.7%) in the QAX576 group; 24 AIMS & METHODS: We assessed TNF- levels in patients with CD who were
AEs were reported in four patients (100%) in the IFX group. Majority of AEs in maintenance treatment with ADA and correlated them with clinical and endo-
were mild or moderate in severity. No death was reported in this study. One SAE scopic disease activity. In this prospective observational cohort study, performed
(procedural pain) was reported in the IFX group. at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) inflix-
CONCLUSION: In this study, QAX576 was well tolerated. As expected IFX was imab-na ve patients with CD in maintenance treatment with ADA were included
a powerful agent to induce fistula closure. Blockade of IL-13 may be effective, and followed-up. Blood samples were drawn at standardized time points (i.e.
too, as compared to historical placebo rates, although the very low patient every 6 months and in case of CD relapse) just before ADA injection.
number does not allow a formal assessment. Antibodies against ADA (AAA) were measured using an homogenous mobility
Disclosure of Interest: G. Rogler Financial support for research from: Abbot, shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples
Abbvie, Ardeypharm, Essex/MSD, FALK, Flamentera, Novartis, Roche, were considered positive for AAA presence if 1.7 U/mL. Disease activity was
Tillots, UCB, Zeller, Lecture fee(s) from: Astra Zeneca, Abbott, Abbvie, assessed at the same points by means of the Harvey-Bradshaw Index (HBI,
FALK, MSD, Phadia, Tillots, UCB, Vifor, Consultancy for: Abbot, Abbvie, remission 55). Moreover, endoscopic activity was assessed at baseline and at
Boehringer, Calypso, FALK, Genentech, Essex/MSD, MSD, Novartis, Pfizer, the time of relapse by means of CD endoscopic index (CDEIS; endoscopic remis-
Roche, UCB, Takeda, Tillots, Vifor, A. Stallmach Financial support for research sion 59).
from: Abbvie, Pentax, Lecture fee(s) from: Abbott, Boehringer Ingelheim, Dr. RESULTS: We have data from 133 blood samples. AAA were observed in 26/
Falk Pharma, MSD, Recordati Pharma, Schering Plough, Shield Holding, Shire, 1339 (19.5%) samples, and 10/26 (38.5%) had a value of AAA 1.7 U/mL.
UCB, Vifor, Consultancy for: 4SC, Abbvie, Astellas, Boehringer Ingelheim, TNF- levels were present in all samples assessed [mean 4.4, range (0-27.2)].
MSD, S. Fichtner-Feigl: None declared, S. Schreiber Lecture fee(s) from: Patients in clinical remission based on HBI had lower TNF- levels compared
MSD, Other: Paid advisor for MSD, A. Sturm: None declared, E. Ramsden to patients who relapsed [3.7 (0.2-20.2) vs. 5.6 (1.3-27.2); p 0.0002]. Similarly,
Other: Employed by Novartis, P. Moulin Shareholder of: Novartis, Other: patients in endoscopic remission based on CDEIS had lower TNF- levels com-
Novartis employee, D. Lee Shareholder of: Novartis, Other: Novartis employee, pared to patients who relapsed [3.1 (0.2-20.2) vs. 4.3 (1.3-27.2); p 0.0034]. Per-
A. Christ Shareholder of: Novartis, Roche, Other: Novartis employee patient median TNF- levels were strongly correlated with median HBI scores
(r2 0.702, p50.0001). Moreover, TNF levels were also correlated with CDEIS
(r2 0.350, p 0.001).
P0345 THE INFLUENCE OF ANTI-ADALIMUMAB ANTIBODIES ON CONCLUSION: TNF- levels strongly correlated with disease activity based on
ADALIMUMAB TROUGH LEVELS, TNF-A LEVELS AND CLINICAL HBI and CDEIS indices in patients with CD in maintenance treatment with
OUTCOME ADA. Indeed, moderate to severe patients often have high sustained TNF-
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1 levels.
1
IRCCS San Martino DIMI, genova, Italy Disclosure of Interest: None declared
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: There is increasing evidence on the role of low trough levels P0347 LONG-TERM OUTCOMES OF PATIENTS WITH ULCERATIVE
and the development of anti-TNF- antibodies for the occurrence of lack/loss of COLITIS TREATED WITH INFLIXIMAB
response to Infliximab (IFX) therapy in patients with Crohns Disease (CD). F.L. Roy1, L. Siproudhis1, C. Brochard1, V. Desfourneaux2, P.-N. DHalluin1,
Therefore, several recent papers and guidelines suggested the need for dosing M. Pagenault1, J.-F. Bretagne1, G. Bouguen1,3,*
IFX concentrations and anti-IFX antibodies in order to treat better CD patients. 1
Service des Maladies de lAppareil Digestif, 2Service de Chirurgie Viscerale, CHU
To date, there are limited data on the role of Adalimumab (ADA) trough levels Pontchaillou, 3INSERM U991, Universite de Rennes 1, Rennes, France
and anti-ADA antibodies (AAA) for the management of CD patients.
AIMS & METHODS: We assessed the role of AAA on ADA trough levels, INTRODUCTION: Data on the long-term efficacy of infliximab for the treat-
TNF- concentrations, clinical biomarker (i.e. C-reactive protein) and clinical ment of ulcerative colitis are scarce. Sustained remission, recurrence and out-
outcome. In this prospective observational cohort study, performed at a single comes after infliximab withdrawal beyond one year as well as predictors of long-
tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66)] infliximab-na ve term outcomes are unknown.
patients with CD achieving disease remission and in maintenance treatment with AIMS & METHODS: The medical records of all patients with ulcerative colitis
ADA were included and followed-up. Blood samples were drawn at standardized and treated with infliximab in a referral center between 2001 and 2012 were
time points (i.e. every 6 months or in case of CD relapse) just before ADA reviewed through September 2013. The cumulative incidence of surgery, remis-
injection. Trough ADA serum concentration and AAA were measured using sion and recurrence with or without infliximab withdrawal were estimated using
an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego, the Kaplan-Meier method. Independent predictors of all outcomes were identi-
United States). Blood samples were considered positive for AAA presence if fied using a Cox proportional hazards model.
AAA were 1.7 U/mL and for ADA trough levels if ADA levels were 5 RESULTS: A total of 100 patients (63 males) with ulcerative colitis and treated
mg/ml. Disease activity was assessed at the same points by means of routine with at least one infliximab infusion were included. At infliximab initiation, 17%
biochemistry and the Harvey-Bradshaw Index (HBI, remission 55, mild disease of patients had severe acute colitis defined by the absence of response following
5-7, moderate disease 8-16, severe disease 416). intravenous steroid and 56% of patients had pancolitis. Concomitant treatment
RESULTS: We have data from 189 blood samples. AAA were observed in 42/ at infliximab initiation included steroids and immunosuppressants for 62% and
189 (22.2%) samples, out of whom 16/42 (38.1%) had levels of AAA 1.7 U/mL. 52% of patients, respectively. After a median follow-up of 55.1 months, the
ADA trough levels were found in 183/189 (96.8%) samples, out of whom 168/183 cumulative probabilities of surgery were 27%, 33% and 36% at 1, 3 and 5
(91.8%) had a value of drug levels 5 mg/ml. Overall, 5/23 (21.7%) patients had years, respectively. A CRP 4 6mg/L at week 6 was associated with colectomy
AAA and 22/23 (95.6%) were positive for ADA levels. Blood samples with AAA (HR 3.43, 95% CI, 1.17-10.9; p .023). Clinical remission was obtained in
had lower ADA trough levels [7.54 (0-26.49) vs. 9.45 (0.14-23.62); p 0.002] and 64% of patients but almost half of the patients relapsed (28/64; 44%). Overall
higher TNF- concentrations [5.9 (4.1-11.5) vs. 3.6 (0-27.2); p 0.0007] than the cumulative probabilities for sustained clinical remission were 19%, 31% and
blood samples without evidence of AAA. Moreover, patients with blood samples 38% at 1, 3 and 5 years, respectively. The absence of infliximab withdrawal was
positive for AAA reported HBI values higher compared to patients without the only factor independently associated with sustained clinical remission
evidence of AAA [10 (3-17) vs. 5 (2-17); p 50.0001]. Finally, no difference was (HR 4.6, 95% IC, 1.66-13.85; p 0.0029). Infliximab was withdrawn in 38 of
found in terms of mean PCR values between patients with AAA and those with- the 64 patients in clinical remission. After a median follow up of 54 months
out [8.1 (3-76.4) vs. 5.2 (2.6-56); p 0.39]. following infliximab withdrawal, 10% (4/38) underwent colectomy, 63.2% (24/
CONCLUSION: Development and presence of AAA decreases ADA trough 38) patients relapsed, and 36.8% (14/38) remained in clinical remission. The
levels and increases TNF- concentrations in blood samples from CD patients cumulative probabilities of relapse after IFX withdrawal at 1, 3 and 5 years
on maintenance treatment with ADA, thus favoring clinical relapse in them as were 24%, 61% and 81%, respectively. A young age 5 21 years at UC diagnosis
demonstrated by the increased values of HBI scores recorded at the time of blood (HR 12, 95% IC, 2.77-58.24; p 0.001) and platelets rate 4 400000/mm3 at
sampling. IFX withdrawal (HR 6.68, 95% IC 1.55-30.82; p 0.011) were associated with
Disclosure of Interest: None declared relapse.
CONCLUSION: After a follow-up of almost 5 years, about one-third of patients
experienced sustained clinical remission and one-third of patients underwent
P0346 TNF-A LEVELS STRONGLY CORRELATED WITH DISEASE surgery. Most of the patients relapsed after infliximab withdrawal. These results
ACTIVITY BASED ON HBI AND CDEIS IN PATIENTS WITH suggest early optimization of infliximab treatment to avoid dreaded outcomes
CROHNS DISEASE IN MAINTENANCE TREATMENT WITH and to continue infliximab among responders to sustain remission.
ADALIMUMAB Disclosure of Interest: None declared
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: In the last two decades the therapeutic paradigm of Crohns
disease (CD) has changed dramatically thanks to the use of biological drugs. In
this scenario, we must consider the pivotal role of tumor necrosis factor-alpha
(TNF-), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD.
High levels of TNF- have been associated with the development of intestinal
inflammation in CD and blocking this cytokine with anti-TNF- molecules may
result in mucosal healing. In addition several studies have shown increased TNF-
levels in the serum and in the intestinal mucosa of patients with CD. However,
little is known about the course of TNF- levels and their relationship with
disease recurrence in CD patients during maintenance treatment with
Adalimumab.
United European Gastroenterology Journal 2(5S) A227
CONCLUSION: There was a significant increase in the incidence of IBD, mainly
MONDAY, OCTOBER 20, 2014 9:0017:00
due to CD. The symptoms usually indicate the type of IBD, and again in pedia-
PAEDIATRIC: LOWER GI POSTER EXHIBITION HALL XL_____________________ tric cases, abdominal pain is more prevalent than diarrhea in the presentation of
P0348 CORRELATION OF PROBE-BASED CONFOCAL LASER CD. The quality of life seems to be similar to that found in other studies, still
ENDOMICROSCOPY FINDINGS IN THE DUODENUM AND showing good internal consistency of the IMPACT-III.
TERMINAL ILEUM OF PEDIATRIC INFLAMMATORY BOWEL Disclosure of Interest: None declared
DISEASE PATIENTS, A PILOT STUDY
A.A. Shavrov1,*, A.Y. Kharitonova1, B. Claggett2, D.K. Brown3,
P0350 CUMULATIVE INCIDENCE AND ASSOCIATED FACTORS OF
D.A. Morozov4, A.A. Shavrov1, J.J. Liu3
1 MUCO-CUTANEOUS MANIFESTATIONS IN PAEDIATRIC-ONSET
Endoscopy Department, The Scientific Center of Childrens Health Russian
CROHNS DISEASE: A POPULATION-BASED STUDY
Academy of Medical Sciences, Moscow, Russian Federation, 2Department of
Medicine, Brigham and Womens Hospital Harvard Medical School, Boston, C. Templier1,*, H. Sarter2, D. Turck3, M. Fumery4, G. Savoye5, B. Catteau1,
3
Division of Gastroenterology, University of Arkansas for Medical Sciences, Little C. Spyckerelle6, E. Laberenne7, O. Mouterde8, D. Djeddi9, S. Buche1, L. Peyrin-
Rock, United States, 4Institute of Pediatric Surgery, The Scientific Center of Biroulet10, E. Delaporte1, C. Gower-Rousseau2 on behalf of Epimad Group
1
Childrens Health Russian Academy of Medical Sciences, Moscow, Russian Dermatology, 2Epidemiology, 3Paediatric Clinic, UNIVERSITY AND
Federation HOSPITAL LILLE, Lille, 4Gastroenterology, University and Hopsital, Amiens,
5
Contact E-mail Address: shavrovnczd@yandex.ru Gastroenterology, University and Hopsital, Rouen, 6Paediatric Clinic, Catholic
University, Lille, 7Gastroenterology, General Hospital, Seclin, 8Paediatric Clinic,
INTRODUCTION: Studies over the past two decades have convincingly demon- University and Hopsital, Rouen, 9Paediatric Clinic, University and Hopsital,
strated the role of barrier dysfunction in the pathogenesis of inflammatory bowel Amiens, 10Gastroenterology, University and Hopsital, Nancy, France
disease (IBD). We have previously found that optical biopsy with probe-based Contact E-mail Address: corinne.gower@gmail.com
confocal laser endomicroscopy (pCLE) could be used to assess mucosal barrier
function and predict disease relapse in pediatric IBD patients. The purpose of INTRODUCTION: Muco-cutaneous manifestations (MCM) are common in
this pilot study is to evaluate the correlation of pCLE findings between duodenal adult patients with Crohns disease (CD), but their frequency in paediatric-
and terminal ileum in pediatric IBD patients. onset CD is unknown.
AIMS & METHODS: This is a prospective study of pediatric IBD (Crohns AIMS & METHODS: The aims of our study were in a population-based paedia-
disease - CD and ulcerative colitis-UC) patients undergoing pCLE during both tric-onset CD cohort: i) to determine the cumulative incidence of MCM, includ-
EGD and colonoscopy in a tertiary referral center. The barrier function was ing aphtous stomatis (AS), erythema nodosum (EN) and pyoderma gangrenosum
assessed with the density of epithelial gaps on pCLE of the duodenum and (PG); and ii) to identify the socio demographic and clinical factors at CD diag-
terminal ileum. Adequate imaging of the duodenum and terminal ileum were nosis associated with a higher risk of developing MCM during the CD course.
defined as at least 3 normal, non-diseased areas sampled; a minimum of 3 villi Patients and Methods: Clinical data at diagnosis and at maximal follow-up were
with the highest number of epithelial gaps were analyzed. The epithelial gap recorded in a population-based paediatric-onset CD cohort (n 537, 517 years
density was calculated based on the total number of epithelial gaps observed at CD diagnosis) diagnosed from 1988 to 2004. Data on MCM were reviewed by
normalized per 1000 epithelial cells counted on adequately imaged villi. a dermatologist. Risks of developing MCM were estimated by survival analysis
RESULTS: A total of 13 IBD patients (9 CD, 4 UC) underwent EGD and and Cox models.
colonoscopy with adequate pCLE imaging of the duodenum and terminal RESULTS: Median age at CD diagnosis was 14.6 years (Q1 12.2; Q3 16.1)
ileum in the study. There were 8 F (62%) and 5 M (38%) with a median age and 53.6% of patients were males. At CD diagnosis, 87 patients (16.2%) had
of 15 yr (range 10 to 20). The median duration of disease at the time of pCLE was MCM including 26 of them (30%) with at least 2 MCM. After a median follow-
3 yr (range 0 to 9); for therapy, 4 patients (31%) were on anti-TNF agents, 6 up of 11 years (Q1 7; Q3 15), 148 patients (28%) developed a total of 175
(46%) were on 5-ASA and/or immunomodulators, 1 (7%) were on steroids, 2 MCM, including 110 (63%) AS, 59 (34%) EN, and 6 (3%) PG. Cumulative
(15%) were on no therapy. The disease distributions for CD were: ileo-colitis in 7 incidence of developing MCM was 21% [17.7 -24.6], 25% [21.6-29.0], 27%
patients (78%), ileitis in 1 (11%) and colitis 1 patients (11%). For UC: 1 patients [23.5-31.2] and 28% [24.3-32.3] at 1, 5, 10 and 15 years, respectively. In multi-
(25%) had pan-colitis, distal colitis in 2 (50%) and proximal colitis in 1 (25%). variate analysis, female gender (HR 2.6 [1.4-4.6]; p 0.002), patients 515 years
The gap density (mean SE) in the terminal ileum was 5.6 1.7 gaps/1000 cells, at diagnosis (HR 2.2 [1.3-3.8]; p 0.003) and L4 location at diagnosis
while in the duodenum was 1.7 0.5 gaps/1000 cells. There were modest correla- (HR 2.2 [1.3-3.6]; p 0.002) were significantly associated with a higher risk
tion between the gap density in the terminal ileum and duodenum with a spear- of developing MCM during the CD course.
man correlation coefficient of 0.42 (p 0.15) CONCLUSION: In this population-based paediatric-onset CD cohort, MCM
CONCLUSION: In this pilot study of pediatric IBD patients, we found pCLE are frequent both at diagnosis and during CD course, and are associated to
findings of barrier function as measured by epithelial gap density in the terminal female gender, young age and L4 location at CD diagnosis. These results rein-
ileum and duodenum had modest correlation. Future larger studies are war- force the need of a close collaboration between dermatologists, paediatric gastro-
ranted to further investigate the correlation of barrier function in the proximal enterologists and gastroenterologists in paediatric-onset CD in order to optimize
and distal intestine. the therapeutic management of these patients.
Disclosure of Interest: None declared Disclosure of Interest: C. Templier: None declared, H. Sarter: None declared, D.
Turck: None declared, M. Fumery: None declared, G. Savoye: None declared, B.
Catteau: None declared, C. Spyckerelle: None declared, E. Laberenne: None
P0349 INCIDENCE OF PEDIATRIC INFLAMMATORY BOWEL declared, O. Mouterde: None declared, D. Djeddi: None declared, S. Buche:
DISEASE IN MINHO-PORTUGAL IS INCREASING None declared, L. Peyrin-Biroulet: None declared, E. Delaporte: None declared,
C.A. Machado1,*, I. Martinho2, C. Laranjeira3, M. Figueiredo4, C. Carvalho5, C. Gower-Rousseau Lecture fee(s) from: Ferring, MSD
A. Reis6, F. Pereira7, E. Trindade8, H. Antunes9,10
1
School of Health Sciences, University of Minho, Braga, 2Paediatrics Department,
Unidade Local de Saude do Alto Minho, Viana do Castelo, 3Paediatrics P0351 LONG-TERM EFFICACY OF ADALIMUMAB IN PAEDIATRIC
Department, Centro Hospitalar do Alto Ave, Guimaraes, 4Paediatrics Department, PATIENTS WITH CROHNS DISEASE
Centro Hospitalar do Medio Ave, Vila Nova de Famalicao, 5Paediatrics W.A. Faubion1, M. Dubinsky2, F. Ruemmele3,*, J. Escher4, J. Rosh5, A. Lazar6,
Department, Hospital de Santa Maria Maior, Barcelos, 6Paediatrics, Centro S. Eichner7, Y. Li7, N. Reilly7, R.B. Thakkar7
Hospital do Tamega e Sousa, Amarante, 7Paediatric Gastroenterology 1
Mayo Clinic, Rochester, 2Cedars-Sinai Medical Center, Los Angeles, United
Department, Centro Hospitalar do Porto, 8Paediatrics, Centro Hospitalar de Sao States, 3Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris,
Joao, Porto, 9Life and Health Sciences Research Institute (ICVS), School of France, 4Erasmus MC-Sophia Childrens Hospital, Rotterdam, Netherlands,
5
Health Sciences, ICVS/3Bs - PT Government Associate Laboratory, University of Goryeb Childrens Hospital/Atlantic Health, Morristown, United States, 6AbbVie
Minho, Braga/Guimaraes, 10Gastroenterology, Hepatology and Nutrition Unit, Deutschland GmbH & Co. KG, Ludwigshafen, Germany, 7AbbVie Inc, North
Paediatrics Department, Hospital de Braga, Braga, Portugal Chicago, United States
Contact E-mail Address: caamachado@sapo.pt
INTRODUCTION: The efficacy of adalimumab (ADA) in children with mod-
INTRODUCTION: INTRODUCTION: Inflammatory bowel disease (IBD) erately to severely active Crohns disease enrolled in the IMAgINE 1 trial has
includes Crohns disease (CD), ulcerative colitis (UC) and indeterminate IBD been reported up to week (wk) 521. Long-term efficacy of ADA in patients (pts)
(IIBD). Although it primarily affects adults, the diagnosis in patients under 18 enrolled in the on-going open-label (OL) extension, IMAgINE 2, is presented.
is about 25% to 30%, being CD the most frequent. Studies report an increase in AIMS & METHODS: Pts who completed IMAgINE 1 through wk 52 were
the incidence of CD, but a stable incidence of UC. A 2010 study in Minho reports allowed to enroll in IMAgINE 2. Pts entering from blinded therapy received
an incidence of 6.4/100000 (CD:66%; UC:34%). OL ADA according to body weight (40 kg: 40 mg ADA every other wk
AIMS & METHODS: Our aim was to characterize patients diagnosed with IBD [EOW]; 540 kg, 20 mg ADA EOW). At or after wk 8, pts experiencing flares
from 2002 to 2013, between the ages of 0 to 17 years and 365 days, residents in (increase in PCDAI 15 points compared to PCDAI at previous visit) could
Minho (districts of Braga and Viana do Castelo), calculate the incidence and move to wkly (EW) dosing. Pts entering IMAgINE 2 from OL ADA (40 mg
evaluate the health-related quality of life. We conducted a retrospective study, by ADA or 20 mg ADA EW) continued to receive the same dose. Remission
collecting information from the patients personal clinical chart. Also performed (PCDAI10) and response (PCDAI decrease 15 points from IMAgINE 1 base-
was a cross-sectional study applying the IMPACT-III questionnaire that line) over time were assessed in pts who entered IMAgINE 2. Missing data were
assesses the quality of life of pediatric patients with IBD above 9 years old. handled using non-responder imputation (NRI) and last observation carried
RESULTS: 137 subjects were found. The incidence in 2002-2013 was 5.0/100000 forward (LOCF). Endpoints are also reported as observed. A data cut-off of
children-years (CD:66%, UC:32%, IIBD:2%), increasing from 2.4/100000 Jun 30, 2013 was used for this analysis.
(CD:65%, UC:35%) in the first three years to 8.8/100000 (CD:75%, UC:23%, RESULTS: Of the 188 randomized pts in IMAgINE 1, a total of 100 pts enrolled
IIBD:2%) in the last three (p 50.0001). Abdominal pain was the most frequent in IMAgINE 2. As of Jun 30, 2013, a total of 54 pts are ongoing in the study.
symptom in CD and hematochezia in UC. In the IMPACT-III, the average Approximately 2/3 of pts entered IMAgINE 2 in remission and almost all entered
score was 136.5 19.2 (n 32), with a Cronbachs alpha 0.91. with response (67% and 95%, respectively). Observed remission and response
A228 United European Gastroenterology Journal 2(5S)
rates remained stable over time during IMAgINE 2 (Table). Mean PCDAI scores 75% for DI, which means high response of treatment efficacy for IFX dose-up.
decreased from 40.1 at IMAgINE 1 baseline to 8.6 at wk 192 of IMAgINE 2 Further study about DI will be needed for the risk factors, for optimal timing of
(Table). Adverse event rates from IMAgINE 1 baseline up to wk 260 have been application in clinical course, and for any possible adverse events in long-term
previously reported and no new safety signals were observed with prolonged follow-up.
ADA use.2 Disclosure of Interest: None declared
Table. Rates of remission and response and observed mean PCDAI scores during
IMAgINE 2
P0353 FOCUSED EDUCATION AND VACCINE ACCESS IN CLINIC
IMPROVE INFLUENZA VACCINATION RATES IN CHILDREN
Week 0 24 48 72 96 120 144 168 192
WITH INFLAMMATORY BOWEL DISEASE
Remission (%) K. Huth1,*, E. Benchimol2, D. Mack2
1
NRI 67.0 59.0 55.0 50.0 54.0 51.0 51.0 42.0 26.0 Pediatrics, University of Ottawa, 2Gastroenterology, Hepatology & Nutrition,
LOCF 67.0 62.2 61.2 57.1 61.2 62.2 63.3 62.2 61.2 Childrens Hospital of Eastern Ontario, Ottawa, Canada
Contact E-mail Address: khuth@cheo.on.ca
Observed 67.0 62.8 66.3 64.1 70.1 73.9 79.7 79.2 81.3
Response (%) INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at
NRI 95.0 88.0 75.0 74.0 72.0 66.0 64.0 48.0 29.0 increased risk of experiencing complications of influenza infection, thus interna-
LOCF 95.0 91.8 85.7 87.8 85.7 85.7 87.8 82.7 81.6 tional guidelines recommend annual influenza vaccination for this population.
The vaccine is available at no cost in primary care physician offices, walk-in
Observed 95.0 93.6 90.4 94.9 93.5 95.7 100 90.6 90.6 clinics and pharmacies in Ontario, Canada, yet vaccine uptake remains low.
Mean PCDAI 10.2 10.3 9.2 8.9 9.4 7.9 6.1 7.5 8.6 AIMS & METHODS: We sought to understand barriers to obtaining influenza
vaccination in a pediatric IBD cohort, and to determine the impact of educa-
tional intervention and vaccine provision in IBD clinic on vaccine uptake. The
The number of pts declined over time due to discontinuations and not all pts had study was completed over two successive influenza seasons. During the 2012-
reached later time points. Results after wk 192 are not shown as few pts had 2013 season (Year 1), we surveyed parents and IBD patients aged 14 years
reached longer study durations. regarding influenza vaccination attitudes and practices. The following year
CONCLUSION: Results of the on-going OL study support clinically meaningful (Year 2), an educational module was developed to address concerns about vac-
efficacy with long-term ADA therapy beyond four years of exposure in children cination identified in Year 1. Parents and patients presenting to IBD clinic in the
with moderately to severely active CD. ten weeks prior to the 2013-2014 influenza season were provided with the educa-
REFERENCES tional module (Phase 1). When the trivalent inactivated influenza vaccine (TIIV)
1. Hyams et al. Gastroenterol 2012; 143: 365-374. became available, patients were offered both the educational module and the
2. Rosh et al. J Crohns Colitis 2014; 8: S243. opportunity for vaccination during their IBD clinic visits (Phase 2). Chi-squared
Disclosure of Interest: W. Faubion Consultancy for: Genentech, Connecticut analysis was used to identify significant differences in vaccination rates in each
Childrens Medical Center - Safety officer on subcontracted award through intervention group. Demographic factors were associated with survey responses
NIH for clinical trial, Other: Board membership (no personal compensation): and vaccination status.
Shire Development, Inc - Pediatric UC Advisory Board, Janssen Services LLC - RESULTS: During Year 1, 180 of 183 parents (98%) completed the survey along
DEVELOP Registry Scientific Advisory Committee, UCB Biosciences Advisory with all 108 adolescents. Median patient age at time of study was 11 years, 63%
board, M. Dubinsky Financial support for research from: Janssen, Consultancy were males, and 67% had Crohns disease. Most patients (74%) were on immu-
for: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus, UCB, F. nomodulator or biologic medications. In Year 1, 47% of patients obtained the
Ruemmele Lecture fee(s) from: Shering-Plough, Nestle, MeadJohnson, Ferring, TIIV, and 34% of patients reported obtaining the vaccine annually. Reasons for
MSD, Johnson & Johnson, Centocor, Other: Board membership: non-vaccination included a perceived lack of benefit (29%) and concerns about
SAC:DEVELOP (Johnson & Johnson), invited to MSD France, Nestle adverse events (20%). Most families (91%) reported they would obtain influenza
Nutrition Institute, invited to Nestle Health Science, invited to Danone, invited vaccination if their physician provided evidence of its benefit. Year 2 patients
to MeadJohnson, Biocodex, J. Escher Financial support for research from: (n 228) did not differ significantly in age, IBD subtype, disease severity or
MSD, Lecture fee(s) from: MSD, Consultancy for: Janssen Biologics, Other: medications from Year 1 patients. 95% of patients and parents who reviewed
Board membership: scientific advisory committee of DEVELOP study (Janssen the educational module reported that it was useful. 71% reported that the
Biologics), J. Rosh Financial support for research from: AstraZeneca, AbbVie, module informed their decision to obtain the TIIV, including 19% who had
Janssen, UCB, Lecture fee(s) from: Abbott Nutrition, Prometheus, Consultancy not planned to obtain the TIIV prior to reviewing the module. In Year 2, the
for: AbbVie, Janssen, Soligenex, Other: Board membership: GI Health vaccination rate in Phase 1 patients who received the educational module alone
Foundation, A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, S. was 75%, compared to 89% of Phase 2 patients who received both the educa-
Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Li Shareholder tional module and the option of obtaining the TIIV in IBD clinic (p 0.0043).
of: AbbVie, Other: Employee: AbbVie, N. Reilly Shareholder of: AbbVie, Other: Amongst the patients who took part in both Year 1 and Year 2 (n 129), serial
Employee: AbbVie, R. Thakkar Shareholder of: AbbVie, Other: Employee: determinations of influenza vaccination rates demonstrated an increase from
AbbVie 45% to 82% (P50.0001).
CONCLUSION: Despite widespread access to the TIIV at no cost, traditional
methods of promoting vaccination have yielded low uptake in IBD patients.
P0352 LONG-TERM SUSTAINED RESPONSE AND DURABILITY OF Providing a focused educational module on efficacy and safety addressed barriers
INFLIXIMAB FOR THE PEDIATRIC INFLAMMATORY BOWEL faced by vaccine-hesitant families and improved influenza vaccination rates.
DISEASE IN KOREA Additional vaccine uptake can be achieved by combining educational interven-
H.-J. JANG1,*, J.S. MOON1, J. YOO1, P. CHUN1, J.S. KO1, H.R. YANG2, tion with provision of influenza vaccination during IBD clinic visits.
J.Y. JANG3, J.K. SEO1 Disclosure of Interest: None declared
1
Department of Pediatrics, Seoul National University College of Medicine,
2
Department of Pediatrics, Seoul National University Bundang Hospital,
3
Department of Pediatrics, SMG-SNU Boramae Medical Center, SEOUL, Korea, P0354 ACCUMULATION OF INTRA-ABDOMINAL ADIPOSE TISSUE IN
Republic Of PEDIATRIC CROHNS DISEASE
Contact E-mail Address: bearinspring@hotmail.com, mjschj@snu.ac.kr K. Frivolt1,2,*, H. Hetterich3, T. Schwerd1, M.S. Hajji1, P. Bufler1,
E. Coppenrath3, S. Koletzko1
INTRODUCTION: Inflammatory bowel disease (IBD) is increasing in Korea, 1
Dr. v. Hauner Childrens Hospital, University Munich Medical Center, Munich,
especially in the pediatric population. Along with the classical treatment of 5- Germany, 22nd Department of Pediatrics, Comenius University Medical School,
ASA, steroid, and immunomodulators, biologic agents such as infliximab (IFX), Bratislava, Slovakia, 3Institute of Clinical Radiology, University Munich Medical
adalimumab are used increasingly. However, the safety and efficacy of IFX has Center, Munich, Germany
not been evaluated much for long-term follow-up. Contact E-mail Address: klarato@gmail.com
AIMS & METHODS: This is a single-center retrospective cohort study of 100
pediatric IBD (Crohn disease 90, Ulcerative colitis 10) who used infliximab from INTRODUCTION: Increased visceral adipose tissue (VAT) inflammation is a
2004 to 2014. The total duration of IFX administration, the dose intensification characteristic hallmark of surgical resections from Crohns disease (CD) patients.
(DI), the sustainability and efficacy of DI, and immunomodulator use with or Recent evidence points towards an active immunological role of VAT in CD
without IFX were analyzed. We also analyzed 3 groups to assess the efficacy and pathogenesis in addition of VAT being a defense mechanism for bacterial trans-
durability of IFX into sustained remission, recaptured response, and treatment location during intestinal inflammation. Magnetic resonance imaging (MRI)
failure group. Recaptured response meant the patients who recaptured remission studies showed accumulation of intra-abdominal VAT in adults, especially in
by dose intensification. patients with fistulas and strictures.
RESULTS: The total duration of follow-up for patients was 61.746.6 months. AIMS & METHODS: We aimed to quantify the abdominal adipose tissue com-
The mean duration of IFX administration was 31.028.0 months. Average age partments using MRI (Achieva, Philips Healthcare, Hamburg, Germany) in 29
of IFX initiation was 14.13.3 years. The interval between IFX initiation and pediatric CD patients compared with 14 control children (CC) undergoing MRI
dose intensification was 23.423.3 months. Dose intensification was in 53 examination of abdomen for other reason. Total abdominal (TA) adipose tissue,
patients out of 100 for the study period. Sustained remission was in 44 patients consisting of subcutaneous (SC) and intra-abdominal (IA) adipose tissues were
out of total and recaptured response was in 42, respectively. Treatment failure retrospectively measured by a radiologist blinded to the clinical data in transverse
was 16 out of 100, who discontinued IFX eventually. We checked for sustained slices centered on the umbilicus and expressed as mean standard deviation in
remission rate annually and the rate was declining over time with 46% at 12-24 cm2. IA/TA and IA/height ratios were assessed and analyzed for association
months, 41% at 24-36 months, and 40% at 36-48 months, respectively. markers. We recorded the mathematically weighted Pediatric Crohns Disease
CONCLUSION: This study shows that almost half of the patients with IFX Activity Index (wPCDAI), disease phenotype, laboratory and anthropometric
maintained sustained remission until 2-year follow-up. And recapture rate was data at the time of MRI. Mann-Whitney test was applied to analyze differences
United European Gastroenterology Journal 2(5S) A229
between patients and CC. The correlation significance was determined by means outcomes (PRO) version for children 8-17 years and an observer-reported out-
of Spearman correlation analysis. P50.05 was considered statistically significant. comes (ObsRO) version for caregivers of children aged 5-10 years.
RESULTS: CD patients included 20 males and 9 females (mean age 14.8 3.6 AIMS & METHODS: This was a twovisit cognitive debriefing interview study
years, range 7.7-18.3) with a mean BMI of 18.3 2.7, range 14.0-23.2. Median involving children with mild to moderate ulcerative colitis (UC) aged 8-17 years
disease duration from diagnosis to MRI was 21 months (range 0-136). Non- and caregivers of children aged 5-10 years. Mild to Moderate UC was
complicated disease behavior (B1) was present in 25/29, 4/29 had stricturing defined based on the Pediatric Ulcerative Colitis Activity Index (PUCAI) score
(B2) and 6/29 perianal disease. CC included 4 males and 10 females (mean age at the time of the interview. The interviews involved an initial set of open-ended
12.8 4.5 years, range 3.0-18.0), BMI (mean 17.6 3.2, range 13.4-23.6). CD questions on the signs, symptoms and impacts of UC to confirm findings from a
patients had higher IA adipose tissue (41.720.3 vs. 28.711.6, p50.05) but previous concept elicitation study, followed by cognitive debriefing of the DUCS
similar SC and TA adipose tissues compared to CC (104.4 70.9 vs. 96.54 along with items to assess global health, and items to examine device usability
50.8 and 146.1 84.7 vs. 125.3 61.5, NS). The IA/TA and IA/height ratios and characteristics of the sample. The visit 1 interview was held in person and
were significantly higher in CD patients compared to CC, respectively (0.310.10 lasted approximately 1 hour. Visit 2 took place by telephone 3 days after visit 1
vs. 0.240.04 and 25.912.7 vs. 18.47.8, p50.05). Patients with disease dura- and lasted about 25 minutes and was used to explore feasibility. Sample char-
tion under 2 years (n 14) had lower IA/TA ratio (0.280.08 vs. 0.350.10, acteristics were analysed using descriptive statistics (mean, SD, median, range for
p50.05) compared to longer disease. The IA/TA ratio correlated with disease continuous variables and N, % for categorical variables). Interview transcripts
duration (p50.05, r 0.425). No association was found between IA/TA and IA/ were analysed using qualitative analysis software, MAXqda, in which codes were
height ratios and disease phenotype or therapy. applied to allow focussed review of responses across the sample. Findings were
CONCLUSION: Intra-abdominal adipose tissue is increased and accumulates used to refine the DUCS to ensure clarity, relevance and comprehensiveness.
with disease duration in pediatric-onset CD. RESULTS: The PRO sample consisted of 38 participants (22 females and 16
Disclosure of Interest: None declared males), with 2 participants completing interviews for 2 different diary versions for
a total of 40 completed interviews. Age at study enrollment ranged from 8 to 17
years (mean of 12.8; SD 2.4; median of 13). The average PUCAI score, adminis-
P0355 PHARMACOKINETICS AND SAFETY OF MULTIMATRIX tered at visit 1, was 12.3 (SD 14.2), range 0 to 45. The caregivers of 7 children
MESALAZINE IN CHILDREN AND ADOLESCENTS WITH participated in the cognitive debriefing interviews of the ObsRO version. One
ULCERATIVE COLITIS caregiver tested two different versions of the eDiary for a total of 8 completed
C. Cuffari1, D. Pierce2, B. Korczowski3, K. Fyderek4,*, H.Van Heusen5, ObsRO interviews. The average age of the 7 caregiver participants was 41.5 years
S. Hossack6, P. Martin5 (SD 6.4; median of 42). The caregivers children were an average age of 8.5 years
1
The Johns Hopkins University School of Medicine, Division of Pediatric (SD 1.7; median of 9). Findings from the visit 1 concept elicitation questions were
Gastroenterology and Nutrition, Baltimore, MD, United States, 2Shire, consistent with those of the initial concept elicitation study. Four rounds of
Basingstoke, United Kingdom, 3Medical College, University of Rzeszow, Rzeszow, revisions were made to the PRO and ObsRO DUCS based on patient/caregiver
4
University Childrens Hospital of Cracow, Cracow, Poland, 5Shire, Wayne, PA, interview feedback, as well as feedback from the FDA. The FDA suggested
United States, 6Covance Clinical Research Unit Limited, Leeds, United Kingdom changes such as changing response scales, as well as the addition of questions
Contact E-mail Address: pmartin@shire.com to capture certain symptoms overnight. Patient input influenced changes such as
clarification of text and graphics, and the selection of the optimal pain scale. The
INTRODUCTION: Oral formulations of mesalazine (5-aminosalicylic acid; 5- eDiarys usability was also assessed. Both child and adult participants found the
ASA) are recommended first-line therapy for adults with active mild-to-moderate device easy to use and navigate.
ulcerative colitis (UC). However, little data are available on the use of mesalazine CONCLUSION: The DUCS eDiaries are content valid instruments capturing
in paediatric UC. This phase 1, multicenter, randomized, open-label study signs and symptoms of pediatric UC and are appropriate for measuring treat-
(NCT01130844) evaluated the pharmacokinetic and safety characteristics of 5- ment benefit in pediatric UC clinical trials.
ASA and its associated metabolite, acetyl-5-ASA (Ac-5-ASA), after once-daily Disclosure of Interest: E. Flood Other: Employee of ICON, which was contracted
administration of multimatrix mesalazine to children and adolescents with UC. by Shire to perform the research for the creation of the DUCS, D. Silberg
AIMS & METHODS: Patients aged 5-17 years with a UC diagnosis of 3 Shareholder of: Shire, Other: Employee of Shire, B. Romero Other: Employee
months were eligible to enrol. Study participants (stratified by body weight) of ICON, which was contracted by Shire to perform the research for the creation
were administered 30, 60, or 100 mg/kg/day multimatrix mesalazine once-daily of the DUCS, K. Beusterien Other: Performed this work when she worked at
for 7 days. In order to attain these doses in children, smaller-sized 300 mg and Oxford Outcomes, which provides consulting services to Shire, M. H. Erder
600 mg multimatrix mesalazine tablets were developed to supplement the existing Shareholder of: Shire, Other: Employee of Shire
approved 1200 mg tablet. Mesalazine was administered to patients at home on
Days 1-4 and on-site on Days 5-7, during which pharmacokinetic blood and
urine samples were collected and safety evaluations performed. Plasma and P0357 AORTIC INTIMA-MEDIA THICKNESS AS AN EARLY MARKER
urine concentrations of 5-ASA and Ac-5-ASA were determined using a validated OF ATHEROSCLEROSIS IN CHILDREN WITH INFLAMMATORY
LC/MS/MS assay. Derived pharmacokinetic parameters for assessment included BOWEL DISEASE
maximum concentration (Cmax, ss), time of Cmax, ss (tmax), area under the curve M. Aloi1,*, L. Tromba2, V. Rizzo1, G. DArcangelo1, A. Dilillo1, S. Blasi2,
for one dose interval (AUCss), renal clearance (CL5SUB4R5/SUB4), and F. Civitelli1, F. Viola1, A. Redled2, S. Cucchiara1
percent of dose absorbed. 1
Pediatric Gastroenterology And Liver Unit, 2Department of Surgical Sciences,
RESULTS: A total of 52 patients (21 at 30 mg/kg; 22 at 60 mg/kg; and 9 at 100 SAPIENZA UNIVERSITY OF ROME, Rome, Italy
mg/kg) were treated. Mean (standard deviation) age was 13.3 (3.06) years, and Contact E-mail Address: marina.aloi@uniroma1.it
median (range) time since UC diagnosis was of 1.83 (0.2- 9.6) years. By Day 5,
steady state plasma concentrations for 5-ASA and Ac-5-ASA were attained for INTRODUCTION: Aims of this study were to determine the presence of
all dose groups. On Day 7, dose-proportional increases in mean AUCss and Cmax, endothelial dysfunction by measuring aortic intima-media thickness (aIMT)
ss for both 5-ASA and Ac-5-ASA were observed between 30 and 60 mg/kg/day and carotid intima-media thickness (cIMT) and to evaluate the role of traditional
cohorts. For 30, 60, and 100 mg/kg/day doses, the mean percentages of 5-ASA risk factors for premature atherosclerosis in children with inflammatory bowel
absorbed from multimatrix mesalazine were 29.4%, 27.0%, and 22.1%, respec- disease (IBD).
tively. The mean CLR ranges for 5-ASA and Ac-5-ASA, respectively, were 5.0- AIMS & METHODS: Thirty-four children with IBD [25 Crohns disease (CD)
6.5 L/h and 10.0-16.2 L/h. Treatment-emergent adverse events were reported by and 9 ulcerative colitis (UC); mean age 11.1 years] and 27 healthy subjects
19.2% of all patients; events were similar among different dose and age groups matched for sex and age were enrolled. In all patients, demographic character-
and no new safety signals were identified. istics and risk factors for atherosclerosis (age, sex, body mass index, blood pres-
CONCLUSION: Across all dose groups, children/adolescents with UC receiving sure, dyslipidemia, active and passive smoking, family history for cardiovascular
multimatrix mesalazine demonstrated pharmacokinetic profiles for 5-ASA and diseases), CD and UC clinical activity scores and inflammatory markers, were
Ac-5-ASA similar to those observed in historical adult data. Multimatrix mesa- evaluated. Aortic IMT and cIMT were measured by high resolution B-mode
lazine was well tolerated across all dose and age groups, and no novel safety ultrasound.
signals were reported. RESULTS: Aortic IMT was significantly higher in patients than controls
Disclosure of Interest: C. Cuffari Consultancy for: Shire, Prometheus and Abbott (p50.001). No significant differences were found for cIMT, although the carotid
Nutritionals, D. Pierce Shareholder of: Shire, Other: Former employee of Shire, thickness was higher in IBD patients than healthy subjects. At a univariate
B. Korczowski: None declared, K. Fyderek Financial support for research from: analysis, inflammatory markers levels and tobacco smoking exposure were sig-
Received a grant from Shire for the study research conducted, H. Van Heusen nificantly related to higher aIMT values, while at a multivariate analysis the
Shareholder of: Shire, Other: Employee of Shire, S. Hossack Other: Employee of inflammatory status was the only independent variable correlated with high
Covance, which received funding from Shire for assistance with the pharmaco- aIMT.
kinetic analysis, P. Martin Shareholder of: Shire, Other: Employee of Shire CONCLUSION: Aortic IMT is an earlier marker of preclinical atherosclerosis in
young children with active IBD, than cIMT. The inflammatory status and the
smoking exposure are significantly correlated with the premature endothelial
P0356 DEVELOPMENT OF THE DAILY ULCERATIVE COLITIS SCALE dysfunction. These data emphasize the importance of controlling the chronic
FOR CHILDREN AND CAREGIVERS: FINDINGS FROM COGNITIVE intestinal inflammation and endorsing smoke-free environments for children
DEBRIEFING INTERVIEWS and adolescents with IBD
E. Flood1, D.G. Silberg2, B. Romero1, K. Beusterien3, M.H. Erder2,* Disclosure of Interest: None declared
1
ICON Commercialisation and Outcomes, Bethesda, MD, 2Shire, Wayne, PA,
3
ORS Health, Washington, DC, United States
Contact E-mail Address: herder@shire.com
INTRODUCTION: To test and refine the Daily Ulcerative Colitis Scale
(DUCS), an electronic daily sign and symptom diary with a patient-reported
A230 United European Gastroenterology Journal 2(5S)
P0358 GROWTH IMPROVEMENT IN ADALIMUMAB-TREATED P0359 TREATMENT OF CORTICOSTEROID NAIVE PAEDIATRIC AND
PAEDIATRIC PATIENTS WITH CROHNS DISEASE: DATA FROM ADOLESCENT PATIENTS WITH ULCERATIVE COLITIS BY
IMAGINE 1 THERAPEUTIC DEPLETION OF MYELOID LINEAGE
T. Walters1,*, W.A. Faubion2, A. Griffiths1, R. Baldassano3, J. Escher4, LEUCOCYTES AS MONOTHERAPY OR IN COMBINATION WITH
F. Ruemmele5, J.S. Hyams6, A. Lazar7, S. Eichner8, Y. Li8, B. Pappalardo8, LOW DOSE PREDNISOLONE AFTER FAILURE OF FIRST-LINE
R.B. Thakkar8 MEDICATIONS
1
The Hospital for Sick Children, Toronto, Canada, 2Mayo Clinic, Rochester, T. Tanaka1,*, S. Sugiyama1, H. Goishi 1, T. Kajihara1, M. Akagi 1, T. Miura1
3
Childrens Hospital of Philadelphia, Philadelphia, United States, 4Erasmus MC- 1
Department of Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan
Sophia Childrens Hospital, Rotterdam, Netherlands, 5Universite Sorbonne Paris- Contact E-mail Address: tomotaka@c.do-up.com
Cite, Hospital Necker-Enfants Malades, Paris, France, 6Connecticut Childrens
Medical Center, Hartford, United States, 7AbbVie Deutschland GmbH & Co. KG, INTRODUCTION: Given that patients with active ulcerative colitis (UC) have
Ludwigshafen, Germany, 8AbbVie Inc, North Chicago, United States elevated and activated myeloid lineage leucocytes including the CD14CD16
monocyte phenotype known to be a major source of tumour necrosis factor-,
INTRODUCTION: Children with Crohns disease (CD) often have impaired selective depletion of these leucocytes by granulocyte and monocyte adsorption
growth. The IMAgINE 1 trial demonstrated the safety and effectiveness of ada- (GMA) should be an effective intervention in UC patients. This thinking is most
limumab (ADA) on inducing and maintaining remission in children with mod- relevant in paediatric and adolescent patients in whom long-term drug therapy
erately to severely active CD1. The impact of ADA therapy on growth in patients may adversely affect their growth and development.
with delayed growth at trial entry is analyzed. AIMS & METHODS: This study was to evaluate the efficacy of GMA as a
AIMS & METHODS: In IMAGINE 1, patients aged 6-17 years with baseline remission induction therapy in children and adolescents with UC in whom
(BL) PCDAI 430 received open-label induction of ADA at weeks 0/2 according first-line medications had failed. In a single centre setting, a total of 27 consecu-
to body weight (40kg, 160/80mg; 540kg, 80/40mg). At week 4, patients were tive children and adolescents, age 11-19 years, bodyweight 31.5-56.5kg were given
randomized to double-blind higher-dose (HD) ADA (40kg, 40mg every other mesalazine or sulphasalazine as a first-line medication. Twenty patients relapsed
week [EOW]; 540kg, 20mg EOW) or lower-dose (LD) ADA (40kg, 20mg while under first-line medication or did not respond to first-line medication and
EOW; 540kg, 10mg EOW) to week 52. Patients were allowed to escalate to received GMA with the Adacolumn, 2 sessions in the first week, and then weekly,
blinded weekly therapy for flare or non-response, followed by open-label HD up to 11 sessions. Patients who achieved a decrease of 5 in the clinical activity
ADA weekly for continued flare or non-response. Change from BL in height index (CAI) were to continue with GMA, while non-responders were to receive
velocity z-score was measured at weeks 26 and 52 in patients with and without 0.5 to 1.0 mg/kg bodyweight/day prednisolone (PSL) plus additional GMA ses-
growth delay at BL (defined as height velocity z-score -1.0) in all ADA patients sions. However, PSL was to be tapered immediately after CAI started to fall. At
regardless of treatment group. Subgroup analyses by BL corticosteroid use, dis- entry and week 12, patients UC severity was clinically and endoscopically eval-
ease severity (based on median BL PCDAI of study population (PCDAI 5 40, uated, allowing each patient to serve as her/his own control.
moderate CD; PCDAI 40, severe CD), and prior infliximab (IFX) use were RESULTS: At entry, all 27 patients were corticosteroid na ve and none had
performed. extensive loss of the mucosal tissue at the affected sites. Seven patients achieved
RESULTS: Overall, statistically significant improvement in growth was observed sustained remission with the first-line medications and did not receive GMA.
at weeks 26 and 52 with ADA maintenance therapy in patients with growth delay Eight patients did not respond well to the first 5 GMA sessions and received
(median height velocity z-score at BL -2.9 and median change from BL at weeks PSL plus GMA, and in 2 of these with severe UC, the PSL dose was temporarily
26 and 52; 2.4 and 3.3, respectively, each p50.001), but not in patients with increased to 2mg/kg bodyweight while 12 patients responded to the first 5 GMA
normal growth (BL median 0.2; median change from BL 0 at weeks 26 and sessions and received additional sessions. At entry, the average CAI was
52). No statistically significant differences between LD and HD ADA were 13.02.4, range 8-17, and the average endoscopic index was 8.81.6, range 7-
observed. Growth improvement trended to be larger in patients with BL corti- 11. The corresponding values at week 12 were 2.10.2, range 1-4 (P50.001) and
costeroid use, with severe CD, and in IFX na ve patients (Table). 2.40.2, range 1-4 (P50.001). PSL was tapered to 0mg within 3 months in the 8
Table. Median BL height velocity z-score values and change from BL at weeks 26 PSL treated patients. Therefore, at week 12, all 27 patients had achieved clinical
and 52 in patients with growth delay (height velocity z-score -1.0 at BL) remission, majority with mucosal healing (complete remission). Except difficul-
ties in achieving blood access causing needle pain in a few cases, no serious GMA
BL Week 26 Week 52 related adverse event was observed, and compliance was good, no refusal to
receive GMA and no withdrawal from the GMA treatment.
LD -3.0 (N 47) 2.5* (N 47) 3.4* (N 30) CONCLUSION: In this study, GMA in paediatric and adolescent corticosteroid
na ve patients with active UC refractory to first-line medication was associated
HD -2.8 (N 42) 2.3* (N 42) 3.3* (N 29) with clinical remission and mucosal healing, while in non-responders to GMA
IFX na ve -3.1 (N 54) 2.7* (N 54) 3.8* (N 41) monotherapy, addition of PSL enhanced the efficacy of GMA and tapering of
IFX experienced -2.3 (N 35) 1.7* (N 35) 1.4* (N 18) the PSL dose immediately after the fall in CAI score was not associated with UC
Corticosteroid use at BL -2.8 (N 38) 2.5* (N 38) 4.3* (N 23) relapse. Therefore, with its favourable safety profile, the majority of young ster-
oid na ve patients with active UC refractory to first-line medication should
No corticosteroid use at BL -2.9 (N 51) 2.3* (N 51) 2.3* (N 36) respond well to GMA and be spared from pharmacological interventions.
Moderate CD -3.2 (N 26) 2.7* (N 26) 3.0* (N 22) Disclosure of Interest: None declared
Severe CD -2.7 (N 63) 2.3* (N 63) 3.8* (N 37)
INTRODUCTION: As compared with Standard Forward Viewing (SFV) colo- P0366 SESSILE SERRATED ADENOMAS, ARE THERE ANY RISK
noscopy, Full Spectrum Endoscopy (Fuse) colonoscopy increases the adenoma FACTORS?
detection rate and thereby impacts the recommended post-polypectomy surveil- G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
lance intervals per current US and European guidelines [1]. S. Lamprinakos1, K. Makris1, C. Tzathas1,*
AIMS & METHODS: As compared to SFV colonoscopy, we aimed to assess the 1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece
cost effectiveness of FUSE colonoscopy in a CRC screening and surveillance Contact E-mail Address: gmicha78@hotmail.com
program. We constructed a Markov model to simulate the occurrence of color-
ectal neoplasia in a cohort of 100,000 subjects ages 50 to 100 years of age. The INTRODUCTION: Evidence is conflicting regarding the risk factors for devel-
cost-effectiveness of FUSE was compared with that of SFV colonoscopy, with opment of Sessile Serrated Adenomas.
each test being assumed to be repeated every 10 years for those 50 to 80 years of AIMS & METHODS: This prospective study was performed in order to identify
age. Sensitivity for adenomatous and hyperplastic polyps 5 mm, 6-9 mm, and differences in the characteristics of patients with Sessile Serrated Adenomas with
high-risk polyps (10 mm; 510 mm with unfavourable histology or multiplicity) and without dysplasia (SSA/D) in comparison to patients with normal colonos-
were derived from the recent RCT tandem Fuse colonoscopy study [1]. Post- copies. Data from127 patients (100 with normal colonoscopies and 27 with SSA/
polypectomy surveillance was modeled according to polyp histology. Medicare Ds) regarding age, sex, smoking habits, BMI, waist-hip ratio and medical history
costs were adopted and used in the analysis. (arterial hypertension, diabetes mellitus, past history of polyps) was collected and
RESULTS: For the modeled cohort, the significantly higher sensitivity of FUSE analyzed by multivariate logistic regression analysis. Four age subgroups: 41-50,
colonoscopy in detecting additional colonic adenomas resulted in an increase in 51-60, 61-70 and 71-80 were analyzed with univariate logistic regression analysis.
CRC prevention from 58% to 74%, corresponding to a gain of 9 days per person Analyses was performed using Stata 9.0
(2,413 life-years for the entire cohort). This 16% increase led to an absolute RESULTS:
reduction in the cost of CRC care from $90 million to $57 million. This $33
million cost savings was only minimally impacted by the higher cost of more SSA/D vs Normal (multivariate) OR P-value 95% C. I.
frequent post-polypectomy colonoscopy surveillance rates, so that FUSE was
associated with a savings of $146 per person. Thus, SFV colonoscopy appeared Age 1.04 0.008 1.01-1.08
to be dominated by the FUSE colonoscopy strategy, with FUSE colonoscopy
being both more effective and less costly. By assuming 68 million of American Current smokers 4.35 0.003 1.63-11.59
subjects between 50 and 80 years of age and an annual incidence of 107,483 CRC Personal medical history of polyps 3.34 0.004 1.48-7.58
cases without screening for a discounted annual CRC care cost of $3.7 billion, the Age OR P-Value 95% CI
additional efficacy of FUSE over SFV would result into the annual prevention of SSA/Ds vs Normal (univariate)
10,318 CRC and the annual saving of $0.3 billion for CRC related costs. 41-50 1.33 0.84 0.07-23.5
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears
to be more cost-effective for CRC screening and surveillance. In particular, the 51-60 9.88 0.032 1.21-80.07
higher associated costs of more frequent post-polypectomy colonoscopy surveil- 61-70 8.72 0.047 1.02-74.11
lance were compensated by the significant overall reduction in CRC treatment 71-80 26.18 0.003 3.03-225.9
costs.
REFERENCES
[1] Gralnek IM, Siersema PD, Halpern Z, et al. Standard forward-viewing colo-
noscopy versus full-spectrum endoscopy: an international, multicentre, rando- No statistical significant difference was observed regarding diabetes mellitus,
mised, tandem colonoscopy trial. Lancet Oncol 2014; 15: 353-360. hypertension, BMI and waist-hip-ratio.
Disclosure of Interest: None declared CONCLUSION: Smoking and personal past history of polyps increase the risk
for SSA/Ds in comparison to normal population. Increasing age also increases
the risk for SSA/Ds, especially after the age of 50.
P0365 SESSILE SERRATED VERSUS CONVENTIONAL ADENOMAS. Disclosure of Interest: None declared
DIFFERENT POLYPS IN DIFFERENT POPULATIONS
G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
S. Lamprinakos1, K. Makris1, C. Tzathas1,* P0367 DRUG ALLERGY AND RISK OF LYMPH NODE METASTASIS IN
1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece RECTAL CANCER
Contact E-mail Address: gmicha78@hotmail.com C. Gao1,*, J.-T. Li1, L. Fang1, H.-C. Zhao1
1
Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of
INTRODUCTION: There are emerging data indicating that Sessile Serrated Health, Beijing, China
Adenomas may have different epidemiological characteristics than conventional Contact E-mail Address: gaochun@bjmu.edu.cn
adenomas.
AIMS & METHODS: This prospective study was aimed to identify any differ- INTRODUCTION: Previous epidemiologic studies have reported that a history
ences in the characteristics of patients with Sessile Serrated Adenomas with and of allergy is associated with reduced risk of colorectal cancer and other malig-
without dysplasia (SSA/Ds) in comparison to patients with conventional nancies. However, no information is available for the association between allergy
Adenomatous Polyps (APs). 85 patients with APs and SSA/Ds were included and risk of lymph node metastasis.
and data regarding age, sex, smoking, BMI, waist-hip-ratio and medical history AIMS & METHODS: Our study was designed to determine this association in
(arterial hypertension and diabetes mellitus) were collected. A univariate and a rectal cancer.
multivariate regression analysis were performed using z test. Patients who were treated at our hospital in the period from January 2003 to
RESULTS: 156 APs and 53 SSA/Ds of 85 patients (mean age 66.19.8 and June 2011, and with a pathological hospital discharge diagnosis of rectal aden-
63.19.4 years, respectively) with their characteristics and the results from uni- carcinoma, were included. The clinical, laboratory and pathologic parameters
variate and multivariate regression analysis are presented in the following table. were analyzed. Multivariate logistic regression model was used to determine
the association. Moreover, for type of allergic drug, sub-group analysis was
SSA/D vs AP (univariate) OR P-value 95% C. I. performed.
RESULTS: 469 patients were included, including 231 with pathological lymph
Sex (women/men) 2 0.034 1.05-3.84 node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis
showed, compared with patients without pLNM, patients with pLNM had a
BMI 0.92 0.031 0.85-0.99 younger age (60.612.8 yr vs. 63.612.2 yr, p 0.012), a lower percentage of
Waist-hip-ratio 0.01 0.06 0.0002- 1.30 drug allergy (8.7% vs. 16.0%, p 0.016), an increased CEA (median/interquar-
Diabetes Mellitus 0.09 50.001 0.02-0.33 tile-range 5.40/2.40-13.95 vs. 3.50/2.08-8.67, p 0.009), and a lower serum
Hypertension 0.24 50.001 0.12- 0.47 sodium (1413.1mmol/L vs. 1422.9 mmol/L, p 0.028). Multivariate analysis
showed that drug allergy was associated with a reduced risk of pLNM
SSA/D vs AP (multivariate) OR P-value 95% C. I. (OR 0.553; 95% CI, 0.308-0.994; p 0.048). In addition, our results showed
Diabetes mellitus 0.1 50.001 0.03-0.36 that: (1) for tumor classification, patients with drug allergy had a higher percen-
Hypertension 0.3 0.001 0.14-0.63 tage of group patients with pT1/ pT2; and (2) for type of allergic drug, this
inverse association was found for penicillins, not for other allergic drugs.
CONCLUSION: Drug allergy is associated with a reduced risk of pLNM in
rectal cancer.
There was no statistical significant difference regarding sex, BMI and waist-hip- Disclosure of Interest: None declared
ratio (p40.05) in the multivariate regression analysis. A peak incidence of SSA/
Ds was observed in the ages of 51-60 years compared to a peak incidence in the
ages of 61-70 years of APs (p 0.001). No significant difference between groups
regarding smoking was observed (p40.05).
United European Gastroenterology Journal 2(5S) A233
rounds for an optimal preventative effect. The diagnostic yield of advanced
P0368 PROGNOSTIC VALUE OF HUMAN PAPILLOMAVIRUS IN ANAL
neoplasia may increase with the use of two FITs per round. Therefore, in this
SQUAMOUS CELL CARCINOMA
study we assessed the diagnostic yield and participation rate of two-sample FIT
P.S. Ravenda1, E. Magni1, E. Botteri1, M. Manzotti1, M. Barberis1, screening during three successive rounds in a population-based screening pilot in
C. Trovato2,*, V. Dellacqua1, M.C. Leonardi1, M. Sideri1, N. Fazio1, the Netherlands.
M.G. Zampino1 AIMS & METHODS: A representative sample of the Dutch population
1
EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy, 2Endoscopy (n 3197) aged 50-75 years was randomly selected and invited by mail for
Division, EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy three rounds of two-sample FIT screening with a 2-year interval. Participants
Contact E-mail Address: cristina.trovato@ieo.it received two identical FIT tests per round to sample on two consecutive bowel
movements. Tests were analyzed using the OC Sensor Micro (Eiken Japan) with
INTRODUCTION: Anal cancer is an uncommon malignancy but its incidence is a positivity cut-off level of 50ng Hb/ml ( 10 mg Hb/g feces). Participants with at
increasing worldwide. Chemoradiation is the standard primary treatment for least one positive test were offered colonoscopy. For each round, we excluded
patients with loco-regional limited disease. However, once patients develop meta- individuals who met exclusion criteria (history of CRC, IBD, colon imaging 3
static spread, the prognosis is very poor. Human papillomavirus (HPV) is present years, life expectancy 55 years, inability to give informed consent) died, moved
in around 80% of anal cancers but its prognostic/predictive value is essentially away or were positive at previous rounds.
unknown. RESULTS: The participation rate was 64.4% (95% Confidence Interval (CI)
AIMS & METHODS: We retrospectively evaluated 50 patients with anal squa- 62.566.4%) at the third round, compared to 62.1% (1647/2652; 95% CI:
mous cell carcinoma treated at our Institution with chemoradiotherapy for loco- 60.2-63.9%) in the second and 61.3% (1875/3061; 95% CI: 59.663.1%) in the
regional disease. HPV status was evaluated from paraffin-embedded tumor tis- first round. One test was positive in 145 (9.8%; 95% CI 8.411.4) individuals and
sues collected at the time of diagnosis by a polymerase chain reaction analysis. in 41 (2.8%; 95% CI 2.03.7) both FITs tested positive. Of the 134 (92%)
RESULTS: Among 50 patients 42 (84%) were HPV-positive. Thirty-two (64%) patients who proceeded to colonoscopy, 5 had CRC and 13 had an advanced
patients were positive to genotype 16, two (4%) to genotype 18 and three (6%) to adenoma (defined as an adenoma 10mm, with 25% villous component or
both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were high-grade dysplasia). The positive predictive value (PPV) for advanced neopla-
more advanced for HPV-positive patients. After a median follow-up of 4 years sia was 13.4% (95% CI 8.6-20.3) for at least one positive test and 18.4% (95% CI
(range 0.4-13.8) 46 (92%) patients were alive. Overall, 8 patients relapsed: 1 loco- 9.0-33.9) when both tests were positive. The two-sample methodology detected
regional, 1 regional and 6 distant recurrences were observed. Four patients died 61.1% additional participants with advanced neoplasia (p 0.28) who would
from metastatic disease. Five-year disease-free survival (DFS) in HPV-positive have been missed with a single FIT test per round; 4 (80%) participants who
and HPV-negative patients was 92.5% and 50.0%, respectively (p 5 0.01). In had CRC and 7 (53.9%) who had an advanced adenoma had only 1 positive test.
multivariate analysis, HPV-positivity was associated with a statistically signifi- Table, 2-sample FIT screening (1positive) in multiple rounds
cant better 5-year DFS. Five-year overall survival in HPV-positive and HPV-
negative patients was 93.3% and 66.7%, respectively (p 0.12). Eligible
CONCLUSION: In our study HPV-positive anal cancers had a statistically sig- invitees Participation PR DR PPV
nificant improved DFS compared to HPV-negative group. Advanced Advanced
Disclosure of Interest: None declared neoplasia CRC neoplasia %
n n (%) n (%) n (%) n (%) (95% CI)
P0369 ASSOCIATION BETWEEN COLORECTAL NEOPLASMS AND
Round 1 3061 1876 (61.3) 239 (12.8) 76 (4.1) 12 (0.6) 34% (28.3 40.7)
METABOLIC SYNDROME IN A PORTUGUESE POPULATION
1,* 1 1 1 1 Round 2 2654 1647 (61.2) 141 (8.6) 26 (1.6) 4 (0.2) 19.0% (13.3 - 26.4)
D. Trabulo , S. Ribeiro , C. Martins , C. Teixeira , C. Cardoso ,
J. Mangualde1, R. Freire1, E. Gamito1, A.L. Alves1, F. Augusto1, I. Cremers1, Round 3 2297 1480 (64.4) 145 (9.8) 18 (0.8) 5 (0.2) 13.4% (8.6 - 20.3)
A.P. Oliveira1
1
Gastroenterology, Hospital de Sao Bernardo - Centro Hospitalar de Setubal,
Setubal, Portugal CONCLUSION: Two-sample FIT screening is associated with a stable and high
Contact E-mail Address: danieltrabulo@yahoo.com participation rate of more than 60% after three rounds. Positivity rates and
detection rates with two-sample FIT screening, are higher compared to historical
INTRODUCTION: There has been a growing recognition of metabolic syn- data of screening with one-sample FIT per round (van Roon Gut 2012). This
drome (MS) as an important risk factor for cardiovascular disease and malig- implies that FIT screening with two samples has an added benefit to detect a
nancies. Several investigators from Eastern countries have considered MS as a maximum number of individuals with advanced neoplasia.
possible risk factor for colorectal neoplasms. Disclosure of Interest: None declared
AIMS & METHODS: The aim of this study was to evaluate the association of
MS and colorectal cancer and adenomas in a Western country, where the inci-
dence of MS is over 27%. P0371 LIFESTYLE, ENVIRONMENT OR GENDER WHAT HAS
Methods: Prospective study between March 2013 and March 2014. MS was BIGGER IMPACT ON THE INCIDENCE OF COLORECTAL
diagnosed according to National Cholesterol Education Program-ATP III. NEOPLASIA?
Demographic characteristics, anthropometric measurements, metabolic risk fac- E. Waldmann1,2,*, G. Heinze3, M. Britto-Arias1,2, D. Sallinger1,2, I. Gessl1,2,
tors and colonoscopy pathologic findings were assessed in patients with MS A. Ferlitsch1,2, M. Trauner1,2, M. Ferlitsch1,2
(group 1) who underwent routine colonoscopy at our department. This data 1
Quality Assurance Working Group of the Austrian Society of Gastroenterology
was compared with consecutive patients without metabolic syndrome (group and Hepatology, 2Div. of Gastroenterology and Hepatology, Dept. of Internal
2), with no differences regarding sex and age. Informed consent was obtained Medicine III, 3Department for Medical Statistics, Division of Clinical Biometrics,
and the ethics committee approved this study. Statistical analysis was performed Medical University of Vienna, Austria, Vienna, Austria
with T-student and 2 tests; p-value0,05 was considered statistically significant. Contact E-mail Address: monika.ferlitsch@meduniwien.ac.at
RESULTS: We evaluated a total of 258 patients, 129 with MS; 50% males;
mean-age 67,1 years (50-87). Among the MS group, 94% had high blood pres- INTRODUCTION: Recommendations for colorectal cancer (CRC) screening
sure, 91% had increased waist circumference, 60% had diabetes, 55% had low are based on patients age and family history of cancer, although men are at
HDL cholesterol level, 50% had increased triglyceride level and 54% had obesity higher risk for adenomas and CRC and develop the lesions earlier than women.
(BMI30kg/m2). 51% presented 4 criteria of MS. MS was associated with Several risk factors such as BMI, gamma GT levels, presence of diabetes and
increased presence of adenomas (43% vs 25%, p 0.004) and colorectal cancer physical activity are known to increase the incidence of adenomas and CRC but
(13% vs 5%; p 0.027), compared with patients without MS. MS was also less is known about the impact of those risk factors on prevalence of colorectal
positively associated with multiple (3) adenomas (35% vs 9%, p 0.024) and neoplasia in men and women.
sessile adenomas (69% vs 53%; p 0.05). No differences existed between loca- AIMS & METHODS: To investigate the impact of risk factors on sex specific
tion (p 0.086), grade of dysplasia (p 0.196) or size of adenomas (p 0.841). adenoma detection rates (ADR) and advanced adenoma detection rates
Increased waist circumference was an independent risk factor for the presence of (AADR). We included patients who attended preventive health check up exam-
adenomas (85% vs 15%, p 0.05). inations and screening colonoscopy at the same time point (within six months) in
CONCLUSION: In our population, MS was associated with colorectal cancer Austria between November 2007 and December 2012.
and adenomas. Central obesity was also associated with an increased risk. RESULTS: The investigated risk factors had greater impact on male patients
Recommendations for colorectal cancer screening in patients with MS may than on female patients. High BMI influenced ADR (p50.0001) and AADR
need to be different from the average risk population. To our knowledge, no (p50.0001) in male patients and ADR (p 0.0229), but not AADR (p 0.2720)
previous study evaluated this association in Portuguese patients. in female patients. High gamma GT levels also increased ADR (p50.0001,
Disclosure of Interest: None declared OR 1.11, CI 1.05-1.16) and AADR (p 0.0045, OR 1.12, CI 1.04-1.21)
in male, but not in in female patients (p 0.5237, OR 1.02, CI 0.96-1.09 for
ADR and p 0.3804, OR 0.95, CI 0.85-1.07 for AADR). Presence of diabetes
P0370 THIRD ROUND OF TWO-SAMPLE IMMUNOCHEMICAL FECAL has an impact on ADR (p 0.0049, OR 1.2) and AADR (p50.0001, OR 1.6)
OCCULT BLOOD TEST SCREENING IN THE NETHERLANDS in male, but not in female patients (p 0.276, OR 1.1 and p 0.234, OR 1.3).
E.H. Schreuders1,*, S. Nieuwenburg1, A. Kapidzic1, E.J. Grobbee1, A.J. Physical activity impacts ADR (p 0.0018, OR 0.8) and AADR (p50.001,
van Vuuren1, W. Spijker2, M.J. Bruno1, E.J. Kuipers1, M.C. Spaander1 OR 0.6) in male as well as AADR in female patients (p 0.0150, OR 0.7)
1
Gastroenterology and Hepatology, Erasmus MC, 2Stichting Bevolkingsonderzoek but not the ADR in female patients (0.0792, OR 0.8).
Zuid-West Nederland, Rotterdam, Netherlands CONCLUSION: Our results show that acknowledged risk factors for colorectal
Contact E-mail Address: e.schreuders@erasmusmc.nl neoplasias seem to affect particularly male patients which raises the need of
implementation of gender specific prevention recommendations for CRC, espe-
INTRODUCTION: Screening for colorectal cancer (CRC) by means of immu- cially for men with risk factors.
nochemical fecal occult blood test (abbr. iFOBT or FIT) requires successive Disclosure of Interest: None declared
A234 United European Gastroenterology Journal 2(5S)
Disclosure of Interest: None declared
P0372 ANTI-HER2/NEU PEPTIDE WAS LABELED WITH TC-99M TO
DETECT HER2-POSITIVE TUMORS IN COLORECTAL HCT-15
DERIVED XENOGRAFTS P0374 COMPARISON OF AUTOMATED AND MANUAL DNA
A.-S. Ho1,*, C.-C. Cheng2, C.-C. Chang3, H.-C. Lin1, T.-Y. Luo2, J. Chang4 ISOLATION FOR DNA METHYLATION ANALYSIS OF BIOPSY,
1
Cheng Hsin General Hospital, Taipei, 2Institute of Nuclear Energy Research, FRESH FROZEN AND FFPE COLORECTAL CANCER SAMPLES
Taoyuan, 3Taipei Medical University Hospital, 4Taipei Medical University, Taipei, A. Kalmar1,2,*, B. Peterfia1,2, B. Wichmann1,2, A. V. Patai1, B.K. Bartak1,
Taiwan, Province of China Z.B. Nagy1, I. Furi1, M. Juhasz1, L. Herszenyi1, Z. Tulassay1,2, B. Molnar1,2
Contact E-mail Address: js.chang@tmu.edu.tw 1
2nd Department of Internal Medicine, SEMMELWEIS UNIVERSITY,
2
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest,
INTRODUCTION: HER2/neu is reported as an overexpressed target on the cell Hungary
surface in variety of solid cancers such as gastric cancer and breast cancer. Here, Contact E-mail Address: alexandra.kalmar@gmail.com
we (1) validated that HER2 is a tumor-treated target in colorectal cancer, and (2)
designed an anti-HER2/neu peptide (AHNP)-labeled Tc-99m to detect the INTRODUCTION: A broad range of biological samples are being analysed with
expression of HER2 in HER2-postive HCT-15-induced tumors. increasing number in the routine pathology; automated DNA isolation can be a
AIMS & METHODS: The aim of this study was to create a HER2-binding promising solution to decrease the hands-on time.
peptide, AHNP, labeled with Tc-99m to detect HER2-positive tumors. First, AIMS & METHODS: Our aim was to analyse the performance of MagNA Pure
the colorectal cancer cells, HCT-15, were used to investigate the binding specifi- 96 nucleic acid isolation system in DNA isolation from fresh frozen, biopsy and
city of AHNP. The AHNP was conjugated with HYNIC and PEG at N and C- formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Furthermore, we
terminus, respectively. The designed AHNP was chelated with Tc-99m through aimed to test the applicability of the isolated DNA in downstream DNA methy-
HYNIC and the isotope-labeled rate was analyzed by iTLC. Then, a lation analyses, and to compare results after automated and manual isolation.
nanoSPECT/CT was used for tumor detection. Fresh frozen (n 20; 10 CRC, 10 normal adjacent tissue (NAT)) tissue speci-
RESULTS: We found that HER2 was overexpressed in colorectal HCT-15 mens, biopsies (n 20; CRC 10, healthy colonic tissue 10), FFPE blocks
tumor cells and the tumors of HCT-15-induced xenograft mice using Western (n 20; 10 CRC, 10 NAT) were collected. DNA isolation was performed from
blots. AHNP labeled with fluorescent FITC was performed to detect the binding the fresh frozen and biopsy samples with QIAamp DNA Mini Kit (Qiagen) and
efficacy of AHNP to HCT-15 in vitro using flow cytometry. The results revealed with automated method with MagNA Pure DNA and Viral NA Small Volume
that AHNP specifically bound to HER2-positive HCT-15 cells compared to kit (Roche Applied Science) on the MagNA Pure 96 system Kit in parallel, the
HER2-negative gastric MKN45 tumor cells, indicating that AHNP can be FFPE samples were isolated with manual QIAamp DNA FFPET kit (Qiagen)
applied to diagnose HER2-positive tumors. Therefore, we labeled nuclear iso- and with automated MagNA Pure DNA and Viral NA Small Volume kit (Roche
tope, Tc-99m, with AHNP coupled with PEG to prolong the half-life of peptide Applied Science). After DNA quantity and quality measurements, DNA methy-
in animals. The labeled rate of Tc-99m with AHNP through HYNIC chelating lation levels for MAL, SFRP1 and SFRP2 were analysed with methylation-spe-
was measured 4 90% using iTLC analysis. However we did not observe appar- cific high resolution melting analysis (HRM).
ent difference in nuclear imaging for detecting tumors in HCT-15-induced xeno- RESULTS: Yield of manually isolated samples were found to be equal in fresh
grafts, suggesting that peptide was unstable or rapidly metabolized in animals. frozen tissue samples and significantly higher compared to the automated
CONCLUSION: Our results showed that HER2 overexpressed in colorectal method in the case of biopsy and FFPE samples. OD260/280 ratio was found
HCT-15 cells as a tumor target. HER2 specific binding peptide, AHNP, can be to be similar in fresh frozen and biopsy samples, while manual isolation resulted
used to detect HER2-positive tumors as a good candidate tool in vitro, however, in higher purity in FFPE samples. OD260/230 ratio was similar in fresh frozen
it was rapidly metabolized in animals. tissue samples after both isolation methods, the automated method was superior
Disclosure of Interest: None declared in biopsy samples and the manual protocol in FFPE samples. DNA integrity was
found to be the highest in fresh frozen samples, and half of the analyzed FFPE
samples showed higher integrity after manual extraction, while the rest of sam-
P0373 BISULFITE-BASED DNA METHYLATION ASSESSMENT FROM ples had similar integrity after both methods. In biopsy and fresh frozen samples
RECENT AND ARCHIVAL FORMALIN-FIXED, PARAFFIN DNA methylation estimations were found to be highly similar after two isolation
EMBEDDED (FFPE) COLORECTAL SAMPLES methods. In the FFPE samples the linearity of the assays lower even in FFPE
A. Kalmar1,2,*, B. Peterfia2, P. Hollosi3,4, B. Wichmann1,2, V.A. Patai1, samples SFRP1 and SFRP2 assays showed good correlation in the methylation
A. Scholler1, I. Furi1, Z. Tulassay1,2, B. Molnar1,2 percent data after the two different isolation methods.
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular CONCLUSION: Similar DNA methylation results were found after automated
Medicine Research Unit, Hungarian Academy of Sciences, 31st Department of and manual DNA isolation, thus automation can be a suitable alternative in
Pathology and Experimental Cancer Research, Semmelweis University, 4Tumor CRC diagnosis workflow beside manual protocols especially for laboratories
Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary with high sample throughput.
Contact E-mail Address: alexandra.kalmar@gmail.com Disclosure of Interest: None declared
P0401 THE SEVERITY OF SYMPTOMS RELATED TO IRRITABLE P0403 VALIDATION OF THE USE OF THE ICD-10 DIAGNOSTIC CODE
BOWEL SYNDROME IS A RISK FACTOR FOR THE FOR IRRITABLE BOWEL SYNDROME IN THE SWEDISH
MISCLASSIFICATION OF SIGNIFICANT ORGANIC DISEASE NATIONAL PATIENT REGISTER
D. Carter1,2,*, E. Bardan1,2, E. Derazne 1, B. novis1,2, M. Beer-Gabel1,2 N. Jossan1,*, A.-S. Backman2, M. Linder2, M. Altman2, M. Simren2, O. Ole`n2,
1
Sackler Faculty of Medicine, Tel Aviv, 2Gastroenterology, Chaim Sheba Medical H. Tornblom1
1
Center, Ramat Gan, Israel Dept of Internal Medicine, Institute of Medicine, Sahlgrenska Academy,
Contact E-mail Address: dr.dancarter@gmail.com University of Gothenburg, Gothenburg, Sweden, Gothenburg, 2Clinical epidemiol-
ogy uniit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden
INTRODUCTION: The diagnosis of Irritable Bowel Syndrome (IBS) is based Contact E-mail Address: hans.tornblom@gu.se
mainly of clinical evaluation. The reported incidence of misclassification of sig-
nificant organic diseases in previously diagnosed IBS patients differs between INTRODUCTION: Irritable bowel syndrome (IBS) is a diagnosis based on
studies. symptom criteria. In order to perform epidemiologic studies based on national
AIMS & METHODS: We examined the incidence and risk factors for the diag- health-care registers there is a need to assess the accuracy of the diagnostic code
nosis of significant organic diseases (inflammatory bowel disease (IBD), Celiac in clinical practice at different time points.
disease, gastrointestinal malignancy and thyroid dysfunction) in a cohort of AIMS & METHODS: The aim of this study was to evaluate the positive pre-
2645 IBS. dictive value of the ICD-10 (International Classification of Diseases, version 10)
RESULTS: During follow-up, organic disease was diagnosed in 27 subjects code for IBS in Sweden in hospital based outpatient care during 2005 (using the
(1.03%): IBD in 23, Celiac disease in 2, IBD and Celiac disease in one and Rome II criteria) and 2010 (Rome III criteria). We identified all Swedish adults
hypothyroidism in one. The mean interval from the diagnosis of IBS to the that had received the ICD-10 code for IBS as the main diagnosis during hospital-
diagnosis of an organic disorder was 13.088.51 months. Increased symptom based outpatient care in 2005 and 2010 by use of the Swedish National Patient
severity was the only significant risk factor for the misclassification of an organic Register. We excluded individuals from the IBS cohort if they had been diag-
disease (HR 2.26, 95%CI 1.01-5.05 p 0.047). The risk ratio for misclassification nosed with predefined diagnoses, incompatible with IBS, during a time span of 6
of organic diseases in moderate to severe IBS was increased by 2.575 (95%CI months before or after the IBS diagnosis. The National Board of Health and
1.10-6.51, p 0.027) in relation to mild IBS. Welfare generated a random sample of 300 identities. Each medical record was
CONCLUSION: The incidence of misclassification of major organic disease in retrieved and read by two of the authors (N. J. and H. T.) who noted if symptoms
IBS patients was low. Increased symptoms severity was the only significant risk compatible with IBS according to Rome II criteria (2005 cohort) or Rome III
factor for the misclassification of organic disorders. Further gastrointestinal eva- criteria (2010 cohort) could be identified.
luation should be considered when symptoms are moderate to severe. RESULTS: We received a total of 248 medical records (2005, n 127; 2010,
Disclosure of Interest: None declared n 121). In 173 patients (70%), the diagnosis fulfilled diagnostic criteria with
a high certainty and in 75 patients (30%) it did not. The proportions of valid
diagnoses were similar in 2005 (Rome II criteria, 68%) and 2010 (Rome III
P0402 BILE ACID DIARRHOEA MASQUERADES AS DIARRHOEA- criteria, 72%) (2 0.67, df 1, p .41). Out of the 75 cases that did not fulfill
PREDOMINANT IRRITABLE BOWEL SYNDROME: RESULTS diagnostic criteria, 24 were labeled probable IBS because of insufficient med-
FROM A DUAL CENTRE PROSPECTIVE STUDY ical data. There was no difference when comparing tertiary (72% correct) and
I. Aziz1,*, S. Mumtaz2, H. Bholah2, F.U. Chowdhury3, D.S. Sanders1, secondary care (69% correct) (p .62), but a significant difference in accuracy
A.C. Ford2 was noted comparing departments of internal medicine (155/210, 74%) and non
1
Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, 2Leeds internal medicine departments (18/38, 47%) (p .001). The most common rea-
Gastroenterology Institute, 3Nuclear Medicine Department, St Jamess University sons for a diagnosis being judged as not valid were: insufficient patient data
Hospital, Leeds, United Kingdom available in 33 patients (13%), symptoms only including abdominal pain/discom-
fort or abnormal bowel habit in 19 patients (8%), an obvious misuse of the
INTRODUCTION: Several studies have suggested that bile acid diarrhoea diagnosis in 12 patients (5%) and too short duration of symptoms in 11 cases
(BAD) can present with symptoms that are compatible with diarrhoea-predomi- (4%).
nant irritable bowel syndrome (IBS-D). However, uncertainty exists as these have CONCLUSION: The use of the ICD-10 diagnostic code for IBS in Swedish
often been retrospective, have not defined IBS-D according to accepted diagnos- secondary and tertiary care has a high validity in departments of internal med-
tic criteria, or have included patients with chronic diarrhoea in the analysis. We icine but less so in other departments. This finding needs to be addressed when
have examined this issue in a well-characterised cohort of patients with rigor- planning and interpreting epidemiologic studies of IBS.
ously defined IBS-D. Disclosure of Interest: N. Jossan: None declared, A.-S. Backman: None declared,
AIMS & METHODS: This was a prospective cross-sectional survey conducted M. Linder: None declared, M. Altman: None declared, M. Simren: None
among consecutive patients with IBS-D attending Gastroenterology clinics in declared, O. Ole`n: None declared, H. Tornblom Lecture fee(s) from: Almirall,
two hospitals in Sheffield and Leeds, UK. All patients underwent 23-seleno 25- Shire, Consultancy for: Almirall, Danone, Shire
homo-tauro-cholic acid (SeHCAT) scanning according to local protocol, with a
retention of 515% at day 7 used to confirm BAD. The degree of BAD was
classed as severe if retention 55%, moderate if 5.0%49.9%, and mild if P0404 ALTERATIONS IN ENTERIC GLIA CELL PHENOTYPE AND
10.0%414.9%. Presence of IBS-D was defined according to the Rome III cri- FUNCTIONS IN IRRITABLE BOWEL SYNDROME
teria. Patients with other known risk factors for BAD, including previous cho- N.L. Lilli1,*, Q. Lucille1, A. Philippe1, R.-D. Malvyne1, D. Tony1, K. Elise2,
lecystectomy, terminal ileal Crohns disease, terminal ileal resection, pelvic or B. Giovanni3, D.G. Roberto3, B.D. V. Stanislas2, C. Emmanuel2, N. Michel1
abdominal radiotherapy, coeliac disease, or microscopic colitis, were excluded. 1
Inserm U913, 2IMAD, Nantes, France, 3Dimec, Bologna, Italy
Participants completed the patient health questionnaire-15, a validated somatisa- Contact E-mail Address: libera.lilli@gmail.com
tion score, and the hospital anxiety and depression score. Demographic data,
including age, gender, lifestyle, and body mass index (BMI) were collected. The INTRODUCTION: Irritable bowel syndrome (IBS) is a complex disease char-
effect of all these factors on presence or absence of BAD was examined by acterized by symptoms including chronic abdominal pain or discomfort and
multivariate logistic regression analysis, with results expressed as odds ratios alteration of bowel habit. Increasing evidence demonstrates a central role of
(ORs) with 99% confidence intervals. intestinal epithelial barrier (IEB) dysfunction, and especially increased paracel-
RESULTS: This is an interim analysis of an ongoing study. In total, 51 patients lular permeability, in the pathophysiology of IBS. The enteric nervous system
with IBS-D according to the Rome III criteria have been recruited to date (37 (ENS), and in particular enteric glial cells (EGC) play a pivotal role in the
(72.5%) female, mean age 47.0 years). In total, 14 (27.5%) were found to have maintenance of IEB.
BAD following SeHCAT scanning. Of these, nine (17.6%) had severe BAD, four AIMS & METHODS: The purpose of this study was to characterize the lesions
moderate, and one mild. Mean age, BMI, anxiety, depression, and somatisation of the EGC in IBS patients and the putative causative role of soluble factors
scores were not significantly different among those with, compared with those produced by the colonic IEB microenvironment in these lesions. Methods:
without, BAD. No predictors of presence of BAD were identified following Eighteen IBS patients (6 constipation-predominant IBS (IBS-C), 6 diarrhea-pre-
multivariate logistic regression. dominant IBS (IBS-D) and 6 mixed bowel habits IBS (IBS-M) patients) and 9
CONCLUSION: Our data suggest that more than one-in-four IBS-D patients, if healthy controls (HC) were included. For each patient gastrointestinal symptoms
investigated, have definite evidence of BAD. In the majority, this is severe. were assessed using the Rome III questionnaire and colonoscopy was performed
Failure to investigate patients to exclude BAD as an underlying cause of symp- with 12 biopsies of left colon. Paracellular and transcellular permeability was
toms compatible with IBS-D results in misdiagnosis and a failure to institute measured on 3 biopsies using the Ussing chambers. Supernatant was obtained
effective therapy, in the form of bile acid sequestrants. This suggests that future by incubation of 4 biopsies in Krebs-Hepes solution during 25 minutes at 37 C.
IBS management guidelines should advocate diagnostic testing to exclude BAD At the end of the incubation time, biopsies were processed for Western blot
before a diagnosis of IBS-D is made. analysis. Both total Glial fibrillary acidic protein (GFAP) expression and the
Disclosure of Interest: I. Aziz: None declared, S. Mumtaz: None declared, H. 55-kDa band as well as S100b were analysed. The mRNA expression levels of
Bholah: None declared, F. Chowdhury: None declared, D. Sanders: This study glial markers (Sox-10; S100b) and inflammatory cytokine TNF-a were measured
was funded by investigator-initiated grant from GE healthcare, A. Ford: This using real-time PCR. Intracellular calcium flux in response to adenosine tripho-
study was funded by investigator-initiated grant from GE healthcare. sphate (ATP) stimulation was measured using Fluo-4 probe in culture of rat
EGC after 48h incubation with patients and HC supernatants or protease-acti-
vated receptor agonists (SLIGRL and Thrombin), serotonin or histamine.
RESULTS: Paracellular and transcellular permeability of biopsies from all sub-
types of IBS patients was similar as compared to HC, except in the IBS-C sub-
type for which transcellular permeability was significantly increased. No
difference in S100b, total GFAP and the specific 55-kDa band expression was
observed for any subtype. Sox-10 and S100b mRNA expression was similar in
biopsies of all IBS subtypes as compared to HC. Interestingly, we observed a
United European Gastroenterology Journal 2(5S) A243
significant increase in TNF-a mRNA expression in IBS-M but not C or D sub- AIMS & METHODS: We evaluated consecutive patients with Rome III-defined
type as compared to control. Intracellular calcium responses (maximal amplitude IBS, and examined whether prevalence of organic GI disease varied according to
and half max duration) to ATP were significantly decreased in rat EGC cultures IBS subtype, or the presence or absence of alarm symptoms. Demographic and
incubated with supernatants of IBS-D and M but not C subtypes as compared to symptom data were collected from 4224 patients with GI symptoms attending
control. No difference in calcic response to ATP was observed in EGC cultures outpatient clinics at two hospitals in Hamilton, Ontario. Participants completed
after incubation with different SLIGRL, thrombin, serotonin and histamine the Rome III diagnostic questionnaire for the functional GI disorders, which was
concentrations. used to categorise IBS subtype. Individuals underwent colonoscopy, with asses-
CONCLUSION: Our study demonstrates that enteric glial phenotype and func- sors blinded to symptom status. Patients with normal colonoscopy and no evi-
tions are altered in IBS in a subtype dependent fashion. The mediators respon- dence of coeliac disease were classed as having no organic GI disease. Prevalence
sible for these changes as well as the functional consequences of these changes of organic GI disease was compared according to IBS subtype, and in patients
remain to be identified. who did, compared with those who did not, report alarm symptoms (weight loss,
Disclosure of Interest: None declared rectal bleeding, anaemia, or family history of colorectal cancer) using a 2 test.
RESULTS: 537 patients met Rome III criteria for IBS (mean age 42yrs, 404
(75.2%) females). Organic GI disease was present in 138 (25.7%), with the com-
P0405 ABDOMINAL PAIN VERSUS ABDOMINAL DISCOMFORT: monest finding Crohns disease (n 46 (8.6%)). 63 patients had IBS-C, 209 IBS-
IMPLICATIONS FOR DIAGNOSTIC ASSESSMENT OF IRRITABLE D, and 265 IBS-M. Prevalence of organic GI disease was significantly lower in
BOWEL SYNDROME (IBS) IBS-C (n 8 (12.7%)) versus IBS-D (n 67 (32.1%)) or IBS-M (n 63 (23.8%))
O. Palsson1,*, S. Heymen1, W.E. Whitehead1 (p 0.005) (Table). In the 410 patients who reported 1 alarm symptom, pre-
1
Department of Medicine, Division of Gastroenterology and Hepatology, valence of organic GI disease was significantly higher (n 116 (28.3%)) com-
University of North Carolina, Chapel Hill, United States pared with 127 patients who did not report any alarm symptom (n 22 (17.3%))
Contact E-mail Address: opalsson@med.unc.edu (p 0.013). In IBS-D, there was a significantly higher prevalence of organic GI
disease in those with alarm symptoms (36.0%) compared with those without
INTRODUCTION: Diagnostic questions in the current Rome criteria for IBS (17.85%) (p 0.02). However, IBS-C and IBS-M prevalence of organic GI dis-
inquire about frequency of abdominal discomfort or pain, whereas the U. S. ease in patients with alarm symptoms versus those without was not significantly
Food and Drug Administration guidelines for IBS clinical trials only reference higher (IBS-C 11.6% versus 15.0%, p 0.708; IBS-M 25.6% versus 17.7%,
abdominal pain frequency. It is unknown to what extent people perceive abdom- p 0.202
inal pain and discomfort differently or whether both are needed in GI diagnosis
questions. Total IBS IBS-D IBS-C IBS-M
AIMS & METHODS: We compared abdominal pain and discomfort ratings in a (n 537) (n 209) (n 63) (n 265)
U. S. nationwide internet community survey of 328 adults, containing the Rome
III diagnostic questions for IBS in the new response formats planned for Rome No organic GI disease (%) 399 (74.3) 142 (67.9) 55 (87.3) 202 (76.2)
IV diagnoses (Gastroenterology 2013;144(5) Suppl.1:S-916), including the stan-
dard in the past 3 months, how often did you have discomfort or pain anywhere Ulcerative colitis (%) 34 (6.3) 19 (9.1) 1 (1.6) 14 (5.3)
in your abdomen? and alternative forms of that question replacing abdominal Crohns disease (%) 46 (8.6) 21 (10.0) 2 (3.2) 23 (8.7)
discomfort or pain with only pain or only discomfort. Also included was a Colorectal cancer (%) 14 (2.6) 5 (2.4) 2 (3.2) 7 (2.6)
multiple-choice question about the extent to which abdominal pain and discom- IBD unclassifiable (%) 24 (4.5) 11 (5.3) 2 (3.2) 11 (4.2)
fort are experienced as separate sensations, and demographic questions. To avoid
over-estimating agreement between alternative question forms, responses from Microscopic colitis (%) 12 (2.2) 8 (3.8) 0 (0) 4 (1.5)
people who reported having neither pain nor discomfort in the abdomen in the Coeliac disease (%) 8 (1.5) 2 (1.0) 2 (3.2) 4 (1.5)
past 3 months were excluded from analysis, as well as those inconsistent on either
of two repeated quality-check questions, leaving 218 for analysis. Analysis cal-
culated percent agreement between alternate question forms, and also Cohens CONCLUSION: Patients with suspected IBS-C are unlikely to have underlying
Kappa (K-values) for diagnostic performance as this controls for rate of chance organic GI disease, compared with IBS-D or IBS-M. Although the incorporation
agreement (K 4 0.8 excellent agreement). of the absence of alarm symptoms into the diagnostic criteria for IBS reduced the
RESULTS: The subjects (52.8% females; mean age 45.8, range 19-85 years) likelihood of organic GI disease, this was only for IBS-D and, because alarm
varied widely in their perception of the relationship between abdominal pain and symptoms are so common, 60% of patients still have normal investigations.
discomfort: 33.9% stated they were entirely or mostly independent sensations, Better ways of diagnosing IBS are needed.
27.1% that they were mostly or entirely the same sensation, and 39.0% that both Disclosure of Interest: None declared
were equally true i.e., they could be either separate sensations or discomfort a
mild version of pain. Only about half of subjects rated frequency of pain alone
(52.8%) and discomfort alone (55.5%) as identical in intensity (i.e., same P0407 SOMATISATION LEVEL VARIES ACCORDING TO IRRITABLE
response option chosen on the 9-point frequency scale) to ratings on the standard BOWEL SYNDROME (IBS) SUBTYPE AND DRIVES BLOATING
pain or discomfort question. However, when the diagnostic frequency thresh- SEVERITY
old for IBS (43 days a month in the past 3 months) was compared, the agree- P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2,
ment with pain or discomfort on that threshold being met (when met by either D. Morgan3, A. Ford4
version) was 72.4% (K 0.63) for the pain alone and 76.8% (K 0.66) for 1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe
discomfort alone, and 81.3% between the latter two (K 0.74). When full IBS Family Digestive Health Research Institute, Gastroenterology Division, McMaster
criteria were examined using the 3 different question versions, the agreement with University, Health Sciences Center, 3Gastroenterology Department, St. Josephs
the standard question version when at least one method qualified subjects as IBS Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess
was 80.8% (K 0.85) for the pain-only version and 87.7% (K 0.90) for dis- University Hospital, Leeds, United Kingdom
comfort-only, with the latter two also showing 87.7% agreement (K 0.90). IBS Contact E-mail Address: um10pp@leeds.ac.uk
diagnosis with discomfort alone diagnosed a slightly higher rate of IBS (71 cases)
compared to the other 2 versions (66 cases each). INTRODUCTION: Literature suggests that somatisation is strongly associated
CONCLUSION: The use of abdominal discomfort or pain as a criterion for with IBS. However, it remains unclear whether the degree of somatisation varies
IBS diagnosis is ambiguous because there is no agreement among U. S. adults according to IBS subtype. Furthermore, whether there is an association between
regarding whether these are qualitatively different sensations. However, in 4 out higher levels of somatisation and more severe IBS symptoms is unknown.
of every 5 cases the same individuals would be diagnosed IBS regardless of which AIMS & METHODS: Demographic and symptom data were collected from
descriptor is used. [Supported by a grant from Salix Pharmaceuticals] 4224 adult patients attending gastrointestinal (GI) outpatient clinics at two hos-
Disclosure of Interest: O. Palsson Financial support for research from: Salix pitals in Hamilton, Ontario. Participants completed the Rome III diagnostic
Pharmaceuticals, S. Heymen Financial support for research from: Salix questionnaire for the functional GI disorders. Somatisation data were collected
Pharmaceuticals, W. Whitehead Financial support for research from: Salix via the Patient Health Questionnaire-15 (PHQ-15), comprising 15 somatic symp-
Pharmaceuticals tom items. To avoid overestimation of the severity of somatisation we excluded
the 3 GI items from the original PHQ-15 questionnaire to form the PHQ-12.
Somatisation severity was categorised according to total PHQ-12 (minimal 3,
P0406 PREVALENCE OF ORGANIC GASTROINTESTINAL DISEASE IN low 4-7, medium 8-12 and high 13) with a maximum somatisation score of 24.
SUSPECTED IRRITABLE BOWEL SYNDROME (IBS) VARIES Mean somatisation score and total number of somatic symptoms reported were
ACCORDING TO SUBTYPE compared between IBS subtypes (diarrhoea-predominant (IBS-D), constipation-
P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2, predominant (IBS-C), and mixed stool pattern (IBS-M)) using analysis of var-
D. Morgan3, A. Ford4 iance. The effect of level of somatisation on the severity of individual IBS symp-
1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe toms, including lower abdominal pain or discomfort, stool frequency, stool
Family Digestive Health Research Institute, Gastroenterology Division, McMaster consistency, bloating or abdominal distension, tenesmus, and urgency was com-
University, Health Sciences Center, 3Gastroenterology Department, St. Josephs pared according to IBS subtype using a 2 test with P values of 50.01 denoting
Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess statistical significance.
University Hospital, Leeds, United Kingdom RESULTS: 840 patients met the Rome III criteria for IBS and provided complete
Contact E-mail Address: um10pp@leeds.ac.uk somatisation data (mean age 38.3 years, 702 female (83.6%)). Of these, 289
patients had IBS-D, 138 IBS-C, and 413 had IBS-M. Mean PHQ-12 scores
INTRODUCTION: In patients who report symptoms compatible with IBS in the were significantly higher in those with IBS-M (n 10.35), compared with IBS-
absence of alarm symptoms, guidelines suggest the diagnosis can be made with- C (n 8.94) or IBS-D (n 9.24) respectively (P50.001). Mean number of PHQ-
out investigations. However, there are few validation studies of the current gold- 12 symptoms reported was also significantly higher in IBS-M patients (7.2) com-
standard, the Rome III criteria, and the prevalence of organic gastrointestinal pared with patients with IBS-C (n 6.2) or IBS-D (n 6.4) respectively
(GI) disease in people with suspected IBS is unclear. (P50.001). High level of somatisation was present in 222 patients (26.4%).
A244 United European Gastroenterology Journal 2(5S)
The prevalence of a high level of somatisation was significantly greater in patients
P0409 ENDOSCOPIC FINDINGS AND CLINICOPATHOLOGIC
with IBS-M (131 patients (31.7%)) compared with IBS-C (31 (22.5%)) or IBS-D
CHARACTERISTICS OF ISCHEMIC COLITIS: A PORTUGUESE
(60 (20.8%)) respectively (p 0.003). For all subtypes of IBS, high levels of
CENTER EXPERIENCE
somatisation were associated with a greater severity of bloating or abdominal
distension (P50.001 for IBS-M and IBS-D, and p 0.004 for IBS-C respec- C. Leitao1,*, A. Santos1, H. Ribeiro1, J. Pinto1, A. Caldeira1, R. Sousa1,
tively). For patients with IBS-M, high levels of somatisation were also associated J. Tristan1, E. Pereira1, A. Banhudo1
1
with a significantly greater prevalence of likelihood of reporting 53 stool per Servico de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saude
week (p 0.001). No other significant associations between somatisation severity de Castelo Branco, Castelo Branco, Portugal
and symptom severity were observed. Contact E-mail Address: catia.f.leitao@gmail.com
CONCLUSION: IBS-M is strongly associated with higher levels of somatisation.
The number of reported somatic symptoms reported is higher in IBS-M com- INTRODUCTION: Ischemic colitis (IC) is the most common vascular disorder
pared with other IBS subtypes. Severity of bloating or abdominal distension of the intestinal tract and the second most common cause of lower digestive
reported by all patients with IBS is strongly associated with high levels of soma- bleeding. The clinical disease course of ischemic colitis may vary from self-limit-
tisation. This suggests psychological stress may drive the severity of this com- ing to life-threatening and has a wide spectrum of endoscopic findings.
monly reported symptom in IBS, and may partly explain why it can be difficult to AIMS & METHODS: In this study, we made a retrospective analysis of endo-
treat. scopy Endings and clinicopathologic characteristics of IC in the endoscopy center
Disclosure of Interest: None declared of our hospital during the last 10 years (2002 to 2012) and try to identify the
predictors of endoscopic severity of IC. The data collected included demographic
(age, gender), clinical (symptoms, comorbidities and medication), laboratory
P0408 INTESTINAL AND SYSTEMIC IMMUNE MARKERS IN (hemoglobin, leucocytes, C-reactive protein, lactate dehydrogenase), and endo-
PATIENTS WITH IRRITABLE BOWEL SYNDROME scopic findings (localization, extension, severity of the lesions) and outcomes
Z. Mujagic1,2,*, E.F. Tigchelaar1,3, A. Smolinska1,4, A.A. Masclee2, (length of hospitalization stay, treatment and death).
S. Zhernakova1,3, F.-J. van Schooten1,4, C. Wijmenga1,3, D.M. Jonkers1,2 RESULTS: The study included 194 patients (92 women; 62 men), with mean age
1
Top Institute Food and Nutrition (TIFN), Wageningen, 2Division of 75 years. The most common comorbid disease was hypertension (56.5%),
Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School followed by cardiovascular disease (21.5%), arrhythmias (14.8%) and cerebro-
for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center vascular disease (6.6%). The majority of patients had a history of drug use
(MUMC), Maastricht, 3Department of Genetics, University of Groningen, (89.6%), 23.4% of them nonsteroidal anti-inflammatory agents and 13.6% digi-
Groningen, 4Department of Toxicology, NUTRIM School for Nutrition, talis preparations. Hematochezias (79.2%) and abdominal pain (73.3%) were the
Toxicology and Metabolism, Maastricht University Medical Center (MUMC), most common presentation symptoms. The average elapsed time between the
Maastricht, Netherlands beginning of the symptoms and the diagnosis was 2,1 days. Ischemic lesions
Contact E-mail Address: z.mujagic@maastrichtuniversity.nl were located mainly in the left colon (77.3%) and were found in more than 2
colonic segments in 42.9%. The endoscopic lesions were grade I in 57.1%, grade
INTRODUCTION: Immune activation (low grade inflammation) and an altered II in 39.6% and grade III in 3.2% of patients. The involvement of more than 2
intestinal microbiota are postulated to be involved in the multi-factorial patho- colonic segments (50.0001), the involvement of sigmoid and descendent colon
physiology of Irritable Bowel Syndrome (IBS), especially in the diarrhea predo- (50.0001), anemia (50.04), and mortality (50.0001) were significantly
minant subtype. Fecal calprotectin and plasma cytokines, as markers of intestinal higher in patients with severe endoscopic lesions. Death occurred in 4 patients
inflammation and systemic immune activation, respectively, and the antimicro- (2.6%) and surgery was performed in only 1 patient. The mean length of hospital
bial protein human beta defesin-2 (HBD-2), have previously been assessed in IBS stay was 7.5 days. The involvement of more than 2 colonic segments (p40.0001),
patients, but results were inconsistent and numbers were too small for subtype longer elapsing time between the beginning of symptoms and the diagnosis
analyses. (p40.0001), antibiotics use (p40.009) and age higher than 80 years (p
AIMS & METHODS: The aim of our study was to compare fecal calprotectin, 50.001) were related to longer hospitalization.
HBD-2 and plasma cytokines levels of a large well characterized IBS cohort to CONCLUSION: In our study, the majority of patients were female, over 50
healthy controls (HC), and to assess differences between subtypes. years of age and with several risk factors. The clinical disease course was self-
Fecal and blood samples were obtained from IBS patients (Rome III) and age- limiting and was associated a low mortality. The involvement of more than 2
and gender-matched HC. Calprotectin and HBD-2 levels in fecal samples were colonic segments, the involvement of sigmoid and descending colon and anemia
analyzed by ELISA, while non-stimulated levels of IL-1, IL-6, IL-8, IL-10, IL- may be predictive factors of endoscopic severity in IC. An intimate knowledge of
12P70 and TNF- were assessed by Luminex assay. Kruskal Wallis test was used endoscopic findings and pathologic characteristics of ischemic colitis plays a
for multi-group comparison and Mann-Whitney U test for 2-group comparisons, pivotal role in decreasing the misdiagnosis rate of ischemic colitis.
with post-hoc Bonferroni correction (for multiple testing). Disclosure of Interest: None declared
RESULTS: We included 164 HC and 264 IBS patients (IBS5SUB4TOTAL5/
SUB4): 92 diarrhea predominant (IBS-D), 48 constipation predominant (IBS-
C), 105 with mixed stools (IBS-M) and 19 with undefined subtype (IBS-U). IBS- P0410 THE CLINICAL CHARACTERISTICS OF PATIENTS WITH
U was not analyzed separately due to small numbers. Calprotectin was higher in PNEUMATOSIS CYSTOIDES INTESTINALIS IN JAPAN
IBS5SUB4TOTAL5/SUB4 compared to HC (median [IQR]: 40.3 [19;81] vs. M. Miura1,*, D. Saito1, M. Hayashida1, A. Sakuraba1, Y. Yamada1,
20.4 [5-48] ug/g, p 50.001, resp), and in all IBS-subtypes compared to HC. HBD- G. Koyama1, S. Takahashi1
2 levels were lower in IBS5SUB4TOTAL5/SUB4 compared to HC (31.0 1
The Third Department of Internal Medicine, Kyorin University School of
[18;48] vs. 37.5 [27;60] ng/g, p 50.01), which was also true for IBS-D vs. HC. Medicine, Tokyo, Japan
The cytokines IL-1 (0.11 [0.11;1.12] vs. 0.11 [0.11;1.46] ug/l, p 50.01) and IL-6
(0.19 [0.19;0.19] vs. 0.52 [0.19;3.13] ug/l, p 50.01) were lower in INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a relatively rare
IBS5SUB4TOTAL5/SUB4 vs. HC, while IL-12p70 (0.08 [0.08;3.52] vs. disease, in which multilocular or linear pneumatic cysts developed under the
0.08 [0.08;1.53] ug/l, p 50.01) and TNF- (0.45 [0.26;0.69] vs. 0.67 [0.38;8.32] mucosa or serosa of the intestinal wall. In recent years, with the advances in
ug/l, p 50.01) were higher IBS5SUB4TOTAL5/SUB4 compared to HC. imaging technologies, the number of reported cases of PCI has been increasing.
The IL10/12 ratio was also lower in IBSTOTAL compared to HC (0.45 Here, we investigated the clinical characteristics of patients with PCI.
[0.26;0.69] vs. 0.67 [0.38;8.32], p 50.01). The findings were consistent for all AIMS & METHODS: 55 patients were diagnosed as PCI at Kyorin University
subtypes, apart for TNF- being only increased in IBS-D and no differences Hospital during the 6-year period from September 2007 to August 2013. We
found between all subtypes and HC for IL-1. No significant differences were conducted a retrospective analysis of the clinical characteristics of these patients,
found for IL-8 and -10. including sex, age, the site of lesion, symptoms and treatments.
CONCLUSION: Calprotectin levels were significantly higher, but mildly ele- RESULTS: The male to female ratio was 29:26 and the median age was 64.7
vated, in IBS patients and all subtypes compared to HC, pointing to low grade years. The diagnosis was made by CT(47 cases), or colonoscopy (8 cases). In
mucosal inflammation in IBS. The overall cytokine levels were low, but com- regard to the site of lesion, the stomach was 2 patients, small intestine was 18
bined systemic cytokine data point to a pro-inflammatory state in the total group patients, ascending colon was 26 patients, transverse colon was 4 patients, des-
of IBS patients as well as in all subtypes. Interestingly, HBD-2 levels were lower cending colon was 2 patients and the sigmoid colon was 2 patients. 31 patients
in IBS patients compared to HC, especially in IBS-D, suggesting an altered host- complained of symptoms of abdominal pain (18), abdominal distension (9), fever
microbe interaction. (2), diarrhea (2), and melena (1). There were 20 patients whose condition was
In conclusion, our data point to a low-grade mucosal and systemic inflammatory idiopathic and 35 patients whose condition was secondary to other underlying
state with reduced intestinal defensin levels in IBS patients when compared to diseases including diabetes (12), malignant tumors (9), intestinal tract necrosis
healthy controls. The findings did not depend on dominant bowel habits, indi- (9), collagenosis (7), constipation (1), chronic obstructive pulmonary disease (1)
cating that immune activation may plays a role in the pathophysiology of all IBS and ileus (1). Eleven patients had a history of steroid use, and 12 patients had a
subtypes. history of treatment with -glucosidase inhibitors. Thirty-four patients received
Disclosure of Interest: Z. Mujagic: None declared, E. Tigchelaar: None declared, in hospital treatment including conservative treatments such as nil by mouth,
A. Smolinska: None declared, A. Masclee Consultancy for: Pentax medical, treatment with prokinetic agents, supplemental oxygen in 24 patients and
Grunenthal GmbH, Ferring, S. Zhernakova: None declared, F.-J. van abdominal operation in 11 patients. Portal venous gas (HPVG) was observed
Schooten: None declared, C. Wijmenga: None declared, D. Jonkers: None in 9 patients, and 8 of these had underlying intestinal tract necrosis.
declared CONCLUSION: In most patients, PCI is mild, asymptomatic and resolves spon-
taneously. The principally used treatment strategy for PCI is conservative treat-
ment. Appropriate consideration of the indications for operation is important for
avoiding unnecessary invasive treatment. However, especially in cases of PCI
complicated by HPVG, underlying intestinal tract necrosis should be borne in
mind and it seems to be important to promptly determine whether emergency
surgery is needed. There are numerous unresolved issues in respect of the patho-
logical characteristics of PCI, therefore, further accumulation and examination
United European Gastroenterology Journal 2(5S) A245
of cases are necessary. Further elucidation of the pathological characteristics and
P0413 RESECT AND DISCARD (RD) STRATEGY FOR COLONIC
establishment of suitable treatments are expected.
POLYPS- AN ASIAN PERSPECTIVE, ARE WE READY?
Disclosure of Interest: None declared
C.T. W. Chia1, Y.M. Yun2,*, S. Thrumurthy3, S.K. K. Tsao1
1
Gastroenterology & Hepatology, Tan Tock Seng Hospital (TTSH), Singapore,
P0411 PROFILE AND OUTCOME OF PATIENTS WITH ISCHEMIC Singapore, 2Monash University, Victoria, Australia, 3University of Aberdeen,
COLITIS Scotland, United Kingdom
R. Oprita1,*, F. Musat1, A. Ragea1 Contact E-mail Address: christopher_tw_chia@ttsh.com.sg
1
Gastroenterology, Bucharest Clinical Emergency Hospital, bucharest, Romania
Contact E-mail Address: ruxandraa@netscape.net INTRODUCTION: The current practice of routinely resecting all diminutive (1-
5mm) and small (6-9mm) colonic polyps and submitting them for histopathologic
INTRODUCTION: - Ischemic colitis incidence is most likely underestimated assessment has several disadvantage in terms of cost-effectiveness and risks from
because the mild form often is of transient nature and misdiagnosed when repeated colonoscopies. The resect-and-discard (RD) strategy has been proposed
patients suffer from other diseases such as inflammatory bowel disease or infec- to reduce retrieval of diminutive polyps (1-5mm) for histology which has been
tious colitis. deemed not to have advanced histologic features. RD strategy for small polyps
AIMS & METHODS: We prospectively studied patients referrd for colonoscopy (6-9mm) are still controversial. The prevalence of advanced histologic features in
for lower gastro-intestinal bleeding from January 2013 until January 2014. the diminutive and small polyp category remains small but not clearly defined.
There were enrolled 74 patients (27 females and 47 males), aged between 20 to 75 AIMS & METHODS: In this cross-sectional study, we aim to find the prevalence
years old, with a median age of 51 years old. of small & diminutive polyps resected that shows advanced histologic features
The findings at colonoscopy will depend on the stage and severity of ischemia. In such as high grade dysplasia (HGD) or carcinoma to determine if RD policy is
the early stages of ischemia, petechial hemorrhages are interspersed with areas of feasible in the local Asian tertiary setting. Data was retrieved from Jan-Dec 2009
pale, edematous mucosa. Later, segmental erythema, with or without ulcerations with assistance from the Pathology Department to identify all submitted colonic
and bleeding, may be observed. The colon single-stripe sign, a single longitudinal polyp specimens. Each patient also had their colonoscopy report (s) and detailed
ulcerated or inflamed colon strip, may characterize milder disease. With more histology report reviewed by 2 separate colleagues within the team to ensure data
severe ischemia, the mucosa appears cyanotic, dusky, gray, or black. consistency. The variables captured include demographics, total polyp number,
Pseudopolyps and pseudomembranes may be appreciated, as well. A chronic polyp distribution in the colon, histology, polyp size and respective number in
stage of ischemia characterized by stricture, decreased haustrations, and mucosal each histology subtype and concurrent colorectal carcinoma (CRC).
granularity may occur several weeks or months later. RESULTS: There were a total 1482 polypectomy specimens retrieved for histol-
There are no endoscopic findings that are specific for ischemia, thus the clinical ogy from 871 patients. The colonic distribution of the polyps was 45.4% right
setting must be considered. sided, 46.1% left sided and 8.5% rectal.
RESULTS: Conditions mandating anticoagulation, such as atrial fibrillation or Please refer to Table 1 for summary of polyp distribution and dysplasia.
dilated cardiomyopathy, were identified in 32% of case patients. Conditions
requiring antiarrhythmic therapy were identified in 25% of case patients; in 4 Tubular Tubulovillous Villous Serrated
of the patients, cocaine was identified as the leading cause. Adenoma Adenoma Adenoma Adenoma
Of 74 patients, 5 required immediate surgery and 3 of them were positive for Colonic polyp histology (TA) (TVA) (VA) (SA) Hyperplastic
clostridium difficile.
CONCLUSION: Ischemic colitis occurs as the result of a compromise in intest- Low grade dysplasia (LGD) 79.2% 26.7% 0.0% 83.9% NA
inal blood flow that can produce a spectrum of injury from transient self-limited High grade dysplasia (HGD) 20.8% 73.3% 100.0%
ischemia to fulminant ischemia or transmural infarction. Its diagnosis requires a No dysplasia NA NA NA 16.1% 100.0%
high index of suspicion, and the clinician should consider the diagnosis in Total number (1482) 1067(72%) 150(10.1%) 3(0.2%) 118(8.0%) 144(9.7%)
patients with acute abdominal pain and bloody stools.
REFERENCES
Reinus JF, Brandt LJ and Boley SJ. Ischemic diseases of the bowel. Gastroenterol
Clin North Am 1990; 19: 319. There were 844 diminutive polyps (1-5mm), 447 small polyps (6-9mm) and 191
Hourmand-Ollivier I, Bouin M, Saloux E, et al. Cardiac sources of embolism large polyps (10mm). The proportion of HGD seen in each of these groups
should be routinely screened in ischemic colitis. Am J Gastroenterol 2003; 98: were 18.7%, 37.6% and 56.5% respectively. The percentage of HGD present in
1573. diminutive and small polyps was relatively high and significant. There were no
Longstreth GF and Yao JF. Diseases and drugs that increase risk of acute large concurrent carcinomatous features seen in all the polyps.
bowel ischemia. Clin Gastroenterol Hepatol 2010; 8: 49. CONCLUSION: These findings showed that a significant proportion of diminu-
Disclosure of Interest: None declared tive polyps (18.7%) and small polyps (37.6%) harboured features of HGD, which
is significantly higher than previous findings of 1% for diminutive polyps in some
literatures. Based on size alone without the aid of narrow band imaging (NBI) or
P0412 CHRONIC KIDNEY DISEASE AND HIGH ECOG PERFORMANCE other forms of image enhanced endoscopy (IEE), we find that RD strategy for
STATUS ARE RISK FACTORS FOR SEVERE ISCHEMIC COLITIS diminutive or small polyps may miss a significant group of patients with
S.R. Jee1,*, S.R. Choi2, G.A. Song3, S.J. Park4, C.S. Song5, H.U. Park6 advanced neoplastic histology who needs earlier colonoscopic surveillance.
1
gastroenterology, INJE UNIVERSITY COLLEGE OF MEDICINE, 2Dong-A There may be merits in the RD approach but this would require incorporation
University, 3gastroenterology, Busan national University, 4gastroenterology, Kosin of other real-time endoscopic modalities such as IEE and more robust evaluation
University, 5gastroenterology, Good Samsun hospital, 6gastroenterology, REFERENCES
Maryknoll Hospital, Busan, Korea, Republic Of Rex DK. Risks and potential cost savings of not sending diminutive polyps for
Contact E-mail Address: tokimom@nate.com histologic examination. Gastro Hepatol 2012; 8: 128130.
Zauber AG, et al. Colonoscopic polypectomy and long-term prevention of CRC
INTRODUCTION: Ischemic colitis is most frequent form of intestinal ischemic deaths. N Engl J Med 2012; 366: 687-696.
disease. However, there have been debates about prognostic factors of ischemic Disclosure of Interest: None declared
colitis
AIMS & METHODS: The aim of this study was to identify risk factors of severe
ischemic colitis. From January 2000 to December 2011, a retrospective study was P0414 THE STRAY PATIENT DEMOGRAPHIC LABEL: IMPLICATIONS
undertaken of patients with ischemic colitis hospitalized at 4 university hospitals FOR PATIENT SAFETY AND QUALITY IN THE ENDOSCOPY UNIT
and 2 secondary hospitals at Busan, Korea. Patients with colon ischemia were D.C. Sadowski1,*, G. Lutzak1
divided into two groups: those with mild disease and those with severe disease. 1
Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Canada
Data collected included age, sex, symptoms (abdominal pain, hematochezia and
abdominal angina), cormobidity (hypertension, diabetes mellitus, ischemic heart INTRODUCTION: Over a 6-month period, 3 separate incidents occurred in our
disease, stroke, arrhythmia, congestive heart failure, peripheral vascular disease, unit where the wrong patient demographic labels were affixed to the endoscopy
chronic obstructive lung disease, chronic kidney disease, hemodialysis, peritoneal biopsy requisition form (EBRF), the biopsy specimen container (BSC) or both.
dialysis, hyperthyroidism, hypothyroidism and irritable bowel syndrome), This type of incident can have a significant impact on patient safety and is an
laboratory findings (total cholesterol, TG, LDL, HDL, total protein, albumin, indicator of poor quality in the specimen control process.
Hg, WBC count, Platelet count, ESR and CRP), endoscopic fidings (location of AIMS & METHODS: The purpose of this study was to identify factors contri-
lesions), and ECOG performance status.
RESULTS: A total of 292 patients were enrolled (mild group: 259, severe group:
a n
buting to this medical error and to develop a process to prevent future occur-
w
rences. A Quality Assurance Review (QAR) was conducted to determine the
r
33). In univariate analysis, location (involving Rt. Colon), chronic kidney disease
(stage V), ECOG, Platelet count, CRP were significant risk factors for severe
ischemic colitis. In multivariate analysis, chronic kidney disease (stage V) (OR,
5.289; 95% CI 1.308-21.378; p 0.019), ECOG (OR, 1.690; 95% CI 1.108-2.579;
p 0.015) were significant risk factors for severe ischemic colitis.
i t h d
systems issues that contributed to these incidents. This review was carried out
at the Royal Alexandra Hospital, Edmonton, Canada. The endoscopy unit at this
W
hospital performs about 18,000 procedures per year. A QAR using Systems
Analysis Methodology (SAM) was conducted to identify issues that contributed
to the patient-specimen mismatches. SAM identified the following system issues:
CONCLUSION: Chronic kidney disease (stage V) and high ECOG performance a) variation in the set-up of nursing workspaces, b) variation in where and when
status were independent risk factors for severe ischemic colitis. More caution the EBRF was completed, and c) the occurrence of stray patient demographic
would be necessary when treatment of patients with ischemic colitis having labels. The QAR identified several recommendations to prevent future mislabel-
these factors. ing: a) standardize how nursing workspaces are set up, b) develop a checklist to
Disclosure of Interest: None declared ensure proper patient identification prior to procedure initiation, proper labeling
of EBRF and BSC, completion of EBRF, and c) remove all patient demographic
labels from the theatre immediately after the conclusion of the procedure.
A246 United European Gastroenterology Journal 2(5S)
RESULTS: Since EBRF and BSC mislabeling incidents are rare events; we uti- RESULTS: For all 9 indications, information about duration, current medical
lized indicators of EBRF information quality as surrogate markers for effective- treatment and weight loss were selected. The remaining selected variables were
ness of the QAR recommendations. We deemed the following factors as key for:
quality indicators of EBRF information: a) completion of clinical history by Dyspepsia: Medical history, nausea/vomiting, reflux, hematemesis, dysphagia,
physician, b) correct identification of specimen anatomic site, c) avoidance of abdominal pain, effect of anti-acid treatment, general condition, abdominal pal-
ra w n
ambiguous terminology, and d) correct patient label on EBRF and BSC. We
tracked these indicators daily. We reported the data weekly to physician leaders
pation (AP), previous gastroscopies and lab-analyses for anaemia and faecal
occult blood (FOBT).
ithd
and other healthcare providers in order to engage them in this initiative. We used Dysphagia: Progression (intermittent, stable, progressive), texture provoking dys-
the Reporting and Learning System (RLS) for patient safety to monitor report- phagia, subjective localization of obstruction, hematemesis, regurgitation of
W
ing of similar incidents. Prior to implementation of the QAR recommendations, undigested foods, presence of reflux, stimulantia, ulcerogenic medication, general
the average number of EBRFs containing deficient information was 16.6/month. condition, previous endoscopies and radiology and lab-analyses for anaemia.
Subsequent to the implementation of QAR recommendations, this number Diarrhoea: Hematochezia, nocturnal diarrhoea, recent antibiotic treatment, gen-
decreased to 6.4/month (p 0.02). However, in the 7 months subsequent to the eral condition, digital rectal exploration (DRE), previous endoscopies and lab-
QAR recommendation implementation, we had 4 further incident of mislabeling analyses for anaemia, FOBT, celiac disease, infection/inflammation, inflamma-
with the wrong patient label and 3 episodes of unlabeled specimen containers. tory bowel disease (IBD) and faecal bacteria/parasites.
CONCLUSION: Stray patient data labels are a significant contributing factor to Bowel changes: Type of change, hematochezia, abdominal pain, B symptoms
EBRF and BSC mislabeling. QARs can reduce the incidence of this medical error (fever, night sweat, weight loss), AP, DRE, general condition, previous endosco-
and improve quality of EBRF completion; however, without health care provider pies and lab-analyses for anaemia, celiac disease, IBD and FOBT.
engagement, serious incidents may still occur. Hematochezia: Blood colour, location of blood (on paper/on faeces/in faeces),
Disclosure of Interest: None declared percentage of bowel movements with observed blood, bowel changes, symptoms
from upper or lower GI-tractus, hematemesis, AP, DRE, previous endoscopies
and lab-analyses for anaemia, IBD and FOBT.
P0415 A NOVEL SAMPLING DEVICE FOR COLLECTING Chronic abdominal pain: Medical history, characterization and location of pain,
MUCOCELLULAR MATERIAL FROM THE UNPREPARED RECTUM nocturnal pain, relation to meals, presence of bowel changes, AP, general con-
J. Booth1,*, J. Lacy-Colson2, M. Norwood3, C. Murray1 dition, previous radiology/endoscopies and lab-analyses for anaemia, liver/pan-
1
Origin Sciences Ltd, Cambridge, 2Surgery, Royal Shrewsbury Hospital, creatic function, IBD and FOBT.
Shrewsbury, 3Surgery, Leicester Royal Infirmary, Leicester, United Kingdom Constipation: Main complaint (hard/ rare/slow etc), frequency and consistency of
Contact E-mail Address: jodie.booth@originsciences.com bowel movements, hematochezia, abdominal pain, effect of treatment-attempts,
predisposing factors, AP, DRE, previous endoscopies and lab-analyses for anae-
INTRODUCTION: Earlier detection of colorectal and other gastrointestinal mia, thyroid disease and FOBT.
malignancies is an urgent objective. Currently much effort is directed at the Jaundice: Medical history, exposure liver-toxic substances, stimulantia, colour
development of in vitro diagnostic tests that evaluate informative protein or changes urine/faeces, abdominal pain, AP, liver stigmata, previous radiology
DNA biomarkers in blood or stool samples. Stool samples are relatively incon- and lab-analyses for liver/pancreatic function, hepatitis serology, specific liver
venient to collect, require special handling facilities, and additionally suffer from diseases and infection/inflammation.
contamination that may interfere with molecular assays. Blood samples, while Weight loss: Presence of any abdominal symptoms, B symptoms, abdominal
more convenient, may not be as informative early in the disease process. Several pain, appetite, food intake, general condition, AP, symptoms/findings from
studies have shown that significant numbers of exfoliated cells and their products other organ-systems, previous radiology and lab-analyses for anaemia, celiac
are retained in a muco-cellular layer overlying the colonic mucosa but distinct disease and FOBT.
from the stool itself, and that this material flows toward the rectum, where it can CONCLUSION: We identified 15 variables considered essential by gastroenter-
be captured for analysis ologists for each of the 9 most common reasons for referrals. Validation of the
AIMS & METHODS: Origin Sciences has developed a novel sampling device, relation between the findings and the quality of referrals remains unknown, and
which incorporates an inflatable nitrile membrane. Following insertion into the need further assessments.
unprepared rectum via a standard proctoscope, the membrane is inflated to make Disclosure of Interest: None declared
contact with the rectal mucosa for 10 seconds. The membrane is then deflated
and retracted into the device prior to removal from the patient. Upon retraction
the material sampled from the rectal mucosa is retained on the inverted mem- P0417 PREVIOUS SCREENING EPISODE PREDICTORS OF REPEAT
brane, which acts as a receptacle for the addition of buffer to preserve the PARTICIPATION IN THE NHS BOWEL CANCER SCREENING
material for subsequent analysis. PROGRAMME
RESULTS: The sampler has now been tested in over 2000 patients and healthy S.H. Lo1, S.P. Halloran2,3,*, J. Snowball2, H.E. Seaman2,3, J. Wardle1,
volunteers, and has shown excellent patient acceptability. Tests and in vitro C.von Wagner1
experiments with monolayers of cultured human cells indicate that the membrane 1
Department of Epidemiology and Public Health, Health Behaviour Research
captures intact cells, which are easily washed off the membrane for further inves- Centre, University College London, London, 2NHS Bowel Cancer Screening
tigation. Detailed evaluation of the mucous-associated soluble material captured Southern Programme Hub, 3University of Surrey, Guildford, United Kingdom
by the device in both normal and diseased states, shows it to be rich in protein Contact E-mail Address: s.halloran@nhs.net
and nucleic acids. Levels of soluble protein material present in the buffer vary
between 90 and 3000 g/mL, with a mean of 710 g/mL. As part of a pro- INTRODUCTION: Effective colorectal cancer (CRC) screening using faecal
gramme to identify novel cancer biomarkers, Origin Sciences has evaluated the occult blood (FOB) tests requires adherence to a programme of repeat participa-
presence of auto-antibodies in the proteinaceous component of the preparation, tion. This study investigated previous screening episode predictors of screening
and has detected informative auto-antibody isotypes IgA, IgG and IgM by uptake among previous responders.
ELISA. The preparation is also rich in nucleic acids. DNA is found in amounts AIMS & METHODS: The NHS Bowel Cancer Screening Programme (BCSP) in
ranging from 0.5 to 21.9 ug/mL. Laboratory experiments have shown that this England offers biennial screening using a guaiac FOB test. Uptake data for the
DNA retains a high degree of integrity and is suitable for PCR amplification, and second (R2) and third (R3) biennial invitation round were studied among 62,099
subsequent sequencing, since we have been able to detect a number of genes by individuals (aged 60-64) in the Southern Hub of the BCSP. R3 invitees comprised
quantitative PCR. three subgroups: Consistent Screeners (screened in R1 and R2), Dropouts
CONCLUSION: The sampling device represents a novel and minimally invasive (screened in R1, not screened in R2) and Late Entrants (not screened in R1,
means of capturing biomarker-rich material from the unprepared rectum. Since screened in R2). Predictors of uptake derived from previous screening episodes
there is minimal contamination by stool, the material collected is readily analy- included late return of the test kit (after more than 28 days), test results and
sable, in principle lending itself to Point of Care tests for a wide range of indica- compliance with follow-up investigations (usually colonoscopy). Age, gender,
tions, including infectious and inflammatory diseases of the GI tract in addition area-level socioeconomic deprivation and screening history were included in
to malignancy. The device can be used as a robust means of collecting material multivariable logistic regression analyses.
for later analysis by a wide range of technologies. RESULTS: Overall uptake among previous responders was 86.6% in R2 and
Disclosure of Interest: None declared 88.6% in R3. In R3, repeat uptake was 94.5% among Consistent Screeners,
59.8% among Dropouts and 78.0% among Late Entrants (differences between
groups, p50.001). Returning the test kit after more than 28 days in a previous
P0416 SYMPTOM-SPECIFIC REFERRAL CONTENT: WHAT DOES THE episode was associated with a reduced likelihood of repeat uptake in R2 (82.3%
GASTROENTEROLOGIST NEED? vs. 88.7%, p50.001) and R3 (84.5% vs 90.5%, p50.001). Receiving an abnor-
S.L. Eskeland1,*, L. Aabakken2, T.de Lange1 mal test result was also strongly associated with reduced repeat uptake in R2
1
Department of Medical Research, Brum Hospital, Vestre Viken Hospital Trust, (61.4% vs. 86.8%, p50.001) and R3 (65.7% vs. 88.8%, p50.001). Furthermore,
2
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, repeat uptake in R2 and R3 was particularly low among subjects who had not
Norway attended their follow-up test (R2: 24.3% vs. 67.1%, p50.001; R3: 43.2% vs.
Contact E-mail Address: s.l.eskeland@medisin.uio.no 69.9%, p50.001).
CONCLUSION: Previous screening episode factors related to various stages of
INTRODUCTION: Low quality referrals are a challenge for gastroenterologists the screening process have been implicated in subsequent uptake. These previous
when assessing and prioritizing the patients. However, it is not known which screening episode predictors could be used to identify individuals at risk of
information the gastroenterologists rely on for this task. We wanted to identify dropping out of screening and provide an opportunity to tailor invitation and
what gastroenterologists considered the most important variables to include in reminder letters to elicit increased uptake by selected sub-populations.
the referral letters for 9 common indications. Disclosure of Interest: None declared
AIMS & METHODS: 25 Norwegian gastroenterologists completed a web-based
survey where they were asked to select the 15 most important variables out of a
list of 29-36 potential variables.
United European Gastroenterology Journal 2(5S) A247
CONCLUSION: We recommend excluding the term Diarrhea as it is not specific
P0418 CAN WE EXPLAIN THE APPARENT DECLINE IN UPTAKE OF
to leakage of diarrhea. The remaining top three terms were ranked identically for
INVITATIONS FOR COLORECTAL CANCER SCREENING IN
participants with and without FI: 1) Bowel Incontinence, 2) Bowel Control
ENGLAND?
Issues, 3) Accidental Bowel leakage. All three terms scored below the median
J. Snowball1, H.E. Seaman1,2, S.P. Halloran1,2,* on the Uncomfortableness domain. The term used most often by providers, fecal
1
NHS Bowel Cancer Screening Southern Programme Hub, 2University of Surrey, incontinence, did not score in the top 10 on any of the 3 domains. Accidental
Guildford, United Kingdom Bowel leakage, recently described as patients preferred term, ranked 3rd. This
Contact E-mail Address: s.halloran@nhs.net information may help improve communication between patients and providers
and enable more patients to receive treatment. Supported by Salix
INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) pro- Pharmaceuticals.
vides biennial guaiac-based faecal occult blood test (gFOBT) screening for color- Disclosure of Interest: None declared
ectal cancer (CRC) to individuals aged 60-74 years (inclusive). Uptake of
screening invitations in England, which averages about 55%, is affected by indi-
vidual factors that include screening history, sex and level of social deprivation. P0420 SORD OVEREXPRESSION AND OTHER ASPECTS OF
Data for 2013 indicate a marked decline in uptake in England during the second DYSREGULATED PROTEIN EXPRESSION IN HUMAN
half of 2013. The BCSP in England is co-ordinated by five regional Hubs; each PRECANCEROUS COLORECTAL NEOPLASMS: A QUANTITATIVE
works with local screening centres that provide follow-up investigations (usually PROTEOMICS STUDY
colonoscopy) for individuals with a positive gFOBT result. The Southern Hub T. Staiano1,*, A. Uzozie2, P. Nanni2, M. Giancarlo2
provides the screening service to about 26% of the population in England (14.6 1
ENDOSCOPY AND GASTROENTEROLOGY UNIT, A. O. ISTITUTI
million); it sends over one million invitations for screening and analyses about g OSPITALIERI DI CREMONA, CREMONA, Italy, 2ENDOSCOPY AND
million test kits every year. Uptake in the Southern Hub averages 61% (2012/ GASTROENTEROLOGY UNIT, University of Zurich, zurig, Switzerland
2013) but demonstrates the decline since June 2013 reported across the rest of the Contact E-mail Address: terrystaiano@libero.it
country, an observation investigated by the Southern Hub research team.
AIMS & METHODS: All BCSP screening activity is recorded on the Bowel INTRODUCTION: Colorectal adenomas are cancer precursor lesions of the
Cancer Screening System (BCSS). Data for the period 2009-2013 were analysed large bowel. A multitude of genomic and epigenomic changes have been docu-
to investigate patterns of uptake according to age, sex, screening episode, index mented in these preinvasive lesions, but their impact on the protein effectors of
of multiple deprivation (IMD) and screening centre. biological function has not been comprehensively explored.
RESULTS: Amongst individuals aged 60-74 years, although subject to marked AIMS & METHODS: Using shotgun quantitative MS, we exhaustively investi-
fluctuations throughout each year, the overall trend was towards increased gated the proteome of 30 colorectal adenomas and paired samples of normal
uptake until June 2013, after which uptake declined sharply. Uptake amongst mucosa. Total protein extracts were prepared from these tissues (prospectively
first-time invitees aged 60 years was the most consistent (55%) between 2009 and collected during colonoscopy) and from normal (HCEC) and cancerous (SW480,
2012, although a marked fall in uptake was evident from mid-2013. The most SW620, CACO2, HT29, CX1) colon epithelial cell lines. Peptides were labeled
deprived showed the greatest fall in the first invitation episode (60-year-olds) and with isobaric tags (iTRAQ 8-plex), separated by OFFGEL electrophoresis, and
there was no change in uptake by the least deprived individuals. Different pat- analyzed by LC-coupled tandem MS. Non-redundant protein families (4325 in
terns observed across screening centres may reflect different start dates resulting tissues, 2017 in cell lines) were identified and quantified. Principal component
in a different mix of episodes, with the population with the longest screening analysis of the results clearly distinguished adenomas from normal mucosal
history possibly subject to screening fatigue. samples, and cancer cell lines from HCEC cells.
CONCLUSION: We have not explained the decline in uptake of CRC cancer RESULTS: Two hundred twelve proteins displayed significant adenoma-related
screening invitations during 2013. A decline in CRC screening uptake has been expression changes (q-value 5 0.02, mean fold change vs. normal mucosa /-
observed by the other BCSP Hubs and by the NHS screening programmes for the 1.4), which correlated (r 0.74) with similar changes previously identified by our
breast and cervix (personal communication), although the decline in uptake of group at the transcriptome level. Fifty-one (25%) proteins displayed direction-
breast and cervix screening has been more gradual. It may be that the public is ally similar expression changes in colorectal cancer cells (vs. HCEC cells) and
reacting to adverse publicity about the benefits of screening surrounding breast were therefore attributed to the epithelial component of adenomas. Although
screening, in particular, although data from the Scottish programme do not benign, adenomas already exhibited cancer-associated proteomic changes: 69
demonstrate the decline observed in England (personal communication). The (91%) of the 76 protein upregulations identified in these lesions have already
benefits of CRC screening are well-recognised and efforts to improve uptake been reported in cancers. One of the most striking changes involved sorbitol
of screening invitations and close monitoring of uptake should continue. dehydrogenase (SORD), a key enzyme in the polyol pathway.
Disclosure of Interest: None declared CONCLUSION: Validation studies revealed dramatically increased SORD con-
centrations and activity in adenomas and cancer cell lines, along with important
changes in the expression of other enzymes in the same (AKR1B1) and related
P0419 PATIENT PREFERENCES FOR TERMINOLOGY USED TO (KHK) pathways. Dysregulated polyol metabolism may represent a novel facet
IDENTIFY FECAL INCONTINENCE of the metabolome remodeling associated with tumorigenesis.
S. Heymen1,*, O. Palsson1, S.M. Kim1, S. Twist1, W.E. Whitehead1 Disclosure of Interest: None declared
1
Medicine, University of North Carolina, Chapel Hill, United States
Contact E-mail Address: steve_heymen@med.unc.edu
P0421 KNOWLEDGE AND PERCEPTION OF DOCTORS ON RISK
INTRODUCTION: Fecal incontinence (FI) affects 9% of non-institutionalized FACTORS AND SCREENING OF COLORECTAL CANCER (CRC)
U. S. adults, but fewer than 30% have discussed this problem with their physi- Y.J. Wong1,*, Z. Poh1, M.L. Ong1, K.L. Shum1, V. Namasivayam1, K.L. Ling1
cian. This is unfortunate because effective treatments are available. Two factors 1
Gastroenterology, Singapore General Hospital, Singapore, Singapore
that may contribute to low consulting rates are embarrassment about this taboo Contact E-mail Address: eugene.wong@mohh.com.sg
topic and unfamiliarity with the terms used by physicians.
AIMS & METHODS: Our goal was to identify terms that are the most accep- INTRODUCTION: CRC has claimed 214,675 lives Europe and is expected to
table and understandable to FI patients to make it easier for clinicians to inquire rise by 12% by 20201. Knowledge and perception of doctors is important to
about and discuss FI with patients, and easier for patients to disclose the pro- future success of CRC screening program as early detection of CRC improve
blem. Thirty patients with FI (29 women) recruited by advertisement participated survival. However, little is known about doctors knowledge and perception
in internet chat rooms of 1-5 persons. They were asked: What words do you use towards CRC. We aim to determine current knowledge and perception of color-
to describe your FI when you are talking to doctors, family members, or ectal cancer screening amongst junior doctors.
friends? with requests to rate 3 domains on a 0-10 scale: 1) the understandability AIMS & METHODS: 169 junior doctors practicing across 7 specialties at a local
of these terms, 2) their appropriateness for discussions with others, and 3) the academic institution were recruited from July -September 2013. Standardized
patients level of discomfort (embarrassment) in using the term. Based on focus questionnaires consisting of 44 questions were administered during structured
group input, 29 terms were selected for participants to evaluate for a national resident teaching sessions that were unrelated to CRC. Individual responses
survey. Thirty-one terms were not included because the investigators deemed were collected. Absent doctors were contacted via email. Standard statistical
them to be offensive (e.g., squirts, shits, taco butt) or because they were adjectives techniques were employed.
describing emotional reactions to FI or characteristics of FI (e.g. Embarrassing, RESULTS: 74% (125/169) of junior doctors responded. Respondents mean age
Disgusting). This sample was stratified by FI status, age, sex, and race/ethnicity. was 27.7 years (23-35). Mean duration of practice locally was 3.2 years (1-8).
RESULTS: The national survey recruited 560 participants (42% with FI). Sixty- Majority (97.6%) were aware that CRC is curable if treated early, and 85.6%
four participants were excluded for answering identical questions inconsistently. recognized that CRC screening reduces mortality. Only 78.4% recognized CRC
The remaining 496 participants had a mean age of 47.5 (range 18-91) years, 48% as the commonest cancer locally. Most CRC risk factors (CRC-RFs) such as age,
of participants were males, and race/ethnicity was 69.6% Caucasian, 15.7% family history, smoking, inflammatory bowel disease and colonic polyps were
Hispanic, and 14.7% African American. Participants were also divided into correctly identified (84.8-100%). However, knowledge of modifiable CRC-RFs
three age groups for analysis: 35 and younger (n 146), 36-64 (n 243) and 65 was poor. Few recognized diabetes mellitus (5.6%), sedentary lifestyle (39.2%)
and older (n 106). Appropriateness ratings are reported here. When we com- and obesity (43.2%) as CRC-RFs. In addition, 10.4% wrongly identified tradi-
pared the ratings from participants with FI and without FI, four of the top five tional medicine as a CRC-RF, and only 45.7% correctly identified the recom-
rated terms were the same for both groups (Bowel Incontinence, Bowel Control mended age for CRC screening according to local guidelines. More fresh
Issues, Accidental Bowel Leakage, and Diarrhea). Women rated all of these graduates (PGY1) correctly identified 80% of CRC-RFs compared to the
terms as significantly more Appropriate than men did. A consistent race/ethnicity rest (40% vs 21.9%; p 0.044). Only 90.4% and 88% identified colonoscopy
pattern showed highest Appropriateness ratings for Caucasians, then Hispanics, and fecal occult blood test (FOBT) as acceptable CRC screening methods. 94.2%
and lowest by African Americans on all of these terms. Ratings also differed felt FOBT had poor test performance. Physicians concerns for colonoscopy
significantly by age group, increasing with age across the three groups for all of included cost (76.9%), risk of perforation (61.5%), bleeding (46.2%), and incon-
these terms. Ratings differed on only one of these terms due to Education level venient bowel preparation (66.7%). In spite of this, 80.8% will offer colonoscopy
(Bowel Control Issues) or Income (Bowel Incontinence). while only 68% will offer FOBT for CRC screening to their patients. There was
A248 United European Gastroenterology Journal 2(5S)
no difference in attitudes and practice patterns between doctors of different post- same operator successively in the left lateral decubitus position and in the stand-
graduate years. ing position. The EUS was perfomed the same day. KESS and Wexner scores
CONCLUSION: Majority of junior doctors correctly identified CRC as a sig- were routinely rated, as well as size and weight of the patients. The calculated
nificant healthcare burden, and that CRC screening and early detection reduces number of patients required for this study was 40.
mortality. However, knowledge on modifiable CRC-RFs is still lacking. Many RESULTS: These are preliminary results (20 patients included in the 40 to be
had concern about FOBT test performance, and more will offer screening colo- included). 17 females and 3 males, with a median age of 41 years (20-73) and a
noscopy. Continual medical education for junior doctors on modifiable CRC-RF median body mass index of 23 kg/m2 (17-36) were included. The indication of
and importance of CRC screening should be emphasized for continual success of examinations was anal incontinence in 8 patients and constipation in 12 cases,
CRC screening. with a median KESS score of 20 (9-32) and a median Wexner score of 9 (7-20).
REFERENCES No manometric measured parameters was significantly different in the supine or
1. GLOBOCAN. Estimated cancer incidence, mortality and prevalence worldwide standing position, whatsoever in the subgroup of incontinent patients or in the
in 2012, 2012. subgroup of constipated patients.
Disclosure of Interest: None declared CONCLUSION: These preliminary results showed no significant difference
between the pressure values measured by 3DHRAM in the supine and standing
position. At this stage of study, two hypotheses can be advanced: 1) the lack of
MONDAY, OCTOBER 20, 2014 9:0017:00 power related to the low effective since we have included only half of the patients
NERVE GUT AND MOTILITY I POSTER EXHIBITION HALL required; 2) no difference whatever the position of the patient when the measure-
XL_____________________ ments are made with 3DHRAM. Analysis of the results when all patients will be
included will provide the answer to this question.
P0422 OSMOTIC LAXATIVES ARE ASSOCIATED WITH LOWER Disclosure of Interest: None declared
RIGIDITY IN IDIOPATHIC PARKINSONISM
A. Augustin1,*, A. Charlett2, C. Weller1, S.M. Dobbs1,3, D. Taylor1, M. Ibrahim4,
P0424 BUSERELIN INDUCES ENTERIC NEURONS TO EXPRESS
I. Bjarnason3, R.J. Dobbs1,3
1 CORTICOTROPIN-RELEASING FACTOR
Pharmaceutical Science, Kings College London, 2Statistics Unit, Centre for
Infectious Disease Surveillance and Control, Public Health England, B. Ohlsson1,*, C. Karlsson2, U. Voss3, G. Molin2, S. Ahrne2, E. Ekblad3,
3
Gastroenterology, Kings College Hospital, 4Diagnostic Immunology Laboratory, E. Sand3
1
Kings College and St Thomass Hospitals, London, United Kingdom Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Contact E-mail Address: sylvia.dobbs@kcl.ac.uk Malmo, 2Food Hygiene, Dept of Food Technology, Engineering and Nutrition,
Division of Applied Nutrition, Lund University, 3Department of Experimental
INTRODUCTION: In idiopathic parkinsonism (IP), flexor rigidity is greater the Medical Science, Neurogastroenterology Unit, Lund University, Lund, Sweden
higher the circulating natural-killer cell count, an effect modulated by CD4 Contact E-mail Address: bodil.ohlsson@med.lu.se
count.1 These counts are higher with hydrogen-breath-test positivity for small-
intestinal-bacterial-overgrowth. Two-thirds of IP-patients are positive at INTRODUCTION: Treatment with gonadotropin-releasing hormone (GnRH)
presentation. analogs have led to severe dysmotility, which implicates roles for the reproductive
AIMS & METHODS: Improving intestinal transit with laxatives might reduce peptide/hormones in the gastrointestinal tract. Administration of the GnRH
rigidity by reducing overgrowth. analog buserelin to rats leads to neurodegeneration and ganglioneuritis.
Relationships of interventions for constipation to rigidity and overgrowth were During these experiments, we have observed that the treated rats have exhibited
explored using generalised linear mixed models. Surveillance yielded 1378 objec- a more stressed behavior than controls. Stress has been shown to increase secre-
tive measures of arm rigidity in 74 IP-patients over 343 person years, with 437 2-h tion of corticotropin-releasing factor (CRF) and to increase intestinal permeabil-
lactulose-hydrogen-breath-tests in 48. Maintenance osmotic laxative (macrogols) ity in humans, and to increase locomotion, rearing, pellet excretion, and altered
was exhibited in 50 (176 person years); bulk-forming laxative (ispaghula husk/ colonic microbiota in rodents. CRF is highly expressed in the enteric nervous
methylcellulose/sterculia) in 52 (196); enterokinetic agent (prucalopride) in 25 system in humans and rodents, and has been shown to abolish the vasoactive
(45); and guanylate cylase-C receptor agonist (linaclotide) in 8 (12). intestinal peptide (VIP)-induced neuronal survival.
RESULTS: Osmotic laxative was the only intervention associated with a change in AIMS & METHODS: The aim of the present study in rat was to evaluate the
rigidity. Flexor rigidity increased (by 6.8 (4.3, 9.4) % per year, p 0.001) where not effect of the GnRH analog buserelin on enteric neurons immunoreactive to CRF
exhibited, stabilised where exhibited (1.4 (95% CI -0.9, 3.8) % per year, p 0.2). and the intestinal microbiota.
Bulk-forming laxative had no additional effect on rigidity (p 0.5). Similarly, the Forty rats were given either buserelin (B) (20 g, 1 mg/ml) or saline (C) sub-
ratio, flexor to extensor rigidity, indicating tendency to simian posture, increased cutaneously, once daily for five days, followed by three weeks of recovery, repre-
(3.2 (0.7, 5.7) % per year, p 0.01) where osmotic laxative was not exhibited, senting one session of treatment. Two weeks after the fourth session, the animals
stabilised where exhibited (-1.6 (-3.9, 0.8) % per year, p 0.2). Bulk-forming laxa- were euthanized. Gastrointestinal tissue were collected and analyzed for neuronal
tive had no additional effect on the ratio (p 0.6). survival and CRF immunoreactivity. Microbial DNA (16S rRNA genes) was
Only bulk-forming laxative was associated with change in breath-hydrogen. Peak extracted from the colonic mucosa and analyzed with molecular genetic methods.
hydrogen was lower by 11 (1. 20) ppm (p 0.03) where exhibited, with no differ- The Terminal Restriction Fragment Length Polymorphism (T-RFLP) method
ential effect of time (p 0.9). (Odds ratio for a positive breath-test where exhib- was used to analyze microbial diversity. Bacterial abundance of the bacterial
ited compared with where not: 0.55). Osmotic laxative had no additional effect groups Clostridium leptum and Enterobacteriaceae was estimated using separate
on peak hydrogen (p 0.3). quantitative PCR assays.
CONCLUSION: Osmotic laxative may reduce rigidity by reducing inflamma- RESULTS: Body weight transiently increased by buserelin treatment at week 5
tion, directly, or by removing an inhibitory effect on anti-parkinsonian medica- and 9 (p 5 0.001). Enteric neurons were reduced in number by approximately
tion. Any effect of overgrowth on rigidity may relate to organisms not flagged by 40% in both submucous and myenteric ganglia of ileum and colon. Enteric
hydrogen-breath-test. neurons in colon immunoreactive to CRF increased in submucous ganglia
REFERENCES (C 10 (6-16)%, B 21 (14-25)%, p 5 0.05) and in myenteric ganglia (C 7
1. Dobbs RJ et al. Leukocyte-subset counts in idiopathic parkinsonism provide (5-9)%, B 19 (18-23)%, p 5 0.01) due to buserelin treatment. In submucous
clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A ganglia, the number of neurons immunoreactive to both nitric oxide synthase
surveillance study. Gut Pathogens 2012; 4: 12. (NOS) and CRF increased due to buserelin treatment (p 5 0.05). In the myen-
Disclosure of Interest: None declared teric ganglia, the number of neurons immunoreactive to NOS or VIP, in addition
to CRF, tended to increase after buserelin treatment (p 5 0.14 and p 5 0.08,
respectively). The CRF fiber density was unaffected by buserelin treatment
P0423 DOES BODY POSITION MODIFY ANORECTAL PRESSURE throughout all the different layers of the bowel wall. The total amount of bacteria
VALUES RECORDED BY THREE-DIMENSIONAL HIGH- and diversity in colon did not differ between groups. The number of bacteria in
RESOLUTION ANORECTAL MANOMETRY? the group of Enterobacteriaceae was significantly lower in buserelin-treated rats
A. Benezech1,2,*, M. Bouvier1,2, J.-C. Grimaud1,2, N. Lesavre3, K. Baumstarck4, compared to saline-treated rats (p 5 0.05), whereas the total amount of bacteria
V. Vitton1,2 in the groups of Clostridium leptum did not differ between broups.
1
Centre dExploration Fonctionnelle Digestive, Service de Gastroenterologie, CONCLUSION: The relative number of enteric neurons expressing CRF was
Hopital Nord, 2Interface de Recherche Translationnelle en Neurogastroenterologie, increased after induction of enteric neuropathy. The enteric nervous system
CRN2M, UMR 7286, Aix-Marseille Universite, 3Centre dInvestigation Clinique shows proof of plasticity, since NOS-immunoreactive neurons starts to express
9502, Hopital Nord, 4Unite dAide Methodologique a` la Recherche Clinique, CRF after buserelin treatment. Despite a marked enteric neuropathy, no signs of
EA3279, Laboratoire de Sante Publique, Aix-Marseille Universite, Marseille, bacterial overgrowth or diminished diversity are at hand in colon.
France Disclosure of Interest: None declared
INTRODUCTION: Inflammatory Bowel Diseases (IBD) dramatically alter the MONDAY, OCTOBER 20, 2014 9:0017:00
quality of life for the young adult and have a high societal cost. Treatments of OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS I POSTER EXHIBITION
IBD have made recent progress but their adverse side effects are numerous and HALL XL_____________________
relapse prevention remains a problem. Enhancing intestinal epithelial barrier
(IEB) functions emerges as a promising new therapeutic approach. The enteric P0435 PHENOTYPIC PLASTICITY OF ALVEOLAR MACROPHAGES IN
nervous system (ENS), a key regulator of gut homoeostasis, exhibits major bar- GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY
rier protective effects. Sacral nerve stimulation (SNS), probably via activation of MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA
the ENS, has been reported to enhance IEB resistance (1) but its putative pro- I.V. Maev1,*, S.V. Lyamina2, I.Y. Malyshev3
tective effects in response to inflammatory challenge remain unknown. 1
Propaedeutics of Internal Diseases and Gastroenterology, 2Pathophysiology,
AIMS & METHODS: Therefore, the aim of this study was to determine whether Propaedeutics of Internal Diseases and Gastroenterology, 3Pathophysiology,
SNS protects barrier dysfunction as well as modulates intestinal inflammation Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
induced by an acute inflammatory stress induced by TNBS. Twelve pigs were Contact E-mail Address: svlvs@mail.ru
implanted for percutaneous bilateral SNS (S3 stimulation) (Medtronic 041828-
004, Minneapolis, USA; 14 Hz, 210ms). Six pigs were stimulated 3 hours prior INTRODUCTION: To date it is known that in spite of different points of view
and 3 hours after administration of rectal enemas of TNBS (15 mg/ml). Control on etiology and variety of cellular and molecular pathogenetic components of
animals (CT) were implanted but not stimulated and also received TNBS enema. pulmonary manifestations in gastroesophageal reflux disease (GERD) and com-
Rectal panparietal biopsies were performed before (T0) and 1h, 3h, 24h after bination of GERD and asthma there is a key feature of inflammation and the
enema. Intestinal para- and transcellular permeability was assessed in Ussing immune response disorder in the form of Th1/Th2 imbalance in the pathogenesis
chambers. In vivo, intestinal inflammation was evaluated by endoscopy and con- of the disease. Th1 or Th2 direction of immune response is mainly predetermined
focal endomicroscopy (CEM) scores. Impact of SNS upon the mucosal changes by innate and adaptive immune response cells - macrophages. Considering the
induced by TNBS was evaluated by combining histological and transcriptomic concept of M1/M2 programming in changing microenvironment, macrophages
approaches. can obtain either pro-inflammatory L1 phenotype, or alternatively anti-inflam-
RESULTS: In CT, a significant and transient increase in rectal para- and trans- matory M2 phenotype and change their phenotype in the disease formation. So
cellular permeability was measured as early as 3h following TNBS enema. 24h we can suppose that Th1/Th2 imbalance is mainly due to impairment ability of
after enemas permeability was still increased in CT as compared to its T0 value. macrophages to adequate change their phenotype, i.e. with impaired phenotypic
In SNS pig, a significant and transient increase in para- and transcellular perme- plasticity of macrophages.
ability occurred as early as 1h following TNBS enema. However, 24h after AIMS & METHODS: Assessment of alveolar macrophages (AM) phenotypic
enemas permeability was similar to its T0 value. At 24h, similar results were plasticity in GERD and its combination with asthma and healthy volunteers
observed at the rectosigmoidal hinge level. Consistently, the SNS pigs exhibited under the influence of different serum (FBS) concentrations. Methods: In vitro
a trend toward a lower UCEIS score (p 0.07, n 5) as compared to CT. At 24h, experiments were carried out on AM, isolated from BALF of patients with
CEM scores revealed that TNBS induced alterations in crypt circularity, tortu- GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16,
osity and brightness were significantly reduced by SNS as compared to control 49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.). AM
(p 0.05, n 6; p 0.008, n 6, respectively). Furthermore, epithelial desqua- phenotype was assessed by flow cytometry (Beckman Coulter, FC500) by cyto-
mation and edema formation was significantly larger in CT as compared to SNS kine production of proinflammatory M1, anti-inflammatory L2 and bivalent
pigs (p 0.03, n 6, both measures). Finally, mRNA expression of key tight L1/L2 cytokines in culture medium (CM) of AM (BenderMedSystems,
junction proteins such as Claudin-1 (p 0.04, n 6) and ZO-1 (p 0.03, n 6) BMS810FF). Phenotypic plasticity of AM was measured as percentage change
were significantly increased in SNS (p 0.04, n 6; p 0.03, n 6, respectively) of markers during 36 hours of AM reprogramming in the presence of 0%, 10%,
as compared to CT pigs. Western blot analysis of ZO-1 also showed that ZO-1 40% standard fetal bovine serum, containing endogenous reprogramming factor
protein expression was increased in SNS as compared to CT animals (p 0.018, surfactant protein D.
n 6). RESULTS: Pooled analysis of M1 and M2 phenotypic plasticity in GERD and
CONCLUSION: Altogether these results show that SNS exhibit major repara- its combination with asthma against HV showed maximum of M1 phenotypic
tive properties on mucosal lesions induced by acute inflammatory stress. These plasticity in GERD M1/M2 index of the macrophages ability to change their
identify SNS as a putative alternative or complementary therapy targeting dis- phenotype towards M1 was 5.33 and this was 8.5 times increased vs combination
eases such as IBD. of GERD and asthma (p50.05). Maximum macrophage phenotypic plasticity
REFERENCES towards M2 phenotype was observed in combination of GERD and asthma and
(1) Neurogastroenterol Motil 2012; 24: 267e110. M1/M2 index of phenotypic plasticity was 5.45 times higher than in GERD.
Disclosure of Interest: None declared CONCLUSION: The ability of AM to change their phenotype under the influ-
ence of the microenvironment in GERD and its combination with asthma was
changed as compared to healthy volunteers. In GERD macrophages possess
P0434 FAECAL INCONTINENCE IN TYPE 2 DIABETICS: COMPARISON more possibilities to obtain M1 phenotype than M2, but the in combination of
WITH NON DIABETIC HEALTHY INDIVIDUALS AND ANALYSIS GERD and asthma macrophages are more predisposed to obtain M2 phenotype.
OF RELATED FACTORS So the studied ability of macrophages to adapt their phenotype to the micro-
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, E.A. Panao5, environment and to reprogram the phenotype of the cells can be thought of as the
M.A. Simoes2 base for new therapy approach in personalized medicine influencing the initial
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of links of inflammatory response and Th1/Th2 imbalance even in initial stages of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital pathological process.
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca, Disclosure of Interest: None declared
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Faecal incontinence is a complaint that some type 2 diabetic
patients frequently refer1. The factors involved with are not well known.
AIMS & METHODS: The aim of this study was to compare the frequency of
faecal incontinence between type 2 diabetic patients and non diabetic healthy
individuals and to analyse some factors involved in this perturbation in diabetics.
A252 United European Gastroenterology Journal 2(5S)
towards M2 phenotype vs HV in combination of GERD and asthma. SP-D
P0436 INCREASED LEPTIN SIGNALING IN ESOPHAGEAL
level in BALF in patients with GERD was 2.66 times decreased vs patients with
ADENOCARCINOMA CELL LINE TREATED WITH PERITUMORAL
combination of GERD and asthma (155.8318.13 ng/ml vs 414.7250.22 ng/ml,
ADIPOSE TISSUE-DERIVED CONDITIONED MEDIUM
p50.05) and 3.42 times decreased vs. HV (155.8318.13 ng/ml vs 533.2021.12,
E. Trevellin1, M. Scarpa2,*, A. Carraro3, L. Saadeh2, M. Cagol2, R. Alfieri2, p50.05). Qualitative analysis of SP-D oligomeric forms in GERD and its com-
U. Tedeschi3, C. Castoro2, R. Vettor1 bination with asthma showed predominance of monomeric forms vs HV with
1
Dept. of Medicine DIMED, University of Padova (Italy), 2Oncological Surgery monomeric and multimeric SP-D oligomers.
Unit, Oncological Institute (IOV-IRCCS), Padova, 3Dept. of General Surgery and CONCLUSION: In GERD with pulmonary manifestations and combination of
Odontoiatrics, University of Verona, Verona, Italy GERD and asthma AM phenotype and quantitative and qualitative composition
of SP-D in BALF vary against healthy volunteers and each other. Shift of AM
INTRODUCTION: Obesity is associated with an increased risk of cancer and it phenotype towards M1 vs healthy and significant maximum decreased SP-D level
has been hypothesized that the action of adipokines (e.g. leptin and adiponectin) in BALF are typical for GERD with pulmonary manifestations, whereas shift of
may influence tumor invasiveness. AM phenotype towards M2 and less decreasing SP-D level in BALF are specific
AIMS & METHODS: Our aim is to investigate if peritumoral adipose tissue may for combination of GERD and asthma. There were no significant differences in
play a direct role by altering the expression of genes involved in migratory/ qualitative oligomeric composition of SP-D in BALF in GERD and its combina-
mesenchymal transition processes in human esophageal adenocarcinoma cells. tion with asthma.
Human esophageal adenocarcinoma cells (OE33) were cultured with conditioned Disclosure of Interest: None declared
medium (CM) derived from adipose tissue fragments of peritumoral and distal
(omental) depots of 15 patients with esophageal adenocarcinoma, undergoing
surgical resection. After 48h we measured mRNA levels of leptin receptor P0438 INITIAL EXPERIENCE WITH HEMOSPRAY IN THE
(ObR), adiponectin receptor (AdipoqR), alpha-smooth muscle actin (-SMA) TREATMENT OF ACUTE UPPER GASTROINTESTINAL BLEEDING
and E-cadherin (CDH1) in OE33 cells using Real Time quantitative PCR. B. Disney1,*, A.K. Kurup1, S. Ishaq1, S. Shetty1, H. Muhammad1
RESULTS: Gene expression of ObR, AdipoqR, -SMA and CDH1 were dra- 1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom, Dudley,
matically increased in OE33 cells cultured with CM, compared to control cells. United Kingdom
Moreover, expression of ObR, AdipoqR -SMA and CDH1 was significantly
higher in OE33 cells cultured with CM of peritumoral depot, compared to cells INTRODUCTION: Upper gastrointestinal bleeding remains a medical emer-
cultured with CM of omental depot. Interestingly, ObR and -SMA expression gency. Endoscopic therapies such as adrenaline injection, heater probe and
was significantly increased in OE33 cells cultured with CM of peritumoral depot clips are used to achieve haemostasis. However, accurate delivery of these
derived from patients with lymph node involvement (N), compared to peritu- endotherapies can be challenging. Hemospray (Cook Medical, Winston-Salem,
moral CM of patients with no positive lymph node (N-). North Carolina, USA), an inorganic haemostatic powder, is licensed for use in
CONCLUSION: Our results suggest that peritumoral adipose tissue may influ- non-variceal acute upper GI bleeding. The delivery system allows a wide area of
ence esophageal adenocarcinoma cells, through the action of secreted factors. In coverage, negating the need for accuracy, and has promising results.
particular, leptin signaling may be involved in the induction of -SMA expres- AIMS & METHODS: Retrospective analysis of all upper GI bleeds utilising
sion in esophageal adenocarcinoma cells, possibly promoting a more aggressive Hemospray following its introduction to Russells Hall Hospital in July 2013.
behaviour of tumor. Patients were identified using the Unisoft endoscopy database and endoscopy
REFERENCES unit logbooks. Data on the use of Hemospray, bleeding lesion identified and use
Prieto-Hontoria PL, et al. Role of obesity-associated dysfunctional adipose tissue of other therapeutic modalities were collected. Outcomes including mortality,
in cancer: a molecular nutrition approach. Biochim Biophys Acta 2011; 1807: 664- primary haemostasis and rebleeding were obtained. The aim of this study was
678. to assess the effectiveness of Hemospray in the real-life setting.
Jeong YJ, et al. Expression of leptin, leptin receptor, adiponectin, and adiponec- RESULTS: Hemospray was used 17 times in 13 patients with acute upper GI
tin receptor in ductal carcinoma in situ and invasive breast cancer. J Breast bleeding (mean age 69 years, range 37-96 years; 69% male). The patients had a
Cancer 2011; 14: 96-103. median Blatchford score of 10 (range 5-13) and Rockall score of 7 (range 3-8).
Zhao L, et al. Possible involvement of leptin and leptin receptor in developing Three patients had Hemospray used on more than one occasion.
gastric adenocarcinoma. World J Gastroenterol 2005; 11: 7666-7670. The cause of bleeding was peptic ulcer in 10/17 patients (58.8%), upper GI malig-
Howard JM, et al. Associations between leptin and adiponectin receptor upre- nancy in 6/17 patients (35.3%) and unknown source in 1/17 patients (5.9%).
gulation, visceral obesity and tumour stage in oesophageal and junctional ade- Hemospray was used as primary endotherapy in 11/17 patients (65%) achieving
nocarcinoma. Br J Surg 2010; 97: 1020-1027. initial haemostasis in 16/17 cases (94%). Technical failure occurred in one patient
Disclosure of Interest: None declared with the cartridge failing to operate and deliver Hemospray. Rebleeding within 30
days occurred with 6/17 uses (35%); 5 of these in the context of peptic ulcer disease
and 1 in upper GI malignancy. When Hemospray was used as primary therapy
P0437 SURFACTANT PROTEIN D AND ALVEOLAR MACROPHAGES rebleeding occurred on 4 occasions compared to 2 when used as second line therapy
PHENOTYPE AS ADDITIONAL MARKERS IN DIAGNOSTICS OF (p 0.57). Blatchford scores were higher in those patients suffering from rebleeding
GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY (12 versus 10, p 0.21). No significant differences in rebleeding was noted between
MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA malignant and non-malignant causes of acute upper GI bleeding. 30-day mortality in
S. V. Lyamina1,*, I.V. Maev2, I.Y. Malyshev3 this patient cohort was 2/13 (15.4%). There were no documented complications of
1
pathophysiology, Propaedeutics of Internal Diseases and Gastroenterology, 2 Hemospray therapy.
Propaedeutics of Internal Diseases and Gastroenterology, 3pathophysiology, CONCLUSION: Hemospray is a safe, and easy to use, endoscopic therapy with
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation excellent initial haemostasis as both a primary or second line treatment. In the
Contact E-mail Address: svlvs@mail.ru context of bleeding as a result of upper GI malignancy Hemospray provided
good palliation. Although there appeared to be a higher rebleeding rate seen
INTRODUCTION: Actual pathogenesis studies of pulmonary manifestations in when Hemospray was used as primary therapy this was not significant and
gastroesophageal reflux disease (GERD) and its combination with asthma may reflect the low numbers in the study.
showed that respiratory system inflammation and imbalance between Th1 and REFERENCES
Th2 immune responses are the main pathologic components of the process. 1. Leblanc S, Vienne A, Dhooge M, et al. Early experience with a novel hemo-
Considering the present-day concept of Th1/Th2 Paradigm and M1/M2 macro- static powder used to treat upper GI bleeding related to malignancies or after
phages programming, immune response disorders depend largely on the balance therapeutic interventions. Gastrointestinal Endoscopy 2013; 78.
of functional phenotypes of alveolar macrophages (AM). One of significant 2. Chen YI, Barkun AN, Soulellis C, et al. Use of the endoscopically applied
bivalent regulatory components of AM activity is surfactant protein D (SP-D). hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary
So we suppose that pooled analysis of AM phenotype with quantitative and experience. Gastrointestinal Endoscopy 2012; 75.
qualitative analysis of SP-D composition in broncho-alveolar lavage fluid Disclosure of Interest: None declared
(BALF) will add to research in pathogenesis of pulmonary manifestations in
GERD and can be used as additional biomarker in GERD and its combination
with asthma. P0439 CORRECT USE OF PROTON-PUMP INHIBITORS FOR STRESS
AIMS & METHODS: This study evaluated pooled data of AM phenotype and ULCER PROPHYLAXIS IN INTENSIVE CARE UNIT: NO GI
quantitative/qualitative composition of SP-D in BALF in patients with pulmon- BLEEDING AND NO CL. DIFFICILE?
ary GERD manifestations and its combination with asthma in comparison with S. Segato1,1, L. Bardelli1, C.C. Cortelezzi1,*, M. Parravicini1, M. Montanari1,
healthy volunteers. Methods: Pooled analysis of AM phenotype in patients with S. Piana1, S. Bonecco1, S. Segato1, G. Bisso1, G. Minoja2
GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16, 1
Gastroenterology, 2Intensive Care Unit, Azienda Ospedaliero Universitaria
49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.) was per- Macchi Varese, Varese, Italy
formed by flow cytometry (Beckman Coulter FC500) by expression of M1 and Contact E-mail Address: sergio.segato@ospedale.varese.it
M2 AM phenotypes CD markers (CD25, CD80 and CD163, CD206, respec-
tively) and cytokine production of proinflammatory M1, anti-inflammatory L2 INTRODUCTION: Despite limited data about their use in critically ill patients,
and bivalent L1/L2 cytokines in culture medium (CM) of AM proton pump inhibitors (PPIs) have become the first line therapy in stress ulcer
(BenderMedSystems, BMS810FF). Quantitative analysis of SP-D in BALF prophylaxis (SUP). PPIs may increase the risk of hospital-acquired pneumonia
was performed by ELISA. Qualitative assessment of SP-D oligomeric forms in and enteric infections, especially Clostridium difficile related diarrhoea. Many
BALF was performed by western blot analysis using tris-acetate gels (Invitrogen, studies showed an overuse of acid suppressive therapy in Intensive Care Unit
NuPAGE, # EA03752BOX). (ICU), with unintended consequences of therapy.
RESULTS: Analysis of AM phenotype in patients with GERD, its combination AIMS & METHODS: The aim of the study was to evaluate the current practice
with asthma vs. HV showed that pooled M1/M2 ratio of AM CD markers and of SUP, the correlation with the evidence-based American Society of Health-
cytokine production was 2.16 and 2.52, 0.91 and 0.84 vs. HV, respectively. The System Pharmacist (ASHP) guidelines and the occurrence of GI hemorrhage,
results indicates shift of AM towards M1 phenotype vs HV in GERD and pneumonia, and CDI in critical care setting.
United European Gastroenterology Journal 2(5S) A253
The study was made on 300 consecutive patients (186 men, 114 women, medium
P0441 OUTCOMES AND PREDICTIVE FACTORS OF
age 63.9 yrs, range 23-99 yrs, median ICU stay 11.42 days range 3-45 days)
TRANSCATHETER ARTERIAL EMBOLIZATION FOR NON-
admitted to ICU of the teaching hospital Macchi Varese between January 1st
VARICEAL UPPER GASTROINTESTINAL BLEEDING
and June 30th 2012 and January 1st and June 30th 2013; patients admitted to
neurocritical care unit and children under 18 yrs were excluded. Data about H.H. Lee1,*, J.M. Park1, C.-H. Lim1, J.S. Kim1, Y.K. Cho1, B. I. Lee1, I.S. Lee1,
clinical indications, drug assumption and outcomes (gastrointestinal haemor- S.W. Kim1, M.-G. Choi1
1
rhage, pneumonia and enteric infections) were collected during ICU stay. Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea,
RESULTS: Mechanical ventilation for more than 48h was the reason for initiat- Republic Of
ing prophylaxis in 294 patients (98%); 6 pts. had a platelet count under 50.000/ Contact E-mail Address: hanyee99@hanmail.net
mm3.
281 pts (93.6%) used PPIs (omeprazole 40mg daily i.v.), 19 pts (6.3%) H2RAs INTRODUCTION: Transcatheter arterial embolization (TAE) has been consid-
(ranitidine 150 mg every 8 hours i.v.), 296 pts (98.6%) antibiotics, 166 pts ered a therapeutic option for upper gastrointestinal (GI) bleeding when endo-
(55.3%) vasoactive drugs. scopic treatment fails.
32 patients (10.6%) developed nosocomial pneumonia; 26 of them had other risk AIMS & METHODS: We aimed to assess the efficacy and clinical outcomes of
factors (1 asthma, 14 chronic obstructive lung disease, 1 AIDS, 10 were older TAE for acute nonvariceal upper GI bleeding and to identify predictors of
than 75 years). One pt had Clostridium difficile related dyarrhea. One pt with a recurrent bleeding within 30 days.
history of active duodenal ulcer had ulcer bleeding. Transcatheter angiography was performed in 66 patients (42 men, 24 women;
CONCLUSION: All SUP were classified as appropriate according to the ASPH mean age, 60.3 12.7 years) who experienced acute nonvariceal upper GI bleed-
guidelines. PPIs represent the first line therapy. Bleeding from stress ulceration is ing during a 7-year period. Clinical information was reviewed retrospectively.
extremely uncommon; Clostridium difficile related dyarrhea is unexpectedly rare Outcomes included technical success rates, complications, and 30-day rebleeding
too. Patients who developed hospital-acquired pneumonia during acid-suppres- and mortality rates.
sive therapy, usually had other risk factors linked to this kind of infection. In this RESULTS: TAE was feasible in 59 patients. The technical success rate was
prospective observational study, the occurrence of GI bleeding and symptomatic 98.3%. Rebleeding within 30 days was observed in 46.6% and was managed
CDI in critically ill patients, treated following ASHP guidelines, is lower than with reembolization in 8 patients, endoscopic intervention in 5, surgery in 2,
reported in other studies. More data from well-designed randomized clinical and conservative care in 12. The 30-day overall mortality rate was 42.4%. Of
trials are needed before any change in practice. the 34 patients whose initial endoscopic hemostasis failed, 31 (91.2%) underwent
Disclosure of Interest: None declared angiographic embolization, which was successful in 30. Rebleeding occurred in
15 patients (50.0%), mainly because of malignancy. Two factors were indepen-
dent predictors of rebleeding within 30 days by multivariate analysis: coagulo-
P0440 A COMPARISON OF THE GLASGOW-BLATCHFORD SCORE pathy (OR, 4.37; CI, 1.2515.29; P 0.021) and embolization in 32 territories
AND AIMS65 SCORE IN PREDICTING NEED FOR CLINICAL (OR, 4.93; CI, 1.4317.04; P 0.012). Catheterization-related complications
INTERVENTION AND MORTALITY IN ACUTE NON-VARICEAL included hepatic artery dissection and splenic embolization.
UPPER GI BLEEDS: A RETROSPECTIVE COHORT STUDY CONCLUSION: TAE controlled acute nonvariceal upper GI bleeding effec-
A.J. Palmer1, F. Moroni1,*, S. McLeish1, G. Campbell1, J. Bardgett1, J. Round1, tively. TAE may be considered when endoscopic therapy is unavailable or unsuc-
C. McMullan1, M. Rashid1, R. Clark1, D. De Las Heras 2, C. Vincent2 cessful. Coagulopathy and embolization of 32 territories were significant
1
Medicine, Raigmore, 2Medicine, Raigmore Hospital, Inverness, United Kingdom predictors of angiographic failure. Correction of coagulopathy before TAE is
Contact E-mail Address: andrew.palmer1@nhs.net recommended.
REFERENCES
INTRODUCTION: The early use of risk stratification scores is recommended by 1. Loffroy R, Guiu B, Cercueil JP, et al. Refractory bleeding from gastroduode-
the International Consensus Upper Gastrointestinal (GI) Bleeding Group for nal ulcers: arterial embolization in high-operative-risk patients. J Clin
patients presenting with acute non-variceal upper GI bleeds (ANVUGIB) 1. Gastroenterol 2008; 42: 361-367.
Such models permit identification of patients who are suitable for early hospital 2. Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from
discharge or even outpatient care. The most widely used is the Glasgow- acute upper gastrointestinal haemorrhage in the United Kingdom. Steering
Blatchford Score (GBS) 2. The score ranges from 0 to 23 and the risk of requiring Committee and members of the National Audit of Acute Upper
clinical intervention and death has been shown to increase with increasing score 3. Gastrointestinal Haemorrhage. BMJ 1995; 311: 222-226.
More recently a simpler scoring system known as AIMS65 was devised, which is 3. Hearnshaw SA, Logan RF, Lowe D, et al. Acute upper gastrointestinal bleed-
based on serum Albumin (530g/dl), INR 41.5, altered Mental status ing in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK
(GCS514), Systolic BP (590) and age 465. One point is scored for the presence audit. Gut 2011; 60: 1327-1335.
of each variable and it has been shown to accurately predict mortality, length of Disclosure of Interest: None declared
stay, and be superior to the GBS in predicting mortality 4,5. However, its ability
predict the need for clinical intervention has yet to be established.
AIMS & METHODS: The aim of this study was to examine the ability of the P0442 DOES DISCHARGE HEMOGLOBIN AFFECT OUTCOME OF
AIMS65 score in predicting the need for clinical intervention and mortality in PATIENTS WITH ACUTE NON-VARICEAL UPPER
comparison to the GBS. To do this we performed a retrospective analysis of 150 GASTROINTESTINAL BLEEDING?
adults who presented to a single district general hospital in Scotland with a J.M. Lee1, H.J. Chun1,*, I.K. Yoo1, S.J. Nam1, S.H. Kim1, H.S. Choi1,
primary diagnosis of ANVUGIB and who underwent upper GI endoscopy E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, C.D. Kim1
between March 2008 & April 2013. GBS and AIMS65 scores were calculated 1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
and requirement for clinical intervention, defined as the need for endoscopic Korea University College of Medicine, Seoul, Korea, Republic Of
treatment, blood transfusion and/ or surgery was recorded. The area under the Contact E-mail Address: jmlee1202@gmail.com
receiving-operator characteristic curve (AUROC) was calculated for each score.
RESULTS: Of the 150 patients 62% were male and 38% female. The mean age INTRODUCTION: Many patients with gastrointestinal bleeding show anemia
was 68 years (SD 16), GBS 7.9 (SD 4.6) and AIMS65 score 1.0 (SD 1.0). The and usually need red blood cell transfusion. Several studies suggested that restric-
overall mortality was 6%. The GBS had a high predictive accuracy and was tive transfusion strategy and low hemoglobin threshold for transfusion showed
superior to AIMS65 in predicting requirement for any clinical intervention acceptable outcomes in patients with acute upper gastrointestinal bleeding [1,2].
(AROC 0.81 vs. 0.70), blood transfusion (AROC 0.85 vs. 0.67) and endoscopic But clinicians are concerned about low hemoglobin affects prognosis and clinical
therapy (AROC 0.67 vs. 0.58). With respect to mortality, AIMS65 was superior outcome after discharge. This study aimed to assess whether discharge hemoglo-
to the GBS (AROC 0.79 vs. 0.68). Patients with a GBS 54 experienced no bin influences on outcomes, or not, in patients with acute non-variceal gastro-
mortality, GBS 4 58 2.6% and for those with GBS 8 10.1%. For the GBS intestinal bleeding.
these cut off values maximised the sensitivity and specificity for inpatient mor- AIMS & METHODS: Retrospective analysis was carried out on patients who
tality. Patients with low risk AIMS65 scores (0 or 1) experienced mortality (4%) had upper gastrointestinal bleeding between January 2011 and December 2012.
questioning its use as a risk stratification tool for safe, early, hospital discharge. We analyzed the patients who had lowest hemoglobin below 10 g/dL during
CONCLUSION: In our population the GBS was superior to the AIMS65 score admission. Patients with variceal bleeding, stroke, or cardiovascular disease
in terms of predicting the need for any clinical intervention, blood transfusion or were excluded. We divided the patients into two groups by discharge hemoglobin
endoscopic therapy. We identified potential cut off values for the GBS that allow (Low discharge hemoglobin group; 8 g/dL hemoglobin 510 g/dL, High dis-
stratification of patients into low, medium and high risk groups on the basis of charge hemoglobin group; 10 g/dL hemoglobin 512 g/dL) and compared
predicted mortality. This warrants further investigation. clinical outcomes and hemoglobin level changes.
REFERENCES RESULTS: A total of 212 patients with upper gastrointestinal bleeding had
(1) Barkun et al. Ann Intern Med 2010; 152: 101-113. undergone the endoscopic hemostasis during study periods. One hundred two
(2) Blatchford et al. Lancet 2000; 356: 1318. patients had satisfied the inclusion criteria. Fifty patients discharged with hemo-
(3) Srygley et al. JAMA 2012; 307: 1072. globin level under 10 g/dL and fifty two patients discharged with hemoglobin
(4) Saltzman et al. Gastrointest Endosc 2011; 74: 1215. level over 10 g/dL. There was no significant difference of endoscopic findings
(5) Hyett et al. Gastrointest Endosc 2013; 77: 551. between two groups. Patients in low discharge hemoglobin group showed a lower
Disclosure of Interest: None declared consumption of pRBC(Low discharge Hb group; 3.2 1.4 pint, High discharge
Hb group; 4.1 1.8 pint, P Value 0.01) and shorter hospital days (Low dis-
charge Hb group; 4.3 2.5 days, High discharge Hb group; 5.6 4.2 days).
Hemoglobin levels were not fully recovered at out-patient department until 7
days after discharge. But, most patients showed hemoglobin recovery at 45
days after discharge (Low discharge Hb group; Hb 12.2 2.0 g/dL at OPD
45, High discharge Hb group;; Hb 11.9 2.0 g/dL at OPD 45). Clinical symp-
toms after discharge were presented no significant difference between two groups.
A254 United European Gastroenterology Journal 2(5S)
CONCLUSION: In patients with acute gastrointestinal bleeding, discharge intent; 63.6% adenocarcinoma), with overall 12-month survival of 30% and 42%
hemoglobin between 8 to 10 g/dL was showed favorable outcomes during out- and 42-month mortality of 12% and 15%, respectively. From January 2009
patient department follow-up. It seems to be tolerable level without additional March 2013 there were: 111 gastric cancers (18% curative therapeutic intent;
pRBC transfusion. Despite of high hemoglobin over 10 g/dL at discharge, there 68.5% male; average age 75) and 230 oesophageal cancers (26.5% therapeutic
was no significant advantage in clinical outcome. Our result can increase the curative intent; 65.2% male; average age 72; 69.1% adenocarcinoma) with over-
evidence available to support restrictive transfusion strategies in patients with all 12-month survival of 40% and 36% and 42-month mortality of 16% and 8%,
acute non-variceal upper gastrointestinal bleeding. respectively (p40.05 for all corresponding follow-up intervals). Sub-group ana-
REFERENCES lysis shows increased survival in the 2009-2013 gastric cancer cohort treated with
1. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper curative intent at 6 months (p50.05) and palliative therapy at 12 months
gastrointestinal bleeding. New Eng J Med 2013; 368: 11-21. (p50.05). There was no significant decrease in survival outcome at any stage
2. Rockey DC. To transfuse or not to transfuse in upper gastrointestinal hemor- of follow up in both cancer groups and cohorts.
rhage? That is the question. Hepatology 2014. doi: 10.1002/hep.26994. CONCLUSION: These findings are in keeping with national outcomes and show
Disclosure of Interest: None declared that the institution of recommendations from the IOG, including centralisation
of curative therapies and access to specialist services, show no significant decrease
in survival outcome for OG cancer. Indeed, there is a modest increase in short-
P0443 EVALUATION OF THE PREDICTIVE VALUE OF REBLEEDING term gastric cancer survival. The lower percentage of patients treated with cura-
RATE OF FORREST SIMPLIFIED CLASSIFICATION tive intent, compared to national data, may reflect the late presentation of OG
J. Moleiro1,*, A. Ferreira2, J. Torres3, E. Barjas3, M. Cravo3 cancers and partially explain survival outcomes in this population.
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E. REFERENCES
P. E., Lisboa, 2Gastroenterology, Centro Hospitalar do Algarve, Portimao, Improving outcomes in upper GI cancers: the manual NHS Executive, DoH,
3
Gastroenterology, Hospital Beatriz Angelo, Loures, Portugal UK, January 2001.
Contact E-mail Address: joana_moleiro@hotmail.com Manual for cancer services: upper GI measures National Cancer Action Team,
2004, 2011.
INTRODUCTION: A simplification of the Forrest classification (FC) into three Cancer Research UK. http://www.cancerresearchuk.org (accessed 22 April 2014)
levels (high risk: Ia; increased risk: Ib to IIc; low risk: III) has recently been National Oesophago-Gastric Cancer Audit (NOGCA), UK The RCS, AUGIS,
proposed (1). BSG, RCR, HSCIC (2010, 2012, 2013)
AIMS & METHODS: Our aim was to evaluate the prognostic value of this new Disclosure of Interest: None declared
simplified classification (SC) in predicting re-bleeding of peptic ulcer (PU) and to
compare it with the traditional FC. We retrospectively identified patients
admitted to our unit between 07/2012 to 02/2014 with upper gastrointestinal P0445 THE FLAME MODEL: SUPPORTING ENDOSCOPY TRAINING
bleeding due to PU. Demographic, clinical, laboratorial and endoscopic data IN LOW RESOURCE SETTINGS
were collected. Therapeutic interventions and cases of re-bleeding and mortality S. Goddard1,*, J. Ansell1, N. Hawkes2
within a 30 days period were registered. The predictive value of the FC and SC 1
School of Postgraduate Medical and Dental Education, Cardiff University,
were compared using logistic regression and ROC curves. 2
Gastroenterology Department, Royal Glamorgan Hospital, Cardiff, United
RESULTS: 81 patients underwent upper gastrointestinal endoscopy due to Kingdom
bleeding PU; the mean age was 70 16 years; 61 (75%) were men. Clinical Contact E-mail Address: goddardsg@cardiff.ac.uk
presentation of PU bleeding was melena in 33 cases (41%), hematemesis in 29
(36%), symptomatic anemia in 8 (10%), hematochezias in 7 (9%) and hemody- INTRODUCTION: Simulation permits selective breakdown of key motor skills
namic instability in 4 (5%). The mean hemoglobin at admission and heart rate for a clinical procedure into basic steps, which is better for acquisition, teaching
were 8.75 g/dL and 94 bpm, respectively. Forty-eight percent of the ulcers were and assessing. (1, 2) Environment doesnt significantly affect skills transfer,
located in the stomach and 52% in the duodenum. Endoscopic therapy was implying endoscopy can be learnt outside the clinical setting. Basic endoscopic
performed in 39 patients (49%), and was effective in 38. One patient (1.2%) competencies can be taught with ex-vivo animal models. (3) The British Society
required surgery. At the 30th day, re-bleeding occurred in 15 patients (19%) of Gastroenterology supported an excursion to Kurdistan whose remit to train-
and the mortality rate was 6%. Re-bleeding occurred in 1 of 2 patients with the-trainers required provision of a suitable model.
Forrest Ia ulcer (high risk) and 8 (38%) with Forrest IIa (increased risk). The AIMS & METHODS: Develop and Validate: Flexible Lightweight Animal
odds ratio for re-bleeding of high risk and increased risk ulcers was 33.00 and Model for gi Endoscopy (FLAME), to support hands-on endoscopy training
14.30 (p 0.013), respectively. The AUROC (for re-bleeding) was 0.733 for SC in a low-resource setting, specifically, to facilitate training in GI haemostasis,
and 0.723 for FC. variceal banding and polypectomy. Pilot prototyping indicated use of a light-
CONCLUSION: FC maintains its predictive value in determining re-bleeding in weight, mouldable, plastic frame with selected ports for the attachment of pre-
PU. The proposed SC maintains the prognostic value of the FC, and therefore is made animal tissue patches with bespoke defects. Potential port sites were ana-
an alternative to assess the risk of re-bleeding. lysed to optimise access and offer different technical challenges. A foil plate and
REFERENCES cling film wrap-around supported use of diathermy and prevented fluid leakage.
Groot NL, Oijen MG, Kessels K, et al. Reassessment of the predictive value of The model was housed in foam and enclosed in a lightweight box. External
the Forrest classification for peptic ulcer rebleeding and mortality: can classifica- Velcro straps provided further anchorage. The model was validated during a
tion be simplified? Endoscopy 2014; 46: 46-52. hands-on training course conducted in Erbil, Iraq in February 2014. Attendees
Disclosure of Interest: None declared completed 11-point realism (visual, anatomical and mechanical) surveys based on
a 7 point Likert scale,(4) separately for GI haemostasis, variceal banding and
polypectomy. Analysis using Wlicoxon signed rank test (PASW Statistics 18) for
P0444 SURVIVAL OUTCOMES AFTER IMPLEMENTATION OF THE UK non-parametric data reported scores against a hypothetical mean of 4.0 for
IMPROVING OUTCOMES GUIDANCE (IOG) FOR OESOPHAGEAL statistical significance (n 17 gave 490% power to detect a difference of 1
AND GASTRIC CANCERS point).
R.K. Fofaria1,*, J. Deacon1, A.Z. Al-Bahrani2, A. Polychronis3, I.R. Sargeant1, RESULTS: 20 delegates (6 consultants, 14 trainees) completed the surveys. For
D. Morris1 polypectomy all scores were greater than 1 point above the 4.0 hypothethical
1
Gastroenterology, Lister and QEII Hospitals, Stevenage, 2General Surgery, mean, range 5.26-5.76 (score of 7 indicates strong agreement with realism). Mean
Watford Hospital, Watford, 3Medical Oncology, Mount Vernon Cancer Centre, overall score was 5.59 [p50.05; CI 4.96-6.22]. For both variceal banding and GI
Northwood, United Kingdom haemostasis, all mean scores were above 4.0 though the overall reality scores did
Contact E-mail Address: rishi.fofaria@nhs.net not reach significant difference; variceal banding - range 4.62-5.31, overall score
4.62; GI haemostasis range 4.5-5.83, overall score 4.56. Separate evaluation of
INTRODUCTION: Oesophago-gastric (OG) cancer is the 3rd most common the overall training course revealed high levels of delegate satisfaction, principally
cause of cancer-related death in the UK. Historically, it has been suggested the hands-on model training elements.
that the UK may have lagged behind European OG survival outcomes because CONCLUSION: The FLAMEs initial evaluation in a course setting demon-
of fragmentation of service provision, suboptimal access to leading specialist strates face and content validity for polypectomy. Whilst banding and GI hae-
centres and delayed presentation and referral of patients from primary care. mostasis values didnt achieve statistical significance ratings for all parameters,
The Improving Outcomes Guidance (IOG) for Upper GI Cancers (2001) and all were higher than the hypothetical mean. The model is cost-effective, easy to
Manual for Cancer Services (2004, 2011) recommended centralising curative transport, robust in practice and was highly valued by delegates in course eva-
therapies, reconfiguring access to diagnostic/staging services and formalising luation. We plan further adaptations with follow-up validation studies.
the role of the Cancer Network and peer-reviewed Network Site Specific REFERENCES
Groups. Lister and QE2 District Hospitals (part of the Mount Vernon Cancer 1. Hamdorf J and Hall J. Acquiring surgical skills. Br J Surg 2000; 87: 28-37.
Network) cover a catchment population of 600,000 people and reconfigured their 2. Kopta J. An approach to the evaluation of operative skills. Surgery 1971; 70:
upper GI cancer services in mid-2009. 297-303.
AIMS & METHODS: Aims: To assess survival outcomes in patients with OG 3. Parra-Blanco A, Gonzalez N, Gonzalez R, et al. Animal models for endo-
cancer over a 9-year period before and after the reconfiguration of a local upper scopic training: do we really need them? Endoscopy 2013; 45: 478-484.
GI cancer network. 4. Sedlack R, Baron T, Downing S, et al. Validation of a colonoscopy simulation
Methods: The medical, endoscopic and computerised notes of multi-disciplinary model for skills assessment. Am J Gastroenterol 2007; 102: 64-74.
team meetings of all patients diagnosed with OG cancer between 1 January 2004 - Disclosure of Interest: None declared
31 March 2013 were retrospectively analysed. Age, sex, histology, tumour site,
treatment intent and number of patients surviving at 6, 12, 24 and 42 months and
at 1 April 2014 were noted. The 2 (Chi-Square) test was used to analyse the
significance of survival outcomes.
RESULTS: From January 2004 - December 2008 there were: 139 gastric cancers
(27% curative therapeutic intent) and 234 oesophageal cancers (23% therapeutic
United European Gastroenterology Journal 2(5S) A255
P0446 THE FIRST REPORT ON THE GASTROPROTECTIVE EFFECT P0448 THE IMPACT OF ERYTHROMYCIN ON MYOELECTRIC
OF TRIPEPTIDE T-34 UNDER CONDITIONS OF WATER- ACTIVITY IN EXPERIMENTAL PIGS
IMMOBILISATION STRESS IN RATS T. Douda1,*, J. Kvetina2, I. Tacheci1, M. Pavlik3, M. Kunes4, M. Kopacova1,
C. Nasadyuk1,*, A. Sklyarov1 S. Rejchrt2, J. Bures2
1 1
Biochemistry, DANYLO HALYTSKY LVIV NATIONAL MEDICAL 2nd Department of Medicine- Gastroenterology, 22nd Department of Medicine,
UNIVERSITY, Lviv, Ukraine Charles University Faculty of Medicine & University Teaching Hospital, Hradec
Contact E-mail Address: nasadyukch@gmail.com Kralove, Czech Republic, 3Centre of Advanced Studies, University of Defence,
Faculty of Military Health Service, 4Biomedical Research Centre, University
INTRODUCTION: There is accumulating evidence that a number of short pep- Teaching Hospital, Hradec Kralove, Czech Republic
tides are envolved in the regulation of the function of gut and may be considered Contact E-mail Address: tomas.douda@fnhk.cz
as new pharmacological drugs for the prevention and treatment of gastric
ulceration. INTRODUCTION: Surface electrogastrography (EGG) is a non-invasive
AIMS & METHODS: Objective of our research was to explore the effect of method for the assessment of gastric myoelectrical activity. Erythromycin, as a
tripeptide T-34 (H-Glu-Asp-Gly-OH) on the area of water-immobilisation potent prokinetic drug, increases the dominant frequency of EGG both in
stress (WIS)-induced gastric lesions in rats and activities of NO-synthases humans and experimental pigs. The aim of this study was to evaluate the effect
(NOS) and lipid peroxidation processes in gastric mucosa (GM). of erythromycin on the porcine EGG power (assessed by areas of amplitudes)
The studies were conducted on white male rats. 30 min before the exposure to and power ratio (simple fraction ratio of the areas of amplitudes after and before
WIS rats were pretreated with T-34 introduced intragastrically (IG) in dose 10mg erythromycin administration).
(n 5) or intraperitoneally (IP) - 2mg (n 5). Control rats were injected 0.5 ml of AIMS & METHODS: Six mature female pigs (3 months old, mean weight
saline (n 5). After 5 hours of WIS, rats were sacrificed, gross inspection of GM 23.22.1, median 23 kg) were included in the study. All EGG recordings were
was conducted and NOS activity, NO and MDA content in GM were deter- performed under general anaesthesia in the morning after 24 hours of fasting (by
mined. In blood plasma L-arginine concentration was measured. means of the MMS EGG System, Enschede, the Netherlands). The baseline EGG
RESULTS: WIS caused the formation of gastric lesions (181.9 mm), accom- recording lasted 15 min., erythromycin ethylsuccinate (1,500 mg) was subse-
panied by acute rise of NO-synthase activity (p50.05), in particular its inducible quently administered by gastric tube into the stomach. The EGG trial recording
isoform iNOS (p50.01), increased production of NO and MDA (p50.05) in lasted 150 min. (ten 15-minute intervals: P1 to P10) after erythromycin adminis-
GM compared to intact rats. The concentration of L-arginine, NO precursor, in tration. Running spectral analysis (based on Fourier transform) was used for
blood plasma decreased (p50.05). Pretreatment with T-34 IG caused 27% initial evaluation of the EGG. The gastric myoelectric activity was estimated
(p50.05) decrease of ulceration area, at that NOS activity decreased for 45% by EGG power analysis and by power ratio assessment.
(p50.05), iNOS activity diminished for 60% (p50.01) in GM compared to RESULTS: Erythromycin increased the EGG power significantly after 15 to 30
control rats. Decrease of NO (p50.05) and tendency to decrease of MDA con- min. from the baseline mean value 828633 (V^2) to 15834238 (at P1) and
tent in GM were also noted, whereas L-arginine concentration in plasma 11022077 (P2 interval), p 0.003. Afterwards, the EGG power decreased to its
increased (p50.05). Pretreatment with T-34 IP also resulted in the decrease of minimum at P4 (237200), p50.001; and increased to 7091213 V^2 after 150
iNOS activity in GM (p50.05) but no statistically significant difference of the min. (at P10), p50.001. The EGG power ratio reached the highest values at P1
area of GM damage was evaluated compared to saline-treated rats exposed to (1.643.98) and P2 (1.914.27), decreased significantly at P4 (0.290.27; p50.001)
WIS. and balanced out after 150 min. at P10 interval (1.152.48; NS: p 0.668).
CONCLUSION: T-34 decreased the indices of nitrooxidative stress in GM under CONCLUSION: A medium single dose of erythromycin caused a significant
the conditions of WIS-induced gastric lesions in rats. IG administration of T-34 increase in the EGG power and power ratio after 15 to 30 min. after intragastric
was superior to IP injection of this compound towards reduction of gastric administration. Both myoelectrical markers decreased after 60 min. and returned
mucosa damage. Deeper studies on the elucidation of the cytoprotective effect close to the initial values after 150 min.
of tripeptide T-34, optimization of dosage and route of application are required. Acknowledgement
Disclosure of Interest: None declared The study was supported by research grant IGA NT/14270-3.
Disclosure of Interest: None declared
P0457
All 67.9% (57.9% 77.1%) 42 67.4% (55.9% - 78%) 34 71.5% (53.3% - 86.7%) 6
Elemental diets 90.8% (84.7% - 95.5%) 13 90.4% (83.5% - 95.5%) 12 94.4% (17/18) 1
Allergy testing-direct elimination diets 46.3% (35.6% - 57.1%) 13 47.9% (36.8% - 59.1%) 12 26.6 (4/15) 1
SFED 73% (66.6% - 78.9%) 6 72.8% (62.5% - 82%) 4 73.1% (64.8% - 80.7%) 2
Gluten-free diet 52.2% (15.3% - 87.8%) 6 45.5% (2.6% - 93.8%) 4 100% (1/1) 1
Milk elimination diet 68.2% (47.8% - 85.6%) 3 66.6% (44.7% - 84.8%) 2 100% (1/1) 1
Subgroups according to quality Medium/High - High 69.8% (58.4% - 80.1%) 32 70.3% (56.5% - 82.4%) 26 70.6% (51.1% - 86.8%) 5
Low Medium/Low 60.6% (35.3% - 83.1%) 10 58.5% (32.2% - 82.3%) 9 100% (1/1) 1
United European Gastroenterology Journal 2(5S) A259
infiltration in the squamous epithelium of the esophagus (eosinophil number
P0460 LONG-TERM EFFICACY OF PROTON-PUMP INHIBITOR
15/HPF for patients using PPI and 20/HPF for patients not using PPI) and
THERAPY IN ADULT PATIENTS WITH PPI-RESPONSIVE
the absence of eosinophilic infiltration in corpus, antrum and duodenum.
ESOPHAGEAL EOSINOPHILIA
Reexamination with upper GI endoscopy was performed after a 2-month
proton pump inhibitor (PPI) therapy. Allergy test results were recorded. J. Molina- Infante1,*, J. Martinek2, M.D. Rivas3, J. Krajciova2, F.J. Moawad4,
Symptoms, serum IgE levels, allergy test positivity, Helicobacter pylori positivity, C. Martinez-Alcala1, B.D. van Rhjin5, J. Barrio6, J. Zamorano3,
endoscopic findings and histologic findings were compared between patients with A.J. Bredenoord5, E.S. Dellon7
1
EoE and those without EoE. Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain,
2
RESULTS: Sixty seven patients were included in the study. Of them, 15 were Gastroenterology, Institutu Klinicke a Experimentaln Medicny, Prague, Czech
male. Mean age of male and female patients were similar (p 0.129). Republic, 3Research Unit, Hospital San Pedro de Alcantara, Caceres, Spain,
4
Histopathological diagnosis of EoE was made in 7 patients (10.4%) and none Gastroenterology, Walter Reed National Military Medical Center, Bethesda,
of them had a history of PPI usage prior to diagnosis. Symptoms of GER and United States, 5Gastroenterology, Academic Medical Center, Amsterdam,
dysphagia were present in 71.4% and 28.57% of patients with EoE, while they Netherlands, 6Gastroenterology, Hospital Rio Hortega, Valladolid, Spain,
7
were present in 28.30% and 1.67% of those without EoE. In patients with Gastroenterology, Center for Esophageal Diseases and Swallowing, University of
histologically proven EoE (n 7), 4 had endoscopic findings compatible with North Carolina School of Medicine, Chapel Hill, United States
EoE (57%), 2 had grade A reflux esophagitis (28.6%) and 1 had normal endo- Contact E-mail Address: xavi_molina@hotmail.com
scopic findings. In patients without EoE (n 60), 1 had endoscopic findings
compatible with EoE and 3 had grade A reflux esophagitis. All patients with INTRODUCTION: Proton pump inhibitor-responsive esophageal eosinophilia
EoE had eosinophil number 20/HPF in tissue samples from upper and middle (PPI-REE) is diagnosed in at least a third of patients with a phenotype suggestive
portion of the esophagus. Serum IgE levels were significantly higher in patients of eosinophilic esophagitis (EoE). However, neither long-term response to PPI
with EoE than in those without EoE (281.59204.12 vs 105.75161.6) therapy in PPI-REE patients nor influencing factors have been evaluated yet.
(p 0.013). H. pylori positivity were similar (p 0.816). Allergy test positivity AIMS & METHODS: We aimed to determine the long-term efficacy of PPI
was 85.7% in patients with EoE and 50% in those without EoE. therapy in PPI-REE and its association to CYP2C19 genotype status.
CONCLUSION: GER is the most common symptom in patients with EoE. Retrospective multicenter study in PPI-REE adult patients, defined by consensus
EoE may be present even in patients with normal endoscopic findings guidelines. After a diagnosis of PPI-REE, PPI therapy was tapered and main-
Serum IgE levels are higher and allergy test positivity are more common in tained at the lowest dose with the target endpoint of clinical remission.
patients with allergic rhinitis and EoE. Histological remission was defined by 5 15 eos/HPF. Follow-up endoscopy
EoE is common in patients with allergic rhinitis. was performed at 12 months or longer on PPI maintenance dose. CYP2C19*2
It is important to question patients with respect to EoE symptoms in patients and CYP2C19*17 were determined from blood samples in Spanish patients.
with allergic rhinitis and high serum IgE levels, especially when corticosteroid RESULTS: 46 PPI-REE patients were included (mean follow-up time: 27 months
therapy is considered. (12-79)). While on clinical remission on low-dose PPI therapy, 34/46 (74%) had
Disclosure of Interest: None declared sustained histologic remission (19 double-dose PPI, 21 single-dose PPI). In 8/12
relapsers (66%) on maintenance PPIs, esophageal eosinophilia recurred exclu-
sively at the distal esophagus. Compared to patients with sustained PPI-response
P0459 CLINICAL AND HIGH RESOLUTION MANOMETRY DATA (n 13), this subset of distal relapsers showed borderline significant higher rates
SUPPORT THE HYPOTHESIS THAT PROTON PUMP INHIBITOR- of CYP2C19*2 rapid metabolizer genotype (100% vs. 53%, P 0.07) and reflux
RESPONSIVE ESOPHAGEAL EOSINOPHILIA REPRESENT A esophagitis at baseline (50% vs. 0%, P 0.08). All distal relapsers re-achieved
GERD-RELATED PHENOMENON histological remission after PPI-dose intensification (omeprazole 40 mg bid).
O. Bartolo1, C.de Cassan1, R. Caccaro1, F. Galeazzi1, T. Morbin1, S. Tolone1, CONCLUSION: 74% of adult PPI-REE patients had persistent clinico-histolo-
R. Salvador1, G.C. Sturniolo1, M. Costantini1, E. Savarino1,* gical remission on low-dose maintenance PPI therapy. While on clinical remis-
1
Department of Surgery, Oncology and Gastroenterology, University of Padua, sion, two thirds of relapsers showed eosinophilic inflammation limited to the
Padua, Italy distal esophagus. Baseline reflux esophagitis and a CYP2C19 rapid metabolizer
genotype were associated to this relapsing pattern and histological remission was
INTRODUCTION: Eosinophilic esophagitis (EoE) and Proton Pump Inhibitor- re-achieved after PPI-dose intensification in all patients.
response esophageal eosinophilia (PPI-REE) present similar phenotypic appear- Disclosure of Interest: None declared
ance, similar histopathology but different response to antisecretory therapy.
Thus, it is unclear if PPI-REE is a gastro-esophageal reflux disease (GERD)-
related phenomenon, a subtype of EoE, or a completely unique entity. High P0461 RESULTS OF LIQUID CYTOLOGY IN THE DIAGNOSIS AND
resolution manometry (HRM) is a novel technique that has been recently MONITORING EOSINOPHILIC OESOPHAGITIS
shown to provide new insights on GERD pathogenesis. In particular, eso- J. Rodr guez Sanchez1,*, B. Lopez Viedma1, E.de la Santa Belda1, P. Olivencia
phago-gastric junction (EGJ) morphology different from type I and weak peri- Palomar1, J. Olmedo Camacho1, M. Garc a Rojo2
stalsis have been strongly associated with GERD. 1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real,
AIMS & METHODS: We aimed to compare HRM features of patients with EoE 2
Pathology, Hospital de Jerez de la Frontera, Jerez de la Frontera, Spain
and PPI-REE. Consecutive patients with symptoms suggestive of EoE underwent Contact E-mail Address: joakinrodriguez@gmail.com
upper endoscopy in order to assess the presence of at least 15 eos/hpf on oeso-
phageal biopsies at mid/proximal esophagus and, then, were treated with twice- INTRODUCTION: Esophagoscopy with biopsy is considered the only method
daily PPI for at least 8 weeks. Thereafter, patients repeated upper endoscopy and for diagnosis and monitoring EoE. Therefore it is important to find out less
were stratified into two groups: EoE, in case of persistence of at least 15 eos/hpf invasive diagnostic methods. Regarding this issue, obtaining oesophageal cytol-
on oesophageal biopsies, and PPI-REE, in case of less than 15 eos/hpf and a 50% ogy is a way to explore to design in the future devices that allow to obtain
decrease from baseline. Patients underwent also HRM with a 5-min baseline samples without endoscopy and biopsy. The aim of the study was to analyze
recording to assess the EGJ and 10 single water swallows (5 mL) at 30-s intervals the accuracy of liquid-based cytology (LC) of the esophagus in the diagnosis and
to evaluate the esophageal peristalsis. Tracings were analyzed based on Chicago monitoring EoE histological activity.
Classification and each EGJ was classified as: Type I, no separation between the AIMS & METHODS: LC specimens were obtained in patients with active EoE
Lower Esophageal Sphincter and the Crural Diaphragm; Type II, minimal (AEoE) (15 eo/hpf) and EoE in remission (EoER) (515 eo/hpf) by oesopha-
separation (41 and 52 cm); Type III, 42 cm of separation. geal aspirate samples collected after instillation of 50 cc of saline solution suc-
RESULTS: Thirty-one patients were identified as having EoE [24M/7F; mean tioned by bronchioalveolar lavage system adapted to the gastroscope. The
age 28 (18-75)], whereas 10 patients were diagnosed with PPI-REE [9M/1F; mean samples were collected in Cytolyt solution (Hologic), obtaining Papanicolaou
age 38 (20-64)]. The two cohorts had similar dysphagia for solids (EoE 71% vs. and May-Grunwald/Giemsa that were assessed by two independent pathologists.
PPI-REE 66%, p 0.6979), bolus impaction (65% vs. 60%, p 1.000) and chest- EoE specimens were compared with LC obtained from patients with GERD.
pain (23% vs. 20%, p 1.000), but different heartburn (26% vs. 60%, RESULTS: Specimens of 36 patients (69.4% male, mean age 30.88 years) were
p 0.0485) and regurgitation (16% vs. 50%, p 0.0446). Endoscopic features included. AEoE (17, 47.2%), EoER (11, 30.5%) and GERD (8, 22.2%). Eo / hpf
had the same frequency between EoE and PPI-REE: rings (45% vs. 50%, proximal oesophageal biopsies (AEoE 28.58 vs EoER 2.09 vs GERD 1.25, p5
p 1.000), furrows (26% vs. 10%, p 0.4101) and plaques (23% vs. 40%, 0.001) and distal (AEoE 23.33 vs EoER 2.36 vs GERD 2.50, p 0.002). LC Eo/
p 0.4132). Esophageal strictures tended to be more frequent in EoE (52% vs. hpf (AEoE 9.23 vs EoER 1.54 vs GERD 2, p 0.01). Linear correlation between
10%, p 0.0592). At HRM testing, EoE patients had higher mean integrated Eo/hpf average biopsy and LC Eo/hpf: r 0.57, p 5 0.001. For diagnosis of
relaxation pressure [9 (2-16) vs. 6 (2-16), p 0.0616] and LES basal pressure [26 EoE, 3 Eo/hpf in LC obtained a Sensitivity 70%, specificity 81%, PPV 86%
(10-54) vs. 17 (1-34), p 0.0388], but similar mean distal contraction integral and NPV 60% (AUC 0.81, p 0.01). For detection of AEoE, 3 Eo/hpf in LC
[1094 (522-2653) vs. 1763 (483-5281), p 0.5613] compared to patients with obtained a sensitivity 70%, specificity 82%, PPV 81% and NPV 66%
PPI-REE. Type II and III EGJs were less common in EoE than in PPI-REE (AUC 0.87, p 0.001).
patients (9% vs. 50%, p 0.0129). Manometric diagnoses were similar between CONCLUSION: LC in oesophageal aspirate obtained by a cutoff in 3 eo/hpf
EoE and PPI-REE: weak peristalsis including large or small breaks and frequent seems to be effective for the diagnosis and monitoring activity in EoE. These
failed peristalsis (16% vs. 40%, p 0.2221), absent peristalsis (3% vs. 10%, results open the door to the development of non endoscopic devices that allow us
p 1.0000) and distal esophageal spasm (3% vs. 0%, p 1.0000). the diagnosis and monitoring of disease noninvasively.
CONCLUSION: Typical reflux symptoms and HRM features GERD-related are Disclosure of Interest: None declared
more common in patients with PPI-REE than in patients with EoE. These data
support the hypothesis that PPI-REE may represent a GERD-related phenom-
enon rather than a subtype of EoE or a separate entity. Further larger studies are
needed to confirm these findings.
Disclosure of Interest: None declared
A260 United European Gastroenterology Journal 2(5S)
AIMS & METHODS: The aim of this study was to investigate both distal and
P0462 CORRELATION BETWEEN CLINICAL, HISTOLOGIC AND
proximal, oropharyngeal acid exposure, with a new device, in patients with non-
ENDOSCOPIC ACTIVITY IN EOSINOPHILIC OESOPHAGITIS.
erosive reflux disease (NERD) with and without globus.
PRELIMINARY RESULTS OF SENECA PROJECT (SPANISH STUDY
A group of 37 patients affected by NERD was enrolled. The presence of reflux
OF ENDOSCOPY AND EOSINOPHILS CORRELATION
symptoms was evaluated and severity was graduated by VAS. In eight patients,
ASSESSMENT)
globus was the main symptom; in the other 29, globus was not present and they
J. Rodr guez Sanchez1,*, J. Molina Infante2, J. Barrio Andres3, I. Perez were thus considered the control group. Patients underwent standard stationary
Mart nez4, A. Bouhmidi Assakali5, J.A. Olmos Jerez6, B. Madrigal Rubiales7, esophageal manometry (6 channelssleeve) and 24-hr pH-impedance esophageal
E.de la Santa Belda1, B. Lopez Viedma1, J. Olmedo Camacho1 monitoring (Sleuth, Sandhill Scientific) combined with 24-hr oropharyngeal pH
1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real, monitoring (Restech Dx-pH Measurement System).
2
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 3Gastroenterology, RESULTS: Distal esophageal acid exposure (pH 54), number of acidic and
Hospital del Rio Hortega, Valladolid, 4Gastroenterology, Hospital Universitario weakly acidic reflux episodes and proximal extension of refluxate were similar
Central de Asturias, Oviedo, 5Gastroenterology, Hospital Santa Barbara, between patients with and without globus. On the contrary, patients with globus
Puertollano, 6Gastroenterology, Hospital Rey Juan Carlos, Mostoles, 7Pathology, showed a significantly longer oropharyngeal exposure to pH55.5 (total duration
Hospital del Rio Hortega, Valladolid, Spain of acid exposure: 222 min 230 min vs 47 min 88 min, p50.05; and percent of
Contact E-mail Address: joakinrodriguez@gmail.com recording: 16.0716.2% vs 3.566.84%, p50.05), compared to patients without
globus; the longest episode of oropharyngeal acid exposure was significantly
INTRODUCTION: Esophagoscopy with biopsies is considered the gold stan- longer in patients with globus than in patients without globus (110 min 115
dard for diagnosis and monitoring EoE. This is due to lack of correlation min vs 15 min 25 min; p50.05). A higher score for heartburn was evident in
between histology, endoscopy and clinical manifestations of the disease. A the group of patients without globus (3.453.31 vs 1.311.44, p50.05); no
novel endoscopic classification for assessment of eosinophilic esophagitis (EoE) difference was found in regurgitation, cough, sore throat, or thoracic pain
activity has been recently proposed (EREFs). We aimed to address the correla- score. Finally, the prevalence of esophageal motor disorders was similar in the
tion of clinical and endoscopic EoE activity scores with histological response two groups.
after different therapeutic interventions. CONCLUSION: Oropharyngeal acid exposure could have an important patho-
AIMS & METHODS: Spanish multicenter prospective study in consecutive physiological role in globus onset. Oropharyngeal pH monitoring seems a more
patients with EoE, according to consensus guidelines. Clinical (Dysphagia accurate diagnostic tool than the standard 24-hr pH-impedance study to define
Symptom Score (DSS) Scale) and endoscopic (EREFS) disease activity, along the role of acid exposure in this subgroup of patients.
with eosinophil peak count, were assesed at baseline and after topical steroids or REFERENCES
elimination diet, including food reintroductions. Histological remission was 1. Selleslagh M, van Oudenhove L, Pauwels A, et al. Nat Rev Gastroenterol
defined by 5 10 eos/HPF at both distal and proximal esophagus. Patients Hepatol 2014; 11: 220-233.
were subclassified: Group A (Baseline), Group B (No histological remission 2. Chevalier JM, Brossard E and Monnier P. 2003; 260: 273-276.
after therapy/food reintroduction) and Group C (Histological remission after Disclosure of Interest: None declared
therapy/food reintroduction).
RESULTS: 79 patients undergoing 128 upper endoscopies have been included so
far (77.2% male, age 34.7 years-old, dysphagia 100%). Group A: 47 (36.7%), P0464 UNDERSTANDING THE CAUSE OF PERSISTENT GERD
Group B: 61 (47.7%) and Group C: 20 (15.6%). DSS score was significantly SYMPTOMS DESPITE PROTON PUMP INHIBITOR THERAPY:
higher in Group A (A 7.16, B 5.15, C 3.70; p 0.006), but no differences IMPEDANCE-PH MONITORING REVISITED
were observed between groups B and C (p 0.12). Regarding endoscopic find- D. Ang1,*, I. Hussain1, F. Kwong Ming1
ings, inflammatory features were significantly decreased after histological remis- 1
Gastroenterology, Changi General Hospital, Singapore, Singapore
sion (furrows: A 63.8%, B 72.1%, C 40%; p 0.034 / exudates (grade 2): Contact E-mail Address: ang_daphne@yahoo.com
A 10.6%, B 18%, C 5%;p 0.002), but not fibrostenotic features (pseudor-
ings: A 68.1%, B 55.4%, C 55%;p 0.44/stricture: A 10.6%, B 9.8%, INTRODUCTION: Non-response to proton pump inhibitor (PPI) therapy in
C 5%;p 0.75). Mucosal edema was common at baseline and persistent patients with reflux symptoms and a normal gastroscopy remains a challenge.
regardless of histological remission (A 61.7%, B 78.7%, C 60%; p 0.09). Impedance-pH (MII-pH) monitoring clarifies the symptom profile and evaluates
CONCLUSION: EoE clinical activity significantly decreased after different ther- patients objectively for acid reflux (AR) and non-acid reflux (NAR).
apeutic interventions, with no differences between patients showing eosinophilia AIMS & METHODS: To study MII-pH characteristics in patients referred for
remission or persistence after therapy. Histological remission was correlated with GERD evaluation who remain symptomatic despite PPIs, and study mechanisms
significant decrease of inflammatory endoscopic features, but not of fibrostenotic related to persistent symptoms. Methods: Between January 2009-December 2013,
findings. Mucosal edema was mostly persistent regardless of histological remis- consecutive patients with typical symptoms (group 1); atypical symptoms (group
sion, suggesting it might belong to the fibrotic remodelling spectrum. 2) and non-cardiac chest pain (NCCP, group 3) underwent 24 hour MII-pH after
REFERENCES PPI washout. Prevalence of (i) oesophageal acid exposure time (AET)44.2%; (ii)
Disclosure of Interest: None declared bolus exposure (BE41.4%), (iii) high reflux numbers (473) and/or (iv) positive
symptom marker based symptom index (SI 50%) and/or symptom association
probability (SAP 95%) for AR or NAR events was compared between groups
P0463 IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE, by chi-square and student t-testing.
GLOBUS IS ASSOCIATED WITH ABNORMAL OROPHARYNGEAL RESULTS: 208 patients (80M, mean age 45.9 12.5) were studied (Table 1).
ACID EXPOSURE Elevated AET occurred in 24 (11.5%). 120 (57.7%) recorded a positive study on
M. Di Stefano1, C. Mengoli1,*, M. Bergonzi1, E. Pagani1, E. Miceli1, MII-pH evaluation despite a normal overall AET. Group 1 and 3 patients had
G.R. Corazza1 significantly more symptomatic AR events (p50.05) compared to group 2.
1
1st Department of Internal Medicine, IRCCC Policlinico S. Matteo, University of Symptomatic NAR related events did not differ significantly different between
Pavia, Pavia, Italy groups. Patients with a positive symptom association for AR events were more
Contact E-mail Address: m.distefano@unipv.it likely to have abnormal BE (p 0.01) and abnormal reflux numbers (p50.05).
Table 1.
INTRODUCTION: Globus, a persistent or intermittent non-painful sensation of CONCLUSION: Use of MII-pH in PPI non-responders identifies AR and NAR
a lump or foreign body in the throat, is frequently associated with gastroesopha- events and serves as an important diagnostic modality to evaluate the symptom
geal reflux disease (GERD): it is estimated that up to 68% of GERD patients profile and guide appropriate therapy, which may extend beyond PPIs.
suffer from globus. However, previous esophageal pH and pH-impedance studies Disclosure of Interest: None declared
failed to define a causative role of acid or non-acid reflux in globus
pathophysiology.
Table to P0464
Group 1 Group 2
Typical Atypical Group 3
(N39M,55F) (N34M,50F) Non cardiac chest pain (N7M,23F)
P0473 IMPEDANCE-PH REFLUX PATTERNS IN PATIENTS WITH NON- P0475 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS
EROSIVE REFLUX DISEASE AND EROSIVE REFLUX DISEASE WITH DIFFERENT FORMS OF GASTROESOPHAGEAL REFLUX
V. Kaibysheva1,*, A. Trukhmanov1, V. Ivashkin1 DISEASE: NON-EROSIVE REFLUX DISEASE, EROSIVE
1
FIRST MOSCOW STATE MEDICAL UNIVERSITY, Moscow, Russian ESOPHAGITIS AND BARRETTS ESOPHAGUS
Federation Y. Evsyutina1,*, A. Truhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1
1
Sechenov First Moscow State Medical University., 2Moscow State University of
INTRODUCTION: Non-erosive reflux disease (NERD) and erosive reflux dis- Medicine and Dentistry, Moscow, Russian Federation
ease (ERD) are the most common phenotypic presentations of gastroesophageal Contact E-mail Address: uselina@mail.ru
reflux disease.
AIMS & METHODS: To assess acid and non-acid reflux patterns in patients INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most
with NERD and ERD using combined esophageal pH-impedance monitoring. common diseases and, according to recent epidemiological studies, clinical and
133 patients (off acid-suppressive medication) complaining of reflux symptoms endoscopic GERD symptoms can be detected in 8-25% of the population
were underwent diagnostic work-up including upper gastrointestinal endoscopy depending on country, race and gender. In the Russian Federation, the preva-
and ambulatory 24-h esophageal pH-impedance monitoring. According to data lence of GERD reaches 11-15%. Despite improvements in diagnosis and treat-
of endoscopy patients were graded to NERD (90 patients (67.6%)) and ERD (43 ment of GERD, there are still many unresolved issues. GERD is characterized by
patients, (32.3%)). disorders in immune response presented by misbalanced cellular (Th1) and
RESULTS: When compared to NERD, ERD patients showed a higher incidence humoral (Th2) parts of immune response which depend on expression of
of acid reflux episodes in 24 h (72 (43;103) vs. 47 (21; 68), p50.05) and higher cytokines.
duration of total esophageal acid exposure (10.8% (6.6; 19.4) vs. 4.5% (1.4;7.1), AIMS & METHODS: To determinate the circulating level of cytokines in
p50.05). Reflux-related acid exposure (pH drops associated with reflux detected patients with different forms of gastroesophageal reflux disease (GERD): non-
by impedance) in ERD patients was twofold higher than in NERD patients erosive reflux disease (NERD), erosive esophagitis and Barretts esophagus. In
(2.2% (1.6; 2.9) vs. 1.08% (0.5;1.9), p50.05). Similarly, reflux-related alkaline prospective cohort study were included 55 patients and randomized in 4 groups:
exposure (pH elevation (pH47) [1] associated with reflux detected by impe- group 1 - 20 patients with NERD (11 men, 9 women; average age 37.75 12.04),
dance) was also higher in ERD patients (1.3% (0.8; 1.7) vs. 0.13% (0; 0.49), group 2 20 patients with erosive esophagitis (13 men, 7 women; average age
p50.05). In contrast to ERD patients, NERD patients had significantly higher 38.3312.55), 3 group 5 patients with Barretts esophagus (5 men; average age
(1.08% (0.46; 1.86) vs. 0.04% (0; 0.2), p50.05) reflux-related weakly acid 34.259.88) and group 4 (control group) 10 healthy volunteers (5 men, 5
exposure (pH drops (pH57) [1] associated with reflux detected by impedance). women; average age 33.379.39). In all enrolled patients were performed the
When compared with accepted normal values [1] NERD patients had signifi- upper gastrointestinal endoscopy and the determination of plasma cytokines
cantly higher mean number of weakly-acid refluxes (41(28;55)). Episodes of (IL-4, IL-8, IL-10, IFN-, TNF-) by flow cytometry. Statistical analyses were
weakly-acid reflux in NERD patients happened mainly at postprandial period. performed using SPSS 17.0 statistical package.
Median acid (chemical) clearance time was twice higher in ERD patients (120 RESULTS: In patients with erosive esophagitis the median rate of IL-8 was 17.54
(76; 166) s.) in comparison to NERDs (60 (49; 116) s.) group. Meanwhile, there pg/mL (95% CI, 15.83 to 19.24), IFN- 72.97 pg/mL (95% CI, 15.24 to 130.7),
was no significant difference in median volume clearance time between ERD and TNF- 16.31 pg/mL (95% CI, 14.03 to 18.58). The expression of IL-8 in patients
NERD patients (23.3 (20.3; 27.6) vs. 19.1 (16.2; 23.6) s, p40.05). In both GERD with erosive esophagitis was 2,3 times higher than in patients with NERD
groups median volume clearance was significantly faster than median chemical (o 0.02) and 5,04 times higher than in patients with Barretts esophagus
clearance (p50.05). Meanwhile, esophageal mucosas exposure to reflux volume (o 0.02). The expression of IFN- in patients with erosive esophagitis was
during 24 hour period, as assessed by impedance monitoring, was similar in both 2,58 times higher than in patients with NERD (o 0.03) and 27,03 times
ERD and NERD patients (3.8% vs.3.1%, p40.05). higher than in patients with Barretts esophagus (o 0.03). The expression of
CONCLUSION: While ERD and NERD patients have similar total esophageal TNF- in patients with erosive esophagitis was 2,22 times higher than in patients
bolus exposure, ERD patients have an increased level of esophageal acid expo- with NERD (o 0.04) and 2,26 times higher than in patients with Barretts
sure and reflux-related esophageal acid and alkaline exposure due to excessive esophagus (o 0.05). In patients with Barretts esophagus the median rate of
number of acid and alkaline reflux as well as long duration of chemical clearance. IL-4 was 14.95 pg/mL (95% CI, 12.75 to 17.15), IL-10 9.2 pg/mL (95% CI,
Similarly, NERD patients have excessive number of postprandial weakly-acid 8.75 to 9.68). The expression of IL-4 in patients with Barretts esophagus was
reflux and increased level of reflux-related esophageal weakly-acid exposure. 2.36 times higher than in patients with erosive esophagitis (o 0.03) and 3.33
Consequently, this observation tends to support a notion that weakly-acid times higher than in patients with NERD (o 0.05). The expression of IL-10 in
reflux is less damaging to esophageal mucosa than acid reflux. Significant patients with Barretts esophagus was 1.59 times higher than in patients with
A264 United European Gastroenterology Journal 2(5S)
erosive esophagitis (o 0.03) and 2.53 times higher than in patients with NERD
P0478 30 MAY BE MORE APPROPRIATE THAN 45 FOR THE
(o 0.03).
CRITICALLY ILL PATIENTS RECEIVING MECHANICAL
CONCLUSION: In patients with erosive esophagitis in comparison with NERD
VENTILATION AND ENTERAL NUTRITION
and Barretts esophagus we found overexpression of pro-inflammatory cytokines
(IL-8, IFN-, TNF-), that reflects their role in the Th1 immune response. In Y. Leng1,*, Y. Liiu1
1
patients with Barretts esophagus in comparison with NERD and erosive eso- Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
phagitis was the overexpression of anti-inflammatory cytokines (IL-4, IL-10), China
that reflects their role in the Th2 immune response. Contact E-mail Address: lengyuxin1980@126.com
Disclosure of Interest: None declared
INTRODUCTION: Semi-recumbent position plays a pivotal role in prophylaxis
for the development of ventilator-associated pneumonia in the critically ills. In
P0476 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS the present study, we aimed to find a more appropriate semi-recumbent position
WITH REFRACTORY TO PROTON PUMP INHIBITORS between 30 and 45 for the critically ill patients receiving mechanical ventilation
GASTROESOPHAGEAL REFLUX DISEASE and enteral nutrition on balancing their advantages in ventilator-associated
Y. Evsyutina1,*, A. Trukhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1 pneumonia (VAP) prophylaxis and disadvantages in organ protection.
1
Sechenov First Moscow State Medical University, 2Moscow State University of AIMS & METHODS: A prospective, randomized clinical study to investigate the
Medicine and Dentistry, Moscow, Russian Federation effect of different HOB (30 or 45 ) on all extent gastroesophageal reflux, prox-
Contact E-mail Address: uselina@mail.ru imal gastroesophageal reflux and development of VAP; intra-abdominal pressure
(IAP), hemodynamic parameters [mean arterial pressure (MAP), abdominal per-
INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most fusion pressure (APP), filtration gradient (FG)] and development of organ failure
common diseases and, according to recent epidemiological studies, clinical and was conducted on 86 consecutive patients admitted to a comprehensive intensive
endoscopic GERD symptoms can be detected in 8-25% of the population care unit (ICU).
depending on country, race and gender. In the Russian Federation, the preva- RESULTS: No significant differences in the incidence of VAP and number of all
lence of GERD reaches 11-15%. 50-60% of patients suffernig from refractory extent reflux were found between 30 group and 45 group. However, the number
GERD who despite the received therapy do not have improved clinical and and percentage of proximal reflux in 45 group were unexpectedly higher than
endoscopic picture, than can be explained with misbalance of Th1 and Th2 30 group (Number: acid: p 0.022; weakly acidic: p 0.257; non acid:
parts of immune response which depend on expression of cytokines. p 0.168; Percentage: acid: p 0.000; weakly acidic: p 0.000; non acid:
AIMS & METHODS: To determinate the circulating level of cytokines in p 0.000). Patients in 45 group had a trendency to develop new onset organ
patients with GERD depending on the response to standard proton pump inhi- failure more easily (45 vs. 30 : 11/42 vs. 5/44, p 0.077), accompanied with
bitors (PPI) therapy. In prospective cohort study were included 50 patients ran- higher IAPs measurement (17.645.32 mmHg vs.14.985.34 mmHg, p 0.023)
domized in 3 groups: group 1 - 20 patients with non- refractory GERD (the and lower MAP, APP, and FG (MAP, p 0.001; APP, p 0.000; FG, p 0.000).
complete response to standard PPI therapy during 8 weeks which was defined CONCLUSION: For mechanically ventilated patients with enteral nutrition,
on disappearance of complaints) - 11 men, 9 women; average age 37.6610.02, keeping the HOB at 45 doesnt show superiority over 30 . Elevating the HOB
group 2 - 20 patients with refractory GERD (the partial response or absence of from 30 to 45 cant reduce the incidence of VAP effectively but brings new
response to standard PPI therapy during 8 weeks which was defined on main- onset organ failure more easily.
tenance of complaints) - 12 men, 8 women; average age 38.259.42, and group 3 REFERENCES
(control group) 10 healthy volunteers (5 men, 5 women; average age 1. Leng YX, Zhang N, Zhu X, et al. Combined effects of elevated body position
34.259.88). In all enrolled patients were performed the upper gastrointestinal on gastroesophageal reflux and intra-abdominal pressure in mechanical venti-
endoscopy and the determination of plasma cytokines (IL-4, IL-8, IL-10, IFN-, lated patients. Chin Crit Care Med 2011; 9: 534-537.
TNF-) by flow cytometry. Statistical analyses were performed using SPSS 17.0 2. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the interna-
statistical package. tional conference of experts on intra-abdominal hypertension and abdominal
RESULTS: In patients with refractory to PPI gastroesophageal reflux disease in compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732.
comparison with patients with non- refractory GERD were higher levels of IL-8 3. Cheatham ML, Malbrain ML, Kirkpatrick A, et al. Results from the interna-
(18.10 pg/mL vs. 6.66 pg/mL; o 0.02), IFN- (61.7 pg/mL vs. 24.10 pg/mL; tional conference of experts on intra-abdominal hypertension and abdominal
o 0.022), TNF- (14.77 pg/mL vs. 7.97 pg/mL; o 0.03). The high level of IL-8 compartment syndrome: II. Recommendations. Intensive Care Med 2007; 33:
is associated with relapse of erosive esophagitis within 2 years (p0.01). 951-962.
CONCLUSION: In patients with refractory to PPI gastroesophageal reflux dis- 4. Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring:
ease in comparison with non- refractory GERD was overexpressed IL-8, IFN-, review and consensus report on detection and definitions of acid, non-acid,
TNF-. Thus the high level of IL-8 was correlated with recurrent erosive eso- and gas reflux. Gut 2004; 53: 1024-1031.
phagitis within 2 years, and this cytokine can be used as the marker defining the Disclosure of Interest: None declared
prediction of a course of a disease.
Disclosure of Interest: None declared
P0479 DETECTION OF BURIED BARRETTS GLANDS AFTER
RADIOFREQUENCY ABLATION (RFA) WITH VOLUMETRIC
P0477 IS THERE A REAL RISK OF THE LONG TERM MEDICAL LASER ENDOMICROSCOPY (VLE)
TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE? A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, D.J. Faber2, T.G.
R. Kroupa1,*, M. Jecmenova1, M. Dastych1, J. Dolina1, A. Hep1 van Leeuwen2, B.L. Weusten1, S.L. Meijer3, J.J. Bergman1, W.L. Curvers1
1 1
Department of Gastroenterology and Internal medicine, University Hospital Brno Gastroenterology and hepatology, 2Biomedical Engineering, 3Pathology,
and Faculty of Medicine Masaryks University, Brno, Czech Republic Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: rkroupa@fnbrno.cz Contact E-mail Address: a.swager@amc.uva.nl
INTRODUCTION: A prolonged acid inhibition may be associated with the INTRODUCTION: The prevalence and clinical relevance of Buried Barretts (BB)
important consequences like nutritional defects, increased risk of fractures or epithelium after radiofrequency ablation (RFA) in Barretts oesophagus (BO) is
infections and development of gastric polyps. The majority of data originate questioned. Recent studies using small optical coherence tomography (OCT)
from retrospective epidemiological studies only. catheters for scanning underneath the neosquamous epithelium demonstrated a
AIMS & METHODS: The aim of the study was to prospectively evaluate the high prevalence of tissue structures that might correspond to BB. Histological
incidence of the possible risk events among patients during the long term acid correlation, however, is lacking. Volumetric Laser Endomicroscopy (VLE) is a
suppressive treatment. novel balloon-based OCT imaging technique that provides a 6-cm long circumfer-
A prospective observational study in gastroesophageal reflux disease (GERD) ential volumetric scan of the oesophageal wall layers to a depth of 3 mm with a
patients requiring a long term treatment with proton pump inhibitors (PPI) was resolution comparable to low-power microscopy.
performed. The development of fractures, pulmonary and enteric infection and AIMS & METHODS: To evaluate if post-RFA subsquamous structures,
gastric polyps were recorded. The results were compared with control group detected with VLE, actually correspond to BB and to pursue direct histological
recruited from endoscopy outpatients without any history of the proton pump correlation of VLE images.
inhibitor intake. In-vivo VLE was performed to detect subsquamous structures suspicious for BB
RESULTS: The cohort of 230 patients on maintenance GERD treatment (44% in patients with 100% endoscopic regression of dysplastic Barretts epithelium
female, age 53.8 14.4) was followed-up for 7.1 years (1631 patient-years). after RFA. Areas with suspicious subsquamous VLE structures were marked
Results were matched with 209 controls. The users of PPI were equally likely with electrocoagulation after which in-vivo VLE was repeated to confirm that
to develop fractures 3.5% (OR 0.53; 95% CI 0.21-1.32) and bronchopneumonia the correct area was demarcated. These areas were subsequently resected endos-
0.4% (OR 0.29; 95% CI 0.03-2.87) as the controls. The development of infectious copically, followed by immediate ex-vivo VLE scanning to reconfirm the pre-
diarrhea was less frequent in PPI users than in controls (OR 0.11; 95% CI 0.01- sence of the subsquamous VLE structures. Extensive histological sectioning was
0.09). No case of hypomagnesemia was diagnosed in PPI users. Only a develop- then performed and all histopathology slides were evaluated by an expert BO
ment of fundic gland polyps was associated with PPI use in 12.6% of exposed pathologist (blinded for VLE images).
patients (OR 2.7; 95% CI 1.07-6.63). RESULTS: In 17 patients, 13 areas with suspicious subsquamous structures were
CONCLUSION: A long term acid suppressing treatment of gastroesophageal seen on in-vivo VLE and resected. Ex-vivo VLE of these 13 ER specimens
reflux disease did not increase the likelihood of fractures, infectious diarrhea, reconfirmed the presence of these subsquamous structures in 12 ER specimens.
bronchopneumonia and hypomagnesemia. Our results could encourage the Extensive histological sectioning of these areas showed BB in one area. The other
importance of prospective evaluation of risk events in subgroups according to subsquamous VLE structures corresponded to dilated (ducts of) (sub)mucosal
the indication of PPI use. glands or blood vessels.
Disclosure of Interest: None declared CONCLUSION: VLE may potentially detect BB under endoscopically normal
appearing neosquamous epithelium. However, most post-RFA subsquamous
structures identified by in-vivo VLE did not correspond to BB. Further studies
United European Gastroenterology Journal 2(5S) A265
are required to identify VLE features that allow for differentiation of BB from
P0481 SENSITIVITY TO OESOPHAGEAL MULTIMODAL
normal subsquamous structures.
STIMULATION IN BARRETTS OESOPHAGUS PATIENTS
Disclosure of Interest: None declared
C. Lottrup1,*, A.L. Krarup1, P. Ejstrud2, M. Ostapiuk2, A.M. Drewes1
1
Mech-Sense, Department of Gastroenterology & Hepatology, 2Department of
P0480 VOLUMETRIC LASER ENDOMICROSCOPY IN BARRETTS Surgery, Aalborg University Hospital, Aalborg, Denmark
OESOPHAGUS: A STUDY ON HISTOLOGICAL CORRELATION Contact E-mail Address: chlo@rn.dk
A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, G.J. Tearney3,
C.L. Leggett4, B.L. Weusten1, D.J. Faber2, T.G. van Leeuwen2, S.L. Meijer5, INTRODUCTION: Oesophageal sensitivity to mechanical and acid stimulation
W.L. Curvers1, J.J. Bergman1 in Barretts oesophagus has previously been shown to be decreased.
1
Gastroenterology and hepatology, 2Biomedical Engineering, Academic Medical AIMS & METHODS: The aim was to investigate the oesophageal sensitivity in
Center, Amsterdam, Netherlands, 3Pathology and Wellman Centre for Barretts oesophagus using a multimodal (mechanical, thermal, electrical, acid)
Photomedicine, Massachusetts General Hospital, Boston, 4Division of pain model.
Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States, Twenty-two patients with Barretts oesophagus (mean age: 64.6 years) were
5
Pathology, Academic Medical Center, Amsterdam, Netherlands compared to twelve healthy controls (mean age: 54.3 years) using oesophageal
Contact E-mail Address: a.swager@amc.uva.nl multimodal pain stimulation following upper endoscopy. A probe with a poly-
urethane bag was placed in the lower oesophagus. The probe was then used to
INTRODUCTION: Volumetric laser endomicroscopy (VLE) is a novel balloon- apply mechanical, thermal, and electrical stimulation as well as a modified
based optical coherence tomography (OCT) imaging technique. It provides a 6- Bernstein test with infusion of 0.1 N HCl. All stimulations were stopped when
cm long circumferential volumetric scan of the oesophageal wall layers to a depth the subject felt moderate pain, defined as 7 out of 10 on a visual analogue scale
of 3 mm with a resolution that is comparable to low-power microscopy. VLE has (VAS 7).
the potential for detection and delineation of early neoplastic lesions in Barretts RESULTS: Five of the Barretts oesophagus patients had oesophagitis (Los
oesophagus (BO). In order to investigate this, it is important that structures Angeles grade A or B) on endoscopy.
identified on VLE can be correlated with histology and -vice versa- that of For mechanical stimulation, the bag distension volume evoking VAS 7 was
areas containing early neoplasia on histology the corresponding VLE features significantly higher in the Barretts group (mean volume 42 vs 28 mL,
can be studied. Most previous OCT studies lack such a direct correlation between P 0.006). For thermal stimulation, there was a non-significant tendency in the
histology and OCT images. Barretts group towards a higher area under the curve to reach VAS 7 (949 vs.
AIMS & METHODS: To investigate the optimal approach for one-to-one cor- 677 s*oC, P 0.14). The stimulus required to reach VAS 7 during electrical
relation of VLE images with histology. stimulation was significantly higher in the Barretts group (32.7 mA vs. 21.9
BO patients with and without early neoplasia underwent endoscopic resection mA, p 0.03. During the modified Bernstein test, the acid volume required to
(ER) of areas marked in-vivo with electrocoagulation markers (ECM). reach VAS 7 or a maximum infusion volume of 200 mL was lower in the
Subsequently ER specimens underwent additional ex-vivo marking with several Barretts group (mean 77 vs. 127 mL, P 0.03). The time passed before feeling
different markers (ink, pin, ECM) followed by ex-vivo VLE scanning. Tissue the first burning sensation during acid infusion was shorter in the Barretts group,
blocks were carefully sectioned guided by the placed markers. After further but just failed to be significant (181 vs. 329 seconds, P 0.056).
histological processing a histopathology slide was sectioned from each block. The referred pain area defined by the subject immediately after sensing VAS 7
When necessary, extensive sectioning of tissue blocks was performed in order was insignificant between groups (P 4 0.05) for all 4 stimulation modalities.
to visualize all markers that were included in the tissue block on histology. All CONCLUSION: Barretts oesophagus patients showed hyposensitivity to
histopathology and VLE slides were evaluated by 2 researchers and considered a mechanical, thermal and electrical stimulation, but hypersensitivity to acid sti-
match if a) 2 markers were visible on both modalities and b) mucosal patterns mulation. This is to some degree different from earlier findings, but the latter
aside from these markers matched on both histology and VLE. All slides were finding could indicate a sensitisation to acid because of oesophagitis underlying
evaluated by an expert BO pathologist. the disease.
RESULTS: From 16 ER specimens (overall diagnosis: 7 non-dysplastic BO, 9 Disclosure of Interest: None declared
dysplastic BO (1 LGD, 4 HGD, 4 EAC)) 120 tissue blocks were sectioned of
which 57 contained multiple markers and thus could potentially be matched with
VLE. Based on several combinations of these markers in total 14 histology-VLE P0482 SURVEILLANCE IN PATIENTS WITH BARRETTS ESOPHAGUS:
matches could ultimately be constructed. Markers that achieved the best yield of A COST-EFFECTIVENESS ANALYSIS
matches respectively were: in-vivo placed ECMs (8 matches with 12 markers), F. Kastelein1,*, S.van Olphen1, E. Steyerberg2, M. Spaander1, C. Looman2,
pins (7 with 11), and ink (4 with 5). Histopathological evaluation was not hin- E. Kuipers1, M. Bruno1, E.de Bekker-Grob2 on behalf of ProBar-study group
dered by marker use. In this pilot study the last 6 ER specimens yielded 9/14 1
Gastroenterology and Hepatology, 2Public health, ERASMUS UNIVERSITY
matches demonstrating a clear learning curve due to methodological improve- MEDICAL CENTER, Rotterdam, Netherlands
ments in marker placement and tissue block sectioning. Contact E-mail Address: f.kastelein@erasmusmc.nl
CONCLUSION: One-to-one correlation of VLE and histology is complex but
feasible. The groundwork laid in this study will provide high-quality histology- INTRODUCTION: Surveillance is recommended for Barretts esophagus (BE)
VLE correlations that will allow further research on VLE structures and VLE to detect esophageal adenocarcinoma (EAC) at an early stage.
features of early neoplasia in BO. AIMS & METHODS: The aim of this study was to evaluate the cost-effective-
Disclosure of Interest: A.-F. Swager: None declared, D. Boerwinkel: None ness of surveillance intervals and treatment strategies. 714 BE patients were
declared, D. de Bruin: None declared, G. Tearney Financial support for research included in a multicenter prospective cohort study and followed during surveil-
from: Ninepoint Medical, Other: Massachusetts General Hospital has a licensing lance according to the ACG guidelines. We used a multi-state-Markov model to
arrangement with Ninepoint Medical. Dr. Tearney has the rights to receive roy- calculate misclassification and true progression rates from no dysplasia (ND) to
alty income from this licensing arrangement., C. Leggett: None declared, B. low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC. These pro-
Weusten Financial support for research from: Ninepoint Medical, Other: Has gression rates were incorporated in a decision-analytic model, which included
rights to receive royalty income from licensing arrangement between costs and quality of life data associated with different surveillance strategies.
Massachusetts General Hospital and Ninepoint Medical, D. Faber: None We evaluated different surveillance intervals for ND and LGD, endoscopic
declared, T. van Leeuwen: None declared, S. Meijer: None declared, W. mucosal resection (EMR) followed by radiofrequency ablation (RFA), RFA
Curvers: None declared, J. Bergman: None declared alone or esophagectomy for HGD or early EAC and esophagectomy with neoad-
juvant chemoradiotherapy for advanced EAC. The incremental cost-effectiveness
ratio (ICER) was calculated in costs per quality-adjusted life year (QALY). The
willingness-to-pay threshold was set at E35.000 per QALY gained.
P0482
Time of occurrence
Diagnosis of gastric after diagnosis of type
PatientGenderAge, yearsType of lesion cancer Locali-zation IGC, months (years) Outcome
multistep process passing from hyperplasia to dysplasia and then to carcinoid. more disease progression. One metachronous recurrence occurred after complete
Epidemiological data suggest that AG is associated not only with T1-GCs, but ER, and it was treated by ER.
also with intestinal-type gastric cancer. The occurrence of gastric cancer in AG CONCLUSION: ER can be used as an effective method as treatment for a small
pts with type I gastric carcinoids has not yet been described. sized and low grade foregut NETs. However, additional treatment should be
AIMS & METHODS: The aim of this study was to describe in a retrospective considered in the patients who diagnosed as NEC from histological result after
case-series the occurrence of gastric cancer in AG pts with type I gastric carcinoid endoscopic treatment because it has high risk of recurrence rate.
in a single tertiary referral center. Between 1994 and 2012, 17 new cases of T1- Disclosure of Interest: None declared
GCs were diagnosed amongst a cohort of AG pts. The clinical charts of these 17
T1-GCs pts were retrospectively evaluated for the occurrence of gastric cancer at
follow-up (median 4.2 years, range 0.5-13). AG diagnosis was based on the P0503 SELF-EXPANDABLE METAL STENTS VERSUS SURGICAL
presence of hypergastrinaemia and atrophy of the body mucosa. Diagnosis of GASTROENTEROSTOMY FOR PALLIATION OF MALIGNANT
T1-GCs was performed when enterochromaffin-like cells proliferation was DUODENAL OBSTRUCTION
4500m (WHO 2010 criteria). H. Saito1,*, M. Ito1, M. Yoshioka1, S. Saito1, F. Masakuni1, S. Ishiyama1,
RESULTS: In 4/17(23.5%) T1-GCs pts (3F, age 40-78yrs), gastric cancer A. Fujiwara1, J. Nasu1, S. Junji1
occurred (median follow-up 5.9 yrs, range 5.1-13; Table1). Three cases were 1
Internal medicine, Okayama Saiseikai General Hospital, OKAYAMA, Japan
intestinal-type adenocarcinomas and one a signet-ring cells diffuse gastric Contact E-mail Address: itoh777-lj@infoseek.jp
cancer, localized in 3 cases in the antrum. In two pts it was detected on
random biopsies during follow-up-gastroscopy, in the other two gastroscopy INTRODUCTION: Surgical gastroenterostomy used to be the first line treat-
was performed due to new symptoms. All pts with gastric cancer had associated ment for palliation of malignant gastroduodenal obstruction. Recently endo-
autoimmune features (pernicious anemia, autoimmune thyroid disease and a scopic placement of self-expandable metal stents (SEMS) has become a
spared antrum), compared to 77%, 46% and 54% of those without gastric broadly accepted treatment for patients with advanced malignant gastroduode-
cancer. nal obstruction as a minimally invasive therapy.
Table1. Pts with type I gastric carcinoid who developed an epithelial neoplastic AIMS & METHODS: We attempted to elucidate the current status of endo-
lesion scopic SEMS for palliation of malignant duodenal obstruction in comparison
CONCLUSION: This case-series shows that in pts with T1-GCs gastric cancer with surgical gastroenterostomy. A total of 39 consecutive duodenal tumor
may frequently occur at long-term follow-up. Thus, these pts should be moni- obstruction patients who were treated at Okayama Saiseikai General Hospital
tored by a long-term surveillance programme, including an accurate bioptic from January 2006 to Dectmber 2011 were reviewed (23 pancreatic cancer, 5
sampling of antral mucosa. gallbladder cancer, 4 duodenal cancer, 2 renal pelvis cancer, 2 colon cancer, 1
Disclosure of Interest: None declared gastric cancer, 1 liver cancer, 1 occult primary cancer). 25 patients were treated
by SEMS and 14 patients by surgical gastroenterostomy. We compared proce-
dure time, time from the procedure to starting oral intake, time from the proce-
P0502 THERAPEUTIC OUTCOMES OF ENDOSCOPIC RESECTION IN dure to starting chemotherapy, technical success rate, complication, hospital
FOREGUT NEUROENDOCRINE TUMORS stay, and mortality.
H.J. Jung1,*, Y.S. Myung1, J.P. Han1, S.J. Hong1, B.M. Ko1, M.S. Lee1 RESULTS: In each and every patients, treatment (eather endoscopic stent
1
Department of Internal Medicine, SoonChunHyang University School of implantation or surgical gastroenterostomy) was clinically successful.
Medicine, Bucheon, Digestive Disease Centerand Research Institute, Bucheon, Endoscopic stenting was found to be associated with a shorter time of procedure
Korea, Republic Of (mean 31.7 vs. 146 min, P50.01), a shorter time from the procedure to starting
Contact E-mail Address: 95970@schmc.ac.kr oral intake (mean 2.96 vs. 6.64 days, P 5 0.01) and a shorter hospital stay (mean
15.3 vs. 25.6 days, P 5 0.02) than the surgical gastroenterostomy. There was no
INTRODUCTION: Endoscopic resection (ER) may benefit to treat the low significant difference between the two groups in the analysis of mortality (mean
grade foregut neuroendocrine tumors (NETs). This study aimed to evaluate 91.5 vs. 158.8 days, p 0.107) and time from the procedure to starting che-
therapeutic outcomes of ER for foregut NETs. motherapy (mean 8.6 vs. 13 days, p 0.177). A single case of complication was
AIMS & METHODS: From January 2003 to February 2013, a total of 40 seen in each group, one case of intestinal perforation in SEMS group (4%) and
patients were confirmed histologically as foregut NETs from the ER one case of intra-abdominal abscess in surgical gastroenterostomy group (7%).
(stomach 16, duodenum 13) and surgical resection (SR, stomach 9, Both cases were able to recover by conservative treatment.
duodenum 2). The clinicopathological characteristics and therapeutic outcomes CONCLUSION: Endoscopic SEMS insertion was superior against surgical gas-
were evaluated retrospectively. troenterostomy in terms of procedure time, start of oral intake period and the
RESULTS: Of 29 patients underwent ER (EMR 23, ESD 6), 28 were diag- length of hospital stay. SEMS in duodenal obstruction is a feasible alternative of
nosed as NET-G1 and 1 as NEC. Of 11 patients underwent SR, 9 were diagnosed surgical gastroenterostomy for the palliation of inoperable malignant duodenal
as NET-G1 and 2 as NEC. Tumor size of ER group was significantly smaller obstruction. With a high clinical success and low complication rate, endoscopic
than SR group (7.4 mm vs. 18.2 mm, P50.01). Depth of invasion was limited to implantation of SEMS seems to be a safe and tolerable procedure for palliative
mucosa and submucosa in 28 NETs of ER group, However, all NETs of SR treatment of malignant duodenal obstruction.
group invaded the submucosa or proper muscle. Complete resections were Disclosure of Interest: None declared
achieved in 22 patients (75.9%) of ER group and achieved in 11 patients
(100%) of SR group. In ER group, immediate procedure-related complications
occurred in 2 cases (bleeding 1, perforation 1), and they were successfully
treated by conservative treatment. There was no complication in SR group.
There was no recurrence in 7 NETs reported as incomplete resection in
margin, but all of 3 NEC patients (ER 1, SR 2) had recurrence during
follow up period. They were treated by additional chemotherapy and had no
A272 United European Gastroenterology Journal 2(5S)
RESULTS: Of 219 patients receiving LDA, 20 (20%) was diagnosed endoscopi-
P0504 CLINICAL OUTCOMES OF SALVAGE ENDOSCOPIC THERAPY
cally with peptic ulceration, which was significantly higher than 7 (3.2%) of 219
AFTER CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER
patients not receiving LDA (OR, 3.0; 95% CI, 1.26 7.35; P 0.016). From
H. Osumi1,*, Y. Toshiyuki1, K. Chin1, A. Ishiyama1, T. Tsuchida1, J. Fujisaki1, multiple logistic regression analysis, LDA smoking habit, NSAID, and PPI
M. Igarashi1 were detected as increased and decreased risk factors for peptic ulcer, respectively
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation (OR, 9.6; 95% CI, 2.27 38.63; P 0.002), (OR, 3.9; 95% CI, 1.03 14.72;
for Cancer Research, Tokyo, Japan P 0.045), (OR, 7.4; 95% CI, 1.73 31.67; P 0.007), (OR, 0.11; 95% CI,
Contact E-mail Address: hiroki.osumi@jfcr.or.jp 0.02 0.45; P 0.002). Age, current alcohol consumption, H2-receptor antago-
nists, and abdominal symptom were not significantly associated with the presence
INTRODUCTION: Chemoradiotherapy (CRT) for esophageal cancer, especially of peptic ulcers.
at stage I, has comparable survival rates to surgery, with a median survival rate CONCLUSION: Long-term administration of LDA increases the risk of peptic
of 5 years. Therefore, in some cases, it is chosen as a first-line treatment for stage ulcer even in the patients who had no peptic ulcer history, and PPIs reduces the
I, II, and III esophageal cancer. However, about 30% of patients who are admi- risk of developing gastric or duodenal ulcers. However this risk is significantly
nistered chemoradiotherapy experience a local recurrence after complete increased in patients with concomitant smoking habit and NSAID. These results
response, so it is important to consider salvage therapy to treat such recurrences. may help identify patients who require more intensive prophylaxis against
Commonly administered salvage therapies include surgery, endoscopic therapy, aspirin-induced ulcerations.
and argon plasma coagulation (APC). Disclosure of Interest: None declared
AIMS & METHODS: The aim of this study is to illuminate the results of
administering salvage endoscopic therapy in cases of recurrent esophageal
cancer that had previously been treated with chemoradiotherapy. 161 patients P0506 CORRELATION BETWEEN THE PREVALENCE OF GALLSTONE
with UICCI-III esophageal cancer who received chemoradiotherapy at the AND HELICOBACTER PYLORI INFECTION
Cancer Institute Hospital between 2005 and 2013 without previously being trea- B.J. Kim1,*, J.G. KIM1, J.-H. Jung1
ted were retrospectively studied. 11 of these patients had local recurrences after 1
Internal Medicine (Gastroenterology), Chung-Ang University College of
receiving chemoradiotherapy, and received salvage endoscopic therapy as treat- Medicine, Seoul, Korea, Republic Of
ment for the recurrence. Their overall survival (OS) and time of recurrence after Contact E-mail Address: gikbj@cau.ac.kr
CRT and salvage endoscopic therapy were studied. Kaplan-Meier analysis and
Cox proportional hazard modeling were used for statistical analysis. INTRODUCTION: Several studies have reported that the presence of
RESULTS: The median observation period for the 11 patients studied was 75.2 Helicobacter DNA in human bile sample, although its pathological role is not
months (39.1-107.6). The clinical stages of esophageal cancer of the 11 patients clear. Moreover, little is known about the association between Helicobacter pylori
studied were as follows (stage I/II/III: 6/1/4). The salvage endoscopic therapies (H. pylori) infection and gallstone.
administered were as follows (EMR/ESD/APC: 7/3/1). The clinical responses of AIMS & METHODS: The aim of this study was to determine whether H. pylori
the patients to chemoradiotherapy were as follows (CR/PR: 8/3). 5 patients infection is associated with an increased risk of gallstone in an asymptomatic
experienced local recurrences again after salvage endoscopic therapy (EMR/ population.
ESD/APC: 4/0/1). Disease-free survival in patients who received salvage EMR We examined 2782 subjects (1635 men and 1147 women) who underwent both
therapy was a median 24 months (8.9-50.1). Patients who were administered upper endoscopy with CLO test and abdominal ultrasound at the Health
salvage APC therapy experienced relapses twice, and recurrence-free survival Examination Center at Chung-Ang University Yong-san Hospital in Korea
among those patients was a median 9 months (3.4-14.6). None of the patients from January 2007 to December 2009. We compared the prevalence of gallstone
who were administered ESD experienced a relapse, and disease-free survival on ultrasound and endoscopic findings such as reflux esophagitis, gastric diseases
among those patients was a median 25.3 months (13.3-32). The complications in the H. pylori infected subjects with that of the H. pylori uninfected subjects.
usually associated with endoscopic therapies were also not observed. There was RESULTS: The overall prevalence of H. pylori infection in our study was 45.6%
no significant difference between salvage therapies in terms of overall survival (1271/2782). When the subjects were divided into two groups according to the H.
(EMR 74.8 months (46.1-100.1), ESD 78.9months (39.1-107.6), APC 66.5 pylori infection status, there was no significant differences of the baseline char-
months). acteristics between the two groups. The prevalence of gallstone in the H. pylori
CONCLUSION: ESD can be considered to be a better salvage therapy than the infected subjects was higher than that of the H. pylori uninfected subjects (5.4%
other endoscopic therapies as the local recurrence rate was lower than that for vs 3.2%, P 0.032). The prevalence of peptic ulcer in the H. pylori infected
either EMR or APC. Even for less serious cases of esophageal cancer, ESD is a subjects was higher than that of the H. pylori uninfected subjects (8.2% vs
preferable choice as a salvage endoscopic therapy after chemoradiotherapy. It 3.4%, P50.001). The prevalence of reflux esophagitis in the H. pylori infected
should be noted, however, that there was no difference in the long-term prog- subjects was lower than that of the H. pylori uninfected subjects (6.2% vs 14.0%,
noses among the different salvage therapies, even after recurrence. In some cases, P 0.012).
ESD may not be ideal as a treatment, such as in patients who have other pre- CONCLUSION: These findings suggest that H. pylori infection is associated
existing diseases that make long-term treatment difficult, or in cases of esopha- with an increased risk of gallstone in asymptomatic population.
geal stenosis, which renders it difficult to use ESD scopes. For such cases, other REFERENCES
salvage therapies can be considered, including surgery and photo-dynamic ther- 1: Attaallah W, Yener N, Ugurlu MU, et al. Gallstones and concomitant gastric
apy (PDT). Helicobacter pylori infection. Gastroenterol Res Pract 2013; 2013: 643109.
Disclosure of Interest: None declared 2: Takahashi Y, Yamamichi N, Shimamoto T, et al. Helicobacter pylori infection
is positively associated with gallstones: a large-scale cross-sectional study in
Japan. J Gastroenterol 2013 Jun 5.
MONDAY, OCTOBER 20, 2014 9:0017:00 3: Abro AH, Haider IZ and Ahmad S. Helicobacter pylori infection in patients
H. PYLORI I POSTER EXHIBITION HALL XL_____________________ with calcular cholecystitis: a hospital based study. J Ayub Med Coll Abbottabad
2011; 23: 30-33.
P0505 LOW-DOSE ASPIRIN-ASSOCIATED GASTRIC AND DUODENAL 4: Lee JW, Lee DH, Lee JI, et al. Identification of Helicobacter pylori in gall-
ULCERS IN JAPANESE PATIENTS WITH NO PREVIOUS HISTORY stone, bile, and other hepatobiliary tissues of patients with cholecystitis. Gut
OF PEPTIC ULCERATION Liver 2010; 4: 60-67.
A. Tanabe1,*, Y. Ito1, Y. Yamaguchi1, N. Okaniwa1, H. Noda1, K. Yanamoto1, Disclosure of Interest: None declared
Y. Tamura1, Y. Kondo1, R. Masui1, S. Izawa1, Y. Hijikata1, K. Tokudome1,
N. Kawamura1, A. Iida1, N. Ogasawara1, Y. Funaki1, M. Sasaki1, K. Kasugai1
1 P0507 HELICOBACTER PYLORI INFECTION AMONGST ARAB
Aichi medical university, Nagakute, Japan
ISRAELI WOMEN WITH HYPEREMESIS GRAVIDARUM- A
INTRODUCTION: Long-term administration of low-dose aspirin (LDA) is PROSPECTIVE, CONTROLLED STUDY
associated with a greater risk of adverse events, including gastroduodenal D. Boltin1,*, S. Abu Elheiga2, T.T. Perez1, A. Sharony2, H. Shamly2, Y. Niv1,
ulcers and their potentially fatal complications (e.g., gastrointestinal bleeding R. Dickman1
and perforation). The identified risk factors for ulcer bleeding with aspirin use 1
Gastroenterology, Rabin Medical Center, Petah Tikva, 2Obstetrics and
are history of ulcer bleeding; aspirin dose; advanced age (470 years); concomi- Gynaecology, St. Vincent French Hospital, Nazareth, Israel
tant use of NSAIDs or anti-coagulants; use of dual anti-platelet therapy; Contact E-mail Address: dboltin@gmail.com
Helicobacter pylori infection; and history of alcohol abuse, diabetes, or renal
failure. Proton pump inhibitors (PPIs) are used to decrease LDA-associated INTRODUCTION: Helicobacter pylori has been associated with hyperemesis
gastroduodenal mucosal and NSAID-induced injuries. In Japan, since 2011, gravidarum in some geographical regions. The prevalence of H. pylori in Arab
treatment with half-dose PPI (lansoprazole 15 mg/day) has been permitted as a Israeli women in the Upper Galilee and its association with hyperemesis grav-
medical service under health insurance for the prevention of NSAID- or LDA- idarum, has not been previously studied.
induced peptic ulcers in patients in the high-risk group who have a history of AIMS & METHODS: The aim of this study was to examine whether H. pylori
peptic ulcers. However, there are few reports in which the use of PPIs reduced the infection is associated with hyperemesis gravidarum in Arab Israeli women.
risk of LDA-associated peptic ulcers in patients without pre-existing peptic ulcers Subjects with hyperemesis gravidarum carrying a singleton fetus, were prospec-
AIMS & METHODS: AIM: To assess the risk factors and the efficacy of med- tively recruited. Women with an uncomplicated pregnancy served as controls. All
ications for development of peptic ulcer disease in Japanese with no prior history patients underwent C13-urea breath testing to assess for H. pylori infection.
of peptic ulceration. RESULTS: A total of seventy two subjects, including 24 patients with hyperem-
METHODOLOGY: We conducted a matched background study using esopha- esis gravidarum and 48 controls, aged 28.85.3 years, were included. H. pylori
gogastroduodenoscopy (EGD) record collected from January 2010 through infection was identified in 73.9% (17/24), and 60.4% (29/48) of cases and con-
December 2010. Consecutive 219 outpatients receiving LDA (75 mg) who had trols, respectively (p ns). H. pylori infection did not correlate with age or the
no peptic ulcer history were matched to 1 control by age and sex who were not number of previous pregnancies (p ns). Control subjects with a history of early
receiving LDA and had no peptic ulcer history. Clinical parameters, concomitant trimester vomiting were not more likely to be infected with H. pylori, compared
drugs, the reason for endoscopy, and endoscopic findings were analyzed. to controls without a history of early trimester vomiting (p ns).
United European Gastroenterology Journal 2(5S) A273
CONCLUSION: H. pylori does not seem to increase the likelihood of hyperem-
P0509 OBESITY AND HELICOBACTER PYLORI INFECTION: IS THERE
esis gravidarum in Arab Israeli women. However, given the apparently high
A LINK?
background prevalence of H. pylori in this population, a larger study is required
to corroborate these findings. M. Sanduzzi Zamparelli1,*, A. Rocco1, D. Angrisani1, D. Compare1,
REFERENCES O.M. Nardone1, M.G. Iannuzzi1, G. Nardone1
1
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter clinical medicine and surgery, Federico II University, naples, Italy
pylori positivity with the symptoms in patients with hyperemesis gravidarum. Contact E-mail Address: marcosanduzzizamparelli@yahoo.it
Arch Gynecol Obstet 2013; 288: 1279-1283.
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity INTRODUCTION: The incidence of obesity is increasing worldwide. The invol-
in patients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105. vement of Helicobacter pylori (H. pylori) in the pathophysiology of obesity is still
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and debated. Among the possible related factors reported, H. pylori infection has
severe hyperemesis gravidarum among immigrant women in Norway: a case- been proposed to play a role by interfering with the release of gastric hormones
control study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46. involved in the regulation of appetite and food intake. However, the data avail-
4: Mansour GM and Nashaat EH. Role of Helicobacter pylori in the pathogen- able until now are conflicting are derive from small series of cases.
esis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284: 843-847. AIMS & METHODS: To analyze the distribution of H. pylori infection in a large
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter cohort of consecutive patients stratified according to sex, age and body mass
pyloripositivity with the symptoms in patients with hyperemesis gravidarum. index (BMI).
Arch Gynecol Obstet 2013; 288: 1279-1283. We enrolled 4653 subject referred to our Gastroenterology Unit between January
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity 2006 to January 2014 to perform 13C-urea breath test (13C-UBT). In all cases we
inpatients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105. recorded: age, sex, weight, height, previous esophagogastroscopy results, pre-
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and vious eradication therapy and H. pylori status. BMI was calculated according
severe hyperemesis gravidarum among immigrant women in Norway: a case- to the following formula: mass (Kg)/height (m)2. The 13C-UBT was performed
control study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46. by administering a solution of 100 ml tap water containing 100 mg of 13C-urea
Disclosure of Interest: None declared and 1.4 g of citric acid. Breath samples were taken at baseline and 30 minutes
after ingestion of the urea. The 13C enrichment in breath was determined by
isotope ratio mass spectrometer. The 13CUBT was considered positive if the
-
P0508 THE PREVALENCE OF HELICOBACTER PYLORI POSITIVITY value over baseline at 30 minutes was 4 5%.
IN THE GENERAL POPULATION IN SWEDEN HAS DECREASED RESULTS: Overall, there were 1916 (41%) male. Mean age was 43.75 years
FROM 38 PERCENT TO 16 PERCENT SINCE 1989 (range 3-88), 323 (7%) subject were 15 year-old. Forty-seven percent (2183)
A. Andreasson1,2, N. Talley3, L. Engstrand4, B. Wallner5, A. Forsberg6, subjects reported previous eradication therapy. BMI was 18 in 188 (4%),
P.M. Hellstrom7, L. Agreus1,* 18.1-25 in 2322 (50%), 25.1-30 in 1576 (35%) and 30.1 in the remaining
1
Karolinska Institutet, Centre for Family Medicine, Huddinge, 2Stress Research 514 (11%) of the cases. H. pylori infection was detected in 1892 (40.7%) with a
Institute, Stockholm University, Stockholm, Sweden, 3Faculty of Medicine, progressive increasing trend according to BMI ( 18: 36%; 18.1-25: 34%,
University of Newcastle, Newcastle, Australia, 4Karolinska Institutet, Stockholm, 25.1-30: 46% and 30.1: 56%; p50.0001).
5
Umea University, Umea, 6Molecular Medicine and Surgery, Karolinska Institutet, CONCLUSION: H. pylori infection is significantly more frequent in obese than
Stockholm, 7Uppsala University, Uppsala, Sweden in normal weight individuals, irrespective of sex and age.
Contact E-mail Address: lars.agreus@ki.se Disclosure of Interest: None declared
Cardiovascular overall 0.16 0.26 -0.10 -0.14 -0.06 INTRODUCTION: Red cell distribution width (RDW) has been shown in pre-
vious studies to be a sensitive predictor for coeliac disease (CD), but it lacks
Ischemic heart disease 0.10 0.15 -0.05 -0.08 -0.16 specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim
Respiratory overall 0.07 0.07 0.00 -0.02 0.03 was to evaluate if spleen size/RDW can be used as an indicator for celiac disease.
Neoplasm overall 0.78 0.72 0.06 -0.11 0.23 AIMS & METHODS: We evaluated 32 patients with small bowel disease (12
Non-hodgkins/leukemia 0.13 0.04 0.08 0.01 0.16 newly diagnosed CD patients and 20 patients with Crohns disease, IBD-CD) and
32 age-matched patients with irritable bowel syndrome (IBS), admitted to our
Digestive overall 0.15 0.11 0.05 -0.03 0.13 clinic over a one-year period. We evaluated the differences in spleen diameter,
RDW and their ratio among the three groups.
RESULTS: Of the 32 patients with small bowel disease, 11 were males, with a
CONCLUSION: Overall, people with CD have no major excess risk of cancer, mean age of 38.34 years. Mean RDW was significantly higher in the CD and
digestive, cardiovascular or respiratory related mortality compared to the general IBD-CD groups than the IBS group (14.49 and 16.73 vs. 13.51, p 0.0099),
population over the 10 year period following initial diagnosis. In addition they whereas mean spleen size was lowest in the CD patients (84.08, 107.85 and
have only a very small excess risk of dying of haematological malignancy. These 112.62 mm respectively). The mean spleen diameter/RDW was 5.82 in the CD
findings should be reassuring to both patients with CD and clinicians managing group, 6.65 in the IBD-CD group and 8.34 in the IBS group (p 0.0001). A ratio
their care. under 6 had a sensitivity of 75% and a specificity of 88.46% in detecting CD.
Disclosure of Interest: None declared CONCLUSION: Spleen diameter/RDW is a simple, widely available score,
which can be used to select patients for futher diagnostic tests. This should be
repeated in larger patient cohorts.
P0522 NUTRIENTS INTAKE IN NON CELIAC PATIENTS ON GLUTEN Disclosure of Interest: None declared
FREE DIET BECAUSE OF PERCEIVED GLUTEN SENSITIVITY:
COMPARISON WITH CELIAC PATIENTS AND WITH NATIONAL
NUTRITIONAL GUIDELINES P0524 CELIAC DISEASE AND DRUG-BASED THERAPIES: INQUIRY
B. Zanini1,*, M. Marullo1, A. Ferraresi1, F. Caselani1, C. Ricci1, F. Lanzarotto1, INTO PATIENTS DEMANDS
A. Lanzini1 F. Branchi1,2,*, C. Tomba1,2, M.T. Bardella1, L. Roncoroni1, M. Locatelli1,2,
1
Department of Clinical and Experimental Sciences, UNIVERSITY AND F. Somalvico1, D. Conte1,2, L. Elli1
1
SPEDALI CIVILI OF BRESCIA, Brescia, Italy Center for the Prevention and Diagnosis of Celiac Disease Gastroenterology and
Contact E-mail Address: b_zanini@tin.it endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico,
2
Universita` degli Studi di Milano, Milano, Italy
INTRODUCTION: Non celiac and non wheat allergic patients that sponta- Contact E-mail Address: lucelli@yahoo.com
neously adhere to gluten free diet (GFD) because of adverse gastrointestinal
and extra-intestinal reactions to gluten containing food are frequently encoun- INTRODUCTION: The gluten free diet (GFD) is the only available therapy for
tered in clinical practice and are commonly referred to as gluten sensitive (GS) patients with celiac disease (CD). Medical research is actively focused on the
patients. In most cases GS patients do not seek dietician advice on GFD, and no search for drug-based solutions as an alternative to GFD, which requires life-
information is available on the nutritional adequacy of their self-made diet. long, strict adherence.
AIMS & METHODS: We carried out a prospective clinical study to assess AIMS & METHODS: We aimed at evaluating the actual need for other-than-
macro- and micro-nutrients of GFD in GS patients compared with that of a GFD therapies perceived by CD patients, along with the impact of GFD itself on
cohort of patients with celiac disease (CD) matched according to gender and their life.
age (range /-4 years), and with the recommendations of the Italian nutritional During the 2012 meeting of the Lombardy section of the Italian CD Patients
guidelines (LARN 2012). Patients in the 2 study cohorts were asked to fill in a Association, adult CD subjects on GFD were invited to fill in a questionnaire
standardized 7-day food diary. Data from diaries were analyzed with Microdiet investigating their clinical profile in relation to GFD compliance, health status
software (Downlee systems, ltd. UK) that returns very detailed information on and quality of life as well as their opinion on GFD, alternative therapies and
diet composition. Nutritional characteristics included: total Kcal, proportion of research priorities.
total energy values of CHO, free sugars, proteins, fats, SFA and PUFA, and total RESULTS: 372 patients (76 M, mean age at diagnosis and at entry 29.7 16.9
amounts of fibres, vitamins A, C, D, B12, folates, sodium, calcium, iron, zinc, and 41.7 13.9 years, respectively) completed the questionnaire. 94% patients
selenium, magnesium and alcohol. For statistical analysis Fishers exact test and reported strict adherence to GFD. Patients reported a significant improvement in
Wilcoxon matched paires test were used as appropriate. health status and quality of life after the diagnosis of CD was made and GFD
was started (p50.001), with a greater improvement of health status than quality
A278 United European Gastroenterology Journal 2(5S)
of life (82% vs 56%, p50.001). GFD was favourably considered and accepted by
P0526 HOW DOES SPECIFIC SEROLOGY MATCH WITH ESPHGAN
88% patients, but a demand for alternative therapies was reported by 65%
SEROLOGIC GUIDELINES FOR DIAGNOSIS OF CELIAC DISEASE
patients. Subjects expressing the need for a drug-based therapy showed a signifi-
IN A PROSPECTIVE COHORT OF ADULTS WITH HIGH PRETEST
cantly lower increase of quality of life on GFD (p 0.002), but no differences
PROBABILITY?
were observed in health status changes. The preferred option for an alternative
therapy was the on demand assumption of drugs, i.e. enzymes (145 subjects), G. I. Longarini1,*, E. Sugai1, H. Hwang1, F. Nachman1, A. Cabanne1,
followed by a vaccine-based strategy (111 subjects). Almost two thirds of the H. Vazquez1, M.L. Moreno1, A.F. Costa1, M. I. Pinto1, S. Niveloni1,
cohort stated they would accept to be enrolled in ad hoc designed clinical trials. E. Smecuol1, R. Mazure1, E. Maurino1, J.C. Bai1
1
CONCLUSION: GFD is favourably accepted and followed by most CD Medicine, Hospital Udaondo, Buenos Aires, Argentina
patients, with significant health status improvement. Nevertheless, a considerable Contact E-mail Address: emiliasugai@yahoo.com
proportion of patients pronounce themselves in favour of the development of
alternative drugs, although a chronic drug therapy is not considered a likely INTRODUCTION: Intestinal biopsy is considered mandatory for the diagnosis
opportunity. of celiac disease (CD). This has been recently challenged by several studies and
REFERENCES the 2012 ESPGHAN guideline proposing an appropriate clinical and serological
1. Schuppan D, Junker Y and Barisani D. Celiac disease: from pathogenesis to algorithm that could be used to reduce the need for duodenal biopsy. This
novel therapies. Gastroenterology 2009; 137: 1912-1933. provocative strategy has been confirmed by some studies but rejected by
2. Aziz I, Evans KE, Papageorgiou V, et al. Are patients with celiac disease others. However, all these studies were performed on the basis of retrospective
seeking alternative therapies to a gluten-free diet? J Gastrointestin Liver Dis analyses of biased populations. Prospective evaluation of patients in whom diag-
2011; 20: 27-31. nosis was based on histological grounds is important to clarify this controversy.
3. Mukherjee R, Kelly CP and Schuppan D. Nondietary therapies for celiac AIMS & METHODS: 1-To review the performance of serology tests in a pro-
disease. Gastrointest Endosc Clin N Am 2012; 22: 811-831. spective and consecutive series of adult patients with high pretest probability for
Disclosure of Interest: None declared CD; 2- to compare performance of serologic tests with the ESPGHAN serologic
algorithm; and 3- to establish the best serologic algorithm for diagnosing CD
using antibody tests detecting different antigens.
P0525 IMPAIRED BONE MICROSTRUCTURE IMPROVES AFTER ONE- We performed a post hoc analysis of data from all patients enrolled in a previous
YEAR ON GLUTEN-FREE DIET. A PROSPECTIVE LONGITUDINAL prospective study (WJG 2010; 16: 3144) where consecutive adults suspected of
STUDY IN WOMEN WITH ACTIVE CELIAC DISEASE intestinal disorders (high pretest population) were enrolled. Diagnosis of CD was
G. I. Longarini1,1,*, M.B. Zanchetta2, A.F. Costa1, V. Longobardi2, based on histology (Marshs stages 3a) in all patients irrespective of serology.
M.P. Temprano1, H. Vazquez1, S. Niveloni1, E. Smecuol1, M.L. Moreno1, CD-related serology consisted of seven different assays but we only report the
H. Hwang1, R. Mazure1, A. Gonzalez1, E. Maurino1, J.C. Bai1 performance of tissue transglutaminase (tTG) IgA, deamidated gliadin peptides
1
Medicine, Hospital Udaondo, 2IDIM, Buenos Aires, Argentina (DGP) IgG and the combination of both (INOVA Diag. Inc.). Serologic perfor-
Contact E-mail Address: mbzanchetta@idim.com.ar mance was compared with the ESPGHAN serologic criterion (cut-off 410 times
the upper limit of normal -ULN-), the best cut-off (area under the ROC) and the
INTRODUCTION: We have recently identified a significant deterioration of cut-off suggested by the manufacturer.
trabecular and cortical microarchitecture in peripheral bones of patients with RESULTS: Sixty-three of 161 patients (39%) had histological criteria for CD.
undiagnosed celiac disease (CD) by using high resolution-peripheral quantitative According to the ESPGHAN criterion, IgA tTG sensitivity was 22% with 100%
computed tomography (HR-pQCT). Such finding may underlie bone fragility positive predictive value (PPV). The best cut-off value (34 AU/mL) would detect
and lead to fractures in these patients. Up to now, the effect of the gluten-free 93.6% of patients with 100% of PPV. Finally, the manufacturer cut-off (20 AU/
diet (GFD) on microstructural parameters of peripheral bones has not been mL) had 95.2% sensitivity and 97.9% PPV. The ESPGHAN criterion used for
assessed. IgG DGP was 3.2% sensitive with a PPV of 100%. The best cut-off (was similar
AIMS & METHODS: Aim: To explore one-year changes of bone microstructure to that of the manufacturer: 20AU/mL) was 95.2% sensitive and had 100% PPV.
associated with the GFD in a prospective cohort of premenopausal women with Any test was positive (420AU/mL) in all patients and both were concomitantly
newly diagnosed CD. positive in 90.5% of cases with100% of PPV.
Materials: We prospectively enrolled 31 consecutive females with newly diag- CONCLUSION: This prospective study indicates that, under particular clinical
nosed CD. Up to now, 25 patients have been reassessed one-year after diagnosis. circumstances, a serologic strategy can be used to avoid duodenal biopsy in the
Clinical and biochemical status, CD specific serology, assessment of the degree of diagnosis of adult patients with CD. The need for biopsy could be avoided in a
compliance with the GFD, bone densitometry and microstructural determina- minority of patients by using the ESPGHAN serologic criterion. Our results
tions (HR-pQCT) were performed at both time points. HR-pQCT bone volu- suggest that the best serologic strategy for a high pretest population seems to
metric and structural measurements were determined at the distal non-dominant be the association of tTG IgA and DGP IgG. In such context, biopsy could be
radius and tibia. Parameters of patients were also compared with those of 22 avoided in more than 90% of the cases when both tests are positive.
healthy women of similar age and body mass index. Disclosure of Interest: G. Longarini: None declared, E. Sugai: None declared, H.
RESULTS: Compared with the baseline z-score, the one-year bone mineral den- Hwang: None declared, F. Nachman: None declared, A. Cabanne: None
sity measured by dual energy x-ray absorptiometry (DXA) improved signifi- declared, H. Vazquez: None declared, M. Moreno: None declared, A. Costa:
cantly at the distal radius (meanSD) (-1.941.27 vs. -1.431.06; p50.02) but None declared, M. Pinto: None declared, S. Niveloni: None declared, E.
not at the lumbar spine level. The microstructure of the trabecular compartment Smecuol Financial support for research from: Astra Zeneca, Lecture fee(s)
in the distal radius was significantly improved (trabecular/bone volume fraction, from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, R. Mazure: None
trabecular density and trabecular thickness: p50.0001) at the one-year time declared, E. Maurino: None declared, J. Bai: None declared
point. At the level of tibia, treatment was associated with significant increment
of the total volumetric density (p50.01), cortical density (p50.002), trabecular
density (p50.0001), trabecular/bone volume fraction (p50.0001) and trabecular P0527 HIGH RATES OF PRIOR CELIAC DISEASE OVERDIAGNOSIS
thickness (p50.002). In contrast, the cortical thickness decreased significantly in AMONG PATIENTS REFERRING TO AN ITALIAN TERTIARY
both sites (p50.001). Compared to the control group there were no statistically CARE CENTER
significant differences in most trabecular parameters measured by HR-pQCT. G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1,
CONCLUSION: This is the first study exploring the effect of a one-year GFD on G. Cammarota1
microstructural parameters measured by HR-pQCT in patients with newly diag- 1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
nosed CD. Our study shows that trabecular parameters impaired at the time of CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
diagnosis improved significantly by treatment reaching values comparable to Contact E-mail Address: gianluca.ianiro@hotmail.it
those in healthy controls. We postulate that bone microarchitecture improvement
underlie the decreased risk of fractures observed after treatment with a GFD. INTRODUCTION: Celiac disease (CD) was formerly considered a rare condi-
Disclosure of Interest: G. Longarini: None declared, M. Zanchetta: None tion and frequently underdiagnosed. Interest in CD has grown in recent years,
declared, A. Costa: None declared, V. Longobardi: None declared, M. not only among gastroenterologists but also among general practitioners and
Temprano: None declared, H. Vazquez: None declared, S. Niveloni: None patients. Furthermore, focus of media on gluten-free diet (GFD) is increasingly
declared, E. Smecuol Financial support for research from: Astra Zeneca, spreading worldwide. Therefore many patients are labeled as celiacs and start a
Lecture fee(s) from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, M. GFD even without completing the correct diagnostic process.
Moreno: None declared, H. Hwang: None declared, R. Mazure: None declared, AIMS & METHODS: Our aim is to assess the impact of overdiagnosis in an
A. Gonzalez: None declared, E. Maurino: None declared, J. Bai: None declared Italian tertiary referral center for CD. We reviewed the clinical history of all
patients referring to our Centre from October 2012 to December 2013. We
included only patients at their first examination. We questioned diagnoses for
the following reasons: EMA/TTG absence or negativity; duodenal biopsy not
performed or unclear; DQ2/DQ8 negativity. Following data of patients with a
doubtful diagnosis were extracted: people who have diagnosed CD (physicians or
patients); reasons for diagnosis (symptoms, DQ2/DQ8, specific antibodies, duo-
denal biopsy), gluten consumption status. Number of patients undergoing a
proper diagnostic process was determined, as well as of patients with a prior
undebatable diagnosis. Diagnosis was revaluated by repetition of serology and
by second-reading of duodenal tissue slides by an experienced pathologist. DQ2/
DQ8 was searched in pertinent cases.
RESULTS: Over the study period, 293 patients attended our Centre, of whom
150 for the first time. Of them, 47 (31.3%) presented with an undebatable diag-
nosis of CD, and 37 (24.7%) were newly diagnosed because of EMA/TTG posi-
tivity associated with duodenal Marsh lesions. In 15 patients (10%) referring for
United European Gastroenterology Journal 2(5S) A279
family history of CD, gastrointestinal symptoms or anemia, CD was excluded by
P0529 IS VISCERAL ADIPOSE TISSUE A RISK FACTOR FOR SMALL
serology and histology assessment. The remaining 51 patients (34%) came for a
BOWEL ANGIOECTAISA?
revaluation of previously diagnosed CD. Forty-five of them (88%) were on a
GFD at the time of the examination. Thirty-five patients (68.6%) were diagnosed A. Yamada1,*, R. Niikura1, Y. Kobayashi1, H. Suzuki1, H. Watabe1, S. Yoshida2,
of CD by their trusted doctor (gastroenterologist, gynaecologist, dermatologist Y. Hirata1, K. Koike1
1
or general practitioner), while the remaining 16 (31.4%) believed to be affected of Department of Gastroenterology, Graduate School of Medicine, 2Department of
CD on their own. Motivations for prior CD diagnosis were often multiple for Endoscopy and Endoscopic Surgery, The University of Tokyo, Tokyo, Japan
each patient: serologic positivity (9 AGA, 5 EMA, 2 TTG) in 16 cases, histolo-
gical features in 19 cases, DQ2/DQ8 positivity in 20 cases, amelioration of symp- INTRODUCTION: Small bowel angioectasia (SBA) is one of the major bleeding
toms after GFD in 16 cases. Reasons for questioning previous diagnosis were sources of obscure gastrointestinal bleeding (OGIB). Little is known about etiol-
also multiple for each patient: EMA/TTG absence or negativity in 45 cases; lack ogy of SBA. Visceral adipose tissue (VAT) expresses some bioactive molecules
of duodenal biopsy in 20 cases; unclear histology in 24 cases; DQ2/DQ8 nega- including vascular endothelial growth factor (VEGF), which is implicated in
tivity in 2 cases. Diagnosis of CD was rejected in 78.4% of doubtful cases normal or pathological vessel formation. In the present study, we investigated
(n 40), being confirmed in only 19.6% (n 10) of them. In one patient, diag- VAT in association with the risk of small bowel angioectasia.
nosis is still ongoing. AIMS & METHODS: We retrospectively investigated 198 consecutive patients
CONCLUSION: Our retrospective study shows that a considerable number of (male: female; 117: 81, mean age 65.8 12.8 years) who underwent capsule
patients referring to an Italian tertiary care center experience previous misdiag- endoscopy (CE) and CT for investigation of overt and occult OGIB at the
nosis and/or overdiagnosis of CD. Such behavior may lead to both a diagnostic University of Tokyo Hospital between January 2009 and September 2013.
delay of other diseases and a remarkable waste of economic resources (tax VAT and subcutaneous adipose tissue (SAT) were measured by CT, and medical
exemptions, gluten-free food vouchers, diagnostic exams), with damage for history of concomitant disease and body mass index were obtained from their
both patients and health services. Greater accuracy in the application of the medical records. Logistic regression analyses were used to evaluate associations.
adequate diagnostic process and a higher adherence to guidelines are needed to RESULTS: Out of 198 OGIB patients, CE found SBA in 18 patients (9.1%).
minimize misdiagnosis of CD. Compared with patients without SBA, those with SBA had signiEcantly higher
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to VAT (96 76.0 cm2, vs. 63.4 51.5 cm2, p 0.016) and higher prevalence of
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V. liver cirrhosis (11(61%) vs. 41(23%), p 0.0011). Prevalences of SBA progres-
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota: sively increased according to VAT; 7.2% in patients with VAT less than 100 cm2,
nothing to declare whereas 12.5% in those between 100 cm2 and 150 cm2, 21.4% more than 150 cm2
(p 0.058 by trend test), respectively. Multivariate analysis showed that VAT
(odds ratio for each 10 cm2 increment, 1.1; 95% confidence interval (CI), 1.01-
P0528 GLUTEN AVOIDANCE BEFORE A DEFINITE DIAGNOSIS IS 1.19; p 0.025), liver cirrhosis (odds ratio, 5.5; 95% CI, 1.98-16.6; p 0.0011)
MORE COMMON AMONG NON-CELIAC SUBJECTS THAN were related to significant risk factors of SBA.
CELIAC ONES CONCLUSION: In addition to liver cirrhosis, visceral adipose tissue is one of
G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1, the risk factors for small bowel angioectasia.
G. Cammarota1 Disclosure of Interest: None declared
1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it P0530 EVALUATION OF GASTRO-INTESTINAL LESIONS IN
PATIENTS UNDERGOING ORAL ANTICOAGULANT THERAPY BY
INTRODUCTION: Gluten is known to trigger not only celiac disease, but also CAPSULE ENDOSCOPY
other conditions, such as non-celiac gluten sensitivity (NCGS) and wheat allergy, C. Marmo1,*, M.E. Riccioni1, R. Cianci2, G. Costamagna1
recently grouped together as gluten-related disorders. Gluten has recently 1
Digestive Endoscopy Unit, 2Institute of Internal Medicine, Catholic University of
shown to cause depression in subjects with NCGS. Furthermore, gluten is able Rome, "A. Gemelli" Hospital, Italy, Rome, Italy
to cause gastrointestinal (GI) symptoms and to alter bowel barrier functions in Contact E-mail Address: clelia.marmo@alice.it
patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Gluten-
free claims are increasingly spreading on the Web and other media, and many INTRODUCTION: Small bowel bleeding is still poorly studied in patients with
subjects start a gluten-free diet (GFD) without any prior medical consultation. long-term anticoagulation therapy. Capsule endoscopy (CE) is the first-line
Such a behavior may lead to a considerable waste of resources and to diagnostic method for evaluation of bleeding in patient after negative upper endoscopy
delay both in celiac and in non-celiac subjects. and colonoscopy.
AIMS & METHODS: Our aim was to assess the impact of gluten avoidance AIMS & METHODS: In this retrospective study, we had investigated the types
before a definite diagnosis in both patients with and without celiac disease. We and frequency of small bowel GI bleeding lesions in patients undergoing oral
reviewed the clinical history of all patients referring to our CD outpatient clinic anticoagulant therapy, by CE. Of a total of 1085 CE obtained between January
from October 2012 to December 2013. We included only patients without a 2003 and June 2013, 679 were performed in patients with obscure gastrointestinal
definite diagnosis of CD at their first examination at our Centre. Patients were bleeding. Of these 96 were obtained in patients undergoing oral anticoagulant
grouped according to their gluten consumption status at the time of examination. therapy, 55 males and 41 females, mean age 70.6 years (range 23-87 years). At
Gluten was reintroduced for at least 2 months before any diagnostic assessment the time of evaluation by capsule endoscopy, the mean level of haemoglobin was
in all subjects already on GFD. The following data were extracted from patients 8.3 g/dl for males (normal values 14-18 g/dl) and 6.7 g/dl for females (normal
on GFD at the time of examination: gender, age, reasons for gluten avoidance values 12-16 g/dl). The mean number of blood units used for transfusions was
without definite diagnosis (GI/extraintestinal symptoms, DQ2/DQ8, specific 5.7 per patient (range 2-20). All patients underwent upper and lower gastro-intest-
antibodies, duodenal biopsy), proposer of GFD (physicians or the patient inal endoscopy, prior to capsule endoscopy (CE). If upper and lower examinations
itself). All patients underwent blood dosage of EMA, TTG and total IgA were negative, CE was performed. The following data were recorded in the data
levels, as well as upper endoscopy with duodenal biopsy. In all patients CD base: patient age, gender, indication for the examination, medical and surgical
was diagnosed because of EMA and TTG positivity associated with Marsh- history, bleeding history (including type of bleeding, total number of transfusions,
type intestinal lesions. Correlation between gluten avoidance and further diag- hospitalizations), number and type of prior diagnostic testing, and details of the
nosis of CD was assessed by Chi-square test. capsule examination.
RESULTS: Over the study period, a total amount of 293 patients attended our RESULTS: In the series of patients undergoing oral anticoagulant therapy: 35/96
Centre, of whom 150 (M 41, F 109 mean age 39 y) for the first time. Ninety-two (36.4%) patients had negative examination; 22/96 (22.9%) had small-bowel
patients came without a definite diagnosis of CD. Of them, 32 (34.8%) were on angiodysplasias, small bowel erosions 21/96 (21.8%), small bowel ulcerations
GFD at the time of examination, and 60 (66.2%) were not. Reasons for GFD 5/96 pts (5.2%), neoplasia 4/96 (4.1%). In the series of patients with OGIB
without definite diagnosis were: GI symptoms (12 cases), extraintestinal symp- without anticoagulant therapy: 102/583 (17.4%) had angiodysplasias, small
toms (7 cases), DQ2/DQ8 positivity (9 cases), antibody positivity (6 cases), his- bowel erosions 48/583 (8.2%), small bowel ulcerations 25/583 (4.2%), neoplasia
tological features (9 cases). Sixteen patients started a GFD on their own (41%), 44/583 (7.5%)
and 23 upon medical advice (58%). Gender did not influence gluten consumption CONCLUSION: Small bowel angiodysplasias remain the main cause of occult
status (p 0.8376). Respectively, CD was diagnosed in 21.9% (7/32) of patients GI bleeding. In our series, patients undergoing oral anticoagulant therapy had
on GFD and 71.8% (43/60) of patients on a gluten-containing diet at the time of high prevalence of small bowel angiodysplasias (36.4% for anticoagulant group
first examination (P50.0001). and 17.4% for control group). Furthermore in the anticoagulant group we have
CONCLUSION: Our study shows that gluten avoidance before a clear definition seen a major occurrence of erosions (21.8% VS 8.2%).
of diagnosis is more common among subjects in whom CD is ruled out at a later Disclosure of Interest: None declared
stage than ones diagnosed of CD afterwards. The increasing interest of physi-
cians and patients in gluten-related diseases, and unmotivated gluten-free claims
may explain such reasons. Also symptom burden and gluten influence on mental P0531 FREQUENCY AND RISK FACTORS FOR REBLEEDING EVENTS
component of patients may play a role in this phenomenon. However, the retro- IN PATIENTS WITH SMALL BOWEL ANGIOECTASIA
spective nature of our study represents a limitation in data analysis. Further, E. Sakai1,*, H. Endo1, S. Umezawa1, A. Fuyuki1, S. Uchiyama1, H. Ohkubo1,
prospective trials are warranted to clarify this issue. T. Higurashi1, T. Nonaka1, A. Nakajima1
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to 1
Gastroenterology, Yokohama City University School of Medicine, Yokohama,
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V. Japan
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota: Contact E-mail Address: eiji525@yokohama-cu.ac.jp
nothing to declare
INTRODUCTION: Small bowel angioectasia is reported as the most common
cause of bleeding in patients with obscure gastrointestinal bleeding (OGIB).
Although the safety and efficacy of endoscopic treatment have been demon-
strated, rebleeding rates are relatively high. To establish therapeutic and
A280 United European Gastroenterology Journal 2(5S)
follow-up guidelines, we investigated the long-term outcomes and clinical pre-
P0533 WHAT IS THE LONG-TERM SAFETY OF A NEGATIVE CAPSULE
dictors of rebleeding in patients with small bowel angioectasia.
ENDOSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL
AIMS & METHODS: A total of 68 patients were retrospectively included in this
BLEEDING?
study. All the patients had undergone CE examination, and subsequent control
of bleeding, where needed, was accomplished by endoscopic argon plasma coa- I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
gulation. Based on the follow-up data, the rebleeding rate was compared between A. Ponte1, S. Leite1, J. Carvalho1
1
patients who had/had not undergone endoscopic treatment. Multivariate analysis Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
was performed using a Cox proportional hazard regression model to identify the Contact E-mail Address: iolandacribeiro@gmail.com
predictors of rebleeding. Rebleeding was defined as evidence of recurrent visible
gastrointestinal bleeding (hematochezia or melena) with recent negative upper INTRODUCTION: Although capsule endoscopy (CE) is the investigation of
and lower endoscopic examinations and/or a reccurent drop of the hemoglobin choice in obscure GI bleeding (OGIB), the clinical outcomes of a negative capsule
level by more than 2 g/dl from the baseline. We defined the OGIB as controlled if remain contradictory according to different studies.
there was no further overt bleeding within 6 months and the hemoglobin level AIMS & METHODS: The aim of the study was to compare the long-term out-
had not fallen below 10 g/dl by the time of the final examination. come of patients with OGIB after a negative and a positive CE and identify risk
RESULTS: The overall rebleeding rate over a median follow-up duration of 30.5 factors for rebleeding.
months (interquartile range 16.547.0) was 33.8% (23/68 cases). The cumulative Methods: Retrospective study of 173 patients who underwent CE for OGIB, from
risk of rebleeding tended to be lower in the patients who had undergone endo- 2005 to 2013; patients with a follow-up time 56 months were excluded. CE with no
scopic treatment than in those who had not undergone endoscopic treatment, lesions or with lesions P0 (petechial lesions; mucosal congestion) or P1 (isolated ero-
however, the difference did not reach statistical significance (P 0.14). In the sions; small angiodysplasias) were considered negative. Rebleeding was defined as a
majority of patients with rebleeding (18/23, 78.3%), the bleeding was controlled documented fall in hemoglobin of 2 g/dL from baseline, evidence of melena or hema-
with additional endoscopic treatment by the end of the follow-up period. tochezia, and the need for blood transfusion, at least 30 days after the index bleed.
Multiple regression analysis identified multiple lesions (3) (OR 3.82; 95% CI We evaluated the demographic characteristics, type of OGIB (overt vs occult),
1.3011.3, P 0.02) as the only significant independent predictor of rebleeding. medication, rebleeding rate after a negative and a positive CE, type of treatment
CONCLUSION: In conclusion, patients with small bowel angioectasia show (endoscopic/surgical) performed in patients with positive CE and the influence on
relatively high rebleeding rates. Although a single session of endoscopic treat- rebleeding. Statistical tests: t-student, 2.
ment was not sufficient to control future rebleeding, in most cases, rebleeding RESULTS: The mean age was 61.7 years; 67% of patients underwent CE
could be controlled with repeated endoscopic treatment and/or iron replacement because of occult GIB; 54.3% of CE were negative; the mean follow-up time
therapy. Careful follow-up is needed for patients with multiple lesions, which was was 27 months ( 23.4) and the overall rebleeding rate was 22.5%. The rebleed-
identified as a significant risk factor for rebleeding. ing rate after a negative CE was significantly lower than after a positive CE (16%
Disclosure of Interest: None declared vs 30.4%, p 0.024). Patients who rebleed needed more transfusions of red blood
cells (mean 6.0) prior to CE when compared with those who did not rebleed
(mean 1.2, p50.001). Age, sex, anticoagulants or anti-agregants did not influ-
P0532 GENE EXPRESSION LEVELS OF ANGIOGENIC FACTORS IN ence the rebeeding rate.
SMALL BOWEL ANGIODYSPLASIA Almost 50% of patients with a positive study underwent endoscopic (56.4% -
G. Holleran1,*, B. Hall1, S. Smith1, D. McNamara1 argon plasma coagulation) or surgical treatment (28.2%), with significantly
1
Department of Clinical Medicine, Trinity College Dublin, Tallaght, Ireland lower rebleeding rate than patients who did not undergo any treatment (23.1%
Contact E-mail Address: grainneholleran@gmail.com vs 37.5%, p 50.02).
CONCLUSION: Conclusions: A negative CE study in patients with OGIB is
INTRODUCTION: Angiodysplasias are known to account for 50% of small associated with a low rate of recurrent bleeding in the long term (16%). It is
bowel bleeding sources, but diagnosis and effective treatment of these lesions is reasonable to take an expectant approach with these patients, thus avoiding the
limited by a poor understanding of the pathophysiology of the condition. By need for unnecessary additional investigations. The endoscopic/surgical treat-
measuring serum angiogenic factors in patients with small bowel angiodysplasias ment decreases the rebeeding rate after a positive CE.
(SBA), we have already identified abnormalities in the angiopoietin pathway; Disclosure of Interest: None declared
with elevated levels of Ang2 and decreased levels of Ang1, associated with the
condition. To determine the significance of these findings we need to determine
whether these factors and their receptors are specifically located in SBA tissue. P0534 SMALL BOWEL CAPSULE ENDOSCOPY IN ELDERLY
AIMS & METHODS: The aim of this study was to measure gene expression levels PATIENTS. INDICATIONS AND FINDINGS
of various angiogenic factors and receptors in SBA tissue compared to adjacent N. Viazis1, K. Katopodi1,*, M. Chanias1, E. Anastasopoulos1, G. Kechagias1,
normal tissue and to normal SB tissue in controls. Following informed consent, K. Markoglou1, M. Mela1, E. Keimali1, D.G. Karamanolis1
patients aged 18-80 years of age undergoing double balloon enteroscopy for a 1
Department of Gastroenterology, EVANGELISMOS HOSPITAL, Athens,
variety of small bowel disorders at Tallaght hospital were invited to participate. Greece
From patients with SBA, one standard biopsy was taken from a single angiodys- Contact E-mail Address: nikos.viazis@gmail.com
plasia lesion, and a further biopsy was taken from macroscopically adjacent normal
mucosa. In controls, a single small bowel mucosal biopsy was taken at random. INTRODUCTION: Given the aging of the European population a growing
Biopsy samples were immediately placed in RNAlater solution and stored in a fridge number of elderly patients need to be subjected to small bowel capsule endo-
overnight before being stored at -80oC for batch analysis. Using a standard techni- scopy. In our study we aimed to determine the indications and findings of
que, RNA was isolated and a reverse transcription reaction was performed on each patients aged 4 80 years old subjected to small bowel capsule endoscopy in
sample using the Fermantas first strand cDNA synthesis kit (Thermo Scientific). our Department, in comparison to those aged 5 80 years old.
The resulting cDNA was used in quantitative PCR reactions to determine the AIMS & METHODS: From March 2003 till August 2013, 3410 patients have been
relative expression of Ang1, Ang2, Tie2, VEGF and TNF. Relative gene expression subjected to small bowel capsule endosopy (Given imaging) in our Department.
was calculated using the comparative cycle threshold (CT) method and was normal- Among them, 131 were 4 80 years old. We analyzed the indications and findings of
ised to the control gene GAPDH. Statistical analysis was performed using SPSS these patients in comparison to the rest of the patients subjected to the test.
version 20. Fold differences of each gene were expressed as a mean and compared RESULTS: Among the 131 patients aged 4 80 years old, the 106 (80.9%) have
between groups, with a p value of 50.05 considered significant. been subjected to small bowel capsule endoscopy because of obscure gastroin-
RESULTS: In total, 20 biopsy samples were collected; including 9 from angio- testinal bleeding. The corresponding percentage for patients aged 5 80 years old
dysplasia mucosa, 7 from adjacent normal mucosa, and 4 from normal mucosa in was 60.2%. The remaining patients have been subjected to the test because of
controls. Detectable levels of genes encoding Ang1, Ang2, Tie2, TNF and VEGF suspected Crohns disease (n 9, 6.8%), chronic diarrhea (n 9, 6.8%) and
were found in all biopsy samples. There were significantly higher levels of Ang1 abdominal pain (n 7, 5.3%). The corresponding figures for those patients
and its receptor Tie2 in angiodysplasia tissue compared to adjacent normal aged 5 80 years old were 21.7%, 3.7% and 4.3% respectively. The findings of
mucosa and to controls, with mean fold differences of 1.77 vs 0.82 and 0.81 the test in both age groups in cases of obscure gastrointestinal bleeding are
for Ang1 (p 0.049), and 1.66 vs 0.76 and 0.52 for Tie2 (p 0.02) respectively. presented in table 1. No patient aged 4 80 years old had any complication
Levels of Ang2 appeared higher in angiodysplasias than both adjacent mucosa due to the small bowel capsule endoscopy investigation.
and controls, however; this was only statistically significant between the angio- Table 1. Findings of small bowel capsule endoscopy
dysplasias and their adjacent mucosa (p 0.04). There were no differences in
levels of TNF or VEGF expression between any of the samples. Patients 4 80 years old Patients 5 80 years old
P0543 FIRST REPORTS OF THE NEW SPATZ 3 ADJUSTABLE P0545 SACCHAROMYCES BOULARDII ADMINISTRATION CHANGES
BALLOON SYSTEM GUT MICROBIOTA AND REDUCES HEPATIC STEATOSIS, LOW
E. Machytka1,*, Z. Kowalczyk2, S. Al Awadhi3, M. Al Falasi3, J. Mason4, GRADE INFLAMMATION AND FAT MASS IN OBESE AND TYPE 2
L. Bene5, S. El Asala6, V. Puig-Divi7, M. Buzga1, J. Brooks8 DIABETIC DB/DB MICE
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic, L. Geurts1,*, A. Everard1, S. Matamoros1, N. Delzenne1, P.D. Cani1
2
Bariatric clinic Pulsmed, Lodz, Poland, 3Rashid Hospital, Dubai, United Arab 1
Louvain Drug Research Institute, Walloon Excellence in Life sciences and
Emirates, 4National Obesity Surgery Center, Manchester, United Kingdom, BIOtechnology (WELBIO), Metabolism and Nutrition Research Group,
5
Rozsakert Medical Center, Budapest, Hungary, 6Alain Hospital, Dubai, United Universite catholique de Louvain, Brussels, Belgium
Arab Emirates, 7Opcion Medical Clinic, Barcelona, Spain, 8Spatz FGIA, Great Contact E-mail Address: patrice.cani@uclouvain.be
Neck, United States
Contact E-mail Address: machytka@obezita-balon.cz INTRODUCTION: Obesity and type 2 diabetes are associated with an altered
gut microbiota and inflammation. Growing evidence suggest that the gut micro-
INTRODUCTION: The original Spatz Adjustable Balloon System for weight biota is involved in the regulation of energy homeostasis. We and others have
loss was introduced in 2010. It was the first intragastric balloon approved for shown that gut microbiota modulation using prebiotics constitute an interesting
1 year implantation with the added feature of balloon volume adjustability. This target in the physiopathology of obesity.
enabled changes to balloon volume during the course of the 1 year implantation AIMS & METHODS: So far, probiotic yeast have not been investigated in this
period. It contained a rigid catheter and metal chain that caused duodenal migra- context. The aim of this study is to evaluate the role of the most studied probiotic
tion. The new Spatz 3 intragastric balloon device, CE Mark approval in 2012, has yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated meta-
a soft catheter to simplify the procedure and decrease complications. In addition, bolic disorders. S. boulardii was administrated daily by oral gavage to leptin-
reports of volume adjustments using a mean 177 ml yields additional 1.7 kg/ resistant obese and type 2 diabetic mice (db/db) for 4 weeks.
month wt loss. It has been suggested that adjusting with larger volumes will yield RESULTS: We found that S. boulardii treated mice exhibited reduced body
better results. We report our experience with the Spatz 3 device in 7 centers. weight, hepatic steatosis, fat mass and both hepatic and systemic inflammation.
AIMS & METHODS: To determine the difference between the reported results These effects were associated with local effects in the intestine, such as an
of the original Spatz Adjustable balloon System and the new Spatz3 Adjustable increased caecum weight and caecum tissue weight. Importantly, we also found
balloon System with respect to ease of use, complications, weight loss results and that S. boulardii induced dramatic changes in gut microbial communities at the
the effect of larger volume adjustments. 158 patients with mean BMI 40.1; mean phylum, family and genus levels. We also found that microbial changes in
weight 109 kg; mean age 37; were implanted with the Spatz3 device. Mean response to S. boulardii were correlated with host metabolism response.
balloon volume was 473 ml (400-600). Adjustments were made for intolerance CONCLUSION: In conclusion, our study demonstrated that S. boulardii acts as
or weight loss plateau. a beneficial probiotic treatment in the context of obesity and type 2 diabetes.
RESULTS: All endoscopists felt that the Spatz 3 device was easier to use than the Disclosure of Interest: L. Geurts: None declared, A. Everard: None declared, S.
original Spatz adjustable balloon system device. Mean wt loss at 12 weeks was Matamoros: None declared, N. Delzenne: None declared, P. Cani Financial
12.5 kg with an 11.7% wt loss and 28.8 % EWL (% excess wt loss). At 24 weeks support for research from: Biocodex
mean wt loss was 16,2 kg; 16.7% wt loss, and 35,3 % EWL. 94 patients reached 9
months with a reported mean wt loss of 23.2 kg; 20.4 % weight loss; and 44.9 %
EWL. And 48 patients after 12 months with mean wt loss of 24.1 kg; 20.6 % P0546 CORRELATION BETWEEN DIET AND NON-ALCOHOLIC
weight loss; and 48.1 % EWL. There were 49 balloon volume adjustments: 11 FATTY LIVER DISEASE: INVESTIGATION OF A COHORT OF
downward adjustments of 100 cc alleviated early intolerance, with added mean ITALIAN PATIENTS
wt loss of 15.3 kg after the adjustment; 38 upward adjustments (mean 327 ml; L. Abenavoli1,*, M. Pellegrini2, M. Busacchi2, G. Marchesini3, E. Bugianesi4,
range 150-500) at a mean month 4,1 yielded additional mean wt loss of 8.7kg A. Barchetti2, S. Bellentani5
after the adjustment. 7 balloons were extracted; early intolerance and refusal to 1
Health Sciences, University Magna Graecia of Catanzaro, Catanzaro,
adjust volume downward (4); gastric ulcer (2); deflation (1). 2
Diagnostic, Clinical and Public Health, University of Modena and Reggio Emilia,
CONCLUSION: The Spatz 3 adjustable balloon is easier and less complicated Modena, 3Clinical Dietetics, Alma Mater Studiorum University of Bologna,
than the original Spatz device. Complications associated with the original cathe- Bologna, 4Division of Gastro-Hepatology, University of Torino, Torino, 5Centro
ter have not been seen in the Spatz 3 device. Larger volume adjustments yield studi Fegato, Azienda USL Modena, Carpi, Italy
greater weight loss results. Contact E-mail Address: l.abenavoli@unicz.it
Disclosure of Interest: E. Machytka: None declared, Z. Kowalczyk: None
declared, S. Al Awadhi: None declared, M. Al Falasi: None declared, J. INTRODUCTION: The Western diet is characterized by a high-energy intake,
Mason: None declared, L. Bene: None declared, S. El Asala: None declared, saturated fats and refined sugars. Excess calorie intake, associated with reduced
V. Puig-Divi: None declared, M. Buzga: None declared, J. Brooks Shareholder physical activity, leads to obesity, type 2 diabetes mellitus, cardiovascular disease
of: Spatz FGIA and non-alcoholic fatty liver disease (NAFLD).
AIMS & METHODS: Within the FP7 - European FLIP (Fatty Liver Inhibition
Program) program we tried to investigate the role of diet in NAFLD, in a large
P0544 WEIGHT MAINTENANCE 2 YEARS AFTER EXTRACTION OF cohort of patients from three different Italian Centers (Modena, Bologna and
THE SPATZ ADJUSTABLE BALLOON Turin). We used the EPIC questionnaire to investigate energy intake (Ei) and
E. Machytka1,*, L. Bene2, G. Lopez-Nava3, M. Buzga1 intake of food in a well-characterized series of 163 NAFLD patients.
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic, Anthropometric measurements, blood tests, insulin resistance, liver ultrasound
2
Rozsakert Medical Center, Budapest, Hungary, 3Hospital Sanchinarro, Madrid, (Hamagouchi score) and liver stiffness were analysed. Nutrient intakes were
Spain compared with Italian reference values.
Contact E-mail Address: machytka@obezita-balon.cz RESULTS: The daily intake of simple sugars (18.4% vs. a reference intake
515%), saturated fats (12% vs. 510%) and the ratio between animal pro-
INTRODUCTION: The Spatz Adjustable Balloon System was developed to teins/vegetal protein in the diet (68% vs. 550%) was higher than recommended,
provide an adjustable intragastric balloon approved for 1 year implantation. whereas the fiber intake was lower (19g vs. 25g). In the patients, a significant
Weight loss results 4 20 kg/year have been reported in the literature. The ques- direct correlation (p50.005) was observed between BMI, waist circumference,
tion is whether treatment with an intragastric balloon also leads to better weight insulin resistance, transient elastography values, Hamagouchi score, and lipid
loss maintenance after balloon removal. A prospective study on the BIB balloon intake.
has reported maintenance of 4 10% weight loss in 25% of patients for up to 2.5 CONCLUSION: The dietary intakes of NAFLD patients are systematically
years after BIB balloon removal. different from the recommended daily intakes for the Italian population. In
AIMS & METHODS: 79 patients from 3 centers who were implanted with the particular the higher-than-recommended intake of simple sugars might be one
Spatz Adjustable Balloon for 1 year were contacted and asked to provide their of the possible causes of NAFLD (Supported by FLIP Project, (FP7/20072013)
weight 1 year and 2 years post balloon extraction. Net weight changes were under grant agreement no. HEALTH-F2-2009-241762).
recorded, and % weight loss was calculated based on weight prior to balloon REFERENCES
implantation. Net weight loss 4 10% was considered successful weight 1. Ratziu V, et al. A position statement on NAFLD/NASH based on the EASL
maintenance. 2009 special conference. J Hepatol 2010; 53: 372-384.
RESULTS: 70 of the 79 patients contacted (88.6%) were responsive in providing 2. Abenavoli L, et al. Transient elastography in non-alcoholic fatty liver disease.
their weight data. The groups data at the original implantation was as follows: mean Ann Hepatol 2012; 11: 172-178.
weight 120.3 kg (80-180); mean BMI 38.8 (30-65). At the time of balloon extraction 3. Centis E, et al. Stage of change and motivation to healthier lifestyle in non-
(12 months) the groups mean weight loss was 24 kg with a 23.8% weight loss. All of alcoholic fatty liver disease. J Hepatol 2013; 58: 771-777.
the 70 patients had reached at least 12 months post Spatz balloon extraction. Fifty Disclosure of Interest: None declared
three of the seventy (75.7%) retained at least 10% weight loss at 1 year post balloon
extraction. 34 of the 70 patients had reached 2 years post extraction, and 26 (76.4%)
retained at least 10% weight loss. The groups mean weight change was 6.7 kg at 1 P0547 FOOD INTOLERANCE AND OBESITY: NEW STRATEGY IN THE
year and 3.4 kg at 2 years after balloon extraction. TREATMENT OF OBESITY
CONCLUSION: The maintenance of 4 10% Weight loss at 1 year and 2 years M. Rotter1,*
after Spatz Adjustable Balloon extraction has been retrospectively documented in 1
Dietology, UKRAINIAN RESEARCH INSTITUTE OF NUTRITION, Kyiv,
75.7% and 76.4% of patients, respectively. This study is limited by its retro- Ukraine
spective review and the small numbers in year 2 and requires prospective Contact E-mail Address: rottermaria@mail.ru
review to confirm these findings. Nonetheless, it suggests a long term benefit
to longer implantation time and/or adjustable balloon function and warrants INTRODUCTION: Challenges associated with the treatment of obesity still
further study. remain high, in spite of efforts made by professionals combating the public
Disclosure of Interest: None declared health issue. A low-calorie diet, which is considered as the most effective
A284 United European Gastroenterology Journal 2(5S)
treatment, is hard for many patients to incorporate due to the discomfort
P0549 ANALYSIS OF 1973 PATIENTS SUBMITTED TO ENDOSCOPIC
brought by hunger. An effective treatment should focus on increasing the quality
TREATMENT OF EXCESS WEIGHT WITH AN INTRAGASTRIC
of a patients life, by creating a treatment that reduces symptoms associated with
BALLOON
obesity, while allowing patients to not experience hunger during the treatment
period. R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3, B. Sander4, A.F. Teixeira5,
AIMS & METHODS: The aim of the study was to compare the difference in M. Galvao Neto6
1
effectiveness between the traditional low-calorie diet and the elimination diet. A Digestive Endoscopy, 2Nutrition Division, Endogastro Med Service, 3Nutrition
Survey was completed by 60 patients, 30 women and 30 men, with the average Division, UNI-RIO Rio de Janeiro University, Rio de Janeiro, 4Digestive
age 37.6 4.7 years. In addition to routine methods of investigation, all patients Endoscopy, Clnica Sander, Belo Horizonte, 5Digestive Endoscopy, Gastros Bahia,
were analyzed on food intolerance using the FED- test, which is based on the Feira de Santana, 6Digestive Endoscopy, Gastro Obeso Center, Sao Paulo, Brazil
immunetermistometrical principle, a new term we used to describe the conduc- Contact E-mail Address: ricfittipaldi@hotmail.com
tivity and viscosity change in the blood after making contact with certain food
extract. The FED- test uses 96 different food extractions to evaluate food intol- INTRODUCTION: Endoscopic methods, especially the intragastric balloon
erance. To evaluate the improvement of a patients condition, questionnaires were (IGB), have been shown to be effective for the treatment of excess weight.
used before and after the treatment to receive any complaints patients had AIMS & METHODS: OBJECTIVE: To assess the efficacy and complications of
throughout the treatment period. Information about complaints was assessed excess weight treatment with an IGB in patients seen at the Endogastro Med
on a Harington scale of a unit from 1 (no symptoms) to 0.1 (maximum symp- Service clinic, Gastro Obeso Center and Sander clinic.
tom). Patients were divided into 3 equal groups - overweight, and 1 or 2 class METHODS: A total of 1973 patients were analyzed. An Allergan IGB (BIB)
obesity. Each group was divided into two subgroups. Patients in the (A) sub- with a volume of 600 to 700 ml was used. The patients had a minimum initial
group were on a low-calorie diet: 1200-1600 Kcal, depending on the age, sex, and body mass index (BMI) of 27 kg/m2 and were followed up by a multidisciplinary
physical activity. Patients of the (B) sub-group were on the individual eucalorie team consisting of a nutritionist, a doctor and a psychologist. For statistical
(with normal energetic value) elimination diet, based on the results from the analysis, the patients were divided into groups according to sex and degree of
FED- testing. excess weight (overweight and grade I, II and III obesity). Data were analyzed
RESULTS: 1. The influence that the type of diet had on weight reduction. using descriptive statistical methods, the Student t-test, and analysis of variance
Among the first two groups with overweight patients, greater weight loss was followed by the Tukey post-test. The level of significance was set at p50.05.
observed in those patients who adhered to the elimination diet. The difference in RESULTS: 107 patients were excluded from the analysis: 70 (3.55%) due to early
BMI accounted for 0.776 0.222 kg \ m2 in the group A and 1.788 0.449 kg/ IGB removal, 13 (0.66%) due to absence of weight loss, 14 (0.71%) due to weight
m2 in the group B. In obese patients, the following similar results were observed: gain, and 10 (0.51%) due to incomplete data. The incidence of fungus was 0.2%
in the elimination diet weight loss was 3.764 kg \ m2 and 4.065 kg \ m2 in in (n 4) and the incidence of leakage was 0.25% (n 5), pregnancy was 0.1%
patients with class 1 and 2 obesity accordingly. In low-calorie diet, BMI reduc- (n 2); Wernick Korsakoff syndrome due to excessive vomiting was 0.05%
tion was 1.291 kg \ m2 and 2.280 kg \ m2 in patients with class 1 and 2 obesity (n 1), gastric perforation and upper digestive bleeding was 0.05% each
accordingly. (n 1). Of the 1866 remaining patients, 1402 were women and 464 were men.
2. Improvements in patients condition. On the elimination diet improvement of Mean age was 37.32 years. The patients showed a significant weight loss, with a
the patients condition amounted to 0.292 in the obese group, and 0.222 in the significantly lower final BMI (mean: 28.934.71 kg/m2; range: 18.98-57.38) than
overweight group. In groups in which patients followed the low-calorie diet, no the initial BMI (mean: 36.475.61 kg/m2; range: 27-74.74) (p50.0001). Mean
significant dynamics in the state of the patients were observed: 0.046 in a group BMI reduction was 7.553.49 kg/m2 (range: 0.36-29.79). Mean percent weight
of obese patients and 0.034 patients in the overweight group. loss was 20.437.82% and mean percent excess weight loss (EWL) was
CONCLUSION: Under the influence of elimination diet BMI reduction was 73.4836.71% (range: 2.22-431.1). Percent EWL was higher in the overweight
significantly better in patients with 1 and 2 class obesity compared to the group, followed by obesities grades I, II and III sequentially (p50.0001). Percent
dynamics of BMI on the standard low-calorie diet (p 0.0037). Between EWL was also higher in women than in men (p50.0001).
groups of patients who were overweight, no significant differences were found CONCLUSION: Endoscopic treatment of excess weight with an IGB has been
(p 0.087). established as an excellent therapeutic option for patients of both genders with
The patients quality of life after 6 months of treatment differed significantly in overweight or different degrees of obesity.
subgroups of those treated with the elimination diet, compared to the subgroups Disclosure of Interest: None declared
of those that received the standard low-calorie diet treatment (p 0.004).
Disclosure of Interest: None declared
P0550 PREDICTIVE RISK FACTORS FOR SUCCESS OF BARIATRIC
THERAPY WITH BIOENTERICS INTRAGASTRIC BALLOON
P0548 ARGON PLASMA FULGURATION TO TREAT WEIGHT REGAIN R. Cerqueira1, M. Correia1,*, M.C. Manso2
AFTER BARIATRIC SURGERY 1
Gastroenterology, Centro Hospitalar entre Douro e Vouga, Santa Maria Feira,
R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3 Santa Maria Feira, 2Biostatistics - Requimte-up, University Fernando Pessoa,
1
Digestive Endoscopy, Endogastro Med Service, 2Nutrition Division, UNI-RIO Rio Porto, Portugal
de Janeiro University, 3Nutrition Division, Endogastro Med Service, Rio de Contact E-mail Address: rute.cerqueira@chedv.min-saude.pt
Janeiro, Brazil
Contact E-mail Address: ricfittipaldi@hotmail.com INTRODUCTION: In obese patients, a large amount of data shows that bar-
iatric therapy with Bioenterics intragastric balloon (BIB) results in weight loss in
INTRODUCTION: The weight regain is a problem after bariatric surgery and some patients. However there is a paucity of data about predictive risk factors for
occurs, in part, by dilatation of the gastro-jejunal anastomosis, which causes a BIB success.
faster gastric emptying and increased food intake. AIMS & METHODS: The aim of this study was to determine the effectiveness of
AIMS & METHODS: Objective: To evaluate the efficacy of endoscopic fulgura- this device on weight loss and predictive risk factors for BIB success. A prospec-
tion of the anastomosis and of the gastric stump using argon plasma (APF) tive study with 147 patients [(75.5% females, mean age 40 (11.9)] submitted to
aiming to reduce the diameter thereof. BIB insertion, which was removed after 41.4 (12.7) weeks. Anthropometric and
Methods: We analyzed 32 patients. 30 of them underwent at least 02 sessions of laboratory parameters were assessed when BIB was positioned and when BIB
FPA. Two patients underwent only one session due to an immediate reduction of was removed. BIB success was defined as weight loss 50% of the weight excess
the anastomosis to a diameter smaller than 10 mm after the first session, wich is (pre BIB weight calculated weight to lower the BMI to 24.9).
the procedure target. The coagulation was held at the anastomosis and in gastric RESULTS: At baseline, mean weight was 97.2 Kg ( 16.1), mean body mass
stump. 80 w power was used in the 1st session, and 70w power FPA in the index (BMI) was 36.5 (5.9) kg/m2, 19 (12.9 %) patients had type II Diabetes
following, with an Agon flow of 2L/min. The objective is to obtain an anasto- Mellitus and mean insulin resistance (HOMA-IR) was 2.9 ( 2). With BIB
mosis with a diameter less than or equal to 10 mm. Data were analyzed with intervention, mean weight and mean BMI decreased, respectively, to 83.5 (
descriptive statistics, students t test and Spearman correlation. 16.9), p5 0.001 and 31.4 (6.3), p50.001. Regarding laboratory parameters,
RESULTS: Of the 32 patients, 87.5 % were women (n 28). The mean regained cholesterol, triglycerides and HOMA-IR were significantly reduced (p50.05).
weight in relation to the maximum weight lost (Nadir) after bariatric surgery was There was no significant improvement in TGP, G-GT, HDL cholesterol and
46.9 % (14 to 76.9). The mean duration of treatment was 170 days (56-338). ferritin. BIB success was observed in 57 (38.8%) patients. Predictive risk factors
There was a significant reduction in body mass index (BMI) at the end of the for BIB success were mean pre-operative weight, 92.8 (13) vs 99.7 ( 16.9)kg,
analysis (32.424.45 kg/m2) compared to the initial mean BMI (mean p 0.011 and mean pre-operative BMI, 35 (3.5) vs 37.5 (6.9), p 0.007; a
BMI 37.054.76 kg/m2) (p 5 0.0001). The average loss of the regained trend was observed for baseline HOMA-IR, 2.7 (2.3) vs 3 (1.7), p 0.056.
weight was 66.92% (22.08-211.11). The average weight loss in Kg was 12.73 CONCLUSION: BIB therapy achieves significant weight loss and significantly
(6.3-25.5). There was significant correlation between the reduction in the BMI improves laboratory parameters of the metabolic syndrome in obese patients.
and the highest number of sessions of FPA (p 0.0003) and between the longer BIB success is associated with baseline weight and baseline BMI further empha-
duration of the treatment (p 0.0212). The analyzed patients remain in sizing that the endoscopic technic has major impact in mild obese, those that are
treatment. not surgical candidates.
CONCLUSION: The FPA has demonstrated great efficacy in the treatment of Disclosure of Interest: None declared
weight regain after bariatric surgery of gastric bypass in Roux-Y.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A285
P0551 PREOPERATIVE ENDOSCOPY IN ASYMPTOMATIC P0553 NUTRIENT INTAKES AT THE TIME OF DIAGNOSIS IN
BARIATRIC PATIENTS IS IT STILL WORTH IT? PATIENTS WITH HIV INFECTION: COMPARISON WITH
S.R. Fernandes1,*, L. Meireles1, L.A. Correia1, L.C. Ribeiro1, J. Velosa1 NATIONAL NUTRITIONAL GUIDELINES AND WITH A COHORT
1
Gastrenterologia e Hepatologia, Hospital Santa Maria - Centro Hospitalar Lisboa OF HEALTHY SUBJECTS
Norte, Lisboa, Portugal B. Zanini1,*, R. Bosio1, N. Brianese1, A. Ferraresi1, A. Arrighi1, E. Quiros-
Contact E-mail Address: Samuelrmfernandes@gmail.com Roldan1, F. Castelli1, A. Lanzini2
1
Department of Clinical and Experimental Sciences, 2UNIVERSITY AND
INTRODUCTION: Obesity represents a major public health problem associated SPEDALI CIVILI OF BRESCIA, Brescia, Italy
with increased risk of diabetes, cardiovascular and cerebrovascular disease and Contact E-mail Address: b_zanini@tin.it
cancer. Surgery has shown to be an effective long term treatment. Preoperative
endoscopy (POE) is recommended by the current "guidelines", but evidence INTRODUCTION: Assessment of nutrient intake is an important key element in
supporting this recommendation in asymptomatic patients is scarce. healthcare of HIV patients because nutritional status is a determinant of HIV
AIMS & METHODS: We sought to determine whether endoscopic findings outcomes and of many co-morbidities including gastrointestinal problems, osteo-
justify routine POE before bariatric surgery. Obese (BMI4 30 kg/m2) and mor- porosis, cardiovascular diseases, diabetes and other metabolic changes (1,2).
bidly obese (BMI4 35 kg/m2) patients undergoing endoscopy in our institution Little is known about nutritional adequacy among HIV patients at the time of
were retrospectively selected. Endoscopic and histological findings and their diagnosis and prior to pharmacological treatment.
impact on surgical strategy were assessed. AIMS & METHODS: We carried out a prospective clinical study to assess
RESULTS: Of 557 patients (78.3 % female, mean age 46.911.5 years), 43.3 % macro- and micro-nutrient components of diet in a cohort of HIV patients at
had a normal endoscopy. Esophageal, gastric and duodenal disease were present the time of diagnosis, and to compare them with Italian recommended levels of
in 22.6 %, 44.2 % and 11.0 % respectively. The most frequent esophageal find- nutrient intake (LARN 2012) and with those of a cohort of healthy subjects,
ings were hiatus hernias (17.2 %) and esophagitis (8.0 %, 97.5 % Class A and B matched with HIV cohort according to gender and age (range 4 years).
of Los Angeles). Gastric changes included erosive (18.3%) and non-erosive gas- Patients in the two cohorts were instructed to fill in a standardized 7-day food
tritis (19.7%), polyps (4.8%) and ulcers (1.6%, all Forrest III). Bulbitis (10.4%), diary. Data from diaries were analyzed with Microdiet software (Downlee
ulcers (0.5%) and polyps (0.2%) composed most common duodenal findings. system, ltd. UK) and nutritional characteristics studied were: total Kcal, propor-
From a total of 218 gastric biopsies 46.3% revealed the presence of tion of total energy value of CHO, free sugars, proteins, fats, SFA and PUFA,
Helicobacter pylori (Hp) bacilli. In 3 patients Barretts esophagus was diagnosed and total amounts of fibre, vitamins A, B12, C, and D, folates, sodium, calcium,
(without dysplasia) and in 2 gastric low grade MALT lymphoma (which iron, zinc. For statistical analysis Fishers exact test and Wilcoxon matched pairs
regressed after eradication of Hp). test were used as appropriate.
CONCLUSION: Our findings were of little relevance and did not alter the RESULTS: 22 HIV patients signed informed consent, 21 returned the diary and
operative strategy. Given the high prevalence of Hp, which has been associated 14 were at present analyzed. Eleven were male, age 42 1 year (mean SD),
with higher postoperative complications, its screening by non-invasive methods BMI 23.8 3.3 Kg/m2 with 4 patients in overweight class, 1 in grade 1 obesity
prior to surgery may be a less expensive alternative. This study suggests that EPO class and 9 in normal BMI class. Comparison of selected nutrient composition
might be dispensable in asymptomatic bariatric patients. with LARN and with healthy subjects are reported in the table.
Disclosure of Interest: None declared
Nutrients HIV patients Healthy subjects HIV Vs LARNx %
P0552 MODIFIED PROBIOTIC ESCHERICHIA COLI NISSLE
CHO, % TEV 48.26.9 40.05.6* - 21
INCREASES COLONIC SHORT CHAIN FATTY ACIDS AND FECAL
BIFIDOBACTERIA AND LACTOBACILLI COUNT IN RATS Fats, %TEV 33.26.0 37.03.4* 36
A.K. Singh1,*, S. Pandey1, A.S. Parihar1, N.K. Gattupalli1 Proteins, %TEV 16.32.2 16.62.6 79
1 Vitamin B12, mg 3.71.4 2.50.8* -21
Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India
Contact E-mail Address: singhashish1186@gmail.com Vitamin D, mg 2.51.8 3.41.6 -100
INTRODUCTION: Short Chain Fatty Acids (SCFAs) are considered as one of Folates, mg 191.644.6 140.349.8* -100
the most important metabolite produced by commensal organism in the gut. Calcium, mg 508.9133.0 771.0253.9 -100
Dietary consumption of complex carbohydrates such as inulin, fructo-oligosac- Iron, mg 7.01.4 9.72.3* -100
charides and sodium gluconate are known to increase SCFAs in the colon. Zinc, mg 8.41.5 8.82.1 -79
However, they limit in their efficacy if not consumed daily. E. coli represents a
major commensal population the human colon. E. coli expresses an apo- form of
membrane bound enzyme, glucose dehydrogenase, which converts glucose to
gluconic acid. However, it is unable to synthesize the cofactor, PQQ CONCLUSION: Daily intake is inadequate in HIV patients at time of diagnosis
(Pyrroloquinoline quinone). E. coli produces gluconic acid when PQQ is supplied for most macro- and micro- nutrients, but is closer to LARN recommendations
in the medium. than in healthy subjects. Nutritional counseling must be provided in HIV na ve
AIMS & METHODS: We hypothesized that, recombinant probiotic E. coli patients in order to improve their nutritional status and to contribute to preven-
Nissle 1917 (EcN) expressing PQQ synthesis genes is able to synthesize large tion of gastrointestinal and metabolic co-morbidities.
amount gluconic acid in the intestine and subsequently increased production of REFERENCES
SCFAs. Hendricks KM, et al. Am J Clin Nutr 2008; 88: 1584-1592.
pqqABCDE gene cluster was cloned and expressed in EcN. Rats were fed with 2) Giudici KV et al. Sao Paulo Med J 2013; 131: 145-152.
starch containing diet along with recombinant probiotic EcN for 60 days. Disclosure of Interest: None declared
RESULTS: Recombinant EcN expressing pqqABCDE gene cluster produces high
amounts of gluconic acid in M9 minimal medium supplemented with glucose
under laboratory conditions. Weekly treatment of recombinant EcN producing P0554 SUPPLEMENTATION WITH A PROBIOTIC MILK DRINK DOES
gluconic acid results in increased production of gluconic acid in the colon. NOT ALTER GUT MICROBIOTA COMPOSITION IN PATIENTS
Additionally, SCFAs (Butyrate and Acetate) concentration was also found to WITH METABOLIC SYNDROME
be elevated by approximately 3 fold and 1.6 fold respectively. mRNA profile of B. Leber1,*, N. Tripolt2, S. Trajanoski3, C. Hogenauer4, H. Sourij2,
colon showed increased expression of mucin and intestinal trefoil factor genes in V. Stadlbauer4
treated rats. The treated rats also had increased fecal Bifidobacteria and lactoba- 1
Transplantation Surgery, 2Endocrinology and Metabolism, 3Center for medical
cilli number. Research - Bioinformatics, 4Gastroenterology and Hepatology, Medical University
CONCLUSION: The present study suggest that engineered probiotic could be a of Graz, Austria, Graz, Austria
potent nutritional supplement against intestinal dysbiosis and other related Contact E-mail Address: bettina.leber@medunigraz.at
pathologies.
REFERENCES INTRODUCTION: Metabolic syndrome (MetS) is associated with disturbances
Kameue C, et al. Dietary sodium gluconate protects rats from large bowel cancer in gut microbiota including changes in the Bacteroidetes/Firmicutes ratio. In
by stimulating butyrate production. J Nutrition 2004; 134: 940-944. animal models, modulation in the composition of gut microbiota through sup-
Rucker R, Chowanadisai W and Nakano M. Potential physiological importance plementation with probiotics is possible. It is not known to date if this is also
of pyrroloquinoline quinone. Alternative Med Review 2009; 14. possible in humans.
Biagi G, et al. Effect of gluconic acid on piglet growth performance, intestinal AIMS & METHODS: We therefore aimed to study whether supplementation
microflora, and intestinal wall morphology. J Animal Sci 2006; 84: 370-378. with a probiotic milk drink containing Lactobacillus casei Shirota (LcS) is able to
Asano T, et al. Effects of gluconic acid on human faecal bacteria. Microbiol Ecol modulate gut microbiota composition in patients with MetS. In a single-center,
Health Dis 1994; 7: 247-256. prospective, randomized-controlled pilot study, 28 subjects with MetS received
Sonnenborn U and Schulze J. The non-pathogenic Escherichia coli strain Nissle either LcS (YAKULT light 3 bottles a day, 65 ml each, containing LcS at a
1917 features of a versatile probiotic. Microb Ecol Health Dis 2009; 21: 122-158. concentration of 108/ml) for 12 weeks (LcS group; n 13) or received standard
Disclosure of Interest: None declared medical therapy (n 15). 6 healthy subjects served as controls. Stool samples
were collected at baseline and after 3 months. Gut microbiota composition was
characterized using 454 pyrosequencing of the amplicon libraries from V1 to V3
hypervariable regions of 16S rRNA genes. Generated sequencing data was ana-
lyzed with Quantitative Insights Into Microbial Ecology (QIIME version 1.7.0)
pipeline in stool samples.
RESULTS: No significant differences in Unifrac distances or Bray-Curtis dis-
tances between samples from the same patients in two time points were found
A286 United European Gastroenterology Journal 2(5S)
(p 0.70 and 0 0.48, respectively). The Bacteroidetes/Firmicutes ratio was not superior and arteria splenica) were performed for the patients. The investigation
different compared to healthy controls and was not influenced by probiotic was undertaken with fasting after feeding test, with the ultrasound scanner
supplementation (Controls: 0.783; LcS baseline: 0.961; LcS 3 months: 1.007; Sonoace-8000 (Medison, South Korea).
Standard baseline: 0.921; Standard 3 months: 0.995). Diversity (using Shannon RESULTS: The signs of malnutrition in patients with hereditary connective
index) and richness of gut microbiota in MetS showed similar distribution com- tissue disorders have been revealed in 70,9% of cases. The degree of malnutrition
pared to healthy controls and was not influenced by probiotic supplementation. has been correlated with the expression of hemodynamic disturbances (r -0,55;
LcS was only detectable in 1 individual of the treatment group after 3 months of o50,001).
supplementation with LcS. By estimating the abdominal blood flow in persons with hereditary connective
CONCLUSION: In our study no difference in gut microbiota composition was tissue disorders more lower volume rates of a blood flow were recorded: along
found between healthy subjects and patients with MetS. The supplementation of vena portae - 1853,0 [1688,0-2297,0] ml/min., in the group of comparison -2149,0
LcS did not change gut microbiota composition, so we conclude that the micro- [1827,0-2400,0] ml/min (o50,05); along arteria mesenterial superior - 988,0
biota variations occurring in the treatment group were not larger than the nor- [837,0-1272,0] ml /min, in the group of comparison - 1136,5 [992,0-1465,0] ml/
mally expected variations during this time period. This is in accordance with our min (o50,05); along the vessels of a celiac trunk: arteria hepatica communis -
previous findings that supplementation with LcS did not influence clinical and 480,5 [425,0-587,0] ml/min, in the group of comparison - 591,5 [536,0-689,0] ml/
biochemical parameters of glucose metabolism, inflammation and innate immune min. (o50,001) and splenic arteries - 600,0 [452,0-709,0] ml/min, in the group of
response. comparison - 700,0 [591,0-795,0] ml/min (o50,01). After meal the persons with
Disclosure of Interest: None declared hereditary connective tissue disorders had fewer high-speed indicators gain and it
didnt exceed 30% from the initial indicators (o50,001).
The data of the abdominal blood flow were correlated with some central hemo-
P0555 QUANTIFICATION OF IN VIVO COLONIC SHORT CHAIN dynamic changes (minute volume of circulation): at the vena portae (r 0.55, o
FATTY ACID PRODUCTION FROM INULIN 50,05), at the arteria hepatica communis (r 0.60, o 50,05), at the splenic
E. Boets1,*, E. Houben1, S. Gomand2, J. Delcour2, K. Verbeke1 artery (r 0.77 o 50,05); by the extent of vegetative sympathetic influences on
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and a vascular tonus: at the arteria hepatica communis (r -0,48, o50,05), at the
Nutrition Research Centre, 2Laboratory of Food Chemistry and Biochemistry, splenic artery (r -0,27, o50,05), at the arteria mesenterial superior (r -0,36, o
Leuven Food Science and Nutrition Research Centre, KU Leuven, Leuven, Belgium 50,05); by splanchnoptosis degree: at the portal vein (r -0,210; o50,05), at the
Contact E-mail Address: eef.boets@med.kuleuven.be arteria hepatica communis (r -0,38; o50,05), at the arteria mesenterial superior
(r -0,86; o50,05).
INTRODUCTION: Short chain fatty acids (SCFA; acetic (Ac), propionic (Pr) CONCLUSION: The signs of malnutrition in patients with hereditary connective
and butyric (Bu) acid) are produced during bacterial fermentation of undigested tissue disorders have been revealed in 70.9% of cases. The degree of malnutrition
carbohydrates in the colon. In this study, we determined the bioavailability of has been correlated with the expression of systemic connecting tissue involve-
each SCFA and applied a stable-isotope dilution method to quantify the colonic ment. The postprandial period abdominal blood flow has been characterized by
production of SCFA after consumption of inulin. the low values of volume rate at the vessels of the celiac trunk, arteria mesenterial
AIMS & METHODS: Six healthy subjects (3F/3M; 297y) each performed 4 superior, and portal vein. Some disturbances of a cardiac hemodynamic, preva-
test days with minimal 1 week interval. On the first 3 test days they received lence of sympathetic influences on vascular tonus, splanchnoptosis presence may
either 400mg 13C-Ac or 340mg 13C-Pr or 990mg 13C-Bu in a pH-dependent colon be considered to be the main causes of blood flow decreasing.
delivery capsule with a standard breakfast. After collection of a basal blood Disclosure of Interest: None declared
sample, they received a primed constant infusion of 2H-labelled SCFA
(Ac:20mmol/kg.h; Pr:2mmol/kg.h; Bu:1mmol/kg.h) for 12h. On the 4th test day,
the SCFA production from inulin fermentation was quantified. The subjects P0557 OPTIMIZATION OF DIAGNOSIS AND TREATMENT OF
received 15g of inulin (Raftilin HP, Beneo-Orafti) with a standard breakfast NUTRITIONAL INSUFFICIENCY IN PATIENTS WITH
and an infusion with 13C-SCFA (Ac:12mmol/kg.h; Pr:1.2mmol/kg.h; INFLAMMATORY BOWEL DISEASE
Bu:0.6mmol/kg.h) for 12h. Additional blood samples were collected at regular A.A. Iakovlev1,*, T.S. Kazaryan1
times during the day. Plasma total SCFA concentrations, 13C- and 2H-SCFA 1
gastroenterology, ROSTOV ON DON STATE MEDICAL UNIVERSITY,
enrichments were measured using gas chromatography (GC), GC combustion Rostov on Don, Russian Federation
isotope ratio mass spectrometry (IRMS) and GC pyrolysis IRMS, respectively. Contact E-mail Address: gastroklinika@yandex.ru
The bioavailability index (F) of the respective SCFA was calculated from the area
under the curve (AUC) of the 13C-SCFA concentration time curve (F AUC x INTRODUCTION: Development of nutritional deficiency (ND) due to the loss
Cl x 100/administered dose). The clearance rate (Cl) was determined using the of nutrients, water and electrolytes with frequent stools, nutrients malabsorption,
2
H-SCFA infusion (Cl infusion rate (i)/steady state (SS) 2H-SCFA concentra- anorexia and increased catabolism is typical for patients with IBD relapse. To
tion). SCFA turnover was calculated using stable-isotope dilution. The infusion determine the frequency and structure of ND in patients with IBD relapse and to
with 13C-SCFA results in a constant 13C-SCFA enrichment in the blood. After evaluate the therapeutic effect of nutritional support (NS) of nutritive mixtures
fermentation of inulin in the colon, SCFA enter the blood and dilute the 13C- during the course of therapy.
SCFA resulting in a decrease of 13C-SCFA enrichment. The total turnover (T) of AIMS & METHODS: Two-phase three step study with prospective monitoring
the SCFA at each time was calculated as follows: T i x [(Tracer enrichment/ in patients with IBD was conducted during 3 years in the period from 2010 to
Plasma enrichment)-1]. The turnover at SS was subtracted from the total turn- 2012. The first phase was carried out using a one-time screening scales MUST
over to obtain the exogenous SCFA turnover. The AUC was calculated to yield and NRS, further in phase 2, the NS structure was refined. 520 patients with IBD
total SCFA appearance in plasma. Finally, the bioavailability index and SCFA were examined: 410 with ulcerative colitis (UC) and 110 with Crohns disease
plasma concentrations were used to quantify the SCFA produced in the colon. (CD).
Results are expressed as medians and interquartile ranges. RESULTS: The 1st, 2d and 3d degree of ND was detected in 111 (27.1%), 96
RESULTS: The bioavailability index of Ac, Pr and Bu were 37 [30-57]%, 21 [17- (23.4%) and 42 (10.2%) patients with UC, respectively. 2d and 3d degree of ND
25]% and 4 [3.5-9]%, respectively. SS turnover of Ac, Pr and Bu were 13 [8-16], was recorded in 48 (43.6%) and 29 (26.4%) cases in patients with CD, respec-
0.23 [0.19-0.31] and 0.26 [0.15-0.34] mmol/kg.min, respectively. The total amount tively. At the second stage of the study, 80 patients with UC were randomized
of Ac in plasma was 661 [512-991] mmol/kg; corresponding to a production of 112 into two major groups, depending on the degree of NN, were divided into groups
[88-194] mmol of Ac in the colon within 12h after inulin ingestion. The AUC of A (2d degree of ND) and B (3d degree of ND). On basic therapy, patients of the
Pr and Bu were 14 [9-22] and 13 [10-15] mmol/kg, respectively. Twelve hours after Ist group received a diet with a high amount of protein (HAPD) and increased
inulin ingestion a total of 0.9 [0.6-1] and 0.7 [0.6-1] mmol of Pr and Bu appeared calorage (2500 kcal / day), while to the patients of the IId group in addition to the
in the circulation. The colonic produced Pr and Bu levels were 4 [2-6] and 19 [11- basic therapy, nutritional mixtures: peptamen and modulen IBD (Nestle) in the
24] mmol, respectively. amount of 1/3 of the daily calorage were prescribed. Efficacy of treatment was
CONCLUSION: In conclusion, inulin is mainly fermented into acetate followed evaluated on the 3 d, 4th, 12th week. At the third stage of the study, during 3
by butyrate and propionate. Stable isotope technology allows to quantify in vivo years, the long-term results were studied using index of the relapse frequency
SCFA production from carbohydrate fermentation and will facilitate the evalua- (IRF). Pick of the IRF was in the 1st group and by the end of the study it was 15
tion of health benefits attributed to SCFA. (75%) and 17 (85%) cases, respectively. In the second group IRF was signifi-
Disclosure of Interest: None declared cantly lower: 9 (45%) and 12 (60%) (p 50,05).
CONCLUSION: In patients with UC and CD relapse ND of the 1st and 3d
degree was recorded an average of 20.3% and 35%, respectively. Use of NS
P0556 ABDOMINAL HEMODYNAMIC IN PATIENTS WITH provides a low rate UC relapse, and thus stable remission of the disease.
MALNUTRITION AND HEREDITARY CONNECTIVE TISSUE Disclosure of Interest: None declared
DISORDERS
G. Nechayeva1, M. Livzan1, E. Lialiukova1,*
1
Omsk state medical academy, Omsk, Russian Federation P0558 TEDUGLUTIDE FOR PATIENTS WITH SHORT BOWEL
SYNDROME-INTESTINAL FAILURE. A SINGLE CENTER
INTRODUCTION: The aim of the research is to study the peculiarities of EXPERIENCE
abdominal hemodynamic in patients with malnutrition and hereditary connective A. Ukleja1, A. Alvarez1,*, K. Alvarez2, L. Lara1
tissue disorders. 1
Gastroenterology, CLEVELAND CLINIC FLORIDA, Weston, United States,
AIMS & METHODS: To study mechanisms of malnutrition at the patients with 2
Nutrition, Licda Nutricion Clnica & Bariatrica, Guatemala City, Guatemala
hereditary connective tissue disorders. Contact E-mail Address: uklejaa@ccf.org
121 patients with hereditary connective tissue disorders were included in the
research (The revised Ghent nosology for the Marfan syndrome, 2010). The INTRODUCTION: Teduglutide (TG) is a novel agent recently approved for the
control group was represented by 40 healthy subjects to be comparable by sex treatment of parenteral support (PS) dependent patients with short bowel syn-
and age. The assessment of malnutrition and ultrasonic dopplerography of the drome (SBS). PS dependence is a major concern for patients with SBS because of
abdominal vessels (vena portae, arteria hepatica communis, arteria mesenterial PS caries a risk of serious complications and affects quality of life. In phase III
United European Gastroenterology Journal 2(5S) A287
trial, TG use lead to significant reduction in PS volume in SBS patients. Limited success rate, but median procedure time decreased from 33 (18-45) to 20 (15-30)
data is available regarding clinical results outside the research protocols. minutes.
AIMS & METHODS: Aims: To evaluate short and long-term outcomes of SBS CONCLUSION: Bedside EM-guided placement of nasojejunal tubes after pan-
patients receiving TG and assess patients interest in TG therapy. Methods: creatoduodenectomy was successful in 58% of patients, which seems acceptable
Retrospective medical chart review was conducted. 19 pts. with SBS were identi- given the potential benefits for the patient. Based on these findings we have
fied. Demographics, length of small bowel, primary diagnosis, past surgical his- included patients after pancreatoduodenectomy in an ongoing randomized multi-
tory, PS (TPN/IV fluids) volume and duration, TG dose and related center trial focussing on the magnitude of benefits of EM-guided placement, such
complications were collected. SBS patients who received TG from 04/2013 to as reduced patient discomfort and costs as compared to endoscopy.
03/2014 were included in the final analysis. Disclosure of Interest: None declared
RESULTS: 6 of 19 SBS pts. received TG (Females 4, Males 2); Race: Caucasian
4, Hispanic 1, African-American 1. Mean age: 45.8 yrs. (range 26-71). Cause of
SBS: vascular 3, RYGB/strangulation 1, surgical resections 2. SB length: range P0560 PROSPECTIVE STUDY OF PERISTOMAL INFECTIONS AFTER
30-120 cm. Colon in continuity 4, stoma 3 (ileostomy 2, colostomy 1). TPN PERCUTANEOUS ENDOSCOPIC GASTROSTOMY OVER A FOUR-
duration: range 114 years. PS volume/week 1-8 Liters. Duration of TG ther- YEAR PERIOD
apy:1-12 months. Complications: bowel obstruction (SBO) 1, stoma swelling 2, C.R. Chimakurthi1,*, S. Lewis1, N. Pitts2, V. Chudleigh3
bloating 4 (subsided). TG discontinuation 1 (SBO*), TG dose reduction 1 (stoma 1
Gastroenterology, 2Endoscopy, 3Remedial Services, Plymouth Hospitals NHS
swelling). PS discontinued 4. Volume reduction in 6/6 pts. Gain or stable weight Trust, Plymouth, United Kingdom
in all while on TG. No biliary/pancreatic complications, TG injection aversion Contact E-mail Address: cchimakurthi@nhs.net
were seen. Reason for no TG therapy in 13 pts.: No TG candidates 4 (recent
cancer 2, post surgery 512 months 1, massive small bowel dilation 1), no insur- INTRODUCTION: Incidence of peristomal infections following percutaneous
ance approval 1, no interest in TG therapy 8. Characteristics of SBS patients who endoscopic gastrotomy in the community is not well known. Data on subsequent
received TG therapy. site infections and the organisms responsible is limited. Despite the use of pro-
phylactic antibiotics, the incidence of peristomal infections is significant and
SB PS PS PS result in substantial morbidity in patients with PEGs.
length Colon Duration Volume Reduction PS TG duration AIMS & METHODS: We aim to evaluate the prevalence of peristomal infection
Pts. Age Sex (cm) present (years) (Week) 420% Stopped (months) in our local community over a four year period after their PEG placement. Other
objectives were to characterise the microbiology from wound site swabs and to
1 52 F 90 N 1.5 8L Y N 1 identify any correlation between peristomal infection and patient characteristics.
2 29 F 30 Y 14 7.2L Y Y 12 Our study also looked at incidence of subsequent peristomal infection rates in the
3 26 F 70 Y 5 6.4L Y Y 9 community prospectively over a 4-year period.
4 36 M 50 Y 2 7.5L Y Y 6 Patients aged 16 and over who have had percutaneous endoscopic gastrostomies
5 61 F 120 N 2 1L Y Y 5 placed at Derriford hospital, Plymouth, UK during years 2008 to 2012 were
included in the study period. Patients with venting gastrostomies and those
6 71 M 90 Y 2 7L Y N 4 (TG stopped*)
who had their gastrostomies placed while undergoing treatment for Head &
Neck cancer were not included in this study. All patients had their PEGs
placed according to British Society of Gastroenterology guidelines with pre-pro-
CONCLUSION: From our eligible SBS patients only 6/14 (43.8%) received TG cedure prophylactic antibiotics. Community enteral feed dieticians followed all
and 4 50% of them expressed no interest in TG therapy. Three PS/nutrient patients at clinically appropriate intervals in the community following discharge
dependent patients with colon in continuity and one with end-stoma discontin- from hospital. They recorded incidence of infections and various other complica-
ued PS completely with TG therapy. All patients had 420% reduction in PS tions over the four-year period. Endoscopy reports, clinical case records, and
volume while on TG. All had significant reduction in stoma/stool output. TG microbiological investigation results were also reviewed. Excel and Stata 10 were
was well tolerated. Further studies with a larger sample size are needed in SBS used for data collection and analysis.
patients to assess clinical benefits of TG and address patient decision process RESULTS: 341 patients underwent percutaneous endoscopic gastrostomy
regarding this therapy. during the study period. 110 patients (31%) needed treatment for an insertion
Disclosure of Interest: A. Ukleja Consultancy for: NPS, A. Alvarez: None site infection. The median time from PEG insertion to first wound site infection
declared, K. Alvarez: None declared, L. Lara: None declared was 85 days (14, 363). Mixed skin commensals (42.7%) followed by
Staphylococcus aureus (29%) were most frequently isolated from gastrostomy
wound site swab. Only one patient had Methicillin resistant staphylococcus
P0559 BEDSIDE ELECTROMAGNETIC GUIDED PLACEMENT OF aureus isolated. The spectrum of organisms for subsequent peristomal infection
NASOJEJUNAL FEEDING TUBES IN PATIENTS AFTER was similar to those causing the first infection. The majority of infections
PANCREATODUODENECTOMY: PROSPECTIVE SINGLE-CENTER resolved with appropriate treatment. Indications for PEG insertion, age, sex
PILOT STUDY and residence did not correlate with peristomal infection. Two patients needed
A. Gerritsen1,*, A.C. Duflou2, M. Ramali2, O.R. Busch1, D.J. Gouma1, replacement with new PEG tubes in view of infection. Both of them needed their
L.M. Mathus-Vliegen2, M.G. Besselink1 PEG tubes replaced thrice further. No specific organisms were associated with
1
Department of Surgery, 2Department of Gastroenterology, Academic Medical the removal and replacement of PEG tubes.
Center, Amsterdam, Netherlands CONCLUSION: Our rates of peristomal infection are similar to previous stu-
Contact E-mail Address: a.gerritsen@amc.nl dies1. Although staphylococcus aureus was frequently isolated from insertion
site, the prevalence of MRSA was much lower in our cohort2. The time from
INTRODUCTION: Early oral feeding is now considered the routine feeding PEG insertion to initial infection was also much longer2.
strategy after pancreatoduodenectomy. Some 35-45% of patients will develop REFERENCES
delayed gastric emptying postoperatively and consequently require nasojejunal 1. Zopf Y, Konturek P, et al. Local infection after placement of percutaneous
tube feeding. Endoscopic placement of a nasojejunal feeding tube by gastroen- endoscopic gastrostomy tubes: a prospective study evaluating risk factors. Can J
terologists is relatively labour-intensive and a cumbersome procedure for Gastroenterol 2008; 22: 987-991.
patients. Bedside electromagnetic (EM) guided placement using the Cortrak 2. Duarte H, Santos C, et al. Peristomal infection after percutaneous endoscopic
Enteral Access System by nurses has been found to be a simple, safe and cost- gastrostomy: a 7-year surveillance of 297 patients. Arq Gastroenterol 2012; 49:
effective strategy in several patient categories. To date, however, an altered anat- 255-258.
omy of the upper gastrointestinal tract is seen as a relative contraindication for Disclosure of Interest: None declared
EM-guided tube placement.
AIMS & METHODS: The aim of this study was to determine the success rate of
bedside EM-guided placement of nasojejunal feeding tubes in patients after P0561 RESTORATION OF BOWEL CONTINUITY CAN REDUCE THE
pancreatoduodenectomy. RISK OF CHRONIC CHOLESTASIS IN PATIENTS WITH A SHORT
We performed a prospective single-center pilot study in all patients requiring a BOWEL
nasojejunal feeding tube after pancreatoduodenectomy between July 2012 and F. Adaba1,*, C. Vaizey1, S. Gabe1, J. Warusavitarne1, J. Nightingale1
March 2014. EM-guided nasojejunal tubes were placed by two specialized nurses 1
St Marks Hospital, Harrow, United Kingdom, London, United Kingdom
with extensive experience with the technique. EM-guided placement was not Contact E-mail Address: f.adaba@nhs.net
performed in patients with upper gastrointestinal stenosis or oesophageal varices
or when it was not possible for logistical reasons. Primary endpoint was the INTRODUCTION: Patients with a short bowel and on home parenteral nutri-
success rate of primary tube placement confirmed on plain abdominal x-ray tion (HPN) have an increased risk of chronic cholestasis. This is may be due to
(AXR). Success was defined as the tip of the tube positioned in the efferent recurrent sepsis, reduced bile flow with biliary stasis or associated with HPN.
jejunal limb. Restoration of bowel continuity can result in HPN requirements being reduced
RESULTS: In our study period, 55 of 126 (44%) patients who underwent pan- or stopped. This study aims to determine the effect of restoration of bowel
creatoduodenectomy required a nasojejunal feeding tube. In 36 patients the tube continuity on the risk of chronic cholestasis (CC).
was placed under EM-guidance at a median of 8 (6-11) days after pancreatoduo- AIMS & METHODS: A retrospective review of patients with short bowel due to
denectomy. Initial tube placement was successful according to the nurse in 25 mesenteric infarction from 2000-2010. Chronic cholestasis (CC) was defined as
(69%) patients and on AXR in 21 (58%) patients. Median procedure time was 25 two of bilirubin, alkaline phosphatase and gamma-glutamyl transferase being 1.5
(15-35) minutes. 22 (61%) patients underwent 50 replacement procedures after times the upper limit of normal for more than 6 months.
previously failed placement attempts (n 31) or after luxation or blockage of the RESULTS: Number of patients with data on liver functions was 101 (55 females,
tube (n 19). 36 replacements were performed endoscopically, with a success rate median age 54 years). Fifteen (54%) of 28 patients with a jejunostomy had CC
of 67%, and 14 under EM-guidance, with a success rate of 71%. No tube while 4 (25%) of 16 patients who had a primary anastomosis and 11(19%) of 57
(re)placement related complications occurred. There was no learning curve patients who had a delayed anastomosis had CC. Univariate analysis showed
effect when comparing the first 10 with the subsequent 26 procedures concerning restoration of bowel continuity reduced the risk of chronic cholestasis
A288 United European Gastroenterology Journal 2(5S)
(p 0.002). Of 11 patients with delayed anastomosis and CC, 3 had resolution of Administration of metformin significantly attenuated the severity of ethanol-
CC, 3 patients died and 5 had continuing CC. induced acute murine gastritis, as assessed by macroscopic and histological eva-
CONCLUSION: Restoration of bowel continuity can reduce the risk of chronic luation of gastric mucosal damage.
cholestasis in patients with a short bowel. CONCLUSION: These results indicate that metformin inhibits NF-B activation
Disclosure of Interest: None declared and ER stress in gastric epithelial cells and that it ameliorates experimental
murine gastritis. These results suggest that metformin is a potential gastropro-
tective agent.
MONDAY, OCTOBER 20, 2014 9:0017:00 REFERENCES
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE Kim JM, Kim SH, Ko SH, et al. The guggulsterone derivative GG-52 inhibits
I POSTER EXHIBITION HALL XL_____________________ NF--B signaling in gastric epithelial cells and ameliorates ethanol-induced gas-
tric mucosal lesions in mice. Am J Physiol Gastrointest Liver Physiol 2013; 304:
P0562 FACTORS RELATED TO LYMPH NODE METASTASIS AMONG G193G202.
ADDITIONAL SURGICAL RESECTION AFTER NON-CURATIVE Koh S-J, Kim JM, Kim I-K, et al. Metformin inhibits NF-B signaling in intest-
ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC inal epithelial cells, and ameliorates murine colitis and colitis-associated colon
CANCER cancer. J Gastroenterol Hepatol 2014; 29: 502-510.
N. Kawata1,*, N. Kakushima1, T. Sugino2, M. Tanaka1, K. Takizawa1, Ma TY, Iwamoto GK, Hoa NT, et al. TNF-alpha-induced increase in intestinal
M. Yoshida1, Y. Kishida1, K. Imai1, K. Hotta1, H. Matsubayashi1, H. Ono1 epithelial tight junction permeability requires NF-kappa B activation. Am J
1
Endoscopy, 2Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Japan Physiol Gastrointest Liver Physiol 2004; 286: G36776.
Contact E-mail Address: n.kawata@scchr.jp Ardite E, Panes J, Miranda M, et al. Effects of steroid treatment on activation of
nuclear factor kappaB in patients with inflammatory bowel disease. Br J
INTRODUCTION: Indication of endoscopic resection for early gastric cancer Pharmacol 1998; 124: 431433.
(EGC) has been determined by the analysis of node-negative cancer using a large Li SN, Wang X, Zeng QT, et al. Metformin inhibits nuclear factor kappaB
database of surgically resected EGC patients. Pathological assessment of tumor activation and decreases serum high-sensitivity C-reactive protein level in experi-
depth and lymphovascular infiltration among surgically resected specimens are mental atherogenesis of rabbits. Heart Vessels 2009; 24: 446453.
likely to be underestimated compared to that of endoscopically resected speci- Disclosure of Interest: None declared
mens because the section interval is thick (five and two millimeters, respectively).
The aim of this study was to clarify the related factors for lymph node metastasis
(LNM) among additional gastrectomy in EGC patients who were judged as P0564 RESTING-STATE FMRI IN PATIENTS WITH NON-SPECIFIC
having a non-curative endoscopic submucosal dissection (ESD). DIGESTIVE TRACT DISEASES
AIMS & METHODS: Clinical and pathological records of 455 patients who G. Piotrowicz1,*, K. Skrobisz-Balandowska2, P. Naumczyk3, A. Sabisz4,
underwent gastrectomy with lymph node dissection for a non-curative ESD K. Markiet2, G. Rydzewska5, E. Szurowska2
during September 2002 to December 2013 were retrospectively studied. 1
Department of Gastrology, Self-Dependent Health Care Unit of Ministry of
Patients with (1) multiple synchronous or metachronous non-curative lesions, Interior, 22nd Department of Radiology, Medical University of Gdansk, 3Institute
(2) recurrent lesions, (3) histological special type, (4) remnant stomach and (5) of Psychology, Department of Social Science, 4Institute of Experimental Physics,
insufficient pathological data of preceding ESD were excluded. Main histological University of Gdansk, Gdansk, 5Department of Gastronenterology, Central Clinical
type (differentiated-type (D-type) or undifferentiated-type (UD-type)), lesion dia- Hospital of the Ministry of Interior in Warsaw, Warsaw, Poland
meter (2cm or 2cm5), tumor depth (mucosa (pT1a) or submucosa (pT1b)), Contact E-mail Address: piotrowicz.grazyna@interia.eu
lymphovascular infiltration, vertical tumor margin (VM) and ulcerative finding
(UL) were examined. INTRODUCTION: The purpose of the study was to assess the differences in
RESULTS: A total of 359 patients (male/female: 287/72) with a median age of 70 brain activity during resting-state fMRI (rs-fMRI) in patients with non-specific
year were enrolled. Additional gastrectomy was performed a median of 70 days digestive tract diseases (Functional Dyspepsia-FD, Inflammatory Bowel
after ESD. Main histologic type were D-type/UD-type 301/58, lesion diameter Diseases-IBD and Irritable Bowel Syndrome-IBS) in comparison to healthy
were 2cm/2cm5 109/250, tumor depth pT1a/pT1b 82/277, lymphovascular group.
infiltration was positive in 177, VM positive or indefinite was observed in 76, AIMS & METHODS: Twelve patients (FD, IBS, IBD) and eleven in control
and UL was positive in 91 patients. LNM was found in 32 patients (9%). group were included into the study.
Univariate analysis revealed that tumor depth (OR: 4.8, 95%CI: 1.1-20.4) and The functional and anatomical images were acquired with a 3T Achieva TX
lymphovascular infiltration (OR: 11.7, 95%CI: 3.5-39.1) were significant related Scanner (Philips Healthcare) with the use of the 8-channel head coil. To evaluate
factors for LNM. Multivariate analysis revealed that lymphovascular inflitration and exclude subjects with brain pathology standard T1 and T2 sequences were
was an independent related factor for LNM (OR: 9.78, 95%CI: 2.76-34.59). applied. No contrast agent was administered. For functional imaging a T2*
LNM was found in 29 patients (16.4%) among 177 patients with positive lym- Gradient Echo-Planar Imaging sequence was used. The rs-fMRI analyses were
phovascular infiltration. In contrast, LNM was found only 3 patients (1.6%) performed with the use of the standard preprocessing. Afterwards an
among 182 patients with negative lymphovascular infiltration. Independent Component Analysis was applied resulting in maps of the Default
CONCLUSION: Lymphovascular inflitration was an independent related factor Mode Network for each of the participants. Those were further compared across
for LNM among additional gastrectomy after non-curative ESD. Detailed search the groups. The following psychological tests were applied: STAI, EAS, EPQ-R,
of lymphovascular infiltration is the most important factor in the pathological CISS, BPCQ.
evaluation of endoscopically resected specimens. RESULTS: Compared to patients with non-specific digestive tract diseases the
Disclosure of Interest: None declared healthy controls DMN comprised additional areas in right hemisphere involving
the Medial Frontal Gyrus and Cingulate Gyrus. The DMN network of the
patients involved additional area in the medial frontal area. See table for detailed
P0563 METFORMIN INHIBITS NUCLEAR FACTOR KAPPAB stereotactic coordinates and Z-scores.
SIGNALING AND ENDOPLASMIC RETICULUM STRESS IN Table 1 Significant additional brain regions of the Default Mode Network of the
GASTRIC EPITHELIAL CELLS, AND AMELIORATED ETHANOL healthy controls compared with patients with non-specific digestive disorders
INDUCED GASTRITIS IN MICE
Y. Choi1,*, S.-J. Koh1, J.W. Kim1, B.G. Kim1, K.L. Lee1 No. of
1
Internal medicine, Seoul National University Boramae Hospital, Seoul, Korea, Anatomical region x y z Z voxels
Republic Of
Contact E-mail Address: spoon0820@naver.com healthy 4 patients Medial Frontal Gyrus 0 66 9 4.16 9
INTRODUCTION: Metformin has been recently reported to provide anti- Cingulate Gyrus 12 24 30 4.25 5
inflammatory or antitumor activity in colitic and colitic tumor animal models Cingulate Gyrus -9 0 36 4.08 6
through inhibition of nuclear factor kappaB (NF-B) signaling. There is no patients 4 healthy Superior Frontal Gyrus -15 63 6 4.06 8
evidence of metformin induced attenuation of gastric mucosal inflammation by
alcohol.
AIMS & METHODS: The aim of this study is to investigate the effect of met-
formin on NF-B signaling and endoplasmic reticulum (ER) stress in human Results of the 2nd level between-group analysis, p50.05 FDR corrected, x, y, z
gastric epithelial cells in vitro and on ethanol-induced acute murine gastritis are MNI coordinates of the most significant center of the activation within the
in vivo. Human gastric epithelial MKN-45 cell lines were pretreated with met- activated cluster. Z Z-value, BA Brodmann
formin and then stimulated with tumor necrosis factor- (TNF-). Interleukin-8 CONCLUSION: Our study showed that the DMNs of the patients and the control
(IL-8) expression was determined by real-time RT-PCR. NF-B DNA-binding altered in the involvement of the medial structures of the prefrontal cortex (Medial
activity in the nuclear extracts was assessed by electrophoretic mobility shift Frontal Gyrus and Superior Frontal Gyrus) as well as the dorsal anterior cingu-
assay (EMSA). The molecular marker of ER stress, including CHOP and lated cortex (the Cingulate Gyrus). Combined with the psychological results, the
XBP1 was evaluated using PCR. In the ethanol-induced acute gastritis model, rs-fMRI indicates differences regarding emotional self-control. Further studies are
mice were given absolute ethanol (50 mg/kg, 250 mg/kg) by oral gavage with or required to establish clinical significance of those findings.
without metformin. Using the extracted gastric tissue, macroscopic assessment, REFERENCES
histological evaluation and immunohistochemical staining for phospho-IB 1. Mayer EA, Naliboff BD and Craig AD. Neuroimaging of the brain-gut axis:
kinase (IKK) was performed. from basic understanding to treatment of functional GI disorders.
RESULTS: Metformin significantly inhibited the upregulated expression of IL-8 Gastronenterology 2006.
in MKN-45 cells stimulated with TNF- in a dose dependent manner. 2. Mayer EA, Aziz Q, Coen S, et al. Brain imaging approaches to the study of
Pretreatment of MKN-45 cells with metformin decreased activity of NF-B in Functional gi disorders: A rome working team report. Neurogastroenterol Motil
TNF- -stimulated cells. CHOP and XBP1 mRNA expression was enhanced in 2009 June.
the presence of TNF-, and it was dampened by pretreatment of metformin. Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A289
P0565 MEDIUM-TERM EFFICACY OF SACRAL NERVE STIMULATION P0568 CHRONIC INTESTINAL PSEUDO-OBSTRUCTION (CIPO): A
FOR IRRITABLE BOWEL SYNDROME MULTI-LEVEL NEUROMUSCULAR-BASED DIAGNOSTIC
J. Fassov1,2,*, L. Lundby2, S. Laurberg2, S. Buntzen2, K. Krogh1 APPROACH
1
Neurogastroenterology Unit, Department of Gastroenterology and Hepatology, R. DAngelo1, R. Rinaldi1, V. Stanghellini2, L. Pironi2, R.F. Cogliandro2,
2
Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark E. Ruggeri2, G. Cenacchi3, V. Donadio3, R. Liguori3, V. Carelli3, R. Lodi3,
Contact E-mail Address: janfas@rm.dk C. Tonon3, R. De Giorgio2,* on behalf of CIPO Bologna Group
1
Int Med Aging Nephrol, S. Orsola-Malpighi Hospital, Bologna, Italy, 2Med Surg
INTRODUCTION: In a recent randomized, controlled, crossover study we con- Sci, 3Biom NeuroMot Sci, Univ of Bologna, Bologna, Italy
cluded that sacral nerve stimulation (SNS) is an effective treatment for severe Contact E-mail Address: rdangelo81@libero.it
IBS.1
AIMS & METHODS: In the present study, we aimed at evaluating the medium- INTRODUCTION: Chronic intestinal pseudo-obstruction (CIPO) is a failure of
term results of SNS in the same group of patients. gut motility leading to recurrent episodes of intestinal sub-occlusion with no
Our criteria for permanent SNS were at least 30% reduction in IBS-specific demonstrable mechanical reason. CIPO diagnosis and management is often
symptom score (GSRS-IBS questionnaire) during the percutaneous nerve evalua- very difficult because of the lack of standardized approach in relation to under-
tion (PNE) test. Primary endpoint was change in the IBS-specific symptom score. lying causes.
Secondary endpoint was change in the IBS-specific quality of life score. AIMS & METHODS: We report our approach to diagnosis of CIPO patients
RESULTS: Forty-three selected patients with severe diarrhoea predominant or with the aim to identify possible underlying neurological causes by using a multi-
mixed IBS underwent a PNE test at our tertiary centre. Among these, 31 (76%, level investigation. Forty-nine CIPO patients (M: 15; age range: 19-63 yrs; F: 34;
as 2 tests were inconclusive) qualified for permanent SNS and 26 (60%) were age range: 16-61 yrs) performed first-level exams including laboratory tests, neu-
actually implanted. Of patients receiving permanent SNS 22 (85%) were eligible rological assessment and electromyography. Three patients did not comply to the
for the present study. At follow-up after median 42 months (range; 12-60) the diagnostic protocol and were excluded. Second-level examinations included
median IBS-specific symptom score (26; range 13 to 64) remained significantly muscle/skin biopsy and/or biochemical/molecular assays based on previous
lower than at baseline (62, range 45 to 80) (P50.0001). The effect was observed results. MR imaging and spectroscopy were performed if mitochondrial encepha-
in all IBS symptom clusters. Also, the median IBS-specific quality of life score lomyopathy was suspected. Biochemical/molecular tests included thymidine
remained significantly improved at follow-up (52, range 26 to 162) compared to phosphorylase activity and a-galactosidase enzyme assay as well as gene analysis
baseline (134, range 82 to 180) (p 0.0001). The effect was observed in all IBS of mitochondrial disorders; transthyretin or enteric smooth muscle actin genes
quality of life domains. Therapeutic success was maintained in 18 patients (82%) were also performed. Full-thickness gut biopsies were obtained only in cases
of whom 5 had had the stimulator for 5 years. undergoing either elective or emergency surgery (because of intestinal sub-
CONCLUSION: The positive effect of SNS for selected patients with severe IBS occlusion).
is maintained at medium-term (1-5 years) follow-up. RESULTS: At the end of the complete diagnostic work up 46 out of 49 patients
REFERENCES (94%) were thoroughly investigated. Three groups of CIPO patients were identi-
1. Fassov J, Lundby L, Buntzen S, et al. A randomised, controlled, crossover fied: A) n 11 had mitochondrial diseases; specifically n 6 had mitochondrial
study of sacral nerve stimulation for irritable bowel syndrome. Ann Surg. Epub encephalomyopathy proved by genetic analysis (4 MNGIE, 1 MERRF, 1 POLG)
ahead of print February 2014. and other n 5 had a likely mitochondrial encephalomyopathy, although not yet
Disclosure of Interest: J. Fassov: None declared, L. Lundby Lecture fee(s) from: confirmed by genetic analysis; B) n 21 had a neuromuscular non-mitochondrial
Medtronic Inc, S. Laurberg Other: Previously member of Medtronic Incs medical diseases; specifically n 16 had neuropathy, in particular n 3 polyneuropathy
advisory board, S. Buntzen Lecture fee(s) from: Medtronic Inc, K. Krogh: None (1 associated with lymphoma, 1 Hu-related autoantibody, 1 idiopathic poly-
declared neuropathy), n 12 small fiber neuropathy demonstrated by skin biopsy, n 1
enteric neuropathy; finally, n 5 had myopathy, in particular n 1 myofibrillar
myopathy and n 4 an undefined myopathy; C) n 14 had an idiopathic CIPO
P0567 PREVALENCE AND SEVERITY OF IRRITABLE BOWEL with no underlying neurological causes including abnormalities of the intrinsic or
SYNDROME IN MORBID OBESITY extrinsic innervation of the gut, as indicated by full thickness analysis and/or
A.S. Schneck1, D. Pishvaie1, R. Anty1, R. Dainese1, M. Vivinus1, X. Hebuterne1, intestinal manometry.
J. Gugenheim1, A. Tran1, A. Iannelli1, P. Thierry1,* CONCLUSION: After an accurate neurological evaluation and tests, only a
1
CHU Nice, Universite de Nice Sophia Antipolis, Nice, France third of CIPO are actually idiopathic. Mitochondrial disorders should be
Contact E-mail Address: piche.t@chu-nice.fr always sought in patients with CIPO, while skin biopsy is suggested as an aid
to unravel a small fiber disorder, a peripheral neuropathy affecting also the
INTRODUCTION: The relationship between irritable bowel syndrome (IBS) autonomic nerve component. Taken together our data suggest that a thorough
and obesity has been poorly investigated. Only few recent reports have suggested neurological evaluation and tests represent an important part in the management
an interesting correlation between obesity and IBS (1,2). of patients with CIPO.
AIMS & METHODS: We aimed to determine the prevalence and severity of IBS Disclosure of Interest: None declared
and associated co-morbidities in a prospective cohort of obese patients. Ninety
morbid obese patients (BMI 40.94.3 kg/m2) were included prospectively before
gastric bypass. The diagnosis of IBS and each subtype (predominance of con- P0569 THE SAME DAY SPLIT CLINIC A PRESCRIPTION FOR
stipation, diarrhea, alternant or undetermined) was performed according to the EFFICIENCY IN THE GASTROENTEROLOGY OUTPATIENT
Rome III criteria using a Bristol scale for stool consistency. Patients were also CLINIC
asked for IBS related co-morbidities including chronic fatigue, migraine, low M.F. Jaboli1,*, M. Grimes1, H. Palmer1, C. Clayman1, T. Rayne1, C. Durcan1,
back pain, gastroesophageal reflux (GER), genitourinary problems and dyspep- I. Mason1, O. Epstein1
sia. Patients had to complete a set of questionnaires at the same time to assess the 1
Gastroenterology, Royal Free Hospital, London, United Kingdom
severity of IBS (IBS Severity Score), gastroesophageal reflux (Reflux Qol), psy-
chological factors including anxiety and depression scale (HAD), fatigue (Fatigue INTRODUCTION: Worldwide, healthcare providers are striving to balance
Impact Scale), and quality of life (SF-12). escalating costs with the patients expectation of efficient access to specialist
RESULTS: Among 90 obese patients, 26 of them (28.8%) fulfilled the Rome III opinion, rapid investigation and treatment. Over the past 65 years, the NHS
criteria for IBS (IBS-D, n 11, IBS-C, n 9, IBS-A, n 1, IBS-U n 5). Obese gastroenterology outpatient journey has remained unchanged. Patients are
patients with or without IBS were similar in age (41.713.1 vs 41.512.0 years assessed at the first visit, followed by one or more hospital visits for gastrointest-
p 0.9), sex (69% vs 65% of females, p 0.3) and BMI (40.93.9 vs 41.1 kg/m2 inal investigations and a return hospital attendance for final assessment. The
p 0.8). Obese patients with IBS reported significantly higher prevalence of same day split clinic has been designed, wherever possible, to condense the jour-
GER (84% vs 25.9%, p50.001), migraines (75 % vs 25% p 0.01), low back ney from months to hours.
pain (80% vs 57% p 0.03), genitourinary problems (19% vs 5% p 0.03), AIMS & METHODS: Over a period of three months, each gastroenterology
chronic fatigue (80% vs 43% p 0.001) and dyspepsia (69% vs 32% referral letter was previewed in advance of the outpatient appointment. Each
p 0.001). Obese patients with IBS had significant higher score of fatigue patient was triaged as solution or complex. For the solution cohort,
(3335 vs 6339, p 0.0009), anxiety (7.03.3 vs 10.43.8 p 0.0001), depres- investigations were predicted and scheduled for the same day as the outpatient
sion (4.93.4 vs 6.84.1 p 0.03), severity of IBS (5855 vs 165100 attendance. Patients were asked to attend the clinic starved and told to expect one
p 0.0001), and poorer quality of life (39.14.736.05.4, p 0.01) than or more same day gastrointestinal investigations. On the appointment day,
those without IBS. Obese patients having both IBS and GER had significant solution patients attended the same day split clinic for: 1) an initial specialist
higher IBS severity scores than those without GER (171.4106 vs 9542, assessment, 2) scheduled investigation(s), 3) a return to the specialist clinic for a
p 0.05). BMI did not correlated with IBS severity whatever the presence of summative assessment & management plan.
Rome III criteria. In a logistic regression model including BMI, anxiety, depres- RESULTS: Of 174 referrals, 95 patients were triaged from the referral letter as
sion, fatigue and GER score, only anxiety was significantly and independently Solution patients, and 81 attended the split clinic (7 did not arrive, 4 post-
associated with the presence of IBS (RR 1.25 CI 95% 1.1-1.51). poned, 3 direct to surveillance colonoscopy). In those who attended, 46 same day
CONCLUSION: A relatively high 28.8% prevalence of IBS was found in obese tests were performed (14 upper endoscopies, 11 sigmoidoscopies, 5 barium swal-
patients. The severity of IBS was not correlated with BMI. However, anxiety was lows, 6 Eso Capsule endoscopies, 5 ultrasound scans, 1 electrogastrogram, 2 CT
independently associated with IBS in obese patients suggesting that psychological abdomen and 2 CT colonoscopy). Twenty-seven patients (34%) were discharged,
factors are key features of IBS whatever the presence of obesity. and twenty-two (27 %) were discharged after a single follow up telephone con-
REFERENCES sultation. Overall, 49 patients designated as Solution patients (60%) required
1. Delgado-Aros S, et al. Am J Gastroenterol 2004. only a single hospital visit. Sixteen patients (17%) were re-designated as
2. Talley NJ, et al. Neurogastroenterol Motil 2004. Complex requiring further tests and 3 (3%) were referred elsewhere. Overall,
Disclosure of Interest: None declared 95 (46 same day tests and 49 return to follow up clinic in old system) return
hospital visits were avoided. The visits were reduced by 40% and the follow up
appointments were down by 60%.
A290 United European Gastroenterology Journal 2(5S)
CONCLUSION: Analytical triage of GP referral letters allows identification & time-international normalized ratio (PT-INR), levels of fibrin/fibrinogen degra-
triage of most solution patients. This facilitates pre-emptive investigation plan- dation products (FDP), C-reactive protein (CRP), DIC scores based on JAAM
ning and scheduling which, in turn, supports a same day split clinic designed to criteria were measured on days 0,3, and 7 to evaluate therapeutic results.
condense months of investigation and follow up into a few hours. The well Furthermore, DIC resolution rate were assessed 3 and 7 days after the start of
planned same day split clinic meets the patients expectation for an efficient DIC treatment.
journey and a quick diagnosis. The inconvenience of numerous hospital atten- RESULTS: Before treatment, DIC scores based on JAAM criteria were 50.95
dances is minimized, whilst appointment capacity is freed up. in the rTM group, and 5.91.3 in the control group (p50.05), respectively.
Disclosure of Interest: None declared However, there were no significant differences between two groups regarding
age, sex, and causative disease of DIC. The duration of rTM administration
was 3.61.44 days (range 1 to 7 days). As shown in the table, significant intra-
P0570 DEVELOPING A EUROPEAN CLINICAL RESEARCH NETWORK group improvement was observed in all parameters except for FDP in both
FOR PAEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND groups. However, there were no significant inter-group differences in comparison
NUTRITION of all parameters. Result from the repeated measures analysis of variance, sig-
N. Croft1,*, V. Tailor1, L.de Ridder2, S. Hussey3 on behalf of PEDDCReN nificant improvements were seen in the DIC scores in the rTM treated group
Steering Group (p 0.001).
1
Centre for Digestive Diseases, Blizard Institute, Queen Mary University of
London, London, United Kingdom, 2Erasmus MC, Rotterdam, Netherlands, Day0 Day3 Day7
3
University College Dublin, Dublin, Ireland
4
Contact E-mail Address: n.m.croft@qmul.ac.uk Platelet count (10 /mL) rTM 11.16.5 10.54.7 17.99.0*
INTRODUCTION: Paediatric European Digestive Diseases Clinical Research control 10.66.9 8.45.7 14.98.7**
Network (PEDDCReN) was established in April 2013. The need for this initiative PT-INR rTM 1.390.32 1.180.16** 1.210.22**
was identified by ENPR-EMA (The European Network of Paediatric Research control 1.430.32 1.220.3** 1.20.19**
at the European Medicines Agency). The Project is supported by LINKS funding FDP (mg/ml) rTM 32.319.4 19.824.5 17.613.7
from the UEG (United European Gastroenterology) and is led by the British,
Irish and Dutch Societies of Gastroenterology in collaboration with ESPGHAN control 37.434.1 24.914.5 22.213.0
and ENPR-EMA. CRP (mg/dL) rTM 14.18.8 9.75.4* 6.65.6**
AIMS & METHODS: The aim of PEDDCReN is to support the development of control 14.57.6 12.26.1 7.55.2**
large studies in paediatric patients in the speciality of Gastroenterology, DIC score rTM 50.95 3.11.8** 2.01.7**
Hepatology and Nutrition (GHN).
We report the preliminary results of an online survey as a first step of control 5.91.3 4.51.9** 3.22.3**
PEDDCReN, identifying investigators resources, expertise and interest in stu- DIC resolution rate (%) rTM 48 68
dies in this area in the UK, Ireland and the Netherlands. control 28.6 50
The survey was designed by the steering group of PEDDCReN and utilised the
web based system REDCap. It takes 5 minutes to complete with 1 respondent per Data are shown with MeanSD *p50.05 vs Day0, **p50.01 vs. Day0
hospital. To date the survey has had responses from paediatric gastroenterolo-
gists in the UK, Ireland and the Netherlands as members of BSG, BSPGHAN,
Irish and Dutch Gastroenterology Societies. As a result of PEDDCReN promo- CONCLUSION: These results suggest that rTM would be the useful medicine
tions in UEG & ESPGHAN newsletters one centre from Italy, Germany, Serbia for treatment DIC in the gastroenterology field.
and Poland has also responded. Disclosure of Interest: None declared
RESULTS: After six months 25 units (including 53 investigators) had replied
representing childrens services with a median of 211 beds (range 15-800). 10 were
stand alone childrens hospitals, 11 were childrens hospitals co-located with P0572 THE EFFECT OF ACUTE SLIGHTLY INCREASED INTRA
adult hospitals, 2 were smaller childrens units in adult hospitals and one was ABDOMINAL PRESSURE ON INTESTINAL PERMEABILITY AND
a neonatal unit. 76% of responding units had neonatal ICUs on site with almost OXIDATIVE STRESS IN A RAT MODEL
all of these carrying out neonatal surgery. All wished to be part of PEDDCReN Y. Leng1,*, G. Yao1
and were happy for contact details to be passed on to both industry and non- 1
Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
industry investigators. The survey identified each units interest in recruiting into China
a range of GI and liver diseases (eg 88% wished to recruit for IBD studies Contact E-mail Address: lengyuxin1980@126.com
whereas only 24% for infant diarrhoea). Less than 33% would also recruit to
liver studies including infective hepatitis. Of the respondents 60% have been a INTRODUCTION: The harm of Intra-abdominal hypertension (IAH) on criti-
principle investigator (in their hospital) and 40% had been chief investigators for cally ill patients has gained great attention. However, there are still 60% under-
their country. 68% were willing to take on phase I or II studies but only 36% had IAH patients in critical care units, whose intra abdominal pressure (IAP) runs
done any in the last 3 years. 64% had a clinical research facility available on site slightly higher, at 5 to 7 mmHg. Among the frequently IAH-affected organ
and 68% have access to research nurses. Sites were also asked whether they systems, the intestine is initially influenced. Nevertheless, the adverse effect of
currently followed up any patients with rare GI or liver diseases such as con- transient exposure to slightly raised IAPs on intestinal mucosa remains unclear.
genital enteropathy (12/25), congenital transport defect (7/25), polyposis syn- AIMS & METHODS: To study the acute effects of different grade nitrogen
dromes (17/25), chronic intestinal pseudo-obstruction (15/25). pneumoperitoneum on colon mucosa, male Sprague- Dawley rats were assigned
CONCLUSION: This shows the ability of PEDDCReN to identify interest, to six groups with different IAPs (baseline, 4mmHg, 8mmHg, 12mmHg,
expertise and resources in 3 countries. This will shortly be extended to the rest 16mmHg, 20mmHg, n 6 per group). During the 90 minutes exposure, we
of Europe. The potential for investigators and industry to utilise this network to dynamically monitored the heart rate and noninvasive hemodynamic paramaters.
support the development of large scale clinical trials and rare diseases studies After decompression slowly, the arterial blood gas analyses were conducted.
within this speciality is a major benefit. Then the structural injury to the colon mucosa was confirmed by light micro-
Disclosure of Interest: None declared scopy. The colon permeability was revealed by expression and localization of
tight junction proteins (claudin 5 and occludin), combined with the absorption of
fluorescein isothiocyanate dextran (FD-4, with another proportion of rats, n 6
P0571 THE EFFICACY OF RECOMBINANT HUMAN SOLUBLE per group). The pro-oxidantantioxidant balance of the colon was determined by
THROMBOMODULIN IN PATIENTS WITH SEPSIS AND the levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), cata-
DISSEMINATED INTRAVASCULAR COAGULATION IN THE lase (CAT) and serum super oxide dismutase (SOD).
GASTROENTEROLOGY FIELD RESULTS: IAPs greater than 12 mmHg significantly disturbed the colonic integ-
T. Ito1,*, A. Nagahara1, T. Osada1, J. Kato1, H. Ueyama1, H. Saito1, rity, expression of tight junction protein, mucosal permeability to FD-4 and the
S. Watanabe1 pro-oxidantantioxidant balance. Interestingly, slight elevation of IAPs not
1
gastroenterology, Juntendo University, Tokyo, Japan reaching the level of IAH also showed a similar undesirable effect. In 8mmHg
Contact E-mail Address: tmitou@juntendo.ac.jp group, mild hyponatremia, hypocalcemia and hypoxemia occurred, accompanied
with the reduction of blood pressure and abdominal perfusion pressure. Whats
INTRODUCTION: Inpatients with digestive disease often have coexisting ser- more, mild microscopically inflammatory infiltration and increase of MDA were
ious infections. Some of them result in disseminated intravascular coagulation also detected in under-IAH groups. 8mmHg-IAP markedly inhibited the expres-
(DIC). Recently, recombinant human soluble thrombomodulin (rTM) was sion of claudin 5 and occludin, though no significant differences were found in
approved and has been used in clinical practice for DIC treatment in Japan. permeability to FD-4 between control and 8mmHg groups.
However, there are few studies to evaluate the efficacy of rTM for DIC in the CONCLUSION: Acute exposure to slightly raised IAPs may bring adverse
gastroenterology field. The purpose of this study is to make a comparison effects on intestinal permeability and pro-oxidantantioxidant balance.
between rTM-treated patients and patients treated other agents, and to evaluate Accordingly, we concluded that for critically ill patients, IAPs should be mon-
the efficacy of rTM. itored dynamically and intervened as soon as possible to avoid the intestinal
AIMS & METHODS: The purpose of this study is to make a comparison mucosal injury and the subsequent gut- derived sepsis.
between rTM-treated patients and patients treated other agents, and to evaluate REFERENCES
the efficacy of rTM. Fifty-three inpatients at our department with sepsis-induced 1. Cheng J, Wei Z, Liu X, et al. The role of intestinal mucosa injury induced by
DIC between January 2009 and February 2014 were retrospectively analyzed. intra-abdominal hypertension in the development of abdominal compartment
The patients were classified into the rTM treatment group (n 25), and conven- syndrome and multiple organ dysfunction syndrome. Crit Care 2013; 17: R283.
tional treatment group (rTM was not used) as the control group (n 28). 2. Gong G, Wang P, Ding W, et al. Microscopic and ultrastructural changes of
Diagnosis of DIC was made according to the criteria of acute DIC of the the intestine in abdominal compartment syndrome. J Invest Surg 2009; 22: 362-
Japan Association of Acute Medicine (JAAM). Platelet count, prothrombin 367.
United European Gastroenterology Journal 2(5S) A291
3. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the interna- the procedures. The patients were examined three, seven and thirty days after the
tional conference of experts on intra-abdominal hypertension and abdominal procedure.
compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732. RESULTS: All the patients were discharged 2 hours after the endoscopic proce-
Disclosure of Interest: None declared dure was completed and none had any post procedural complications (fever,
delayed bleeding, perforation or abdominal pain).
CONCLUSION: These results demonstrate that when this closure is utilized
TUESDAY, OCTOBER 21, 2014 9:0017:00 patients can be safely discharged from the hospital 2-3 hours after endoscopic
POSTER PLUS VIDEO II POSTER EXHIBITION HALL XL_____________________ removal of a polyp. The technique is quick, (it was coined Lucky Loop in
honor of Luky Luke the fast solitary gunslinger cartoon character created by
P0573 USE OF A NOVEL SELF-EXPANDING METAL STENT TO Maurice De Bevere) easy and economic and can be also used in cases of large
ALLOW FOR ENDOSCOPIC DRAINAGE AND NECROSECTOMY gastrointestinal perforations or in patients that cant stop double or triple anti-
OF PANCREATIC FLUID COLLECTIONS platelet therapy.
M.T. Huggett1,*, K.W. Oppong1, S.P. Pereira2, V. Mitra1, R.M. Charnley3, REFERENCES
M.K. Nayar1 1 Hong SP. Clin Endosc 2012; 45: 282-284.
1
Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne, United 2 Ryska O, et al. Gastroent Hepatol 2011; 65: 207210.
Kingdom, 2University College Hospital, London, United States, 3Department of 3 Samarasena JB, et al. Endoscopy 2012; 44: E424-E425.
HPB surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom Disclosure of Interest: None declared
Contact E-mail Address: matthewhuggett@doctors.net.uk
INTRODUCTION: Post-inflammatory peri-pancreatic fluid collections are fre- P0575 PERFORMANCE CHARACTERISTICS OF COLORECTAL FULL
quent sequelae of severe acute pancreatitis. Collections are at risk of suppurative SPECTRUM ENDOSCOPY (FUSE) PROSPECTIVE, PARALLEL,
infection complicated by pancreatic necrosis. Over the last decade there has been RANDOMIZED STUDY
an increasing emphasis on minimally invasive drainage procedures, including H. Neumann1,*, G.E. Tontini1,2, M. Vieth3, C. Gunther1, M. Grauer1,4,
EUS-guided cyst-gastrostomy, and these approaches seem to be associated M.F. Neurath1
with lower morbidity and mortality. Access to the necrosis cavity has however 1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
been severely limited by having to maintain the tract with small diameter plastic Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
stents. Recently, a novel flanged fully covered self-expanding metal stent Bayreuth, 4Klinikum Neumarkt, Neumarkt, Germany
(FCSEMS; NAGI stent, Taewoong Medical, Korea) has been developed to
allow for better drainage of infected necrosis and easier endoscopic access into INTRODUCTION: Full Spectrum Endoscopy (FUSE) provides a 330 field of
the cavity. Setting: A non-randomised prospective multicentre phase II study to view, thereby potentially allowing the endoscopists to see more anatomy in com-
determine the safety and efficacy of FCSEMS endoscopic cyst- gastrostomy in parison to standard forward viewing endoscopes (FVE). Recent data has already
the management of complex/infected pancreatic fluid collections. shown that FUSE is feasible to significantly reduce adenoma miss rates.
AIMS & METHODS: Patients were included if they had evidence of a pancreatic AIMS & METHODS: The aim of this prospective, parallel, randomized study
fluid collection which was deemed to be amenable for EUS- guided drainage after was to assess the performance characteristics of FUSE in comparison to FVE.
discussion at a HPB multidisciplinary meeting. Patients selected for EUS-guided Patients were randomly assigned to undergo colonoscopy with FUSE (Group A)
drainage had cross sectional imaging (MR or CT) performed within 2 weeks of or FVE (Group B) after a previous sample size calculation. Performance char-
the procedure and then an EUS assessment was made of the necrotic component. acteristics including time to cecum, withdrawal time, total examination time,
The collection was punctured using a cystotome and the FCSEMS inserted over a medication, patient and endoscopists satisfaction, and polyp detection rates
guidewire with fluoroscopic control. Repeat procedures were performed as were recorded.
necessary. RESULTS: 57 patients were included (male 52%; mean age 56 years, Range 21
RESULTS: A total of 11 patients (8 male, 3 female) were included in the study. 88 years). Time to cecum (minutes, mean SD) was 4.05 0.6 minutes for
Median age was 57.3 years. The aetiology of the collection was gallstones in 6 FUSE and 5.48 0.6 for FVE (P 50.05). Withdrawal times were 12 4.4
patients, idiopathic in 3, ischaemic in 1 and drug-induced in 1. Ten patients had minutes and 15 4.5 minutes for FUSE and FVE, respectively. Total examina-
evidence of at least 30% necrosis within the collection. Mean diameter of the tion time was 16.5 4.4 minutes in the FUSE group and 20.1 4.5 minutes in
collection was 15cm and EUS-guided puncture was initially performed in all the FVE group. Sedation was less required in the FUSE group as compared to
patients. The tract was dilated with a balloon in 6 patients. Stent insertion was FVE (mean propofol dosage, 170 mg vs. 230 mg). Significantly more patients
either with a 20mm (7 patients) or 30mm (4 patients) length FCSEMS. Ten needed analgesia in the FVE group (meperidine; p 0.01). Patient and endosco-
patients underwent endoscopic necrosectomy, with a median of 3 procedures pists satisfaction were high throughout the cases and not different between both
(range 1-10). Significant reduction in the size of collection was achieved in all groups. Per patient polyp detection rates were 37% and 18% for FUSE and
patients. Adverse events included stent migration in 3 (2 spontaneously and 1 FVE, respectively.
during necrosectomy). Two patients died of complications of severe acute CONCLUSION: Advancement times of the scope to the cecum and withdrawal
pancreatitis. times were faster with the FUSE scope as compared to standard FVE.
CONCLUSION: FCSEMS insertion is feasible and safe for drainage of pancrea- Satisfaction rates of patients and endoscopists were similar in both groups
tic fluid collections. It allows repeated through the stent necrosectomy proce- while patients needed more sedation and analgesia in the FVE group.
dures and appears to be a major advance in the management of infected Although more polyps were found in the FUSE group the study was not powered
pancreatic necrosis. to compare adenoma detection rates between both groups.
Disclosure of Interest: None declared Disclosure of Interest: None declared
P0574 LUCKY LOOP: A VARIANT OF AN ENDOLOOP CLIP P0576 DEVELOPMENT AND VALIDATION OF A SIMPLE
WOUND CLOSURE TECHNIQUE AFTER COLONIC DEFIANT CLASSIFICATION SYSTEM FOR IN VIVO DIAGNOSIS OF
POLYP REMOVAL COLORECTAL POLYPS USING VIRTUAL CHROMOENDOSCOPY
E. Rosa-Rizzotto1,*, C. Lucchini1, F. De Lazzari1 THE VISIBLE STUDY
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital, Padua, H. Neumann1,*, C. Gunther1, L.C. Fry2, M. Vieth3, G.E. Tontini1,4,
Italy M. Grauer1,5, M.F. Neurath1, K. Monkemuller2
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany,
INTRODUCTION: This report describes a variant of an iatrogenic wound clo- 2
University of Alabama at Birmingham, Birmingham, United States, 3Klinikum
sure technique after endoscopic mucosal Bayreuth, Bayreuth, Germany, 4IRCCS Policlinico San Donato, San Donato
resection (EMR) or endoscopic submucosal dissection (ESD). After removal of Milanese, Italy, 5Klinikum Neumarkt, Neumarkt, Germany
defiant polyps without signs of perforation or important bleeding, iatrogenic
wounds are generally not closed as second intention healing is expected. In the INTRODUCTION: Although the diagnostic performance of virtual chromoen-
past patients were often hospitalized after those procedures for 2-3 days, but doscopy (VCE) has already been reported, validated classification systems allow-
when discharged a 6.5% prevalence of delayed bleeding persists(1). The com- ing both experienced and inexperienced endoscopists to apply VCE have not
bined technique of endoloop plus clip or clip alone to close iatrogenic wounds or been established.
perforations during operative endoscopies is a well established practice. Clips AIMS & METHODS: To develop and validate a simple classification system for
plus endoloop technique have been coined King Closure(2) or clutching rose differentiating hyperplasic and adenomatous colorectal lesions by using VCE.
stems techniques(3). In the first phase, the capacity of experienced endoscopists to predict the histol-
AIMS & METHODS: We propose a tobacco-pouch suture technique for ogy of colorectal polyps was assessed. In the second phase, a simplified classifi-
wounds that are a maximum of 4 cm diameter, anchoring a single endoloop cation was developed allowing histologic prediction. Thirdly, the validity of the
with 5-6 long type clips cirumferencially to the wound edge perimeter and closing classification was evaluated among inexperienced raters, including medical stu-
the loop using a single double channel endoscope. A hemoclip short type is dents and GI fellows. Last, a pilot clinical evaluation was performed during real-
placed over the plastic tube that tightens the loop to fix the suture at the end time colonoscopy. The study was performed in a multicenter, international
of the procedure. setting.
Sixteen (8 ESD and 12 EMR) patients underwent endoscopic removal of polyps RESULTS: A simple classification system for differentiating hyperplasic and
425 mm 5 40 mm between June and December 2013. All the iatrogenic wounds adenomatous colorectal lesions by using VCE was developed and validated.
were closed with the technique described in the video. The mean time to perform Diagnosis was made in 78% to 89% (mean 82.5%) of polyps with high confi-
the procedure was 8 min (range 6-13 min). High definition endoscopes PCF- dence. Sensitivity and specificity ranged from 95% to 98% and 78% to 100%,
H180AL and GF-H180J (OLYMPUS, Tokyo, Japan) with an external artificial respectively. During real-time colonoscopy, diagnosis was made with high-con-
second channel, a 30 mm diameter endoloop (PolyLoop, OLYMPUS, Tokyo, fidence in 84% of polyps with sensitivity of 91%, specificity of 85%, and accu-
Japan) and Clips HX-610-090L and HX-610-135S (EZ-Clip, OLYMPUS, racy of 93%. Positive and negative predictive values were 93% and 93%,
Tokyo, Japan) were used. Carbon dioxide insufflation was used during all of respectively.
A292 United European Gastroenterology Journal 2(5S)
CONCLUSION: We developed and validated for the first time a simple classi- percentage of polyps for which pCLE correctly differentiated between non-ade-
fication system for differentiating hyperplasic and adenomatous colorectal nomatous, adenomatous and carcinomatous polyps.
lesions by using VCE during real-time colonoscopy. RESULTS: The overall diagnostic accuracy of real time pCLE for colorectal
Disclosure of Interest: None declared polyps was 75% and was not different between the endoscopists (74% vs.
76%, p 0.81). Accuracy remained stable when comparing the first 25 proce-
dures with the last 25 procedures of both endoscopists (respectively 76% vs.
P0577 THE OBSERVATION OF SECOND-GENERATION AUTO- 72%, p 0.75 and 76% vs. 76%, p 1.00). According to the size of the
FLUORESCENCE IMAGING (AFI) HELPS EASILY TO DETECT OF polyps, accuracy was non-significantly different (67% for 68 polyps 5 mm,
FLAT COLON NEOPLASIA FOR NON-EXPERT ENDOSCOPISTS 86% for 21 polyps 10 mm and 89% for 18 polyps 410 mm; p 0.08).
S. Saito1,*, D. Ide1, H. Inomata1, T.R. Ohya1, N. Tamai1, T. Kato1, Sensitivity for detecting neoplasia in polyps 5 mm was 65% (59% for right
M. Ikegami2, H. Tajiri3 sided polyps and 73% for left sided polyps).
1
Endoscopy, 2Dept. of Pathology, 3Division of Gastroenterology and Hepatology, CONCLUSION: The diagnostic accuracy of two endoscopists starting to use real
Dept. of Internal Medicine, THE JIKEI UNIVERSITY SCHOOL OF time pCLE for colorectal polyps was 75% and remained stable during the first 50
MEDICINE, Tokyo, Japan procedures. Sensitivity for detecting neoplasia in small polyps was below the
Contact E-mail Address: ssaito@jikei.ac.jp required 90% and suggests that real-time pCLE cannot be used to guide
follow-up decisions and that histologic evaluation of removed polyps is still
INTRODUCTION: We reported about the features of observation for colon required.
polyps by using the AFI system 1). Namely, hyperplastic lesion is shown as Disclosure of Interest: None declared
dark green color similar to surrounding mucosa. In contrast, most of the neo-
plastic lesion is changed to magenta color at the localized tumor area. And also,
this strength of change is suggested to correlate with the histological grading. In P0579 NOVEL COMPUTER-AIDED DIAGNOSIS SYSTEM FOR
this study, we examined the benefits of using this system to detect the colon COLORECTAL LESIONS USING ENDOCYTOSCOPY
neoplasia for beginner endoscopists. Y. Mori1,*, S.-E. Kudo1, K. Wakamura1, M. Misawa1, Y. Ogawa1,
AIMS & METHODS: Two studies were used to clarify for the usefulness by M. Kutsukawa1, T. Kudo1, T. Hayashi1, H. Miyachi1, F. Ishida1, S. Hamatani1,
second-generation AFI observation. One method used four pictures (white light H. Inoue1
conventional image (WHL), indigo carmine dye sprayed image (CE), NBI and 1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
AFI). Another method used short movies, which recorded WHL and AFI within HOSPITAL, Yokohama, Japan
about one minute, respectively. At first study, twenty-four cases (flat type intra- Contact E-mail Address: ibusiginjp@hotmail.com
mucosal lesion 22 cases and depressed submucosal invasive cancer; 2 cases) were
retrospectively reviewed. In contrast, thirty cases (sessile serrated (SS) lesion; 12 INTRODUCTION: Endocytoscopy (EC) enables observation of nuclei at 450-
cases, intramucosal (IM) lesion; 13 cases and submucosal invasive cancer (SM); 5 fold magnification during gastrointestinal endoscopy, thus allowing precise pre-
cases) were reviewed at second study. These pictures and videos were shown to a diction of lesion pathology, however it requires training and experience.[1,2]
group of 5 beginner endoscopists (non-experienced for using AFI system) and a AIMS & METHODS: The aim of the present study was to develop and evaluate
group of 4 expert endoscopists (experienced more than 1000 cases). The used a computer-aided diagnosis (CAD) system for EC imaging of colorectal lesions.
scope is CF: FH260AZI with second generation Lucera Elite system (Olympus The proposed CAD system comprised image acquisition, nuclear segmentation,
Medical Systems, Tokyo, Japan). feature extraction, and classification into three pathological groups (non-neo-
RESULTS: At first study, the visualization score was defined as follows: the plastic, adenoma, and cancer). The classification algorithm was programmed
worst visualization was scored as 0 and the best as 10. And to evaluate the based on six features of nuclei that were significantly relevant to pathological
visualization of colon neoplasia, we calculated the average visual analog scale classification by multivariate analysis: area (p 0.009), standard deviation of
(VAS) scores for each groups. The mean AFI visualization score; 8.9 was sig- area (P50.001), circularity (P50.001), circularity of the top 20 nuclei
nificantly higher than that of WHL; 6.5, CE; 8.2 and NBI; 7.1 by non-experi- (P50.001), shortest diameter (P50.001), and longest diameter (P50.001). To
enced group. And there was difference in average visualization scores between validate this CAD system, we conducted a pilot study using test sets of EC
AFI; 7.5 and another modalities (WHL; 4.8, CE; 7.2 and NBI; 5.8) by experi- images from 176 small colorectal polyps (132 neoplastic lesions and 44 non-
enced group. At second study, the strength changing to the magenta color from neoplastic lesions, all 10mm). The performance of the CAD system for predic-
dark green with excitation light was evaluated by 10-point VAS. In non-experi- tion of neoplastic change was compared with diagnoses by two expert endosco-
enced group, the score of SS lesion, IM lesion and SM lesion were 2.3, 5.2 and pists and two trainee endoscopists. The average time for diagnosis and intra-
7.8, respectively. In contrast SS lesion, IM lesion and SM lesion were 2.4, 5.7 and observer agreement (using 20 EC images at a 4-week interval) were also measured
7.8 in experienced group, respectively. It was shown almost same as VAS scores and compared among the three groups.
between non-experienced and experienced as result. RESULTS: The CAD system automatically output the pathological prediction
CONCLUSION: AFI provided significantly better visualization to detect and of all subject images immediately on their input. The CAD system provided a
differentiate non-neoplastic lesion and neoplastic lesion for beginner endosco- sensitivity of 92.0% and an accuracy of 89.2% which were comparable with those
pists. It suggested that it is not difficult to diagnose the indication of endoscopic provided by the experts (p 0.868 and 0.256, respectively) and significantly
treatment for neoplastic changes within intramucosal layer using AFI system for higher than those provided by the trainees (P50.001 and 0.002, respectively).
non-experienced endoscopist. It was also expected to detect flat elevated lesion The CAD system achieved a feasible specificity of 79.5%, which was not signifi-
more easily by non-experienced endoscopists. cantly different from that achieved by the experts and trainees (p 0.081 and
REFERENCES 0.728, respectively). The CAD system also enabled instant diagnosis which took
1) Saito S, Aihara H, Tajri H, et al. Autofluorescence imaging makes it easy to only 0.3 seconds for each lesion with perfect reproducibility (Kappa 1). (See
differentiate neoplastic lesions from non-neoplastic lesions in the colon. In: New Table)
challenges in gastrointestinal endoscopy. Tokyo: Springer Inc., 2008, pp. 330-337.
Disclosure of Interest: None declared Computer-aided P value P value
diagnosis (CAD vs (CAD vs
(CAD) Experts Trainees experts) trainees)
P0578 THE ACCURACY OF REAL-TIME PROBE BASED CONFOCAL
LASER ENDOMICROSCOPY FOR DIFFERENTIATION OF Sensitivitiy, % 92.0 92.7 81.8 0.868 50.001
COLORECTAL POLYPS DURING COLONOSCOPY Specificity, % 79.5 91.0 75.6 0.081 0.728
T.D. Belderbos1,*, M.G. van Oijen1, L.M. Moons1, P.D. Siersema1 Accuracy, % 89.2 92.3 80.4 0.256 0.002
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Time for diagno- 0.3 4.5 16.0 50.001 50.001
Netherlands sis, seconds
Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl Intra-observer Almost perfect Substantial Substantial NA NA
agreement (Kappa 1) (Kappa 0.79) (Kappa 0.71)
INTRODUCTION: Reliable real-time differentiation between neoplastic and
non-neoplastic colorectal polyps during colonoscopy may guide treatment deci-
sions and reduce the need for post hoc histologic evaluation of resected polyps. In
the hands of experts, probe based confocal laser endomicroscopy (pCLE) has CONCLUSION: This fully automated CAD system provides excellent sensitivity
been suggested to be a highly accurate technique for this. Previous studies have and accuracy with acceptable specificity, ultra-rapidness, and perfect objectivity.
shown a short learning curve for offline interpretation of pCLE images of color- Thus, it can be a powerful tool for decision support during screening
ectal polyps. It is however not known whether colonoscopists starting to use this colonoscopy.(This study was registered as UMIN000012797 and supported by
technique can also accurately differentiate colorectal polyps during routine colo- JSPS KAKENHI Grant Number 25860564.)
noscopy by using real time pCLE to directly evaluate images. REFERENCES
AIMS & METHODS: The primary aim was to determine the diagnostic accu- 1. Mori Y, et al. Comprehensive diagnostic ability of endocytoscopy compared
racy of real-time pCLE for the differentiation of colorectal polyps during the first with biopsy for colorectal neoplasms: a prospective randomized noninferiority
50 pCLE cases of two endoscopists routinely performing colonoscopy. The sec- trial. Endoscopy 2013; 45: 98-105.
ondary aim was to compare the sensitivity for diagnosing neoplasia small polyps 2. Kudo S, et al. Diagnosis of colorectal lesions with a novel endocytoscopic
(5 mm) in this study with a sensitivity threshold of 90% that is required for classification a pilot study. Endoscopy 2011; 43: 869-875.
selective polypectomy or resect and discard strategies. We included patients of Disclosure of Interest: None declared
45 years or older undergoing colonoscopy for screening, surveillance or diagnos-
tic work-up between August 2012 and April 2014. After a training to obtain and
interpret pCLE images two senior endoscopists performed 50 pCLE procedures
each. Intravenous fluorescein was used as contrast agent. All polyps were
resected endoscopically and histologic diagnosis by an expert pathologist was
used as reference. Primary outcome was the diagnostic accuracy, defined as the
United European Gastroenterology Journal 2(5S) A293
P0580 TRANS-ANAL SUBMUCOSAL ENDOSCOPIC RESECTION P0582 DIAGNOSTIC ALGORITHM FOR HIGH LIVER IRON
(TASER): A NEW ENDO-SURGICAL APPROACH TO THE OVERLOAD. WHEN IS MRI INDICATED?
RESECTION OF BENIGN GIANT RECTAL LESIONS A. Castiella1,*, E. Zapata1, I. Urreta2, J.M. ALUSTIZA3, L. ZUBIAURRE1,
Z.P. Tsiamoulos1,*, J. Warusavitarne2, T. Elliott1, B.P. Saunders1 E. Salvador3, G. Letamendi4, B. Arrizabalaga5, U. Mendarte6, P. Otazua7,
1
Wolfson Unit for Endoscopy, 2Department of Colorectal Surgery, St Marks L. Rincon8, M.D. de Juan9, J. I. Emparanza2 on behalf of Burnia Group
1
Hospital/Academic Institute, London, United Kingdom GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epide-
miology, DONOSTIA HOSPITAL, 3radiology, osatek donostia, DONOSTIA,
4
INTRODUCTION: Trans-anal surgical (TEMS/TAMIS) and advanced endo- hematology, Galdakao Hospital, galdakao, 5radiology, Cruces Hospital,
scopic resection (ESD, P-EMR) procedures have the potential to provide com- Baracaldo, 6GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA,
7
plete and successful eradication of giant rectal polyps. Both approaches however GASTROENTEROLOGY, mondragon hospital, mondragon,
8
have limitations in terms of practicality and safety. We describe a new endo- GASTROENTEROLOGY, Bidasoa Hospital, irun, 9immunology, DONOSTIA
surgery technique called Trans-Anal Submucosal Endoscopic Resection HOSPITAL, DONOSTIA, Spain
(TASER) which combines the advantages of both the endoscopic and transanal Contact E-mail Address: agustincastiella@yahoo.es
surgical approach.
AIMS & METHODS: The GelPoint Path trans-anal access port allows simulta- INTRODUCTION: HIO is considered if the Hepatic iron index4 1.9 (estimated
neous passage of an endoscope and two laparoscopic retractors. Working with by MRI).
the endoscopic image the laparoscopic retractors (Johen 33mm forceps) allow AIMS & METHODS: To develop and validate a diagnostic algorithm for high
dynamic tissue retraction to facilitate endoscopic dissection (Flush knife BT) or iron overload (HIO) based on laboratory and genetic variables.
snare placement (Olympus snare master/spiral snare). All procedures were per- We collected a retrospective cohort with all consecutive patients between 2001-2008
formed under general anesthesia and with patients in the lithotomy position. studied by Magnetic Resonance Imaging (MRI) to determine liver iron concentra-
RESULTS: Eleven patients (mean age 55 years, 3 male/8 female) underwent tion (LIC). This cohort served as the derivation set. We analyzed all variables using
TASER for 11 lesions, distributed from the lower rectum to the recto-sigmoid univariate statistics with the MRI acting as the gold standard. We studied the best
junction and with a median size of 85mm, range 40-180mm. Polyp morphology combination of the diagnostics variables to build the algorithm.
was (3/11 flat (Paris 2a), 4/11 sessile (Paris 1s) and 4/11 mixed type (Paris 2a1s). We validated the algorithm in a prospective cohort, collecting all patients
In all cases a circumferential mucosal incision was made and histology confirmed referred to our hospital for study of iron metabolism alteration since 2009
free lateral margins in all cases. 10/11 rectal polyps were adenomatous and one onwards. We estimate the sensibility, specificity and predictive values with
had a small focus of moderate differentiated adenocarcinoma (incomplete local 95% CI.
excision). RESULTS: Retrospective cohort: 242 patients (198 men/44 women), mean age
Complete endoscopic excision in a single session was achieved in 10/11 cases 52,4 (SD 13.3). Thirty six of them had HIO. Nearly half of the patients (117/
(91%). Median completion time of the procedure was 215min, range 120- 242 48.4%) had both Transferrin saturation index (TSI) and Ferritin elevated
480min. Tissue retraction was used in every case and resection was completed and 28 (11.5%) were C282Y homozygous. The final algorithm was as follows:
by ESD alone (4/11), ESD EMR (4/11) ESD EMR trans-anal surgical We consider a patient as having HIO with the simultaneous occurrence of TSI
excision (3/11). Intra-procedural bleeding occurred in 8 cases, controlled with and Ferritin elevated and C282Y homozygosis. HIO is discarded if TSI or
hemostatic clips and Coagrasper (Olympus); surgical suturing was required in Ferritin are within normal values. The rest should be studied by MRI.
one case (1/8). Prophylactic clips (2/11) and surgical sutures (1/11) were placed to Prospective cohort: 177 patients (148 men/29 women), mean age 56 (SD 13.9).
treat deep muscle injury. There were no perforations and no delayed bleeding The nosological characteristics of the algorithm in this validation study are:
episodes. Patients were discharged the day following TASER in all cases. CONCLUSION: MRI is not necessary in 77% of the patients for HIO diagnosis.
Surveillance at 3-6 months revealed no recurrence in 6 cases, whereas in four MRI is indicated inpatients not C282Y homozygous with raised TSI and
cases the follow up procedure is still pending. The malignant polyp case was Ferritin.
referred to surgery with a good clinical outcome (T3, N0, M0). Disclosure of Interest: None declared
CONCLUSION: TASER appears to be a safe and efficient approach providing
an optimal platform for resection of large rectal lesions. In our experience it
provides the optimal platform for the minimally-invasive management of these P0583 LIVER IRON CONCENTRATION (LIC) IN PATIENTS REFERRED
high risk lesions. FOR HYPERFERRITINEMIA (HF) TO A SECONDARY HOSPITAL:
Disclosure of Interest: None declared ANALYSIS OF THE DIFFERENT GROUPS ACCORDING TO HFE
MUTATIONS AND TRANSFERRIN SATURATION INDEX (TSI)
A. Castiella1,*, E. Zapata1, L. Zubiaurre1, A. Iribarren1, M.D. De Juan2,
TUESDAY, OCTOBER 21, 2014 9:0017:00 J.M. ALUSTIZA3, P. OTAZUA4, F. MUGICA5, E. Elosegui5, A. Arriola5,
LIVER & BILIARY II POSTER EXHIBITION HALL XL_____________________ E. Utrilla6, J. I. Emparanza7
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro,
P0581 EVALUATION OF FERRITIN 41000 CUTOFF POINT TO 2
IMMUNOLOGY, DONOSTIA HOSPITAL, 3osatek radiology, osatek,
DIAGNOSE LIVER IRON OVERLOAD 4
GASTROENTEROLOGY, MONDRAGON HOSPITAL,
5
A. Castiella1,*, E. Zapata1, I. Urreta2, L. Zubiaurre1, A. Iribarren1, GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA, 6internal
J.M. Alustiza3, E. Salvador3, A. azkune4, E. zubillaga4, L. Rincon5, J. medicine, zarauz health center, zarauz, 7clinical epidemiology, DONOSTIA
I. Emparanza2 on behalf of Burnia Group HOSPITAL, DONOSTIA, Spain
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epide- Contact E-mail Address: agustincastiella@yahoo.es
miology, Donostia hospital, 3Radiology, Osatek Donostia, 4Internal Medicine,
Donostia hospital, Donostia, 5GASTROENTEROLOGY, Bidasoa Hospital, Irun, INTRODUCTION: Olynyk et al (1) analyzed in Australia in 2009 the LIC by MRI
Spain of 52 consecutive patients who were referred for HF to a tertiary hospital. They
Contact E-mail Address: agustincastiella@yahoo.es described three different groups according to HFE mutations and TSI (A Group: no
predisposing mutations (PM) for Hereditary Hemochromatosis (HH) and TSI 4 45
INTRODUCTION: Ferritin41000 has been associated with high grade fibrosis %, B Group: PM for HH: C282Y/C282Y; C282Y/H63D, and TSI 4 45 %; C
in hemochromatosis and in liver iron overload disorders. Group: no PM for HH and normal TSI). They concluded that LIC in B Group was
AIMS & METHODS: To establish the nosologic characteristics of ferritin significantly higher than in A and C groups. In the Basque Country, predisposing
41000 ng/ml to diagnose high liver iron overload (hepatic iron index4 1.9) mutations differ, with relevance of the H63D/H63D mutation (2).
(HIO) and for the diagnosis of significant iron overload in liver (4 60 micromol AIMS & METHODS: To study the relevance of HFE mutations and TSI in
Fe/g) (SIO). determining LIC of HF patients attending the outpatient clinic at a secondary
Cohort of consecutive patients studied by MRI for quantification of liver iron hospital.
concentration (LIC). Variables: age, sex, ferritin and LIC. We calculate the mean Prospective study of 132 consecutive patients with HF. January to December
and standard deviation for quantitative variables and absolute and relative fre- 2010. In 120 HFE study was available. In 79 LIC was obtained by MR. In 71
quencies for qualitative variables. patients values of HFE mutations, TSI, and LIC by MR were available. The LIC
The relationship between ferritin and LIC is analyzed using a simple linear was measured in mmol / g (normal 36 mmol /g) by MR (Alustiza et al method
regression model. (3)).
To establish the nosological characteristics of ferritin we calculated the sensitivity RESULTS: mean age: 55.68 14.26 (23-83), 55 men and 16 women (77.5 %,
(S), specificity (Sp), positive predictive value (PPV) and negative (NPV) with 22.5 %). The mean age for men was 53.07 13.61; 64.63 13.14 in women. The
their 95% CI. mean LIC by MR in men was 35.66 36.85; 38.81 29.75 in women. Patients in
RESULTS: Total number of patients was 538 (449 men), with a mean age of 53.6 A Group: 21, 14 with normal LIC, 7 raised LIC; B Group: 19-H63D/H63D;
(SD 13.4). Mean ferritin value was 804.5 (SD 655.2). 56 patients (10.4%) had C282Y/H63D-, 11 normal LIC, 8 raised LIC; C Group: 31 patients, 23 normal
HIO and 125 (23.2%) had (SIO). Mean LIC in patients with ferritin4 1000 was LIC, 8 raised LIC. The mean LIC in A Group: 38.80 45.18 (5-210), B group:
55.9 micromol Fe /g. The PPV for HIO is 27.1% (19.9 to 35.8) and NPV of 48.96 37.51 (15-160), C group: 28.12 18.85 (5-75). We compared the LIC
94.3% (91.6 to 96.1). With our prevalence of 10.4%, the expected results by mean values of the 3 groups using ANOVA, with no significant differences.
chance alone would have been: PPV 10.7% (5 to 21.5) and NPV 89.6 (86.6 CONCLUSION: In our study, the LIC in different groups of patients referred
to 92), close to the values obtained with ferritin 4 1000. To diagnose SIO, PPV for HF to a secondary hospital, with different predisposition to HH (PM, raised
of ferritin 41000 is 50% (41.1 to 58.9) and NPV of 84.3% (80.5 to 87.5). In this TSI), are similar. The different HFE mutations and TSI values do not appear to
case, the expected results by chance would have been: PPV 24.6% (17.7 to 33.1) be relevant in the LIC of these patients.
and NPV 77.1% (72.9 to 80.9). REFERENCES
CONCLUSION: Ferritin4 1000 has a low value for the diagnosis of HIO or for (1). Olynyk, et al. Clin Gastroenterol Hepatol 2009; 7: 359-362.
SIO. (2). Castiella, et al. J Gastroenterol Hepatol 2010; 25: 1295-1298.
Disclosure of Interest: None declared (3). Alustiza, et al. Radiology 2004; 230: 479-484.
Disclosure of Interest: None declared
A294 United European Gastroenterology Journal 2(5S)
and Chief Medical Officer of Keystone Nano, M. Pinzani: no conflict of interest
P0584 GLUCAGON-LIKE PEPTIDE-1 (GLP-1) ANALOGUE,
to declare, K. Rombouts: no conflict of interest to declare
LIRAGLUTIDE, INHIBITS OXIDATIVE STRESS AND
INFLAMMATORY RESPONSE IN THE LIVER OF RATS WITH DIET
INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE P0586 APOC3 ( 455T4C) POLYMORPHISM CONFERS
H.T. Gao1, L.S. Xu1,*, Z.G. Zeng1, L.C. Guan1, W.P. Deng1 SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE
1
Guangdong General Hospital, Guangzhou, China IN A HAN CHINESE POPULATION
M. Li1,*, S. Zhang1, X. Liao1, K. Chao1, J. Yao1, B. Zhong1
INTRODUCTION: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, 1
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen
has been demonstrated to reduce hepatic steatosis. However, the mechanisms University, Guangzhou, China
of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim Contact E-mail Address: sophiazhong@medmail.com.cn
of the present study was to investigate the beneficial effect of liraglutide on diet
induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechan- INTRODUCTION: Genetic variation in apolipoprotein C3 (APOC3) was
isms in rats. reported to be associated with nonalcoholic fatty liver disease (NAFLD), but
AIMS & METHODS: NAFLD was induced by in Sprague-Dawley rats by its role in Chinese population is not well understood.
feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg AIMS & METHODS: To investigate the association between the apolipoprotein
body weight/day) was injected intraperatoneally to the rats subjected to HFHC C3 (APOC3, -455T4C) polymorphism and nonalcoholic fatty liver disease
diet 4 weeks before sacrificing. Body and liver weight, fasting blood glucose (NAFLD), we recruited 300 NAFLD patients and 300 healthy controls to a
(FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation cohort representing Han Chinese at The First Affiliated Hospital, Sun Yat-sen
in the liver were determined. Markers of oxidative stress, such as malondialde- University, from January to December 2012. Polymerase chain reaction-restric-
hyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro- tion fragment length polymorphism (PCR-RFLP) and DNA sequencing were
inflammatory cytokine tumor necrosis factor-a (TNF-a) were detected with used to genotype the APOC3 (-455T4C) variants.
RIA or ELISA kits. Serum and hepatic adiponectin were measured. The expres- RESULTS: After adjusting for age, gender, and BMI, TC and CC genotypes
sion of JNK-1 and phosphorylated JNK1 were examined with Western blot. were found to increase the susceptibility to NAFLD compared to that of the TT
RESULTS: Liraglutide improved insulin resistance, decreased hepatic steatosis genotype, with odds ratios (ORs) of 1.94 (95% CI, 1.26-2.98) and 3.01 (95% CI,
and reversed liver dysfunction. The hepatic levels of MDA, FFAs, TNF-a were 1.76-5.16), respectively. Further stratification analysis indicated that the CC
significantly decreased. While, the SOD and adiponectin levels in the liver were genotype was more susceptible to insulin resistance (IR) than the TT genotype,
significantly elevated by liraglutide treatment. Administration of liraglutide also with OR of 2.59 (95% CI, 1.26-5.30). The CC genotype also was associated with
inhibited the expression of JNK-1 and phosphorylated JNK-1. a much higher risk of hypertension, hypertriglyceridemia, and low levels of high-
CONCLUSION: Liraglutide exerted anti-oxidative and anti-inflammatory density lipoprotein cholesterol (P50.05). No association was found between the
effects in the liver and consequently reverse hepatic steatosis and insulin resis- APOC3 (-455T4C) polymorphism and body-mass index, level of fasting plasma
tance. Such effects might be mediated by the elevation of adiponectin levels and glucose, serum uric acid, total cholesterol, and low-density lipoprotein choles-
the inactivation of JNK1. terol (P40.05).
Disclosure of Interest: None declared CONCLUSION: APOC3 (-455T4C) genetic variation is involved in the suscept-
ibility to develop NAFLD, IR, and some metabolic syndrome disorders in the
Han Chinese population.
P0585 SHORT CHAIN C6-CERAMIDE LIPOSOMAL UPTAKE AFFECTS Disclosure of Interest: None declared
INFLAMMATION, PROLIFERATION, FIBROSIS AND OXIDATIVE
STRESS IN MCD-INDUCED NASH IN VIVO
F. Zanieri1, L. Longato2,*, S. Omenetti1, S. Galastri1, S. Madiai1, T. V. Luong2, P0587 SERUM ADIPOKINES IN PATIENTS WITH NON ALCOHOLIC
T. Fox3, S.S. S. Velandy3, M. Kester3, M. Pinzani2, K. Rombouts2 FATTY LIVER DISEASE, IS THERE A ROLE FOR PREDICTING
1
Department of Experimental and Clinical Medicine and Center of Excellence for THE SEVERITY OF LIVER DISEASE?
the study at molecular and clinical level of chronic, degenerative and neoplastic M.A. Amin1,*, K. Al-Ashmawi1, O. Shaker2, S. Mussa1
1
diseases to develop novel therapies DENOthe, University of Florence, Florence, internal medicine, 2biochemistry, Cairo University, Cairo, Egypt
Italy, 2Division of Medicine, University College of London, Institute for Liver & Contact E-mail Address: monasleman@hotmail.com
Digestive Health, Royal Free, London, United Kingdom, 3Department of
Pharmacology, Penn State University College of Medicine, Hershey, United States INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is considered to
Contact E-mail Address: k.rombouts@ucl.ac.uk be among the most common liver diseases world-wide. NAFLD encompasses a
broad spectrum of pathological conditions ranging from simple steatosis (SS) to
INTRODUCTION: Ceramides are members of the sphingolipid family and are steatohepatitis (NASH), fibrosis and finally even cirrhosis. Adiponectin (A) has
an integral part of the lipid bilayer of cell membranes. Ceramides exert biological been associated with inhibition of fibrogenesis and liver protection while leptin
effects through cellular proliferation, differentiation and cell death. The role of (L) contributes to fibrogenesis in various chronic liver diseases, notably in
changes in endogenous ceramides to the pathogenesis of NAFLD to NASH is NASH.
sparse. In this study the effect of exogenous liposomes containing short chain C6- AIMS & METHODS: To determine the validity of serum adipokines including
Ceramide (Lip-C6) was evaluated in a NASH model and in vitro in primary leptin, adiponectin, and A/L ratio to act as a potential markers for NAFLD and
human Hepatic Stellate Cells (hHSC) as possible Lip-C6 target. to discriminate NASH from SS.
AIMS & METHODS: NASH was induced by feeding mice for 9 weeks a methio- Patients and methods: Eighty four patients who have bright liver on abdominal
nine-and choline-deficient (MCD) diet, or control diet (CD), followed by a single ultrasonography and 28 healthy individuals served as control group. Serum
tail-vein injection of Lip-C6. The effect of Lip-C6-treatment was investigated by Leptin and Adiponectin were estimated by ELISA technique. Liver biopsy was
measuring ALT/AST, histology, Q-PCR and protein analysis. Possible changes done for 46 patients and according to histopathological examination they were
in hepatic ceramide magnitude/species specificity and sphingosines were mea- divided into 21 patients with SS and 25 patients with NASH.
sured by employing untargeted LC-MS/MS lipidomics. The effect of Lip-C6 RESULTS: The serum concentration of adiponectin was significantly lower in
on primary hHSC proliferation, cytotoxicity and signaling pathways was NASH than SS group (P 50.001). There was no significant difference between
investigated. serum concentration of leptin in both groups (p 0.4). A/L ratio in NASH group
RESULTS: MCD-Lip-C6 treatment did not exacerbate MCD-induced NASH was significantly lower than SS group (P 50.001). Adiponectin was negatively
when analyzing ALT/AST, steatosis, lobular inflammation, ballooning, apopto- correlated with BMI, total cholesterol and LDL-C in both groups. A/L ratio in
sis and fibrosis. Protein analysis showed that Lip-C6-treatment affects the endo- NASH group was significantly positively correlated with adiponectin (P50.001)
genous antioxidant system KEAP1-Nrf2-NQO1 in MCD-fed mice. MCD-fed while it was significantly negatively correlated with leptin (P50.001). In SS
mice showed a reduction in p-JNK, cleaved caspase-3/PARP, the mRNA stabi- group A/L ratio was significantly negatively correlated with leptin (r -0.863,
lizing protein ELAV1/HuR and its downstream target phosphorylated p62 when P50.001).
compared to CD-fed mice which were not affected by Lip-C6-treatment. CONCLUSION: In patients with NAFLD, the serum adiponectin and A/L ratio
Exogenous liposomal short chain ceramide C6 treatment does not affect inflam- can discriminate simple steatosis from NASH and predict the severity of liver
mation markers TNFalpha and NFKB signalling pathway. A strong phosphor- injury.
ylation of AMPK was induced in Lip-C6-treated MCD-fed indicating a Disclosure of Interest: None declared
stimulation of energy producing catabolic pathways. Of particular note, Lip-
C6-treatment reverses the significant decreases in phosphatidylcholines (PC)
and phosphatidylethanolamines (PE) species and rearranges the significant P0588 MYOSIN LIGHT CHAIN KINASE INVOLVED IN INTESTINAL
increases in specific sphingolipid species in MCD-fed mice. Moreover, Lip-C6- BARRIER FUNCTION CHANGE OF MICE WITH NAFLD
Rhodamine was taken up by primary hHSC and Lip-C6-treatment inhibits pro- Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1
liferation and cytotoxicity in a concentration-dependent manner. 1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking
CONCLUSION: These results demonstrate that a single injection of short chain University Peoples Hospital, Beijing, China
C6-ceramide liposomes does not exacerbate inflammation, apoptosis, prolifera- Contact E-mail Address: medicalyuan@foxmail.com
tion and oxidative stress in MCD-induced NASH, possibly by restoring changes
in membrane lipid content induced by NASH. INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in
Disclosure of Interest: F. Zanieri: no conflict of interest to declare, L. Longato: no the mechanisms of barrier dysfunction, and some studies showed nonalcoholic
conflict of interest to declare, S. Omenetti: no conflict of interest to declare, S. fatty liver disease (NAFLD) had intestinal barrier function change. The present
Galastri: no conflict of interest to declare, S. Madiai: no conflict of interest to study aimed to identify whether MLCK was involved in the pathogenesis of
declare, T. V. Luong: no conflict of interest to declare, T. Fox: no conflict of nonalcoholic fatty liver disease (NAFLD).
interest to declare, S. S. S. Velandy: no conflict of interest to declare, M. Kester AIMS & METHODS: The NAFLD mice model was established by giving high-
Directorship(s) for: Penn State Research Foundation has licensed ceramide fat diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administra-
nanotechnology to Keystone Nano, Inc. (PA, USA) and M. K. is cofounder tion. Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The level
United European Gastroenterology Journal 2(5S) A295
of ALT, AST was assessed. The degree of liver steatosis was observed by HE we hypothesised that its combination with antiretrovirals can specifically exacer-
stain. Intestinal mucosal tight junction was observed by electron microscope, and bate the hepatotoxic effects of the latter drugs.
the occludin protein was stained by immunofluorescence. AIMS & METHODS: To analyse the acute mitochondrial effects of clinically
RESULTS: MLCK expression increased in NAFLD and NASH groups vs con- relevant concentrations of the purine analogues ABC and didanosine (ddI), to
trol group. ALT and AST elevated in the NAFLD and NASH group, which assess their impact on mitochondrial function and the viability of hepatic cells,
could be reduced by MLCK inhibitor ML-7 (Table.1, *P50.05 vs NAFLD and to explore potential synergisms with APAP and other hepatotoxic drugs.
group, ** P50.05 vs NASH group). The liver pathology showed no significant Several parameters of mitochondrial function (oxygen consumption, mitochon-
change after ML-7 administration. The intestinal tight junctions occludin protein drial membrane potential - m-, reactive oxygen species ROS- production,
were seemed to be ameliorated by ML-7,but there were no significant difference. intracellular ATP levels, GSH levels) and cellular viability were assessed in
non-HIV-infected Hep3B and hepatocyte-like HepaRG cells treated (1-48h)
U/L Control NAFLD NAFLDML-7 NASH NASHML-7 with the purine analogues ABC and ddI. Further experiments were performed
in the presence of sub-damaging concentrations of different hepatotoxic stimuli
ALT 20.330.843 20.002.014 13.800.663 31.703.208* 18.801.597** (APAP, the antiretroviral drugs ritonavir and nevirapine, and ethanol). Data
were reported as mean/-SEM, and their statistical significance versus vehicle
AST 46.672.704 44.002.075 37.602.349 117.612.23* 73.105.382** was analyzed by one-way ANOVA. Correlations were analysed using
Spearmans correlation coefficient.
RESULTS: Clinical concentrations of purine analogues produced an immediate
CONCLUSION: MLCK inhibitor ML-7 could protect liver function via improv- and significant decrease in mitochondrial function, evident in a concentration-
ing the intestinal barrier of NAFLD mice. dependent inhibition of O2 consumption, increased ROS production, and a
REFERENCES reduction of m and intracellular ATP levels. This mitochondrial dysfunction
1. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and did not compromise cell survival, as the aforementioned parameters returned to
tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49: previous values after 24h treatment. However, co-administration of these drugs
1877-1887. with APAP concentrations below those considered toxic in hepatic cellular
2. Wang N, Yu H, Ma J, et al. Evidence for tight junction protein disruption in models exacerbated the deleterious effects of both treatments on mitochondrial
intestinal mucosa of malignant obstructive jaundice patients. Scand J function and cellular viability, thus decreasing intracellular GSH concentrations.
Gastroenterol 2010; 45: 191-199. Such effect was not observed with the other hepatotoxic stimuli evaluated.
Disclosure of Interest: None declared Interestingly, a significant positive correlation was detected between GSH
levels and cell viability.
CONCLUSION: The combination of ABC or ddI with low concentrations of
P0589 EPITHELIAL MYOSIN LIGHT CHAIN KINASE-DEPENDENT APAP significantly effects GSH concentrations in a way that increases the risk of
BARRIER DYSFUNCTION INVOLVED IN INTESTINAL BARRIER APAP-mediated liver injury. Our findings are of considerable relevance given
FUNCTION CHANGE OF MICE WITH NAFLD that APAP is currently prescribed to patients taking NRTI and that HIV infec-
Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1 tion itself has been reported to undermine intracellular GSH levels.
1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking Disclosure of Interest: None declared
University Peoples Hospital, Beijing, China
Contact E-mail Address: medicalyuan@foxmail.com
P0591 THE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE
INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in INHIBITOR EFAVIRENZ MODIFIES THE INFLAMMATORY
the mechanisms of barrier dysfunction, and a lot of studies showed the intestinal RESPONSE OF HEPATIC CELLS
barrier permeability increased in nonalcoholic fatty liver disease (NAFLD). A. Blas-Garc a1,2,*, F. Alegre1,2, D. Ortiz-Masia2, L. Milian-Medina1,
AIMS & METHODS: The research aimed to identify whether MLCK was a N. Apostolova3,4, J. V. Esplugues1,2
regulator in the intestinal barrier permeability change of nonalcoholic fatty liver 1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
disease (NAFLD). The NAFLD mice model was established by giving high-fat Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administration. Universidad Jaime I, Castellon de la Plana, Spain
Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The intestinal Contact E-mail Address: ana.blas@uv.es
mucosal tight junction was observed by electron microscope, and the LPS con-
centration of portal vein was detectedd by ELISA. INTRODUCTION: Efavirenz (EFV) is the most widely used drug in the treat-
RESULTS: ment of HIV-infection, but has recently been associated with oxidative stress,
MLCK expression increased significantli in fatty liver (NAFLD) and NASH, mitochondrial dysfunction and endoplasmic reticulum stress in hepatocytes. As
which could be blocked by ML-7. The intestinal epithelial tight junction of mitochondrial damage and ER-stress are frequently related to inflammatory
NASH were broader compared with control group, which could be improved disease, we have evaluated the effects of EFV on the cytokine/chemokine expres-
by MLCK inhibitor ML-7 (Table 1). The LPS in portal vein of NASH mice was sion pattern of hepatic cells. In addition, we have explored the possible involve-
higher, suggesting the intestinal barrier permeability dysfunction. After MLCK ment of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kB)
was blocked by ML-7, the LPS in portal vein decreased significantly. and NLRP3 inflammasome, both of which trigger signalling pathways implicated
in hepatic inflammation and liver injury.
nm Control NAFLD NAFLDML-7 NASH NASHML-7 AIMS & METHODS: Non-HIV-infected Hep3B cells were treated with clini-
cally-employed concentrations of EFV (10 and 25mM). Inflammation-related
TJ 14.900.329 19.801.197* 19.200.997* 26.61.200* 14.900.666# gene expression was studied with Real time PCR. Activation of NF-kB was
confirmed by Western blot. An electrophoretic mobility shift assay (EMSA)
was carried out to determine the binding of NF-kB to promoters of some of
the genes whose expression was found to be up-regulated. Chemokine secretion
Table 1: The tight junction of intestinal epithelial of different groups. was evaluated in culture supernatant samples using an immunoassay kit. Data
CONCLUSION: The intestinal barrier function was restored by specifically (n3) were analysed with one-way ANOVA followed by a Newman-Keuls test.
inhibiting MLCK, suggesting that MLCK activity was responsible for the *p50.05, **p50.01, ***p50.001 (vs control).
change of barrier function in NAFLD. RESULTS: EFV induced mRNA expression of the inflammatory mediators
REFERENCES TNF, IL-6, PAI-1, TXNIP and NLP3 in a significant and concentration-depen-
1. Al-Sadi R, Guo S, Ye D, et al. TNF- modulation of intestinal epithelial tight dent manner. Furthermore, EFV reduced IkBa protein levels, thus increasing
junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol 2013; NF-kB translocation to the nucleus. The EMSA assay demonstrated that
183: 1871-1884. trans-activation of PAI-1 was mediated by interaction of NF-kB with a consen-
2. Al-Sadi R, Guo S, Ye D, et al. Mechanism of IL-1beta modulation of intest- sus sequence located within the PAI-1 promoter. Nevertheless, EFV also signifi-
inal epithelial barrier involves p38 kinase and activating transcription factor-2 cantly reduced the production and secretion of IL-8 and IP-10, chemokines
activation. J Immunol 2013; 190: 6596-6606. involved in the progression of liver injury.
Disclosure of Interest: None declared CONCLUSION: Due to its inhibitory effects on mitochondrial function, EFV
promotes a pro-inflammatory response through NF-kB- and NLRP3-dependent
pathways. Interestingly, EFV also reduced the secretion of IL-8 and IP-10, thus
P0590 ABACAVIR AND DIDANOSINE ENHANCE ACETAMINOPHEN- playing a dual role in regulating the inflammatory response. In the context of
INDUCED HEPATOTOXICITY THROUGH GSH DEPLETION lifelong use of EFV, these effects could accumulate and exacerbate the liver
A. Blas-Garc a1,2,*, V.M. V ctor2,3, M. Polo1,2, H.A. Funes1, A. Mart -Rodrigo1, toxicity induced by other stimuli such as other antiretroviral drugs, co-infections
N. Apostolova3,4, J. V. Esplugues1,2 (hepatitis B and/or C) or co-morbidities associated with HIV infection.
1
Pharmacology, Universidad de Valencia-CIBERehd, 2FISABIO-Hospital Disclosure of Interest: None declared
Universitario Dr. Peset, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: ana.blas@uv.es
INTRODUCTION: Liver disease is a leading cause of mortality among HIV-
infected patients and has been related in some cases to combined Antiretroviral
Therapy (cART). Little is known about the acute effects of nucleoside/nucleotide
reverse transcriptase inhibitors (NRTI) on hepatic cells, although the purine
analogue abacavir (ABC) has been reported to induce an acute mitotoxic effect
in vitro. Since acetaminophen (APAP), a well-known hepatotoxic drug, is com-
monly prescribed to HIV-infected patients and also interferes with mitochondria,
A296 United European Gastroenterology Journal 2(5S)
measurement of BMD and risk factors are needed to elucidate the mechanism
P0592 LIVER FUNCTION AND ELASTICITY MONITORING DURING
of bone fractures in ALD.
RHEUMATOID ARTHRITIS DISEASE MODIFYING TREATMENT
Disclosure of Interest: None declared
A.A. Popov1,*, E.G. Martemyanova2
1
Internal Medicine Dept.#2, URAL STATE MEDICAL UNIVERSITY,
2
Preobrazhenskaya Clinic, Ekaterinburg, Russian Federation P0594 IS SQSTM1/P62 A DEFENCE AGAINST EFV-INDUCED
Contact E-mail Address: art_popov@mail.ru HEPATOTOXICITY?
F. Alegre1,2,*, A. Blas-Garc a1,2, M. Polo1,2, H.A. Funes2, N. Apostolova3,4, J.
INTRODUCTION: Rheumatoid arthritis (RA) requires early intervention with V. Esplugues1,2
disease modifying drugs (DMARDs) in order to prevent disease progression and 1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
disability [1]. Liver safety issues may delay or limit DMARDs administration [2]. Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
AIMS & METHODS: Aim: to assess liver function tests and liver elasticity Universidad Jaime I, Castellon de la Plana, Spain
during first year of RA DMARDs treatment in everyday clinical practice. Contact E-mail Address: fernando.alegre@uv.es
Methods: 20 consecutive rheumatologists out-patients (16 females) aged from 26
to 56 (mean 47.7) were enrolled in a prospective cohort study. All had newly INTRODUCTION: Sequestome 1/p62 is a multifunctional protein known to be
diagnosed established seropositive RA according to ACR/EULAR 2010 criteria. involved in autophagy, during which it acts as a substrate carrier and becomes
Viral hepatitides being preliminarily excluded, anthropometry, serum ALT, AST, degraded. It has also been reported that p62 plays important roles in other
GGTP, bilirubine levels, were registered as safety measures by 2, 4, 12, 24, 36, 48 cellular events, including oxidative stress responses, proteostasis, inflammation
week. Liver ultrasound elastography (FibroScan, Echosens, France) was per- and cell survival, while, interestingly, it is implicated in several liver diseases, such
formed twice: at enrollment and end of study visit. RA disease activity was as non-alcoholic steatohepatitis. The non-nucleoside reverse transcriptase inhi-
assessed by DAS28 index by 12, 24, 26 and 48 week. All patients were adminis- bitor Efavirenz (EFV) is widely employed in combined antiretroviral therapy to
tered oral methotrexate 10-25 mg weekly or leflunomide 20 mg daily as treat HIV1 infection, and, though generally considered safe, has been associated
DMARDs. Ibuprophen up to 1200 mg per 24 hours was allowed as on with hepatotoxic events. Although the underlying mechanisms of the deleterious
demand rescue treatment. Rescue medication consumption was registered by hepatic effects of EFV are still unclear, evidence points to altered lipid metabo-
tablets count. All patients received advices on smoking cessation, diet optimiza- lism, mitochondrial dysfunction/mitophagy and endoplasmic reticulum stress in
tion, physical exercises and daily activies adjusted to body mass index and human hepatocytes.
comorbidities. AIMS & METHODS: To analyse the implication of p62 in EFV-induced toxicity
ra w n
RESULTS: All patients had comorbidities by DMARDs initiation. The most
frequent were arterial hypertension (11 pts.), dyslipidemia (20 pts.), obesity (5
in hepatocytes. The human hepatoma line Hep3B and cells lacking functional
mitochondria (Hep3B rho-zero obtained through pharmacological interruption
d
pts.), high fasting glucose (7 pts.), type 2 diabetes mellitus (5 pts.). In 13 subjects of mtDNA replication) were exposed to clinically relevant concentrations (10 and
only 1 subject.
i t h
metabolic syndrome (MS) was diagnosed. Non-alcocholic steatohepatitis
W
(NASH) was diagnosed in 8 patients, while normal liver elasticity was found in
P0604
fulfilling the criteria for HPS and PPS. The study sample included 70 patients
with alcoholic liver cirrhosis;22 patients with grade A, 24 patients with grade B,
P0604 THE SENSITIVITY AND SPECIFICITY OF INHIBITORY and 24 patients with grade C according to the Child-Pugh clinical score. Systemic
CONTROL TEST IN THE DIAGNOSIS OF MINIMAL HEPATIC circulation measurements included: heart rate (HR), mean arterial pressure
ENCEPHALOPATHY: A META-ANALYSIS (MAP), cardiac index (CI), systemic vascular resistance (SVRI) and cardiac
M.T. T. Panlilio1,*, A.Q. Taguba1, M.E. VIllamayor1, J.P. Ong1 stroke volume (CSV)1. Neurohumoral parameters included: NT-proBNP, nora-
1
Section of Gastroenterology, University of the Philippines Manila-Philippine drenalin (NA) and plasma renin activity (PRA). HPS was diagnosed if the pre-
General Hospital, Manila, Philippines sence of impaired arterial oxygenation (PaO2580mmHg and alveolar-arterial
Contact E-mail Address: mttpanlilio@gmail.com oxygen gradient 15mmHg; for patients older than 64 years PaO270 mmHg,
and A-a gradient 20 mmHg) and pulmonary vascular abnormalities were
INTRODUCTION: Minimal hepatic encephalopathy (MHE) is a complication found. PPH was characterized by increased mean pulmonary artery pressure
of liver cirrhosis that does not show symptoms of overt hepatic encephalopathy 425 mmHg at rest and if the diameter of the main pulmonary artery is 29
(OHE). This state reflects alterations in cognitive function, but clinically exhibit a mm with concomitant segmental arteryto-bronchus ratio 4 1:1 at least in three
normal mental status examination. Patients with MHE have been shown to have out of four pulmonary lobes, or the ratio of the main pulmonary artery diameter
higher rates of automobile accidents, it predicts the development of OHE, and is to the aortic diameter 41.
associated with poor survival. RESULTS: HPS and PPH were found in 28 (40%) patients. Patients with HPS
Diagnosis of MHE is difficult, as the absence of clinical evidence of encephalo- were mostly patients from group B (57.2%) and C (42.8%) with respect to the
pathy is key to its diagnosis. Neuropsychological testing, specifically the degree of liver failure, while all patients with PPH were patients with advanced
Psychometric Hepatic Encephalopathy Score (PHES), is accepted as a reference liver failure. When correlating systemic hemodynamic and neurohumoral para-
standard in the diagnosis of MHE. Newer computer-assisted techniques, such as meters in relation to the presence of HPS and PPS no significant difference was
the Inhibitory Control Test (ICT), have been studied to improve the detection of found. (Table 1).
MHE. ICT is a simple computer-based test, consisting of presentation of several CONCLUSION: The combined application of the Doppler and contrast echo-
letters at 500-millisecond intervals. The ease of performing the test in the out- cardiography is a simple, non-invasive and reproducible method that enables the
patient setting may make it a good test for detecting MHE. diagnosis of both HPS and PPH. Systemic hemodynamic parameters remained
AIMS & METHODS: This study aims to determine the sensitivity and specificity unchanged among patients with HPS and PPS.
of Inhibitory Control Test in diagnosing minimal hepatic encephalopathy. REFERENCES
COCHRANE and MEDLINE were searched for articles published between 1. Zekanovic D, LJubicic N, Boban M, et al. Doppler ultrasound of hepatic and
January 2003 to October 2013. Studies that compared ICT with psychometric system hemodynamics in patients with alcoholic liver cirrhosis. Dig Dis Sci 2010;
tests in cirrhotics were included. Data analysis was performed using the validated 55: 458-466.
application Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). The Disclosure of Interest: None declared
DerSimonian-Laird random effects method was used to produce summary estimates
of sensitivity, specificity, likelihood ratios (LR), and diagnostic odds ratio (DOR).
RESULTS: The search strategy identified 133 studies. Based on pre-stated cri- P0606 DO COAGULATION AND PLATELET FUNCTION DISORDERS
teria, three studies were included in the final review. There were 235 patients with INFLUENCE THE PREVALENCE OF VARICEAL BLEEDING IN
liver cirrhosis and a matched control group that underwent both psychometric PATIENTS WITH LIVER CIRRHOSIS?
testing and ICT. Pooled data showed that the ICT had a sensitivity of 88% P. Rogalski1,*, E. Wroblewski1, M. Rogalska-Plonska2, A. Swidnicka-
(I2 0%), specificity of 72% (I2 69.2%), and DOR was 21.2 (95% CI: 8.08 Siergiejko1, A.A. Baniukiewicz1, A. Dabrowski1
55.24). A symmetrical sROC depicted an area under the receiver operator curve 1
Department of Gastroenterology and Internal Medicine, 2Department of Infectious
(AUC) of 0.89 (standard error 0.03). Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
CONCLUSION: Inhibitory Control Test is a good tool to exclude cirrhotic
patients without minimal hepatic encephalopathy. It is effective in discriminating INTRODUCTION: Bleeding from gastro-esophageal varices is a life-threatening
patients with MHE from those without MHE and therefore has potential as a condition and occurs in approximately one third of patients with liver cirrhosis
screening test. However, more high-quality studies are needed to establish test during their lifetime. On the other hand patients with history of variceal bleeding
accurarcy. have 70% risk of recurrent bleeding within the next year since the first episode.
REFERENCES Coagulation disorders in patients with liver cirrhosis are complex, and their role
Stinton LM and Jayakumar S. Minimal hepatic encephalopathy. Can J in variceal bleeding remains unclear. Previous studies have shown that the results
Gastroenterol 2013; 27: 572-574. of standard laboratory tests such as prothrombin time (PT) and activated partial
Hisamuddin K, et al. Is the ICT as accurate as standard psychometric testing for thromboplastin time (APTT) provide a narrow measure of procoagulant system
diagnosing hepatic encephalopathy? Nat Clin Pract Gastroenterol Hepatol 2008; only and do not predict bleeding in cirrhotic patients. Thromboelastometry has
5: 132-133. been used for decades for intraoperative transfusion guidance and it can show
Bajaj JS, et al. Inhibitory control test for the diagnosis of MHE. Gastroenterol defects in multiple components of hemostasis. Multiplate impedance platelet
2008; 135: 15911600. aggregometry (IPA) allows rapid evaluation of platelet aggregation in whole
Bajaj JS, et al. Inhibitory Control Test Is a Simple Method to Diagnose MHE blood.
and Predict Development of OHE. American J Gastroenterol 2007: 754-760. AIMS & METHODS: The aim of our study was to compare the character of
Sharma P, et al. Inhibitory control test, critical flicker frequency, and psycho- coagulation disorders in patients with liver cirrhosis and a history of variceal
metric tests in the diagnosis of MHE in cirrhosis. Saudi J Gastroenterol 2013; 19: bleeding with non-bleeding cirrhotic patients. We compared standard laboratory
4044. clotting tests, thromboleastometry (ROTEM thromboelastometer) and IPA
Disclosure of Interest: None declared parameters of cirrhotic patients with medium-large varices who have never
bled (non-bleeding group) with patients with a history of variceal bleeding at
least 3 weeks before (bleeding group). The following thromboelastometry para-
P0605 SYSTEMIC HEMODYNAMICS IN PATIENTS WITH ALCOHOLIC meters were measured: clotting time (CT), clot formation time (CFT), maximum
LIVER CIRRHOSIS AND HEPATOPULMONARY SYNDROME OR clot firmness (MCF) and the clot amplitude at 5, 10 and 15 minutes in three tests
PORTOPULMONARY HYPERTENSION with specific activators to evaluate the extrinsic (EXTEM) and intrinsic
N. Ljubicic1,*, D. Zekanovic1, T. Pavic1, M. Nikolic1, I. Budimir1, A. Biscanin1 (INTEM) systems, and the clotting factors alone after platelet inactivation
1
Division of Gastroenterology, Department of Internal Medicine, Sestre milosrd- (FIBTEM). In addition, IPA was performed with ADP as an activator and
nice University Hospital, University of Zagreb School of Medicine and University aggregation was quantified as area under the curve (AUO).
of Zagreb School of Dental Medicine, ZAGREB, Croatia RESULTS: Blood was sampled from 44 patients (23- non-bleeding group, 21-
Contact E-mail Address: neven.ljubicic@kbcsm.hr bleeding group). Baseline characteristics of the bleeding and non-bleeding groups
were comparable apart from a more prolonged PT in the bleeding group [15,8
INTRODUCTION: There is a lack in knowledge about the correlation of sys- (14,1 - 17,3) vs 14,3 (13,5-16,0), p 0.045]. The severity of liver disease according
temic circulation parameters and the degree of liver failure with respect to the to ChildPough score was comparable in both groups [8,00 points (8,0-10,0)
presence of hepatopulmonary syndrome (HPS) and portopulmonary hyperten- non-bleeding group vs 9,0 (8,0-10,0) bleeding group, p 0.889]; 5 patients
sion (PPH). class A, 23 patients - class B, 16 patients - class C. In FIBTEM there was
AIMS & METHODS: The aim of this study was to evaluate the changes in the significantly lower amplitude at 15 minutes in the bleeding group compared
systemic circulation by using non-invasive diagnostic approach in the patients with non-bleeding group [12.0 (9,5-14,5) vs 15.0 (11,0-19,0), p 0.049]. The
A300 United European Gastroenterology Journal 2(5S)
other results of thromboelastometry and aggregometry parameters did not differ Strong correlation of liver stiffness R 0.61 (p50.01) and moderate correlation
significantly between both groups, which suggest a compensatory role of platelets of spleen stiffness R 0.48 (p5 0.01) with oesophageal varices grade were
in EXTEM and INTEM tests. The compensatory role of platelets is also sup- established. To predict the presence of oesophageal varices liver TE cut-off
ported by the results of IPA in which we demonstrated higher value of AUO in value 21.5kPa had sensitivity 0.86 and specificity 0.83; spleen TE cut-off value
bleeding group in comparsion with non-bleeding group [273.0 (99,0-557,0) vs 57.0 kPa had sensitivity 0.73 and specificity 0.75. Area under the ROC curve was
189.00 (132,0-640,0), NS]. 0.86 for liver TE and 0.76 for spleen TE.
CONCLUSION: Despite prolonged PT in bleeding group, the patients with liver CONCLUSION: Liver transient elastography strongly correlates and spleen TE
cirrhosis with and without history of variceal bleeding have similar efficiency of moderately correlates with HVPG and oesophageal varices grade. Liver TE
blood clotting, which may suggest compensatory role of platelets in these accurately predicts significant portal hypertension and oesophageal varices in
patients. patients with chronic liver disease and is more sensitive and specific than
Disclosure of Interest: None declared spleen TE. Therefore liver transient elastography could be reproducible outpa-
tient screening tool for portal hypertension or oesophageal varices.
Disclosure of Interest: None declared
P0607 REAL WORLD EXPERIENCE OF RIFAXIMIN FOR HEPATIC
ENCEPHALOPATHY - EFFECTIVE MAINTENANCE OF
REMISSION AND REDUCTION OF HOSPITAL ADMISSIONS IN A P0609 NUTRITIONAL EVALUATION OF THE CIRRHOTIC PATIENT
LARGE SECONDARY CARE PATIENT COHORT WITHOUT ASCITES: IS THERE A ROLE FOR ANTHROPOMETRIC
H. Preedy1, A. Fowell1, R. Aspinall1,* PARAMETERS?
1
Gastroenterology & Hepatology, Portsmouth Hospitals NHS Trust, Portsmouth, S.M. D. Giestas1,*, A. Giestas1, C. Agostinho1, C. Sofia1
1
United Kingdom Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal
Contact E-mail Address: r.j.aspinall@doctors.org.uk Contact E-mail Address: silviagiestas@gmail.com
INTRODUCTION: Rifaximin has been shown to maintain remission of chronic INTRODUCTION: Malnutrition due to chronic liver disease is common and its
hepatic encephalopathy (HE) and reduce hospital admissions (Bass et al 2010). assessment is difficult. The anthropometric parameters, often used in clinical
However, the literature mainly reflects tertiary centres and could include referral practice, have limited use in the nutritional evaluation of cirrhotic patients
bias. Therefore, we examined the real world utility of rifaximin in a large mainly those with ascites/edema. Some studies demonstrate that Maastricht
secondary care acute hospital, serving a population of 650,000. Nutritional Index (MI) is the best assessment in early stages of the disease,
AIMS & METHODS: All patients with cirrhosis and chronic HE who were however the best method of nutritional evaluation in cirrhotic patients remains
commenced on rifaximin between May 2010 and November 2012 were identified controversial.
from a departmental database and pharmacy records. Analysis included formal AIMS & METHODS: Aim: To determinate the role for anthropometric para-
review of casenotes, pathology, hospital admission statistics and calculation of meters in the nutritional evaluation of cirrhotic patients without ascites and
MELD, UKELD and Childs-Pugh scores. Data were analysed for the 6 months compare it with the MI.
prior to rifaximin usage and at 3, 6 and 12 months later. Patients and Methods: Prospective study of cirrhotic outpatients without ascites
RESULTS: The study population comprised 42 patients, 62% male, mean age 59 (diagnosis based on histological evidence and/or high clinic/ biochemical /imagi-
years. Cirrhosis aetiology was alcohol 55%, NASH 24%, autoimmune 10%, ological suspicion). Exclusion criteria: enteric nutrition, amputation, malabsorp-
HCV 5%, miscellaneous 6%. At initiation, 24% of patients were using alcohol tion syndrome, chronic pancreatitis, inflammatory bowel disease, chronic kidney
and 19% took quinolone secondary prophylaxis against spontaneous bacterial disease, acquired immunodeficiency syndrome, neuromuscular diseases and
peritonitis. Mean baseline prognostic scores were Childs-Pugh 9.4 (SD 2.1), oncologic advanced disease. Included patients where classified according Child-
MELD 15.0 (SD 7.9), UKELD 51.2 (SD 5.1). Survival at 3, 6 and 12 months Pugh Score; weight (kg), height (cm) and body mass index (BMI) were evaluated;
post-rifaximin was 78%, 67% and 62% respectively. There was a significant and based in MI they were stratified in mild (40-3), moderate (43-6) and severe
reduction in Childs-Pugh scores at 3 and 6 months (p50.01) but not 12 (46) impaired nutritional status.
months and no significant change in MELD or UKELD. Comparing the 6 RESULTS: 50 cirrhotic patients were included in the study, 84% (n 42) had
months pre/post rifaximin, hospitalisation days fell from 233 to 143, a mean of alcoholic cirrhosis, the mean age was 58/-11.4 years and 60% were male
5.6 per patient, representing a saving of E1,829 in healthcare tariff costs. The (n 30). Concerning cirrhosis severity: 88% (n 44) were Child-Pugh A and
number of admission episodes fell from 25 to 11. 12% (n 6) Child-Pugh B. 8% (n 4) had a BMI518.5%, regardless of age,
CONCLUSION: In an unselected real world cohort of patients with chronic gender or etiology. MI detected malnourishment/malnutrition in 38% (n 19) of
hepatic encephalopathy, rifaximin was associated with fewer readmission spells patients: 24% (n 12) mild and 14% (n 7) moderate impaired nutritional
and a reduction in bed days with potential savings in healthcare utilisation costs. status. In MI evaluation no statistically difference was found between etiology,
The efficacy of rifaximin for the maintenance of remission in patients with gender and age. No association between malnutrition and disease severity (Child-
chronic HE can be demonstrated in a secondary care environment. Pugh Score) was found with both methods.
REFERENCES CONCLUSION: In this study anthropometric parameters underestimate malnu-
Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encepha- trition in cirrhotic patients when compared with the Maastricht Nutritional
lopathy. N Engl J Med 2010; 362: 1071-1081. Index, which detected malnutrition in early stages of hepatic disease.
Disclosure of Interest: H. Preedy: None declared, A. Fowell: None declared, R. Disclosure of Interest: None declared
Aspinall Consultancy for: RA has received consultancy fees from Norgine UK
P0626 STUDY ON IL28B SNP RS12979860 AND SNP RS8099917 P0628 ASSOCIATIONS OF REACTIVE OXYGEN SPECIES AND IRON
GENOTYPING AND TREATMENT RESPONSE WITH PEGYLATED METABOLISMS WITH DEVELOPMENT OF HEPATOCELLULAR
INTERFERON AND RIBAVIRIN IN EGYPTIAN PATIENTS WITH CARCINOMA AFTER PEGYLATED INTERFERON THERAPY IN
CHRONIC HEPATITIS C VIRUS INFECTION JAPANESE PATIENTS WITH CHRONIC HEPATITIS C
M.A. Amin1,*, N. Algarem1, D. Sabri2, E. Qasem3, E. hasan4 S. Nanba1,*, F. Ikeda1, H. Seki1, K. Yamamoto1
1
internal medicine, 2biochemistry, Cairo University, 3internal medicine, 4pathology, 1
Department of Gastroenterology and Hepatology, Okayama University Graduate
National liver institute, Cairo, Egypt School of Medicine, Dentistry and Pharmaceutical Sciences, okayama, Japan
Contact E-mail Address: monasleman@hotmail.com
INTRODUCTION: Chronic hepatitis C (CHC) may induce reactive oxygen
INTRODUCTION: Hepatitis C virus (HCV) infection is a common universal species (ROS) and excessive iron deposition in the liver.
problem especially in the Arab world. A single nucleotide polymorphism near the AIMS & METHODS: The present study was planned to clarify the impact of
IL28B gene on chromosome 19 coding for interferon-lambda-3 is associated with surplus ROS and iron deposition on virological response to the therapy with
an approximately 2-fold difference in SVR rates among patients of different pegylated interferon plus ribavirin and development of hepatocellular carcinoma
ethnicities. (HCC) thereafter for CHC patients. A total of 210 CHC patients who received
AIMS & METHODS: The aim was to assess the value of IL28B SNP rs12979860 combination therapy of pegylated interferon and ribavirin are enrolled. Liver
and SNP rs8099917 as a predictor of virological response to Pegylated interferon histology was evaluated for all the patients before the therapy. Hepatic ROS
plus ribavirin in treatment of Egyptian patients with chronic hepatitis C virus was assessed with immunohistochemical staining of 8-hydroxy-2-deoxyguanosine
infection. Our study included 604 HCV infected Egyptian patients with genotype (8-OHdG). Hepatic iron deposition was assessed by Prussian blue staining.
4. All patients received pegylated Interferon 2a and 2b plus ribavirin. We divided Factors associated with hepatic 8-OHdG levels were analyzed by stepwise logistic
our cases according to their response to treatment into two groups: group I (344 regression analysis. Proportional hazard models were utilized to identify patient
patients) responded to treatment and group II (260) non responder patients. characteristics associated with HCC development after interferon therapy.
Analysis of both IL28 rs8099917 and IL28rs12979860 by real time PCR techni- RESULTS: Severe hepatic iron deposition was significantly associated with high
que were done to all patients. level of 8OHdG in stepwise logistic regression analysis (p 50.0001). Interferon
RESULTS: TT genotype of IL28 rs8099917 was associated with a higher therapy resulted in sustained virological responses (SVR) in 104 patients. Hepatic
response rate to treatment than other genotypes. TT genotype was present in 8OHdG was significantly associated with SVR in univariate analysis for the
53.2% of responders Vs 17.7% of non responders (P50.001) while GG genotype patients with HCV genotype 1, without statistical significance in multivariate
was present in 6.4% of responders Vs 37.7% of non responders (P50.001). T analysis. Hepatic iron deposition showed no significant associations with SVR
allele was present in 73.4% of responders Vs 40 % in non responders while G for the patients with HCV genotypes 1 or 2. During the follow-up after interferon
allele were present in 26.6% of respnders Vs 60% in non responders (P50.001). therapy (median period of 4.6 year), HCC development was observed in 14
The response rate was lower in patients with T allele compared to those with C patients (16%). Heavy alcohol drinking, low platelet counts, non-SVR and
allele of IL28 rs12979860 and CC genotype were present in 47.4% of responders high levels of hepatic 8OHdG had significant associations with HCC develop-
Vs 5% of non responders and TT genotype were present in 6.1% of responders ment (p 0.0276, 0.0102, 0.0067, and 0.0003, respectively).
Vs 33.1 % of non responders (P50.001). The C allele was present in 70.6% of CONCLUSION: Hepatic 8OHdG level was useful in prediction of HCC devel-
responders Vs 36% of non responders while T allele was present in 29.4% of opment after interferon therapy for CHC patients.
responders Vs 64% of non responders (P 5 0.001). Disclosure of Interest: None declared
CONCLUSION: IL28B polymorphisms are strong predictors of virological
response in chronic hepatitis C with genotype 4 and analysis of IL-28B genotype
might be used to guide treatment for these patients. P0629 HCV AND HBV PREVALENCE IN THE POPULATION: LARGE
Disclosure of Interest: None declared DISPARITY BETWEEN HEPATITIS C IN THE GENERAL
POPULATION, COMPARING WITH HIGH RISK GROUPS
S. Carvalhana1,2, R. Pinto3, J. Leitao4, A.P. Silva5, C. Alves6, M. Bourbon6,
P0627 IMPACT OF HEPATITIS C VIRUS ON ALLOGRAFT SURVIVAL A. Carvalho4, H. Cortez-Pinto1,2,*
AFTER RENAL TRANSPLANTATION 1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
P. Magalhaes-Costa1,*, L. Lebre1, D. Machado2, C. Chagas1 metabolismo, FML, 3Hospital prisional de Sao joao de Deus, Caxias, Lisbon,
1 4
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental, Internal medicine, CHUC, Coimbra, 5Gastroenterology, CHVNG, Vila Nova de
2
Nephrology and Renal Transplantation, Hospital Santa Cruz, Lisboa, Portugal Gaia, 6INSA, Lisbon, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: The long-term impact of hepatitis C virus (HCV) infection INTRODUCTION: The burden of hepatitis B and C infections around the world
on kidney allograft survival remains controversial. Some studies found a signifi- is high. With the upcoming very effective treatments for hepatitis C and the
cant deleterious effect of HCV infection on allograft survival and also higher rather effective treatments for hepatitis B, there is urge to identify these patients
mortality in this group of patients. and estimate their prevalence in each country.
AIMS & METHODS: In this retrospective, single-center study, we aimed to AIMS & METHODS: Hepatitis B and C prevalence was evaluated in a sample of
compare the differences in kidney allograft survival over a long-term follow-up three groups: adult general population (GP): 989 individuals, prison population
period between non-infected vs infected patients. Study population (HCV (PP): 784, and drug-users (DU): 19832. HBsAg, HBsAb, HBcAb, anti-HCV
infected patients) was selected from a kidney transplant center database (1985 - (Cobas, Roche), ALT and AST were done. In the general population, anti-
2013) and compared to a random sample extracted from the same database. HCV positive individuals were tested for HCV PCR.
Groups were compared using Chi-square test, student-T test, Mann-Whitney RESULTS: Prevalence of Anti-HCV was: GP: 5/989 (0.5%); PP: 147/784
U test and survival methods (Kaplan-Meier) when appropriate. Statistical ana- (18.8%) and DU: 11862/19839 (59.8%). Prevalence of HBsAg was GP: 12/
lyses were carried using SPSS 20.0 IBM@ (Chicago, IL, United States). 989(1.2%); PP: 32/784 (4.1%) and DU: 927/18305 (5.0%). Interestingly,
RESULTS: We identified 34 patients with HCV infection and the random among individuals that were anti- HCV positive in the GP, only 20% were
sample population was 80 patients. The mean follow-up period, for both HCV PCR positive. In Portugal, adult GP is estimated about 8 600 000
A306 United European Gastroenterology Journal 2(5S)
individuals, PP are about 14 000, and DU are about 30 000. So, according to the HSF1 expression during tumour formation. Radiofrequency ablation (RFA) in
percentages found, it is expected that we have about 69 000 individuals with anti- small animals was optimized to investigate the HSF1-induced-and related signal-
HCV, and it is expected that 105 000 are HBs Ag positive. It is possible that the ling pathways in the treatment of liver metastasis.
prevalence of HCV PCR positive individuals is much lower in the general asymp- RESULTS: shRNA-HSF1-nanoliposomes were taken up by 99% of cells with-
tomatic population. Even assuming a 50% prevalence of HCV RNA positive out inducing cytotoxicity. Sub-lethal heat treatment of 45 and 50 degrees Celsius
among anti-HCV positive patients, it would result in about 34 500 individuals induced p-ERK, p-AKT and HSF1-related proteins at different timepoints inves-
with active infection and potentially needing treatment. Prevalence of elevated tigated and this coincided with a nuclear to cytosolic shift of HSF1, HSP70/90,
aminotransferases among patients with either hepatitis B or C in the GP was not AKT and ERK. Apoptosis was only significantly induced after 10 days post-heat
different from those with negative markers (17.6% vs. 8.1%, p n.s.). treatment. In vivo, tumours highly expressed HSF1, HSP70/90, AURBK and p-
CONCLUSION: Hepatitis C showed high disparity in prevalence according to ERK and p-AKT. Radiofrequency-ablated tumours showed an increase in HSF1
the risk groups, with low prevalence on the general population and very high in and HSP70/90 protein expression after 6 and 10 days post-RFA, suggesting the
risk groups. Differently, the prevalence of hepatitis B showed a more homoge- involvement of HSF1 during the process of tumour recurrence.
neous pattern of distribution. These results suggest that screening for hepatitis C CONCLUSION: This study demonstrates that HSF1 is highly expressed in CRC
in the general population is not cost-effective, but risk groups such as drug-users liver metastasis and suggest its possible involvement in tumour recurrence after
or people in prisons should be regularly screened. employing radiofrequency ablation.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences Disclosure of Interest: F. Zanieri: no conflict to declare, V. Carloni: no conflict to
Disclosure of Interest: None declared declare, S. Omenetti: no conflict to declare, C. Amabile: no conflict to declare, N.
Tosoratti: no conflict to declare, S. Cassarino: no conflict to declare, S. S. S.
Velandy: no conflict to declare, M. Kester: no conflict to declare, M. Pinzani: no
P0630 THE MITOGEN-ACTIVATED PROTEIN KINASE ERK5 IS conflict to declare, K. Rombouts: no conflict to declare
INVOLVED IN HEPATOCELLULAR CARCINOMA CELL
PROLIFERATION IN VITRO AND IN VIVO
G. Di Maira1, E. Rovida2,3, N. Navari1, S. Cannito4, P. Dello Sbarba 3, P0632 BASIC FIBROBLAST GROWTH FACTOR MEDIATES ACQUIRED
M. Parola4, F. Marra1,* RESISTANCE TO SORAFENIB IN HEPATOMA CELLS
1
Dip. Medicina Sperimentale e Clinica, 2University of Florence, Florence, Italy, M. Osawa1,*, Y. Matsuda2, T. Wakai3, M. Kubota1
3
Dip. Patologia Oncologia Sperimentale, University of Florence, Florence, 4Dip. 1
Division of Pediatric Surgery, Niigata University Graduate School of Medical and
Medicina Oncologia Sper. Universita` di Torino, University of Turin, Turin, Italy Dental Sciences, 2Department of Medical Technology, Niigata University Graduate
Contact E-mail Address: giovanni.dimaira@unifi.it School of Health Sciences, 3Division of Digestive and General Surgery, Niigata
University Graduate School of Medical and Dental Sciences, Niigata, Japan
INTRODUCTION: Despite great progress in the diagnosis and management of Contact E-mail Address: mamix.3211@gmail.com
hepatocellular carcinoma (HCC), the molecular mechanisms underlying the
tumor development and progression remain poorly understood, overall limiting INTRODUCTION: Sorafenib is a multikinase inhibitor used to treat patients
the patients outcome. ERK5 is a member of the MAPK family and has been with hepatocellular carcinoma (HCC). The main obstacle to efficient cancer
implicated in fundamental biologic processes relevant for tumor development. treatment with this agent is the acquired drug resistance that develops in many
AIMS & METHODS: The aim of this study is to evaluate the relevance of this patients. We aimed to determine whether sorafenib-treated hepatoma cells
pathway ERK5 in HCC biology. release soluble factors that cause sorafenib resistance.
Huh-7 and HepG2 were cultured by standard methods. ERK5 was silenced by AIMS & METHODS: HepG2 cells were incubated with sorafenib for 24 hours.
siRNA transfection or with shRNA and lentiviral vectors. The specific ERK5 The culture medium was rinsed, the cells were maintained for 24 more hours, and
inhibitor XMD8-92 was also used. In vivo development of HCC was evaluated cytokines released into the medium were analysed by enzyme-linked immunosor-
using the Huh-7 xenograft model in athymic nude mice. bent assay. The culture medium was transferred to the newly seeded HepG2 cells,
RESULTS: In vitro experiments demonstrated that ERK5 silencing or specific which were then maintained with a different concentration of sorafenib for 2 to
inhibition, using an inhibitor called XMD8-92, causes growth arrest of HCC 48 hours. Cell growth and apoptosis in sorafenib-treated cells were analysed by
cells, affecting in particular the G1/S transition. This phenotype was associated MTT and annexin V assay. Cell signalling was analysed by western blotting.
with an increase in p27Kip protein expression a critical negative regulator of cell RESULTS: The level of basic fibroblast growth factor (FGF-2) in the culture
cycle progression typically expressed in G0/G1 arrested cells. Additionaly knock medium of sorafenib-treated cells was increased to 1.8-fold that of the controls
down of ERK5 activity induces a marked inhibition of c-Rel expression, a (14.3 vs. 7.7 pg/mL, respectively; p 5 0.05), while other growth factors such as
member of NFk family required for the normal proliferative regeneration of transforming growth factor beta and insulin growth factor were unchanged.
hepatocytes. In a mouse model of HCC xenograft, administration of XMD8-92 When the cells were maintained in the culture medium of sorafenib-treated
significantly decreased tumor volume This reduction is associated with a reduced cells, the cell numbers were increased by 1.35-fold (p 5 0.05), and the levels of
proliferation, as observed by Brdu incorporation assay. Moreover XMD8-92- phosphorylated Akt, extracellular signal-regulated kinases 1/2, and nuclear
treated xenografts the expression of c-Jun, a proto-oncogene essential for cell factor kappa B were increased by 2.5- to 4.0-fold. The annexin V assay
proliferation, was reduced compared to control samples. Finally as already showed that the effect of sorafenib on cell apoptosis was inhibited in the cells
observed in vitro, XMD8-92 treatment induced a strong decrease of c-Rel tran- maintained in the medium of sorafenib-treated cells (apoptotic rates after sora-
scription factor expression. fenib treatment in control cells vs. cells maintained in the medium of sorafenib-
CONCLUSION: This study disclose a strong regulation of cell proliferation in treated cells: 76.5% vs. 17.7%, respectively; p 5 0.05), which was rescued by
HCC, affecting the biological activity of different oncogenic targets. Affecting pretreatment with the FGF receptor inhibitor PD173074.
this pathway could be considered a novel and effective approach for the treat- CONCLUSION: FGF-2 might be an essential mediator of acquired resistance to
ment of HCC. sorafenib. Combination treatment with sorafenib and FGF-2 inhibitor may be
Disclosure of Interest: None declared effectively used to treat patients with HCC in the future.
Disclosure of Interest: None declared
w n
sorafenib, and 57 consecutive patients received RT in our hospital. Overall sur-
a
ithdr
Mycophenolate Mofetil were two most common immunosuppression regimes vival was compared between the two groups with PVTT by propensity score (PS)
used post LT. Post transplant survival appeared to be slightly worsen in HCV/ analysis. Factors associated with survival were evaluated by multivariate
HCC patients compared to NAFLD/HCC, although it did not reach statistical analysis.
W
significance (p 0.113). Post LT freedom from recurrence of HCC among the RESULTS: The median treatment period with sorafenib was 45 days, while the
two cohort was similar (p 0.848). median total radiation dose was 50 Gy. The Child-Pugh class and the level of
CONCLUSION: Despite the NAFLD/HCC being older and with higher meta- invasion into hepatic large vessels were significantly more advanced in the RT
bolic risk factors, a significant proportion could undergo active therapy. group than in the sorafenib group. Median survival did not differ significantly
Furthermore, patients with NAFLD/HCC selected for transplantation seemed between the sorafenib group (4.3 months) and the RT group (5.9 months;
to have better long term outcomes, possibly due to stricter selection for trans- P 0.115). After PS matching (n 28 per group), better survival was noted in
plantation as well as variations in tumor biology between the two groups. the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months;
REFERENCES P 0.025). A Cox model showed that des-g-carboxy prothrombin 51000 mAU/
1. Mittal S and El-Serag HB. Epidemiology of hepatocellular carcinoma: con- mL at enrollment and RT were significant independent predictors of survival in
sider the population. J Clin Gastroenterol 2013; 47(Suppl.): S2-S6.
A310 United European Gastroenterology Journal 2(5S)
ra w n
the PS model (P 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P 0.007, HR,
0.434; 95% CI, 0.235 to 0.779; respectively).
expressed as median (95% confidence interval). The survival curves according to
best response were compared using the log-rank test.
t h d
CONCLUSION: RT is a better first-line therapy than sorafenib in patients who
i
have advanced unresectable HCC with PVTT.
W
Disclosure of Interest: None declared
RESULTS: Conventional RECIST1.1 could not stratify OS. Meanwhile, OS was
significantly stratified according to anti-tumor response in a-RECIST. Disease
control rate (DCR) 60.9%, DC vs. PD, 17.2 (6.328.1) vs. 9.3 (5.013.6)
months (p 0.048); objective response rate (ORR) 8.7%, OR vs. non-OR,
N/A vs. 10.4 (7.113.6) months (p 0.048). e-RECIST was superior to a-
P0647 PROGNOSTIC SIGNIFICANCE OF AFP AND PIVKA-II RECIST: DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4)
RESPONSES TO INITIAL TRANSARTERIAL months (p 0.011); ORR 8.7%, OR vs. non-OR, N/A vs. 10.4 (7.113.6)
CHEMOEMBOLIZATION IN PATIENTS WITH UNRESECTABLE months (p 0.048). In addition, Saga criterion was superior to e-RECIST:
HEPATOCELLULAR CARCINOMA DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4) months
T. Ichikawa1,*, N. Machida1, H. Sasaki1, Y. Tawa1 (p 0.011); ORR 30.4%, OR vs. non-OR, 20.4 (14.226.6) vs. 9.0 (5.412.5)
1
Department of Gastroenterology, Itabashi Chuo Medical Center, Itabashi-ku, months (p 0.007).
Tokyo, Japan CONCLUSION: Our findings suggest that Saga criterion, a new imaging assess-
Contact E-mail Address: ichikawtakeshi@gmail.com ment using automatic measurements of tumor volume and density on CT, has
potential as a surrogate marker for anti-tumor response to sorafenib with regard
INTRODUCTION: It remains unclear whether response of alpha-fetoprotein to survival.
(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) Disclosure of Interest: None declared
to initial transarterial chemoembolization (TACE) are associated with improved
survival in patients with unresectable hepatocellular carcinoma (HCC).
AIMS & METHODS: The aims of this study were to evaluate the prognostic P0649 POPULATION SCREENING FOR LIVER DISEASE USING
significance of response of AFP and PIVKA-II to initial TACE and to identify HEPATIC TRANSIENT ELASTOGRAPHY
risk factors associated with outcomes in patients with unresectable HCC. We B.M. Goncalves1,*, L. Malheiro1, D. Fernandes1, J.-B. Soares1, C. Rolanda1,
retrospectively analyzed 114 patients with unresectable HCC not amenable to R. Goncalves1, P. Bastos1
surgery and radiofrequency ablation who had been treated with TACE between 1
Gastroenterology, Hospital de Braga, Braga, Portugal
September 2005 and October 2013. All laboratory values including AFP and Contact E-mail Address: brunommgoncalves@gmail.com
PIVKA-II were measured 1 week before TACE and 1 month after TACE. The
AFP or PIVKA-II response was assessed for patients who had a level before INTRODUCTION: Transient Elastography (TE), a noninvasive technique for
TACE of 100 ng/ml or 100mAU/ml; a positive response was defined as a liver fibrosis evaluation, has been used in patients with various types of chronic
reduction by 4 50% compared with the level before TACE. We compared liver diseases. It is a simple, fast, painless, reproducible and well-accepted tech-
three groups of pre-TACE AFP 100 ng/ml with response vs. pre-TACE nique with instantaneous results that could be a valuable screening tool.
AFP 100 ng/ml and no response vs. pre-TACE AFP 5 100 ng/ml using However, there is a shortage of studies on its usefulness as a screening procedure
univariate analysis. Three PIVKA-II groups were also compared. Prognostic in apparently healthy people.
factors were evaluated using univariate (log-rank test) and multivariate analyses AIMS & METHODS: The purpose of the study was to evaluate the impact of TE
(Cox proportional hazard model). in the population screening of liver disease. It was conducted a prospective study
RESULTS: The median overall survival (OS) was 20.9 months. Pre-TACE AFP where TE was performed in 365 individuals without known liver disease that
level 100 ng/ml and tumor diameter 3 cm were associated with poor OS (AFP attended general gastroenterology clinic in a referral hospital. A positive screen-
100 ng/ml vs. AFP 5 100 ng/ml; 9.3 vs. 31.3 months; P 5 0.0001, tumor ing was defined for values of liver stiffness (LS) 8 kPa. For these individuals
diameter 3 cm vs. diameter 5 3cm: 12.5 vs. 31.3 months; p 0.0013) and additional clinical, laboratory and ultrasonographic investigation was proposed
remained significant negative predictors for OS on multivariate analysis (AFP for determination of liver disease.
4100 ng/ml; hazard ratio (HR) 3.5; p 0.0003, tumor diameter 3 cm; HR 3.1; RESULTS: Of the 365 individuals evaluated, 89 were excluded for invalid
p 0.0015). In the difference of AFP response to TACE, the OS of pre-TACE (n 47) or failed (n 42) TE. In the multivariate analysis, body mass index
AFP 100 ng/ml with response compared with that of pre-TACE AFP 100 430Kg/m2 and waist circumference 4102cm in men or 488cm in women
ng/ml and no response showed no significant difference (p 0.992). Although were associated with failure of LS measurement (p 0.031 and 0.001, respec-
there were not significant differences in OS between patients with pre-TACE tively). Of the 276 valid exams, 21 (7.6%) obtained a LS value 8 kPa, including
PIVKA-II 5 100 mAU/ml and those with pre-TACE PIVKA-II 100 mAU/ nine patients with LS 13 kPa. The average value of LS in the remaining
ml (p 0.1642), the OS of responders of PIVKA-II to initial TACE was signifi- participants with negative screening was 4.9 1.2 kPa. In the group with positive
cantly longer than that of non-responders in those with pre-TACE PIVKA-II screening it was observed that 28.6% patients had normal liver tests. In 17 (81%)
100 mAU/ml (p 0.0032). patients a cause of liver disease was determined, while all participants with LS
CONCLUSION: The response of AFP to initial TACE does not prolong survival 13 kPa had a diagnostis. Alcoholic liver disease was the most prevalent etiology
in patients with unresectable HCC. The response of PIVKA-II to initial TACE is (47%) followed by non-alcoholic fatty liver disease (41%).
associated with improved survival. Elevated AFP (100 ng/ml) and tumor dia- CONCLUSION: TE revealed to be a useful method to screen liver disease in the
meter 3 cm at diagnosis are associated with a dismal treatment response and general population, diagnosing a significant number of asymptomatic patients.
prognosis after TACE. In the presence of an abnormal LS, the patient should be referenced for further
Disclosure of Interest: None declared evaluation.
Disclosure of Interest: None declared
P0657 STEATOSIS OF PANCREAS IN THE STRUCTURE OF TUESDAY, OCTOBER 21, 2014 9:0017:00
METABOLIC SYNDROME IN OVERWEIGHT AND OBESE PANCREAS II POSTER EXHIBITION HALL XL_____________________
CHILDREN
P0659 EUS GUIDED NECROSECTOMY TEMPORARY
M. Gurova1,*, A. GusevA2, V. Novikova3 CYSTOGASTROSTOMY WITH COVERED STENT FOR
1
Department of Pediatrics, Belgorod State National Research University, PANCREATIC NECROSIS
Belgorod, 2Department of Pediatrics, Kursk Regional Children Hospital, Kursk,
3 A. Krishnan1,*, R. Ramakrishnan1 on behalf of None
Department of Pediatrics, Federal Centre of the Heart, Blood and Endocrinology, 1
Fortis Malar Hospitals, Chennai, India
named after V. A. Almazof, Saint-Petersburg, Russian Federation
Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Involvement of pancreas in pathological process in case of INTRODUCTION: Pancreatic pseudocyst with infected necrotic tissue is asso-
obesity is caused by its important role in regulation of metabolic processes, of ciated with a high rate of complications and death. Standard treatment is open
energetic balance and body weight. necrosectomy but is associated with significant morbidity, mortality, and pro-
AIMS & METHODS: This study is aimed at assessing frequency of detectability longed hospital stay. Endoscopic cyst drainage with necrosectomy is an alterna-
of ectopic fat deposition in the pancreas in obese and overweight children and at tive and less invasive technique.
comparing this detection frequency of other components of metabolic syndrome AIMS & METHODS: Aim: to evaluate pseudocyst drainage with cystogastrost-
(MS). omy and endoscopic necrosectomy for infected pancreatic necrosis with fully
Methods: The cross-sectional study was conducted among 120 children aged 11- covered self-expanding metallic stents (CSEMS).
15 years, separated into 2 groups: 60 overweight children (1st group) and 60 12 patients underwent endoultrasound guided endoscopic necrosectomy and tem-
obese children (2nd group). Diagnosis of the non-alcoholic fatty liver disease porary cystogastrostomy for infected pancreatic necrosis by using CSEMSs.
(NAFLD) and non-alcoholic fatty pancreas disease (NAFPD) was based on Patient details, disease severity scores, scores for severity assessed at CT, treat-
sonographic data. Peculiarities of carbohydrates and lipid metabolism and pan- ment procedures, length of hospital stay, and outcome for patients undergoing
creatic exocrine function were investigated. endoscopic therapy were recorded. Patients proceed to intervention if infection is
RESULTS: Complete MS was diagnosed only in 15% of children with obesity. strongly suspected on clinical and radiological grounds or is confirmed bacter-
Some components of MS according IDF recommendations (2005) were found in iologically. After the necrosis cavity had been accessed, with the assistance of
88.3% of obese children and 66.7% of overweight ones (p 0.002). The most endoscopic ultrasound, a large orifice was created and necrotic debris was
common components were the following hyperinsulinemia (90% vs 66.7%, removed using special short fully covered 15mm diameter SEMS with large
p 0.0027), insulin resistancy according results of HOMA-index (51.7% vs flares was deployed across the tract under radiological control. Completeness
65%, p 0.12), increasing triglycerides level (36.7% vs 6.7%, p 0.00l), decreas- of the necrosectomy procedure was ascertained by visualization of a clear pseu-
ing level of LPHD (78.3% vs 40%, p 0.001). Sonographic data compatible with docyst cavity on endoscopy.
NAFLD were two times higher in children with obesity 56.7% vs. 30% RESULTS: A total of 12 patients (10 men, 2 women; median age 39, range 19 -
(o 0.005), whereas NAFPD data were found with equal frequency in over- 76) were treated successfully. Median APACHE 2 score on presentation was 11
weight and obese children - 85% and 86.7% accordingly (p 0.88). These results (range 318). Two patients presented with organ failure and needed intensive
were associated with decreasing level of the elastase-1 in 23.3% children with care. Necrosis was successfully treated endoscopically in all patients, requiring a
obesity. median of 2 endoscopic interventions (range 14). The tissue samples obtained at
CONCLUSION: Sonographic results compatible with NAFPD were found more the first necrosectomy confirmed infection in 12 patients. Complication included
than in 2/3 cases in overweight and obese children and they had appeared earlier superinfection in patient who made an uneventful recovery. After median of 5
than sonographic results of NAFLD which were found only in 1/3 cases of weeks the metal SEMS was extracted by endoscopy. The patients have remained
overweight children and cases of obese patients. These results were associated asymptomatic and median follow-up was 4 (211) months.
at first with carbohydrate metabolism disturbances (insulin resistancy), whereas CONCLUSION: Endoscopic necrosectomy and temporary cystogastrostomy
atherogenic dyslipidemia in our study was not prominent. In 23% obese children with self-expanding metallic stent approach is feasible, safe, and effective in
with sonographic changes considered as pancreatic steatosis signs of mild exo- patient with infected pancreatic necrosis. The benefits of this endoscopic
crine insufficiency were found. approach using fully covered self-expandable metallic stent in terms of less mor-
Disclosure of Interest: None declared bidity is conceivable and our report demonstrates that such an approach is
feasible.
Disclosure of Interest: None declared
P0658 A REPORT OF 267 CASES OF CHILDHOOD PANCREATITIS:
INCREASING PREVALENCE, ETIOLOGIC CATEGORIZATION,
DYNAMICS, SEVERITY ASSESSMENT AND OUTCOME P0660 EUS-GUIDED PANCREATIC PSEUDOCYST DRAINAGE: AN
U. Poddar1,*, S.K. Yachha1, A. Srivastava1, S.S. Baijal2, S. Kumar2, R. Lal3, ASSESSMENT OF EFFICACY, SAFETY, LONG-TERM FOLLOW-UP,
V.A. Saraswat4 AND TECHNICAL FEASIBILITY OF SINGLE-STEP APPROACH
1
Pediatric Gastroenterology, 2Radiology, 3Pediatric Surgery, 4Gastroenterology, A. Krishnan1,*, R. Ramakrishnan1 on behalf of None
1
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India Fortis Malar Hospitals, Chennai, India
Contact E-mail Address: ujjalpoddar@hotmail.com Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Paediatric pancreatitis although reported has not emanated INTRODUCTION: Pancreatic pseudocyst is common complication of acute and
from developing world as a large single center study. More so, natural history of chronic pancreatitis. While surgery is associated with significant complications
acute pancreatitis as a continuum of recurrent acute and chronic pancreatitis is and mortality, percutaneous drainage is associated with prolonged hospitaliza-
not well established. tion and often times the need for other adjunctive treatment.
AIMS & METHODS: To look at prevalence, aetiologic categorization, AIMS & METHODS: Assess the safety and efEcacy of single-step EUS-guided
dynamics, severity assessment and outcome in children with pancreatitis. pseudocyst drainage, evaluate the technical Feasibility.
METHODS: From January 2002 to December 2013 consecutive children (18 69 patients who had undergone Single-step EUS guided drainage of pancreatic
years of age) diagnosed to have pancreatitis were included for analysis. pseudocyst were included. Controlled radial expansion wire guided balloon dila-
Pancreatitis was classified as acute (AP), acute recurrent (ARP) and chronic tion of the puncture tract was performed followed by insertion 10 Fr double
pancreatitis (CP) as per standard definitions. Severity of acute pancreatitis was pigtail stents were inserted into the pseudocyst from either the stomach or the
assessed by 2012: revised Atlanta classification. Follow-up data was assessed till duodenum in adults and 7F stents in children.
March 2014. RESULTS: The mean age of 39 years. Median size was 12.5 cm in diameter. 56
RESULTS: Pancreatitis was diagnosed in 267 children (mean age of 11.29 3.49 patients had infected and rest had non-infected pseudocyst. Stent placement was
years). AP in 50% (n 133), ARP in 22% (60) and CP 28% (74). The number of successful in all. The technical success rate was 100%, and the treatment success
cases increased progressively from 18 in the 1st quarter of the study to 37 in 2nd rate was 98.5%. 54 patients had cystogastrostomy and rest of the patients had
quarter, 64 in 3rd quarter and 148 in the last quarter. Aetiology of AP was trauma cystoduodenostomy with cyst drainage. There was one case with perforation and
in 22% (n 29), biliary 10.5% (14), viral infection 7% (9), drugs 5% (7), others required an emergency operation. 98.5% patients had complete resolution of a
causes in 4.5% (6) and idiopathic 51% (68). Grading of pancreatitis was severe in pseudocyst. The double pigtail stent was removed in all cases after median dura-
13% (17, 6 died), moderately severe (local complications) 55% (73) and mild tion of 10 weeks. Regarding long-term outcomes, recurrence of a pseudocyst was
32% (43). Over a median follow-up of 12 (range, 3 to 96) months, 23.5% (27 / not observed over a median follow-up of 58 weeks.
115) developed either acute recurrent (n 9) or chronic pancreatitis (18). CONCLUSION: Single-step EUS-guided transmural drainage is safe and asso-
Progression from acute to ARP/CP was observed mostly in idiopathic group ciated with high success rate. It can be the first choice for therapy of pancreatic
(22/27). In ARP group, 10 were due to biliary causes (choledochal cysts 8, gall- pseudocyst with good technical feasibility, efficacy, and safety with long-term
stones 2), pancreas divisum 3, duodenal diverticulum 1 and the remaining 46 results are acceptable.
(76.6%) were idiopathic. Over a median follow-up of 12 (range 3 to 120) months Disclosure of Interest: None declared
31% (11/35) of idiopathic ARP cases developed CP. Almost half of CP (39 /74)
were chronic calcific, 6 were familial, 4 had associated pancreas divisum and the
remaining 64 (86%) were idiopathic. Among CP (n 63), over a median follow-
up of 13 (range, 3-120) months, 3 cases developed diabetes mellitus, one steator-
rhoea, none had cancer and there was no mortality.
CONCLUSION: There is almost eight fold increase in the prevalence of pan-
creatitis over last 12 years. Among AP (mainly idiopathic subgroup) 23% pro-
gressed to ARP and chronic pancreatitis. The majority of ARP was idiopathic
(77%) and a third of them progressed to CP. Thus a subset of pancreatitis seems
to be a continuum of acute to ARP and CP.
Disclosure of Interest: None declared
A314 United European Gastroenterology Journal 2(5S)
of patients affected by an initial episode of AP admitted to a single tertiary
P0661 EUS-GUIDED INTERVENTION IN WALLED-OFF PANCREATIC
referral center.
NECROSIS (WOPN): SINGLE CENTER EXPERIENCE WITH LONG
AIMS & METHODS: 196patients admitted to our center for an initial episode of
TERM FOLLOW-UP
AP were consecutively enrolled and prospectively followed for 52.5 (26.8) month-
M.C. Sulz1, C. Meyenberger1,* s[mean (SD)]. Clinical characteristics,exogenously and endogenously associated-
1
Department of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. factors,and evolution to RAP and CP were analyzed.
Gallen, Switzerland RESULTS: 40patients developed RAP and 13 of these developed CP. The annual
Contact E-mail Address: michael.sulz@kssg.ch relapse rate was 5.4 (CI 95% 4.0-7.4) per 100 person-years. In univariate analysis,
RAP was associated with idiopathic etiology (p50.001), pancreas divisum (PD)
INTRODUCTION: Necrotising pancreatitis is associated with high morbidity (p 0.001), higher cigarettes and alcohol intake (p50.001; p 0.023). CP was
and mortality [1-3]. Walled-off pancreatic necrosis (WOPN) is defined as a associated with severe AP first-episode (p 0.048), PD (p 0.03), and cigarettes
mature, encapsulated necrotic collection with well defined wall. Early interven- smoking (p 0.038). By multivariate analysis,PD was an independent risk factor
tion (5 4 weeks) should be avoided whenever possible [4, 5]. Compared to the for RAP development (OR 11.5, 95% CI 1.6-83.3). Severe AP first episode
traditional surgical necrosectomy, the endoscopic treatment shows significant increased the risk of progressing to CP by nine-fold (OR 9.3, 95% CI 1.8-
reduction of major complications, of pancreatic fistula, and of pro-inflammatory 47.2). Mutation frequencies of CFTR and SPINK-1 N34S were substantially
response (IL-6). We present the largest prospective single-center experience higher compared to the general population but not statistically significant.
regarding endoscopic treatment of WOPN in Switzerland with long term CONCLUSION: Understanding the factors that may predispose to RAP and CP
follow-up and add data to the increasing experience with this technique. holds important clinical implications for the prevention of disease progression.
AIMS & METHODS: To evaluate the short- and long term outcome of patients Special attention should be given to patients who experienced a severe first attack
with walled-off pancreatic necrosis (WOPN) after endoscopic treatment. This of AP, given the increased risk of developing CP.
retrospective, observational study at a single center with tertiary care endoscopy Disclosure of Interest: None declared
in Switzerland included all patients with necrotising pancreatitis from 2002 until
2013 complicated by WOPN who underwent endoscopic treatment (two experi-
enced interventionalists). Clinical short term success (530 days) was defined as P0663 A PROSPECTIVE MULTICENTER EVALUATION OF THE
resolution of patients symptoms requiring no further interventions. Clinical fail- RADIOLOGICAL PERFORMANCE OF THE REVISED ATLANTA
ure was defined as failure to either resolve the collection, or requiring other CLASSIFICATION
interventions, and/or complications requiring other therapeutic modalities (e.g. H. Sternby1,*, R.C. Verdonk2, A. Dimova3, P. Ignatavicius 4, L. Ilzarbe5,
surgery), and/or death. Approval was obtained by the local Ethical committee. P. Koiva6, A. Nieminen7, T.L. Bollen8 on behalf of Pancreas 2000 Atlanta Group
RESULTS: 35 Caucasian patients with WOPN (median age 64.1 y, range 40-85 1
Dep of Surgery, ICS, Malmo, Sweden, 2Dep of Gastroenterology, AZ,
y; ASA II and III 51.3% and 35.9%; 73.1% males) underwent endoscopic treat- Nieuwegein, Netherlands, 3Dep of Surgery, UHP, Sofia, Bulgaria, 4Dep of
ment. The biliary disease was the primary cause of necrotising pancreatitis Surgery, HLUHS, Kaunas, Lithuania, 5Dep of Gastroenterology, HdM,
(57.1%). The median duration of pigtails was 52 days (range 8-552 days), the Barcelona, Spain, 6Dep of Gastroenterology, ETCH, Tallinn, Estonia, 7Dep of
median duration of transpapillary stents was 82.5 days (range 5-563 days). The Surgery, HUS, Helsinki, Finland, 8Dep of Radiology, AZ, Nieuwegein,
short- and long term results results are shown in Table 1. Netherlands
Contact E-mail Address: hannasternby@gmail.com
Short- and longterm outcome %
INTRODUCTION: The Revised Atlanta Classification defines morphological
Complete clinical success 62.3 features and descriptions of acute pancreatitis (AP) and its complications to
enable standardized reports and communication. New computer tomography
Radiological success 75.3 (CT) criteria are introduced to describe local complications in AP. However,
complete/ partial 20.8/54.5 these CT criteria have not yet been validated in an international setting.
Short term mortality (530d) 11.5 AIMS & METHODS: The aim of this study was to analyze the interobserver
Complication rate 26.7/15.4/11.5 agreement of the revised Atlanta criteria for CT findings in AP. Patients with a
Overall/related to endotherapy/to drainage first episode of AP who obtained a CT were consecutively enrolled at six
European centers. The CTs of each center were prospectively scored separately
Rate of additive radiological drainage 15.4 by a local radiologist at each center and an expert central radiologist (repre-
Rate of additive surgery 23.1 senting the reference standard) using the criteria stated in the Revised Atlanta
Hospital stay, days, median (range) 41 (3-114) Classification. No specific training was provided for the local radiologists before
Time of follow-up, months (median, range) 30.5 (1-180) scoring. Interobserver agreement was determined using Kappa statistics. Clinical
data was collected retrospectively.
Longterm clinical well-being 76.9 % RESULTS: 285 patients (56 % males) with a median age of 58 years with 388
Long term mortality (related to disease) 12.0 % CTs in total were enrolled. Aetiology of AP was gallstones in 36.6 %, alcohol in
After endoscopic treatment/after surgery 4.0/8.0% 35.9 %, and idiopathic in 27.5 % of the patients. AP was mild in 37,5 % of the
Secondary clinical failure (%) 21.7 % patients, in 51.5 % moderately severe, and severe in 10.9 %. Overall interobser-
ver agreement was moderate to substantial. However, the agreement differed
Re-treatments (%) 14.3 % substantially between the participating centers. The center independent kappa
Elective surgery 23.8 % values for the different categories are shown in the table below.
P0664 ORAL UDENAFIL AND ACECLOFENAC FOR THE PREVENTION P0666 CLINICAL PREDICTABILITY OF FLUID COLLECTIONS IN
OF POST-ERCP PANCREATITIS IN HIGH-RISK PATIENTS: A ACUTE PANCREATITIS USING INTERLEUKIN-6 LEVEL AND
RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY NOVEL APACHE-IL SCORE
H.-C. Oh1,*, T.Y. Lee2, J.S. Choi3, T.Y. Park1, J.H. Do1, Y.K. Cheon2, S. Appasani1,*, J. Basha1, M. manrai1, P. Siddappa1, T. Yadav2, V. Gupta2,
T.J. Song4 P. Sarotra3, S.K. Sinha1, R. Kochhar1
1 1
GASTROENTEROLOGY, CHUNG-ANG UNIVERSITY COLLEGE OF Gastroenterology, 2Surgery, 3Clinical Pharmacology, PGIMER, Chandigarh,
MEDICINE, 2GASTROENTEROLOGY, Konkuk University, Seoul, India
3
GASTROENTEROLOGY, Inje Univ Busan Paik Hosptial, Busan, Contact E-mail Address: drasreekanth@gmail.com
4
GASTROENTEROLOGY, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: ohcgi@cau.ac.kr INTRODUCTION: Cytokine storm occurring in early phase of acute pancrea-
titis (AP) plays an important role in development of local & systemic complica-
INTRODUCTION: Acute pancreatitis is a common complication of ERCP. tions. Fluid collections contribute significantly to the morbidity of this illness,
Combination therapy with oral udenafil and aceclofenac may reduce the occur- hence its predictability in early phase could help in clinical triage.
rence of post-ERCP pancreatitis by targeting different pathophysiological AIMS & METHODS: AIMS
mechanisms underlying acute pancreatitis. This study aimed to determine To prospectively evaluate the role of cytokine estimation at admission to predict
whether combining udenafil and aceclofenac reduces the rates of occurrence of the formation of fluid collections and correlate it with standard scoring systems.
post-ERCP pancreatitis. MATERIALS AND METHODS
AIMS & METHODS: A prospective, randomized, double-blind, placebo-con- 110 consecutive patients (69% males, age 1770yrs) with AP were evaluated after
trolled, multicenter study was conducted in four academic medical centers. an informed consent from Jan2012-March2013. Patients were stratified into
Between January 2012 and June 2013, a total of 216 patients who underwent mild, moderate & severe pancreatitis as-per revised Atlanta criteria and were
ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients treated with nutritional & organ support. Serum cytokine (Interleukin (IL) 6,
were determined to be at high risk for pancreatitis on the basis of validated 10, Tumor Necrosis Factor (TNF) Alpha) and fibronectin levels were analyzed
patient and procedure-related risk factors. quantitatively at admission (ELISA). APACHE, BISAP & SIRS scores were also
RESULTS: Demographic features, indications for ERCP, and therapeutic pro- calculated. Cytokine levels were compared with standard parameters while ana-
cedures were similar in each group. There was no significant difference in the rate lyzing severity, development of fluid collections and outcome of AP using SPSS
(15.8% [17/107] vs. 16.5% [18/109], p .901) and severity of post-ERCP pan- v17.0.
creatitis between the udenafil/aceclofenac and placebo groups. One patient in RESULTS: The median levels of IL-6 were higher in patients with severe pan-
each group developed severe pancreatitis. On multivariate analyses, suspected creatitis (761.78pg/ml, n 42) than in those with mild pancreatitis (277.80pg/ml,
sphincter of Oddi dysfunction and endoscopic papillary balloon dilatation with- n 40) and moderate pancreatitis (397.50pg/ml, n 28, p 0.038). At a cut off
out sphincterotomy were associated with post-ERCP pancreatitis. of 488pg/ml, IL-6 had a sensitivity of 85% & specificity of 75% in predicting
CONCLUSION: Combination therapy with udenafil and aceclofenac was not severe pancreatitis (AUC 0.702, p 0.016). The median IL-6 levels were higher
effective for the prevention of post-ERCP pancreatitis. in patients with necrosis (635.0pg/ml) than in those without (372.5pg/ml,
Disclosure of Interest: None declared p 0.008) as well in patients with organ failure than those without (540.35pg/
ml vs. 406.42pg/ml, p 0.046). Serum IL-10, TNF Alpha and fibronectin levels
did not correlate with these events. Pearson & Spearman bivariate analysis
P0665 NASOGASTRIC TUBE FEEDING VERSUS NASOJEJUNAL TUBE revealed good correlation of IL-6 with CTSI (0.432, p 0.001), APACHE
FEEDING IN SEVERE ACUTE PANCREATITIS score (0.354, p 0.032), BISAP score (0.316, p 0.019) and SIRS score (0.487,
J.M. Rubio1,* p 0.007).
1
Section of Gastroenterology, Philippine General Hospital, Manila, Philippines Patients who developed fluid collections had higher IL-6 levels than those who
Contact E-mail Address: jowi5271@yahoo.com did not (524.28pg/ml vs 358.21pg/ml, p 0.031). IL-6 levels also correlated with
the type of collection (acute necrotic collection vs. acute peripancreatic fluid
INTRODUCTION: Severe acute pancreatitis is a major cause of morbidity and collection, p 0.017). Standard APACHE score predicted only severity and
mortality. Reviews have advocated enteral nutrition over parenteral nutrition in necrosis but did not correlate with fluid collections. Hence we postulated a
its management. Nasogastric tube is easier to insert than nasojejunal tube. The new APACHE-IL score by adding 2 points to standard APACHE score if IL-
objective of this study is to determine the efficacy of nasogastric tube feeding in 6 levels were elevated (4488pg/ml). At a cut off of 6, APACHE-IL score had a
terms of exacerbation of pain, mortality, pancreatic infection and complications sensitivity of 85% and specificity of 80% in predicting development of fluid
such as diarrhea in comparison to nasojejunal feeding. collections (AUC 0.746, p 0.027).
AIMS & METHODS: RCTs among patients with severe acute pancreatitis CONCLUSION: IL-6 level at admission is an effective predictor of severity of
comparing NGT feeding to NJT feeding were selected for inclusion. Search for acute pancreatitis (as per revised Atlanta) as well as of development of organ
randomized controlled trials was carried out using search engines such as failure, necrosis and fluid collections. We recommend IL-6 to be measured for
PubMed, Ovid, Google scholar. Search terms were severe acute pancreatitis, early risk stratification and APACHE-IL score for fluid collection prediction.
enteral nutrition and other synonyms listed in MeSH. The data were analyzed Disclosure of Interest: None declared
using Review Manager RevMan5.
RESULTS: 86 studies were found. Only 3 studies were included. NGT feeding
did not result in an increase in exacerbation of pain as compared to NJT feeding P0667 SLC26A6 VARIANTS ARE NOT ASSOCIATED WITH CHRONIC
(CI 0.31-3.22, p value 0.99). There was no significant difference between NGT PANCREATITIS
and NJT feeding in terms of mortality (CI 0.38-2.06, p value 0.77). NGT feeding A. Balazs1,*, E. Hegyi1,2, B.C. Nemeth3, I. Hritz1, F. Izbeki4, J. Gervain5,
showed a trend towards benefit in reducing pancreatic infection (CI 0.17-1.76, p A. Szepes6, G. Gyimesi7, Z. Dubravcsik7, A. Csiszko8, D. Kelemen9,
value 0.31). NGT feeding showed a trend toward causing diarrhea (CI 0.56- 4.05, Z. Szentkereszty8, B. Bod10, J. Sumegi11, J. Novak12, A. Parniczky13,
p value 0.42). N. Lasztity13, G. Veres14, C. Andorka14, R. Szmola15, J. Czelecz16, A. Vincze17,
CONCLUSION: NGT feeding is comparable to NJT feeding in exacerbation of J. Bajor17, G. Farkas18, L. Czako1, T. Takacs1, Z. Rakonczay19, J. Maleth19,
pain, incidence of infection, complications such as diarrhea and mortality. NGT A. Pap15, P. Hegyi1 on behalf of Hungarian Pancreatic Study Group
feeding can be used as an alternative to NJT feeding in institutions where an 1
First Department of Medicine, University of Szeged, Szeged, Hungary, 22nd
endoscopy guided NJT insertion cannot be done Department of Pediatrics, University Childrens Hospital, Comenius University
REFERENCES Medical School, Bratislava, Slovakia, 3Department of Molecular and Cell Biology,
1. Kumar A, Singh N, Prakash S, et al. Early enteral nutrition in severe acute Boston University, Boston, United States, 4Fejer Megyei, Szent Gyorgy Hospital,
pancreatitis: A prospective randomized controlled trial comparing nasojejunal 5
Fejer Megyei, Szent Gyorgy Hospital, Szekesfehervar, 6Bacs-Kiskun County,
and nasogastric routes. Clin Gastroenterol 2006; 40: 431-434. 7
Bacs-Kiskun County, Municipality Hospital, Kecskemet, 8Department of Surgery,
2. Eatock FC, Chong P, Menezes N, et al. A randomized study of early naso- University of Debrecen, Debrecen, 9Department of Surgery, University of Pecs,
gastric tube versus nasojejunal feeding in severe acute pancreatitis. Am J Pecs, 10Dr Bugyi Istvan, Hospital, Szentes, 11B-A-Z County, Hospital, Miskolc,
Gastroenterol 2005; 100: 432-439. 12
Pandy Kalman, County Hospital, Gyula, 13Heim Pal Childrens Hospital,
3. Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding 14
Paediatric Department, Semmelweis University, 15National Institute of
through nasogastric and nasojejunal tube in severe acute pancreatitis. Pancreas Oncology, 16Bethasda Childrens Hospital, Budapest, 17Department of Internal
2012; 41: 153-159. Medicine, University of Pecs, Pecs, 18Department of Surgery, University of Szeged,
4. Petrov M, Correia M and Windsor J. Nasogastric tube feeding in predicted 19
First Department of Medicine, University of Szeged, Szeged, Hungary
severe acute pancreatitis. A systematic review of the literature to determine safety Contact E-mail Address: anitabalazs@outlook.com
and tolerance.
5. McClave S, Chang W, Dhaliwal R, et al. Nutrition support in acute pancrea- INTRODUCTION: Cystic Fibrosis Transmembrane Conductance Regulator
titis: A systematic review of the literature. J Parenter Enteral Nut (CFTR) mutations are established risk factors for chronic pancreatitis (CP).
6. Feldman M, Friedman L and Brandt L. Sleisenger and Fordtrans gastrointest- CFTR variants increase disease risk by causing impairment of pancreatic
inal and liver disease. 9th ed., 2010. ductal bicarbonate secretion. However, the role of genetic variations in the bicar-
Disclosure of Interest: None declared bonate secreting SLC26A6 anion transporter has remained largely unexplored so
far.
AIMS & METHODS: Our aim was to investigate the role of the SLC26A6 gene
in CP. 96 subjects with CP (cases) and 99 subjects with no pancreatic disease
(controls) were recruited from the Hungarian National Pancreas Registry. In a
discovery cohort of 30 idiopathic CP cases the entire SLC26A6 coding sequence,
including 21 exons and the exon-intron boundaries were amplified and
sequenced. Further genotyping of p. V206M and p. P397P mutations in CP
and controls was carried out by RFLP.
A316 United European Gastroenterology Journal 2(5S)
RESULTS: Sequencing analysis of the discovery cohort revealed four common association with CP. No associations were found between the p. N34S mutation
mutations: intronic mutations c.2371_23103del, c.183-4C4A and and promoter region variants of the SPINK1 gene.
c.113432C4A; and exonic missense mutation p. V206M. These four mutations Supported by TAMOP, OTKA and MTA and Collegium Talentum scholarship
were found in linkage disequilibrium indicating a conserved haplotype. We found (to E. H.).
this haplotype in 18 heterozygous and 2 homozygous cases, and in 24 hetero- Disclosure of Interest: None declared
zygous and 2 homozygous controls (allele frequency 11.4% and 14.1% respec-
tively). A synonymous mutation p. P397P was also detected in a single case.
CONCLUSION: We found a novel, common haplotype in the SLC26A6 gene, P0670 QUANTIFICATION OF EXOCRINE DUCTAL PANCREATIC
which did not show association with CP. Supported by TAMOP and OTKA FUNCTION USING A SHORT ENDOSCOPIC SECRETIN TEST AND
Disclosure of Interest: None declared AUTOMATIC DUODENAL BICARBONATE MEASUREMENT
F. Erchinger1,2,*, O.A. Gudbrandsen2, T. Engjom2,3, E. Tjora4, D. Hoem5,
T. Hausken2,3, O.H. Gilja2,6, G. Dimcevski2,3
P0668 PANCREATIC EXOCRINE INSUFFICIENCY IN PATIENTS WITH 1
Medical Department, Voss Hospital, Voss, 2Department of Clinical Medicine,
HIV AND CHRONIC DIARRHOEA University of Bergen, 3Department of Medicine, 4Department of Pediatrics,
A. Jeevagan1,*, M. AUSTIN1, S. Soni2 5
Surgical Department, 6National Centre for Ultrasound in Gastroenterology,
1
Gastroenterology, 2Sexual Health and HIV, Lawson Unit, Royal Sussex County Haukeland University Hospital, Bergen, Norway
Hospital, BRIGHTON, United Kingdom Contact E-mail Address: friedemann.erchinger@helse-bergen.no
Contact E-mail Address: arun.jeevagan@nhs.net
INTRODUCTION: A short endoscopic secretin test has recently been evaluated
INTRODUCTION: Chronic Diarrhoea (CD) in HIV-infected patients is an in different patient groups and provides useful information about exocrine ductal
important cause of morbidity and has significant impact on their quality of pancreatic function(1-3). Bicarbonate in duodenal juice is an important parameter
life. Pancreatic exocrine insufficiency has been shown to be associated with in direct pancreas function testing. Gold standard is measurement of bicarbonate
HIV and has been suggested as an important non-infective cause of diarrhoea by back titration right after endoscopy, but this is time consuming, and requires
and fat malabsorption in these individuals. specialised equipment and highly skilled laboratory staff. A simplified method is
AIMS & METHODS: HIV-positive patients undergoing investigation for CD warranted.
between January 2011 and August 2013 were identified. Demographics and clin- AIMS & METHODS: The aim was to determine if back titration can be replaced
ical data including measurement of faecal elastase were taken from the patients by an automated spectrophotometric method.
medical records. Patients examined with short endoscopic secretin test suspected to have decreased
RESULTS: 60 patients were referred by the HIV team to Gastroenterology clinic pancreatic function of various reasons. Bicarbonate in duodenal juice was ana-
for investigation of CD. There were 55 (92%) male and mean age was 44 years. lysed both by back titration and automatic spectrophotometry. In our short
All were receiving antiretroviral therapy. No patients had a diagnosis of chronic endoscopic secretin test duodenal juice is suctioned in three aliquots of 5 minutes.
pancreatitis. 31/60 patients had raised faecal calprotectin, one had stool culture Both fresh and thawed samples were analysed.
positive for giardiasis, one had lymphocytic gastritis and so 34 patientswere RESULTS: 122 samples from 49 patients (25 men/24 women) were analysed.
excluded from the study. Out of these, 27 patients who had faecal elastase mea- Correlation coefficient of all measurements was r 0.98. Correlation coefficient
surements and 9/27 (30%) had pancreaticin sufficiency. of fresh versus frozen samples conducted with automatic spectrophotometry
CONCLUSION: In patients with HIV on antiretrovirals, in whom inflammation (n 27): r 0.96.
and infection had been excluded, approximately 30% of patients were confirmed CONCLUSION: The measurement of bicarbonate in both fresh and thawed
to have pancreatic exocrine insufficiency. This prevalence is greater than that samples, by automatic spectrophotometric analysis correlates excellent with mea-
seen in HIV-negative individuals with chronic diarrhoea. HIV treatment with surements made by back titration. This is a major simplification of direct pan-
didanosine or stavudine-containing antiretroviral regimens used to be the main creas function testing, and makes it possible to perform such tests standardised in
culprit but these drugs are seldom used in the management of HIV nowadays and all hospitals, in a time- and centre-independent way.
other causes must be considered. Faecal elastase sampling should form part of REFERENCES
the routine work-up for HIV-positive patients with chronic diarrhoea. Treatment (1) Erchinger F, Engjom T, Tjora E, et al. Quantification of pancreatic function
with pancreatic enzyme supplementation is effective treatment of chronic diar- using a clinically feasible short endoscopic secretin test. Pancreas 2013.
rhoea in these patients. (2) Tjora E, Wathle G, Erchinger F, et al. Exocrine pancreatic function in hepa-
Disclosure of Interest: None declared tocyte nuclear factor 1beta-maturity-onset diabetes of the young (HNF1B-
MODY) is only moderately reduced: compensatory hypersecretion from a hypo-
plastic pancreas. Diabet Med 2013.
P0669 THE ROLE OF SPINK1 PROXIMAL PROMOTER VARIANTS IN (3) Tjora E, Wathle G, Engjom T, et al. Severe pancreatic dysfunction but
CHRONIC PANCREATITIS compensated nutritional status in monogenic pancreatic disease caused by car-
E. Hegyi1,2, A. Geisz3, T. Takacs2, G. Farkas, Jr4, Z. Szepes2, J. Novak5, boxyl-ester lipase mutations. Pancreas 2013.
F. Izbeki6, J. Gervain6, I. Hritz2, A. Szepes7, D. Kelemen8, Z. Dubravcsik7, Disclosure of Interest: None declared
B. Bod9, R. Szmola10, J. Sumegi11, Z. Szentkereszti12, Z. Rakonczay, Jr2,
A. Balazs2,*, P. Hegyi2, M. Sahin-Toth3, L. Czako2 on behalf of Hungarian
Pancreatic Study Group P0671 EFFICACY OF ANTIOXIDANT THERAPY IN IMPROVING
1
2nd Department of Pediatrics, Comenius University Medical School, University PAINFUL CHRONIC PANCREATITIS: A SYSTEMATIC REVIEW
Childrens Hospital, Bratislava, Slovakia, 2First Department of Medicine, G. Ianiro1,1,*, L. Valerio2, M. Siciliano1, F. Scaldaferri1, I. Boskoski3,
University of Szeged, Szeged, Hungary, 3Department of Molecular and Cell G. Costamagna3, A. Gasbarrini1
Biology, Boston University Medical Center, Boston, United States, 4 Department 1
Dept of Internal Medicine, Division of Gastroenterology, CATHOLIC
of Surgery, University of Szeged, Szeged, 5Bekes Megyei Pandy Kalman Hospital, UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy, 2Dept of
Gyula, 6Fejer Megyei Szent Gyorgy Hospital, Szekesfehervar, 7Bacs-Kiskun Cardiovascular Medicine, Amsterdam Medical Center, Amsterdam, Netherlands,
Megyei Hospital, Kecskemet, 8Department of Surgery, University of Pecs, Pecs, 3
Digestive Endoscopy Unit, CATHOLIC UNIVERSITY SCHOOL OF
9
Dr. Bugyi Istvan Hospital, Szentes, 10National Institute of Oncology, Budapest, MEDICINE, ROME, Italy
11
Borsod-Abauj-Zemplen Megyei Hospital, Miskolc, 12 Department of Surgery, Contact E-mail Address: gianluca.ianiro@hotmail.it
University of Debrecen Medical School and Health Science Center, Debrecen,
Hungary INTRODUCTION: To date, there is no standardized treatment for pain caused
Contact E-mail Address: hegyi.peter@med.u-szeged.hu by chronic pancreatitis. Medical, endoscopic or surgical therapy are the currently
available approaches. Antioxidants have been proposed on the rationale that
INTRODUCTION: Serine protease inhibitor Kazal type 1 (SPINK1) provides they may slow down the damage of the gland produced by oxidative stress.
an important line of defense against premature trypsinogen activation within the Although several trials have been carried out over the years, no one of them
pancreas. The most common SPINK1 mutation p. N34S seems to increase the showed convincing results.
risk of chronic pancreatitis (CP), but the precise pathophysiological mechanism AIMS & METHODS: Our aim was to systematically review the literature related
of this mutation remains a subject of debate. to the efficacy of antioxidants in improving painful chronic pancreatitis. This
AIMS & METHODS: To determine the frequency of the p. N34S SPINK1 systematic review was conducted in accordance with the PRISMA guidelines. All
mutation in Hungarian patients with alcoholic chronic pancreatitis (ACP) and the original reports in which human subjects, both children and adults, with
idiopathic chronic pancreatitis (ICP) and to identify a possible pathogenic pro- chronic pancreatitis were treated with antioxidants were considered for inclusion.
moter variant linked with the p. N34S mutation. 70 subjects with CP (cases) (34 Inclusion criteria also required the pain as endpoint, and the report of efficacy
ACP and 36 ICP) and 70 subjects with no pancreatic disease (controls) were outcomes. No language restriction was set up. Animal model studies, studies
enrolled from the Hungarian National Pancreas Registry. Direct sequencing of presented only as abstracts, case reports and case series with less than 10 patients
the SPINK1 proximal promoter region (1 kb) was performed. The p. N34S were excluded. The following databases were used to perform the literature
SPINK1 mutation was analysed by RFLP. search: PubMed, SCOPUS, Web of Science, the Cochrane Library. The last
RESULTS: The p. N34S mutation was present in 3/70 patients, all with the search was run on 27 February 2013. The following MeSH terms and keywords
diagnosis of ICP, while it was absent in healthy controls (P 0.24). Two pro- were used alone or in combination: antiox*; vitamin supplement; antioxidant
moter variants (c.-253T4C and c.-807C4T) were found as common polymorph- supplement; vitamin A supplement; vitamin B6 supplement; vitamin B12 supple-
isms indicating no clinical significance. Additionally, three rare promoter ment; folic acid supplement; vitamin C supplement; vitamin D supplement; vita-
variants (c.-14G4A, c.-108G4T, and c.-215G4A) were identified in cases. min E supplement; selenium supplement; beta-carotene supplement; lycopene
The c.-215G4A variant was linked with the pathogenic c.1942T4C mutation. supplement; isoflavone supplement; chronic pancreatitis. A quality appraisal of
The clinical significance of the c.-14G4A and c.-108G4T variants is unclear so the selected studies was performed.
far. RESULTS: The literature search retrieved 3590 studies; of these, 9 met our
CONCLUSION: We identified two novel variants in the proximal promoter inclusion criteria. Six were blinded randomized clinical trials, 2 open trials, and
region of SPINK1 which will be further investigated to determine their possible 1 a prospective cohort study. Their comparability was severely limited because of
United European Gastroenterology Journal 2(5S) A317
differences in the endpoints chosen, which include pain-free days, pain scores, remaining biopsy revealed pancreatic tissue with some areas of fibrosis. Samples
quality of life scores, and supportive care needed; possibly severe selection bias from the other seven patients (70%) were not adequate for cytohistological
and low statistical power due to small sample size were found in some studies. diagnosis due to the absence of tissue and a poor cellularity. There was one
The few points of partial convergence include a potential reduction in the need of complication (10%), a mild acute pancreatitis requiring hospitalization for 48
supportive therapies and inefficacy of antioxidants in alcoholic pancreatitis. hours.
CONCLUSION: Available evidence is inconclusive: confirmation or refusal of CONCLUSION: EUS-FNB is feasible in the context of patients with EUS find-
the efficacy of antioxidant therapies against pain in chronic pancreatitis needs to ings of early CP. Samples obtained by the commercially available needles are
be investigated by further randomized controlled trials, with adequate design and however not adequate for histological evaluation. In addition, the risk of com-
standardized outcome variables, so as to allow for comparison. plications exists. EUS-FNB for the diagnosis of early CP should be avoided
Disclosure of Interest: G. Ianiro: nothing to declare, L. Valerio: nothing to unless new more appropriate needles are developed and can be evaluated for
declare, M. Siciliano: nothing to declare, F. Scaldaferri: nothing to declare, I. efficacy and safety in well-designed clinical trials.
Boskoski: nothing to declare, G. Costamagna: nothing to declare, A. Gasbarrini: Disclosure of Interest: J. Iglesias-Garc a Lecture fee (s) from: Cook-Medical,
nothing to declare Consultancy for: Cook-Medical, J. Larino-Noia: None declared, I.
Abdulkader: None declared, B. Lindkvist: None declared, J. E. Dominguez-
Munoz: None declared
P0672 AUTOIMMUNE PANCREATITIS IN CHILDREN- SINGLE
CENTRE EXPERIENCE
G. Oracz1,*, B. Cukrowska2, K. Wejnarska1, E. Kolodziejczyk1, J. Kierkus1, P0674 A CROSS SECTIONAL STUDY TO ASSESS THE PREVALENCE
J. Ryzko1 OF PANCREATIC EXOCRINE INSUFFICIENCY AMONG DIABETES
1
Dep. of Gastroenterology, Hepatology and Feeding Disorders, 2Dep. of Pathology, MELLITUS PATIENTS IN TURKEY
The Childrens Memorial Health Institute, Warsaw, Poland K. Demir1,*, C. Karaca1, E. Ahishali2, M. Mastanzade3, N. Gul4, F. Turker4,
Contact E-mail Address: grzegorz_oracz@poczta.onet.pl S. Celik4, F. Akyuz1, F. Besisik1, K. Karsidag4
1
Gastroenterology Department, Istanbul University Medical School,
INTRODUCTION: The etiology of chronic pancreatitis in children is varied and 2
Gastroenterology Department, Dr. Lutfi Kirdar Kartal Training and Research
includes gene mutations, anatomic anomalies, and others. The reported paedia- Hospital, 3Internal Medicine Department, 4Endocrinology Department, Istanbul
tric experience with chronic pancreatitis (CP) is small and little is known about University Medical School, Istanbul, Turkey
the role of autoimmune pancreatitis (AIP). Contact E-mail Address: mehmet.berktas@kappa-crt.com.tr
AIMS & METHODS: The aim of the study was to assess the frequency of
autoimmune markers in children with CP. INTRODUCTION: Pancreatic exocrine function insufficiency (PEI) is common
136 children with CP hospitalized at the Department of Gastroenterology, The in diabetes mellitus patients. Apparently, some patients with decreased exocrine
Childrens Memorial Health Institute, between 2005 and 2014 were examined for function are type 3c diabetes mellitus (DM) and misdiagnosed as type 2 or type 1
the presence of AIP; the level of IgG4 was determined, and the tests for anti- DM. There are only few data about PEI in DM patients in Turkey. This study
tissue antibodies were conducted. AIP was diagnosed according to the IAP aims to investigate exocrine insufficiency among DM patients in Turkey.
guidelines, i.e. on the basis of immunological criteria (presence of antibodies: AIMS & METHODS: The objective of the study is to assess the prevalence of
IgG4 and autoantibodies), radiological criteria (swelling of the pancreatic pancreatic exocrine insufficiency among type 1 and type 2 diabetes mellitus
head, and changes in the pancreatic duct), and response to corticosteroid ther- patients in Turkey. The abstract aims to present preliminary results of the study.
apy. Clinical data were recorded and analyzed. This is a cross sectional, non-interventional study which was conducted in
RESULTS: Anti-tissue antibodies were detected in 85/136 children (62.5%), and Turkey between October 2013 and February 2014. Adult patients (older than
29/75 patients (38.6%) showed an increased IgG4 level. Based on the IAP cri- 18 years) previously diagnosed type 1 or 2 DM, admitted to endocrinology
teria, a suspicion of AIP was raised in 8 patients. This diagnosis was definitely department with or without symptomatic gastrointestinal problems, followed
confirmed in 4 cases, based on clinical improvement observed after corticosteroid for more than five years were included to the study.
therapy. Due to the inactive phase of the disease, the immunosuppressive therapy PEI was evaluated by measuring faecal elastase-1 concentration, level 5100 g/g
was not implemented in the remaining suspected patients. In 41/85 (48.2%) stool was evaluated as severe PEI, whereas 100, 5200 g/g stool as mild-to-
patients with autoimmune markers we found gene mutations predisposing to moderate PEI and 200 g/g stool as normal (1). Upper detection limit of
CP. In 18/85 children (21.2%) anatomic anomalies were fund. There was no method used for faecal elastase-1 concentration was 500 g/g stool.
difference in the severity of the disease and clinical course between children RESULTS: Based on data of 211 DM patients [58.8% female, median (min-max)
with autoimmune stigmata and patients without autoimmune markers. age 58.2 (18.5-85.7) years], 146 (69.2%) were previously diagnosed type 2 DM
CONCLUSION: In children with CP, similarly to adults, there is a high fre- whereas others were type 1 DM. Median (min-max) DM duration of type 1 and 2
quency of biochemical markers of autoimmunity. AIP can be the cause of CP in patients was 15.6 (5.0-43.6) and 13.5 (5.5-37.5) years, respectively.
children. Median (min-max) faecal elastase-1 concentration of type 1 and 2 DM patients
Disclosure of Interest: None declared was 465.5 (104.0-500.0) and 474.0(52.0-500.0) g/g stool, respectively.
In entire study population, severe PEI prevalence was 1.9% (0.0% for type 1
DM, 2.7% for type 2 DM) whereas mild-to-moderate PEI prevalence was 12.3%
P0673 MATERIAL OBTAINED BY ENDOSCOPIC ULTRASOUND- (17.2% for type 1 DM, 10.3% for type 2 DM). Overall; 14.2% of patients (17.2
GUIDED FINE NEEDLE BIOPSY IS NOT ADEQUATE FOR THE % of type 1 DM, 13.0% of type 2 DM patients) have reduced PEI.
HISTOLOGICAL DIAGNOSIS OF EARLY CHRONIC PANCREATITIS CONCLUSION: Preliminary results of the study revealed that PEI prevalence
J. Iglesias-Garc a1,*, J. Larino-Noia1, I. Abdulkader2, B. Lindkvist3, among type 1 and type 2 patients was higher in Turkey and many DM patients
J.E. Dominguez-Munoz1 might be misclassified. In conclusion, evaluation of pancreatic exocrine function
1
Gastroenterology, 2Pathology, University Hospital of Santiago de Compostela. in DM patients should be essential part of daily practice.
Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain, REFERENCES
3
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 1. Luth S, Teyssen S, Forssmann K, et al. Fecal elastase-1 determination: gold
Gothenburg, Sweden standard of indirect pancreatic function tests? Scand J Gastroenterol 2001; 36:
1092-1099.
INTRODUCTION: Diagnosis of early chronic pancreatitis (CP) is a clinical Disclosure of Interest: K. Demir Financial support for research from: Research
challenge and it is hampered by the lack of methods for histological confirma- grant from Abbott Turkey, C. Karaca: None declared, E. Ahishali: None
tion. Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB), with the use declared, M. Mastanzade: None declared, N. Gul: None declared, F. Turker:
of ProcoreTM histology needles provides adequate samples for the histological None declared, S. Celik: None declared, F. Akyuz: None declared, F. Besisik:
evaluation of solid pancreatic lesions, but the efficacy and safety of this technique None declared, K. Karsidag: None declared
for early CP is unknown.
AIMS & METHODS: We aimed at evaluating the efficacy and safety of EUS-
FNB with ProcoreTM needles for the histological diagnosis of early CP. P0675 STUDY OF THE LIPID PROFILE AND THE OXIDATIVE STRESS
Methods: A prospective, pilot study with consecutive inclusion of patients OF DIABETIC PATIENTS WITH CHRONIC PANCREATITIS
between January and September 2013 was designed. Inclusion criteria: Patients M. Sliwinska-Mosson1,*, S. Milnerowicz2, W. Sajewicz1, H. Milnerowicz1
4 18 years old submitted to our Endoscopy Unit to undergo EUS examination 1
Department of Biomedical and Environmental Analyses, 2Department of
because of the clinical suspicion of chronic pancreatitis. Only patients with 3-4 Gastrointestinal and General Surgery, University of Medicine Wroclaw, Wroclaw,
EUS criteria of CP were finally included. EUS-guided FNB was performed by Poland
two experienced endosonographers in these patients under deep sedation after Contact E-mail Address: mariola.sliwinska-mosson@umed.wroc.pl
signing the informed consent. A linear slim Pentax echoendoscope (EG 3270 UK)
attached to a Hitachi Ascendus ultrasound device was used for EUS. FNB of the INTRODUCTION: Smoking patients with chronic pancreatitis (CP) are at high
body of the pancreas was performed with ProcoreTM needles of different sizes. risk for antioxidant deficiencies (1). Moreover, this disease may lead to the
Samples obtained were immersed into a Cytolit solution for cytohistological development of diabetes mellitus type II (DM2), which additionally enhances
evaluation. All samples were evaluated by a single expert pathologist. The quality the oxidative stress (2). The main characteristics of DM2 are insulin resistance
of the samples obtained and the histological findings (inflammatory cells infiltra- in muscle and liver cells accompanied by loss of -cell function. However, adi-
tion and fibrosis) were evaluated. Complications were recorded. pose tissue and pancreatic cell activity, may be involved in disease development
RESULTS: The study was stopped after the inclusion of 10 patients (mean age (3). Most recently a trend for positive correlation between HDL cholesterol and
50.3 years, range 33-70 years, 6 male) due to unsatisfactory results. Pancreatic amylase in DM2 patients was shown.
EUS-FNB was feasible in all cases. A 19G ProcoreTM needle was used in 5 cases, AIMS & METHODS: In the present study we evaluated the lipid profile and
a 22G needle in 2 and a 25G needle in 3 cases. Sample quality was considered total peroxyl radical trapping potential (TRAP), glutathione (GSH), thiobarbi-
adequate for histological evaluation in only 3 cases (30%), (2 performed with a turic acid reactive substances (TBARS) in non-smoking and smoking patients
19G needle and one with a 25G needle). Two out of these three biopsies revealed with CP suffering from diabetes. The relationship between different parameters
a normal pancreatic tissue and the diagnosis of CP could not be confirmed. The was examined. The blood was collected from 50 healthy persons and 63 patients
A318 United European Gastroenterology Journal 2(5S)
with diagnosed chronic pancreatitis (CP). Diabetes mellitus was diagnosed in 24
P0677 CONTRAST ENHANCED ULTRASOUND OF THE PANCREAS
patients. The concentration of cotinine and lipid profile in plasma was estimated
SHOW IMPAIRED PERFUSION IN PANCREAS INSUFFICIENT
by the ELISA and diagnostic tests, respectively. Lipid peroxidation levels were
CYSTIC FIBROSIS PATIENTS
assessed by TBARS, and TRAP was measured by using luminescence.
Glutathione level was determined in blood hemolysates with the colometric T. Engjom1,2,*, K. Nylund1,2, F. Erchinger2,3, B. Lrum4,5, G. Dimcevski1,2,
method. R. Jirik6, O.H. Gilja2,7
1
RESULTS: The concentration of HDL were statistically lower in smoking Department of gastroenterology, Haukeland University Hospital, 2Department of
patients with CP with or without diabetes as compared to the control group, Clinical Medicine, University of Bergen, Bergen, 3Department of medicine, Voss
while the concentration of TG and LDL were statistically highest in smoking Hospital, Voss, 4Department of Thoracic Medicine, Haukeland University
diabetics compared to all groups (p50.001). It was also observed that the con- Hospital, 5Department of Clinical Science, University of Bergen, Bergen, Norway,
6
centration of TBARS was statistically significant increased in non-smoking and International Clinical Research Center - Center of Biomedical Engineering, St.
smoking patients with CP (3.5 1.3 [mmol /l], 4.75 1.0 [mmol /l]), and patients Annes University Hospital, Brno, Czech Republic, 7National Centre for
with CP and DM (5.3 2.6 [mmol/l]) as compared with control group (3.41.9 Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
[mmol/l]). In smoking patients with DM, a statistical highest level of TRAP Contact E-mail Address: trond.engjom@helse-bergen.no
compared to all study groups was found (p50.0001). Statistical analysis of the
results showed that the decline in the concentration of GSH is associated with INTRODUCTION: Pancreatic insufficiency is a prevalent feature of cystic fibro-
cigarette smoking and diabetes. The lowest concentration of GSH was observed sis (CF). The affected CF pancreas is dominated by fatty infiltration, atrophy
in smoking patients with CP and diabetes, the highest in non-smoking control and necrosis. Little is known about pancreatic perfusion in CF.
group (p50.0001). AIMS & METHODS: We aimed to evaluate pancreatic perfusion assessed by
CONCLUSION: The lipid profile is altered in smoking patients with CP, parti- contrast-enhanced ultrasound (CEUS) in CF patients with known exocrine pan-
cularly in those who also have DM. In these patients, a glutathione deficiency creatic function.
and an elevated plasma concentration of lipid peroxidation products were asso- CEUS was performed in CF patients (n 39) and healthy controls (n 32).
ciated with significantly higher LDL. In the diabetic patients group, a positive Exocrine pancreatic function was assessed by secretin-stimulated endoscopic
correlation between TRAP and TBRAS was found, which points to the induction short test and/ or faecal elastase. The CF patients were defined as pancreas
of the antioxidant potential on intensification of lipid peroxidation. sufficient through fecal elastase 4200mg/g or duodenal bicarbonate 480mmol/
REFERENCES L. Perfusion data was analyzed on stored DICOM-files using DCE-US software
1.Sliwinska-Mosson M, et al. Pancreatology 2012; 12: 295-304. (http://www.isibrno.cz/perfusion/) and a dedicated perfusion model. Mean tran-
2.de M Bandeira S, et al. Int J Mol Sci 2013; 5: 3265-3284. sit-time (MTT), blood flow (BF) and blood-volume (BV) was calculated.
3. Eleftheriou P, et al. Hell J Nucl Med 2014; 17(Suppl. 1): 35-39. Exclusions due to image quality and image analysis in the CF group were
Disclosure of Interest: None declared made without knowledge of pancreatic function.
RESULTS: 26 CF patients and 20 controls were included. 13 CF patients and 12
controls were excluded due to poor image quality. Subjects were divided as
P0676 CLINICAL FEATURES OF PANCREATIC INVOLVEMENTS OF follows: CF, pancreatic insufficient (CFI, n 13), CF pancreatic sufficient
VON HIPPEL-LINDAU DISEASE IN KOREA (CFS, n 13) and healthy controls (HC, n 20). Results are displayed in the
T. Park1,*, S. Lee1 table (meanSD) (s seconds, ml millilitre)
1
Department of Gastroenterology, Asan medical center, University of Ulsan
College of Medicine, Seoul, Korea, Republic Of CFI (n 13) CFS (n 13) HC (n 20) P
Contact E-mail Address: ptymd@hotmail.com
MTT (s) 8.03.2 4.01.9 2.91.4 P50.001
INTRODUCTION: Von Hippel-Lindau disease (VHL) is autosomal dominant
disorder characterized by development of multiple tumors in central nervous BF (ml/min/100ml) 18.410.5 76.8.054 117.470 P50.001
system and visceral organs. There have been reported a few studies about clinical BV (ml/100mL): 2.31.3 4.12.5 4.82.5 P50.05
courses of pancreatic involvements of VHL.
AIMS & METHODS: In this study, we report clinical features of pancreatic
involvements of VHL in Korea. We conducted retrospective cohort study of CONCLUSION: The pancreatic insufficient CF patients had significantly longer
55 patients who were diagnosed with VHL-associated pancreatic lesions from MTT (p50.001), lower BF (p50.001) and lower BV (p50.05) compared to
1995 to 2013 in Asan Medical Center. Demographic, genetic, radiologic features healthy controls and pancreatic sufficient CF patients. CEUS can non-invasively
and clinical features of VHL-associated pancreatic lesions were analyzed by differentiate between healthy pancreatic tissue and exocrine insufficient pancrea-
medical record review. tic tissue due to cystic fibrosis.
RESULTS: 55 patients had VHL-associated pancreatic lesions (87.3%). Median Disclosure of Interest: None declared
onset of age was 33 years (12-67 years) and male and female ratio was 31:24.
Median observation period was 1731 days (3-5077). Genetic test was performed
in 35/55 patients (63.6%) and VHL gene mutations were confirmed in 28/35 P0678 PARADUODENAL PANCREATITIS MANAGED BY PANCREAS-
patients (80%). VHL gene mutation was located on exon 1 in 13 patients SPARING DUODENAL RESECTIONS. WHY, WHEN AND HOW
(46.4%), exon 2; 4 (14.3%), exon 3; 9 (32.1%) and others 2 (7.2%). Mean V. I. Egorov1,*, A. Vankovich2, R. Petrov3, N. Starostina4
involved number of organs was 2.51 0.72. Most common subtype of VHL 1
Surgical Oncology, 5th City Hospital, Sechenov First State Medical University,
was type I as 44/55 patients (80%). Pancreatic involvements were included single 2
Surgical Oncology, Vishnevsky Institute of surgery, 3Surgical Oncology,
simple cyst (n 5, 9.1%), multiple simple cysts (n 14, 25.5%), serous cystade- Ostroumov 14th City Hospital, Sechenov First State Medical University,
noma (n 29, 52.7%) and neuroendocrine tumor (n 17, 30.9%). Initial pre- 4
Radiology, 5th City Hospital, Moscow, Russian Federation
sented VHL-associated tumors as only pancreatic lesions were observed in only 2 Contact E-mail Address: v.egorov61@gmail.com
of 55 patients (3.6%) and pancreatic symptoms were only 4 patients (7.3%). Of
55 patients, 11 patients received surgical treatment and 2 patients received EUS- INTRODUCTION: The term paraduodenal pancreatitis (PP) was proposed as
guided ethanol ablation therapy as local treatment for neuroendocrine tumor and an umbrella for cystic dystrophy in heterotopic pancreas (duodenal dystrophy),
42 patients were observed regularly without intervention (20%, 3.6%, 76.4% paraduodenal cyst and groove pancreatitis, by reasoning that these conditions
respectively). One patient received distal pancreatectomy as radiologic diagnosis mimic pancreatic head tumors and share certain histological evidences. It is still
of neuroendocrine tumor, however, final pathologic diagnosis was serous cysta- unclear what organ paraduodenal pancreatitis originates of.
denoma, which was thought to be solid microcystic serous adenoma (SMSA). AIMS & METHODS: To assess the results of different types of treatment for
One patient was died of pulmonary hemorrhage due to pulmonary metastasis of paradudenal pancreatitis.
VHL-associated renal cell carcinoma. 1. Prospective analysis of 65 cases of PP (2004-2013), comparing preoperative
CONCLUSION: Most common presentation of pancreatic involvement in VHL and histopathological findings in 42 surgical specimens; 2. Assessment of clinical
was serous cystadenoma. Pancreatic tumors as primary presenting lesion in VHL presentation and the results of DD treatment.
are relatively rare and most of pancreatic lesions were asymptomatic. Nationwide RESULTS: Preoperative diagnosis was correct in all the cases except one, when
epidemiologic study is needed to verify natural course and prognosis of pancrea- cystic tumor of the pancreatic head was suspected (1.9%). Patients were pre-
tic involvement in VHL. sented with abdominal pain (100%), weight loss (76%), vomiting (30%) and
REFERENCES jaundice (18%). CT, MRI and endoUS were the most useful diagnostic modal-
1. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet ities. Ten patients were treated conservatively, 26 underwent pancreaticoduode-
2003; 361: 2059-2067. nectomies (PD), pancreatico- and cystoenterostomies(8), Nakao procedures(4),
2. Lee KH, Lee JS, Kim BJ, et al. Pancreatic involvement in Korean patients with duodenum-preserving pancreatic head (DPPH) resections(5), and 12 pancreas-
von Hippel-Lindau disease. J Gastroenterol 2009; 44: 447-452. preserving duodenal resections (PPDR). No mortality. Full pain control was
3. Hammel PR, Vilgrain V, Terris B, et al. Pancreatic involvement in von Hippel- achieved after PPRDs in 83%, PDs in 85%, and after PPPH resections and
Lindau disease. The Groupe Francophone dEtude de la Maladie de von Hippel- draining procedures in 18% of cases. Diabetes mellitus developed thrice after PD.
Lindau. Gastroenterol 2000; 119: 1087-95. CONCLUSION: 1. The diagnosis of PP can be confidently determined by
4. Igarashi H, Ito T, Nishimori I, et al. Pancreatic involvement in Japanese modern methods prior to surgery; 2. PD is the main surgical option for PP
patients with von Hippel-Lindau disease: results of a nationwide survey. J treatment at present; 3. Early diagnosis makes pancreas-preserving duodenal
Gastroenterol 2014; 49: 511-516. resection the treatment of choice for PP; 4. The effectiveness of PPDR provides
5. Neumann HP, Dinkel E, Brambs H, et al. Pancreatic lesions in the von Hippel- compelling proof that paraduodenal pancreatitis is an entity of duodenal
Lindau syndrome. Gastroenterology 1991; 101: 465-471. origin.
Disclosure of Interest: None declared Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A319
AIMS & METHODS: We have evaluated the therapeutic effect of HIFU therapy
P0679 CHANGED PLASMA ADIPONECTIN CONCENTRATION AND
for locally advanced pancreatic body cancer (PBC). We treated PBC patients
ITS CORRELATION WITH CLINICOPATHOLOGICAL
using HIFU therapy as optional local therapy as well as systemic chemo /
PARAMETERS IN PANCREATIC ADENOCARCINOMA PATIENTS
chemo-radiotherapy, with whom an agreement was obtained in adequate IC,
A. Saray1,*, R. Mesihovic1, Z. Vukobrat-Bijedic1, N. Vanis1, S. Gornjakovic1, from the end of 2008 in our hospital. This study took approval of member of
A. Husic-Selimovic1, A. Mehmedovic1, V. Papovic1, S. Glavas1, A. Valjevac2 ethic society of our hospital. HIFU device used is FEP-BY02 (Yuande Bio-
1
Dept. of gastroenterology and hepatology, CLINICAL CENTER UNIVERSITY Medical Engineering, Beijing, China). The subjects were 20 locally advanced
OF SARAJEVO, 2Laboratory for molecular medicine, Medical Faculty, University PBC patients.
of Sarajevo, Sarajevo, Bosnia and Herzegovina RESULTS: The mean tumor size after HIFU therapy changed to 36.5 (15-57)
Contact E-mail Address: sarayaida19@gmail.com mm from 39.5 (20-57) mm at pre-therapy. There were no significant changes in
tumor size. The mean treatment data was the following; mean number of treat-
INTRODUCTION: Recently it has been shown that low prediagnostic plasma ment sessions, 2.7 (2-5); mean total treatment time, 2.3 (1.8-4.7) hours, and mean
adiponectin levels are associated with an elevated risk of pancreatic cancer (PC). total number of ablation: 2852 (760-6420) shots. The effects of HIFU therapy
However, no studies exist in which association between adiponectin levels and was the following; the rate of complete tumor ablation was 75%, the rate of
pancreatic tumor stage were tested. symptom relief effect was 82%, the effectiveness of primary lesion was CR:0, PR:
AIMS & METHODS: The aim of the study was to analyze plasma concentra- 3, SD:14, PD:3, and primary disease control rate (DCR) more than SD was
tions of adiponectin in PC patients and to compare these concentrations to 83.3%. There was no adverse event. The following therapy after HIFU therapy
clinicopathological parameters. Baseline levels of adiponectin were determined was; operation 2, chemotherapy 15, and BSC 3 cases, respectively. Mean survival
in 40 consecutive patients with newly diagnosed pancreatic adenocarcinoma and time (MST) after diagnosis was 41.5 months, and MST after HIFU therapy was
40 healthy control subjects. The association between adiponectin and tumor 19.1 months. Mean duration time from diagnosis till HIFU therapy was 16.3
stage (TNM classification) and tumor grade were evaluated using nonparametric months. MST after diagnosis in HIFU with chemotherapy or chemo-radiother-
Spearmans correlation test. Control subjects were matched to case patients by apy and chemotherapy alone (10 patients in our hospital) was 41.5 vs 23.1
smoking status, age and BMI. months, respectively (p50.05, p 0.04, Log-rank). Combination therapy with
RESULTS: Overall median adiponectin concentrations were lower in PC HIFU was better result than common chemotherapy alone.
patients versus control subjects (7.1 vs 9.3 mg/mL, p50.001). In PC patients CONCLUSION: This study suggested that HIFU therapy has the potential of
with TNM stage III-IV (n 21) median adiponectin concentrations were signifi- new method of combination therapy for locally advanced pancreatic body
cantly lower than in PC patients with TNM stage I-II (n 19) (5.7 vs 7.3 mg/mL, cancer.
p50.001). Mean adiponectin concentrations were lower in high grade intrae- Disclosure of Interest: None declared
pithelial neoplasia tumors (n 18) compared to low grade tumors (n 13) (5.1
vs 6.5 mg/mL, p50.05). Adiponectin concentrations were inversely correlated
with tumor size and tumor TNM stage (r -0.834, p50.01) and tumor grading P0682 EVALUATION OF UPFRONT SURGERY AS CURATIVE-INTENT
(r -0.615, p50.01) of pancreatic adenocarcinoma patients. THERAPY CONCEPT IN LOCALLY ADVANCED PANCREATIC
CONCLUSION: This study identified, for the first time, an inverse correlation CANCER
between adiponectin levels and tumor size and TNM stage suggesting a potential C. Ansorge1,*, G. Saliba1, M. Karimi2, N. Kartalis3, L. Lundell1, M. Del Chiaro1,
role for adiponectin in progression of pancreatic adenocarcinoma. J. Blomberg1, R. Segersvard1
Disclosure of Interest: None declared 1
Department of Surgical Gastroenterology, Karolinska University Hospital,
2
Department of Oncology, Karolinska University Hospital, Division of Surgery,
Department of Clinical Science, Intervention and Technology (CLINTEC),
P0680 PREOPERATIVE ENDOSCOPIC BILIARY DRAINAGE Karolinska Institutet, 3Department of Radiology, Karolinska University Hospital,
PROCEDURES INFLUENCE SURVIVAL FOLLOWING RESECTION Division of Medical Imaging and Technology, Department of Clinical Science,
FOR AMPULLARY CARCINOMAS Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,
K. Urbonas1, A. Gulbinas2,*, J. Pundzius1, G. Barauskas1 Sweden
1
Surgery, 2Institute for Digestive Research, Lithuanian University of Health
Sciencies, Kaunas, Lithuania INTRODUCTION: Representing the 4th most common cancer mortality, pan-
Contact E-mail Address: kestasu@gmail.com creatic cancer remains an unsolved health problem. The majority of patients are
diagnosed at an advanced disease stage with limited therapy options. Currently,
INTRODUCTION: Carcinoma of Papilla of Vater has the best survival rate of in addition to the limitations, the treatment of non-metastatic locally advanced
all periampullary carcinomas. Patients typically manifest symptoms early in the pancreatic cancer (LAPC) is characterized by substantial methodological hetero-
course of the disease with abdominal pain, jaundice, and weight loss. This may geneity among pancreatic centers due to variation of applied definitions, regimes
account for early diagnostic and relatively high resection rate. Aim of our study and surgical procedures. Based on radiological criteria of mesenteric vessel invol-
was to identify the independent factors influencing a long term survival for vement, the radiological assessment of technical resectability in our institution
patients who underwent pancreatodudenectomy for ampullary adenocarcinoma. distinguishes between primarily resectable LAPC (B-tumors, superior mesenteric/
AIMS & METHODS: of our study was to identify the independent factors portal vein involvement 450% of the circumference, 52cm length) and primar-
influencing a long term survival for patients who underwent radical surgical ily unresectable LAPC assessed as potentially resectable after neoadjuvant che-
treatment for ampullary adenocarcinoma. moradiotherapy (NACRT, C-tumors, SMV/PV 450%, 42cm and/or superior
Methods. Data of 64 patients with ampullary adenocarcinoma who underwent mesenteric artery involvement 550%, 52cm).
major surgery was prospectively collected and analyzed. Demographic, clinical AIMS & METHODS: The aim of the present study was to evaluate the perfor-
and histopathological examination data were assumed to have the impact on mance of primary resection and neoadjuvant treatment followed by attempted
survival. The Kaplan-Meier method and log-rank tests were used for univariate resection as curative-intent concepts in LAPC. A single-center prospective cohort
analysis. Cox proportional hazard model was applied to indentify prognostic study was conducted including patients with B- and C-tumors in the pancreatic
factors that were independently associated with survival. head between 2008 and 2013. Histological confirmation preceded NACRT
RESULTS: The mean of survival time was 109 months, whereas five years (Gemcitabine and Capecitabine). Toxicity, therapy response and postoperative
cumulative survival was 62 percent. Univariate analysis revealed preoperative complications were recorded according to established classifications. Overall
endoscopic biliary drainage (stenting) (p50.001), microvessels infiltration (OS) and progression-free survival (PFS) was analyzed; OS was calculated
(p50.001), patients age over 70 years (p50.005), lymphonodes infiltration from date of decision until death, PFS either from date of surgery or date of
(p50.021) and T stage (p50.048) as a factors influencing survival. confirmed stable disease/partial remission (SD/PR) after NACRT until date of
Preoperative endoscopic biliary drainage (HR 5.25; CI (1.94-14.21)), microvessels tumor progression. Patients with specimen histology other than ductal adenocar-
infiltration (HR 3.85; CI (1.09-13.51)) and patients age 470yrs (HR 2.35; CI cinoma were retrospectively excluded.
(1.03-5.39) were independent factors influencing survival in multivariate analysis. RESULTS: Ninety-nine patients with histologically confirmed pancreatic cancer
CONCLUSION: Preoperative endoscopic biliary drainage seems to have the were included. Of 30 patients with B-tumors, 22 underwent curative-intent resec-
most significant influence on survival, therefore necessity of procedure should tion (CIR). Of 69 patients with C-tumors, 64 underwent NACRT, 22 had SD/
be carefully assessed before the operation. PR, and 15 underwent CIR. The resection rate in B-tumors was significantly
Disclosure of Interest: None declared higher (73%) than in C-tumors (22%); however, both groups had comparable
median OS rates (B-tumors 10.5, C-tumors 11 months). In B-tumors, median OS
in intra-operatively confirmed unresectability was 8, in CIRs 11.5, and if fol-
P0681 HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) THERAPY lowed by adjuvant treatment 14 months (median PFS in CIRs 9.6 months). In C-
FOR LOCALLY ADVANCED PANCREATIC CANCER tumors, median OS in patients with discontinued NACRT was 4, with post-
A. Sofuni1,*, F. Moriyasu1, T. Sano1, M. Fujita1, T. Tsuchiya1, K. Ishii1, NARCT tumor progression 11, and with confirmed SD/PR 19 months
N. Ikeuchi1, J. Umeda1, R. Tanaka1, R. Tonozuka1, S. Mukai1, K. Kamata1, (median PFS after CIR 21 months).
S. Tsuji1, F. Itokawa1, T. Itoi1 CONCLUSION: In patients with technically resectable LAPC, primary resection
1
Gastroenterology and hepatology, TOKYO MEDICAL UNIVERSITY, Tokyo, was not proven to be a sustainable therapy concept, and the preoperative radi-
Japan ological resectability assessment does not seem to have prognostic significance.
Contact E-mail Address: a-sofuni@amy.hi-ho.ne.jp Provided that a timely histological confirmation can be guaranteed, the indica-
tion for NACRT, and followed by attempted resection in SD/PR cases, should be
INTRODUCTION: Even with recent advances in the diagnostic imaging tech- extended to patients with technically resectable LAPC.
nology, most cases of pancreatic cancer (PC) are diagnosed at an unresectable Disclosure of Interest: None declared
stage. The results of chemotherapy and chemo-radiotherapy for the condition
were not satisfactory. However, locally advanced PC can expect the possibility of
additional therapy including the surgical treatment and the prolongation of the
prognosis by the strategy of combination therapy. HIFU therapy being pro-
moted as a new method to ablate the tumor is expected for locally advanced PC.
A320 United European Gastroenterology Journal 2(5S)
AnnexinA1: 96.9%; SSH: 93.6%; FAK: 59.4%; collagen-I: 32.3%; FAS:
P0683 STENT ON DEMAND IS SAFER THAN PROPHYLACTIC
28.6%; MMP: 12.9; HSP70: 14.3%. Expression of collagen-I was associated
DOUBLE BYPASS SURGERY WHEN A PLANNED RESECTION
with a shorter survival (150.898.2 vs 285.4147.2 days, p 0.029). FAK
FOR PANCREATIC CANCER CANNOT BE PERFORMED
expression was associated with a smaller tumor size (36.19.5 vs 48.214.2,
J. Wennerblom1,*, C. Williamsson2, B. Tingstedt2, C. Jonsson1 p 0.02). Finally, lack of SHH was associated with normal serum Ca19.9 levels.
1
Dept. of Surgery, Gothenburg University, Gothenburg, 2Dept. of Surgery, Lund CONCLUSION: Some tumor proteins expressed in unresectable PC can be
University, Lund, Sweden evaluated by immunohistochemistry in EUS-FNB samples to predict survival
and response to palliative chemotherapy. Expression of collagen-I is associated
INTRODUCTION: For decades routine use of prophylactic hepaticojejunost- with a shorter survival in patients receiving palliative therapy with gemcitabine.
omy and gastroenterostomy has been advocated when a curative intention must Further prospective studies including a larger number of patients are required to
be abandoned due to peroperative findings of locally advanced or metastatic confirm these data.
disease in pancreatic cancer (1). The development of Self Expanding Metal Disclosure of Interest: None declared
Stents (SEMS) has challenged this routine.
AIMS & METHODS: The aim of the present study was to retrospectively com-
pare the results for patients operated 2004-2013 from two Swedish referral cen- P0686 CLINICAL IMPACT OF KL-6 MEASUREMENT OF PANCREATIC
tres with local guidelines for different surgical strategies when signs of JUICE FOR DIAGNOSING PANCREATIC MASSES
irresectability were discovered during surgery. K. Matsumoto1,*, K. Harada1, Y. Takeda1, T. Onoyama1, S. Kawata1, M. Ueki2,
At Lund University Hospital, Lund the abdomen was closed immediately in Y. Murawaki1
patients without gastric outlet syndrome (GOS) and if the patient later developed 1
Gastroenterology, 2Promoting next-generation highly advanced medicine, Tottori
jaundice and/or GOS a SEMS was inserted (n 74). At Sahlgrenska University University Hospital, Yonago, Japan
Hospital, Gothenburg prophylactic double bypass surgery (DBS) was performed Contact E-mail Address: ayano0620@hotmail.co.jp
when the patient was found to have a non-curable disease (n 77).
RESULTS: There was no difference between the cohorts regarding age, sex and INTRODUCTION: Pancreatic juice cytology (PJC) is considered optimal for the
ASA-class. The need for immediate reoperations did not differ between the two differential diagnosis of pancreatic masses and is thought to be the most exact
groups. However, delayed gastric emptying (DGE) as well as other complications diagnostic modality for intraductal papillary mucinous carcinoma (IPMC).
according to the Clavien-Dindo system (2) was significantly more frequent after However, the accuracy of PJC has been unsatisfactory, ranging from 46.7% to
DBS than when using the stent strategy. These findings probably explain the 93.0%. Therefore, to improve the accuracy of diagnosis for pancreatic malig-
longer post operative hospital stay in the DBS group (11 vs. 9 days nancy, alternative modalities are needed. MUC1, a membrane-associated mucin
(p 0.001). The long term survival after surgery was not better in the DBS- widely expressed in gastrointestinal tissues, has a variety of types based on dif-
group than for the SEMS patients (318 vs. 380 days, p 0.075). ferent glycoforms in its extracellular domain. Many investigations have shown
that aberrant expression of MUC1 in gastrointestinal cancer tissue has clinico-
Double Bypass SEMS P-value pathological and biological importance in cancer. KL-6 mucin, one kind of
MUC1, has also been investigated; it appears to have a significant relationship
Survival 318 (23-808) 380 (15-1151) 0.075 with malignant tumor behavior, especially cancer cell invasion and metastasis in
various gastrointestinal cancers.
Length of Stay 11 (6-66) 9 (4-42) 0.001 AIMS & METHODS: The aim of this study was to evaluate the clinical impact
Removal nasogastric tube 2 (1-17) 1 (1-22) 0.046 of the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.
Fluid intake 4 (1-18) 2 (1-23) 0.005 This study comprised 70 consecutive patients with pancreatic masses (34 pan-
Food intake 6 (3-19) 4 (1-31) 0.0001 creatic ductal adenocarcinomas [PDACs], 5 intraductal papillary mucinous car-
cinomas [IPMCs], 12 pancreatic inflammatory lesions and benign stricture of the
DGE (A,B or C)* 27 (35%) 14 (19%) 0.03 main pancreatic ducts [MPDs] and 19 intraductal papillary mucinous adenomas
Reoperations * 5 (6.5%) 7 (9.4%) 0.55 [IPMAs]). All patients underwent PJC and measurement of the KL-6 concentra-
Complications* 42 (55%) 25 (34%) 0.013 tion of pancreatic juice, which was obtained from the pancreatic duct. After
Overall Clavien-Dindo Score 0.001 pancreatic juice was centrifuged at 1000 rpm for 5 minutes, cytological examina-
tion of the cell pellet was performed. The supernatant (10 L) was used to
measure the KL-6 concentration. Human KL-6 levels were assayed in duplicate
using a PICOLUMI KL-6 kit (EIDIA, Tokyo, Japan) an electrochemilumines-
CONCLUSION: The more conservative approach to primarily close the abdo- cence immunoassay (ECLIA) specific for human KL-6.
men and to treat the patient with SEMS on demand seems safer and results in a RESULTS: The average KL-6 concentration of pancreatic juice was significantly
shorter initial hospital stay and does not seem to impair the long time survival for higher for PDACs (167.7 396.1 U/mL) than for pancreatic inflammatory
the patients compare to the DBS-routine. lesions and benign MPD strictures (17.5 15.7 U/mL P 0.034).
REFERENCES Furthermore, KL-6 was significantly higher in IPMCs (86.9 21.1 U/mL)
1. Lillemoe KD, Cameron JL, Hardacre JM, et al. Ann Surg 1999; 230: 322-328. than in IPMNs (14.4 2.0 U/mL P 0.026). The cut-off level of KL-6 concen-
2. Dindo D, Demartines N and Clavien PA. Classification of surgical complica- tration was 16 U/mL for differentiating PDACs and IPMCs from pancreatic
tions: a new proposal with evaluation in a cohort of 6336 patients and results of a inflammatory lesions and IPMNs. The sensitivity, specificity, positive predictive
survey. Ann Surg 2004; 240: 205-213. value, negative predictive valu, and accuracy of KL-6 concentration alone were
Disclosure of Interest: None declared 79.5%, 64.5%, 73.8%, 71.4% and 72.9%, respectively, whereas those of PJC
alone were 82.1%, 96.8%, 97.0%, 81.1% and 88.6%, respectively. Adding the
KL-6 concentration to PJC diagnosis increased the sensitivity and accuracy of
P0685 POTENTIAL BIOMARKERS EVALUATED FROM TISSUE PJC by 15.3% (P 0.025) and 8.5% (P 0.048), respectively.
SAMPLES OBTAINED BY ENDOSCOPIC ULTRASOUND-GUIDED CONCLUSION: The KL-6 concentration of pancreatic juice may be useful for
FINE NEEDLE BIOSPY (EUS-FNB) MAY PREDICT PROGRESSION diagnosing PDAC, as well as PJC.
AND RESPONSE TO GEMCITABINE THERAPY IN UNRESECTABLE Disclosure of Interest: None declared
PANCREATIC CANCER
J. Iglesias-Garc a1,*, M. Luaces-Regueira2, L. Nieto-Garc a2, M. Castineira-
Alvarino2, I. Abdulkader3, J. Larino-Noia1, J.E. Dominguez-Munoz1 P0687 NEW DIAGNOSTIC STRATEGIES FOR THE EARLY DIAGNOSIS
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for OF PANCREATIC CANCER
Research in Digestive Diseases, 2Foundation for Research in Digestive Diseases, K. Hanada1,*, A. Okazaki1, M. Shinzato1, Y. Izumi1, Y. Teraoka1,
3
Pathology, University Hospital of Santiago de Compostela, Santiago de K. Kanemitsu1, J. Ikemoto1, N. Hirano1
1
Compostela, Spain Gastroenterology, Onomichi General Hospital, Onomichi, Japan
Contact E-mail Address: kh-ajpbd@nifty.com
INTRODUCTION: Due to the poor prognosis of advanced unresectable pan-
creatic cancer (PC), predicting response to palliative chemotherapy is essential to INTRODUCTION: Detection of pancreatic cancer (PC) at an early stage with
avoid adverse events of otherwise unnecessary treatments. The majority of stu- curative surgery is the approach with the potential to significantly improve long-
dies on expression of tumor proteins have been performed on surgical specimens term patient outcome. However, the rate of tumor detection of computed tomo-
of resectable PC. We hypothesize that the expression of some tumor proteins may graphy (CT) in the case with small pancreatic cancer was not satisfied. For the
predict prognosis and response to gemcitabine in patients with unresectable PC. diagnoses of PC less than 10mm, the rate of tumor detection was higher for
AIMS & METHODS: Aim of the present study was to analyze the role of several endoscopic ultrasonography (EUS) than for CT or other modalities, and the
tumor proteins evaluated in EUS-FNB samples as biomarkers of progression and histologic diagnosis with EUS guided fine needle aspiration (EUS-FNA) was
response to treatment in patients with unresectable PC. helpful in confirming the diagnosis. For the diagnosis of PC in situ, EUS and
Patients diagnosed with unresectable PC by EUS-FNB, who received palliative magnetic resonance pancreatocholangiography (MRCP) played important roles
treatment with gemcitabine were retrospectively included. Availability of EUS- in detecting of the local irregular stenosis of the pancreatic duct. Endoscopic
FNB tissue samples embedded in paraffin block was required for final inclusion. retrograde pancreatography (ERP) and sequential cytodiagnosis of pancreatic
Candidate proteins (collagen-I, annexinA1, FAK, FAS, HSP70, SSH and MMP) juice using endoscopic nasopancreatic drainage (ENPD) multiple times were
were evaluated by specific immunohistochemistry. Statistical analysis was per- useful in the diagnosis of PC in situ.
formed by Mann-Whitney U and McNemar test. AIMS & METHODS: In 2007, Onomichi Medical Association tried to start a
RESULTS: From 277 EUS-FNB samples of patients with unresectable PC, an social program for diagnosis of the small pancreatic cancer. Specialized doctors
adequate sample for ancillary studies in patients who received palliative treat- for pancreatic cancer (SDPC) in medical centers enlightened practicing doctors
ment with gemcitabine was available in 37 patients (65.111.7 years, 62.2% about risk factors of PC, abnormal findings of US, or elevated serum pancreatic
men). Mean survival time was 220 days (range 16 to 519 days). Tumor size enzymes. Simultaneously, if practicing doctors experienced the patient with these
was 41.212.8mm. Frequencies of protein expression in tumor areas were previous problems, they actively consulted SDPC.
United European Gastroenterology Journal 2(5S) A321
RESULTS: From January 2007 to June 2013, a total of 4969 cases were con-
P0691 RISK FACTORS OF DELAYED ULCER HEALING AFTER
sulted with SDPC in Onomichi General Hospital. Methods of image diagnosis of
GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION
CT, MRI, and EUS were performed in 4157, 2303, and 1692 cases. Among these
cases, ERP was performed in 550 cases. ENPD and the repeated cytology using J.H. Lim1,*, S.G. Kim1, J. Choi1, J.P. Im1, J.S. Kim1, H.C. Jung1
1
pancreatic juice were performed in 59. EUS-FNA was performed in 257. As a Departement of Internal Medicine and Liver Research Institute, Seoul National
result, 338 cases were proved as adenocarcinoma histocytologically. There were University College of Medicine, Seoul, Korea, Republic Of
13 cases with stage 0, and 28 cases with stage Ia and Ib histopathologically.
CONCLUSION: To detect of early stage of PC, the relationship between SDPC INTRODUCTION: Post-endoscopic submucosal dissection (ESD) iatrogenic
in medical centers and practicing doctors is very important. ENPD and repeated ulcer is known to have specific histologic features and heal faster than peptic
cytology using pancreatic juice also may play important roles in diagnosis of the ulcer. However, some iatrogenic ulcers show delayed healing.
early stage of PC. AIMS & METHODS: The aim of this study is to clarify risk factors of delayed
Disclosure of Interest: None declared ulcer healing after gastric ESD. For this, we reviewed medical records of patients
who had ESD for gastric high-grade adenoma or early gastric cancer between
January 2005 and February 2012. Delayed ulcer healing was defined as sustain-
n
P0688 A COMPARATIVE STUDY BETWEEN A 22-GAUGE ASPIRATION ing unhealed iatrogenic ulcer at 3 months after the ESD. To find potential risk
w
NEEDLE AND A 25-GAUGE BIOPSY NEEDLE FOR EUS-GUIDED factors we reviewed following parameters: age, sex, comorbidity that might influ-
SAMPLING OF PANCREATIC MASS LESIONS
Y.S. Moon1,*, J.H. Kim2, M.J. Yang2, J.C. Hwang2
1
Gastroenterology, Haeundae Paik Hospital, Busan, 2Gastroenterology, Ajou
ithdra
ence mucosal healing, history of peptic ulcer, laboratory abnormalities, antipla-
telet or NSAID usage, size of the specimen, location and histologic type of lesion,
Helicobacter pylori status, and hot biopsy.
Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: EUS biopsy needles have recently been developed in order to
obtain both histologic and cytologic specimens.
AIMS & METHODS: We conducted this study to compare 22-gauge (G) aspira-
W
RESULTS: Among 2040 subjects, 11 were excluded because of anticoagulation,
3 because of embolization for post-ESD bleeding, and 346 were excluded because
of loss of 3 month follow-up endoscopy. Out of the total 1680 patients enrolled,
95 had delayed ulcer healing. In multivariate analysis, diabetes (OR 1.743; 95%
CI: 1.017-2.989, p 0.043), coagulation abnormality (OR 3.195; 95% CI: 1.535-
tion needles (FNA) and 25G biopsy needles (FNB) for EUS-guided sampling of 6.650, p 0.002), specimen size greater than 4cm (OR 2.999; 95% CI 1.603-5.611,
solid pancreatic masses. Thirty-four patients with solid pancreatic masses under- p 0.001), and hot biopsy (OR 7.149; 95% CI 1.738-29.411, p 0.006) were
went EUS-guided sampling with a 25G FNB from June 2012 to April 2013, and revealed to be independent risk factors of delayed ulcer healing. Meanwhile,
thirty-four patients with solid pancreatic masses, who underwent EUS-guided persistent Helicobacter pylori infection was not shown to be related to the delayed
sampling with a 22G FNA from June 2011 to May 2012, served as the historical ulcer healing.
control group. EUS-guided sampling was performed using the standard techni- CONCLUSION: Patients those who undergo ESD for large gastric lesions and
que without an on-site cytopathologist. massive hemostasis, especially with diabetes or coagulation abnormalities, tend
RESULTS: The diagnostic rates of cytology were 97.1% (33/34) with 22G FNA to have delayed healing of iatrogenic ulcer. For such patients initial dosage
needles and 85.3% (29/34) with 25G FNB needles (P 0.197). The diagnostic increment of PPI or addition of other anti-ulcer agents after ESD should be
rates of histology were 23.5% (8/34) with 22G FNA needles and 41.2% (14/34) considered.
with 25G FNB needles (P 0.194). There was no significant difference in the Disclosure of Interest: None declared
mean number of needle passes (5.09 vs 5.76, P 0.089) or needle malfunctions
(2.9% vs 11.8%, P 0.356) between 22G FNA and 25G FNB needles, respec-
tively. No complications were identified in either group. P0692 CHARACTERISTIC ENDOSCOPIC FINDINGS OF
CONCLUSION: The 25G FNB needle was not superior to the 22G FNA needle HELICOBACTER PYLORI-NEGATIVE EARLY GASTRIC
in the diagnostic yield of histology for EUS-guided sampling of pancreatic mass UNDIFFERENTIATED ADENOCARCINOMA
lesions, as the diagnostic yield, technical performance, and safety profiles were J. Fujisaki1,*, Y. Horiuchi1, H. Osumi1, T. Hirasawa1, T. Yoshio1,
comparable between both of them. Y. Yamamoto1
Disclosure of Interest: None declared 1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: junko.fujisaki@jfcr.or.jp
TUESDAY, OCTOBER 21, 2014 9:0017:00
ENDOSCOPY AND IMAGING II POSTER EXHIBITION HALL INTRODUCTION: Helicobacter Pylori (HP) negative gastric cancer is rare.
XL_____________________ Recently, we experienced HP negative early gastric cancer.
AIMS & METHODS: The purpose of this study is to evaluate the clinical char-
P0689 EFFECTIVENESS OF ENDOSCOPIC MANAGEMENT FOR acteristics of HP-negative Early Gastric Undifferentiated adenocarcinoma. We
ANASTOMOTIC LEAKAGE AFTER GASTRECTOMY IN GASTRIC examined 35 cases (19 males and 16 females) with 36 lesions of Helicobacter
CANCER Pylori (H.pylori)-negative Early gastric undifferentiated adenocarcinoma. All
J.Y. Lee1,*, Y.-W. Kim1, I.J. Choi1, C.G. Kim1, S.-J. Cho1, K.W. Ryu1, cases were treated by Endoscopic Submucosal Dissection. All cases had no his-
H.M. Yoon1, B.W. Eom1, S.J. Kim1 tory of H.pylori eradication, no inflammatory changes on the resected specimen,
1
Center for Gastric Cancer, National Cancer Center, Goyang, Korea, Republic Of and no sign of atrophy on endoscopy, with negative results for pepsinogen and
Contact E-mail Address: jylee@ncc.re.kr urea creath tests.
RESULTS: Of the 36 lesions, 35 were diagnosed as signet-ring cell carcinoma,
INTRODUCTION: Anastomotic leakage after gastrectomy is an important with only 1 case of poorly differentiated adenocarcinoma. The mean lesion size
determinant of early and late morbidity and mortality. Various methods for was 7.4mm. The macroscopic type was 0-IIc in 30 (83%) lesions and 0-IIb in 6
postoperative leakage are used including conservative, endoscopic or surgical lesions. 33 (92%) lesions showed pale lesion in color. The depth classification was
treatment. intramucosal in 36 lesions. Of the 36 intramucosal lesions, 3 (8%) were limited to
AIMS & METHODS: We aimed to evaluate the effectiveness and safety of the proliferative of the mucosa, 22 (61) invaded from the proliferative zone to the
endoscopic intervention for the management of leakage after gastrectomy. We upper side, and only 1 (2%) case invaded the lower mucosa. With respect to the
retrospectively reviewed 57 patients with anastomotic leakage after gastrectomy background mucosa, 25 (69%) lesion originated from the fundic gland area, 5
for gastric cancer that was treated with endoscopic interventions between (14%) originated from the intermediated zone, and 6 (17%) originated from the
December 2007 and March 2014. Clinical aspects of leakages and endoscopic pyloric glands. The inciddent of HP-N-UEG was 2.3% of all ESD cases.
managements, closure rates and treatment related complications were evaluated. CONCLUSION: HP negative early gatric cancer was rare. However, we experi-
RESULTS: Anastomotic leakages were found at esophagojejunostomy (n 26), enced HP negative early gastric undifferentiated adenocarcinoma. These cases
duodenal stump (n 14), gastroduodenostomy/gastrojejunostomy (n 10), may have considerable relevance in the near future.
wedge resection (n 3), esophagogastrostomy (n 2) or jejunal stump (n 2). Disclosure of Interest: None declared
Median size of leak was 8mm (range, 2 - 40mm). The leakages were treated by
endoclips (n 13), endoclips with detachable snare (n 31) or stent (n 13).
Simultaneously, abscess around the leak was drained by external drains P0693 CHROMOENDOSCOPY WITH INDIGO CARMINE DYE ADDED
(n 32). After endoscopic treatment, complete closure was achieved in 42 TO ACETIC ACID FOR DELINEATING EARLY GASTRIC CANCERS
patients (73.7%) and partial closure in 13 patients (22.8%). In all patients with IS USEFUL AND EASIER THAN MAGNIFYING ENDOSCOPY WITH
partial closure, final closure of leak was achieved by continuing conservative NARROW BAND IMAGING
treatment. Among remaining two patients, one with failed endoscopic treatment K. Nagao1,*, H. Noda1,1, N. Ogasawara1, T. Shimura2, M. Ebi2, S. Izawa1,
went on to receive surgery and the other died due to septic shock during endo- Y. Kondo1, Y. Ito1, Y. Tamura1, M. Sasaki1, K. Kasugai1
scopic treatment. Treatment related complication (esophageal fistula) occurred in 1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute,
one patient who was treated with stent. The complete closure rate of the leaks at 2
Gastroenterology and Metabolism, Nagoya City University Graduate School of
duodenal or jejunal stump was significantly lower than that of leaks at other sites Medical Sciences, Nagoya, Japan
(P 0.027), whereas the size of leak and the method of endoscopic management
were not associated with the complete closure rate. INTRODUCTION: Endoscopic submucosal dissection (ESD) was developed to
CONCLUSION: Endoscopic management using clips or stent represents an improve the rate of en bloc resection for early gastric cancer (EGC). Although a
effective and safe method for anastomotic leakage after gastrectomy in gastric clear diagnosis of EGC demarcation is important for proper treatment, demarca-
cancer and it can be an easily available minimally-invasive option which may tions are often obscure. To achieve a successful ESD outcome, it is very impor-
reduce leakage related mortality and morbidity. tant to accurately determine the lateral extent of the tumor. The determination of
Disclosure of Interest: None declared EGC demarcation has traditionally been performed with conventional endo-
scopy and chromoendoscopy (CE) using indigo carmine dye. However, it is
sometimes difficult to identify the margins of the tumors, especially those of
superficial or flat-type tumors. Various techniques using magnifying endoscopy
A322 United European Gastroenterology Journal 2(5S)
(ME) have been developed to enhance images of EGC demarcations. Magnifying
P0695 ADDITORY RISK FACTORS FOR PYLORIC STENOSIS AFTER
endoscopy with narrow band imaging (ME-NBI) has reportedly been useful in
ENDOSCOPIC SUBMUCOSAL DISSECTION, AND VARIOUS
overcoming this problem but the use of MENBI is limited by the technical
MANAGEMENTS
difficulties in manipulating the scopes. Therefore, easier methods are required
that make it possible to accurately determine the lateral extent of these tumors. K.S. Lee1,*, M.J. Yang1, S.J. Ahn1, S.J. Shin1
1
Chromoendoscopy with indigo carmine dye added to acetic acid (CE-IA) has Department of Gastroenterology, Ajou University School of Medicine, Suwon,
recently been reported to improve the diagnostic yield in terms of recognizing the Korea, Republic Of
tumor borders in patients with EGC. Our purpose was to compare the diagnostic Contact E-mail Address: kiseong@hotmail.com
performance of CE-IA with that of ME-NBI and conventional ME (CME). We
investigated three methods to determine which is more effective in enhancing the INTRODUCTION: Endoscopic mucosal dissection (ESD) is useful method for
recognition of EGC demarcations. local resection of early gastric neoplasia. 1,2 But, ESD can cause early and late
AIMS & METHODS: The study group included 266 lesions of consecutive 259 complications commonly known as bleeding, perforation, and stricture forma-
patients with differentiated EGC who underwent ESD at Aichi Medical tion. 3 In previous study, Coda S, et al., circumferential extent of a mucosal
University Hospital between January 2006 and March 2014. The recognition defect 4 3/4 and longitudinal extent 45 cm were each significantly related to
of demarcations were evaluated using CME (n 193), ME-NBI (n 43) and the occurrence of post-ESD stenosis in both cardiac and pyloric resections. And
CE-IA (n 30). All observations were made on optimal foci and at the highest endoscopic balloon dilatation can be an effective treatment of them. 4
magnification ratios possible. For CE-IA, 2030 mL of 1.5% acetic acid was AIMS & METHODS: The aim of this study is to clarify the previous risk factors
sprinkled onto the lesion and 10-20 mL of 0.2% indigo carmine dye was similarly and determine the additory risk factor. And we report another management
sprinkled 30-60 seconds later using a washing pipe. The recognition of demarca- methods for pyloric stenosis after ESD. Retrospectively a total of 1621 early
tions between the lesion and the normal mucosa were classified as distinct or gastric neoplasia resected by ESD at a single institution between 2005 and
indistinct by observation of CME, ME-NBI and CE-IA. 2012. Pyloric stenosis is defined when a 1 cm diameter endoscope could not
RESULTS: The demarcations of the lesions were distinct in 64.8% (125/193) passed through the pyloric ring.
with CME, in 81.4% (35/43) with ME-NBI and in 90.0% (27/30) with CE-IA. RESULTS: Among 126 cases which resected from the pylorus, stenosis occurred
ME-NBI and CE-IA clarified the demarcation in a significantly higher percen- in six cases. Significant differences were found between longitudinal diameter
tage compared with CME (P50.05). However, the determination rate of EGC of resected specimen (5cm) and the others (55cm) (odd ratio 15.362,
demarcation did not differ between ME-NBI and CE-IA. The mean duration of p 0.037), circumferential mucosal defect over the half (270 ) and the others
determination procedure for demarcation with CE-IA was significantly shorter (5270 ) (odd ratio 23.840, p 0.015). Also the number of repeated ESD was
than that with ME-NBI (6.973.75 min vs. 8.57 4.33 min, P50.05). significant different between the single lesion and the others (2 times) (odd
CONCLUSION: CE-IA and ME-NBI are useful in determining the lateral extent ratio 26.169, p 0.040). Six patients of pyloric stenosis received endoscopic
of EGCs. The mean duration of determination procedure for EGC demarcation balloon dilatation for treatment of post-endoscopic resection stricture and 4
was significantly reduced using CE-IA compared with ME-NBI. The demarca- patients has improved symptoms. But two patients received an additional pro-
tions of EGDs were recognized most easily using CE-IA. cedure for treatment of pyloric stenosis. One of them underwent subtotal gas-
Disclosure of Interest: None declared trectomy and other was treated with metallic pyloric stent.
CONCLUSION: The risk factors of pyloric stenosis were the longitudinal dia-
meter of resected specimen (45cm) and circumferential mucosal defect over 75%
P0694 CLINICOPATHOLOGICAL FACTORS INFLUENCE ACCURATE of pyloric ring in this study. In addition, repeated ESD limited pylorus also
ASSESSMENT OF ENDOSCOPIC ULTRASONOGRAPHY FOR caused pyloric stenosis. We thought the diameter of specimen and circumferential
EARLY GASTRIC CANCER defect are important factors as previous study. 4 And this study revealed another
K. Yanamoto1,*, N. Ogasawara1, T. Shimura2, A. Shimozato1, Y. Kondo1, risk factor: repeated procedure is additional risk factor of pyloric stenosis after
H. Noda1, Y. Ito1, M. Sasaki1, K. Kasugai1 ESD. In treatment of post-endoscopic resection stricture, balloon dilatation is
1
Aichi Medical University School of Medicine, Nagakute, 2Department of effective treatment. But, according Coda S, et al., procedure is needed more than
Gastroenterology and Metabolism, Nagoya City University Graduate School of nine times on average. 4 Frequent the procedures decrease quality of life.
Medical Sciences, Nagoya, Japan Therefore more confident short-term treatment is needed. Pyloric stent is
useful management of pyloric stricture. But it is too expensive and has complica-
INTRODUCTION: The advent of endoscopic ultrasonography (EUS) has sig- tions like stent-migration. This is must be resolved first.
nificantly improved the preoperative diagnosis and staging of gastric cancers. REFERENCES
EUS is the most reliable nonsurgical method available for assessing primary 1. Rembacken BJ, Gotoda T, Fujii T, et al. Endoscopic mucosal resection.
tumor with a high diagnostic rate of accuracy in staging gastric cancer. This Endoscopy 2001; 33: 709-718.
assessment is an important factor in choosing a proper treatment such as endo- 2. Soetikno RM, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection.
scopic resection or surgery. Especially in early gastric cancers (EGC), the size, Gastrointest Endosc 2003; 57: 567-579.
gross appearance, histologic diagnosis, degree of differentiation, and depth of 3. Oda I, Suzuki H, Nonaka S, et al. Complications of gastric endoscopic sub-
invasion are very important factors to be considered for therapeutic decision mucosal dissection. Dig Endosc 2013; 25(Suppl. 1): 71-78.
making. Endoscopic submucosal dissection (ESD) currently is widely accepted 4. Coda S, Oda I, Gotoda T, et al. Risk factors for cardiac and pyloric stenosis
as a standard treatment strategy for EGC without any risk of lymph node after endoscopic submucosal dissection, and efficacy of endoscopic balloon dila-
metastasis because the ESD procedure facilitates en bloc resection even in tion treatment. Endoscopy 2009; 41: 421-426.
patients with large or ulcerous lesions. Therefore, it has become more important Disclosure of Interest: None declared
in treatment planning to determine the depth of invasion accurately before treat-
ment. The aim of this study was to evaluate the clinicopathological factors affect-
ing the diagnostic accuracy of EUS and to compare the diagnostic accuracy P0696 ULTRA THIN ENDOSCOPE WITH NARROW BAND IMAGING
evaluated by endoscopic findings with that by EUS in EGCs. (NBI) IN DIAGNOSTIC OF GLUTEN DEPENDENT AND
AIMS & METHODS: During the period from April 2009 to January 2014, 136 INDEPENDENT SMALL INTESTINAL ATROPHY IN INFANT AND
patients (94 men and 42 women; age range, 44-88 years; mean age, 72.1 years) UP TO 36 MONTHS AGE CHILDREN
with an endoscopic diagnosis of EGCs underwent EUS to define pretreatment K. Marakhouski1,*
staging. Diagnoses of invasion depth by EUS or endoscopic findings were 1
Endoscopy, RSPC "Mother and child", Minsk, Belarus
divided into intramucosal (M) and submucosal invasion (SM). All patients
underwent curative treatment by either ESD or standard surgical intervention, INTRODUCTION: Using high-resolution endoscopy is sharply limited at this
and all lesions were evaluated by histopathological examination. Both EUS- age. It remains unclear whether there are differences in the high-resolution endo-
determined diagnosis and conventional endoscopy-determined diagnosis were scopic assessment of the small intestinal mucosal pit pattern at congenital intest-
compared with the final histopathological evaluation of resected specimens, inal atrophy (non gluten) and atrophy at a gluten sensitivity enteropathy.
and the impact of various clinicopathological parameters on diagnostic accuracy AIMS & METHODS: Inclusion criteria were: child wasnt older 36 month and
was analyzed. has low weight gain (WHO criteria) and non bloody diarrhea. Investigation
RESULTS: The accuracy of invasion depth were 83.0 % for EUS and 74.5 % for performed with permission and control of the local ethic committee. We analyzed
conventional endoscopy, respectively. There was significant difference related endoscopy results of 32 cases (13 girls).
with the accuracy of invasion depth between EUS and endoscopic findings Endoscopy: the EXERA III with an endoscope GIF - N180 4.9 mm in diameter
(p50.01). The diagnostic accuracy of EUS for predicting tumor invasion depth was used Evaluation of duodenal mucosa was done with narrow band imaging
was significantly affected by the tumor location and the tumor size. Lesions (NBI, more brightly than in EXERA II light source) and for additional sign of
located in the posterior wall of the stomach larger than 3 cm were significantly atrophy water flow with addtion of semethicon was done too. Two biopsy speci-
associated with lower diagnostic accuracy in predicting the tumor invasion. These mens were taken minimally. The description of a biopsy was carried out by a
lesions had higher probability of overstaging estimated by EUS. However, no standard technique with special orientation biopsies specimens, by two indepen-
significant differences were found in histopathological differentiation, tumor dent pathology experts. Four criteria were used for endoscopic and histological
gross appearance and ulceration. Unexpectedly, the observation time for EUS (HYS) intestinal atrophy assessment: definitely yes, probably yes, probably no,
was the same as that for conventional endoscopy (6.83.1 minutes vs. 6.14.2 definitely no. The main group was divided on two subgroups: A - age up to 6
minutes). months (group of strictly non gluten enteropathy) and B - 6 - 36 months (prob-
CONCLUSION: EGCs larger than 3 cm located in the posterior wall of the ably gluten dependent enteropaty).
stomach should be cautiously considered in the decision on treatment modality RESULTS: Age in group A (N 17) was: mean 2.9 (CI 95% 2-4), median -
by pretreatment EUS staging. Moreover, observation time for EUS was so short 3.0 (CI 95% 1-4). Frequency of the HYS definitely yes atrophy was in 5,
that a sedation was not considered to be required during EUS investigation. probably yes- 1. Atrophy rate was 35% (Exact 95% C. I. (Fishers) 14.2-
Disclosure of Interest: None declared 61.7). Frequency of the endoscopic definitely yes atrophy was in 6, probably
yes- 2. Endoscopy sensitivity 0.67(CI 95% 0.35 - 0,88, specificity 1,00 (CI
95% 0.68 - 1,0), odds ratio (Fleiss)- 33(CI 95% 1,6 - 151,23). If endoscopy
negative, expected HYS negative will definitely to no atrophy.
United European Gastroenterology Journal 2(5S) A323
Age in group B (N 15) was: mean 23,5 (CI 95% 18,5-28,4), median - 21,0
P0698 DEVELOPMENT OF PROPOFOL SEDATION FOR
(CI 95% 17-33). Frequency of the HYS definitely yes atrophy was in 4, prob-
THERAPEUTIC ENDOSCOPY UNDER DEEP SEDATION WITH
ably yes- 0. Atrophy rate was- 26,7% (Exact 95% C. I. (Fishers) 7,8-55,1), and
SPONTANEOUS RESPIRATION
not different significant from group A. Frequency of the endoscopic definitely
yes - atrophy was in 4, probably yes - 1case. Sensitivity 0.8 (CI95% 0.38 - 0,96; K. Matsumoto1,*, K. Matsumoto1, A. Nagahara1, Y. Nakagawa1, H. Ueyama1,
specificity 1,00 (CI95% 0.72 - 1,00), odds ratio (Fleiss) 63 (2,22 - 313,23), and Y. Shimada1, D. Asaoka1, M. Hojo1, S. Watanabe1
1
LR (Test Negative) 0.2. gastroenterology, juntendo univ., bunkyo-ku, Japan
CONCLUSION: In infant and up to 36 months age children with low weight
gain and non bloody diarrhea small intestinal atrophy rates are from 14.2% to - INTRODUCTION: In recent years, propofol sedation has attracted attention for
61.7%. We found no difference in the two groups (gluten associated or not) used use during therapeutic endoscopy under deep sedation with spontaneous respira-
to assess ultra thin with NBI endoscopy sensitivity, specificity, and it has value as tion. However, a standard protocol for propofol sedation has not yet been
a good standard for visual endoscopic evaluation of duodenal villi changes as a established.
method for exclusive intestinal atrophy. AIMS & METHODS: Our aim was to establish a simple and safe protocol for
Disclosure of Interest: K. Marakhouski Other: "Olympus" CIS expert propofol sedation during therapeutic endoscopy. This study retrospectively
investigated 89 patients (67 male, 22 female; mean age 71.2 years) who underwent
endoscopic submucosal dissection (ESD) or endoscopic mucosal resection
P0697 PROSPECTIVE ASSESSMENT OF THE LEVEL OF TEMPORAL (EMR) of the esophagus and stomach under anaesthesia with 1.0% propofol.
AROUSAL AND SAFETY OF NURSE-ADMINISTERED PROPOFOL Patients were assigned to 1 of 5 groups (phases 1 5) each corresponding to a
SEDATION FOR ESOPHAGOGASTRODUODENOSCOPY different dosing protocol. After beginning phase 1, when it was deemed that the
K. Kusumoto1,*, A. Hamada1, Y. Mizumoto2 dose of propofol was insufficient or excessive, the dose was adjusted and the next
1
Tango central hospital, Kyotango, 2National Hospital Organization Kyoto phase was begun in a different group of patients. In all phases, the initial dose of
Medical Center, Kyoto, Japan 1.0% propofol was administered after bolus injection of pethidine hydrochloride
Contact E-mail Address: kusumoto1024@gmail.com (0.5 mg/kg), and 1.0 mL of propofol was added every minute until anaesthesia to
level 6 on the Ramsey Sedation Scale was achieved. Subsequently, continuous
INTRODUCTION: Propofol sedation is widely used, mainly in Europe and the drip infusion was performed to maintain the depth of sedation. Induction and
US, not only as an induction agent for general anesthesia but also in the field of maintenance doses in each phase are shown in the table below. When the patient
gastroenterological endoscopy. Especially in the US, the certified registered nurse showed movement, a bolus injection of 1.0 mL propofol was repeated every
anesthetists perform general and local anesthesia for many endoscopic proce- minute until suitable sedation was obtained, and continuous drip infusion was
dures under anesthesia management, independently from doctors. However, increased to a dose of 5 mL/h. Oxygen saturation and blood pressure were
quite a few states prohibit individuals other than anesthetists from performing monitored during all procedures. A BIS monitor was used at phase 5.
propofol sedation from the safety aspect. Propofol sedation, which is easy to Continuous drip infusion was stopped temporarily under the following condi-
give and wean off, by nurse-administered propofol sedation (NAPS) is quite tions: SpO2 590%, BP 580 mm Hg, or BIS score 560 (5 seconds or more).
meaningful, and could thereby reduce labor costs and charges for recovery rooms Following recovery, the rate of continuous drip infusion was decreased to 5 mL/
and curb medical expenses. h. We calculated the dose of propofol at the time of induction and during the
AIMS & METHODS: We prospectively examined the safety of propofol seda- maintenance phase, the number of additional bolus injections, and the average
tion at the time of esophagogastrodudenoscopy (EGD). Between July 2013 and total dose of propofol. The incidence of cardiorespiratory suppression was eval-
January 2014, EGD was performed under NAPS in outpatients, and time to uated for each phase. The incidence of BIS below 60 was also evaluated in phase
arousal and safety were prospectively assessed. Propofol was administered manu- 5.
ally in a prespecified regimen, and, before the test and at 10 and 60 min after the RESULTS: During induction, no cardiorespiratory suppression occurred in any
test, the mean blood pressure, Sp02, grasping power of both hands, visual acuity of the phases. During the maintenance phase, circulatory suppression occurred
of both eyes, Mini Mental State Examination (MMSE) score, and reflex nerve more frequently in phases 1-4 than in phase 5. In contrast, no respiratory sup-
test were assessed and compared. pression occurred in any of the phases.
We hypothesized that MMSE score recovers to the pretest value 60 min after Table: Propofol dosing and the incidence of adverse events during each phase of
the completion of EGD under propofol sedation. To prove this hypothesis, we study
tested non-inferiority of MMSE at 60 min after the test against that before the CONCLUSION: This newly developed propofol anesthesia protocol (phase 5)
test. We calculated that 87 eligible patients were needed to obtain a significant could be safe for therapeutic endoscopy under deep sedation with spontaneous
difference, and estimated the number of patients to be included at 104, expecting respiration.
20% of the patients to be ineligible. Quantitive variables were evaluated by t-test, Disclosure of Interest: None declared
and the significance level of 50.05 was considered statistically significant.
RESULTS: 95 patients (mean age: 55.5 14.9 years; male/female ratio: 37/58
cases; mean examination time: 315.6 115.8 s; mean induction dose of propofol: P0699 MAGNIFICATION ENDOSCOPY WITH ACETIC ACID-
0.097 0.019 mL/kg; and mean total dose: 0.129 0.027 mL/kg) were included ENHANCEMENT AND NARROW-BAND IMAGING FOR
for analysis. All patients could be successfully sedated and opened their eyes PREDICTING HISTOLOGIC CHARACTERISTICS OF GASTRIC
immediately after the test. Before the test vs. 10 min after the test, the mean MUCOSAL NEOPLASMS
blood pressure (mmHg) was 95.19 13.20 vs. 90.13 12.34 (p 5 0.01); grasping K. Shibagaki1,*, Y. Amano2, N. Ishimura3, H. Taniguchi4, H. Fujita1,
power of right hand (kg) was 27.7 8.08 vs. 26.2 8.49 (p 5 0.01); grasping K. Kobayashi5, Y. Kinoshita3
power of left hand (kg) was 26.4 8.08 vs. 25.3 8.22 (p 5 0.01); and MMSE 1
Gastroenterology, Tottori Municipal Hospital, Tottori, 2Gastroenterology, Kaken
(points) was 27.3 2.2 vs. 26.8 2.4 (p 5 0.05); all of which showed significant Hospital, International University of Health and Welfare, Ichikawa,
differences. Before the test vs. 60 min after the test, the mean blood pressure 3
Gastroenterology, Faculty of Medicine, Shimane University, Izumo, 4Tottori
(mmHg) was 95.19 13.20 vs. 91.80 11.88 (p 5 0.01), showing a significant Municipal Hospital, Tottori, Japan, 5Pathology, Tottori Municipal Hospital,
decline. No occasional symptoms were observed in all patients. Tottori, Japan
CONCLUSION: EGD under NAPS was performed safely and all factors other
than mean blood pressure returned to the pretest condition 60 min after the test. INTRODUCTION: Magnification endoscopy with narrow-band imaging
Blood pressure was also in an acceptable range as per discharge criteria, and the (NBIME) that visualizes the capillary patterns of gastric surface structure is
patients were considered to be allowed to be safely discharged from hospital after useful for predicting the histologic characteristics of superficial gastric neo-
60 min. plasms. NBIME with acetic acid-enhancement (A-NBIME) clearly visualize the
REFERENCES microstructure pattern of gastric mucosal surface.
Dumonceau JM, Riphaus A, Aparicio JR, et al. European society of gastroin- AIMS & METHODS: We performed a prospective study to compare the diag-
testinal endoscopy, european society of gastroenterology and endoscopy nurses nostic reliability of white light endoscopy (WLE), NBIME, and A-NBIME for
and associates, and the european society of anaesthesiology guideline: non- the histologic characteristics of gastric mucosal neoplasms. Consecutive 220 gas-
anesthesuiologist administration of propofol for GI endoscopy. Endoscopy tric neoplasms (49 adenomas, 144 differentiated adenocarcinomas, and 27 undif-
2010; 42: 960-974. ferentiated adenocarcinomas) were photographed with WLE, NBIME and A-
Disclosure of Interest: None declared NBIME.
Macroscopic patterns by WLE, capillary patterns by NBIME and microstructure
patterns by A-NBIME were respectively classified into type M1/M2/M3, type
C1/C2/C3/C4 and type S1/S2/S3, by referring to the previously reported
Table to abstract P0698
Phase1 (n27) Phase 2 (n11) Phase 3 (n7) Phase 4 (n14) Phase 5 n30)
Dose of initial bolus injection (mg/kg) 0.5 0.33 0.5 0.5 0.5
Dose of continuous drip infusion (mg/kg/h) 5 3.3 3.3 2.5 2.5
Average number of additional bolus injections at introductory phase 1.07 (06) 4.0 (113) 1.6 (05) 3.8 (07) 3.6 (017)
Average number of increasing maintenance dose 0.7 (05) 1.5 (02) 1.3 (05) 2.6 (15) 1.9 (07)
Average total dose (mL) 48.5(17109) 60.1 (24135) 49.6 (16133) 44.4 (1295) 52.1 (7.5170)
SpO2 5 90% 0 0 0 0 0
Blood pressure 5 80 mm Hg 11 (40.7%) 3 (27.3%) 3 (42.9%) 4 (28.6%) 3 (4.8%)
BIS score 5 60 (45 seconds) NA NA NA NA 1 (1.6%)
A324 United European Gastroenterology Journal 2(5S)
classifications as described below. Macroscopic pattern; Type M1: the protruded
P0701 GASTRIC ATROPHY WAS A RISK FACTOR FOR THE
and whitish lesions with roundish edge and smooth or often nodular surface.
PRESENCE OF MISSED SYNCHRONOUS LESION AFTER
Type M2: the irregular-shaped and depressed, flat, or elevated lesion in red or
ENDOSCOPIC SUBMUCOSAL DISSECTION
similar color to the surrounding mucosa. Type M3: the depressed and whitish
lesions often with variously sized nodules on the lesion. Capillary pattern; Type K.H. Kim1,*, S. I. Seo1, B.Y. Choi1
1
C1: capillaries with homogenous diameters and distributions. Type C2: capil- Department of Internal Medicine, Division of Gastroenterology & Hepatology,
laries with heterogeneous diameters and irregular distributions. Type C3: capil- Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul,
laries grow in disorder with unclear mucosal microstructure. Type C4: capillaries Korea, Republic Of
are invisible or obviously decreased. Microstructure pattern; Type S1: glandular Contact E-mail Address: minsoksumin@naver.com
crypts present, homogeneously sized, shaped and arranged foveolae or grooves.
Type S2: glandular crypts present, heterogeneous. Type S3: glandular crypts are INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
absent or severely decreased. accepted as a minimally invasive therapy for gastric adenoma or early gastric
Endoscopic images were independently reviewed by three expert endoscopists. cancer (EGC). However, the risk of secondary gastric neoplasms developing
Type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME, and type S1/S2/S3 in A- during the surveillance period after ESD has become a important medical pro-
NBIME were used as the indicator of adenoma/differentiated adenocarcinoma/ blem. In particular, there is a high possibility that ESD can miss synchronous
undifferentiated adenocarcinoma, respectively. Type C4 in NBIME was excluded gastric neoplasms compared with surgery.
from the analysis of histologic diagnostic accuracy. The histologic diagnostic AIMS & METHODS: In the present study, we aimed to investigate predictive
accuracy and interobserver diagnostic agreement was compared among factors associated with the presence of missed synchronous gastric neoplasms
modalities. after ESD for gastric adenoma or EGC. We performed ESD in 370 patients
RESULTS: The kappa values of interobserver agreement for WLE, NBIME, and with EGC or gastric adenoma from January 2008 through December 2012 at
A-NBIME diagnosis were 0.33(0.31-0.36), 0.58(0.55-0.61), and 0.61(0.54-0.67), our institution. The patients with endoscopic surveillance interval less than 1
showing an insufficient diagnostic agreement for WLE and a statistically good year, patients without curative resection, and patients with additional surgery
diagnostic agreement for both NBIME and A-NBIME. Adenomas/differentiated were excluded from the study. Missed synchronous gastric neoplams were
adenocarcinomas/undifferentiated adenocarcinomas were statistically related to defined as any gastric neoplasms detected within one year after ESD, but initially
type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME and type S1/S2/S3 in A- unidentified. We compared clinical, endoscopic, and pathological factors
NBIME, respectively (P50.01). Type C4 of capillary pattern by NBIME did not between patients with missed synchronous gastric neoplasms and patients with-
show a statistical correlation to the specific histologic characteristics. The diag- out missed synchronous gastric neoplasms.
nostic accuracy of WLE, NBIME, and A-NBIME were 79.0%, 74.1%, and RESULTS: Missed synchronous gastric neoplasms were found in 4.3% (16/370)
90.5%, showing statistical superiority of A-NBIME (P50.01). No additional of the patients. Among the 16 missed synchronous gastric neoplasms, three
effect of NBIME to WLE. (18.8%) cases were carcinomas. In the univariate analysis, open-type gastric
CONCLUSION: A-NBIME is superior to WLE and NBIME in the predictive atrophy, gastric atrophy and intestinal metaplasia more than moderate degree
histological diagnosis of gastric mucosal neoplasms with good clinical feasibility. were significantly associated with the presence of missed synchronous gastric
Disclosure of Interest: None declared neoplasms. In multivariate logistic regression analysis, only gastric atrophy
more than moderate degree was the independent risk factor for the presence of
missed synchronous gastric neoplasms (Exp (B) 8.608, 95%CI: 1.03645.549).
P0700 HIGHEST POWER MAGNIFICATION IS SUPERIOR TO LOW CONCLUSION: Gastric atrophy could be an independent risk factor for the
POWER MAGNIFICATION FOR DELINEATION OF EARLY presence of missed synchronous lesion after ESD. Careful endoscopic surveil-
GASTRIC CANCERS USING NARROW BAND IMAGING lance should be performed after ESD for patients with severe gastric atrophy.
K. Uchita1,*, K. Yao2, N. Uedo3, T. Iwasaki1, K. Kjima1, A. Kawada1, Disclosure of Interest: None declared
M. Okazaki1, S. Iwamura1
1
Gastroenterology, Kochi Redcross Hospital, Kochi, 2Endoscopy, Fukuoka
University Chikushi Hospital, Fukuoka, 3Gastrointestinal Oncology, Osaka P0702 EFFECT OF ELECTRICAL CURRENT MODE ON CLINICAL
Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan COURSE AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL
Contact E-mail Address: ucchy31@yahoo.co.jp DISSECTION
K.H. Song1,*, S.M. Kim1, J.H. Park1, K.C. Huh1
INTRODUCTION: Curative endoscopic submucosal dissection (ESD) of early 1
Konyang University, Deajon, Korea, Republic Of
gastric cancers requires accurate determination of the horizontal extent of inva- Contact E-mail Address: postit2@daum.net
sion. A number of studies have since reported superior diagnostic ability for
magnifying endoscopy with narrow-band imaging (ME-NBI) over conventional INTRODUCTION: Several modes of electrical current are available for endo-
endoscopy (CE) in delineating the lateral extent of early gastric neoplasias. scopic submucosal dissection (ESD) of gastric epithelial tumor. There has been
However, there are few studies that have reported the actual magnifying ratio no data regarding whether the electrical current mode effects on clinical course
used when performing ME. The added benefits of ME-NBI over CE in terms of after gastric ESD, including incidence of post ESD coagulation syndrome, ulcer
the difference in magnification level have yet to be elucidated. healing rate.
AIMS & METHODS: The aim of this study was to investigate the improvement in AIMS & METHODS: AIM Clinical courses were surveyed according to the
diagnostic accuracy for tumor delineation obtained with different magnification setting of two different dissecting mode: endocut or swift, to provide relating
levels of ME-NBI following CE. This study comprised a series of 161 consecutive data on optimal adoption of mode for gastric ESD.
early gastric cancers resected en bloc using ESD in 158 patients between July 2008 METHODS Among 286 consecutive sessions of gastric ESD, 200 lesions were
and June 2012. Each patient underwent sequential CE, LM-NBI and HM-NBI surveyed after excluding cases: usage of endoknives other than IT2 knife, tumor
examinations during the same procedure as preoperative diagnostic examinations with nearby scar, synchronous tumor, subepithelial tumor. Only one of endocut
1 to 2 weeks prior to ESD. On the day of the ESD procedure, or the preceding day, or swift mode was adopted for submucosal dissection in eaach session of ESD.
using HM-NBI we again identified the lesion margin, and made markings 3-5 mm All the procedure were performed using an electrosurgical unit, VIO 300D
outside the DL. After ESD with reference to the pathohistological findings, we (ERBE, Germany). The ESD pathology, location of tumor, procedure and resec-
identified the markings, and reconstructed the lateral extent of the cancer on the tion time, incidence of post ESD syndrome were assessed with demographic data.
each endoscopic image (CE, LM-NBI, HM-NBI). The histologically determined Patients with pyrexia (body temperature 438.3_C) and upper abdominal pain or
cancer margins were used as the gold standard. The primary endpoint was the tenderness after ESD, with or without symptoms of peritoneal irritation were
added benefit, as measured using the successful delineation rate, for the delineation defined as having post ESD coagulation syndrome. Follow up endoscopy was
of gastric cancer margins using CELM-NBI vs CE, and for CELM-NBIHM- performed at 3 months after the endoscopic therapy and rated as ulhealed if the
NBI vs CELM-NBI. We derived the successful delineation rate with 95% con- ulcer was in A1 to H2 rated by Sakita-Miwa stage.
fidence intervals (CI) for early gastric cancers using each examination method, CE, RESULTS: In total of 200 sessions, we applied endocut mode for 116 cases
CELM-NBI, and CELM-NBIHM-NBI and used McNemars test with (58%) and swift mode at for 84 cases (42%). The demographic data between
Bonferronis multiple comparison correction to calculate p values. the two groups were not significantly different. Total of 16 post ESD coagulation
RESULTS: The clinical characteristics were as follows: average age 71 years; 116 syndromes were notified. Multivariate analysis revealed adoption of swift mode
males and 45 females; mean lesion diameter 19.2 mm (14.4 mm, range 5-120 (OR 6.90, 95%CI: 1.83-25.92) and malignant pathology (OR 5.93, 95%CI: 1.46-
mm); and macroscopic type using the Paris classification type 0-I 4 lesions 24.02) was related post ESD coagulation syndrome. Ulcer healing rate judged at
(2.5%), type 0-IIa 64 lesions (39.8%), type 0-IIb 38 lesions (23.6%), and type 3 months after ESD tended to be delayed for endocut mode, even though it was
0-IIc 55 lesions (34.2%). The location of the lesion was the upper part of the not statistically significant.
stomach in 46 cases (28.6%), middle part in 41 (25.5%), and lower part in 74 CONCLUSION: Mode of electrical current may be related to the incidence of
(46.0%). The successful delineation rates (95% CI) using CE, CELM-NBI and post ESD coagulation syndrome or ulcer healing after gastric ESD. Randomized
CELM-NBIHM-NBI were 72.7 (68.5-79.9%), 88.9 (83.9-93.7%), and 98.1 and controlled studies are warranted.
(95.8-100%). The diagnostic accuracy improved significantly for CELM-NBI REFERENCES
compared with CE (P50.001) and for CELM-NBIHM-NBI compared with Lee H, et al. Clinical features and predictive factors of coagulation syndrome
CELM-NBI (P50.001). after endoscopic submucosal dissection for early gastric neoplasm. Gastric
CONCLUSION: ME-NBI is an extremely useful modality for the delineation of Cancer 2012; 15: 83-90.
the margins of early gastric cancers. HM-NBI is superior to LM-NBI in improv- Disclosure of Interest: None declared
ing the successful delineation rate, following CE.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A325
Table 1. Demographic, endoscopic procedures, propofol dose and adverse events
P0703 TRANASAL VERSUS PERORAL PERCUTANEOUS
in both groups
ENDOSCOPIC GASTROSTOMY: A PROSPECTIVE CASE
Table to abstract P0704
CONTROL STUDY
L.-F. Lin1,* Propofol AE (%)
1
Gastroenterology, Pingtung Christian Hospital, Pingtung, Taiwan, Province of ASA I/II/III Colonoscopy dose EGD / Desaturation/
China Age Weight (%) EGD n n (%) Colonoscopy Bradycardia
Contact E-mail Address: lin.lian.feng@gmail.com
75 years 81 4 68.56 12,4 17.3/70.3/12.4 439 307 72.99 37.4/ 2.6/0.3
80.5934
INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a challenge
575 years 51.3 13 68.55 12,4 62.8/34.9/2.3 439 307 120.54 4.8**/ 0.8/0.3*
in patients with difficult oral intubation. Some cases of successful transnasal 129.12 55.9**
insertion of PEG were reported. But no any case control study was conducted
to compare transnal and oral insertion of PEG.
AIMS & METHODS: This work is to investigate the difference between trans-
nasal and peroral insertion of percutaneous endoscopic gastrostomy in clinical Data are presented as mean SD (range: 95% CI of the mean). Abbreviations:
outcome. A prospective, case-control study was conducted to compare transnasal ASA (American Society of Anaesthesiology); EGD
(T-PEG) and peroral (O-PEG) placement of a 20 Fr PEG tube in dysphagic (Esophagogastroduodenoscopy). AE: adverse events. *P 5 .005; **P 5 .001
patients without conscious sedation. Additional spraying lidocain solution and CONCLUSION: Propofol is safe when administered by non-anesthesiologists.
epinephrine solution to the nasal cavity and using ultrathin 5 mm endoscope Patients 75 years globally require almost 40% less propofol than patients 575
(Olympus GIF-N-260) were applied to the T-PEG. The other premedication years. These results support the use of a lower dose of propofol in the elderly.
and procedure are same as conventional pull-method PEG. Neither the nasal REFERENCES
cavity nor the oral cavity were decolonized in all patients. The success rate, Disclosure of Interest: None declared
operation time, occurrence of choking during PEG, nasal bleeding, stomal site
infection, post-PEG complication were recorded and analyzed.
RESULTS: Thirty-nine insertions of T-PEG and thirty-eight insertions of O- P0705 CHANGES IN GASTRIC INTESTINAL METAPLASIA
PEG were attempted in 77 chronic dysphagic patients form home or nursing EXTENSION IN ANNUALLY FOLLOWED-UP PATIENTS: 1-YEAR
home. Mean age is (T-PEG vs O-PEG) 76.310.3 vs 79.56.9 years, male RESULTS OF A STUDY PERFORMED BY MEANS OF NARROW
gender 67% vs 48%, operation time 14.6 4.0 vs 113 minutes (p: 0.028), BAND IMAGING WITH MAGNIFICATION ENDOSCOPY
choking occurred in 3 vs 5 patients. One failed insertion and two nasal bleeding L. Gemignani1, P. Dulbecco1, E. Giambruno1, G. Bodini1,*, M. Furnari1,
occurred in T-PEG. There are nine stomal site infection (8 pseudomonas aeru- M. Giacchino1, F.E. Gianiorio1, L. Mastracci2, F. Grillo2, F. Sarocchi2,
ginosa infection including one systemic infection) in T-PEG and 14 stomal site V. Savarino1, E. Savarino3
infects (8 pseudomonas aeruginosa) in O-PEG (p 50.001). One systemic infec- 1
Department of Internal Medicine, 2Department of Pathologic Anatomy,
tion of urinary tract, one buried bumper, and one soiling of stoma were observed University of Genoa, Italy, Genoa, 3Department of Surgical, Oncological and
respectively in T-PEG and O-PEG. No PEG related mortality occurred within 3 Gastroenterological Sciences, University of Padua, Padua, Italy
months after all PEG procedures. Contact E-mail Address: alphaone81@gmail.com
CONCLUSION: Transnasal insertion is feasible in placing a 20 Fr PEG but it
causes rare nasal bleeding rate and needs longer operation time. Stomal site INTRODUCTION: Gastric Intestinal Metaplasia (GIM) is a precancerous con-
infection is less but more dominant pseudomonas infection occurred in T- dition potentially leading to gastric cancer. However, this occurs in a limited
PEG. In conclusion, T-PEG is an alternative for patients who had difficulty in number of cases and, therefore, the need of endoscopic surveillance and
oral intubation. It needs more studies to concern the prophylaxis of pseudomo- follow-up is controversial. Moreover, there is no universal consensus regarding
nas infection. which patients should be better investigated and followed-up in the long-term
Disclosure of Interest: None declared period. Most of the experts among pathologists and gastroenterologists recom-
mend to perform an upper endoscopy with multiple biopsies every three-year
only in patients with extensive GIM, but no studies have validated the effective-
P0704 PROPOFOL REQUIREMENTS FOR GASTROINTESTINAL ness of this protocol, so far.
ENDOSCOPY IN PATIENTS OLDER THAN 75 YEARS OLD AIMS & METHODS: Our aim was to investigate whether changes in extension
L. Achecar1,*, X. Garc a Aguilera1, A. Gonzalez1, M. Del R o1, G. Arranz1, and/or progression of GIM occur during a strict yearly endoscopic follow-up
M.Van Domselaar1 program. Between November 2011 and December 2013, we prospectively eval-
1
Endoscopy unit, Hospital Universitario de Torrejon de Ardoz, Madrid, Spain uated consecutive patients with an histologically defined diagnosis of GIM by
Contact E-mail Address: xagarcia@torrejonsalud.com means of Narrow Band Imaging with Magnification Endoscopy (NBI-ME) and
multiples gastric biopsies (2 antrum 1 angulus 2 corpus). Helicabacter pylori
INTRODUCTION: Numerous studies support the efficacy and safety of propo- infection was excluded. Patients with a GIM extension higher than 20% were
fol in digestive endoscopy in which propofol is administered by non-anesthesiol- offered to repeat the endoscopic examinations every year and, to date, 20 out of
ogist during endoscopic procedures. There is literature on the safety of sedation 121 accepted and were included in the follow-up program. Endoscopic examina-
with propofol in elderly patients. However, there are no clear guidelines regard- tions have been performed by experienced endoscopists (each of them with more
ing the dose of propofol to be used in this group of patients in which comorbidity than 1000 NBI-MEs performed). Biopsies were taken at sites suggestive for GIM
can make them more fragile, making the standard dose/kg of weight excessive to based on NBI-ME appearance (i.e. presence of light blue crests on the surface of
achieve a safe sedation. gastric mucosa) or randomly if no evident mucosal alterations were seen. Biopsies
AIMS & METHODS: The aims of this study were to establish the dose of were assessed by two expert and blinded pathologists, who evaluated the percen-
propofol in patient 75 years compared with patients 575 years and to evaluate tage of extension of GIM at both times.
the safety of propofol when is administered by non-anesthesiologist. Between RESULTS: The median time between the two observations was 13 months
June 2012 and March 2014, we prospectively recorded all endoscopic procedures (range 11-18). As shown in the Table, patients were divided in three categories,
and safety data. Only diagnostic procedures were included for this study. We according to the changes in GIM extension, which was considered stable if there
excluded: patients 518 years, not sedated by endoscopist, therapeutic and were tiny variations (0-5%) between the two observations, or raised/lowered
incomplete procedures, and also patients with two endoscopies performed on otherwise. At 1-year, in all patients, the second evaluation confirmed the presence
the same day. To reduce variability and determine whether the differences of GIM. In patients with worsened extension, the mean percentage of GIM
between the doses of propofol in both groups were related to age, all patients increase was 20%, whereas the mean percentage of GIM lowering was 26%in
75 years were matched on a 1:1 basis with the 575 years group in terms of patients with a reduced GIM extension.
weight, body mass index (BMI) and endoscopic procedure. All esophagogastro-
duodenoscopies (EGDs) and colonoscopies received an initial dose of propofol GIM STABLE GIM
0.5-1 mg/kg. Colonoscopies also received a fixed dose of 50 mcg of fentanyl. MEDIAN AGE EXTENSION GIM EXTENSION
Subsequently, boluses of 10-20 mg propofol were administered to maintain an N AGE RANGE LOWERED EXTENSION RAISED
adequate level of sedation. Vital signs were recorded before, during and after the
procedure. A statistical analysis was performed with the SPSS v20.0 program. Females 13 67 56-71 3 (23%) 3 (23%) 7 (54%)
RESULTS: There were 439 diagnostic EGDs and 307 diagnostic colonoscopies
performed in patients 75 years. When compared with patients 575 years, there Males 7 64 53-85 4 (57%) 1 (14%) 2 (29%)
were significant differences between groups in mean propofol dose, and mild OVERALL 20 64 53-85 7 (35%) 4 (20%) 9 (45%)
adverse events. No serious adverse events occurred. Patients 75 years required
significantly less propofol than patients 575 years, 72.99 37.4mg vs. 120.54
4.8mg for EGDs (P 5 0.001) and 80.5934mg vs 129.12 55.9mg (P 5 0.001) CONCLUSION: Our results demonstrate that already at 1-year the extension of
for colonoscopies (39.4% less in EGDs and 37.5% in colonoscopies). Table 1 GIM and, therefore, the risk of developing a gastric cancer GIM-related, worsens
shows the demographic, endoscopic procedures, propofol dose and adverse in about 45% of the patients. Thus, these data seem to support a more close
events in both groups. follow-up in patients with a GIM extension higher than 20% at histologic
assessment.
Disclosure of Interest: None declared
A326 United European Gastroenterology Journal 2(5S)
specimen orientation was present in 79.8 % of samples with jumbo forceps and in
P0706 DOES MAGNIFYING ENDOSCOPY WITH NARROW BAND
59.1 % with large capacity forceps (not significant). Intestinal metaplasia was
IMAGING IMPROVE DIAGNOSTIC ACCURACY FOR DEPTH OF
present in 69.8 % with jumbo forceps vs. 78.6 % of samples with large capacity
INVASION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA?
(not significant). The diagnostic yield of both types of forceps was comparable.
M. Imajoh1,*, T. Yano1, T. Kadota1, T. Kato1, S. Osera1, H. Morimoto1, CONCLUSION: Radial Jaw 4 Jumbo biopsy forceps, if used with diagnostic
T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1 endoscope, provides more adequate biopsy specimen as compared to Radial Jaw
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center 4 large capacity biopsy forceps. The diagnostic yield seems to be comparable.
Hospital East, Kashiwa city, Japan Disclosure of Interest: None declared
Contact E-mail Address: maomiimajo@gmail.com
INTRODUCTION: While accurate estimation for the depth of invasion in eso- P0708 OPTIMIZED IMPEDANCES OF INJECTION SOLUTIONS LEAD
phageal squamous cell carcinoma (ESCC) is essential to indicate relevant treat- TO IMPROVED CUTTING RESULTS IN ENDOSCOPIC RESECTION
ment methods, it is difficult to evaluate conventional endoscopy alone. N. Al-Dayaa1, M. Losle1,2, K.-E. Grund1,2,*
Microvascular patterns identified using magnifying narrow band imaging (M- 1
Surgical Endoscopy and Experimental Endoscopy, University Hospital, Tubingen,
NBI) have been reported to be useful for the diagnosis in the depth of invasion 2
supported by: Federal Ministry of Economics and Technology based on a resolu-
for superficial ESCC. Recently, a classification regarding the microvascular pat- tion of the Bundestag, Berlin, Germany
terns of superficial ESCC using M-NBI was advocated from the Japan Contact E-mail Address: chir.endo@uni-tuebingen.de
Esophageal Society, however, it is not clear whether the depth of invasion can
be estimated more accurately according to this classification compared with INTRODUCTION: The endoscopic resection of large ( 4 20 mm) lesions in the
estimation using conventional white light endoscopy (WL) alone. gastrointestinal tract is a high challenge for interventional endoscopy and radio-
AIMS & METHODS: The aim of this study was to evaluate whether the diag- frequency surgery. There is no easy, fast and safe way to remove large lesions en-
nostic accuracy of in M-NBI is higher than that in WL alone. In this study, we bloc. An important reason is the interaction between submucosal injection, tissue
enrolled patients with superficial ESCC who had undergone pretreatment eva- and high-frequency parameters in respect to electrical impedances. This interac-
luation using both WL and M-NBI, and who received endoscopic resection or tion is only partly understood and poorly investigated. Preliminary studies led to
surgery in our institution from June 2012 to December 2013. The patients who the conclusion that problems in the cutting process like cutting delay, perforation
had been previously treated with chemotherapy or chemoradiotherapy were and thermal artifacts are due to unsuitable impedances.
excluded. The microvessels of tumor surface observed by M-NBI were classified AIMS & METHODS: Our aim was to improve the cuttings results (avoiding of
into 3 groups; type B1 consisted of loop-like vessels with atypia, including dilata- cutting delay and high thermal load of the intestinal wall) by optimizing the
tion and meandering; type B2 were non-loop vessels; and type B3 were large impedances of the tissue. Therefore we analyzed various submucosal injection
vessels 3 or more times larger than type B2. Type B1, B2, and B3 vasculatures solutions in respect to impedances (surface and tissue) and rf-cutting.
were correlated with lesions invading to EP/LPM, MM/SM1, and SM2 or With standardized gold probes (1 mm/15 mm) and a special RF-impedance-
deeper, respectively. Investigators who were blinded to the pathological diagnosis meter (f 100 kHz, 10 V - 1 MV) the specific impedances of various solutions
estimated retrospectively the depth of invasion in the endoscopic pictures by WL and the impedances on the surface and in the tissue after submucosal injection of
alone, and then using the pictures by M-NBI. We sorted the lesions into 3 groups 3 ml were measured in a standardized bio-model (porcine stomach). Additionally
(EP/LPM, MM/SM1, and SM2/SM3) and the diagnoses for individual modal- the elevations during 30 min were observed. The following solutions were injected
ities were compared to the pathological results. Finally, sensitivity, specificity, into the submucosa: 0.9% saline, 4% gelatin, 6% hydroxyethyl starch, 10%
and positive predictive value (PPV) were analyzed. glycerol/5% fructose in 0.9% saline, 10% glucose and aqua destillata.
RESULTS: A total of 198 lesions were examined. Sensitivity, specificity, and Additionally 5% albumin, 20% albumin, human blood and blood plasma and
PPV of WL-alone were 92%, 85%, 90% for EP/LPM; 63%, 89%, 51% for a new experimental substance.
MM/SM1; and 74%, 97%, 90% for SM2/SM3, respectively. Sensitivity, specifi- RESULTS: Aqua destillata and 10% glucose showed a highly significant higher
city, and PPV of M-NBI were 85%, 71%, 81% for EP/LPM; 50%, 75%, 28% for (p 0.0001) specific impedance compared to the standard 0.9% saline (factor
MM/SM1; and 39%, 100%, 100% for SM2/SM3, respectively. The concordance 360). After injection also the impedances on the surface and in the tissue were
rate for diagnoses between both modalities was 87% in EP/LPM, 59% in MM/ significantly higher (p 0.01, resp. p 0.0001). The elevation showed no sig-
SM1, and 45% in SM2/SM3. In cases of a concordance between WLE and NBI- nificant difference between the tested solutions. Cutting experiments in a stan-
ME, the PPV was 90% for EP/LPM, 61% for MM/SM1, and 100% for SM2/ dardized setting showed the expected improvements: no cutting delay, less
SM3. thermal load of the intestinal wall, smooth cut without carbonization but with
CONCLUSION: While the concordance rates between WL and M-NBI was adequate zone of hemostasis.
unfavorable in MM/SM1, and SM2/SM3, PPV was high in the diagnosis was CONCLUSION: Clinically used injection solutions show a highly significant
concordant cases between both modalities. However, the difficulty of evaluating difference of specific impedances. After injection they lead to different impe-
the invasion depth for MM/SM1 lesions remains unsolved. dances on the surface and in the tissue. Better cutting results (avoidance of
REFERENCES delayed cut, high thermal load and thermal artifacts) obviously depend on an
1 Oyama T and Monma K. A new classification of magnified endoscopy for optimized impedance of the tissue. Therefore injection solutions with optimal (i.e.
superficial esophageal squamous cell carcinoma. Esophagus 2011; 8: 247-251. higher) impedances should be further investigated and preferred to conventional
2 Muto M, Horimatsu T, Ezoe Y, et al. Improving visualization techniques by agents.
narrow band imaging and magnification endoscopy. J Gastroenterol Hepatol REFERENCES
2009; 24: 13331346. Park YM, Cho E, Kang HY, et al. The effectiveness and safety of endoscopic
Disclosure of Interest: None declared submucosal dissection compared with endoscopic mucosal resection for early
gastric cancer: a systematic review and metaanalysis. Surg Endosc 2011; 25:
2666-2677.
P0707 RJ 4 JUMBO VS. RJ 4 LARGE CAPACITY FORCEPS IN TISSUE Kim YJ, Kim ES, Cho KB, et al. Comparison of clinical outcomes among
SAMPLING IN PATIENTS WITH BARRETTS ESOPHAGUS: FINAL different endoscopic resection methods for treating colorectal neoplasia. Dig
RESULTS OF A PROSPECTIVE, RANDOMIZED STUDY Dis Sci 2013; 58: 1727-1736.
M. Kollar1,*, J. Maluskova1, E. Honsova1, J. Krajciova2, J. Spicak2, J. Martinek2 Farin G and Grund KE. Principles of electrosurgery, laser, and argon plasma
1
Clinical and transplant pathology department, 2Hepatogastroenterology depart- coagulation with particular regard to colonoscopy. In: Waye JD, Rex DK and
ment, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Williams CB (eds) Colonoscopy prociple and practice. Singapore: Wiley-
Contact E-mail Address: marek.kollar1@seznam.cz Blackwell Verlag, 2009, pp. 328345.
Disclosure of Interest: None declared
INTRODUCTION: Good quality of biopsy specimen is required for reliable
diagnosis of early neoplasia in patients with Barretts esophagus (BE). Studies
comparing large capacity vs. jumbo forceps have shown inconsistent results. P0709 PERCUTANEOUS TRANSESOPHAGEAL GASTROTUBING
The aim of this study was to assess the quality of biopsy specimen obtained by WITHOUT RADIATION EXPOSURE WITH ENDOSCOPIC
2 different-sized biopsy forceps (Radial Jaw 4 large capacity (outer diameter 2.4 ASSISTANCE
mm) vs Radial Jaw 4 jumbo (outer diameter 2.8 mm) in patients with BE. We M. Murakami1,2,*, K. Nishino1, S. Murakami1, Y. Takaoka1, K. Mori1,
hypothesized that RJ4 jumbo forceps if used with a standard diagnostic endo- B. Murakami1, M. Azuma2, S. Tanabe2, M. Kida2, W. Koizumi2
scope (channel 2.8 mm) provides a better quality of biopsy specimen as compared 1
Internal medicine, MURAKAMI MEMORIAL HOSPITAL, saijo,
to the large capacity forceps. 2
Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan
AIMS & METHODS: A single center, randomized (forceps order), prospective Contact E-mail Address: masato@mrakami-kinen.or.jp
and single blind (pathologist) study. Twenty-one patients with BE (5 women, 16
men) were enrolled. All patients underwent an upper GI endoscopy with trimodal INTRODUCTION: Percutaneous transesophageal gastrotubing (PTEG) was
imaging. Targeted or random biopsies with both types of forceps used in random developed as an alternative route to access the gastrointestinal tract for patients
order were obtained from each patient during a single endoscopy with a diag- where Percutaneous Endoscopic Gastrostomy was contraindicated with condi-
nostic endoscope. Main outcome measurement was specimen adequacy (defined tions such as prior gastrectomy, gastric anterior wall malignancies, or massive
as a well oriented biopsy specimen 2 mm in diameter or greater with mucosa ascites. PTEG was originally developed to be performed under fluoroscopy with-
present). out endoscopy. However, endoscopy may enhance the safety of the procedure.
RESULTS: A total of 288 biopsy specimen were analyzed (large capacity: 159, AIMS & METHODS: The aim of this study is to evaluate the clinical usefulness
jumbo forceps: 129). A significantly higher proportion of biopsy samples of PTEG supported by endoscopy. A rupture-free balloon (RFB) catheter is
obtained with jumbo forceps was adequate as compared to large capacity forceps inserted into the lower esophagus. Percutaneous balloon puncture with a specia-
(54.3 % vs. 18.9 %, p50.0001). lized needle is then performed from the left side of patients neck under ultra-
Biopsies with jumbo forceps had a larger diameter (median 2.4 mm vs. 2 mm; sonographic control. A guide wire is inserted through the needle into the RFB,
p50.001). Muscularis mucosae was detected in 67.4 % of specimen with jumbo followed by a dilator and sheath. A placement tube is then inserted through the
forceps vs. 31.4 % with large capacity forceps (p50.0001). Excellent or good sheath, and the sheath is removed. We started to perform PTEG under
United European Gastroenterology Journal 2(5S) A327
endoscopy without fluoroscopy in a total of 99 patients (63 men and 36 women, accepted by high volume ER centers like our institution. If the pathological
mean age 74.0 years) in whom PEG was not feasible. PTEG was performed for examination of resected specimens show that they do not meet the criteria includ-
nutrition in 53 patients and for decompression in 46. ing expanded indications, we diagnose them as non-curative. From Apr 2000 to
RESULTS: Satisfactory results were achieved in all 100 patients. Median follow- Jul 2013, 75 patients underwent ER as the expanded indication lesion, and were
up was 60.5 days in patients who received decompression because of the obstruc- diagnosed as non-curative by pathological examination in our hospital. They
tion due to malignancies and 231.0 days in those who received nutrition. Two of underwent additional gastrectomy and their pathological findings in ER and
the 99 patients in the endoscopic assistance required fluoroscopy because of the surgical specimens were retrospectively analyzed. And the cases with pathological
tube insertion into the jejunum. There were no major complications, but one LN- metastasis, which have not been detected before ER, were picked up and
patient had tracheal penetration, which was managed conservatively. Other com- their characteristics were analyzed.
plications were minor oozing bleeding in six patients that did not require blood RESULTS: LN- metastasis was found in 9 cases (12%). 7 cases were primary
transfusion, subcutaneous emphysema in two patients, which were managed gastric cancers, and 2 cases were residual gastric cancers. In the 7 primary cases, 5
conservatively. Nine accidental (four self) tube removals occurred more than 2 cases had no residual cancer in surgical specimen, while LN- metastases existed.
weeks after the procedure, without any problem in reinsertion. The overall com- Focus on these complete endoscopic resection cases, 1 case was pathologically
plication rate associated with endoscopically assisted PTEG was 14.1%. No undifferentiated type and 5 cases were mixed type. The depth of invasion was
patient required surgical treatment or died after PTEG. SM1 in 1 case, and SM2 in 4 cases. Lymphatic-vascular capillary involvement
CONCLUSION: PTEG supported by endoscopy is as feasible, safe, and useful was found in all cases. In these cases, LN- metastases were found only in local D1
as PTEG supported by fluoroscopy, the original procedure. The use of endo- lymph node lesion. Lymph node relapse was found in 2 SM2 cases in the com-
scopy enhances the safety of the procedure and allows better confirmation of plete endoscopic resection cases at an early date, one case was in 5 months and
each step involved. another in 6 months after surgical resection. Both of them had not only lympha-
Disclosure of Interest: None declared tic capillary involvement but also vascular one.
CONCLUSION: Our data indicate that SM1/SM2 gastric cancer with patholo-
gically mixed type, regardless of predominant type, have high risk of LN- metas-
P0710 ASSESSMENT OF THE SIMPLIFIED NARROW BAND IMAGING tasis even if complete endoscopic resection of local lesion has been performed.
PATTERN CLASSIFICATION IN BARRETTS OESOPHAGUS Lymphatic-vascular capillary involvement also may be a predictive factor of LN-
M. Kato1,*, K. Goda2, Y. Shimizu3, A. Dobashi2, M. Takahashi3, M. Kato3 metastasis and risk factor of recurrence. In these cases, we should perform gas-
1
Endoscopy, The Jikei University Katsushika Medical Center, 2Endoscopy, The trectomy with appropriate LN- dissection keeping the risk of recurrence in mind
Jikei University School of Medicine, Tokyo, 3Gastroenterology and Hepatology, and consider adjuvant chemotherapy according to the risks.
Hokkaido University Hospital, Sapporo, Japan Disclosure of Interest: None declared
Contact E-mail Address: masakato89@gmail.com
INTRODUCTION: Various narrow band imaging (NBI) pattern classifications P0712 HIGH DEFINITION (HD) ENDOSCOPY WITH I-SCAN FOR THE
in Barretts oesophagus (BO) have been proposed, but are not readily applied to DETECTION OF MARKERS OF COELIAC DISEASE: A FEASIBILITY
routine clinical practice due to their multiplicity or complexity. STUDY
AIMS & METHODS: We evaluate inter- and intra-observer agreement as well as P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1
accuracy of a new simplified NBI pattern classification using NBI magnifying 1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
endoscopic images. Kingdom
A simplified binary classification is based upon NBI mucosal and vascular pat- Contact E-mail Address: peter.mooney@sth.nhs.uk
terns: 1) regular pattern (non-neoplastic BO) 2) irregular (Barretts neoplasia,
BN). Four endoscopists consisting of 2 experts and 2 non-experts assessed 248 INTRODUCTION: Coeliac disease (CD) remains underdiagnosed. Previous stu-
NBI magnifying endoscopic images (neoplasia 72, non-neoplasia 176) based on a dies have shown that up to 13% of patients with CD have undergone a previous
simplified binary NBI pattern classification. The endoscopists assessed two times gastroscopy where the opportunity to take duodenal biopsies and make a diag-
a randomly-arranged NBI magnifying endoscopic image sequence. The interval nosis had been missed. Clinicians may rely on the presence of endoscopic markers
between the 1st and the 2nd assessment was 6 weeks. Primary endpoint was inter- of CD to guide biopsy however these have been shown to lack the required
observer agreement among endoscopists. Secondary endpoints were intra-obser- sensitivity. A routine duodenal biopsy approach may solve this problem but
ver agreements in each endoscopist and diagnostic accuracies of sensitivity, spe- this is time consuming and expensive. Methods to improve the macroscopic
cificity, positive predictive value (PPV) and negative predictive value (NPV) in detection of CD at endoscopy to guide biopsy would seem advantageous. A
predicting BN as well as scores of diagnostic confidence level and image quality. single trial on I-Scan, a commercially available digital enhancement technique,
RESULTS: A median score for image quality was 5 (excellent) in both the 1st and has shown promising results in identifying markers of villous atrophy (VA)1.
2nd assessment. Inter-observer agreement (multi-kappa value) among endoscoc- However this was an uncontrolled, unblinded trial in high prevalence population
pists for BN prediction was calculated as 0.79 (substantial) and 0.86 (almost (35% CD). We aimed to assess the utility of I-Scan in a lower prevalence popula-
perfect) for the 1st and 2nd assessment. Intra-observer agreement (kappa-value) tion in a randomised controlled trial.
which were 0.95, 0.94 (experts) and 0.83, 0.83 (non-experts), respectively, were all AIMS & METHODS: Patients on a single coeliac enriched endoscopy list were
almost perfect. Mean sensitivity and specificity of NBI patterns for predicting randomised into 2 groups. Group 1 standard HD white light endoscopy (WLE)
BN were 92.7% (experts, 90.3%; non-experts, 95.1%) and 95.9% (experts, and group 2 WLE plus I-Scan. The presence of endoscopic markers of CD,
99.4%; non-experts, 92.3%) in the 1st assessment as well as 95.5% (experts, scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vas-
95.8%; non-experts, 95.1%) and 95.7% (experts, 99.1%; non-experts, 92.3%) cularity was noted throughout the duodenum. All patients received 4 biopsies
in the 2nd assessment, respectively, with high confidence level in both assess- from the second part of the duodenum and at least 1 biopsy from the bulb.
ments. NPV was 98.9% (experts, 96.2%; non-experts, 97.9%) and 99.3% Coeliac serology was taken at the time of endoscopy. Macroscopic markers of
(experts, 98.3%; non-experts, 97.9%) in the 1st and 2nd assessment, respectively. CD are compared VA on histology as the gold standard. 3, 10-point likert scales
CONCLUSION: A simplified binary NBI pattern classification for BO showed for pain, discomfort and distress were used to assess tolerability.
substantial to almost perfect inter- and intra-observer agreement and signifi- RESULTS: 253 patients (149 female, mean age 53.3 SD 18.2) have been recruited
cantly high diagnostic accuracies in both experts and non-experts. A simplified to date (127 into group 1 and 126 in group 2). In total 27 (prevalence 10.7%) new
binary NBI pattern classification seems applicable to routine clinical practice. diagnoses of CD have been made (14 in group 1 and 13 in group 2). I-Scan
Disclosure of Interest: None declared appears to enhance the appearance of markers for CD and in 2 patients in
group 2 CD markers that were not noted to be seen on WLE became apparent.
Preliminary results show that endoscopic markers of CD across both groups
P0711 PREDICTIVE FACTORS FOR LYMPH NODE METASTASIS currently have a sensitivity of 78.6% (58.5 91.0), specificity 87.6% (82.4
AFTER NONCURATIVE ENDOSCOPIC RESECTION FOR EARLY 91.5), positive and negative predictive values of 44.0% (30.3 58.7) and 97.1
GASTRIC CANCER (93.4 98.8). Median tolerability scores were good in both groups but better in
M. Inoue1,*, T. Omori1, R. Nakamura1, T. Takahashi1, N. Wada1, the I-Scan group than WLE alone (4/30 versus 8/30 p0.005)
H. Kawakubo1, H. Takeuchi1, Y. Saikawa1, Y. Kitagawa1 CONCLUSION: The addition of I-Scan to standard endoscopy to aid the diag-
1
Department of Surgery, School of Medicine, Keio University, Shinjyuku-ku, nosis of CD is well tolerated and is feasible. I-Scan appears to enhance the
Tokyo, Japan markings of coeliac disease, however a larger study is required to truly evaluate
the effectiveness of I-Scan as an adjunct to standard endoscopy to increase CD
INTRODUCTION: Endoscopic resection (ER) is widely accepted as an appro- diagnosis.
priate treatment modality for early gastric cancer. The indication criteria for ER REFERENCES
is established, and additional treatment, including gastrectomy with lymph node 1. Cammarota G, Ianiro G, Sparano L, et al. Image enhanced endoscopy with I-
dissection, is recommended when pathological examination of resected specimens Scan technology for the evaluation of duodenal villous patterns. Dig Dis Sci
do not meet the criteria. In some non-curative ER cases, pathological examina- 2012; 58: 1287-1292.
tion after additional surgery reveals lymph node metastasis which have not been Disclosure of Interest: None declared
detected before ER. There is a possibility that the discovery of risk factors of LN-
metastasis in non-curative ER case can expand the indications of endoscopic
treatment for early gastric cancer. P0713 EFFECT OF AGING ON COMPLICATIONS OF ENDOSCOPIC
AIMS & METHODS: The aim of this study is to examine the predictive factors SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC
of LN- metastasis which could not be detected before ER in non-curative ER CANCER (EGC)
cases. The indication criteria for ER in Japan is as follows; the lesion clinically M. Kato1,*, T. Michida1, A. Soga1, A. Kusakabe1, M. Kato1, C. Hibino1,
diagnosed as intramucosal differentiated cancer which is 52 cm in size with no Y. Shiode1, K. Murai1, Y. Matumura1, T. Kawai1, T. Saito1, Y. Nakada1,
ulceration findings. Expanded indications for some differentiated cancers (intra- M. Hamano1, K. Yamamoto1, M. Naito1, T. Ito1
mucosal cancers either 53 cm in size with ulceration findings or with no ulcera- 1
Japan Community Health care Organization Osaka hospital, Osaka, Japan
tion findings regardless of tumor size) and some undifferentiated cancers Contact E-mail Address: minoru-kato-514@okn.gr.jp
(intramucosal cancers 52 cm in size with no ulceration findings) have been
A328 United European Gastroenterology Journal 2(5S)
INTRODUCTION: As ESD has been widely used as a minimally invasive treat- CONCLUSION: Autologous blood is effective, comparable to diluted epinephr-
ment for EGC, opportunity to perform it for elderly patients is increasing. ine in achieving initial hemostasis from actively bleeding gastroduodenal ulcers,
However, there are few reports about safety and efficacy of ESD for them. We associated with 8% rebleeding rate and had no complications.
evaluated the effect of aging on complications of ESD for EGC. Disclosure of Interest: M. Emara: none, E. Darwiesh: none, A. Bihery: none, T.
AIMS & METHODS: We perform a prospective study of the expanded indica- Zaher: none
tion of ESD for EGC (Soetikno, et al. J Clin Oncol. 23(20):4490-8). ESD was
performed in 891 patients from April 2006 to March 2013 according to the
indication. Patients were divided into elderly group (75 years or older; 344 P0715 ENDOSCOPIC RESECTION AS A DIAGNOSTIC THERAPY FOR
cases) and non-elderly group (the rest; 547 cases). We compared the incidence BORDERLINE LESION OF GASTRIC CANCER; A MULTICENTRE
of complications such as post-ESD bleeding, perforation, pneumonia, and delir- PROSPECTIVE OBSERVATIONAL STUDY
ium between the groups. M. Kato1,2,*, A. Maekawa2, S. Egawa3, M. Komori4, T. Yamada2,5,
RESULTS: No emergent surgery was experienced in all cases. One patient in K. Yamamoto6, H. Ogiyama7, M. Nakahara8, N. Kawai9, T. Yabuta10,
non-elderly group died of pneumonia. The incidence of pneumonia and delirium A. Mukai11, Y. Hayashi2, T. Nishida6, M. Tsujii2, T. Takehara2
were significantly higher in elderly group than in non-elderly group (7.0% in 1
Department of Gastroenterology, National Hospital Organization, Tokyo Medical
elderly group vs 1.7% in non-elderly group; P50.01, 10.2% in elderly group Centre, Meguro-ku, Tokyo, 2Department of Gastroenterology and Hepatology,
vs 1.0% in non-elderly group; P50.01, respectively). There was no significant Osaka University Graduate School of Medicine, Suita, 3Department of
difference between two groups in the incidence of post-ESD bleeding and per- Gastroenterology, Kansai Rosai Hospital, Amagasaki, 4Department of
foration (3.8% in elderly group vs 4.9% in non-elderly group; p 0.42, 7.0% in Gastroenterology, Osaka Rosai Hospital, Sakai, 5Department of Gastroenterology,
elderly group vs 5.7% in non-elderly group; p 0.57, respectively). Among the National Hospital Organization Osaka National Hospital, Osaka, 6Department of
elderly group, the incidence of delirium was significantly higher in patients who Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, 7Department of
have dementia than in those who havent (79.2% in dementia patients vs 5% in Gastroenterology, Itami City Hospital, Itami, 8Department of Gastroenterology,
non-dementia patients; p50.01), and pneumonia was observed relatively more Ikeda Municipal Hospital, Ikeda, 9Department of Gastroenterology, Osaka Police
often in patients who have a history of chronic obstructive pulmonary disease Hospital, Osaka, 10Department of Gastroenterology, Sakai Municipal Hospital,
(COPD) than in those who havent (10.9% in COPD patients vs 6.1% in non- Sakai, 11Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan
COPD patients; p 0.17).
CONCLUSION: ESD for EGC were safely performed even in elderly patients INTRODUCTION: It is often difficult to discriminate between gastric adenocar-
without critical complications. However, pneumonia and delirium would be more icinoma and dysplasia/adenoma using endoscopic forceps biopsy. Endoscopic
encountered after ESD in elderly patients, so we have to take care additionally resection (ER) is, therefore, applied for borderline malignant lesions for the
about them. purpose of total biopsy in clinical practice. We have reported that about 40% of
REFERENCES patients with borderline lesion were diagnosed as adenocaricinoma after ER from
Soetikno, et al. J Clin Oncol 23: 4490-4498. a multicenter retrospective analysis (M. Kato, et al. J Gastroenterol. 2010).
Disclosure of Interest: None declared However, true incidence rate of adenocarcinoma is still unknown due to its
retrospective study design.
AIMS & METHODS: The aim of this study is to confirm the feasibility of ER
P0714 ENDOSCOPIC INJECTION OF AUTOLOGOUS BLOOD VERSUS for gastric borderline malignant lesions.
DILUTED EPINEPHRINE FOR CONTROL OF ACTIVELY BLEEDING This is a multi-centre prospective observational study from 10 hospitals (UMIN
GASTRODUODENAL ULCERS: A RANDOMIZED CONTROLLED Clinical Trials Registry: UMIN000007476). Patients were included if they were
STUDY diagnosed as Category 3.1 or 4.1 based on Vienna classification using endoscopic
M.H. Emara1,*, E. Darwiesh1, A.S. Bihery1, T. I. Zaher1 forceps biopsy specimen. After inclusion, patients underwent ER in each hospital
1
Tropical Medicine, ZAGAZIG UNIVERSITY, Zagazig, Egypt and data was prospectively collected concerning macroscopic findings (size and
Contact E-mail Address: emara_20007@yahoo.com morphological type based on Paris classification), findings of magnified endo-
scopy with narrow band imaging (NBI-ME), outcomes of ER, and pathological
INTRODUCTION: A variety of endoscopic methods are available to achieve findings. Primary endpoint was cancer-bearing rate in patients diagnosed as
hemostasis from an actively bleeding ulcer and reduce the risk of rebleeding e.g. adenocarcinoma after ER. Secondary endpoints were the association between
endoscopic injection of diluted epinephrine, applications of endoscopic clips and final diagnosis and findings of macroscopic appearance and NBI-ME, and the
argon plasma coagulation. Preliminary report showed that autologous blood short-term outcomes of ER.
through tamponade effect, cellular components and its viscosity is effective RESULTS: A total of 105 patients were included from April 2012 to February
and easy applicable technique that can control bleeding from the actively bleed- 2014. Among them, 48 patients were diagnosed as adenocarcinoma after ER and
ing gastroduodenal ulcers. cancer-bearing rate was 46%. Larger ( 20mm) and smaller (5 20mm) lesions
AIMS & METHODS: The aim of this study was to test if endoscopic injection of were not significantly different in cancer-bearing rates (43% vs 57%, p 0.2589).
autologous blood is superior to endoscopic injection of diluted epinephrine in Similarly, depressed and elevated lesions were not significantly different (50% vs
controlling bleeding from gastroduodenal ulcers. One hundred patients with 55%, p 0.7469). NBI-ME could predict accurately the pathological diagnosis
actively bleeding gastroduodenal ulcers were randomly assigned to autologous after ER in 52% of the patients. En bloc margin negative resection was achieved
blood injection (Group A, n 50) or diluted epinephrine (group B, n 50) along in 103 patients (98.1%). Perforation and post-procedural bleeding occurred in 3
the edges of the ulcers. Groups were compared for rates of initial hemostasis, patients (2.9%) and 2 patients (1.9%), respectively. All these adverse events were
rebleeding and complications. managed conservatively and no patients required emergent operation or blood
RESULTS: transfusion.
CONCLUSION: The present study showed that diagnostic ER for gastric bor-
Group A Group B derline malignant lesion is clinically safe and useful because of acceptable com-
(Autologous blood) (Diluted epinephrine) plication and high cancer-bearing rate.
N 50 (No & %) N 50 (No & %) P Disclosure of Interest: None declared
INTRODUCTION: Gastric endoscopic submucosal dissection (ESD) has gradu- INTRODUCTION: Identification of a precise demarcation line (DL) is indis-
ally come to be recommended as the optimal treatment for early gastric cancer; pensable for performing pathological complete en bloc endoscopic submucosal
however, one of the primary issues is postoperative bleeding. Although second- dissection (ESD) for early gastric cancer (EGC). Recently, chromoendoscopy
look endoscopy is conventionally performed to reduce the risk of postoperative with combination use of indigo carmine and acetic acid was reported as a
bleeding, its benefit has not yet been clearly elucidated. The objective of this novel technique for identifying the DL; however, this technique is not effective
study was to elucidate the benefit of second-look endoscopy. in all EGC cases.
AIMS & METHODS: From among 488 lesions in patients who underwent AIMS & METHODS: The aim of this study was to evaluate the usefulness of
gastric ESD between May 2004 and April 2013 at our hospital, a total of 29 chromoendoscopy with indigo carmine and acetic acid for marking dots around
lesions in patients who had a residual lesion, perforation, or concurrent aspira- lesions during ESD for EGC. We examined 98 consecutive patients with 109
tion pneumonitis, or in patients in whom the treatment modality had been intramucosal EGCs (mean diameter, 17.8 12.4 mm; location, U 21/M 34/L
switched to open surgery or there was no evidence of cancer in the resected 54; main histologic type, 96 intestinal and 13 diffuse) resected by en bloc ESD
specimen were excluded, and the remaining 459 lesions were included in the after chromoendoscopy with indigo carmine and acetic acid at Hiroshima
analysis. The patients were divided into those who had bleeding within 24 University Hospital between December 2012 and February 2014. We identified
hours after ESD (immediate bleeding) and those in whom bleeding occurred the DL by chromoendoscopy with indigo carmine and acetic acid just before
24 hours or more after the procedure (delayed bleeding); the underlying disease, ESD (mean chromoendoscopy observation time, 71.6 s), and then marking dots
age, lesion site, diameter of the resected specimen, and lesion diameter were were placed around the EGC. Four physicians participated in the evaluation of
analyzed to identify the risk factors for postoperative bleeding after ESD. improved EGC visibility. Conventional endoscopic images were presented to
RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459 each of the physicians in random order for comparison with chromoendoscopy
cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%) images. Physicians scored each of the chromoendoscopy images for visibility of
excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases the DL, and the four physicians scores for each image were tallied. EGCs were
(53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the classified into two groups: useful for identifying the DL or useless. The tumor
210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant diameter, histologic type (intestinal/diffuse), macroscopic type (elevated, 0-I &
difference between the two groups. Overall, the following factors were identified IIa & IIb; depressed, 0-IIaIIc & IIc), tumor lesion (U or M/L), tumor depth
as the risk factors for postoperative bleeding: young age (P 0.005), lesions in (intramucosal/submucosal), tumor color (reddish/normal or pale), atrophic gas-
the L segment (P 0.042), and large size of the resected specimen (P 0.005). tritis around tumor (present/absent), intestinal metaplasia around tumor (pre-
The risk factors identified in the immediate bleeding group were lesions in the L sent/absent), and rate of histologically positive horizontal margin were evaluated
segment (P 0.032), large size of the resected specimen (P 5 0.001), and large in each group.
tumor size (P 0.011), and those in the delayed bleeding group were young age RESULTS: Forty-two of the 109 cases (38.5%) were useful for chromoendo-
(P 0.013) and concomitant renal disease (P 0.011). scopy with indigo carmine and acetic acid, which were compared to the other 67
CONCLUSION: The results of this study suggest that second-look endoscopy cases. Univariate analysis showed that histologic type (intestinal type), macro-
after gastric ESD may not be useful for preventing postoperative bleeding. scopic type (elevated type), and atrophic gastritis around the tumor (present)
Disclosure of Interest: None declared were associated with the usefulness of chromoendoscopy using indigo carmine
and acetic acid. Multivariate analysis with logistic regression showed that macro-
scopic type (elevated type) and atrophic gastritis around the tumor (present) were
P0718 EARLY CLINICAL EXPERIENCE OF THE EFFECTIVENESS OF independently associated with the usefulness of chromoendoscopy using indigo
HEMOSPRAY IN ACHIEVING HAEMOSTASIS IN PATIENTS WITH carmine and acetic acid for identifying the DL of EGCs (P 5 0.05). The histo-
ACUTE NON-VARICEAL BLEEDING logically positive horizontal margin after ESD was 0% (0/42) in useful cases, and
N. Sagar1,*, T. Iqbal1 7.5% (5/67) in useless cases.
1
Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, United CONCLUSION: To make precise markings around EGCs before ESD, chro-
Kingdom moendoscopy with indigo carmine and acetic acid is useful for elevated-type
Contact E-mail Address: dr.nidhisagar@gmail.com EGC or in cases of existing atrophic gastritis around EGCs.
Disclosure of Interest: None declared
INTRODUCTION: Despite advances in management, mortality from acute
upper gastrointestinal bleeding remains high at 10%1. Current endoscopic mod-
alities have found to be effective in achieving haemostasis in 85-95% of cases,
however 5-10% of patients still experience rebleeding despite combination ther-
apy2. Bleeding may occur from sites, which are challenging to access or lesions
that are large and actively bleeding causing poor views for effective endoscopic
therapy. Hemospray is a novel powder designed to be a simple endoscopic tech-
nique in applying to large surface areas even in difficult positions.
A330 United European Gastroenterology Journal 2(5S)
wards. Mean scores of OBPS were 4.422.23 and 6.152.38 in educated and REFERENCES
control ward, respectively (p50.001). Rate of poor preparation (OBPS 56) in 1. Geboes K, Ectors N, DHaens G, et al. Is ileoscopy with biopsy worthwhile in
educated ward was significantly lower than that of control (31.1% vs. 58.8%, patients presenting with symptoms of inflammatory bowel disease? Am J
p50.001). PDR of educated ward was significantly higher than that of control Gastroenterol 1998; 93: 201-206.
ward (74.8% vs. 52.0%, p 0.001). Compliance with preparation and diet 2. Morini S, Lorenzetti R, Stella F, et al. Retrograde ileoscopy in chronic non-
instructions in education group was superior to that in control (p50.001). bloody diarrhea: A porspective, case-control study. Am J Gastroenterol 2003; 98:
Control group was more likely to be anxious before colonoscopy (p50.001) 1512-1515.
while education group showed a higher level of satisfaction with better sleep 3. Melton SD, Feagins LA, Saboorian MH, et al. Ileal biopsy: Clinical indica-
quality (p50.001). In multivariate analysis, no ward nurse education (OR 2.36, tions, endoscopic and histopathologic findings in 10.000 patients. Dig Liver Dis
p 0.025), constipation (OR 6.52, p50.001) and no additional water ingestion 2011; 43: 199-203.
(OR 2.05, p 0.042) were factors associated with poor bowel preparation. Disclosure of Interest: None declared
CONCLUSION: Ward nurse education is effective to improve the quality of
inpatient bowel preparation, PDR, and compliance. Additional effort is needed
to control constipation and to encourage additional water ingestion for better P0741 PHARMACODYNAMIC AND CLINICAL EVALUATION OF LOW-
inpatient bowel preparation. VOLUME POLYETHYLENE GLYCOL (PEG)-BASED BOWEL
Disclosure of Interest: None declared CLEANSING SOLUTIONS (NER1006) USING SPLIT DOSING IN
HEALTHY AND SCREENING COLONOSCOPY SUBJECTS
M. Halphen1,*, B. Tayo1, S. Flanagan1, L. Clayton1, R. Kornberger2
P0740 WHEN SHOULD I TAKE TERMINAL ILEAL BIOPSIES? 1
Norgine Ltd, Uxbridge, United Kingdom, 2PAREXEL International, Berlin,
EXPERIENCE FROM A SINGLE UNIT Germany
L.J. Neilson1,2,*, R. Bevan1,2, C.J. Rees1,2 Contact E-mail Address: MHalphen@norgine.com
1
South Tyneside District Hospital, South Shields, 2Northern Region Endoscopy
Group, Newcastle, United Kingdom INTRODUCTION: The effectiveness of PEG3350electrolytes based solutions
Contact E-mail Address: neilson.laurajane@hotmail.co.uk for bowel cleansing prior to endoscopy is well established but require patients to
drink 3L of fluid. Reducing this volume without compromising efficacy/safety
INTRODUCTION: Terminal ileum (TI) intubation at colonoscopy may be is the next challenge.
useful in the investigation of patients with diarrhoea or possible inflammatory AIMS & METHODS: This open-label, randomised, 2-part (Part A: healthy
bowel disease.1,2 The yield of TI biopsies has been shown to be variable and there subjects; Part B: screening colonoscopy subjects), phase II study investigated
are no standards for current practice.2,3 Furthermore, in the UK, concerns the pharmacodynamics (stool weight), tolerability, and clinical efficacy of dose-
remain regarding the potential for prion transmission. and taste-optimised low-volume PEG-based formulations (NER1006) after split
AIMS & METHODS: We aim to establish the yield of TI biopsies in a single dosing compared with MOVIPREP. Subjects (4070y) were randomised to 1 of
unit. 4 treatment arms in Parts A and B (1:1:1:1): 3 formulation arms for NER1006; 1
All TI biopsies recorded on the pathology system in a 3-year period were for MOVIPREP. NER1006 consisted of different PEG3350 formulations,
reviewed. Colonoscopy reports for these cases were reviewed, as well as case mineral salts (including ascorbate), electrolytes and flavouring, reconstituted
records to establish if biopsy results were clinically relevant (defined as leading with water plus additional intake of specified volumes of water (Table).
to a change in management). Statistical analysis was performed using SPSS. P Treatment was administered on Day 1 (evening dose) and Day 2 (morning
values were calculated using the Fishers exact test to show any difference in dose). The primary endpoint in Parts A and B was 24h stool weight (desired
biopsy yield between normal and abnormal looking mucosa for each indication. target 2750g). Cleansing success rate (Harefield Cleansing Scale) was a co-
The values were calculated for all abnormal biopsy results, and for clinically primary endpoint in Part B. Secondary endpoints included time and volume of
relevant biopsy results. study drug to reach clear effluent, safety and tolerability (vomiting rate).
RESULTS: 129 TI biopsies were taken between September 2010 and September RESULTS: 120 subjects were included in each part (n 30/arm). 24h stool
2013, 49 (38%) male and 80 (62%) female. Mean age 44 years (s.d. 17.2). There weight was significantly 42750g for NER1006 formulations OPT002 and
were 29 (22.5%) cases of known inflammatory bowel disease (IBD). 5 (3.9%) OPT003 in Part A, and OPT003 and OPT007 in Part B. Reversed order of
cases were completion colonoscopies after colorectal cancer surgery, where TI administration of the split dose (i.e., TF043 morning/TF048 evening) in
biopsies are taken to prove a complete examination. OPT002 was as efficacious, with a similar safety profile. Most subjects in the
CONCLUSION: We demonstrate that when investigating patients with diar- NER1006 arms reached clear effluent. Mean volume of study drug required and
rhoea, abdominal pain, or IBD, if the terminal ileum is visually normal, biopsies time to reach clear effluent are shown in the Table. In Part B, cleansing success
do not add to the clinical picture. There is a higher yield of relevant biopsy rate was: 100% for OPT003 and OPT007; 90% for OPT006 and OPT004. For
abnormalities when the TI appears abnormal. We can recommend within our subjects who completed dosing, vomiting rates were 57.0% and 53.5% for all
practice that a visual assessment of a normal terminal biopsy is adequate, thereby treatments in Parts A and B, respectively, with no significant differences between
reducing unnecessary biopsies. This reduces the workload for pathology labora- arms in either part.
tories, reduces risk from biopsies, and improves patient care as normal results can CONCLUSION: In healthy and screening-colonoscopy subjects, the new low-
be communicated sooner to the patient. volume, split-dose bowel preparation NER1006 achieved high quality bowel
cleansing comparable with MOVIPREP. Stool output was consistently higher
with NER1006 treatments, and safety/tolerability profiles between treatments
were comparable.
Table to abstract P0741
Table Pharmacodynamics of different technical formulations (TF)/administration volumes of NER1006
Part A:
1 (OPT001) TF048 (750875) TF043 (500875) 2951 (0.2176) 15.8 1139
2 (OPT002) TF043 (500875) TF048 (750875) 3219 (0.0042) 12.3 900
3 (OPT003) TF047 (5001000) TF043 (5001000) 3399 17.8 944
4 (OPT004) MOVIPREP (1000500) MOVIPREP (1000500) (50.0001)
2491 (0.8764) 17.7 1929
Part B:
1 (OPT003) TF047 (5001000) TF043 (5001000) 3050 (0.0268) 14.9 860
2 (OPT007) TF047 (500500) TF043 (500500) 3215 (0.0004) 16.9 956
3 (OPT006) TF047 (5001000) TF044 (5001000) 2675 (0.4907) 17.7 935
4 (OPT004) MOVIPREP (1000500) MOVIPREP (1000500) 2487 (0.9691) 16.3 1790
A336 United European Gastroenterology Journal 2(5S)
Disclosure of Interest: M. Halphen Consultancy for: Norgine, B. Tayo Other: describe the white light findings in CD. CLE findings were classified using the 4
Norgine, S. Flanagan Other: Norgine, L. Clayton Other: Norgine, R. grade classification system of inflammation, describing crypt architecture, infil-
Kornberger Financial support for research from: Norgine tration of the cells, microvasculature alteration and leakage of fluorescein. CLE
images were collected for each segment of the colon, and targeted biopsies were
taken for histologic analysis.
P0742 OLYMPUS NEAR FOCUS NARROW BAND IMAGING (NBI) VS RESULTS: Of the 24 PSC patients, 20 had co-existent IBD (10UC, & 10CD).
CONVENTIONAL NBI FOR IN VIVO ENDOSCOPIC HISTOLOGY OF Absence of rectal inflammation based on CLE findings was seen in 20/24
COLONIC POLYPS: A RANDOMIZED CONTROLLED TRIAL patients. 10/24 had moderate to severe inflammation present in the right colon
M. Bustamante1,*, L. Puchades1, M. Ponce1, L. Arguello1, V. Pons1 with irregular, decreased or necrotic crypts. Two patterns of fluorescein leakage
1
Gastrointestinal Endoscopy Unit, Hospital Universitari i Polite`cnic La Fe, were observed. A) In 10 patients leakage of fluorescein were observed in spaces
Valencia, Spain amongst epithelial cells, or non-uniform abundant leakage in the lumen of the
Contact E-mail Address: bustamante_mar@gva.es crypts associated with moderate to severe inflammation; B) In 12 patients we
observed uniform leakage of the fluorescein into the lumen of crypts in the left
INTRODUCTION: A lower diagnostic accuracy of pathologic in vivo diagnosis side of the colon, associated with normal crypt architecture and micro-vascula-
with NBI has been described in nonacademic settings compared to expert centers. ture - the absence of active inflammation was confirmed by histology. The
Recently, Olympus has launched the 190 series, which has a pushbutton-con- remaining 2 patients did not showed leakage of fluorescein. Four patients did
trolled optical magnification system (near focus). not have a diagnosis of IBD but 3 of these patients had subtle inflammation on
AIMS & METHODS: Aims: to assess the reliability of the near focus system CLE characterized by cellular infiltration within the lamina propria in the sig-
compared to conventional NBI in the histologic prediction (adenoma vs hyper- moid colon and rectum (by histology). One had a new diagnosis of UC after
plastic) of small (6-9 mm) and diminutive (1-5 mm) colonic polyps. Secondary examination by CLE and colonoscopy.
objective was to assess the fulfillment of PIVI criteria.1 CONCLUSION: CLE effectively characterizes the inflammation of PSC IBD
Patients and methods: Patients scheduled for colonoscopy were consecutively patients, confirming that these patients are likely have a different phenotype with
included. Patients were assigned to 190 series (group 1) or 180 series (group 2) inflammation in the right side of the colon and rectal sparing. The finding of
endoscopes using a computer-generated random number sequence. A sample size uniform leakage of fluorescein into the lumen of the crypts, in the absence of
calculation was performed, and a minimum of 136 lesions per group was pro- active inflammation, may represent a defect in the intestinal barrier. Even
grammed. All examinations were performed by the same endoscopist (MBB) with patients not known to have IBD associated with PSC may demonstrate subtle
expertise in NBI analysis. NICE classification criteria2 were used for in vivo infiltration of mononuclear cells into the lamina propria as demonstrated at
histological diagnosis. CLE.
RESULTS: 98 patients were included (49 women, 50%), median age 63 yr. CRC Disclosure of Interest: None declared
screening was the most frequent indication (51%). Group 1 was comprised of 51
patients (52%). Finally 333 lesions were included, 82.6% from 1 to 5 mm of
diameter, and 231 (69.4%) adenomas. Under NBI examination, the histology of P0744 ANALYSIS OF THE ENDOCYTOSCOPIC IMAGE OF
277 lesions (83.2%) was predicted with high confidence. The 51 patients from COLORECTAL LESION FROM THE ASPECT OF MICRO
group 1 harbored 171 lesions (142 predicted with high confidence) and the 48 VASCULAR PATTERN
patients from group 2 harbored 162 lesions (135 predicted with high confidence). M. Misawa1,*, S.-E. Kudo1, H. Nakamura1, S. Kataoka1, S. Hayashi1,
Sensitivity, specificity and diagnostic accuracy for lesions diagnosed with high H. Oikawa1, N. Toyoshima1, Y. Mori1, T. Kudo1, N. Ogata1, T. Hayashi1,
confidence in both groups are summarized in table 1. There were no differences K. Wakamura1, Y. Wada1, H. Miyachi1, F. Ishida1
in diagnostic accuracy between both groups (92.2% vs 89.6%, p 0.5). 1
Digestive disease center, Showa University Northern Yokohama Hospital,
Yokohama-shi, Japan
(%) Group 1 Group 2
(CI 95%) INTRODUCTION: Endocytoscopy (EC) is an ultra-magnification technique,
High which can be performed to evaluate structural and cellular atypia with observa-
High confidence confidence tion of lumens and nuclei in the surface layer of the mucosa. EC has made it
High Diminutive High Diminutive possible to diagnose living tumor cells in vivo and to obtain an ultra-magnifica-
confidence lesions confidence lesions tion pathological image simply by applying the scope to the target mucosa during
an endoscopic examination. On the other hand, analysis of the surface micro-
Sensitivity 91.8 (85.9-97.7) 90.0 (82.8-97.2) 91.2 (84.8-97.6) 87.7 (78.9-96.5) vessels of colorectal lesions using magnifying narrow-band imaging is useful for
identifying the appropriate treatment method for colorectal lesions. In addition,
Specificity 93.2 (84.6-100) 94.1 (84.7-100) 86.4 (75.1-97.6) 86.4 (75.1-97.6) the surface microvessels can be analyzed using EC.
Accuracy 92.2 (87.5-97.0) 91.2 (85.6-96.9) 89.6 (84.1-95.1) 87.2 (80.4-93.9) AIMS & METHODS: The aim of this study was to investigate whether the
observation of surface microvessels using EC was useful in predicting the histo-
pathology of colorectal lesions.
Six (10.3%) of the 54 diminutive lesions located in rectum and sigmoid colon and The study included 273 patients who underwent complete colonoscopy and endo-
diagnosed as hyperplastic with NBI were finally categorized as adenomas. The scopic or surgical treatment between April 2006 and December 2013. A total of
overall NPV for the diagnosis of adenoma was 89.7%. In 61 (95.3%) out of the 337 lesions (10 normal mucosae, 23 hyperplastic polyps, 210 adenomas, and 94
64 patients in whom a colonoscopy control was scheduled, there was an agree- submucosally invasive cancers) were retrospectively evaluated. The colonic sur-
ment between NBI and the final pathological diagnosis (kappa 0.9), without face micro-vascular patterns observed using EC were classified into the following
differences between groups. 3 groups: EC-V1, the surface microvessels were obscure; EC-V2, the surface
CONCLUSION: The near focus technology does not increase the diagnostic microvessels were clearly observed, and their caliber and arrangement were uni-
accuracy of conventional NBI at least for an expert examinator. NBI achieves form; and EC-V3, the surface microvessels were thick, and their caliber and
a good accuracy for in vivo pathological diagnosis, fulfilling PIVI criteria; there- arrangement were non-homogeneous.
fore it may represent an alternative to pathological diagnosis in a near future. RESULTS: The sensitivity, specificity and accuracy of EC-V1 for diagnosis of
REFERENCES hyperplastic polyp were 97.0%, 99.0% and 98.8%, respectively. As regards the
1 ASGE PIVI on real-time endoscopic assessment of the histology of diminutive sensitivity, specificity and accuracy of EC-V3 for diagnosis of invasive cancer
colorectal polyps. Gastrointest Endosc 2011; 73: 419-422. were 84.7%, 97.7% and 94.1%, respectively.
2 Hewett DG, et al. Validation of a simple classification system for endoscopic CONCLUSION: Vascular patterns of colorectal cancers observed by endocyto-
diagnosis of small colorectal polyps using narrow-band imaging. scopy were useful in predicting the histopathology of colorectal lesions.
Gastroenterology 2012; 143: 599-607. Disclosure of Interest: None declared
Disclosure of Interest: None declared
INTRODUCTION: Controversy exists as to whether the colitis seen in patients INTRODUCTION: Endoscopic resection (ER) is increasingly used to treat small
with primary sclerosing cholangitis (PSC) represents a different entity than that rectal neuroendocrine tumors (NETs). Currently, several guidelines recommend
classically observed in patients with Crohns disease (CD) or ulcerative colitis ER as a treatment of rectal NETs less than 10 mm without muscularis invasion.
(UC). Specific differences have been described in the nature of the endoscopic However, limited data are available on the long-term outcomes of rectal NETs
and histological findings. Confocal laser endomicroscopy (CLE) is a new tech- treated by ER. In addition, the significance of known risk factors for metastasis
nology which enables real time endoscopy and histological investigation. PSC of rectal NETs, including lymphovascular invasion, remains elusive.
colitis has not been investigated by CLE. AIMS & METHODS: The aim of this study was to clarify the prognosis of rectal
AIMS & METHODS: To describe the CLE appearance in the colon in patients NET patients treated by ER and to characterize the known risk factors for
with PSC, with or without associated IBD. Patients and Methods 24 patients (16 metastasis of these lesions. Ninety-eight patients underwent ER for rectal
male: median age 43y, range 20-71y) with PSC underwent colonoscopy with CLE NETs at our institution between 1997 and 2011. Among them, 3 patients who
(Pentax, Tokyo) between 02/12 and 12/13. The Mayo endoscopy sub-score was underwent colectomy for colorectal cancers after ER of rectal NETs and 8
used to grade endoscopic findings in UC, and the SES-CD score was used to patients with a follow-up period shorter than 1 year were excluded. Thus, a
United European Gastroenterology Journal 2(5S) A337
total of 87 patients with 91 lesions were included in this study. The patients
P0747 OPTIMISATION OF ENDOSCOPIC FOLLOW-UP WAITING
records were retrospectively analyzed for clinical outcomes and pathological
LISTS IN A NEW ZEALAND DISTRICT HEALTH BOARD
findings including size, invasion depth, and lymphovascular invasion. Also, we
additionally evaluated tumor proliferation by Ki-67 immunohistochemistry and N. Bhala1,*, H. Myint1, J. Lewis1, C. Virtue1, A. Simpson1, R. Cameron1
1
lymphovascular invasion using elastic staining and double staining immunohis- Department of Gastroenterology, Capital & Coast District Health Board,
tochemistry (CD31/synatophysin and D2-40/synaptophysin). Wellington Hospital, New Zealand
RESULTS: ER procedures included endoscopic submucosal resection with a Contact E-mail Address: neeraj.bhala@ccdhb.org.nz
ligation device (ESMR-L) (n 82), EMR (n 5), and ESD (n 4), with an R0
resection rate of 90.1% (ESMR-L 76/82, EMR 3/5, and ESD 3/4, respectively). INTRODUCTION: New Zealand (NZ) has the one of the highest bowel cancer
No major complications were observed. All cases were followed up without death rates in the Western world, so prompt access to lower GI endoscopy for
surgery after ER; with the median follow-up period of 68 months (range, 12 new referrals is of importance in diagnosis, treatment and prevention. However,
167), no metastasis or recurrence was detected and the 5-year overall survival rate partly as a result of follow-up colonoscopy demands, waiting lists have increased
was 95.9%. The median tumor size of these cases was 5 mm (range, 213) and no substantially, and so the NZ Ministry of Health has funded initatives to ensure
lesion showed invasion beyond the submucosal layer. Based on the results of Ki- appropriate clinical investiagtions are being done for the right indication at the
67 immunohistochemistry, all 91 lesions were classified as NET G1 (WHO 2010 right time.
classification). The original diagnoses based on haematoxylin and eosin staining AIMS & METHODS: We sought to evaluate an optimisation exercise of follow-
identified no case with lymphatic invasion and only one case with positive venous up lower GI endoscopy lists in a single District Health Board covering a popula-
involvement. However, additional analysis using elastic staining and double tion of around 300.000 people in the lower North Island of North New Zealand.
staining immunohistochemistry revealed lymphovascular invasions in 33 lesions Evidence-based criteria were agreed by the endoscopy user multi-disciplinary
(36.3%) by elastic staining, 9 lesions (9.9%) by CD31/synaptophysin double group for recall criteria for repeat colonoscopy for a number of conditions,
staining, and 23 lesions (25.3%) by D2-40/synaptophysin double staining. including: colorectal cancer resections; colorectal adenoma follow-up; family
Collectively, lymphovascular invasion was identified in a total of 42 lesions history of colorectal cancer; and inflammatory bowel disease surveillance.
(46.2%) with at least one of these staining procedures. Size of NETs with lym- These were then applied to those patients on the waiting list for repeat endo-
phovascular invasion (median, 5 mm; range, 313) was significantly but only scopic appearances in 2014 by a single consultant gastroenterologist.
slightly larger than that of NETs without lymphovascular invasion (median, 4 RESULTS: Of 511 patients on the waiting list, 497% were for repeat colonos-
mm; range, 210; p 0.02, MannWhitney U test). copies. 164 procedures (32.1%) did not meet the criteria for repeat procedures,
CONCLUSION: Long-term clinical outcomes of rectal NETs following ER were and were cancelled. Within 2 months of this exercise, only four primary care
favorable. While lymphovascular invasion was believed to be a strong risk factor practitioners (2.5%) sent queries regarding cancellation, which were dealt with.
for metastasis, a detailed analysis revealed that it was frequently present even in 183 (35.8%) did meet the criteria, but were not being done at the appropriate
minute rectal NETs. The present results raise a question on the clinical signifi- time interval, so were deferred (range 6 months - 3 years). 165 (32.3%) did meet
cance of lymphovasucalar invasion in small rectal NETs. the indication for repeat procedure in the appropriate time interval, and were
Disclosure of Interest: None declared approved and duly listed.
CONCLUSION: Initiatives to apply evidence-based criteria for repeat endo-
scopic procedures can improve quality, productivity and prevent unnecessary
P0746 HIGH PRESSURE JET INJECTION OF VISCOUS SOLUTIONS procedures. In this real-life application in NZ, a third of repeat endoscopy work-
FOR ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD): ABOUT load were removed from waiting lists, and more than an additional third were
THE 45 FIRST HUMAN CASES IN 4 EXPERT CENTERS deferred to a clinically appropriate time, allowing new referrals to be seen sooner.
M. Pioche1,2,*, V. Lepilliez3,4, P. Deprez5, M. Giovannini6, F. Caillol6, Centrally funded initiatives to apply evidence-based guidelines to help manage
H. Piessevaux7, J. Rivory4, O. Guillaud4, M. Ciocirlan8, D. Salmon9, waiting lists may be relevant to other populations.
I. Lienhart4, C. Lafon2, J.-C. Saurin4, T. Ponchon4 Disclosure of Interest: None declared
1
Gastroenterology and endoscopy, Edouard Herriot Hospital, 2Inserm U1032,
3
Gastroenterology and endoscopy, Hopital Prive Jean Mermoz, 4Gastroenterology
and endoscopy, Hopital Edouard Herriot, Lyon, France, 5Gastroenterology and P0748 PICOSALAX PROVIDES SUPERIOR BOWEL CLEANSING TO
endoscopy, Hopital Saint-Luc, Louvain, Belgium, 6Gastroenterology and endo- TRADITIONAL POLYETHYLENE GLYCOL IN THE ELDERLY
scopy, Institut Paoli Calmette, Marseille, France, 7Gastroenterology and endo- POPULATION
scopy, Hopital Saint Luc, Louvain, Belgium, 8Carol Davila institute, Bucharest, R. Gingold-Belfer1,*, A. Geller1, A. Vilkin1, Y. kelner1, Y. Niv1, Z. Levi1
Romania, 9Pharmacy, Hopital Edouard Herriot, Lyon, France 1
Gastroenterology Department, Rabin Medical Center, Petah Tikva, Israel
Contact E-mail Address: mathieupioche@free.fr Contact E-mail Address: rachelgingoldbelfer@gmail.com
INTRODUCTION: Long lasting lifting is a key factor during ESD and can be INTRODUCTION: Lately, life expectancy was prolonged. Therefore, endo-
obtained by water-jet injection of saline solution or by injection of viscous scopic procedures are performed in an elderly population too. The level of
macromolecular solutions. In a previous animal study, we assessed the ability bowel cleansing during colonoscopy is one of the quality indicators that were
of the Nestis Enki II system to combine jet injection and macromolecular viscous determined in order to improve the procedures efficacy. An elder age is one of
solutions. In the present work, we used this combination in humans in the dif- the factors for poor preparation.
ferent sites of the digestive tract. AIMS & METHODS: Aims: We aimed to evaluate the level of bowel cleansing
AIMS & METHODS: To assess the effectiveness and safety of Nestis system of the elderly population, by assessing the bowel preparation with Picosalax as
using viscous solutions. We report retrospectively all the consecutive cases of compared to polyethylene glycol (PEG).
ESD procedures made with Nestis Enki II system with injection of viscous solu- Methods: Included 6,844 patients aged 75y (mean 81.1y4.6) who underwent
tions. Information was collected about: the lesion (site, histology), the procedure colonoscopy at our endoscopy unit during 2003-2013. 3,659 (53.5%) patients
(time, perforations, bleedings, monobloc or piece meal resection), the piece (size, were men. 1,258 patients had preparation with Picosalax and 5,444 with PEG.
R0, Rx or R1 resection) and the outcomes for the patient (curative treatment, The quality of bowel cleansing was assessed according to the Aronchick scale.
surgery, recurrence, delayed complications). Multivariable logistic regression analysis for good preparation were used and
RESULTS: 45 resections were complete macroscopically. Procedures were per- included: the patients age, gender and bowel preparation type.
formed by 6 operators: 5 experts and one beginner with only one previous RESULTS: Total, good preparation was achieved in 1,024 (79.8%) patients who
experience in human ESD (11). The lesions were: 22 lateral spreading tumors used Picosalax as compared to 3,528 (63.4%) with PEG (p50.001). Fair pre-
of the rectum 11 gastric lesions, 10 esophageal lesions, 1 of the right colon and 1 paration was achieved in 183 (14.5%) patients by Picosalax as compared to 1,322
of the second duodenum. The average maximal lesion diameter was 4.8 cm (SD (24.3%) by PEG. Bad and poor preparations were reported in 44 (3.5%) and 7
2.4, range 2-11 cm), the average surface was 19.8 cm2 (SD 17.7, range 2.2-72 (0.6%) patients who used Picosalax as compared to 544(10%) and 50 (0.9%),
cm2) and the average time of procedure was 79.9 min (SD /- 50.3, range 19-225 respectively. By using multivariable logistic regression analysis, good prepara-
min). Three adverse events occurred with two diminutive perforations (and two tion, was significantly associated with female gender [OR: 1.38 95% confidence
delayed bleedings treated conservatively. R0 resection rate was 91.1%. interval (CI) 1.24-1.52, p50.001] and Picosalax preparation [OR: 2.15 95% CI
Obstruction of the catheter occurred in 6 cases in bloody situations. 1.85-2.5, p50.001, PEG- ref]. An increased age, was negatively associated with
CONCLUSION: This is the first multicenter report on a new water jet system good preparation [OR: 0.9595% CI 0.97-0.99, p 0.009].
allowing injection of viscous solutions. This system is safe and effective and CONCLUSION: Female gender is significantly associated with good preparation
allows working in retroflexed position with different viscous solutions. in patients aged 75y. The usage of Picosalax was associated with a 2.15 odds
Disclosure of Interest: M. Pioche Financial support for research from: Nestis, V. ratio for predicting good bowel preparation. Despite lack of conventional guide-
Lepilliez: None declared, P. Deprez: None declared, M. Giovannini: None lines of bowel preparations regimens for the elderly population, the usage of
declared, F. Caillol: None declared, H. Piessevaux: None declared, J. Rivory: Picosalax is indicated as an effective preparation for this age group, too.
None declared, O. Guillaud: None declared, M. Ciocirlan: None declared, D. REFERENCES
Salmon: None declared, I. Lienhart: None declared, C. Lafon: None declared, J.- 1. Jang JY and Chan HJ. Bowel preparations as quality indicators for colono-
C. Saurin: None declared, T. Ponchon: None declared scopy. World J Gastroenterol 2014; 20: 2746-2750.
2. Romero VR and Mahadeva S. Factors influencing quality of bowel prepara-
tion for colonoscopy. World J Gastroenterol 2013; 5(2): 39-46.
Disclosure of Interest: None declared
A338 United European Gastroenterology Journal 2(5S)
2. Tatlidil R, Jadvar H, Bading JR, et al. Incidental colonic fluorodeoxyglucose
P0749 MULTIPURPOSE USE OF THE OVER-THE-SCOPE-CLIP
uptake: correlation with colonoscopic and histopathologic findings. Radiology
SYSTEM: SWISS EXPERIENCE IN A TERTIARY CENTER
2002; 224: 783787.
M.C. Sulz1, R. Bertolini1, R. Frei1,*, G.-M. Semadeni1, C. Meyenberger1 3. Putora PM, Muller J, Borovicka J, et al. Relevance of incidental colorectal
1
Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, FDG-PET/CT-enhanced lesions. Onkologie 2013; 36: 200-204.
Switzerland Disclosure of Interest: None declared
Contact E-mail Address: michael.sulz@kssg.ch
INTRODUCTION: The Over-the-scope-clip (OTSC) system (Ovesco Endoscopy P0751 VARIATIONS IN ADENOMA DETECTION RATES IN THE
AG, Tubingen, Germany) is a fairly new endoscopic device suitable to close ENGLISH FLEXIBLE SIGMOIDOSCOPY SCREENING
gastrointestinal (GI) perforations, post-surgical fistulae or to resect submucosal PROGRAMME
tumors. It can also be used as hemostatic tool in GI bleeding and for esophageal R. Bevan1,2,*, C. Nickerson3, R. Blanks4, J. Patnick3, R. Loke5, B. Saunders6,
stent fixation. To the best of our knowledge, in literature there are only case J. Stebbing7, R. Tighe8, A. Veitch9, J. Painter1, C. Rees1,2
reports or small case series regarding the efficacy and safety, so far human 1
South of Tyne Bowel Cancer Screening Centre (BCSC), Gateshead, 2Northern
clinical randomized controlled trials are not available. The available case series Region Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes,
and reports are inhomogeneous concerning indication, study design, site of appli- Sheffield, 4Cancer Epidemiology Unit, Oxford, 5West Kent & Medway BCSC,
cation and definition of success. Tunbridge Wells, 6St Marks BCSC, London, 7Surrey BCSC, Guilford, 8Norwich
We present a prospective case series reflecting our all-day clinical experience with BCSC, Norwich, 9Wolverhampton BCSC, Wolverhampton, United Kingdom
OTSC in a tertiary endoscopy center in Switzerland. This case series illustrates Contact E-mail Address: roisinbevan@hotmail.com
the primary successful closure in over 80% of GI lesions, mainly fistulae or
anastomotic leakages and adds data to the increasing experience with this tool. INTRODUCTION: The English Bowel Cancer Screening Programme has been
AIMS & METHODS: Aim: To evaluate the outcome of the over-the-scope-clip expanded to include a one-off flexible sigmoidoscopy offered to all 55 year olds,
system (OTSC) regarding various indications in all-day clinical practice in called BowelScope Screening. Screening commenced in May 2013, with 6 pilot
Switzerland. sites performing flexible sigmoidoscopies in the first 8 months of screening.
Methods: This is a prospective, consecutive case series conducted at a hospital AIMS & METHODS: We aim to describe ADR in BowelScope Screening. The
with tertiary care endoscopy from September 2010 until January 2014. NHS Bowel Cancer Screening System database was interrogated and ADRs
Indications were fistulae, anastomotic leakages, perforations, deroofed submu- reviewed for each screening centre and screening endoscopist. ADR was reviewed
cosal lesions for biopsy, refractory bleeding and stent fixation in the gastroin- graphically, with a funnel plot, constructed using the log odds method.
testinal (GI) tract. Primary technical success was defined as an adequate RESULTS: 49 endoscopists have performed 4444 sigmoidoscopies at 6 screening
deployment of the OTSC on the target lesion. Clinical success was defined as centres. Endoscopists had performed 2-330 procedures (median 66, mean 91). 29
resolution of the problem, for instance no need for surgery or further endoscopic endoscopists had performed 50 procedures; of these, 17 had performed 100
intervention. In case of recurrence retreatment of a lesion with a second inter- procedures.
vention was possible. Complications were classified into those related to seda- Centre 2 has a higher ADR than the other centres. When considering all proce-
tion, endoscopy or deployment of the clip. dures, this difference reaches statistical significance when compared to centres 3,
RESULTS: A total of 28 OTSC system applications were carried out in 21 5, and 6 (p50.05), and approaches significance when compared to centre 1
patients (median age 64 years [range 42-85], 33% females). Main indications (p 0.0687) and centre 4 (p 0.0548). When considering only the procedures
were fistulae (52%), most of them after percutaneous endoscopic gastrostomy done by endoscopists who have performed 50 or 100 sigmoidoscopies, there
(PEG) tube removal and anastomotic leakage after GI surgery (29%). Further remains a significant difference (p50.05) between centre 2 compared to centres 5
indications were unroofed submucosal lesions after biopsy, upper gastrointestinal and 6, but not to the other centres. A funnel plot of individual endoscopist ADRs
bleeding or esophageal stent fixation. 48% of the OTSC were applied in the demonstrates one endoscopist below the 99.8% control limit.
upper and 52% in the lower GI tract. The range of lesion size was 2-20 mm Overall BowelScope ADR is 8.6%. ADR by centre is shown in Table 1.
(mean 8 mm). Primary technical success and clinical success were achieved in Table 1 - ADR by centre and endoscopist volume
85% and 67%, respectively. In 53% of cases the suction method was used with-
out accessories like Twin grasper or Tissue anchor. No endoscopy-related or All Centres
OTSC-related complications were described. Centre 1 Centre 2 Centre 3 Centre 4 Centre 5 Centre 6
CONCLUSION: OTSC is a useful tool for endoscopic closure of various GI Endoscopist
lesions like fistulae or leakages. Future randomized prospective multicenter trials procedure ADR ADR ADR ADR ADR ADR ADR ADR
are needed. counts % % % % % % % range %
Disclosure of Interest: None declared
All 8.8 11.7 8.9 7.6 6.5 7.3 8.6 0.0-60.0
50 8.9 11.3 8.1 8.6 6.4 6.4 8.6 3.1-14.0
P0750 INVESTIGATING THE INVESTIGATION - INCIDENTAL 100 9.0 11.3 8.9 8.6 3.1 5.2 8.7 3.1-13.0
COLONIC HOTSPOTS ON PET-CT SCANS
R. Sinha1,*, W.S. Ngu2, A. Ramadas1, A. Reddy2, R. Anandavelu1, D. Aitken2,
M. Jha2 CONCLUSION: Adenoma detection rates within BowelScope screening show
1
Gastroenterology, 2Colorectal surgery, South Tees NHS Foundation Trust, variation between centres. There is also variation between endoscopists in terms
Middlesbrough, United Kingdom of individual ADRs, although all but 1 endoscopist are above the 99.8% lower
Contact E-mail Address: rohits78@gmail.com control level on funnel plot. These variations require further exploration at both
centre and individual level, and feedback and education methods will be used to
INTRODUCTION: Positron emission tomography (PET) measures metabolic improve ADRs.
changes at a cellular level enabling detection of early stage disease. Incidental Disclosure of Interest: None declared
2-deoxy-[18FF]fluoro-2-D-glucose (FDG) colonic uptake is detected in 1.3-3% of
patients with up to a third resulting in false positive results 1. Follow-up endo-
scopy is recommended to further distinguish these FDG avid lesions 2. Cancer P0752 FLEXIBLE SIGMOIDOSCOPY SCREENING IN THE ENGLISH
detection rates of 7.8-18.9% have been quoted in various studies 1,3 BOWEL CANCER SCREENING PROGRAMME - EARLY RESULTS
AIMS & METHODS: Our aim was to evaluate incidental colonic FDG avid FROM THE BOWELSCOPE PILOT SITES
lesions on PET-CT by endoscopy. R. Bevan1,2,*, C. Nickerson3, J. Patnick3, R. Loke4, B. Saunders5, J. Stebbing6,
An analysis of retrospectively collected database of all patients (n 1564) who R. Tighe7, A. Veitch8, J. Painter1, C. Rees1,2
had PET-CT for extra-colonic malignancy between January 2011 to September 1
South of Tyne Bowel Cancer Screening Centre, Gateshead, 2Northern Region
2013 was performed. Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes, Sheffield,
RESULTS: Fifty-nine (3.77%) patients had focal colonic FDG uptake and 44 4
West Kent & Medway Bowel Cancer Screening Centre, Tunbridge Wells, 5St
(2.87%) patients went on to have colonoscopy. Marks Bowel Cancer Screening Centre, London, 6Surrey Bowel Cancer Screening
Indications for PET CT for those undergoing endoscopy was lung carcinoma Centre, Guilford, 7Norwich Bowel Cancer Screening Centre, Norwich,
(22), oesophageal carcinoma (5), gastric carcinoma (3), head and neck carcinoma 8
Wolverhampton Bowel Cancer Screening Centre, Wolverhampton, United
(7), lymphoma (6) and unknown primary (1). Kingdom
Median age was 68 with a male preponderance (2.4:1). Contact E-mail Address: roisinbevan@hotmail.com
Location on PET CT was categorized to sigmoid (22), rectal (9), anorectal (4),
caecal (3), hepatic flexure (2), transverse (1), splenic flexure (1), ascending (1) and INTRODUCTION: UK population colorectal cancer (CRC) screening has been
descending (1). successfully implemented with Bowel Cancer Screening Programme (BCSP)
Findings on endoscopy ranged from polyps (21), normal (9), diverticulosis (8), faecal occult blood testing biannually from age 60-75.
sigmoid cancer (4), caecal cancer (1) and colitis (1). A large UK study of once-only flexible sigmoidoscopy (FSIG) demonstrated a
In total, out of the all patients who had endoscopy, 19 (43.2%) were found to reductions in CRC incidence of 33% & death rates of 43%1. This, with the
have low-grade tubullovillous adenomas, 5 (11.1%) had cancer, whilst 2 (4.4%) screening centre infrastructure developed for the FOB programme, allowed pro-
had hyperplastic polyps on histology. vision of a new arm of BCSP, offering FSIG to 55 year olds in England, known
CONCLUSION: These findings are in keeping with other series and suggests to as BowelScope screening.
carry on with current practice of following up these "hot-spots" with endoscopic BowelScope screening began May 2013, with 6 pilot sites performing FSIGs in
investigations. the first 7 months.
REFERENCES AIMS & METHODS: We aim to describe procedural data from the early
1. Israel O, Yefremov N, Bar-Shalom R, et al. PET/CT detection of unexpected months of BowelScope screening. Data were obtained from The Bowel Cancer
gastrointestinal foci of 18F-FDG uptake: incidence, localization patterns, and Screening System (BCSS) database for all participants invited and participating
clinical significance. J Nucl Med 2005; 46: 758762. in BowelScope FSIGs May-Dec 2013. Procedural data were recorded, including
United European Gastroenterology Journal 2(5S) A339
insertion depth, adenoma detection rates (ADR), cancer detection, discomfort
P0754 PATIENTS EXPERIENCE OF COLONOSCOPY IN THE ENGLISH
levels, entonox usage & colonoscopy conversion rates.
BOWEL CANCER SCREENING PROGRAMME
RESULTS: 13927 people have been invited to or opted into BowelScope screen-
ing at 6 screening centres. Overall uptake is 43.5% (range 37.0-51.9%). 4 cancers A. Ghanouni1, A. Plumb2, C. Rees3,4, P. Hewitson5, H. Miller3, R. Bevan3,6,*,
have been detected. Polyps were detected in 16.4-23.8% of procedures (mean C.Von Wagner1
1
20.7%). Mean ADR was 8.4%. One centre has a significantly higher ADR Epidemiology and Public Health, 2Centre for Medical Imaging, UCL, London,
3
than the other 5 sites (p50.05). (see Table 1). South of Tyne Bowel Cancer Screening Centre, Gateshead, 4School of Medicine,
Table 1 BowelScope outcomes by anonymised centre Pharmacy and Health, Durham University, Stockton on Tees, 5Nuffield
Department of Population Health, University of Oxford, Oxford, 6Northern Region
Screening Attended B/S with ADR Colonoscopy Entonox Endoscopy Group, Newcastle, United Kingdom
Centre Invitees (%) adenoma(s) % Cancer required (%) used
INTRODUCTION: In the English Bowel Cancer Screening Programme, colono-
1 3125 1128 (51.9) 100 8.9% 1 39 (3.5) 121 scopy is the standard investigation to exclude cancer in participants who receive a
2 1866 524 (37.0) 64 12.1% 0 23 (4.4) 94 positive faecal occult blood test result. A questionnaire is sent to all patients 30
3 3779 1070 (40.9) 90 8.4% 0 50 (4.7) 60 days post-test. These data were used to assess patients experience of
4 986 311 (46.6) 25 8.0% 0 12 (3.9) 15 colonoscopy.
AIMS & METHODS: Anonymised data were extracted from the Bowel Cancer
5 1970 625 (47.4) 38 6.1% 2 21 (3.4) 28
Screening System. These included all patients who had colonoscopy between 01/
6 2181 479 (37.2) 30 6.2% 1 18 (3.8) 25
01/11 and 31/12/12. Questionnaire items on the pre-test experience (whether
TOTAL 13927 4135 347 8.4% 4 163 (3.9) 343 patients understood the risks/benefits), the hospital experience (the test itself,
issues of dignity/privacy) and post-test complications (bleeding/pain) were ana-
lysed. Pearson chi-square tests were used to compare experiences by gender, high
Most (52.7%) procedures were completed in 6-10 minutes. 78.6% of procedures vs. low levels of socioeconomic deprivation (using Index of Multiple Deprivation
were reported as causing no or minimal pain only, with only 34 procedures scores), and whether patients reported receiving sedation or not.
(0.8%) reporting severe pain. RESULTS: After excluding patients outside the target date range and those who
CONCLUSION: Uptake has varied between centres, but is lower than for the did not have colonoscopy, 76,717 patients were eligible for analysis, of whom
FOB arm of the BCSP. The average ADR is 8.4% (range 6.1-12.1%), lower than 60,581 (79.0%) responded to the questionnaire. Nearly all patients felt they
in the UK flexible sigmoidoscopy screening trial (12.1%, range 8.6-15.9%1) understood the risks (95.7%) and benefits (98.2%) of the test, and 97.8% felt
although the age range studied in the trial differs from this cohort. the preparation instructions were clear. Comparison by gender and deprivation
Further work will be required to investigate the variation in uptake rates and to did not yield clinically meaningful (3%) differences. In terms of the hospital
improve these rates. ADR variations may also need to be addressed in future experience, virtually all patients felt they were treated with respect (98.5%) and
work. had privacy (98.0%), but 20.8% experienced more discomfort than expected
REFERENCES (although only 5.2% asked for the test to be stopped/paused). Procedural dis-
1. Atkin W, et al. Once-only flexible sigmoidoscopy screening in prevention of comfort was moderated by gender, with more women than men reporting higher-
colorectal cancer: a multicentre randomised controlled trial. Lancet 2010; 375: than-expected discomfort (25.4% vs. 17.9%; p5.0005), and requesting that the
1624-1633. test be stopped/paused (7.1% vs. 3.9%; p5.0005). Use of sedation showed only a
Disclosure of Interest: None declared weak association with patient experience: 22.2% of sedated vs. 20.2% of non-
sedated patients reported unexpected discomfort; 6.4% vs. 4.8% asked for the
test to be stopped/paused; both p-values 5.0005). Post-test, 14.3% of patients
P0753 PATIENT-REPORTED EXPERIENCE OF COMFORT AND reported pain and 6.9% reported rectal bleeding. Pain was more common in
DIGNITY IN FLEXIBLE SIGMOIDOSCOPY: DATA FROM THE NHS women (18.0% vs. 11.9%; p5.0005) but there were no other clinically mean-
BOWEL SCOPE SCREENING PILOT ingful differences post-test related to gender or deprivation level.
C.Von Wagner1, H. Bowyer1, R. Bevan2,3,*, C. Rees3,4, W. Atkin5, J. Wardle1 CONCLUSION: Most patients referred for colonoscopy as part of the Bowel
1
Epidemiology and Public Health, UCL, London, 2Northern Region Endoscopy Cancer Screening Programme have a positive colonoscopy experience. The most
Group, Newcastle, 3South of Tyne Bowel Cancer Screening Centre, Gateshead, negative aspect of the experience was the test being unexpectedly uncomfortable.
4
School of Pharmacy and Health, Durham University, Stockton on Tees, Patients are extensively counselled pre-procedure but more emphasis on mana-
5
Department of Surgery and Cancer, Imperial College, London, United Kingdom ging expectations, along with continued measures to reduce discomfort and pain
are required, particularly for women.
INTRODUCTION: The NHS Bowel Cancer Screening Programme started flex- Disclosure of Interest: None declared
ible sigmoidoscopy (FS) screening (also known as Bowel Scope Screening, BSS)
at six centres across England (Gateshead, Guildford, London, Medway,
Norwich, Wolverhampton) in March 2013. The aim of this analysis was to P0755 ENDOSCOPIC RESECTION OF GIANT COLONIC POLYPS
investigate the extent to which high levels of patient satisfaction recorded in SIZE MATTERS!
previous UK trials can be replicated in the early stages of a routine screening R. Bhattacharyya1,*, G. Longcroft-Wheaton1, P. Bhandari1 on behalf of
programme. Portsmouth, UK
AIMS & METHODS: We used data from an ongoing study monitoring patient- 1
Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, United
reported experience in the pilot phase of the BSS Programme. We report data Kingdom
from the post-AM questionnaire which is given to patients at the end of their FS
appointment and supposed to be completed on the following day. INTRODUCTION: Colonic polyps sized 50mm and above are traditionally
RESULTS: As of January 2014, we had received 2,324 questionnaires. treated by surgical resection. Endoscopic resection has now become increasingly
Satisfaction with the test was high with 98.8% of patients being either satisfied common as the expertise of western endoscopists improves. There is very little
(21.1%) or very satisfied (77.7%). Nonetheless, 43% of patients reported mod- published literature on endoscopic resection of these giant polyps.
erate (34%) or severe pain (9%) which was high compared with the St Marks AIMS & METHODS: The aim of the study was to evaluate the feasibility, safety
demonstration programme1 and the UK Flexible Sigmoidoscopy Trial2. Women and efficacy of endoscopic resection of giant polyps 50mm in size.
were three times as likely to report severe pain during the test than men (14.3% vs This was a prospective cohort study. All patients who underwent endoscopic
4.6%), and twice as likely to find the test as more painful than they had expected resection of colonic polyps 50mm from 2007-2013 were prospectively entered
(39.9% vs 20.1% respectively). Only about 1 in 10 patients reported being mod- into a database. We excluded all polyps with fibrosis related to previous inter-
erately (9.8%) or severely (1.4%) embarrassed during the test, with women being vention. All patients were tertiary referrals from experienced gastroenterologists.
slightly more likely than men to fall into these categories (13.4 vs. 8.9%). Women All procedures were performed by a single experienced endoscopist.
also had a much stronger preference for the test to be carried out by a female RESULTS: N 124 polyps in 122 patients. Mean polyp size 71mm. Range 50-
practitioner than men (41.2% vs 7.1% respectively). 170mm. 27(22%) in right colon and 97 (78%) in left colon. M:F ratio 1.1:1. All
CONCLUSION: The vast majority of patients were satisfied with their experi- polyps were resected in a piecemeal fashion. The mean procedure time was 120
ence of FS screening. However, levels of pain appear high when compared with minutes (range 90 to 240).
previous trials. Emphasis should be placed on ensuring that patients have as The complication rate was 11/124(8.9%). All these patients required inpatient
comfortable a procedure as possible. Additional consideration should be given stay. There were 9 bleeds (3 immediate and 6 delayed), 1 post polypectomy
to women being able to choose the sex of the practitioner performing the test. syndrome and 1 case of split muscle fibres (clipped endoscopically). 1 case of
REFERENCES immediate bleeding required surgery to control the bleeding. All the others were
1 Robb K, Lo S, Power E, et al. Patient-reported outcomes following flexible managed conservatively. 4 of the 9 bleeds required blood transfusion. The com-
sigmoidoscopy screening for colorectal cancer in a demonstration screening pro- plication rate was independent of polyp size, resection technique or site of the
gramme in the UK. J Med Screen 2012; 19: 171-176. lesion.
2 Taylor T, Williamson S, Wardle J, et al Acceptability of flexible sigmoidoscopy Follow up data was available for 90 polyps. The recurrence rate was 21/
screening in older adults in the United Kingdom. J Med Screen 2000; 7: 38-45. 90(23.3%). Of the 21 recurrences, 16/21(76%) patients achieved complete clear-
Disclosure of Interest: None declared ance with a further 1 to 2 endoscopic procedures. The recurrence rate was sig-
nificantly dependent on polyp size and was not dependent on the resection
technique or the site of the lesion. Recurrence gradually increased with an
increase in polyp size up to 70mm. Recurrence was seen in 3/34(8.8%) polyps
55mm, in 7/54(12.9%) polyps 60mm and in 9/63(14.2%) polyps 70mm.
However, in polyps 470mm, the recurrence rate greatly increased to 12/
27(44%) (p 0.002).
A340 United European Gastroenterology Journal 2(5S)
histologic excision, polyp fly away, retrieval rate, early bleeding (48 hours),
delayed bleeding (2 weeks) and perforation.
Size RESULTS: A total of 157 polyps were removed. Median (range) polyp size was
4.0mm (3-7mm). There was no significant difference in the patients demographic
Recurrence 55mm 60mm 70mm 470mm details or polyp characteristics between the two groups. Endoscopic completeness
21/90 (23.3%) 3/34 (8.8%) 7/54 (12.9%) 9/63 (14.2%) 12/27 (44.4%) of excision was significantly higher with the Exacto snare compared to the
p 0.002 Olympus snare (90.2% vs. 73.3%, p 5 0.05). There was also a trend towards a
higher complete histological excision rate with the Exacto snare (71.9% vs. 64.4%),
but this did not reach statistical significance (p 0.4). Polyp fly away occurred
less often with the Exacto snare (14.6% vs. 35.3%, p50.05), but there was no
CONCLUSION: 1) It is safe and feasible to endoscopically resect polyps 50- significant difference in the polyp retrieval rate (84.3% vs. 83.8%, p 0.9). There
170mm in size. were no significant complications with either snare. Where the completeness of
2) Recurrence is significantly dependent on polyp size. excision was assessable (complete or incomplete), there was a fair level of agree-
3) Giant polyps resected endoscopically have a significant recurrence rate. The ment (kappa 0.36) between endoscopic and histological assessment.
majority of these can be cleared by further endoscopic procedures. However, we CONCLUSION: This is the first study we are aware of that compares complete-
believe that the recurrence rate in polyps above 70mm is very high and surgery ness of excision with different snares. Our findings suggest that snare type may be
should be considered in these cases. an important factor determining completeness of excision when removing small
4) Complication rates are independent of size. polyps by the cold snare techniques.
Disclosure of Interest: None declared Disclosure of Interest: None declared
P0756 ADVISABILITY OF COLORECTAL ENDOSCOPIC P0758 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
SUBMUCOSAL DISSECTION IN ELDERLY: TREATMENT AND MANAGEMENT OF PATIENTS WITH COLORECTAL LESIONS: A
LONG-TERM OUTCOMES CONSENSUS REPORT BASED ON CLINICAL EVIDENCE
R. Kobayashi1,*, K. HIRASAWA1, H. KANEKO1, M. MAKAZU1, C. SATO1, S.K. Singh1,*, R. Arsenescu2, H. Bertani3, F. Caillol4, D. Carr-Locke5,
A. KOKAWA1, S. MAEDA2 K. Chang6, A. Dlugosz7, J.-P. Galmiche8, S.-I. Gan9, K.Y. Ho10, V. Konda11,
1
Division of Endoscopy, Yokohama City University Medical Center, 2Department H. Neumann12, F. Prat13, P. Sharma14, K. Wang15, A. Zfass16
1
of gastroenterology, Yokohama City University Graduate School of Medicine, Gastroenterology / Endoscopy, Boston University / VA Boston, Boston, MA, 2The
Yokohama city, Japan Ohio State University, Columbus, United States, 3Nuovo Ospedale Civile
Contact E-mail Address: ryo_1001@yokohama-cu.ac.jp SantAgostino Estense, Modena, Italy, 4CLCC Institut Paoli-Calmettes, Marseille,
France, 5Beth Israel Medical Center, New York, 6University of California Irvine
INTRODUCTION: Endoscopic submucosal dissection (ESD) is becoming wide- Medical Center, Orange, United States, 7Karolinska University Hospital
spread as a treatment of superficial colorectal neoplasm; however, the efficacy Huddinge, Stockholm, Sweden, 8CHU Nantes, Nantes, France, 9Virginia Mason
and safety of colorectal ESD in elderly patients has not been fully evaluated. Medical Center, Seattle, United States, 10National University Hospital, Singapore,
AIMS & METHODS: In the present study, we assessed the treatment and long- Singapore, 11University of Chicago Medical Center, Chicago, United States,
term outcomes of colorectal ESD in elderly patients. 12
Universitaetsklinikum Erlangen, Erlangen, Germany, 13Hopital Cochin, Paris,
Between April 2008 and March 2014, 285 consecutive superficial colorectal France, 14VA Kansas City Medical Center, Kansas City, 15Mayo Clinic Rochester,
tumors in 267 patients were treated using ESD. Patients were divided into two Rochester, 16VA Richmond Medical Center, Richmond, United States
groups; elderly (75 years of age or older) and non-elderly (less than 75 years of Contact E-mail Address: singhsk@bu.edu
age), then were retrospectively compared to patient and tumor characteristics
and treatment outcome. INTRODUCTION: Recent studies have highlighted the role of Confocal Laser
Long-term outcomes in elderly patients were also evaluated. Endomicroscopy (CLE) for the characterization of colorectal lesions in vivo,
RESULTS: The elderly group comprised 93 lesions in 83 patients and non- specifically for the real time characterization of polyps and endoscopic mucosal
elderly group comprised 192 lesions in 184 patients. resection (EMR) sites.
No significant differences were observed between the two groups with respect to AIMS & METHODS: We sought to develop consensus recommendations for the
patient and tumor characteristics as the following factors: sex, tumor location, role of CLE in the management of patients with colorectal lesions. To this end, a
tumor depth, tumor size, tumor morphology. single CLE expert developed a series of preliminary statements on the use of CLE
In all patients, the rates of en bloc resection, R0 resection and curative resection for the characterization of colorectal lesions based on the available clinical evi-
were 98.9% (282/285), 90.2% (257/285) and 82.5% (235/285) respectively. Mean dence. Twenty statements were submitted for external review by a group of 16
procedure time was 67.2 minutes (range 10-273 minutes), the rate of delayed gastrointestinal CLE experts using a modified Delphi approach. After two
bleeding was 3.9% (11/285) and the rate of perforation was 9.5% (27/285). rounds of votes to assess the quality of evidence and strength of recommenda-
There were no significant differences between the two groups in the rates of en tions based on relevant studies, statements were adopted if the threshold of
bloc resection, R0 resection, curative resection, delayed bleeding, perforation, agreement exceeded 75%.
and procedure time. RESULTS: 15 of 20 statements achieved consensus and were adopted: CLE has
In 83 elderly patients, during a median follow-up period of 20.2 months (range been shown to be highly accurate for real-time histopathological classification of
1.4-63 months), 6 patients were excluded from the long-term prognosis analysis colonic neoplasia in situ. CLE criteria can be used to accurately and reliably
because of missing follow-up. Four of 16 patients who judged as non-curative identify normal, hyperplastic, adenomatous (dysplastic), and cancerous
resection underwent additional surgery, and the others requested only observa- mucosa; criteria for serrated neoplasia require further validation. CLE criteria
tion. Two of 77 patients (2.6%) died of infection of unknown cause (n 1) and characterize colonic tissue accurately both in real time during endoscopy as well
heart failure (n 1). The 3- and 5-year overall survival rates were 96.4% and as off-line. CLE can be used to define the extent of flat lesions. The combination
87.7%, respectively. However, we did not observe local or distant recurrences in of CLE and virtual chromoendoscopy (VCE) is highly accurate for classifying
any of the patients were followed up. Therefore, the 3- and 5-year disease-specific colonic polyps 55 mm both in real time and offline and should undergo further
survival rates were 100%. study toward enabling a resect-and-discard approach. A diagnosis of intramu-
CONCLUSION: Because there was no significant difference in treatment out- cosal carcinoma and/or high-grade dysplasia by CLE alone is sufficient to trigger
come between in elderly and non-elderly group, colorectal ESD could be used as an appropriate therapeutic resection. CLE can be used to classify lesions and
a treatment choice for superficial colorectal tumors in elderly patients. However, define margins for EMR/ESD. CLE has a role in resurveillance 3-12 months
many of the elderly non-curative cases were observed without additional surgical following EMR/ESD of advanced colonic neoplasia. Absence of residual neo-
treatment, implying that such patients are necessary for careful follow-up by plasia by CLE and VCE at 3-12 months obviates the need for re-EMR/ablation.
computed tomography (CT) or measuring tumor markers. The extent of therapy for residual neoplasia post-EMR can be guided in real time
Disclosure of Interest: None declared by the combination of CLE and VCE.
CONCLUSION: According to a panel of 16 gastrointestinal endoscopy experts
in Confocal Laser Endomicroscopy, CLE is an important adjunct to current
P0757 A COMPARATIVE STUDY OF TWO DIFFERENT SNARES FOR endoscopic practice for the management of colorectal lesions. Standardized
THE COMPLETENESS OF POLYP EXCISION guidelines are in development to serve as an educational resource for physicians
S. Din1,*, A. Ball1, S. Riley1, P. Kitsanta2, S. Johal1 to provide increasingly personalized, state-of-the-art care for their patients.
1
Gastroenterology, 2Histopathology, Sheffield Teaching Hospitals NHS Disclosure of Interest: None declared
Foundation Trust, Sheffield, United Kingdom
INTRODUCTION: Polypectomy with cold snare is a frequently used technique P0759 IMMEDIATE AND DELAYED BLEEDING AFTER ERCP:
for the removal of small colorectal polyps. The influence of snare type on com- RESULTS FROM SINGLE CENTRE EXPERIENCE AT A DISTRICT
pleteness of excision is unknown. We have therefore compared the effectiveness GENERAL HOSPITAL IN JAPAN
of two different snares. H. Hisai1,*, T. Hirako1, Y. Ikeda1, S. Miura1, Y. Koshiba1, E. Miyazaki1
AIMS & METHODS: Patients attending for colonoscopy at Sheffield Teaching 1
Department of Gastroenterology, Japanese Red Cross Date General Hospital,
Hospitals, England were prospectively included in the study. We assessed the Date, Japan
endoscopic and histological completeness of excision following cold snare of 3-
7mm polyps using the Exacto mini-snare (diameter 0.30mm) and Olympus mini- INTRODUCTION: Bleeding following endoscopic retrograde cholangiopan-
snare (diameter 0.47mm). Prior to the study, consensus regarding the endoscopic creatography (ERCP) including endoscopic sphincterotomy (ES) is one of the
completeness of excision was standardised to complete, incomplete or uncertain most frequent complications, and has been reported in 1-10% of patients.
using the Delphi method. Completeness of excision was aided by chromoendo- Haemorrhage that cannot be controlled by conservative management needs to
scopy (indigo carmine 0.1%). The primary outcome was endoscopic complete- be controlled endoscopically, radiologically, or surgically. However, there are few
ness of excision. Secondary outcome measures included: completeness of reports about the incidence and the outcomes at a district hospital.
United European Gastroenterology Journal 2(5S) A341
AIMS & METHODS: The aim of this study was to assess the incidence of
P0761 SEQUENTIAL PERFORMANCE OF DOUBLE GUIDEWIRE
ERCP-related haemorrhage and the clinical outcomes in the district general
TECHNIQUE AND TRANSPANCREATIC PRECUT
hospital setting. A review of all patients undergoing ERCP at our institution
SPHINCTEROTOMY IN DIFFICULT BILIARY CANNULATION
from April 1996 and March 2014 was performed to assess the ERCP-related
haemorrhage. ERCP-related haemorrhage was classified according to the J. Park 1,*, J.H. Chang1,2, C.W. Kim1, S.W. Han1
1
timing of bleeding. Immediate bleeding was defined as any haemorrhage The Catholic University of Korea, Seoul, 2Internal Medicine, The Catholic
during ERCP and warranting endoscopic haemostasis within the procedure fol- University of Korea, Bucheon, Korea, Republic Of
lowing epinephrine spray. A diagnosis and severity of delayed bleeding was made
according to Cottons classification (GIE 1991). INTRODUCTION: Double guidewire technique (DTG) and transpancreatic
RESULTS: Out of 6002 ERCPs, we performed ES in 975 patients, needle knife precut sphincterotomy (TPS) are alternative techniques in failed standard biliary
sphincterotomy (NKS) in 195 patients, NKS followed by ES in 22 patients, cannulation during endoscopic retrograde cholangiopancreatography (ERCP)
endoscopic papillectomy in 12 patients and endoscopic large balloon dilatation when a guidewire proceeds into the pancreatic duct. However, the sequential
in 47 patients. No patients were taking anticoagulants at the time of ERCP. performance of TPS after DTG has not been evaluated.
During ERCP, 48 patients (0.80%) experienced immediate bleeding. All patients AIMS & METHODS: We aimed to investigate the usefulness and complications
underwent endoscopic haemostatic method including balloon tanponade, dilute of seqeuntial DTG-TPS in comparison with needle knife precut (NK). We con-
epinephrine (1:10000), heater probe, clipping, covered metallic stent and com- secutively enrolled 612 patients with na ve papilla undergoing ERCP for biliary
bined hemostatic procedures. Initial haemostasis was achieved in all patients. cannulation between March 2010 and April 2014. In cases of unsuccessful stan-
However, delayed bleeding occurred in 3 patients (6%). By definition, delayed dard technique, DTG or NK was performed according to the guidewire passage
bleeding occurred in 26 patients (0.43%). There were 14, 5 and 7 cases of mild, through the pancreatic duct. TPS was sequentially performed when DTG had
moderate and severe bleeding, respectively. The time period between ERCP and failed. Patients demographics, laboratory, and procedure-related data were ana-
haemorrhage ranged from 1 d to 14 d (median 4 d). The time to onset of delayed lyzed retrospectively.
bleeding was not significantly different between patients with or without immedi- RESULTS: During 612 ERCPs, DTG and NK was attempted in 67 and 58
ate bleeding. Seventeen out of 26 (65%) were managed endoscopically with patients, respectively. Sequential DTG-TPS were performed in 38 patients.
various haemostatic methods including dilute epinephrine, heater probe, argon Successful biliary cannulation was performed in 42%, 74%, and 66% of the
plasma coagulation, clipping, fibrin glue, covered metallic stent and combined DTG, TPS, and NK group, respectively (P 0.002). The cannulation rate was
procedures. Initial haemostasis was successfully attained in all patients. The re- higher in the sequential DTG-TPS group (85%) than in the NK group
bleeding rate was 15% (4 of 26). The treatment for the 4 patients with re-bleeding (P 0.014). Post-ERCP pancreatitis (PEP) occurred in 37% of the sequential
was as follows: 1 underwent 1 session, 1 underwent 2 sessions and 2 underwent 3 DTG-TPS group and in 10% of the NK group (P 0.002). In the sequential
sessions of endoscopic combined procedures (2 patients required fibrin glue) and DTG-TPS group, PEP developed in 24% patients with pancreatic duct (PD)
the bleeding was finally controlled. No patients required angiographic embolisa- stent, but in 62% patients without PD stent (P 0.023). Among them, one
tion and surgery. No complications of the hemostatic procedure occurred in any patient without PD stent expired due to severe pancreatitis.
patients. There was no bleeding-related death. CONCLUSION: The sequential DTG-TPS is a useful alternative technique for
CONCLUSION: Early recognition and appropriate management of ERCP- biliary cannulation compared with NK in patients who have failed standard
related haemorrhage is crucial for optimal results. technique. Their rate of PEP was higher than that in the NK group, but PD
Disclosure of Interest: None declared stent had a protective role over PEP.
Disclosure of Interest: None declared
INTRODUCTION: Probe-based Confocal Laser Endomicroscopy (pCLE) INTRODUCTION: Endoanal ultrasonography shows good accuracy in defini-
increases diagnostic accuracy via targeted biopsies and greatly impacts manage- tion of the anatomy of perianal fistulae, including those associated with Crohns
ment decisions, with accuracy rates above 80%. The improved diagnostic cap- disease (CD). Several studies have been proposed ultrasonographic features to
ability of pCLE may result in high post-procedure health resource utilization discriminate anal fistulae associated with CD in relation to cryptoglandular
with increases in subsequent surgical and interventional procedures. Our aim fistulae.
was to examine downstream revenue and profit generated from surgical and AIMS & METHODS: Our aim was to evaluate several ultrasonographic features
interventional radiology procedures after pCLE. that may distinguish these two types of fistulae.
AIMS & METHODS: A retrospective chart review was performed in a tertiary Retrospective study including fifty-eight patients who underwent endoanal ultra-
care institution. We identified patients who underwent diagnostic pCLE between sonography 2D between 2008 and 2013. The perianal fistulae variables studied
August 2011 and December 2012 for indeterminate pancreaticobiliary lesions. were the complexity, transversal diameter, presence of secondary tracks and
Revenue data was generated using AllScripts EPSi and billing information to fistulous debris. For patients with CD was also calculated the adapted perianal
generate financial estimates. disease activity index (PDAI excluding the influence in sexual activity).
RESULTS: 67 patients underwent diagnostic pCLE for indeterminate pancrea- Statistical analysis was performed using the SPSS program vs20.0 and a p value
ticobiliary lesions during the study period. Of these, 12 (18%) patients had sub- of less than 0.05 was considered statistically significant.
sequent procedures related to their diagnosis. Diagnoses included RESULTS: Fifty-eight patients were included, 48% with CD with a mean PDAI
adenocarcinoma (n 8), intraductal papillary mucinous neoplasm (n 1) and of 7.63.2. In CD patients a higher PDAI was statistically associated to more
United European Gastroenterology Journal 2(5S) A345
complex fistulae (8.5 vs 5.5, p 0.028). 38% of all patients had been previously opposite when stable scope) and drainage (transductal if early guidewire passage
submitted to a surgery intervention for fistula resolution. The ultrasonographic or if failed cannulation of native papilla in benign obstruction, transmural if
features that correlated with the presence of fistulae associated with CD were the otherwise) were used. Caliber of access duct was 9.1 mm (IQR 6.3-15.6) for
complexity (OR:5; IC95% 1.6-15.3; p 0.004), the presence of secondary tracks extrahepatic (27%) and 5.5 mm (IQR 4.0-7.9) for intrahepatic access (73%).
(OR:3.2; IC95% 1.1-9.5; p 0.036) and the presence of fistulous debris (OR:5.9; Number of ERCP/PTBD over study period was 1048/5 (EUSBD 4.2% of
IC95% 1.6-15.3; p 0.002). There was no statistical difference between crypto- ERCP; PTBD 11% of EUSBD). Clinical success was defined as bilirubin 5
glandular fistulae and fistulae associated with CD with respect to dimensions 80% baseline values, symptom disappearance and hospital discharge. Adverse
(4.1mm vs 4.9mm, p 0.24). events as per consensus. Follow-up through chart review and phone contact.
CONCLUSION: In our study, the complexity of the perianal fistulae and also RESULTS: Technical success was achieved in 43 patients (97.7%) and clinical
the presence of secondary tracks and debris revealed to be strong predictors of success in 70%. There were adverse events in 6 patients (13.6%): 5 mild (3 mild
Crohns related perianal fistulae. bleedings, 1 acute pancreatitis, 1 hypoxemia) and 1 fatal case of cholecystitis.
Disclosure of Interest: None declared Transductal EUSBD was performed in 11 patients (7 DAG and 4 RV techni-
ques), and transmural EUSBD in 36 (26 HGS/hepaticojejunostomy and 10 CDS/
choledocogastrostomy, including dual DAG-HGS in 4). Fully covered metal
P0776 NOVEL COMPUTER-AIDED QUANTITATIVE ANALYSIS OF stents were used in 90.6% for transmural EUS-guided biliary drainage (22
THE DISTRIBUTION OF CONTRAST IN CONTRAST-ENHANCED Hanaro stent, 7 Wallflex stents). A variety of stent-anchorage techniques were
EUS FOR DIFFERENTIAL DIAGNOSIS OF PANCREATIC TUMORS employed in 65% of these patients (hemoclips, flaps, double pig-tails, balloon
H. Imazu1,*, T. Kato1, M. Chiba1, S. Koyama1, T.L. Ang2, H. Tajiri3 expansion or more than one anchorage technique). Accurate follow-up was
1
Department of Endoscopy, THE JIKEI UNIVERSITY SCHOOL OF obtained in 35 patients. After a mean of 146 days (SD 141), 5 dysfunctions
MEDICINE, Tokyo, Japan, 2Department of Gastroenterology and Hepatology, occurred (2 patients with plastic stents [1 migration, 1 occlusion], 3 with metal
Changi General Hospital, Singapore, Singapore, 3Division of Gastroenterology and stents [2 angulation, 1 late migration]).
Hepatology, Department of Internal Medicine, THE JIKEI UNIVERSITY CONCLUSION: After a decade-long usage, the dominant strategy for EUSBD
SCHOOL OF MEDICINE, Tokyo, Japan was transmural fully covered metal stents with ancillary anchorage. No short-
Contact E-mail Address: himazu21@aol.com term migration, minimal late dysfunction and comparable adverse event rate to
purported less invasive RV were found. Intriguing higher rate of intrahepatic Vs
INTRODUCTION: Differentiating between pancreatic carcinoma (PC) and extrahepatic possibly explained by patient selection/PTBD use patterns warrants
chronic pancreatitis (CP) with pseudotumor is still challenging, even with con- clarification.
trast-enhanced EUS (CE-EUS) or EUS-FNA. We developed the novel compu- Disclosure of Interest: None declared
ter-aided diagnostic software (Madara, Inspeedia Inc., Kariya, Japan) to
quantify the pattern of contrast distribution in CE-EUS.
AIMS & METHODS: The aim of this study was to evaluate the utility of CE- P0779 FACTORS ASSOCIATED WITH THE ACCURACY OF EUS-
EUS with Madara for differential diagnosis of PC and CP with pseudotumor. GUIDED FINE NEEDLE ASPIRATION FOR THE DIAGNOSIS OF
Consecutive patients who had PC or CP with pseudotumor and underwent CE- SOLID PANCREATIC MASSES
EUS from January 2011 to December 2013 were retrospectively analyzed. A J. Iglesias-Garc a1,*, D.de la Iglesia-Garc a1, N. Vallejo-Senra1, J. Larino-Noia1,
curvilinear echoendoscope (GF-UCT260), Aloka Prosound 10 processor and I. Abdulkader2, L. Uribarri-Gonzalez1, J.E. Dominguez-Munoz1
intravenous administration of 0.015ml/kg of Sonazoid were used for CE-EUS. 1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Using our software, a region of interest (ROI) which divided into 100 cells was Research in Digestive Diseases, 2Pathology, University Hospital of Santiago de
placed to cover an area within pancreatic mass. Differences of grade of gray scale Compostela, Santiago de Compostela, Spain
levels between the adjoining cells within the ROI were detected, and the number
of adjoining cells which showed a difference of the gray scale level was automa- INTRODUCTION: Endoscopic ultrasound (EUS)-guided fine needle aspiration
tically calculated in each frame rate of CE-EUS (heterogeneity index). A hetero- (FNA) and biopsy (FNB) are accurate techniques for sampling pancreatic solid
geneity index curve was also automatically generated to depict the changes of the lesions. Diagnostic yield of FNA/FNB may be influenced by different factors,
heterogeneity index over time, and the mean heterogeneity index from start to but information on this regard is lacking.
one minute after injection of Sonazoid was calculated. Moreover, using a con- AIMS & METHODS: Aim of our study was to evaluate potential factors asso-
ventional software to quantify the degree of enhancement, in which time inten- ciated with the diagnostic accuracy of EUS-FNA/FNB for the differential diag-
sity curve (TIC: Hitachi/Aloka Co., Ltd., Tokyo, Japan) was generated to nosis of solid pancreatic masses.
depict the changes in the signal intensity, maximum intensity gain (MIG: peak 447 consecutive patients (mean age 66.4 years, range 17-92, 262 male), who
intensity base intensity) was also calculated. The final diagnosis of PC was underwent EUS-FNA/FNB for the evaluation of solid pancreatic lesions over
based on the results of surgery or EUS-FNA, while CP was diagnosed from the last 4 years were identified from a prospectively collected endoscopy data-
EUS-FNA, the clinical course and other imaging tests. base, and included in the study. EUS was performed using a convex array
RESULTS: Fifty-nine patients (39 with PC and 20 with CP) were analyzed. The echoendoscope (Pentax EG-3870UTK and EG-3270UK). FNA/FNB was per-
heterogeneity index curve showed bell and flat curve type in 9 patients with formed with standard cytology and ProcoreTM histology needles (Cook Medical
CP, irregular curve type in 11 patients with CP and 37 with PC, and flat curve Inc, Limerick Ireland). The impact of the type of scope, location and size of the
type in 2 with PC. Thus, bell and flat curve type was specific to CP, while lesion, on-site cytopathological evaluation, number of needle passes and type of
flat curve type were specific to PC. The mean heterogeneity index in PC needle on the diagnostic accuracy of FNA/FNB was evaluated. Overall diagnos-
patients was significantly higher than CP patients (15.6 vs. 6.1, p50.0001). tic accuracy was calculated by using surgical histopathology in operated cases
Flat curve type of heterogeneity index curve and the mean value of heterogeneity and global clinical and radiological assessment and follow-up in non-operated
index showed sensitivity of 92.3% and specificity of 90% for differentiating cases as gold standard. Data were analyzed by multivariate stepwise logistic
between PC and CP with pseudotumor. On the other hand, MIG in CP patients regression.
was significantly higher than PC patients (21.1 vs. 15.7, p 0.01), and showed RESULTS: Mean size of solid pancreatic masses was 36.116.4 mm. 283 tumors
sensitivity of 71.8% and specificity of 65%. Combined assessment of heteroge- were located in the head of the pancreas, 124 in the body, and 40 in the tail. Final
neity index curve and MIG with time intensity curve, using the cut-off value of diagnosis was pancreatic adenocarcinoma in 294 cases, inflammatory lesions in
heterogeneity index of 10.3 and MIG of 14.3, yielded sensitivity of 94.3% and 74 cases, neuroendocrine tumor in 23 cases, pancreatic metastasis in 17 cases,
specificity of 95% to differentiate between PC and CP with pseudotumor. cystic lesions with solid components in 36 cases and pancreatic lymphoma in 3
CONCLUSION: CE-EUS with Madara diagnostic software to quantify the cases. Overall diagnostic accuracy was 87.5% (95%CI 84.1-90.2). Size of the
pattern of contrast distribution might be useful for making a differential diag- lesion (OR 1.03; 95%CI 1.00-1.06; p 0.014), onsite evaluation of the FNA/
nosis between PC and CP with pseudotumor. FNB sample (OR 4.36; 95%CI 1.3-14.9; p 0.019), and the use of ProcoreTM
Disclosure of Interest: None declared needles (OR 3.02; 95%CI 1.4-6.5; p 0.005) were independently associated with
a correct diagnosis after FNA/FNB.
CONCLUSION: EUS-guided FNA/FNB is an accurate technique. Factors asso-
P0777 TRANSMURAL STENT PLACEMENT AS THE DOMINANT ciated with a higher diagnostic yield are large lesions, onsite cytopathological
STRATEGY FOR ENDOSCOPIC ULTRASOUND-GUIDED BILIARY evaluation and the use of the ProcoreTM needles.
DRAINAGE Disclosure of Interest: J. Iglesias-Garc a Lecture fee(s) from: Cook-Medical,
I. Penas Herrero1,*, N. Alcaide1, R. Sanchez-Ocana1, P. Gil-Simon1, C. De la Consultancy for: Cook-Medical, D. de la Iglesia-Garc a: None declared, N.
Serna-Higuera1, M. Perez-Miranda1 Vallejo-Senra: None declared, J. Larino-Noia: None declared, I. Abdulkader:
1
Gastroenterology, Hospital Universitario Ro Hortega, Valladolid, Spain None declared, L. Uribarri-Gonzalez: None declared, J. E. Dominguez-
Contact E-mail Address: mpmiranda5@hotmail.com Munoz: None declared
INTRODUCTION: Over the past years, capsule endoscopy (CE) has been estab- INTRODUCTION: Small bowel capsule endoscopy (SBCE) represents the gold
lished as an imaging technique in the diagnosis of small bowel diseases. The aim standard diagnostic technique in case of obscure gastrointestinal bleeding.
of this study was to examine the limitations of this method by analysing a large Moreover, its use is gaining acceptance also as diagnostic procedure when an
number of consecutive CEs. organic disease of the small bowel (i.e. duodenum/jejunum/ileum) is suspected.
AIMS & METHODS: This was a retrospective study, including 1193 consecutive On the other hand, SBCE is an expensive, invasive tool and data about its cost/
examinations performed at our centre in 1091 patients (male/female 517/574, effectiveness are lacking. Thus, non-invasive markers of small bowel disease are
mean age SD: 61.83 17.46a, range: 9-93a) between 2002 and 2012. In 1061 desirable in order to increase the rate of positive SBCE examinations.
examinations the system of Given (Yoqneam, Israel) was used. In 132 exam- AIMS & METHODS: We aimed to evaluate the role fecal markers of inflamma-
inations the capsule endoscope MiroCam (IntroMedic, Seoul, South Korea) tion (i.e. fecal calprotectin and lactoferrin) and intestinal permeability test (i.e.
was used. lactulose-mannitol ratio, L/M) in predicting the presence of enteropathy at
RESULTS: Complications requiring an endoscopic or surgical intervention SBCE. We included consecutive patients who underwent SBCE because of symp-
occurred in 0.34% (4/1193) of examinations: In two patients the capsule was toms suggestive of small bowel disease (i.e. chronic diarrhea, chronic anemia,
retained in a duodenal diverticulum or a hiatal hernia, respectively. In both signs of malabsorption) and with negative upper and lower endoscopy. Patients
cases the capsule could be removed endoscopically. In one patient with dosed levels either of fecal calprotectin (normal values, n.v., 0-50 ug/g) or lacto-
Crohns disease (CD) the capsule was retained in a stenosis of the terminal ferrin (n.v. 0-7 ug/ml) and performed L/M test (n.v.50.030) at the time of SBCE.
ileum and was removed during colonoscopy after dilation of the stricture. One Erosions, aftous lesions, ulcers and vascular abnormalities at SBCE were con-
patient underwent surgery after the capsule was retained in a stenosis caused by sidered positive for small bowel disease presence.
CD. RESULTS: In this retrospective analysis of prospective collected data, 101 con-
Technical defects of the capsule or the data recorder occurred in 16 (1.34%) CEs: secutive patients (66F/35M; mean age 40 years) with dosed levels either of fecal
Hence the passage through the small intestine was not completely recorded calprotectin or lactoferrin were included. In 51 (50%) patients, SBCE detected
(n 12) or the pictures could not be used for further evaluation (n 4). the presence of small bowel disease. Sixty-three (62%) patients had increased
Transit abnormalities: In 1017 examinations (85.25%) the cecum was reached levels of fecal markers, whereas in 38 (38%) patients these markers were
within the recording period. normal. The diagnostic accuracy of fecal markers for the detection of small
bowel disease was 62.4%, with 75% sensitivity and 46% specificity, a positive
A348 United European Gastroenterology Journal 2(5S)
likelihood ratio (PLR) of 1.49 and a negative likelihood ratio (NLR) of 0.51. for constipation, we believe that Prucalopride could be useful in the preparation
Sixty-seven out of 101 patients performed also L/M test. This was abnormal in 46 of colon capsule endoscopy, speeding up intestinal transit and therefore making
(69%) patients and normal in 21 (31%). In 36/67 (54%) patients, SBCE was the examination shorter, increasing the excretion rate. This article presents the
positive for small bowel disease. The diagnostic accuracy of L/M test for the results obtained in terms of transit times, total examination time and expulsion
detection of small intestine disease was 76%, with 75% sensitivity and 56% rates.
specificity, a PLR of 1.7 and a NLR of 0.45. The alteration of at least one AIMS & METHODS: Pilot study with 50 patients (cases) with the new pre-
between fecal markers and L/M test has a diagnostic accuracy of 56.7%, whereas paration compared with 50 control patients with the standard preparation (PEG/
having both fecal markers and L/M test abnormal had a diagnostic accuracy of Fosfosoda/). Each video is read by two researchers.
64.6%. Preparation protocol: - Two days of residue-free diet - Day before the test, liquid
diet - Resolor 2 mg, 1 on each day of the diet and 2 on the examination day -
N Sensitivity % Specificity % PLR NLR Moviprep, 1 liter in the evening prior to the examination and 1 liter in the
patients (95%CI) (95%CI) (95%CI) (95%CI) morning of the examination Then 2 boosters of half a liter each in alarms 1
and 2.
Fecal markers 101 75 (60-86) 50 (34-64) 1.36 (1.08-2.05) 0.57 (0.30-0.88) RESULTS: A cohort with 41 men and 59 women, mean age of 54.6 years old
L/M test 67 75 (58-88) 56 (40-71) 1.70 (1.15-2.50) 0.45 (0.24-0.84) (10-90). Expulsion rate over time of 87% in the cases with respect to 55.5% in the
At least 1 abnormal 67 83 (67-94) 26 (12-45) 1.12 (0.87-1.45) 0.65 (0.25-1.66) controls (p 0.188). The mean gastric transit time (75 vs. 49.5 minutes; p 0.12),
Both abnormal 48 79 (60-92) 42 (20-66) 1.37 (0.89-2.10) 0.49 (0.20-1.19) intestinal transit time (81.4 vs. 44 minutes; p 0.001) and colon transit time (252
vs. 232 minutes; p 0.79) were shorten.
CONCLUSION: The higher excretion rate as well as the shortened gastric and
intestinal transits, without modifying the colon transit, with the new preparation
CONCLUSION: Although fecal calprotectin and lactoferrin are established mar- (PrucalopridePolyethylene glycol plus ascorbic acid), allow conducting a higher
kers of colonic inflammation, their diagnostic yield in detecting small intestinal quality study of the colon over time and with less adverse effects and better
disease through SBCE seems suboptimal. Their combination with L/M test mini- tolerance as a result of excluding sodium phosphate.
mally improves this diagnostic accuracy, whereas that of L/M test alone appears This procedure may be considered as an alternative, particularly for patients in
the most satisfactory. It remains to establish whether performing either fecal whom sodium phosphate-based preparations are contraindicated.
markers or L/M test (or both) might be cost-effective in the selection of patients REFERENCES
to address for SBCE when a small bowel disease is suspected. 1. Spada C, et al. Meta-analysis shows colon capsule endoscopy is effective in
Disclosure of Interest: None declared detecting colorectal polyps. Clin Gastroenterol Hepatol 2010; 8: 516522.
2. Hansen MB. Small intestinal manometry. Physiol Res 2002; 51: 541-556.
3. Fireman Z, Paz D and Kopelman Y. Capsule endoscopy: improving transit
P0789 A THERAPEUTIC WIRELESS ROBOTIC ENDOSCOPE time and image view. World J Gastroenterol 2005; 11: 5863-5866.
CONTROLLED VIA THE INTERNET REMOTELY 4. Manabe N, et al. New-generation 5-HT4 receptor agonists: potential for treat-
H. Ohta1,*, S. Katsuki2 ment of gastrointestinal motility disorders. Expert Opin Investig Drugs 2010; 19:
1
Gastroenterology, Sapporo Orthopedics and Cardiovascular Hospital, Sapporo, 765-775.
2
Gastroenterology center, Otaru Ekisaikai, Otaru, Japan 5. Tack, et al. Diagnosis and treatment of chronic constipation a European
Contact E-mail Address: hideohta@true.ocn.ne.jp perspective. Neurogastroenterol Motil 2011; 23: 697-710.
7. Quigley, et al. Clinical trial: the efficacy, impact on quality of life, and safety
INTRODUCTION: A few researchers have tried to make the paradigm shift and tolerability of prucalopride in severe chronic constipation a 12-week, ran-
from diagnosis to treatment with the capsule endoscopy (CE) application. domized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2009;
Though technical innovation is rapidly spreading throughout the CE field, 29: 315-328.
there are still several crucial problems with both the hardware and software 8. Gu a Europea Spada C, Hassan C, Galmiche JP, et al. Colon capsule endo-
which were highlighted by the system we presented at the last UEGW in scopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Berlin. This report presents a wirelessly controlled robotic endoscope equipped Endoscopy, 2012.
with some newly developed tools; a syringe for injecting or spraying drugs or Disclosure of Interest: None declared
contrast medium, a scalpel for cutting and a rubber band for suturing.
AIMS & METHODS: Our goal is to realize a patient-friendly, swallowable,
therapeutic and wirelessly controlled robotic endoscope. We tested three newly P0791 COMPARATIVE STUDY OF SMALL BOWEL TRANSIT TIME IN
developed therapeutic tools in a phantom, which had part of its inner wall TWO SMALL-BOWEL CAPSULE ENDOSCOPY SYSTEMS
covered with a patch of porcine stomach. 1) A 0.3ml syringe for injecting or I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
spraying was driven by a spring and switched on electrically. The amount used A. Ponte1, S. Leite1, J. Carvalho1
was dependent on the drug, dye or contrast medium. 2) The rubber band (similar 1
Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
to a variceal ligater) was held between two cylinders and released by a spring. Contact E-mail Address: iolandacribeiro@gmail.com
When the spring was released the outer cylinder pushed the band over the
mucosa. 3) The scalpel blade was vibrated by a motor similar to a harmonic INTRODUCTION: Some studies1 suggest that the MiroCam endoscopy cap-
scalpel. All the tools were triggered by signals originating from a controller in the sule (CE) has a small bowel transit time (SBTT) greater than Given CE, which
hospital via a smartphone next to the phantom. In addition, similar to the pre- may result in greater detection of positive lesions.
vious version the tools were controlled via the Internet. AIMS & METHODS: Aims: To compare the SBTT, the detection of positive
RESULTS: It was possible to control all the new tools in the phantom both lesions and percentage of complete studies between Mirocam and Given .
locally (Bluetooth) and via the Internet. However, the cuts made by the scalpel in Methods: retrospective study of 429 patients who underwent CE between 2005-
the mucosa were a little bit jagged. In retrospect, it would have been better to 2013. Lesions were considered positive according to the indication of CE:
move the robotic endoscope slowly backwards during cutting to improve the obscure gastrointestinal bleeding (OGIB) - multiple erosions/ ulcers, typical
operators view of the lesion, so that they could have made a cleaner cut. The angiodysplasias, tumor and blood; suspected Crohns disease (CD)/ evaluation
tools occupied a large volume and therefore it was difficult to fit all the tools in a of the extension of CD - multiple erosions/ ulcers and blood; abdominal pain -
single robotic endoscope. To enable the robotic endoscope to be swallowed, it tumor, multiple erosions / ulcers and blood. Statistical tests: t-student; X2
will be necessary to equip it with only one or two tools. The best approach might RESULTS: The mean age was 54.2 years. MiroCam CE was performed in
be to build several specialized robotic endoscopes and the number of endoscopes 48.7% of patients and Given CE in 51.3% patients. Indications for performing
that a patient would swallow would be determined by their circumstances. CE: OGIB 62.5%, suspected CD/ evaluation of the extension of CD - 21.2%,
CONCLUSION: This study has built on the previous study by increasing the polyposis 5%, abdominal pain 4.4% and others 6.8%.
number of therapeutic tools from two to five and hopefully, it has brought The mean gastric transit time (GTT) in MiroCam and Given CE was
treatment by a robotic endoscope, a little bit closer. However, the current pro- identical (38min vs 41min, p 0.52). The mean SBTT of MiroCam CE
totype has a number of limitations (e.g. too large to be swallowed and the tools was superior to Given CE - 5h17min vs 4h45min, p 0.004. We did not find
could only be used once) and these will need to be addressed if treatment by any differences between the two CE with respect to mean age (MiroCam - 54.9
robotic endoscope is to become a reality. years; Given - 53.6 years, p 0.46), sex (Mirocam - female sex 57%; Given -
Disclosure of Interest: H. Ohta: None, S. Katsuki: None female sex - 61.3%, p 0.35), percentage of diabetic patients (10.1% MiroCam
- 10.1%; Given - 14.5%, p 0.2), percentage of complete exams (MiroCam -
90%; Given - 89%, p 0.63) and positive lesions (MiroCam - 38.2%, -
P0790 KINETICS OF COLON CAPSULE ENDOSCOPY: A NEW MODEL Given - 39.5%, p 0.78). There were also no differences regarding the indica-
OF PREPARATION tions for CE (p 0.051).
I. GUTIERREZ-DOMINGO1,*, C. GUTIERREZ-GONZALEZ1 on behalf of CONCLUSION: Our study suggests that the SBTT of MiroCam CE was
Instituto de Patolog a Digestiva de Sevilla, A. GUTIERREZ-DOMINGO1, superior to Given CE, but it does not influence the positive findings or com-
I. MORENO-GARCIA1 plete examination rate. However, a longer SBTT is associated with a longer
1
Digestive Diseases, Instituto de Patologa Digestiva de Sevilla, Sevilla, Spain reading time, an important aspect in daily clinical practice.
Contact E-mail Address: ignaciogutierrezdomingo@hotmail.com REFERENCES
1 - Pioche M, et al. Prospective, randomized comparison of two small-bowel
INTRODUCTION: Up until now, the use of colon capsule endoscopy (CCE) capsule endoscopy systems in patients with obscure GI bleeding. Gastrointest
has been limited by the inabilities to achieve a complete examination. A pilot Endosc 2011; 73: 1181-1188.
study was conducted to determine the efficacy of a new preparation based on Disclosure of Interest: None declared
associating Prucalopride (Resolor) and polyethylene glycol plus ascorbic acid
(Moviprep). Prucalopride is a highly selective serotonin 5HT4 receptor agonist
which stimulate the release of acetylcholine necessary for smooth bowel muscle
contraction and therefore peristalsis. After observing its benefits on the treatment
United European Gastroenterology Journal 2(5S) A349
RESULTS: Between the first (WLE only) and the second (FICE aided) reading,
P0792 THE USE OF SMALL BOWEL CAPSULE ENDOSCOPY IN
in terms of accuracy, there was a 19.5% [95% CI:15.7% to 23%] improvement
OCTOGENARIANS; THE EDINBURGH EXPERIENCE
(from 52% to 71.5%) in the global evaluation of all images (p50.001), coming
L. Bartzis1, A. Koulaouzidis1,* from a 26% [95% CI: 22% to 30%] improvement (from 47% to 73%) in the
1
Centre for Liver & Digestive Disorders, The Royal Infirmary OF Edinburgh, evaluation of true ulcerative images (p50.001), and a 12% [95% CI: 3.5% to
Edinburgh, United Kingdom 22%] decrease (from 75% to 63%) in the evaluation of faked ulcerative images
(p50.01), results reproduced for all three readers. FICE 1 and 2 settings were
INTRODUCTION: Over the last 13 years, the clinical use of capsule endoscopy rated as most useful.
(CE) has revolutionised the investigation pathways for the small-bowel. CONCLUSION: This study demonstrates that FICE virtual chromoendoscopy
Although (as procedure) non-invasive, there are reports of capsule aspiration (mostly settings 1 and 2) applied for VCE is useful to enhance surface patterns
in certain patient-groups.[1] Moreover, CE video sequence review is a time-con- and color differences and to better categorize difficult to interpret small bowel
suming process and on occasions with limited diagnostic yield (DY). There is mucosal ulcerative lesions. However, care must be taken, and individual images
scarcity of data on the use of CE in octogenarians.[2-4] should only be evaluated as part of a succession in a recording, as the technology
AIMS & METHODS: Aim: We aim to report our centres experience in using CE could also misguide the interpretation of artifacts as ulcerative lesions.
in octogenarians. Setting: University hospital & tertiary referral centre for CE for REFERENCES
the South East of Scotland. Retrospective study; the small-bowel CE database of 1. Gupta T, et al. Evaluation of Fujinon intelligent chromo endoscopy-assisted
our unit was interrogated for patients480 years of age who underwent CE. capsule endoscopy in patients with obscure gastroenterology bleeding. World J
Categorical data are reported as mean SD (range). The Fischers exact, the Gastroenterol 2011; 17: 4590-4595.
chi-square and the t (unpaired) tests were used to compare datasets. A two- 2. Imagawa H, et al. Improved detectability of small-bowel lesions via capsule
tailed P value of 50.05 was considered statistically significant. endoscopy with computed virtual chromoendoscopy: a pilot study. Scand J
RESULTS: 1,477 patients underwent small-bowel CE between 2005 and 2013. 93 Gastroenterol 2011; 46: 1133-1137.
CE were performed in 84 (35M/59F) octogenarians; mean age 84 2.9 years. 3. Duque G, et al. Virtual chromoendoscopy can be a useful software tool in
PillCamSB1/SB2 & MiroCam were used in 61 & 32 CE examinations, respec- capsule endoscopy. Rev Esp Enferm Dig 2012; 104: 231-236.
tively. Ten (11.9%) patients had more than 1 CE. One patient was unable to Disclosure of Interest: None declared
swallow the capsule, and in another the capsule was retained in the stomach. The
CE report was unavailable in one case. Indications for small-bowel CE were iron
deficiency anaemia (IDA): 44, obscure gastrointestinal bleeding (OGIB): 29, P0794 THE CORRELATION OF WIRELESS VIDEO CAPSULE
OBIGIDA: 6, diarrhoea: 4,?small-bowel varices:1. Forty-five (53.6%) patients ENDOSCOPY AND OTHER RADIOLOGICAL IMAGING IN THE
subsequently died. The mean time from small-bowel CE to death was 23 20.9 INVESTIGATION OF SUSPECTED AND ESTABLISHED SMALL
months, (range: 0.13-83 months). The DY (all findings) of CE in our octogenar- BOWEL CROHNS DISEASE
ian cohort was 56.8%. Vascular lesions (any P class)/active bleeding were found P. Moore1,*, G. Holleran1, B. Hall1, D. McNamara1
in 33, inflammatory pathology in 9, and other findings in 4 CE. No neoplastic 1
Tallaght Hospital, Tallaght, Ireland
pathology was identified. The DY was independent to the indications for the Contact E-mail Address: moorepe@tcd.ie
procedure (P 0.166), the small-bowel CE system used (P 0.068), the patient
final outcome i.e. deceased/alive (P 0.051) and/or the time from CE to death INTRODUCTION: Background: In recent times there have been significant
(P 0.053). advances in both the radiological, CT and MRI Enterocolysis (CTE / MRE)
CONCLUSION: CE in patients 480 years of age has high DY, but sinister and the endoscopic, video capsule endoscopy (CE) investigation of small bowel
pathology in this cohort is rare. Furthermore, small-bowel CE has limited disease. The optimal complimentary and appropriate use of various new evolving
impact on the final patient outcome in this patient-group. and standard diagnostic modalities remains to be established. In particular, their
REFERENCES role in identifying small bowel Crohns disease remains unclear. Early identifica-
1. Koulaouzidis A, et al. Small-bowel capsule endoscopy: a ten-point contem- tion of ileal Crohns disease is desirable to guide treatment and impact on long-
porary review. World J Gastroenterol 2013; 19: 3726-3746. term outcome.
2. Koulaouzidis A, et al. The use of small-bowel capsule endoscopy in iron- AIMS & METHODS: Aim: To compare the diagnostic performance of CE and
deficiency anemia alone; be aware of the young anemic patient. Scand J radiological imaging in detecting small bowel Crohns disease in the local popu-
Gastroenterol 2012; 47: 1094-1100. lation and to correlate the findings of CE with other various imaging modalities.
3. Tsibouris P, et al. Capsule endoscopy findings in patients with occult or overt Method: A retrospective analysis was undertaken of a database of patients who
bleeding older than 80 years. Dig Endosc 2012; 24: 154-158. underwent capsule endoscopy from 2009 to 2013 at Tallaght Hospital. Those
4. Sidhu R and McAlindon ME. Age should not be a barrier to performing patients who underwent CE for known histologically-confirmed or suspected
capsule endoscopy in the elderly with anaemia. Dig Dis Sci 2011; 56: 2497-2498. Crohns disease were identified. This cohort was cross-referenced with the
Disclosure of Interest: L. Bartzis Financial support for research from: Grant from Hospital Radiology Report system Keogh for the same period. Patient demo-
the Hellenic Society of Gastroenterology, A. Koulaouzidis Financial support for graphics, radiological procedures, CE and radiology findings were recorded. The
research from: ESGE-Given Imaging research grant 2011, Lecture fee(s) from: diagnostic yield and correlation coefficient was calculated for radiological tests
Dr Falk Pharma, Other: Travel support: Dr FalkPharma, Abbott,MSD compared to CE.
RESULTS: Results: In all, 263 patients, 155 female (59%), mean age 41 years,
had a CE for known (n 29, 11%) or suspected (n 234, 89%) Crohns disease.
P0793 USEFULNESS OF FLEXIBLE SPECTRAL IMAGING COLOR In all 110 (42%) had active disease on CE. In only 96 (37%) patients additional
ENHANCEMENT (FICE) IN DIFFICULT TO INTERPRET MUCOSAL radiological tests were available for comparison, 73 (76%) and 23 (24%) in
ULCERATIVE LESIONS OF THE SMALL BOWEL positive and negative CE cases. Of 28 CTEs, 28 SBFTs and 17 Abdominal
M. Rimbas1,2,*, L. Negreanu2,3, L. Ciobanu4, C. Spada5, A. Bengus2, CTs performed in positive CE subjects only 37 (51%) also reported evidence
C.R. Baicus2,6, G. Costamagna5 of active Crohns disease, overall correlation coefficient k 0.49, 95% CI 0.37-
1
Gastroenterology Department, Colentina Clinical Hospital, 2Internal Medicine 0.61. SBFT was the least sensitive test, 32% (9/28), while CTE and Abdominal
Department, Carol Davila University of Medicine and Pharmacy, 3Internal CTs had similar diagnostic yields of 64% (11/17) and 61% (17/28). Correlation
Medicine Department, Emergency University Hospital, Bucharest, 4Regional was better among patients without active Crohns disease, with 20 of 23 radi-
Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of ological tests, 7 CTEs, 7 SBFTs and 9 Abdominal CTs also being reported as
Medicine and Pharmacy, Cluj-Napoca, Romania, 5Digestive Endoscopy Unit, normal, correlation coefficient k 0.87, 95% CI 0.72-1.0. The incremental diag-
Universita Cattolica del Sacro Cuore, Rome, Italy, 6Clinical Research Unit nostic yield for CE in patients with suspected or known Crohns disease in our
RECIF, Reseau dEpidemiologie Clinique International Francophone, Bucharest, cohort compared to radiological investigations was 34%, CE 76% and all
Romania Radiology 42%. Table 1: Diagnostic yield according to test.
Contact E-mail Address: mrimbas@gmail.com
Number (%) CE CTE CT-Abd SBFT
INTRODUCTION: Identification of subtle small bowel mucosal lesions can
sometimes be challenging, as small differences in mucosal hue or pattern are Positive 73 (76%) 18 (51%) 11 (42%) 11 (31%)
difficult to detect. To overcome this problem, chromoendoscopy virtual techni-
ques based on narrowing the bandwidth of the conventional white light endo- Negative 23 (24%) 17 (49%) 15 (58%) 24 (69%)
scopy (WLE) image were imagined, possibly allowing for contrast-enhanced Total 96 35 (36%) 26 (27%) 35 (36%)
assessment of the nature of small-bowel mucosal lesions. However, data on the
already implemented FICE (Flexible spectral Imaging Color Enhancement) soft-
ware application in videocapsule endoscopy (VCE) are limited.[1-3] CONCLUSION: Despite its poor diagnostic yield and the advent of new diag-
AIMS & METHODS: This is a multicenter study involving a selection of mixed nostic modalities SBFT remains a frequently employed test in CD.
de-identified images of 250 difficult to interpret small bowel ulcerative lesions Notwithstanding the inherent bias in our study, the findings suggest the correla-
(selected as the least representative visualization of an unequivocally confirmed tion between CE and standard and targeted small bowel radiology is at best
erosion from a succession of images, comprising small or shallow mucosal moderate, with CE having a higher diagnostic yield. CE should be considered
defects, erosions lacking a clear rim of erythema or located marginally in the in all subjects with suspected Crohns disease.
field of view, or lesions with a poor image quality due to luminal content), and 50 Disclosure of Interest: None declared
artifacts mimicking ulcerative lesions, all selected from the 64 VCE recordings in
a prospective study (ClinicalTrials.gov ID NCT00768950). The evaluation was
performed by three blinded experienced VCE readers in two steps, initially as
white light images, then with the addition of all available FICE settings (1,2,3
and Blue), labeling them as real or faked lesions and rating each FICE setting as
useful or not. The comparison of accuracies in correctly categorizing the images
was performed between the two readings (McNemars test).
A350 United European Gastroenterology Journal 2(5S)
INTRODUCTION: Mesenteric panniculitis (MP) is a rare, non-specific inflam- The optimal positioning of the magnet to aid pyloric traversing was posteriorly
matory process affecting the adipose tissue of the mesentery. Symptoms may be between vertebrae T5 to L2, in an area 10cm to the left and 18cm to the right
absent or there may be fever, abdominal pain, vomiting or diarrhea. MP is (83% cases). Age455yrs (p 0.03) and the ability to view the pylorus from
characterised on computed tomography (CT) scan by an increased mesenteric station 3 (p 0.04) was associated with an extreme pyloric canal vector.
fat density called misty mesentery and the presence of lymph nodes within the CONCLUSION: CT modelling has provided important data regarding the opti-
fatty mass; and sometimes the presence of a hypodense halo surrounding blood mal stations in the stomach to position a magnetic capsule endoscope to allow
vessels and nodes called fat ring sign, and/or a hyperdense pseudocapsule maximal luminal mucosal visualisation and traversing the pylorus. Although
surrounding the mesenteric fat. Prior studies suggested an association of MP there is some extreme variation in the upper GI anatomy, the majority of cases
with malignancy and also with acute abdominal disorders, infectious or inflam- will allow the use of a single standard method in performing MACE which may
matory diseases. However data are heterogeneous and mainly retrospective and be very useful for screening purposes.
patients care and follow-up remain unclear. Disclosure of Interest: None declared
AIMS & METHODS: We aimed to evaluate the prevalence of cancer in patients
with MP on abdominopelvic CT scans, and to study clinical and radiological
course of patients. A prospective and descriptive study was performed in a P0797 INVESTIGATION OF URGENT REFERRALS WITH
French University hospital. All CT scans performed in the Radiology department UNEXPLAINED IRON DEFICIENCY ANAEMIA: IS A CT SCAN
between January 2012 and February 2013 with a diagnosis of MP were recorded. RELEVANT?
The diagnosis of MP was defined as the presence of misty mesentery, infra- J. Iqbal1,*, G. Kaur1
centimetric nodes, and the absence of invasion of the adjacent small-bowel loops 1
Surgery, SCUNTHORPE GENERAL HOSPITAL, Scunthorpe, United
and vascular structures. Clinical and radiological characteristics of patients with Kingdom
MP were recorded, and patients with isolated MP were followed-up in the Contact E-mail Address: gkaur@email.com
Gastroenterology department. An initial search for associated disease, especially
for cancer, was performed and prospective 1-year follow-up was proposed. INTRODUCTION: Anaemia is a common medical problem and can be due to
RESULTS: MP was diagnosed based on CT findings in 100 consecutive patients deficiency of one or more nutrients, blood loss or a variety of medical problems.
among 9027 abdominopelvic CT scans (1.1%) over the study period; 54 patients Generally, anaemia of almost any degree requires medical assessment so that the
(54%) had cancer, of which 12 (22 %) were melanomas and 11 (20 %) were correct cause can be ascertained and appropriate treatment given. The patients
lymphomas. MP was present at the time of diagnosis (35/54), or appeared within symptoms and initial FBC findings will influence both the urgency and direction
the subsequent months (7/54). Twenty-two patients had MP associated with of initial clinical investigation. Upper and lower GI investigations should be
acute abdominal disorders, and 24 patients had isolated MP. Among those considered in all males and post-menopausal females with iron deficiency anae-
patients and during the prospective follow-up only one cancer was diagnosed, mia unless there is an obvious alternative cause. NICE guidelines for referral for
and it was a basal cell carcinoma. Regarding radiological aspects of MP: a suspected colorectal/ Upper GI cancer includes referral of patients with unex-
pseudocapsule was found in 58 % of cases, a fat ring sign in 63 % of cases plained iron deficiency anaemia who are men of any age with a haemoglobin of
and a left-sided location in 88 % of cases. There were no significant difference 11 g/100 ml or below and who are non-menstruating women with a haemoglobin
between the radiological characteristics of MP according to the associated dis- of 10 g/100 ml or below. Unexplained iron deficiency anaemia does not usually
eases, especially cancer. prompt a referral to chest physicians, gynaecologists nor the urologists.
CONCLUSION: This study is one of the largest to describe MP diagnosed at CT AIMS & METHODS: All our urgent referral patients with iron deficiency anae-
scan and the first to propose prospective evaluation of patients. MP is frequently mia are investigated with upper and lower GI endoscopy where possible and a
associated with cancer, mainly melanoma and lymphoma, already documented at CT scan of the chest abdomen and pelvis. We aimed to evaluate our management
the time of MP diagnosis. However data from follow-up suggest that when PM is of these patients with respect to investigations performed, especially the cost
isolated, or associated with other disease there does not appear to be underlying effectiveness of a adding on a CT scan to the upper and lower GI scopes that
or incidental cancer. are always part of this investigation.
Disclosure of Interest: None declared All Urgent referrals to the Colorectal unit over a 3 month period were retro-
spectively analysed. CT scan, Colonoscopy and Flexible sigmoidoscopy data was
collected as well as any histology obtained from biopsies taken.
P0796 CT RADIOLOGICAL MODELLING OF THE UPPER GI TRACT Of 73 urgent referrals, 54 were referred with Iron deficiency anaemia. Of these, 46
ANATOMY; ESSENTIAL CLUES TO PERFORMING MAGNETIC (85%) underwent a Lower GI scope (37 Colonoscopy and 9 Flexible sigmoido-
ASSISTED CAPSULE ENDOSCOPY (MACE) scopy); 8 did not undergo any scope - 1 failure, 1 refusal (both underwent CT
I. Rahman1,*, M. Kay1, T. Bryant1, S. Pelitari1, P. Patel1 pneumocolon) and 6 patients who were considered too frail, poor mobility etc.
1
University Hospital Southampton, Southampton, United Kingdom 43% patients undergoing colonoscopy were reported normal; of the 57% with
Contact E-mail Address: imdi81@hotmail.com findings, 28% were found to have bowel cancer. 98% patients referred urgently
with unexplained iron deficiency anaemia underwent a CT scan; of these, 15
INTRODUCTION: Capsule endoscopy, employed to investigate the small (28%) were normal. Of the remaining 38 patients, 47% had significant findings
bowel, is now being further developed to visualise the upper GI tract. In a pig with respect to malignancy (half of which were bowel related) and the remaining
model, using a hand held magnet, we have demonstrated that magnetic assisted 53% had other relevant non-cancer pathology (40% of which was bowel related).
capsule endoscopy (MACE) in the stomach is feasible. However, it is unclear Hence, CT scans picked up non bowel related pathology that would not have
what the best methodology is to achieve complete gastric luminal views in been found on colonoscopy alone in 39% patients referred urgently with iron
humans. Our aim was to utilise CT modelling of the abdomen to determine deficiency anaemia, 17% of which was significant with respect to malignancy.
the optimal placements of a capsule endoscope in the stomach to allow complete CONCLUSION: Patients with iron deficiency anaemia are generally referred to
mucosal visualisation and to determine the optimal placement of the hand held gastroenterology / colorectal surgery for further investigations, with appropriate
magnet to aid pyloric traversing. urgency. These patients are usually investigated with a gastroscopy and colono-
AIMS & METHODS: Using multiplanar reformatting, 100 good quality con- scopy. We found our routine use of an addition of a CT scan chest, abdomen and
trast abdominal CT scans were analysed to assess luminal visualisation by a pelvis yielded useful results, both related to malignant and non malignant non-
magnetic capsule endoscope from 5 fixed stations throughout the stomach. bowel related pathology. This helped us guide further management appropri-
From each station, we assessed the ability of a capsule endoscope to visualise ately, with an urgency dependent on the causative pathology. We would therefore
6 anatomical landmarks (cardia, fundus, body, incisura, antrum and pylorus). recommend the routine use of a CT scan in the investigation of a patient referred
Success of visualisation of an anatomical area was only accepted when 490% urgently with iron deficiency anaemia, unless contraindicated for any reason.
mucosal visualisation was achieved from a particular station. The pyloric canal Disclosure of Interest: None declared
angles were calculated to create a vector. We mapped the position of this vector
on the patients skin (pyloric canal vector surface point) to determine the optimal
placement of the magnet that would allow traversing of the capsule endoscope P0798 PATIENT-RELATED FACTORS AFFECTING PATIENT
through the pylorus. ACCEPTANCE FOR REDUCED-LAXATIVE CT COLONOGRAPHY:
RESULTS: There were 65 female and 35 male patients. Mean age of patients was WHO DOES PREFER TO CT COLONOGRAPHY?
53 years (s.d/-18 years). Best mucosal visualisation of the stomach landmarks K. Nagata1,2,*, A. Iyama3, H. Kanazawa2, T. Mikami3, H. Sugimoto2
was achieved from 3 stations; fundal dependant, antral dependent and opposite 1
Department of Gastroenterology, Tokyo International Clinic, Chiyoda-ku,
the antral dependent points. Maximal visualisation of the whole of the stomach, 2
Department of Radiology, Jichi Medical University, Shimotsuke, 3Department of
required combining 2 stations as shown in Table 1 Radiology, Sakakibara Sapia-tower Clinic, Chiyoda-ku, Japan
Contact E-mail Address: Nagata7@aol.com
INTRODUCTION: Although CT colonography (CTC) is minimal invasive pro-
cedure, the actual patient acceptance for CTC varies between patients.
AIMS & METHODS: The aim of this prospective study was to assess patient
tolerance and to identify the patient-related factors affecting the patient
United European Gastroenterology Journal 2(5S) A351
acceptance of reduced-laxative CTC in screening purpose. A total of 1242 out- there is a low risk on serious complications and, due to the burdensome proce-
patients at average risk for colorectal cancer were consecutively enrolled in this dure, the population uptake is low. MR colonography may have potential as a
study. All patients underwent reduced-laxative fecal-tagging CTC with 64-detec- CRC screening tool since it has comparable test characteristics as colonoscopy
tor row CT using carbon dioxide insufflation. Patients age, gender, height, but is less invasive. Furthermore, innovators in the field of MR technology are
weight, and the bowel habits were recorded before the procedure. After the striving to develop a targeted contrast agent that specifically detects adenomas at
procedure, acceptance and preference were evaluated using self-assessed ques- high risk of progressing to CRC. This might even further increase the potential of
tionnaires regarding tolerance assessment for overall procedure and preference MR colonography for CRC screening.
for future testing. AIMS & METHODS: To explore the potential of conventional and targeted MR
RESULTS: Percentages of patients in good tolerance category for CTC were colonography in terms of (cost-)effectiveness using the Adenoma and Serrated
83.9% (897/1069). Sixty percent (641/1062) of patients were willing to accept pathway to Colorectal CAncer (ASCCA) model.
CTC as a future method of examination. Discomfort factors during CTC were Thirteen screening strategies were evaluated, differing in primary screening
abdominal distention (64.8%) and abdominal pain (4.9%). Among the patient instrument and number of screening rounds. The strategies under consideration
factors, only the older age affected the degree of discomfort during CTC (over 60 were conventional MR colonography, targeted MR colonography, colonoscopy
vs. under 60, odds ratio 1.59, p 0.006). Patient factors of gender, BMI, con- and CT colonography with two, three and four screening rounds at a ten year
stipation/laxative use, history of abdominal surgery, and previous colonoscopy screening interval. In addition, eleven rounds of biennial faecal immunochemical
or barium enema experiences were not related to patient tolerance during CTC. test (FIT) screening were evaluated because this is the current Dutch screening
CONCLUSION: An uncomfortable CTC procedure may be expected in elder programme. For each strategy, both realistic and perfect participation rates were
patients. Overall, reduced-laxative CTC has excellent patient tolerance. taken into account. Incremental costs and effects were estimated from a societal
Disclosure of Interest: None declared perspective with an ICER less than the Dutch GDP per capita in 2012, i.e.
E35,823/LYG, considered as cost-effective.
RESULTS: All screening strategies were cost-effective compared to no screening.
P0799 INCIDENTAL SLIDING HIATAL HERNIA: FINDINGS AND For conventional MR colonography, the ICER ranged between E1,271/LYG to
RELATIONSHIP WITH CT WITH WATER ENEMA AND CT E3,003/LYG for two to four screening rounds at a participation rate of 34%. For
COLONOGRAPHY participation rates of 62% and 100%, this range was respectively E1,576/LYG to
M. Revelli1, M. Furnari2,*, L. Bacigalupo3, F. Paparo3, D. Astengo1, E3,777/LYG and E1,971/LYG to E4,577/LYG. However, conventional MR
E. Savarino4, G.A. Rollandi3 colonography screening was more expensive than other screening strategies at
1
E. O. Ospedali Galliera, Unit of Radiology, 2Di. M. I., Gastroenterology Unit, comparable LYG, for all participation rates. For example, colonoscopy at two to
UNIVERSITY OF GENOA, 3Unit of Radiology, E. O. Ospedali Galliera, genoa, four screening rounds at realistic participation (22%) led to cost-savings of E71
4
Division of Gastroenterology, Department of Surgery, Oncology and to E87 at 0.025 to 0.035 LYG per person. The effectiveness of targeted MR
Gastroenterology, University of Padua, Padua, Italy colonography was only slightly higher than of conventional MR colonography
Contact E-mail Address: matteorevelli@gmail.com but it was considerably more costly, even under the most favourable assumptions
regarding test characteristics and costs per test.
INTRODUCTION: Barium-contrast radiography originally constituted the first CONCLUSION: This is the first study to evaluate the cost-effectiveness of MR
development in diagnosing hiatal hernia (HH) and reflux disease however, con- colonography screening for CRC. Although conventional and targeted MR colo-
ventional radiology is no more a gold standard investigation for their assessment. nography are cost-effective compared to no screening, at the moment they cannot
We observed in clinical practice a worrisome rate of HH type I reported as extra- compete with more established screening tests because of the high costs per test.
colonic finding during CT with water enema (CT-WE) and CT colonography Disclosure of Interest: None declared
(CTC), likely induced by increased intra-abdominal pressure due to colon dis-
tension. HH has been positively related with the incidence and severity of reflux
disease and with the risk of its complications. Although HH is not a life-threa- P0801 PRELIMINARY STUDY OF PHOTODYNAMIC DIAGNOSIS
tening condition it is our opinion that erroneous reporting of HH may trigger USING 5-AMINOLEVULINIC ACID IN GASTRIC AND
consecutive diagnostic unnecessary processes that induce unmotivated anxiety COLORECTAL TUMORS
and expensive and time-consuming for the patient and the socio-sanitary system. M. Nakamura1,*, J. Nishikawa1, K. Hamabe1, A. Goto1, J. Nishimura1,
AIMS & METHODS: To determine whether colonic distension at CT-WE and H. Shibata1, M. Nagao1, S. Hashimoto1, T. Okamoto1, I. Sakaida1
CTC can induce a small incidental physiologic sliding hiatal hernia and whether 1
Department of Gastroenterology and Hepatology, Yamaguchi University
exist differences between water and gas distension achieved with the two different Graduate School of Medicine, Ube, Yamaguchi, Japan
techniques. We retrospectively evaluated 400 consecutive patients, 200 under-
going CT with water enema and 200 undergoing CT colonography, including INTRODUCTION: Photodynamic diagnosis (PDD) using 5-aminolevulinic acid
59 subjects who also underwent a routine abdominal CT evaluation at a different (5-ALA), has been performed to detect the accumulation of fluorescent proto-
time, used as internal control, while a separate group of 200 consecutive patients porphyrin IX (PpIX) in tumors. 5-ALA is a precursor of the fluorescence-emit-
who underwent abdominal CT evaluation was used as external control. Two ting PpIX, and PpIX accumulates specifically in tumor cells and emits
abdominal radiologists assessed the CT exams for the presence of a sliding fluorescence when the excitation light irradiated on them. This property of 5-
HH, grading the size as small, moderate, or large; the internal control groups ALA may improve the endoscopic diagnosis of gastric and colorectal tumors.
were directly compared with the corresponding CT-WE or CTC study looking AIMS & METHODS: In this preliminary study, we investigated the utility of 5-
for a change in hernia size. We used the Fisher exact test applying a size-specific ALA using PDD in the detection of gastric and colorectal tumors. This prospec-
correction factor, in order to account for the effect of colonic distention: these tive single-center study investigated inter-subject variability in patients with early
corrected values were then individually compared with the external control stage gastric or colorectal tumor indicated for endoscopic resection. Patient
group. selection criteria were age 2080 years, either sex, and provision of informed
RESULTS: Sliding HH was present in 51% (102/200) of the CT-WE patients and consent. After oral administration of 5-ALA, endoscopic resection of gastric
in 48.5% (97/200) of the CTC patients. Internal control CT of the 31 patients or colorectal tumors was performed, then the resected specimens were subjected
with a hernia at CT-WE showed resolution of the hernia in 58.1% (18/31) of to fluorescence endoscopy to examine for red fluorescence. Endoscopic, macro-
patients, including 76.5% (13/17) and 45.5% (5/11) of small and moderate HH. scopic, and histopathologic findings of the tumors were assessed.
Comparison CT of the 28 patients with HH at CTC showed absence of the it in RESULTS: Ten patients (7 men and 3 women) with a total of 13 lesions (10
57.1% (16/28) patients, including 68.8% (11/16) and 50% (5/10) of small and gastric and 3 colorectal tumors) were enrolled in this study. Fluorescence was
moderate HH. Its prevalence in the external control group was 22% (44/200), detected in 7 (53.8%) of the 13 lesions. No significant differences were observed
lower than the CT-WE and CTC cohorts prevalence of 51% (p 5 0.0001) and in sex, age, color of the tumor, tumor diameter, macroscopic type, histological
48.5% (p 5 0.0001). After applying the correction factors for the CT-WE and type, invasion depth, lymph node metastasis, or procedure time between the cases
the CTC groups, the estimated residual prevalences (16% and 18.5%, respec- with and without fluorescence. The detection rate of fluorescence tended to be
tively) were much closer to that of the external control patients (p 0.160 for CT- high for elevated lesions. Liver dysfunction developed in 4 (40.0%) of the 10
WE and p 0.455 for CTC). patients.
CONCLUSION: Incidental findings at CT-WE and CTC should be considered CONCLUSION: The results of this preliminary study suggest the utility of PDD
according to the clinical background. Small sliding HH should not be reported in using 5-ALA for screening gastric and colorectal cancers.
patients with unrelated symptoms undergoing CT-WE or CTC: when encounter- Disclosure of Interest: None declared
ing these findings, accurate anamnesis and review of medical history looking for
GERD-related symptoms are essential, in order to address these patients to a
correct diagnostic iter, taking advantage from appropriate techniques such as GI P0802 INCREASED VISCERAL TO SUBCUTANEOUS FAT RATIO IS
endoscopy or esophageal manometry. ASSOCIATED WITH LOWER RISK OF IBD RELATED SURGERY
Disclosure of Interest: None declared IN PATIENTS WITH CROHNS DISEASE ON INFLIXIMAB
P. Brown1,*, D. Tolan2, L. Warren3, T. Clark3, G. Dowson3, J. Hamlin3,
V. Subramanian1
P0800 THE POTENTIAL OF MR COLONOGRAPHY AS A SCREENING 1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St James
TOOL FOR COLORECTAL CANCER: A COST-EFFECTIVENESS University hopsital, Universityof Leeds, 2Radiology, 3Gastroenterology, St James
ANALYSIS University Hospital, Leeds Teaching Hospital NHS Trust, Leeds, Leeds, United
M. Greuter1,*, E. Demirel1, J. Berkhof1, R. Fijneman1, J. Stoker2, G. Meijer1, Kingdom
V. Coupe1 Contact E-mail Address: v.subramanian@leeds.ac.uk
1
VU University Medical Center, 2Academic Medical Center, Amsterdam,
Netherlands INTRODUCTION: Fat wrapping and mesenteric hypertrophy are characteris-
Contact E-mail Address: mj.greuter@vumc.nl tics of Crohns disease (CD). In patients with CD, mesenteric adipose tissue
releases higher levels of adiponectin, which could up-regulate production of
INTRODUCTION: For colorectal cancer (CRC), a range of screening modalities tumor necrosis factor- and increase the risk for aggressive disease. We have
is available. Based on diagnostic accuracy, colonoscopy is the preferred test but
A352 United European Gastroenterology Journal 2(5S)
previously shown that a higher visceral to subcutaneous fat ratio was associated
P0804 QUANTITATIVE ASSESSMENT OF GLOBAL SMALL BOWEL
with complicated (stricturing or fistuling) CD (reference).
MOTILITY IN CHRONIC INTESTINAL PSEUDO-OBSTRUCTION
AIMS & METHODS: The aim of this study was to investigate the effect of
AND CONTROLS: A PRELIMINARY STUDY
visceral fat accumulation on clinical outcomes in patients with CD on
Infliximab. We identified patients with a confirmed diagnosis of CD on S.K. Butt1,*, A. Menys2, D. Atkinson2, A. Plumb2, S.A. Taylor2, N. Zarate-
Infiximab who had computed tomography or magnetic resonance imaging Lopez1, A. Emmanuel1
1
scans of their abdomens within 12 weeks of starting infliximab, from the biolo- Gastroenterology, 2Centre for medical imaging, UCLH, London, United Kingdom
gics database of Leeds Teaching Hospital NHS Trust. Areas of subcutaneous and Contact E-mail Address: s.butt@ucl.ac.uk
visceral fat were measured in 1 cross-sectional scan, taken at the level of the
umbilicus using a previously validated method. All measurements were made INTRODUCTION: In this preliminary report, we present the initial results of a
using AdodeTM CS3 with magic wand function. The outcomes of interest were prospective investigation comparing MRI quantified global small bowel motility in
1) IBD related flare (defined as increase in dose or steroid use or need for IBD healthy controls and patients with proven clinical and radiological Chronic Intestinal
related hospitalization or surgery), 2. Any IBD related surgery and 3) IBD pseudo-obstruction (CIPO). Diagnosis is initially difficult and often delayed, many
related resectional surgery. patients undergoing unnecessary surgical intervention prior to final diagnosis. MRI
RESULTS: 150 patients with CD on Infliximab met our predefined inclusion offers a potential non-invasive modality of diagnosis and monitoring, employing
criteria. The mean age of the patients was 37.2 13.9 years. On multivariate post-processing quantitation of global metrics describing small bowel motility1.
analysis a higher visceral to subcutaneous fat ratio was associated with a lower AIMS & METHODS: Subject selection: 11 healthy non-smoking volunteers (7
risk of all IBD related surgery (HR 0.125 and 95% CI 0.02 0 0.81) and a lower Male, mean age 33[22 to 48]) and 5 CIPO patients (3 Male, mean age 53[32 to 82])
risk of an IBD related flare that almost reached significance (HR 0.39, 95% CI were recruited. CIPO patients stopped any medications that influenced small bowel
0.13-1.14). Females were less likely to need IBD related surgery (p 0.03) and motility for one week prior to scan including opioids, anti-emetics & anti-diarrhoeals.
ileal and ileo-colonic disease was associated with a higher risk of surgery com- Study overview: Participants underwent a single MRI motility scan before and
pared to colonic disease (p 0.03). Only structuring and fistulating disease phe- immediately after an injection of 0.5mg IV neostigmine, a cholinomimetic with
notype was significantly associated with a higher risk of resectional surgery potent prokinetic action.
(p 0.0.2). MR Protocol: The motility scan protocol used a 3D Balanced Turbo Field Echo
CONCLUSION: Higher visceral to subcutaneous fat on cross sectional imaging (BTFE) motility sequence capturing one coronal volume through the abdomen
at baseline is associated with better clinical outcomes in patients with CD on and pelvis per second over a 20 second breath hold (2.5x2.5x10 in mm resolution,
Infliximab. This could imply that mesenteric fat hypertrophy has a protective FA 20, TE 1.7ms, TR 3.5ms, 15cm thickness in 15 reconstructed slices)
role in CD. Motility Analysis: Dynamic time-series data was registered using a modified 2D
REFERENCES optic-flow technique for each slice through the abdominal volume2. The deforma-
Erhayiem B, Dhingsa R, Hawkey CJ, et al. The ratio of visceral to subcutaneous tion fields generated by the registration process were used to provide a motility
fat area is a biomarker of complicated Crohns disease. Clin Gastroenterol metric (arbitrary unit, AU) expressed as the standard deviation of pixels Jacobian
Hepatol 2011; 9: 684-687. (a measure of local area change) and averaged across a user defined ROI.
Disclosure of Interest: None declared ROI Placement: A radiologist, with 5 years experience reading MRE, placed
regions of interest (ROIs) around the small bowel in each coronal slice over
the 15-slice volume. The radiologist was blinded both to subject group and
P0803 "DOUBLE-DUCT" SIGN - WHAT IS THE CLINICAL whether the scan was pre-
SIGNIFICANCE? RESULTS: 1) Mean baseline small bowel motility scores in CIPO patients was
K. Padala1,*, T. Gardner1, R. Sinha2, O. Elneima1, S. Niaz1, J.R. Greenaway2, 0.19AU (range 0.1 to 0.25) and in controls 0.35AU (range 0.275 to 0.37) with a
D. Joy2 statistically significant difference of 0.17AU, p 0.0026 (CI 0.09 to 0.23).
1
Gastroenterology, 2Endoscopy, South Tees NHS Foundation Trust, 2) The mean percent increase in small bowel motility scores in CIPO patients
Middlesbrough, United Kingdom following noestigmine was 29% (95% CI from 19 to 50%) and in controls 10%
Contact E-mail Address: rohits78@gmail.com (range 0 to 34) with a statistically significant difference in groups response to
neostigmine of 19%, p 0.029 (95% CI from 4 to 40%).
INTRODUCTION: Double-duct sign on endoscopic retrograde cholangio- CONCLUSION: This study demonstrated significant differences in both resting
pancreatography (ERCP) is considered suggestive of pancreatic or biliary malig- and cholinomimetic-induced global motility between CIPO patients and healthy
nancy [1]. This sign is frequently encountered in radiological imaging. We wish to controls. Despite marked bowel distension in the CIPO patients, motility
investigate the prognostic value of the double-duct sign in patients who undergo appeared present but reduced compared to controls, and responded to provoca-
magnetic resonance cholangio-pancreatogram (MRCP), attempting to define the tion with neostigmine suggesting the bowel still exhibits the expected pro-kinetic
associated features, which would predict underlying malignant disease [1,2]. effects following pharmacological stimulation. With just five patients this is a
AIMS & METHODS: An analysis of retrospectively collected database of all preliminary study, nevertheless initial results appear promising and support our
patients (n 2,741) who had MRCP over a four-year period; January 2010 to ongoing investigation program.
December 2013 was performed. All the radiological reports showing both a REFERENCES
dilated common bile duct (CBD) and pancreatic duct (PD) or the double- 1) Menys, et al. Radiol 2013; 269: 443-450.
duct sign were included. These were all interpreted and reported by specialist 2) Odille, et al. MRM 2012; 68: 783-793.
gastrointestinal radiologist. The demographics, liver biochemistry, final diagnosis Disclosure of Interest: None declared
and outcome for all patients with the double duct sign were accessed using the
radiology PACS system, biochemical results WebICE, hospital letters and
case notes. Follow up information was available for a mean of 36 months P0805 MALIGNANT GASTRODUODENAL OBSTRUCTION
(range 12-48 months). TREATMENT WITH SELF-EXPANDABLE METALLIC STENTS IN A
RESULTS: 81 patients (annual incidence 2.2% - 3.3% incidence) had double- SINGLE REFERRAL CENTRE
duct sign with a mean age of 71 years. The ratio of male to female patients was L.C. R. Freitas1,*, L. Meireles1, P. Sousa1, J. Lopes1, L.C. Ribeiro1, J. Velosa1
(F: M) 1.2:1. The commonest cause of double duct sign was choledo-cholithiasis 1
Gastrenterology and Hepatology Department, Hospital de Santa Maria, Lisbon,
(27.2%) followed by malignancy (20%). Patients with jaundice in the context of Portugal
double-duct sign had a higher incidence of malignancy (48%). More than half Contact E-mail Address: luisfreitas29@gmail.com
of the patients, (48/81; 59%) with double-duct sign were anicteric. None of the
anicteric patients were found to have malignancy (p 0.002). Of the anicteric INTRODUCTION: Endoscopic treatment is a valid choice in treating malignant
patients, 25% (12/48) had completely normal liver test and the remaining 75% gastroduodenal obstruction, when patients are not candidates to surgery. Self-
(36/48) had some abnormality of the liver enzymes (raised GGT and/or Alkaline expandable metallic stents (SEMS) have been increasingly used in this context.
phosphatase). Four patients in the anicteric group had benign tumours (1 case of AIMS & METHODS: To retrospectively analyze the use of SEMS in malignant
benign IPMN [Intra-ductal papillary mucinous neoplasm] and 3 cases of benign gastroduodenal obstructions, in one referral centre, over a period of 8 consecutive
ampullary tumour, histology confirming low grade and high grade dysplasia years.
without evidence of invasive malignancy on resection specimens). The benign RESULTS: SEMS were successfully inserted in 43 patients in this period (male sex
nature was confirmed on clinical, pathological and radiological follow-up. All 21 (48.8%); mean age 70.67/-13.46 years), all of them complaining with stasis
four patients remained anicteric over the period of follow-up (mean 24 months; symptoms. Primary tumor was gastric adenocarcinoma in 26 patients (60.5%),
and one unrelated death at 18 months). Our results show that double duct sign pancreatic adenocarcinoma in 12 patients (27.9%), and cholangiocarcinoma, gall-
in the absence of jaundice makes a malignant aetiology unlikely. bladder and colon cancer in 5 patients (11.6%). The median time between tumor
CONCLUSION: In patients with cross-sectional imaging evidence of double- diagnosis and stent placement was 27.5 days (range 0-980). Complications to the
duct sign, the absence of jaundice makes a malignant aetiology unlikely. procedure occurred in 3 patients (7%): hypovolemic shock, perforation and aspira-
Conversely, in jaundiced patient a malignant cause is much more likely. tion pneumonia. Clear clinical improvement (tolerance to oral intake) was seen in
REFERENCES 26 patients (60.5%). In 10 patients (23.3%), reintervention due to stent occlusion
1. Baillie J, et al. Biliary imaging: a review. Gastroenterology 2003; 125: 1565. was necessary, including stent-in-stent placement in 6 patients, balloon dilation in 2
2. Ahualli J. The double duct sign. Radiology 2007; 244: 314-315. and argon plasma coagulation in 2. Median survival after sent insertion was 42
Disclosure of Interest: None declared days (range 1-420), with 15 patients (34.9%) dying within less than 30 days after
the procedure, with no statistical significant differences between different ages and
different types of primary tumor.
CONCLUSION: When feasible, SEMS placement is a safe and efficient therapy
for malignant gastroduodenal obstruction. The relatively high percentage of
patients that were dead one month after stent placement, in our series, may
reflect an over-selection of patients that had too advanced a disease to benefit
from this technique.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A353
2 Small AJ, et al. Endoscopic placement of self-expandable metal stents for
P0806 SELF EXPANDIBLE METAL STENTS IN VARICEAL BLEEDING
malignant colonic obstruction: long-term outcomes and complication factors.
AS THE BLAKEMORE-SENGSTAKEN TUBE OF NOWADAYS? A
Gastrointest Endosc 2010; 71: 560-572.
SINGLE INSTITUTION EXPERIENCE
Disclosure of Interest: None declared
M. Muller1,*, T. Seufferlein1, M. Wagner1, A. Kleger1
1
Department of Gastroenterology, Universitatsklinikum Ulm, Ulm, Germany
Contact E-mail Address: martin.mueller@uniklinik-ulm.de P0808 ENDOSCOPIC STENT PLACEMENT OR SURGICAL
GASTROJEJUNOSTOMY FOR THE PALLIATION OF MALIGNANT
INTRODUCTION: Despite a dramatic reduction of lethality rates due to upper GASTRIC OUTLET OBSTRUCTION CAUSED BY UNRESECTABLE
gastrointestinal bleeding, esophageal variceal bleeding remains a challenge and OR METASTATIC GASTRIC CANCER
still accounts for a mortality rate of up to 50 % within the first 6 weeks. Rapid M. Murakami1,*, R. Takenaka1, C. Sakaguchi1, S. Oka1, Y. Baba1, N. Okazaki1,
and efficient varical ligations in combination with vasoactive terlipressin are key D. Kawai1, H. Tsugeno1, K. Takemoto1, S. Fujiki1
requirements for the initial patients stabilization. However, a relevant proportion 1
Gastroenterology, Tsuyama, Japan
of esophageal varical bleeding remains refractory, thus, making a call for addi-
tional tools to achieve hemostasis. Self expandible metal stents (SEMS) incorpo- INTRODUCTION: Malignant gastric outlet obstruction (GOO) is traditionally
rate such a tool. treated with gastrojejunostomy (GJJ). Recently, endoscopic placement of a self-
AIMS & METHODS: We report 12 cases of stent application in patients with expanding metal stent (SEMS) to the GOO was covered by insurance and spread
variceal bleeding between 2011 and 2014. A retrospective analysis reporting a widely in Japan because it was a minimally invasive and effective method. The
series of clinically relevant parameters in combination with bleeding control rates aim of this study was to verify the usefulness of SEMS compared with GJJ.
and adverse events was performed. AIMS & METHODS: We conducted a retrospective study comparing the
RESULTS: The initial bleeding control rate was 100 %. Despite this success, we patients treated with endoscopic SEMS placement from April in 2010 to
observed a 30% mortality within the first 42 days due to non-hemorrhage asso- December 2013 with those treated with GJJ from April in 2000 to December
ciated reasons in the cirrhotic patients. Interestingly, we found in 7 out of 12 2013 in the management of malignant GOO caused by gastric cancer. Endoscopic
patients stent dislocation even after a proven correct position 24 h after hemos- SEMS placement was performed by using WallFlex duodenal stent (Boston
tasis. The stent removal procedure appeared to be safe with slight reactivation of Scientific, Tokyo, Japan). Following variables were evaluated between the
bleeding in only one of our patients. Of note, our study cohort required an SEMS group and the GJJ group; age, gender, clinical stage of gastric cancer,
extensive amount of hospital care. procedure time, Gastric Outlet Obstruction Scoring System (GOOSS) score,
CONCLUSION: Self expandible metal stents seem to be safe and efficient in fasting period after placement, period of hospitalization after placement, survival
patients with therapy refractory variceal bleeding. Despite high rates of stent period after placement, and complications.
migration no serious adverse events were observed in short term observation. RESULTS: The study subjects consisted of 16 patients in the SEMS group and
This contrasts strongly with the formerly used Blakemore-Sengstaken tubes. 28 patients in the GJJ group. Between the 2 groups, there were no significant
Thus, SEMS should be considered as the new Gold standard in case of refractory differences in median age (70 years vs. 72 years), percentage of women (31% vs.
esophageal bleeding. 18%), percentage of clinical stage at IV (81% vs. 89%), median GOOSS score (1
Disclosure of Interest: None declared vs. 1). The technical success rates were 100% both in the SEMS group and the
GJJ group. Median procedure time for SEMS stent placement was shorter than
that for GJJ (25 minutes vs. 128 minutes; P 5 0.0001). The clinical success rates
P0807 SAFETY AND EFFICACY OF COLONIC STENTING: 7 YEAR were 88% in the SEMS group and 71% in the GJJ group (p 0.28). The median
EXPERIENCE FROM A DISTRICT GENERAL HOSPITAL IN THE UK GOOSS score after SEMS placement was similar to that after GJJ (3 vs. 3).
M. Hu1,*, V. Mitra1, V. Krishnan1, D. Majumdar1, B. Chaudhury1, J. Hancock1, However, the time to oral intake was significantly less in the SEMS group
D. Dwarakanath1 than in the GJJ group (2 days vs. 7 days; p 5 0.0001). Early adverse event
1
Department of Gastroenterology, University Hospital of North Tees, Stockton-on- (occurring 5 1 week) rates did not differ significantly between the 2 groups:
Tees, United Kingdom (6% in the SEMS vs. 7% in the GJJ group). The median postprocedure length
Contact E-mail Address: deepak.dwarakanath@nth.nhs.uk of hospital stay was shorter in the SEMS group than in the GJJ group, but not
significant (17 days vs. 26 days; p 0.13). Median postprocedure survival periods
INTRODUCTION: A significant proportion of patients with colon cancer pre- was similar in 2 treatment groups (68 days vs. 109 days; p 0.85). Late adverse
sent with partial or complete bowel obstruction. Emergency decompression sur- event (occurring 1 week) occurred in 2 patient in the SEMS group and 3
gery may be associated with up to 25% mortality1. Self expandable metal stents patients in GJJ group.
(SEMS) provide an alternative low-risk option for managing these patients2 and CONCLUSION: Endoscopic stent placement is preferable to GJJ in terms of
have been routinely used as the first line of treatment of these patients in our shorter treatment time and more rapid improvement of food intake. Endoscopic
hospital. The aim of this study was to assess the safety and efficacy of SEMS in stent placement seems to contribute to improve quality of life for the palliation of
malignant colonic obstruction (MCO) in a district general hospital (DGH) malignant GOO cause by gastric cancer.
setting. Disclosure of Interest: None declared
AIMS & METHODS: A retrospective study of patients presenting with MCO
and treated with uncovered SEMS between 2007 and 2013 was carried out. All
stents were deployed by experienced gastroenterologists. Data including patient P0809 ESOPHAGEAL COVERED STENTS FIXATION USING
demographics, indication and treatment intent, site of lesion, stent type, proce- ENDOSCOPIC OVER-THE SCOPE CLIPS VERSUS ENDOSCOPIC
dure outcome, adverse events, and outcome at six months were obtained using SUTURING SYSTEM (WITH VIDEO)
the endoscopy reporting software and hospital patient record. M. Diana1,2,*, L. Swanstrom2, P. Halvax2, A. Le`gner2, Y.-Y. Liu2, S. Cho2,
RESULTS: 78 patients were included. 53 (68%) had elective and 25 (32%) had A. Alzaga2, N. Demartines1, J. Marescaux2
emergency stenting. Median age was 77 years (range 47-96 years). 53 (68%) 1
Visceral Surgery, University Hospital of Lausanne, Lausanne, Switzerland,
patients were male. 4 (16%) out of 25 patients who underwent emergency stent- 2
General, Digestive and Endocrine Surgery, IRCAD/IHU UNIVERSITY
ing subsequently had curative surgery. 6 (11.3%) patients in the elective stenting HOSPITAL STRASBOURG, Strasbourg, France
group (n 53) had curative surgery. Overall, SEMS was used as a bridge to Contact E-mail Address: michele.diana@ircad.fr
surgery in 10 (12.8%) patients while 68 (87.2%) underwent palliative stenting.
The sites of malignancy were as follows: sigmoid colon 40 (51.3%), descending INTRODUCTION: Endoscopic prosthesis migration from the originally stented
colon 15 (19.2%), rectum 14 (17.9%), transverse colon 7 (9.0%) and anastomotic area occurs in up to 40% of cases and may lead to serious life-threatening
recurrence post left hemicolectomy 2 (2.6%). Procedure related serious compli- complications. Endoscopic suture fixation of the stent using the OverStitchTM
cations included one case of stent related perforation (proceeded to palliative Suturing System (Apollo Endosurgery, Inc.) significantly reduces migration.
rescue Hartmanns procedure) and one of contrast extravasation (successfully However, suturing with the OverStitchTM has a steep learning curve and is
managed conservatively). 3 patients presented with early stent failure from time-consuming. A novel memory shape over-the-scope endoscopic clip, the
blocked stent patency was restored in one with endoscopy, one underwent PadlockTM clip, has been developed recently by Aponos Medical. The device is
Hartmanns procedure and the third patient chose to be palliated. The stents a preloaded point & shoot single-use instrument.
did not adequately restore luminal patency in 2 patients despite optimal position- AIMS & METHODS: The aim of this study was to demonstrate that the anchor-
ing. Stent migration was discovered in 2 patients who represented with partial ing of a covered Self-Expandable Metallic Stent using the PadlockTM clip is as
obstruction. 2 patients with rectal stents complained of discomfort and were effective as endoscopic suturing by means of the OverStitchTM and that
managed conservatively. The technical success rate was 98.7% (n 77) and the PadlockTM fixation can be faster and user-friendly. Eleven pigs were involved
clinical success rate (functional stent without complication) was 88.5%. The 30- in this experimental study. A fully covered esophageal stent (Wall-Flex, Boston
day all-cause mortality was 10.3% (n 8) with none being attributable to the Scientific) of 12.3cm in length, 18mm in diameter, was placed under endoscopic
procedure. guidance at the esophagogastric junction. Five pigs underwent stent fixation with
CONCLUSION: Our study shows that a safe and effective colonic stenting 1 figure-of-eight suture using the OverStitchTM. In 4 pigs, the stent was fixed by
service can be delivered in a DGH setting. There was no procedure related firing the Aponos Clip over a loop of Vicryl 0, which was attached to the upper
mortality compared to emergency decompression surgery which has a higher edge of the stent. In two pigs, the stent was placed but not fixed and was used as a
mortality rate1. This relates to service delivery by experienced operators. We control. A laparotomy was performed and a specifically designed pulling device
suggest that all DGH with acute surgical admissions should provide this service made of 4 fishing hooks attached to a plastic ring was anchored to the distal part
to reduce the morbidity and mortality related to emergency decompression of the stent at 4 cardinal points after performing a gastrotomy. A suture attached
surgery. to the plastic ring was passed over the holding hook of a Digital Dynamometer
REFERENCES (Chatillon II, Ametek, Inc.). Constant traction was applied on the sutures until
1 Tekkis PP, et al. The Association of Coloproctology of Great Britain and full stent mobilization was achieved. The force required to remove the stent was
Ireland study of large bowel obstruction caused by colorectal cancer. Ann Surg recorded.
2004; 240: 76-81. RESULTS: Mean force to mobilize the stent was higher in the OverStitchTM
group when compared to the PadlockTM group (23.99N; SD 14.91 vs. 19.97N;
A354 United European Gastroenterology Journal 2(5S)
SD 7.62), but the difference was not statistically significant. In the 2 control pigs, perforation (0% in cSEMS group vs 4% in cSEMS-BS group), death from all
the force required was 7 and 11 Newtons respectively. Mean suturing time was causes (13% in cSEms group vs 28% in cSEMS-BS group, p 0.06). We report
statistically significantly higher when compared to the time required to apply the 3% of stent obstruction due tumor ingrowth.
PadlockTM clip (455.4sec; SD 144.83 vs. 155sec; SD 12.9; p 0.002). CONCLUSION: Concomitant biliary stenting is not recommended before cov-
CONCLUSION: Full-thickness PadlockTM clip application is faster and may ered duodenal SEMS placement in patients with no concomitant biliary
achieve a comparable stent fixation when compared to endoscopic suturing obstruction.
with the OverStitchTM. Disclosure of Interest: None declared
Disclosure of Interest: M. Diana: None declared, L. Swanstrom Consultancy for:
Unpaid consultant for Apollo Endosurgery and Aponos, P. Halvax: None
declared, A. Le`gner: None declared, Y.-Y. Liu: None declared, S. Cho: None P0812 ENDOSCOPIC THERAPY OF ESOPHAGEAL LEAKS WITH
declared, A. Alzaga: None declared, N. Demartines: None declared, J. STENTS: EXPERIENCE IN A REFERRAL CENTER
Marescaux: None declared P. Sousa1,1,*, L. Meireles1, L.C. Freitas1, J. Lopes1, C. Noronha Ferreira1,
R. Palma1, L. Carrilho Ribeiro1, J. Velosa1
1
Gastrenterologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria,
P0810 ENDOSCOPIC DILATATION OF BENIGN PYLORIC STENOSIS: Lisboa, Portugal
IS IT A GOOD ALTERNATIVE TO SURGERY? Contact E-mail Address: patlizbms@gmail.com
M. Acharki1,*, M. Bakkar2, N. Kabbaj2
1
EFD hepato gastro enterology, 2EFD hepato gastro enterology, Ibn Sina Hospital, INTRODUCTION: Esophageal leaks have an important morbi-mortality. The
Rabat, Morocco best approach is still unclear; some studies show a potential benefit of stents.
Randomized controlled trials are difficult in this area.
INTRODUCTION: Pyloric stenosis is a common complication of ulcerative AIMS & METHODS: The aim of this study was to evaluate the efficacy of
disease which requires surgery. The endoscopic dilatation is now a good esophageal stents for the treatment of esophageal leaks.
alternative. Retrospective analysis of stent use for esophageal leaks. In a period of 60 months
AIMS & METHODS: Aim: evaluate the efficiency of the endoscopic dilatation demographic data, leak etiology, endoscopic procedures, time until closure and
in the managment of benign pyloric stenosis due to ulcer diseases. fistulas relapse were analyzed.
It is a prospective study from January 2009 to January 2014 including 21 RESULTS: 45 consecutive patients were included (29 males; mean age 63 years).
patients. The dilatation was performed using a hydrostatic balloon. 42% had post-operative leaks (10 after gastric sleeve, 6 after Y-Roux and 3 after
RESULTS: There were 13 men and 8 women. Mean age was 48 years (35-70 subtotal esophagectomy), 42% had malignant esophagopulmonary fistulas (16
years). 58 dilations were performed. In 11 cases (52 %), patients had ulcer disease esophageal and 3 bronchogenic), 7% had boerhaave syndrome and 9% had
and in 6 cases (29 %) non steroidal anti -inflammatory medication. The duration iatrogenic perforation (2 foreign body and 2 after esophageal dilation). The
of symptoms was 13 months (3 months - 3 years). Vomiting and epigastric pain median time for post-operative fistula detection was 16 days (4-145).
were the predominant clinical signs (90%). All patients underwent an upper In 36 of the 45 patients the initial approach was using a stent. Of these, in 16
endoscopy and had pyloric stenosis and / or pyloro - bulbar stenosis. 12 cases patients this was the only endoscopic therapy done. Metallic stents were inserted
(57%) had impassable strictures. The average number of dilatations was three per in 40 (13 partially covered, 27 fully covered) and plastic in 5. The rest of patients
patient (1-5). 17 patients (81%) had favorable response. The average follow-up had another therapeutic endoscopic procedure - another stent (n 10), through-
time was 30 months (3-60 months). the-scope (TTS) clip (n 3), nasoenteric tube (n 10), over-the-scope clip (n 2)
CONCLUSION: Through this prospective study, we identified factors of success and argon-plasma coagulation (n 6).
and failure of endoscopic dilation in benign pyloro-bulbar stenosis: the passable The median time for leak closure was 48.5 days (13-308). In 6 cases the fistulas
nature of the stenosis, the extent of the stenosis, the distance between the pylorus closure wasnt documented.
and the dental arches reflecting gastric distension and food stasis. In 4 patients there was relapse of the leak in a median of 125 days after the initial
Disclosure of Interest: None declared closure. All cases were managed endoscopically - metallic stent (n 3), argon-
plasma coagulation (n 6), nasoenteric tube (n 3) and TTS clip (n 1). In 3
cases there was closure in a median of 27 days after the diagnosis.
P0811 PREVIOUS BILIARY STENTING IS NOT REQUIRED BEFORE In 12 patients the overall endoscopic approach failed and surgery was needed in 8
ENDOSCOPIC PLACEMENT OF DUODENAL COVERED SELF patients and percutaneous drainage in 4.
EXPANDABLE METAL STENTS The observed complications were: stent migration (n 10), upper GI bleeding
F. Goutorbe1, O. Rouquette1,*, A. Mulliez2, M. Goutte1, A. Abergel1, (n 2). There was no need for surgery in any case or death for a procedure
M. Dapoigny1, G. Bommelaer1, L. Poincloux1 related complication.
1
Gastroenterology and Hepatology department, 2Clinical research and innovation CONCLUSION: The use of esophageal stents seems to be a safe and effective
department, CHU ESTAING, Clermont Ferrand, France therapy for esophageal leaks.
Contact E-mail Address: fgoutorbe@chu-clermontferrand.fr Disclosure of Interest: None declared
P0829 HIRSUTENONE AMELIORATES EPITHELIAL BARRIER P0831 NOTCH SIGNALING AND TNF-A SYNERGISTICALLY
DISRUPTION THROUGH CONVERGENCE OF EGFR/AKT AND PROMOTES INTRACELLULAR PROTEIN ACCUMULATION OF
ERK1/2 PATHWAYS ON HEME OXIDASE-1 INDUCTION IN HUMAN OLFM4 IN THE INFLAMED MUCOSA OF ULCERATIVE COLITIS
INTESTINAL EPITHELIAL CELLS G. Ito1,*, R. Okamoto1,2, H. Shimizu1, S. Fujii1, T. Nakata1, K. Suzuki1,
W.-Y. Jiang1,2, H. Jin1,2, G.S. Seo3, S.H. Lee1,2,* K. Tsuchiya1, T. Nakamura1, M. Watanabe1
1
College of Pharmacy, Wonkwang University, 2BK21plus program & Department 1
Gastroenterology and Hepatology, 2Center for Stem Cell and Regenerative
of Smart Life-Care Convergence, Wonkwang University, Graduate School, Medicine, Tokyo medical and dental university, Tokyo, Japan
3
Digestive Disease Research Institute, Wonkwang University College of Medicine, Contact E-mail Address: rokamed2@tmd.ac.jp
Iksan, Korea, Republic Of
Contact E-mail Address: gsseo@wku.ac.kr INTRODUCTION: The intestinal epithelium is maintained by the stem cell
residing at the bottom of the crypt. Olfactomedin-4 (OLFM4) is one of the
INTRODUCTION: Oxidative stress-induced disruption of epithelial tight junc- specific marker genes of the human intestinal stem cell. The gene encodes secre-
tions (TJ) plays a critical role in the pathogenesis of intestinal disorders, includ- tory-type, as well as intracellular-type, OLFM4 proteins. Reports have shown
ing inflammatory bowel disease (IBD). that secretory-type OLFM4 facilitates cell adhesion and may take part in muco-
AIMS & METHODS: The current study investigated the protective effect of sal defense, whereas intracellular-type OLFM4 can exhibit anti-apoptotic prop-
diarylheptanoid hirsutenone against disruption of the intestinal barrier in vitro erty. Also, it has been shown that the expression and secretion of OLFM4 is
and in a mouse model of colitis. Caco-2 cells were stimulated with tert-butyl upregulated in the inflamed mucosa of ulcerative colitis (UC), where Notch
hydroperoxide (t-BH). Monolayer permeability was assessed by measuring the signaling is highly activated. However, the expression of the intracellular-type
transepithelial electrical resistance and inulin flux. Colitis was induced in mice by OLFM4 protein in the inflamed mucosa, or the mechanism regulating its expres-
intrarectal administration of trinitrobenzene sulfonic acid (TNBS). The mRNA sion, remains unclear.
and protein levels were analyzed by real-time polymerase chain reaction (PCR) AIMS & METHODS: We aimed to identify the expression of intracellular-type
and immunoblotting, respectively. OLFM4 in the normal and inflamed mucosa of the human colonic tissue, and
RESULTS: Hirsutenone prevented the t-BH-induced increase in permeability by also to clarify the molecular mechanism regulating its expression in the inflamed
inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly mucosa. Expression of intracellular-type OLFM4 in colonic tissues of normal
stimulated tyrosine phosphorylation of the epidermal growth factor receptor and UC patients was analyzed by immunohistochemistry (IHC). Human colonic
(EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends epithelial cell lines, Ls174T and DLD1, were employed to analyze the expression
on the activation of both ERK1/2 and Akt signaling pathways. Interestingly, of OLFM4 in response to various inflammatory stimuli. Involvement of Notch
hirsutenone-mediated activation of Akt, but not ERK1/2, signaling was EGFR- signaling in OLFM4 protein expression was examined by using a sub-line of
dependent. Hirsutenone increased heme oxygenase-1 (HO-1) expression through Ls174T cells (Ls174T-NICD cells) in which Doxycycline-dependent activation
both EGFR/Akt- and ERK1/2-dependent pathways, contributing to the protec- of Notch signaling can be induced. Using those cell-lines, the expression of
tive effects against TJ dysfunction. Hirsutenone administration improved the secretory-type OLFM4 protein was quantified by ELISA, whereas that of intra-
clinical parameters and tissue histological appearance, stimulated HO-1 expres- cellular-type OLFM4 protein was examined either by immunoblot analysis or by
sion, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU immunocytochemistry.
incorporation in the colonic epithelium of TNBS-treated mice. RESULTS: IHC analysis of the normal human colon tissues showed that
CONCLUSION: Hirsutenone reversed disordered intestinal permeability by acti- OLFM4 is expressed mostly at the apical surface of epithelial cells residing at
vating EGFR/Akt and ERK1/2 pathways, which are involved in HO-1 expres- the lower crypt, indicating dominant expression of secretory-type OLFM4.
sion regulation. These findings highlight the potential of hirsutenone for clinical However, in the inflamed mucosa of UC patients, an increased number of colonic
applications in the treatment of IBD. epithelial cells clearly expressed OLFM4 in their cytoplasm, indicating high-level
Disclosure of Interest: None declared expression of intracellular-type OLFM4. In vitro analysis using human colonic
epithelial cell-lines showed that, among various pro-inflammatory cytokines,
TNF- significantly upregulates secretion of OLFM4, but do not promote accu-
P0830 DIFFERENTIAL EXPRESSION IN ALPHA7 NICOTINIC mulation of the intracellular-type OLFM4. In contrast, forced activation of
RECEPTOR IN MUCOSAL MACROPHAGES OF IBD PATIENTS: A Notch signaling never induced secretion of OLFM4, but induced accumulation
ROLE FOR NICOTINE MODULATION OF INFLAMMATION? of intracellular-type OLFM4. Upon addition of TNF- under forced activation
L. Spagnol1,2, G. Girardin1,*, P. Brun2, M. Scarpa2,3, M. Scarpa3, R. DInca`1, of Notch signaling, those stimuli synergistically up-regulated the accumulation of
G.C. Sturniolo1, I. Castagliuolo2, F. Galeazzi1 intracellular-type OLFM4 protein to a remarkably high-level, but did not give
1
Dpt of Surgical, Oncologicall and Gastroenterological Science, Section of any additional change to secretion of the OLFM4 protein.
Gastroenterology, Padova University-Hospital, 2Dpt of molecular medicine, Immunocytochemistry clearly confirmed the cytoplasmic accumulation of
Microbiology and clinical microbiology, 3Dpt of Surgical, Oncologicall and OLFM4 protein by the synergistic effect of TNF- and Notch activation.
Gastroenterological Science, Surgical Oncology Unit, Veneto Institute of CONCLUSION: Notch signaling and TNF- synergistically promotes accumu-
Oncology, Padova, Italy lation of intracellular-type OLFM4 protein in human colonic epithelial cells. As
Contact E-mail Address: giulia.girardin@gmail.com it has been suggested that those type of OLFM4 protein can exhibit anti-apop-
totic function, such an accumulation may contribute to protect human colonic
INTRODUCTION: It is well accepted that in animal models of intestinal inflam- epithelial cells in the inflammatory environment.
mation nicotine activates a cholinergic counter-inflammatory mechanism Disclosure of Interest: None declared
through the alpha7 nicotinic acetylcholine receptors (7nAChR). However in
inflammatory bowel diseases (IBD) nicotine shows opposing effects on intestinal
inflammation: its beneficial in ulcerative colitis (UC) while it increases risk of P0832 PPAR-GAMMA EXPRESSION IN THE COLON IS REGULATED
surgery and relapse in Crohns disease (CD). BY THE MIR27A UNDER HYPOXEMIC CONDITION
AIMS & METHODS: In this study we measured 7nACh expression on periph- G. Bouguen1,2,*, J.-B. Delobel1, C. Rauch1, B. Clement1, L. Dubuquoy3,
eral and intestinal mucosa-derived macrophages from patients with UC, CD and A. Corlu1, L. Siproudhis1,2
healthy controls (HV) and evaluated the effect of nicotine on LPS-induced cyto- 1
INSERM U991, Universite de Rennes 1, 2Service des maladies de lAppareil
kines production in macrophages. Peripheral blood derived macrophages (Mc) Digestif, CHU Pontchaillou, Rennes, 3INSERM U995, Universite de Lille 2, Lille,
were obtained by supplementing blood monocytes from UC and CD patients (in France
clinical remission) and HV with M-CSF (7 days). 7nAChR mRNA and protein Contact E-mail Address: guillaume.bouguen@chu-rennes.fr
levels were evaluated by qRT-PCR and FACS analysis using -bungarotoxin
(Bgt)-FITC. Mc were pre-incubated with nicotine (1mg/ml 30min) and then INTRODUCTION: The peroxisome proliferator-activated receptor- (PPAR)
stimulated with LPS (1mg/ml 24 hrs). TNF levels were measured on supernatant is a key factor of mucosal homeostasis and the pharmaceutical target of 5-ami-
using ELISA. Colonic mucosa macrophages (Mi) were isolated from biopsies nosalycilates. Thus, understanding of the primarily decrease expression of
of UC (n 12), CD (n 11) and HV (n 17) and 7nAchR expression was PPAR during UC remains challenging and of therapeutic interest. Mucosal
evaluated by FACS analysis using Bgt-FITC. Macrophages were incubated hypoxemia has been well described during UC. The aim of the study was to
for 24 hrs with LPS (1mg/ml) in presence or absence of nicotine (1mg/ml) and assess and to study the link between hypoxia and PPAR expression in intesintal
TNF and IFN assessed by staining with specific antibodies and cytofluori- epithelial cell during UC.
metric analysis. AIMS & METHODS: In Vitro, PPAR mRNA and protein were quantified in
RESULTS: Mc from UC showed greater 7nAchR mRNA levels then cells various epithelial cell lines 1) during exposure to hypoxia (1%O2) at several time
from CD (p 0.006), while no differences were found with HV. FACS analysis points 2) after chemical induction of HIF-1 3) after transfection of miR-27a or
confirmed greater 7AChR expression in UC patients than in CD (90.75 Gmean knockout of miR-27a (a microRNA induced by hypoxia and with high affinity to
in UC Vs 15.62 Gmean in CD, p 0.031) but not in HV. Although nicotine PPAR in silico) and 4) after stimulation by sildenafil (a phosphodiesterase type
significantly decreased LPS-stimulated TNF release in Mc from HV, CD 5 inhibitor used for blood vessel dysfunction). Ex vivo, PPAR and miR27a
and UC, no differences were observed among groups. Indeed, in UC derived expressions were quantified from mucosal biopsies of surgical specimens from
Mi 7nAChR levels were significantly higher than in CD and HV cells controls or patients with UC.
(p50.01 vs both). Furthermore, nicotine significantly specifically reduced LPS- RESULTS: In vitro, exposure of Caco-2 and HT29 cells to hypoxia (1% O2)
induced TNF upregulation in Mi from UC patients (from 18.912.57 to decreased significantly mRNA and protein expression of PPAR (at least 50%)
10.811.99 %fluorescence, p 0.013) but not in CD and HV whereas nicotine as compared to normoxic condition (21% O2) at days 2. To assess the link
had no effect on LPS-induced IFN upregulation in Mi in the different experi- between hypoxia and the decreased expression of PPAR, we first induced
mental groups. HIF-1 expression, a key factor of cells response under hypoxic condition, by
CONCLUSION: The selective 7nAchR upregulation in Mi from UC patients chemical treatment of cultured cells lineages (deferoxamine, cobalt chloride and
and their responsiveness to the anti-inflammatory effects of nicotine may explain dimethyloxaloylglycine). No effect was observed either on PPAR expression
nicotines protective effects in UC but not in CD patients. neither on miR27a expression. Regarding this result suggesting an independent
Disclosure of Interest: None declared HIF-1 way that controls PPAR expression during hypoxia, we focused on
A360 United European Gastroenterology Journal 2(5S)
miR-27a. MiR-27a was induced by hypoxia in epithelial cells. When miR-27a tissues (p 0.00003 and p 000002 vs. control). The levels of IL-23 or IL-17 in
was overexpressed by transfection in caco-2 cells during normoxic condition, affected tissues from UC and CD groups were comparable.
PPAR expression was decreased. Conversely, PPAR was not affected by As IL-17/IL-23 axis directly influences MMP-9 activity, we measured the con-
hypoxia after knockout for miR27a of caco-2 cells by transfection of miR-27a centration of MMP-9 in complex with TIMP-1 or TIMP-2. The UC group had
inhibitors. Ex vivo, we confirmed a decreased of PPAR expression in colonic significantly higher MMP-9/TIMP-1 level in unaffected tissue compared with
mucosa of patients with UC and higher miR-27a expression as compared to control (p 0.001), while in CD an opposite tendency was observed.
controls. In order to affect the variation of PPAR expression during hypoxia Regarding MMP-9/TIMP-2, there was a decrease in unaffected tissue in both
we used the sildenafil. The sildenafil raised PPAR expression in caco-2 cells UC and CD groups compared with control (p 0.07 and p 0.08, respectively).
exposed to hypoxia. Furthermore the use of sildenafil resulted in the absence of Further analysis revealed that IL-23 correlates with MMP-9/TIMP-1 in UC and
overeexpression of miR-27a expression during hypoxia. with MMP-9/TIMP-2 in CD. In the UC group serum IL-23 negatively correlated
CONCLUSION: A direct relationship was observed between hypoxia and with MMP-9/TIMP-1 in unaffected tissue (r -0.903), but positively in affected
PPAR expression. Mir-27a which is overexpressed during hypoxia and in colon sections (r 0.72). In CD subjects, there was a strong negative correlation
patients with UC might be the key factor involved during hypoxia to control between serum IL-23 and MMP-9/TIMP-2 in unaffected tissue (r -0.94); and
PPAR expression. These results open new insight into the pathophysiology of positive correlations between tissue IL-23 and MMP-9/TIMP-2 in both unaf-
UC and the role of hypoxia as well as new therapeutic strategy such as the use of fected and affected areas (r 0.66 and r 0.62, respectively).
sildenafil. CONCLUSION: It is believed that higher IL-23 levels decrease the content of
Disclosure of Interest: None declared MMP-9/TIMP complexes, which in turn may lead to elevated MMP-9 levels and
MMP-9-induced tissue damage. The correlations between serum and tissue IL-23
and MMP-9/TIMP-1 in UC or MMP-9/TIMP-2 in CD, in particular in unaf-
P0833 MECHANISMS UNDERLYING THE EFFECTS OF CALCITONIN fected mucosa, may therefore be an indicator of an ongoing inflammatory pro-
GENE-RELATED PEPTIDE IN A RAT COLITIS MODEL cess. However, further studies are necessary to explain the interaction between
H. Yamasaki1,*, R. Yamauchi1, K. Kuwaki1, S. Yoshioka1, H. Takedatsu1, cytokines, especially IL-23 and pro- and anti-proteolytic proteins in inflamed and
K. Mitsuyma1,2, T. Torimura1 non-inflamed areas in IBD subjects.
1
Department of Medicine, 2Infllamatory Bowel Disease Center, KURUME Disclosure of Interest: None declared
UNIVERSITY SCHOOL OF MEDICINE, Kurume, Japan
INTRODUCTION: Calcitonin gene-related peptide (CGRP), a vasodilative neu- P0835 CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE E.
ropeptide, is involved in potent tissue repair and anti-inflammatory actions. COLI INDUCE SECRETION OF EXOSOMES WITH PRO-
Previous studies have shown that the administration of CGRP prevents colonic INFLAMMATORY ACTIVITY BY INTESTINAL EPITHELIAL CELLS
injury. However, the mechanism of action responsible for the effect of CGRP on J. Carriere1,*, H. Nguyen1, A. Darfeuille-Michaud1
colitis remains unknown. 1
UMR 1071 Inserm, University of Auvergne, Clermont-Ferrand, France
AIMS & METHODS: Colitis was induced by the oral feeding of 3% dextran
sulfate sodium to rats for up to 7 days. After the induction of colitis, CGRP (200 INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel dis-
g/L/day) was administered via the tail vein twice a day for 7 consecutive days. ease of which the etiology involves environmental, genetic and microbial factors.
Disease severity was assessed by clinical and endoscopic evaluation, and histo- Our group and others have shown a high prevalence of the invasive E. coli
logic scoring. The tissue levels of pro-inflammatory cytokines (interleukin [IL]- strains, designated adherent-invasive E. coli (AIEC), in the intestinal mucosa
1, IL-6, and tumor necrosis factor [TNF]-) and CGRP receptors (receptor of CD patients. Exosomes are small endosomal-derived vesicles involved in cell
activity-modifying protein-1 [RAMP1] and calcitonin receptor-like receptor) to cell communication and have been implicated in various diseases including
were determined using real time-PCR. Bone marrow cell induction and colonic cancer and infectious disorders. It has been reported that mammalian cells
blood flow were also investigated. Additionally, the cytokine response in periph- infected with pathogens can release exosomes containing microbial compounds.
eral blood mononuclear cells stimulated by lipopolysaccharide with or without AIMS & METHODS: Here, we investigated the capacity of CD-associated
CGRP was examined in vitro. AIEC bacteria to induce secretion of exosomes by intestinal epithelial cells and
RESULTS: The administration of CGRP, but not a control vehicle, improved to determine the inflammatory characteristics of the released exosomes. Human
the clinical disease activity (P 0.009) and the endoscopic disease activity intestinal epithelial T84 cells cultured on transwell filters were infected with an
(P 0.009). CGRP decreased the mRNA levels of IL-1 (P 0.032), IL-6 AIEC reference strain LF82. Exosomes were purified using the ExoQuick exo-
(P 0.032) and TNF- (P 0.016) and increased the mRNA level of RAMP1 some precipitation reagent. Exosomes released into the apical or basolateral
(P 0.001). CGRP increased the colonies of CFU-GM in the bone marrow compartments of LF82-infected T84 cells were tested for their ability to promote
(P 0.016) and the number of endothelial progenitor cells in the peripheral a pro-inflammatory response in na ve macrophagic cells.
blood (P 0.040) and enhanced the colonic blood flow (P 0.032). The RESULTS: Electron microscopy and immunogold-labeling for an exosomal
mRNA and protein levels of the inflammatory cytokines in lipopolysaccharide- marker, CD63, analyses showed that differentiated T84 cells infected with
stimulated peripheral blood mononuclear cells were significantly reduced after AIEC LF82 secreted an increased amount of exosome compared to uninfected
the addition of CGRP in vitro. cells. This was confirmed by increased levels of four exosomal markers (CD63,
CONCLUSION: The administration of CGRP effectively suppresses colonic CD81, CD9 and Hsp70) as assessed by Western blot. Exosomes apically secreted
injury through the down-regulation of pro-inflammatory cytokines and the up- by infected T84 cells but not from uninfected cells significantly induced produc-
regulation of protective events, including bone marrow-derived cell induction, in tion of the pro-inflammatory cytokines TNF- and IL-6 in human macrophages,
addition to promoting colonic blood flow. Consequently, CGRP is an attractive and this was not due to the presence of lipopolysaccharide, known to induce a
and novel therapeutic target for the treatment of inflammatory bowel disease. pro-inflammatory response.
Disclosure of Interest: None declared CONCLUSION: In conclusion, our study shows that upon infection with CD-
associated AIEC bacteria, differentiated intestinal epithelial cells release exo-
somes that can trigger pro-inflammatory responses in na ve macrophagic recipi-
P0834 SERUM IL-23 DIFFERENTLY CORRELATES WITH COLONIC ent cells.
MMP-9/TIMP-1 AND MMP-9/TIMP-2 IN CROHNS DISEASE, BUT Disclosure of Interest: None declared
NOT ULCERATIVE COLITIS PATIENTS
A. Piechota-Polanczyk1, M. Jonakowski1, A. Pilarczyk1, M. Wlodarczyk2,
A. Sobolewska2, M. Wis niewska-Jarosinska2, J. Fichna1,* P0836 DIAGNOSIS AND PERSISTENCE OF HISTOLOGICAL CHANGES
1
Department of Biochemistry, 2Department of Gastroenterology, MEDICAL IN LYMPHOCYTIC COLITIS
UNIVERSITY OF LODZ, Lodz, Poland J. Rasmussen1,*, P. Engel2, L.K. Munck3,4
1
Contact E-mail Address: jakub.fichna@umed.lodz.pl Department of medicin, Kge Sygehus, Kge, 2Department of pathology, Roskilde
Hospital, Roskilde, 3Department of medicin, Kge Hospital, Kge, 4Faculty of
INTRODUCTION: Intestinal alterations in IBD are triggered and sustained by Health and medical sciences, University of copenhagen, copenhagen, Denmark
over-expression of pro-inflammatory cytokines. Cytokine quantification may Contact E-mail Address: jul.rasmussen@gmail.com
become a non-invasive tool to monitor the disease progression and effectiveness
of therapy, or assist in understanding disease etiology. Currently, there are lim- INTRODUCTION: The topographic distribution of histological changes in
ited non-invasive biomarkers for monitoring IBD progression; however, the role microscopic colitis (MC) remains controversial. The main conception has been
of selected cytokines like IL-23 and IL-17, or proteolytic proteins like matrix that in order to detect or rule out MC, biopsies from the right colon is necessary.
metaloproteinases (MMP) or their tissue inhibitors (TIMP), is under However this has to some extent been proposed on the basis of a selected popu-
consideration. lation of patients included in randomised trials with collagenous colitis (CC). A
AIMS & METHODS: The aim of this study was to evaluate if IL-17 and IL-23 sigmoideoscopy is more gentle with the patient, cheaper and often more acces-
correlate with MMP-9/TIMP complexes in IBD and if those parameters differ in sible and thus would be preferred if sufficient in detecting MC.
affected and unaffected colon mucosa. AIMS & METHODS: Aims: To access the topography of histological changes in
Serum and biopsy specimens from affected and unaffected colonic mucosa of 19 the colon diagnostic of lymphocytic colitis (LC) in a complete series of consecu-
patients with IBD (9 with ulcerative colitis, UC and 10 with Crohns disease, CD) tive, non-selected patients and to provide the sensitivity of left- and right-side
and 8 controls were included in our study. Serum and tissue cytokines, and tissue biopsies respectively. Furthermore to analyse the persistence of changes in
MMP-9/TIMP-1 and MMP-9/TIMP-2 were quantified at the protein level by repeated endoscopies.
ELISA. Methods: Retrospective review of the pathologic descriptions in the Danish
RESULTS: The UC subjects had significantly lower serum IL-23 (p 0.002) and National Pathology Database in patients diagnosed with lymphocytic colitis in
slightly higher serum IL-17 level (p 0.09) compared with control. In unaffected the coverage area of Kge Hospital from 2000 through March 2014. Biopsies
tissues, there was a significant decrease in IL-23 content (p 0.002 vs. control). from the rectum were excluded.
In CD patients no difference in serum IL-23 or IL-17 content was measured; RESULTS: LC was diagnosed in 238 patients; in 81 (34%) by sigmoideosopy
however, both IL-23 and IL-17 were significantly decreased in unaffected colon and in 136 (57%) by colonoscopy. A medical history of watery diarrhoea could
be retrieved in 196, 1 did not have diarrhoea. The median number of biopsies
United European Gastroenterology Journal 2(5S) A361
taken was 6 (mean 7.6). Biopsies were taken from both right and left colon in 122 INTRODUCTION: Mucins are secreted by the intestinal epithelium and consti-
(51%) and showed LC in both left and right colon of 119 (98%). At the diag- tute an efficient component of innate immune defenses to promote homeostasis
nostic endoscopy 3 patients (2%) had changes in the left colon only and no one and protect against bacteria. Enteric pathogens, such as Shigella and Vibrio
had changes in the right colon only. The histological diagnosis in the right colon cholerae, can produce proteases designated mucinases that are capable of cleav-
were: normal (1), chronic inflammation (1) and incomplete LC (1). The sensitiv- ing mucins. Ileal lesions of patients with Crohns disease (CD) are abnormally
ity of left sided biopsies for the primary diagnosis of LC were 100% (95% CI: 97- colonized by adherent-invasive Escherichia coli (AIEC).
100%) and right sided 98% (94-100%). A second endoscopy following the diag- AIMS & METHODS: Genome analysis of the AIEC strain LF82 revealed the
nostic one was performed in 50 (21%) of the 238 patients after a median of 13.5 presence of a chromosomal gene, designated asm, similar to the Hbp gene of the
months (mean 27.2) with a median of 6.5 biopsies (mean 7.1). LC was recon- avian pathogenic E. coli strains (79% of homology). Hbp has a mucinolytic
firmed in 28 (56%). Other histological changes found were: normal (4), chronic activity. To determine whether the Asm protein cleaves mucins, we generated
inflammation (2), incomplete LC (2), CC (2) and non specific changes (10). In 3 the LF82asm isogenic mutant and transcomplemented this mutant with the
patients histological changes diagnostic of collagenous colitis were found in one cloned asm gene.
or more of the endoscopies following the diagnostic one. Looking at the total RESULTS: Concentrated supernatants from LF82 strain and transcomplemen-
number (161) of colonoscopies diagnostic of LC (with biopsies from both right ted LF82Dasm/asm yielded zones of clearing on mucin gels, whereas LFDasm
and left colon) done in the population, 1 patient (1%) had changes in the right did not exhibit mucinolytic activity. We showed, by using a simple column pene-
colon only and 3 patients (2%) had changes in the left colon only. Prior non- tration assay, that Asm promoted mucus penetration of LF82. No difference in
diagnostic endoscopies were performed in 22 patients (9%) with a median of 4 adhesion and invasion between LF82 and LF82asm was found in the colonic
(mean 5) biopsies. In these histological changes were: normal (4), chronic inflam- epithelial HT29 cells, which are not mucin hyperproducing. However, a signifi-
mation (10), incomplete LC (4) and non specific changes (4). cant difference between these strains was observed in the mucin hyperproducing
CONCLUSION: While a full colonoscopy can be necessary in order to exclude cell line HT29-16E, suggesting a role for Asm in mucus penetration. These results
other diagnoses, biopsies from the left colon are suffice for diagnosing or exclud- were also obtained by confocal and electronic microscopy. To evaluate the invol-
ing LC in patients with chronic watery diarrhoea. The histological findings are vement of Asm in LF82 colonization in vivo, CEABAC10 transgenic mice were
not permanent and can change from one type of microscopic colitis to another orally challenged with LF82 or LF82Dasm strains. The numbers of bacteria
suggesting that the different types of microscopic colitis are closely related. counted in the feces and of intestinal mucosal-associated bacteria were increased
Disclosure of Interest: None declared in mice infected with LF82 compared to those infected with LF82Dasm.
Quantification of asm mRNA levels showed that bile salts act as an activator
of Asm transcription as well as ileal pH.
P0837 METABOLIC PROFILING OF FECAL VOLATILE ORGANIC CONCLUSION: In conclusion, Asm has a mucinolytic activity that promotes
COMPOUNDS IN ULCERATIVE COLITIS PATIENTS mucus penetration of AIEC strains and enhances adhesion and invasion to
L. Boesmans1,*, K. Windey1, G. Vandermeulen1, V. De Preter1, K. Verbeke1 epithelial cells. Asm contributes to gut colonization of AIEC in murine model.
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and Thus, mucinases could be one of the key factors of AIEC implantation in CD
Nutrition Research Centre, KU Leuven, Leuven, Belgium patients.
Contact E-mail Address: leen.boesmans@med.kuleuven.be Disclosure of Interest: None declared
P0859 ACIDITY OF INTESTINAL CONTENTS IN THE DISTAL PARTS P0861 INFLAMMATORY LOAD MEASURED BY SPECT-CT RELIABLY
OF THE COLON IN PATIENTS WITH ULCERATIVE COLITIS CORRELATES WITH HISTOLOGY AND FECAL CALPROTECTIN IN
I. Gubonina1,*, V. Grinevich1, V. Ekimov1, N. Sherstneva2 ULCERATIVE COLITIS
1
2nd Therapy Department, 2Military Medical Academy, Saint-Petersburg, Russian J.F. Brandse1,*, R. Bennink2, S.van Eeden3, P.A. Baars4, M. Lowenberg1,
Federation C.Y. Ponsioen1, G.R. van den Brink5, G.R. DHaens1
1
Contact E-mail Address: giv70@bk.ru Department of Gastroenterology & Hepatology, 2Nuclear Medicine, 3Pathology,
4
Experimental Immunology, Academic Medical Center, Amsterdam, 5Department
INTRODUCTION: It is nececcary to determine the possibility of using mesala- of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam,
zine-delivering drugs with different release mechanisms depending on the pH Netherlands
value in patients with UC relapse. Contact E-mail Address: j.f.brandse@amc.uva.nl
AIMS & METHODS: To evaluate the acidity of intestinal contents in the distal
parts of the colon in patients with ulcerative colitis (UC) relapse. 43 patients with INTRODUCTION: Assessing inflammatory activity is essential in therapeutic
left-sided UC and 24 patients with extensive UC having mild or moderate relapse decision making in Ulcerative Colitis (UC). Novel scintigraphy techniques
were evaluated. The evaluation of the pH of the chymus with use of a universal including SPECT-CT are promising to measure inflammatory load in chronic
indicator test strip, as well as analysis of changes in the oM of intestinal contents inflammatory conditions such as UC. Leukocyte scintigraphy therefore needs to
depending on clinical, laboratory and endoscopic indicators of ulcerative colitis be validated using other established markers of inflammation.
activity, were carried out in all these patients. The control group consisted of 16 AIMS & METHODS: We aimed to prospectively validate leukocyte SPECT-CT
healthy volunteers. as a tool to measure and quantify inflammatory load in patients with different
RESULTS: On the whole, there was a trend towards acidification of chymus in extent and severity of UC.
patients with left-sided UC as compared to healthy volunteers (oM 6.760.21 UC patients with an indication for full colonoscopy were included. Within 1
vs. oM 6.940.2, respectively); however, this difference was not statistically week and without any changes in therapy both colonoscopy (Mayo score,
significant. In the group of patients with extensive UC, a decrease in pH to UCEIS) with biopsies (Geboes score) and leukocyte scintigraphy were per-
below 6.0 (20.8%) was noted significantly more often as compared to the patients formed. In addition, serum CRP and fecal calprotectin (Buhlmann ELISA)
with left-sided UC (4.7%, o50.05) or control group subjects (0%, o50.05). were measured and clinical questionnaires (CCAI, Mayo) were collected.
Statistically significant correlation between the pH of the intestinal contents Patients peripheral blood leukocytes were isolated and labelled with 200 MBq
with ulcerative colitis activity index (correlation coefficient (CC) -0.23), fecal technetium-99m HMPAO. SPECT combined with a low-dose CT was performed
calprotectin value (CC -0.25), UC duration (CC -0.21) or duration of UC 60 min after reinjection of labelled cells. To quantify inflammation in each colon
treatment (CC 0.35) was not revealed. segment the uptake of leukocytes was calculated as a ratio to the mean uptake in
CONCLUSION: In patients with left-sided UC, acidity of the intestinal contents bone marrow of 4 lumbar vertebrae and expressed as SPECT inflammation score
in the distal parts of the colon did not differ from that in the healthy volunteers in each colon segment and a Summed Activity Score (SAS) for the inflammatory
and did not depend on disease activity or duration of ulcerative colitis. Decrease activity in all 5 colonic segments together.
in the pH of the intestinal contents to below 6.0 was noted significantly more RESULTS: Twenty-six UC patients were studied. 3/26 were using anti-TNF, 4/
often in patients with extensive UC as compared to patients with left-sided UC or 26 thiopurines, 3/26 prednisone and 20/26 5-ASA at inclusion. At endoscopy 6/
healthy volunteers. In the treatment of patients with decreased intraluminal pH 26 (23%) of patients had proctitis, 8/26 (31%) left-sided and 12/26 (46%) pan-
levels, preference should be given to drugs with oM-independent release of active colitis. According to endoscopic Mayo score, 1/26 (4%) of patients had inactive,
ingredient. 5/26 (19%) mild, 8/26 (31%) moderate and 12/26 (46%) severe disease. The
Disclosure of Interest: None declared median (IQR) full Mayo score was 7 (5-10), CCAI: 6 (2-9), serum CRP 4.1
mg/L (1.7-12.5) and fecal calprotectin 449 ug/g (245-1142). According to
SPECT-CT patients were classified as having 9/26 mild, 12/26 moderate and 5/
P0860 ITS ALL IN THE STOOL. FAECAL CALPROTECTIN TO HELP 26 severe disease in their most affected segment. At the level of individual seg-
GUIDE ANTI-TNF THERAPY; A RETROSPECTIVE STUDY ments, significant correlations (Spearman) were observed between the SPECT
J. Gulliver1,*, G. Baker1, K. Millington 1, K. Zacchariah1, R. Makins1 inflammation score and endoscopic Mayo: r 0.54 (P50.01), UCEIS r 0.56
1
Gastroenterology, Cheltenham General Hospital, Gloucestershire Hospitals NHS (P50.01) and histologic Geboes score r 0.59 (P50.01). The Summed Activity
Foundation Trust, Cheltenham, United Kingdom Score correlated much better with fecal calprotectin r 0.55 (P50.01) than with
Contact E-mail Address: james.gulliver@glos.nhs.uk CRP: r 0.24 (p 0.24), CCAI: r 0.43 (P50.05) or clinical Mayo: r 0.54 (P50.01).
CONCLUSION: SPECT-CT assessment of UC disease severity in the most
INTRODUCTION: Faecal calprotectin (FC), a protein derived mainly from inflamed colon segment is correlated with both endoscopic and histologic
neutrophils and monocytes, is detected in increased quantities in the stool of scores. The total inflammatory load in UC at SPECT-CT is better reflected by
patients with inflammatory bowel disease (IBD). Recently, the National fecal calprotectin than by serum CRP.
Institute of Clinical Excellence (NICE) in the United Kingdom (UK) has recom- Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie and Takeda,
mended its use as a biochemical test to differentiate between IBD and functional R. Bennink: None declared, S. van Eeden: None declared, P. Baars: None
bowel disease; furthermore, it can also be used to evaluate disease activity or declared, M. Lowenberg: None declared, C. Ponsioen: None declared, G. van
response to treatment. We routinely assess patients symptoms and biological den Brink: None declared, G. DHaens Financial support for research from:
markers including FC at least annually once established on anti-TNF therapy. Abbott Inc, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma,
This assessment is brought forward if there is a suspicion of ongoing disease Photopill, Lecture fee(s) from: Abbott Inc, Tillotts, Tramedico, Ferring, MSD,
activity. UCB, Norgine, Shire, Consultancy for: Abbott Laboratories, Actogenix,
AIMS & METHODS: We sought to assess the impact of FC testing on our Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Jansen
clinical management, specifically for our patients with Crohns disease receiving Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL Biopharma,
anti-TNF therapy. We interrogated our pathology database to collect FC results Pfizer, SetPoint, Shire, Takeda, Teva, UCB
from all patients at Gloucestershire Hospitals NHS Foundation Trust who were
established on anti-TNF therapy for Crohns disease. FC samples had been
obtained either as part of annual assessment or earlier due to ongoing symptoms. P0862 A COCOON IMMUNISATION STRATEGY AMONG
We then reviewed the patients notes to determine what actions, if any, had been HOUSEHOLD CHILDREN OF ADULTS PATIENTS WITH
taken as a consequence of the FC results. INFLAMMATORY BOWEL DISEASE
RESULTS: FC results were available from 28 of 31 patients collected during K. Waszczuk1,*, E. Waszczuk2, A. Mulak2, L. Szenborn1, L. Paradowski2
2011 and 2012. Results were subdivided based on the FC level into four groups. 1
Department of Pediatric Infectious Diseases, 2Department of Gastroenterology
1) 5 50ug/g (n 9, 32.1%); 2) 50-100ug/g (n 7, 25%); 3) 100-200ug/g (n 5, and Hepatology, Wroclaw Medical University, Wroclaw, Poland
17.9%) and 4) 4200ug/g (n 7, 25%). Contact E-mail Address: karolkap@gmail.com
Across all four groups anti-TNF therapy was unaltered in 14 patients (50%) and
stopped in 3 (11%). The dose was increased but frequency of treatment main- INTRODUCTION: In order to protect patients with inflammatory bowel disease
tained in 2 (7%), and frequency increased in a further 2 (7%). Frequency was (IBD) against serious infections, vaccination of their household children is
reduced in one patient from 8 weekly to 10 weekly (3.5%). Two patients were lost recommended.
to local follow up. AIMS & METHODS: The aim of our study was to assess the not mandatory and
More specifically, in group 1, 34% had their anti-TNF therapy unaltered and not reimbursed vaccination coverage including pneumococcal, rotavirus, influ-
22% had their therapy stopped with consequent significant cost savings. In con- enza, and varicella vaccines among household children of adult patients with
trast; 43% of patients in group 4 had their anti-TNF therapy altered, either by IBD as the Cocoon Strategy. A self-designed survey was conducted in 138
increasing dose or frequency of administration. Regarding further investigations IBD patients hospitalised in the Department of Gastroenterology and
no patient with a FC result 4100ug/g went on to have a colonoscopy compared Hepatology at Wroclaw Medical University from November 2013 to March
with 33% of patients with an FC 550ug/g. 2014. The survey comprised questions about household children vaccination
CONCLUSION: FC is a useful tool when judging clinical response to anti-TNF coverage and the reasons of its refusal as well as the history of infectious diseases
therapy in patients with Crohns disease. Once treatment is established it allows in the patients. Randomly, patients completed the survey with a physician pre-
identification of patients for whom anti-TNF therapy can be further optimised or sent to determine questions comprehension. In order to provide test-retest relia-
stopped. It also helps guide the need for further investigation, if either to re-stage bility a group of ten patients completed it twice. Fisher exact test was used for
disease extent and severity or if considering alternative diagnoses. cross-classification tables.
REFERENCES
A368 United European Gastroenterology Journal 2(5S)
RESULTS: The survey data from 52 IBD patients having household children (25 retained small bowel capsule endoscopy (SBCE), suspicious of Crohns disease
women, 27 men, mean age: 36 years) were analysed. Two patients declared and further evaluation of protein-losing enteropathy in 17, 10, 7, 3, 2, 1 case,
refusing one obligatory vaccination of their children, while 40% of the patients respectively. The mean number of DBE examination per patient was 2.41.4.
reported at least one not reimbursed vaccine administration. Most frequently, Types of scope were type T, type P (thin type), and type B (short type) in 49, 41
children obtained pneumococcal (31%), rotavirus (23%), varicella (14%), and and 5 cases. The choice of the scope had depended on the therapeutic capability
influenza (10%) vaccines. The most common reasons for non-immunisation was or the facility of deeper insertion. The insertion roots were antegrade (from
unawareness of the existing recommendations (46%), fear of adverse effects of mouth) in 31 patients and retrograde (from anus) in 64 patients. The mean
the vaccines (18%) and not believing in vaccines efficacy (10%). In one case a insertion time was 6531 minute. The antegrade vs. retrograde was 4525 vs.
medical health care worker discouraged from immunisation. There was statisti- 3440 minutes (p 0.005). The mean total examination time was 8334 min.
cally significant association between not reimbursed vaccines coverage and edu- The antegrade vs. retrograde was 8334 vs. 5626 min. (p50.0001). The mean
cational level of the patients (p50.001). Despite the fact that 28% of IBD insertion depth was 9593 cm. The antegrade vs. retrograde was 17875 vs.
patients could not definitively recall varicella infection, none of their household 5570 minutes (p50.0001). Balloon dilation therapies were performed in 18
children nor they were vaccinated against chickenpox. procedures in 8 patients. In 10 patients, the prior SBCE had been done and 6
CONCLUSION: The use of not mandatory vaccines recommended in Poland in patients were retained. All the retained SBCE were removed by double balloon
IBD patients family members is insufficient. Frequently, patients have serious endoscopy. In only one out of 10 patients, DBE had not shown any severe
doubts concerning safety and efficacy of vaccinations. Therefore, further vac- stricture and SBCE was used for the mucosal evaluation repeatedly. No compli-
cines promotion and education of patients as well as their health care providers cation was encountered in diagnostic and therapeutic DBE.
are needed. A particular concern is associated with not vaccinating against influ- CONCLUSION: DBE showed that ileal lesions were more common and oral
enza and varicella, which pose a high risk of infection. Non-immunised and VZV DBE was time-consuming in Crohns disease. The evaluation with DBE also can
seronegative IBD patients should be vaccinated, and in case of their immunosu- pick out the patient who can undergo the SBCE. The dilation therapy may delay
pression, vaccination of household children is required. the timing of the surgical interventions. DBE, especially the retrograde DBE,
Disclosure of Interest: None declared have a potential to improve the outcome of Crohns disease.
Disclosure of Interest: None declared
INTRODUCTION: Deep enteroscopy has been widely used for various small
bowel diseases. One of the most common diseases that affected the small bowel is P0866 QUALITY OF LIFE IN ULCERATIVE COLITIS ASSOCIATION
Crohns disease. The idea is being accepted that the mucosal healing is important BETWEEN THE SHORT INFLAMMATORY BOWEL DISEASE
parameter for the better outcome of Crohns disease. However the efficacy and QUESTIONNAIRE (SIBDQ) AND THE SHORT HEALTH SCALE
safety of the DBE is not fully understood. (SHS) AND THEIR RELATIONSHIPS WITH CLINICAL AND
AIMS & METHODS: We conducted a retrospective case series study to eluci- ENDOSCOPIC DISEASE ACTIVITY
date the efficacy of DBE in Crohns disease. We enrolled the consecutive 40 K. Theede1,*, M. Kiszka-Kanowitz1, I. Nordgaard-Lassen1, A.M. Nielsen1
patient who underwent the 95 DBE examinations since 2003. Patients character- 1
Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre,
istics, indications of the deep enteroscopy, duration of procedures, therapeutic Hvidovre, Denmark
interventions and complications were assessed.
RESULTS: Subjects were 7 females and 33 males, mean age was 3813 years INTRODUCTION: Health Related Quality of Life (HRQoL) is an important
old. The indications of DBE were mucosal evaluation for known Crohns disease, part of Inflammatory Bowel Disease (IBD) assessment, and is affected by both
obscure gastrointestinal bleeding, small bowel obstruction, removal of the disease activity, psychological, and social factors. Several HRQoL questionnaires
United European Gastroenterology Journal 2(5S) A369
have been developed, but are primarily used in the setting of clinical trials. Little patients. A TST of 415mm should be used as a cut-off to identify patients at
is known about the relationship between HRQoL and disease activity and risk for latent TB in these patients. Smoking is a risk factor for TST positivity.
between the different HRQoL questionnaires. We aimed to assess the association Disclosure of Interest: None declared
between the SIBDQ and the SHS and their associations with clinical and endo-
scopic disease activity.
AIMS & METHODS: Prospectively, 110 patients with ulcerative colitis under- P0868 INCREASED EXTRACELLULAR MATRIX PROTEINS TURN-
went sigmoidoscopy and completed the SIBDQ and the SHS. The SIBDQ is a OVER IN PATIENTS WITH CROHNS DISEASE
validated 10-question tool measuring physical, social, and emotional status (score L.E. Godskesen1, M.D. Jensen1,*, L. Klinge1, J. Mortensen2, A.-C. Bay-Jensen2,
10-70, poor-good). The SHS is a four-part visual analogue scale questionnaire A. Krag1, J. Kjeldsen1
measuring bowel symptoms, activities of daily life, worry, and general well-being 1
Department of Gastroenterology, Odense University Hospital, Odense C, 2Nordic
(score 0-40, good-poor). Clinical disease activity was assessed using the Mayo Bioscience A/S, Herlev, Denmark
score (0-12) and was divided into remission (2), mild (3-5), moderate (6-9), and Contact E-mail Address: line@napoleon.dk
severe (10-12) activities. The endoscopic grade of inflammation was assessed
using Mayo Endoscopic Score (MES, 0-3). INTRODUCTION: Ongoing inflammation in Crohns disease (CD) may lead to
RESULTS: The median age was 37 years (19-80), and 56 % were female. The development of intestinal fibrosis and patients may present with stenosis.
median disease duration was 4.5 years. 29 % had mucosal healing, 20 % active Inflammation is a dynamic process with a permanent remodeling of the extra-
proctitis, 16 % active proctosigmoiditis, 18 % active left-sided colitis and 18 % cellular matrix (ECM). Small fragments of the ECM generated during this pro-
pancolitis. According to the MES, 29 % had mucosal healing, 26 % had mild, 31 cess, so called neoepitopes, are released into the circulation and could be used as
% moderate and 14 % severe inflammation. According to the Mayo score, 37 % biochemical markers of disease activity or markers of fibrosis.
were in clinical remission, 21 % had mild, 31 % moderate and 11 % severe AIMS & METHODS: This study investigates a panel of these novel developed
disease activity. markers in patients with suspected or known CD.
HRQoL significantly decreased with increasing clinical disease activity (Mayo 106 patients referred for evaluation of CD had serum samples drawn. Patients
score) when assessed with both SIBDQ (2 51.9, p50.0001) and SHS were evaluated with colonoscopy, small-bowel imaging (capsule endoscopy, MR
(2 56.2, p50.0001). HRQoL also significantly decreased with increasing endo- enterography, and CT enterography), fecal calprotectin, and C-reactive protein.
scopic disease severity (MES) when assessed by both SIBDQ (2 33.1, 35 patients had newly diagnosed CD, 26 had CD with active inflammation or
p50.0001) and SHS (2 40.3, p50.0001). Overall, we found a significant dif- stenosis, 11 had known CD without inflammation or complication, and 34 had
ference in HRQoL between patients with mucosal healing (MES 0) and active no evidence of Crohns disease. The following neoepitopes were measured by
inflammation (SIBDQ, inactive/active, 59.1/45.6, p50.0001 and SHS, inactive/ competitive ELISAs; MMP-mediated of type I, III, IV collagen (C1M, C3M,
active, 6.8/19.7, p50.0001). Moreover, we found a strong association between C4M), N-terminus pro-collagen type I (P1NP), and MMP-degraded, citrulli-
SIBDQ and SHS using linear regression (SHS -0.73SIBDQ52.1, nated vimentin (VICM).
p50.0001). Data were not normally distributed and Kruskal-Wallis one-way analysis of
CONCLUSION: In this study we demonstrate that HRQoL is not only strongly variance was used for comparison. ROC-curve analysis were used to test the
associated with clinical disease activity, but also with the endoscopic disease biomarkers ability to discriminate CD from non-CD.
severity. We also demonstrate that SIBDQ and SHS are strongly associated RESULTS: Serum levels of C3M were significantly elevated in patients with CD
with each other. compared to patients without CD (median 24.4 and 19.1, respectively; P 0.01).
Both SIBDQ and SHS show significantly decreasing HRQoL with increasing C3M discriminated CD from non-CD with an AUC of 0.66. Concentrations of
clinical disease activity as well as with increasing endoscopic disease severity. C1M and C4M were also elevated but statistical significance was not reached
The study also shows significant difference in HRQoL between patients with (C1M: median 68.9 and 62.9; P 0.12. C4M: median 70.5 and 67.2; P 0.15). In
mucosal healing and endoscopic active disease. Both questionnaires seem equally patients with CD, C1M and C3M concentrations were higher in clinically active
adequate in determining the disease impact on HRQoL. disease (CDAI 4 150) compared to quiescent disease (C1M: median 75.0 and
HRQoL is from the patients perspective one of the most important parts of IBD 63.2; P 0.02. C3M: median 24.5 and 22.7; P 0.10), and C3M concentrations
management. SIBDQ and especially SHS can be completed quickly during reg- were higher in CD involving the colon compared to small bowel CD (median 26.2
ular visits, and can be used as an easy tool for HRQoL monitoring. Significant and 22.1; P 0.05). C1M, C3M and C4M correlated with CRP (Spearmans rho
changes must be followed by exploration of the possible causes including assess- 0.76, 0.40, and 0.45, respectively; P 5 0.001) but not with fecal calprotectin.
ment of disease activity. Concentrations of ECM degradation markers were not significantly increased in
Disclosure of Interest: K. Theede Financial support for research from: Research patients with stricturing CD compared to patients without CD. In subgroup
grant from AbbVie Inc. and Ferring Pharmaceuticals, M. Kiszka-Kanowitz: analysis of patients with diagnosed CD and elevated CRP compared to non-
None declared, I. Nordgaard-Lassen Financial support for research from: CD and normal CRP C1M, C3M and C4M discriminated CD from non-CD
Research grant from AbbVie Inc. and Ferring Pharmaceuticals, Consultancy (AUC of 0.95, 0.88 and 0.90).
for: Advisory Board AbbVie Inc., A. Nielsen Financial support for research CONCLUSION: Turnover of ECM proteins is increased in patients with CD.
from: Research grant from AbbVie Inc. and Ferring Pharmaceuticals, These neoepitopes may distinguish between patients with CD and patients with-
Consultancy for: Advisory Board AbbVie Inc. out CD and between active CD and disease in remission. Further studies of these
promising markers of the ECM are warranted.
Disclosure of Interest: L. E. Godskesen: None declared, M. Jensen: None
P0867 IS THE TUBERCULIN SKIN TEST ALONE ACCURATE IN declared, L. Klinge: None declared, J. Mortensen Other: Employee at Nordic
MODEATE-TO-SEVERE BCG VACCINATED PATIENTS WITH Bioscience, A.-C. Bay-Jensen Other: Employee at Nordic Bioscience, A. Krag:
INFLAMMATORY BOWEL DISEASE TREATED WITH None declared, J. Kjeldsen: None declared
IMMUNOSUPPRESSIVES TO TEST FOR LATENT TUBERCULOSIS?
K.B. Gecse1,*, Z. Kurti1, A. Balint2, K. Farkas2, B.D. Lovasz1, A. Szabo1,
M. Mandel1, A. Gyurcsanyi1, Z. Vegh1, A. Mohas1, T. Molnar2, L.S. Kiss1, P0869 INTESTINAL EPSTEIN- BARR VIRUS IS ASSOCIATED WITH
P.A. Golovics1, P.L. Lakatos1 MUCOSAL LYMPHOPROLIFERATION AND SUBSEQUENT
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department INTESTINAL SURGERY IN INFLAMMATORY BOWEL DISEASE
of Medicine, University of Szeged, Szeged, Hungary PATIENTS
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu L. Nissen1,2,*, I. Nagtegaal2, D.de Jong1, W. Kievit1, L. Derikx1, M. Lynch2,
H.van Krieken2, F. Hoentjen1
INTRODUCTION: There are few data available on effect of immunomodulator/ 1
Gastroenterology and Hepatology, 2Pathology, RadboudUMC Nijmegen, The
biological therapy on the accuracy of tuberculin skin test (TST, Mantoux skin Netherlands, Nijmegen, Netherlands
test) and interferon-gamma release assay (IGRA) in BCG vaccinated immuno- Contact E-mail Address: loes.nissen@radboudumc.nl
suppressed IBD patients.
AIMS & METHODS: Our aim was to define the accuracy of the TST and IGRA INTRODUCTION: Thiopurine therapy increases the risk of (Epstein- Barr virus
tests in a BCG vaccinated referral IBD cohort treated with immunosuppressives associated) lymphomas for Inflammatory Bowel Disease (IBD) patients up to
and/or biologicals. Data of 135 consecutive moderate-to-severe IBD (98 CD, 37 four times. Epstein- Barr virus (EBV) can cause a wide spectrum of lymphopro-
UC) patients were analyzed (male/female: 64/71, median age at diagnosis: 24.0; liferative reactions, ranging from morphologically benign with normal B lym-
IQR: 18-31 years, duration: 7.0; IQR: 4-13 years). Patients were treated with phocytes (BL) and lymphoplasmacytic infiltrate in the lamina propria (LI) to
immunosuppressives (azathioprine, steroids) and/or anti-TNF therapy. Blood aggressive lymphomas with atypical BL and LI.
samples for IGRA were collected during routine laboratory testing parallel EBV can be detected in colonic mucosa in up to 60 % of the IBD patients, but
with TST. The result of TST was determined according to international guide- there is no consensus on when to perform EBV testing on intestinal mucosa. We
lines. Both in- and outpatient records were collected and comprehensively hypothesized that EBV testing can be guided by histological features including
reviewed. morphology of BL and LI.
RESULTS: TST positivity rate was 21.6%, 20.1%, 13.4% or 12.7% with cut-off AIMS & METHODS: The aim of this study was to determine the value of the
values of 5, 10, 15 and 20mm. IGRA positivity rate was 7.7% with indeterminate histology of the inflammation in predicting EBV presence in intestinal mucosa
result in 1.2%. The correlation between TST and IGRA was significant, with and to correlate EBV positivity with clinical endpoints such as intestinal surgery
moderate-to-good kappa values if TST results were 415mm (kappa: 0.32-0.34, and development of lymphoma.
p50.001). In addition, a TST of 14 and 17mm was also identified as best cut-off All IBD patients who underwent EBV testing by EBV-encoded RNA in situ
value in a ROC analysis (AUC: 0.70, p 0.04). There was no association between hybridization (EBER) in intestinal biopsies between January 2005 and October
the type and number of immunomodulators used or any disease phenotype char- 2013 in our centre were identified. All biopsies were revised by a blinded, expert
acteristics and the TST or IGRA results. Importantly, smoking was identified as gastro-intestinal pathologist and scored on three histological features: number of
a risk factors for TST but not IGRA positivity (OR: 3.80, 4.88, 9.87 and 8.98, EBV positive cells per high power field (HPF); normal or atypical LI and normal
p50.002, for TSTcut-off 5, 10, 15 and 20mm). or atypical BL. Demographic and clinical data were collected from patient charts.
CONCLUSION: The TST and IGRA are partly complimentary methods and Adverse events that were registered included intestinal surgery and lymphoma.
accuracy is acceptable also in BCG vaccinated and immunosuppressed IBD
A370 United European Gastroenterology Journal 2(5S)
We used the Chi square test or Fishers exact test to identify an association with and 9% had inactive disease (64% mild, 20% moderate and 7% severe disease).
EBV positivity. Mean MEGS was 2018, with 82% having active disease and 18% inactive
RESULTS: 58 IBD patients were included, 28 were EBV positive and 30 were disease (p50.01 in comparison to endoscopy, sensibility 88%, specificity 75%,
EBV negative. Ulcerative colitis was more frequent in the EBV positive group VPP 97%, VPN 38%). MEGS, was significantly higher in penetrating than in
(82,1 % versus 56,7 %; p 0.052) non-penetrating and non-stricturing disease (respectively 359 vs 711, p5
EBV positive patients had significantly more frequent atypical LI (57.1 % versus 0.001). MEGS was significantly correlated with SES-CD (p50.01), in particular
3.3 %; p 50.001). The specificity for predicting EBV presence of the atypical for the ileal (p50.01) and ceacum-ascending colon subscores (p 50.05). Severity
LI is high (96.7 %), just as its positive predictive value (94.1 %). At time of of the disease at endoscopy did not correlate to severity at MEGS (p 0.7). Both
biopsy, EBV positive patients used more often combinations of two or more anti- MEGS and SES-CD show significant correlations with CDAI (p50.01) and
inflammatory drugs (5-aminosalicytes excluded; 50 % versus 16.7 %; p 0.007) CRP (p50.05), yet SES-CD only correlated significantly with FC (p50.001).
Eighteen EBV positive patients (64.29 %) had 20 pre-defined complications (18 The extramural involvement subscore, observed in half of patients, regardless of
colectomies, 2 lymphomas). Within the group of EBV positive patients, those the behavior and severity at endoscopy, was associated to CRP positivity
who developed complications had a significantly higher EBV load (50 % versus (p50.05), not with fecal calprotectin (p 0.67). Increasing staging of grading
10 %; p 0.048), expressed as the frequency of 10 EBV positive cells per HPF. at endoscopy was significantly correlated to the risk of extramural involvement
11 patients had atypical LI and BL, including 2 lymphomas: those were treated (p 0.008)
with chemotherapy. In the other 9 patients at least one immunosuppressive drug CONCLUSION: MRI is capable of identifying disease activity, although it
was stopped. In all patients the atypical LI showed resolution. 8 of the 9 patients results less accurate in the assessment of severity as measured at endoscopy.
became EBV negative and 1 patient had reduction of EBV positive cells. The presence of positive CPR suggests the need of MRI for the staging of
CONCLUSION: In the present study, atypical LI was associated with mucosal patients with active luminal disease.
EBV in IBD patients. A high EBV load is correlated with adverse events. REFERENCES
Reduction of immunosuppression may decrease intestinal EBV associated 1 Makanyanga J, et al. Eur Radiol 2014.
lymphoproliferation. 2 Daperno M, et al. Gastrointest Endosc 2004.
Disclosure of Interest: None declared Disclosure of Interest: None declared
P0870 SCREENING OF NOVEL PLASMA MICRORNAS ASSOCIATED P0872 ASSAY SPECIFIC DIFFERENCES IN CONSECUTIVELY
WITH DISEASE PROGRESSION IN ULCERATIVE COLITIS MEASURED F-CALPROTECTIN IN PATIENTS WITH IBD
M. Patel1,2,*, A.M. Verma1,2, M. I. Aslam1,2, K. West2, J. Jameson2, FOLLOWED OVER TIME
J.H. Pringle1, B. Singh2 K. Amcoff1, M. Lampinen2, M. Stridsberg3, J. Halfvarson1,4, M. Carlson2,*
1
Cancer Studies & Molecular Medicine, University of Leicester, 2University 1
School of Health and Medical Sciences, Orebro University, Orebro, 2Department
Hospitals of Leicester, Leicester, United Kingdom of Medical Sciences, Gastroenterology Research Group, Uppsala University,
3
Contact E-mail Address: maleene@doctors.org.uk Department of Clinical Chemistry and Pharmacology, Uppsala, 4Dep of Internal
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden
INTRODUCTION: New biomarkers are required to monitor patients with Contact E-mail Address: jonas.halfvarson@orebroll.se
Ulcerative Colitis (UC) and predict complications such as dysplasia and colitis
associated cancer (CAC). Accurate plasma based biomarkers would allow phy- INTRODUCTION: Faecal calprotectin (FC), an abundant neutrophil protein,
sicians to make clinical decisions, thereby avoiding unnecessary invasive tests. has recently been introduced as a non-invasive marker for monitoring of disease
AIMS & METHODS: This feasibility study aimed to identify novel microRNAs activity in inflammatory bowel disease (IBD). However, it has been difficult to
(miRNAs) in the plasma of patients with Ulcerative Colitis related to disease define a definite threshold to discriminate between remission and active disease.
progression. AIMS & METHODS: We, aimed to compare the results of different FC-assays
RESULTS: Primary analysis of the array data identified the differential expres- in a well-characterized cohort of patients with IBD, followed over time. Patients
sion of several miRNAs from which the following miRNAs 122,125b, 139-3p, (n 13) with established IBD provided faecal samples and reported clinical activ-
331-5p, 375, 383-3p, 409-3p, 720, 1274B were chosen for validation. Analysis of ity every third months prospectively for a two year period. Relapse was defined
variance was used to assess differences between groups. MiR-375 was shown to as increasing symptoms and intensified treatment. FC was measured with three
be significantly up-regulated in the CAC cohort (p 0.002) when compared to different assays; Calprotectin Elisa Buhlmann Laboratories AG, Basel,
UC and PSC. MiR-375 was found to be an effective biomarker of disease pro- Switzerland; Phadia Elia Calprotectin, ThermoFischer Scientific, Freiburg,
gression over disease duration, with Cox-regression analysis showing a Cox Germany; and PhiCal Calprotectin Elisa, Immundiagnostik AG, Bensheim,
hazard ratio of 1.91 (p 0.01). Germany. Disease status, defined as clinical remission or relapse, i.e. active dis-
CONCLUSION: Peripheral plasma miRNAs have the potential to act as bio- ease, was determined at the time of collection of each fecal sample in each
markers of disease progression in Ulcerative colitis. This study provides the first patient. Samples were grouped as corresponding to clinical remission or active
evidence that miRNA-375 is up regulated in cases of CAC. This finding needs to disease. However, samples collected three months after a relapse were excluded to
be extended to a larger validation cohort. reduce possible bias due to prolonged intensified therapy, steroid dependent
Disclosure of Interest: None declared disease or ongoing subclinical inflammation.
RESULTS: In total, the 13 patients prospectively provided 91 faecal samples
during the two year period. The median (IQR) concentration of FC was 187
P0871 THE INS AND OUTS OF MRI AND ENDOSCOPY IN THE (57 582) mg/g, 52 (15 415) mg/g and 55 (9 158) mg/g using the Buhlmann-,
EVALUATION OF DISEASE ACTIVITY AND SEVERITY IN Phadia- and Immundiagnostik assay, respectively (p50.0001). Based on the cut-
CROHNS DISEASE off provided by the manufactures, i.e. 450 mg/g, the FC assay was positive in 74
M. Serio1,*, A. Pierro2, G. Maselli2, K. Efthymakis1, A. Milano1, F. Laterza1, (81 %), 47 (52 %) and 50 (55 %) of the 91 samples when analyzed by the
A. Bonitatibus1, G. Sallustio2, M. Neri1 Buhlman-, Phadia- and Immundiagnostik assay, respectively. Modest to fairly
1
Medicine and Aging Sciences and CESI, Universita` "G. DAnnunzio", Chieti, good correlations were observed between the Buhlmann- and the Phadia assay,
2
Radiology Department, Fondazione di Ricerca e Cura Giovanni Paolo II, the Buhlmann- and the Immundiagnostik assay and the Phadia- and the
Universita` Cattolica del Sacro Cuore, Campobasso, Italy Immundiagnostik assay (R2 0.70, R2 0.80 and R2 0.86, respectively).
Contact E-mail Address: mneri@unich.it However, Bland-Altman plots revealed overall poor agreement between the
assays. Assay specific sensitivity, specificity and predictive values for defining
INTRODUCTION: Endoscopy is the gold standard for activity assessment in clinical remission vs. active disease for each assay based on different cut-offs
luminal Crohns disease (CD) but, due to the full thickness involvement of the are shown in table 1.
bowel wall, or presence of complications, CD activity is the result of an integra- Table 1. Assay specific sensitivity, specificity and predictive values for defining
tion of endoscopic, clinical, laboratory, and imaging data. Recently, a radiolo- clinical remission vs. active disease for each assay based on different cut-offs
gical score which integrates both mural and extramural involvement has been
validated for a global disease evaluation (1). FC cut-off
AIMS & METHODS: to examine the relationships among MRI, laboratory (mg/g) Bu 50 Ph 50 Im 50 Bu 100 Ph 100 Im 100 Bu 150 Ph 150 Im 150
inflammatory markers, clinical activity scores and endoscopy in a series of CD
patients. Sensitivity 86% 71% 86% 86% 64% 36% 79% 50% 14%
45 consecutive patients with endoscopically proven CD underwent at the time of Specificity 26% 66% 62% 50% 72% 78% 56% 76% 80%
enrollment MRI enterography, performed utilizing a 1.5 T system, for the staging NPV 87% 89% 94% 93% 88% 81% 90% 84% 77%
of disease at diagnosis and activity assessment. Endoscopic activity was measured PPV 24% 37% 39% 32% 39% 31% 33% 37% 17%
by a quantitative score (Simple Endoscopic Score for Crohns Disease, SES-CD
(2), range 0-40) with active disease being present for a 43 score and mild,
moderate ad severe disease for ranges of respectively 4-10, 11-19 and 420.
MRI activity was measured by a previously validated quantitative score Bu; Buhlmann assay, Ph; Phadia assay, Im; Immundiagnostik assay, NPV; nega-
(Magnetic Resonance Enterography global score, MEGS, range 0-296), with tive predictive value, PPV; positive predictive value
active disease being present for a 40 score. For all participants the Crohns CONCLUSION: By cross-comparisons pronounced inter-assay differences were
Disease Activity Index (CDAI) was completed and CRP and fecal calprotectin revealed. Although moderate to fairly good correlations between the FC assays
(FC) were measured (positivity cut-off respectively 4 0.50 mg/dl and 4150 g/ were observed, Bland-Altman plots showed overall poor agreement.
gr). Disclosure of Interest: None declared
RESULTS: We enrolled 19 males and 26 females, mean age 3714 years, mean
disease duration 5 years. According to Montreal disease classification the phe-
notype was L1 in 47%, L2 in 6% and L3 in 47%; the behavior was B1 in 24%, B2
in 56%, B3 in 20% and perianal disease in 2%; resectional surgery related to CD
was observed in 20%. According to SES-CD, 91% of patient had active disease
United European Gastroenterology Journal 2(5S) A371
of IBD patients developing or not cancer (IBD-C n 6/30; 20% vs IBD-K n 3/
P0873 RESIDUAL ABNORMALITIES AFTER MAYO ENDOSCOPIC
15; 20%). In IBD-C, IMM were used in 10 (33%)(combined anti-TNFs in 2;6.
SUBSCORE DEFINED COMPLETE MUCOSAL HEALING
7%).
DEMONSTRATED BY NOVEL ISCAN ENDOSCOPIC AND REFINED
CONCLUSION: In a retrospective matched-pair study, a comparable low fre-
HISTOLOGICAL GRADINGS
quency of colon cancer was observed in IBD patients treated or untreated with
M. Iacucci1,*, M. Fort Gasia1, R. Panaccione1, S. Ghosh1, X. Gui2 anti-TNFs.
1
IBD clinic. Division of Gastroenterology, 2Department of Pathology, University of Disclosure of Interest: None declared
Calgary, Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca
P0875 IS THERE A ROLE FOR THE NEW SEROLOGICAL MARKERS IN
INTRODUCTION: High definition(HD)- iSCAN endoscopy can characterize in PREDICTING DISEASE COURSE IN AN IBD POPULATION
details the mucosa in patients with ulcerative colitis (UC) and may provide more COHORT? LESSONS LEARNT FROM A PROSPECTIVE IRISH
information about inflammation and mucosal healing (MH). However, the gold POPULATION
standard of mucosal healing is still histological diagnosis. More refined histologic M.N. Shuhaibar1,*, C. OMorain1
and high definition iSCAN endoscopic criteria may redefine mucosal healing. 1
Department of Gastroenterology/ Clinical Medicine, AMNCH/Trinity College
AIMS & METHODS: 78 patients (40 male, median age 42y, range 19-90y) Dublin, DUBLIN, Ireland
with UC were assessed by HDiSCAN colonoscopy (Pentax EC-3490Fi; Pentax, Contact E-mail Address: mnshuh@gmail.com
Japan) as well as by white light endoscopy (WLE). Mayo endoscopic subscore
and UC endoscopic index of severity (UCEIS) score were assigned to patients INTRODUCTION: Crohns disease and Ulcerative colitis are the two main
according WLE findings. Mucosal pattern on iSCAN was graded as 1 normal, forms of inflammatory bowel disease. There are different disease phenotypes
2 mosaic pattern, 3 tubular-gyrus, 4 nodular rosette. The vascular pattern within those groups and yet another 10-17% of patients may not have either
was graded as 1 normal, 2 spiral isolated vessels, 3 crowded tortuous ves- diagnosis and can be then be classified as indeterminate colitis until later on in
sels, 4 Irregular vessels. A histological grading and scoring system that assesses their disease course when they are reclassified into either main group as symp-
all changes possibly seen in IBD was developed for a detailed and comprehensive toms progress. Furthermore, some patient with gastrointestinal symptoms may
evaluation. This system (GUI-ECAP system) was designed to reflect all histologic not have IBD initially, but develop it in future. Several antibodies have been
changes in IBD categorized as 1) Extent of inflammation (focal, multifocal, linked to CD and different IBD subtypes.
diffuse), 2) Chronicity (crypt architectural alteration, Paneth cell metaplasia), AIMS & METHODS: The aim of our study was to determine the prevalence of
3) Activity (surface epithelium changes, neutrophilic cryptitis, crypt abscess, the new anti-glycans antibody panel in a prospective homogenous IBD cohort to
crypt destruction, lamina propria mononuclear cellularity, lamina propria neu- help differentiating those with IBD from healthy controls. We aimed to assess
trophil infiltration, and basal plasmacytosis), and 4) Plus additional findings, panels role in discriminating between CD and UC with their different phenotype
including eosinophilia and lymphoid follicles/aggregates. An established histolo- and their predictive value for disease course and treatment stratification in the
gic grading system, New York Mount Sinai score was used to validate the grad- future.
ing of inflammation. Antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA),
RESULTS: In this cohort of 78 patients with UC, 23 (29%) patients had Mayo laminaribioside (ALCA), Chitobioside (ACCA), mannobioside (AMCA) were
endoscopic subscore of 0. Of these 23 patients with complete MH, 18 patients tested in serum samples of 103 IBD patients, 199 healthy matched controls.
(78%) had abnormal vascular pattern on iSCAN and 7 (30%) had abnormal Antibody response was matched to disease type and course. A backward step
mucosal pattern on iSCAN. By using ECAP histologic scoring all 23 patients multiple-regression analysis was performed along with 2- sample t-test for uni-
(100%) showed various histologic abnormalities including crypt architectural variate biomarker analysis.
alteration [19, (83%)], surface epithelium abnormality [16, (70%)], crypt destruc- RESULTS: The anti-glycans antibody panel was useful in differentiating IBD
tion [3, (13%)], increase in lamina propria mononuclear cells [15, (65%)], basal patients from healthy matched controls. Overall, 72% of IBD patients tested
plasmacytosis [11, (48%)], lamina propria neutrophilic infiltration [5, (21%)] and positive for anti-glycans antibodies and of those 64% were positive for
other additional findings [19, (83%)]. gASCA, compared to 49% for ACCA antibody. gASCA was highly sensitive
CONCLUSION: The subtle histologic abnormalities underlying the apparently and specific in CD patients.
healed mucosa with Mayo endoscopic subscore of 0 can be detected by using CONCLUSION: From applying the anti-glycans antibody panel, combination of
refined histological scoring system (GUI-ECAP) in combination with iSCAN. gASCA IgA, Anti-L and Anti-C antibodies were statistically very significant in
Sensitive endoscopic techniques such as iSCAN and histologic scoring such as differentiating CD from UC (with a p 50.0001). gASCA was very specific to CD
ECAP can detect residual abnormalities in the majority of patients with see- and correlated with severe disease course requiring surgery or fistulas, requiring
mingly complete MH in UC. anti -TNF therapy in the lateral years.
Disclosure of Interest: None declared Disclosure of Interest: None declared
P0874 COLORECTAL CANCER IN IBD PATIENTS TREATED OR P0876 CLINICAL OUTCOMES IN PATIENTS WITH INTERMEDIATE
UNTREATED WITH ANTI-TNFS: A RETROSPECTIVE MATCHED- RAISED FAECAL CALPROTECTIN LEVELS
PAIR STUDY IN A 13 YEARS FOLLOW UP M. Mcfarlane1, A. Dhaliwal1, S. Chambers1,*, C. Nwokolo1, A. Patel1,
M. Ascolani1,*, G. Condino1, C. Petruzziello1, S. Onali1, E. Calabrese1, E. Lolli1, R. Arasaradnam1,2
A. Ruffa1, F. Pallone1, L. Biancone1 1
Gastroenterology, UHCW, Coventry, 2CSRI, University of Warwick, Warwick,
1
Universita` Tor Vergata, Rome, Italy United Kingdom
Contact E-mail Address: biancone@med.uniroma2.it Contact E-mail Address: r.arasaradnam@warwick.ac.uk
INTRODUCTION: In murine models, blocking TNF-alpha showed efficacy in INTRODUCTION: Calprotectin is a calcium binding protein of the S100 family
colitis-associated colon cancer. Chronic inflammation in Inflammatory Bowel associated with inflammation. A recent systematic review has confirmed its value
Disease (IBD) colitis has been associated with colorectal cancer (CCR). in distinguishing between organic (inflammatory bowel disease - IBD) and non-
AIMS & METHODS: In a monocentric retrospective matched-pair study, the organic gastrointestinal disease (irritable bowel syndrome - IBS). Those with FC
frequency of colon cancer was compared in a cohort of IBD patients treated or levels below 50 mcg/g have a negative predictive value of 492% to exclude
untreated with anti-TNFs. In a matched-pair study, the role played by clinical organic gastrointestinal disease. Conversely, FC levels greater than 250mcg/g,
characteristics of IBD in determining the frequency of colon cancer was also correlates with endoscopic disease activity in those with IBD; sensitivity of 90%.
evaluated. Clinical records of all IBD patients in follow up from 2000 to 2013 The aim of our study was to determine the clinical outcome in patients presenting
at our tertiary IBD referral center developing cancer of the lower GI tract (IBD- with an intermediate raised level of FC between 50-250 mcg/g.
K)(small intestine, appendix, CCR, anal canal) were reviewed. Each IBD-K AIMS & METHODS: FC test results from July 2012 to October 2013 were
patient was retrospectively matched with 2 IBD patients with no cancer of the reviewed. FC testing was performed using the PhiCal ELISA method. 482
lower GI tract (IBD-C), for IBD type (MDC/RCU), gender, age (5yrs). Anti- patients were identified from the UHCW pathology database: 390 normal
TNFs (Infliximab or Adalimumab1 dose) and IMM (6mos) use was reported. (550mcg/g), 51 intermediate (50-250mcg/g) and 41 high (4250mcg/g).
Data expressed as median (range). Students T test and Chi squared test used as Excluding paediatric patients (under 16), left 47 intermediate and 35 high results.
appropriate. Where possible clinical information was obtained from the UHCW Clinical
RESULTS: From 2000 to 2013, the study population included 2387 IBD results and reporting system. If no information was found then general practi-
patients: anti-TFNs use in 384 (16%). Cancer of the lower GI tract developed tioners (GPs) were contacted for further details (long term clinical data could not
in 15/2387 (0.62%) patients (9CD,6UC), including 12 CCR, (6UC,6CD), 1 ileal be found for 5 intermediate and 9 high patients).
adenocarcinoma (1CD), 1 carcinoid of the appendix (1CD), 1 anal canal carci- RESULTS: We studied a subset of 50 of the 390 normal FC values (550mcg/g)
noma (1CD). In the 15 IBD-K patients, age at diagnosis of cancer was 51 (28-73) which served as a comparator group. Of these, 9 (18%) were referred to second-
yrs, IBD duration 19yrs (1-47): there were 9 CD of the ileum (I) (n 4), colon (C) ary care gastroenterology, with 3 (6%) still in secondary care 6 months post FC.
(n 2), ileum-colon (IC) (n 3) and 6 UC distal (n 3), left-sided (n 1) or total None were diagnosed with IBD.
(n 2). Among the 15 IBD-K patients, 3 (20%) received anti-TNFs and/or IMM Of the 26 patients with high FC (4250mcg/g), 8 did not have details provided by
(combined in all 3). In these 3 patients, cancer included CCR (n 2) or carcinoid their GPs, 8 (31%) were known IBD patients and 3 (12%) were not investigated -
(n 1) in 2CD (2F,age 40 and 54yrs, CD duration 28 and 26 yrs; I-C, fistulizing) declining referral or patient mortality. 6 (23%) had a new diagnosis of IBD and 1
and 1UC (1F, CCR, age 30, duration 19yrs; pancolitis). Among the 384/2387 (4%) with post infective IBS. 15 (58%) were still in secondary care 6 months after
(16%) IBD patients treated with anti-TNFs, CCR developed in 3 (0.78%)(com- FC testing.
bined IMM in 3). Among the 2003/2387 (84%) patients anti-TNFs na ve, Of the 42 intermediate (50-250mcg/g) patients, 17 did not have information
12(0.6%) developed cancer of the lower GI tract,including CCR in 10 (0.5%) provided by their GPs and 2 (5%) were known IBD patients. 8 patients (19%)
(p ns vs anti-TNFs treated patients). IBD-C included 30 patients were diagnosed with colon cancer or were still under investigation. 3 (7%) had a
(18CD,12UC;14 M/16 F, age 54,range 37-75), with CD (13 I;2 C;3 I-C) or UC new diagnosis of IBD and 12 (29%) with non IBD conditions (e.g. BAM,
(distal 11, left-sided 1). Anti-TNFs use was reported in a comparable proportion
A372 United European Gastroenterology Journal 2(5S)
Diverticular disease and IBS). 13 (31%) patients were still in secondary care 6 REFERENCES
months after initial FC see table 1. Robinson A. Review article: inflammatory bowel diseaseempowering the
Within the intermediate group, 10 patients had FC 5 100mcg/g, none were patient and improving outcome. Aliment Pharmacol Ther 2004; 20(Suppl. 4):
diagnosed with IBD and 20% remained in secondary care 6 months post FCP. 84-87.
Of the 16 available patients with FC of 100-250, 3 (23%) had a new diagnosis of Disclosure of Interest: None declared
IBD and 7 (54%) were still in secondary care 6 months after FC.
NRI Observed
P0888 DRUG SURVIVAL AND REASONS FOR DISCONTINUATION OF
ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASE (IBD)
OL EOW OL EW OL EOW OL EW
IN CLINICAL PRACTICE
n/N (%) n/N (%) n/N (%) n/N (%)
J.P. Gisbert1,2,*, M. Arredondo2,3, M. Chaparro1,2, I. Canamares2,4,
E. Dauden2,5, G. Fernandez-Jimenez2,3, V. Meca2,6, A. Morell2,4, J. Aspa2,7, Remission 3/12 (25.0) 3/15 (20.0) 3/6 (50.0) 3/9 (33.3)
L. Carmona2,8, J.M. Alvaro-Gracia2,9 Response 6/12 (50.0) 6/15 (40.0) 6/6 (100) 6/9 (66.7)
1
Gastroenterology Unit, Hospital de La Princesa, CIBERehd and IP, 2Biologic
Therapies Unit, 3Documentation Service, 4Pharmacy service, 5Dermatology Mucosal healing 1/12 (8.3) 2/15 (13.3) 1/7 (14.3) 2/7 (28.6)
Service, 6Neurology Service, 7Medical Director, Hospital de La Princesa, 8Institute
for Musculoskeletal Health, 9Reumatology Service, Hospital de La Princesa,
Madrid, Spain CONCLUSION: Escalation to weekly ADA dosing demonstrated clinical benefit
Contact E-mail Address: javier.p.gisbert@gmail.com in patients who met protocol criteria for dose escalation. No new safety risks
were observed with EW ADA dosing.
INTRODUCTION: Since its introduction, anti-TNF therapy has shown to be REFERENCES
effective for the treatment of IBD in several clinical trials. However, its long-term 1. Sandborn WJ, et al. Inflamm Bowel Dis 2011; 17: 141-151.
effectiveness and reasons for discontinuation in clinical practice might be differ- 2. Rutgeerts P, et al. Gastroenterology 2012; 142: 1102-1111.
ent from those observed in clinical trials Disclosure of Interest: J.-F. Colombel Consultancy for: AbbVie, Bristol Meyers
AIMS & METHODS: Aims: To evaluate the drug survival and reasons for Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Merck & Co.,
discontinuation of the first anti-TNF therapy in IBD patients in clinical practice. Millenium Pharmaceuticals Inc., Pfizer Inc. Prometheus Laboratories, Sanofi,
Methods: IBD patients under anti-TNF therapy from 2000 to 2012 in our center Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma
were included. Data regarding the first anti-TNF treatment were extracted from (previously named Celltech Therapeutics, Ltd)., P. Rutgeerts Financial support
clinical records fulfilled prospectively. Kaplan-Meier method was used to esti- for research from: AbbVie, Centocor, Merck and UCB Pharma, Lecture fee(s)
mate the long-term drug survival of the treatment. from: AbbVie, Centocor, Merck and UCB Pharma, Consultancy for: AbbVie,
RESULTS: 160 IBD patients were included: 130 with Crohns disease (mean age Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now
4214 years; 47% male) and 30 with ulcerative colitis (mean age 4517 years; Takeda) and UCB Pharma, W. Sandborn Financial support for research from:
63% male). The distribution of first biologic in Crohns disease was 76 (58%) AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen,
adalimumab and 54 (42%) infliximab, while in ulcerative colitis it was 1 (3%) Millennium, Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire
adalimumab and 29 (97%) infliximab. Time to a probability of 50% discontinua- Pharmaceuticals, and UCB Pharma., Lecture fee(s) from: AbbVie, Bristol-
tion was 3.94 years in Crohns disease compared with 0.97 years in ulcerative Myers Squibb, and Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI
colitis (p50.001). The reasons for discontinuation of the drug, respectively in Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman,
Crohns disease and ulcerative colitis, were: intolerance (20% and 19%), lack of Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic
response (30% and 24%), loss of response (22% and 19%), remission achieve- Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer-Ingelheim
ment (17% and 29%), and others (11% and 10%). The probability of maintain- Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL,
ing (retention rate) the anti-TNF treatment in Crohns disease was 69% at 1 year, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies,
59% at 2 years, 52% at 3 years, 50% at 4 years, 45% at 5 years, and 41% at 10 Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai
years. The corresponding figures for ulcerative colitis were 48% at 1 year, 41% at Medical Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly,
2 years, 36% at 3 years, 31% at 4 years, and 15% at 5, 6 and 7 years Enteromedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion
CONCLUSION: The probability of maintaining the first anti-TNF drug in Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation,
Crohns disease patients is around 50% after 5 years of treatment. Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human
Discontinuation rate was even higher in ulcerative colitis, with only 15% of Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios
patients maintaining anti-TNF therapy at 5 years. The most frequent reasons Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda
for discontinuation of anti-TNF therapy were lack of response, loss of response, Pharmaceuticals, Merck Research Laboratories, MerckSerono, Merck & Co.,
remission achievement and intolerance Millennium, Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S,
Disclosure of Interest: J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc.,
a consultant and advisory member for, and has received research funding from PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories,
A376 United European Gastroenterology Journal 2(5S)
ProtAb Limited, Purgenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient Table: Clinical outcomes based on continuous clinical response at Wk54 in the
Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, PURSUIT-SC maintenance study*
Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. Table to abstract P0890
A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts
Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Non-CCR: CCR:
Biogenics Limited (VBL), Warner Chilcott UK Limited, D. Wolf Financial sup- Non-CCR: Combined CCR: Combined
port for research from: AbbVie, Elan Pharmaceuticals, Given Imaging, Clinical endpoints PBO GLM PBO GLM
GlaxoSmithKline, Genentech, Janssen, Millennium Pharmaceutical, Pfizer,
Prometheus Laboratories, Receptos, Shire Pharmaceutical, Tsumura, and UCB Randomized pts receiving con- 60 87 27 73
Pharma., Consultancy for: AbbVie, Elan Pharmaceuticals, Genentech, Given comitant steroids at Wk 0
Imaging, Janssen, Prometheus Laboratories, Salix Pharmaceuticals, UCB (n)
Pharma, and Warner Chilcott. He has received lectures fees from AbbVie,
Janssen, Prometheus Laboratories, Santarus, Salix Pharmaceutical, Shire Pts not receiving corticosteroids 1.7 4.6 66.7 75.3
Pharmaceutical, and UCB Pharma., W. Reinisch Consultancy for: AbbVie, at Wk54(%)
Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Remission: Randomized pts(n) 106 156 48 146
Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Pts in clinical remission at 0.9 1.9 68.8 67.1
Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Wk54(%)
Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, Mucosal healing:Randomized 106 156 48 146
MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & pts(n)
Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Pts with mucosal healing at 1.9 2.6 87.5 90.4
Zyngenia, Austria and 4SC., G. Van Assche Financial support for research Wk54 (%)
from: AbbVie, Janssen Biologicals, MSD, Pfizer, Lecture fee(s) from: AbbVie, IBDQ score:Randomized pts 105 156 48 144
Ferring, MSD, Janssen, UCB Pharma, Shire, Consultancy for: AbbVie, Biogen, (n)
BMS, MSD, Janssen Biologicals, Novartis, S. Eichner Shareholder of: AbbVie, Change from Wk0 through -38.9(32.1) -36.9(37.6) 10.6(18.2) 11.3(28.1)
Other: Employee: AbbVie, Q. Zhou Shareholder of: AbbVie, Other: Employee: Wk54 [mean(SD)]
AbbVie, J. Petersson Shareholder of: AbbVie, Other: Employee: AbbVie, A. Pts with IBDQ score 4170 at 18.1 24.4 81.2 75.0
Robinson Shareholder of: AbbVie, Other: Employee: AbbVie, R. Thakkar Wk54 (%)
Shareholder of: AbbVie, Other: Employee: AbbVie
P0890 CLINICAL OUTCOMES IN CONTINUOUS CLINICAL CONCLUSION: These data continue to support that patients induced into clin-
RESPONDERS WITH MODERATELY TO SEVERELY ACTIVE ical response who maintain a clinical response through Wk54 are more likely to
ULCERATIVE COLITIS: SUB-ANALYSES FROM THE PURSUIT-SC have better clinical outcomes.
MAINTENANCE STUDY Disclosure of Interest: J. Colombel Financial support for research from: Janssen
J. Colombel1,*, W. Reinisch2, P. Gibson3, W.J. Sandborn4, B.G. Feagan5, Research & Development, LLC, W. Reinisch Financial support for research
C. Marano6, R. Strauss6, J. Johanns6, H. Zhang6, H. Weng7, R. Yao7, from: Janssen Research & Development, LLC, P. Gibson Financial support
D. Tarabar8, Z. Hebzda9, P. Rutgeerts10 for research from: Janssen Research & Development, LLC, W. Sandborn
1
Hopital Claude Huriez, Lille Cedex, France, 2Universitatsklinik fur Innere Financial support for research from: Janssen Research & Development, LLC,
Medizin III/McMaster University, Vienna/Hamilton, Austria, 3Alfred Hospital, B. Feagan Financial support for research from: Janssen Research &
Melbourne, Australia, 4University of California San Diego, La Jolla, United Development, LLC, C. Marano Other: Employee of Janssen Research &
States, 5Robarts Research Institute, University of Western Ontario, London, Development, LLC, R. Strauss Other: Employee of Janssen Research &
Canada, 6Janssen Research & Development, LLC., Spring House, 7Merck Sharp & Development, LLC, J. Johanns Other: Employee of Janssen Research &
Dohme, Kenilworth, United States, 8Military Medical Academy, Belgrade, Serbia, Development, LLC, H. Zhang Other: Employee of Janssen Research &
9
Klinika Chorob Wewnetrznych, Krakow, Poland, 10University Hospital, Development, LLC, H. Weng Other: Employee of Merck Sharp & Dohme, R.
Gathuisburg, Belgium Yao Other: Employee of Merck Sharp & Dohme, D. Tarabar Financial support
for research from: Janssen Research & Development, LLC, Z. Hebzda Financial
AIMS & METHODS: The objective was to evaluate long-term clinical outcomes support for research from: Janssen Research & Development, LLC, P. Rutgeerts
in patients with moderately to severely active UC who achieved complete con- Financial support for research from: Janssen Research & Development, LLC
tinuous response (CCR) compared with patients who did not achieve CCR (non-
CCR) through Wk54 of SC golimumab (GLM) maintenance therapy. During
PURSUIT-Maintenance, GLM induction responders (464 patients) were rando- P0892 INTRA-ABDOMINAL ABSCESSES IN CROHNS DISEASE:
mized to receive PBO, SC GLM 50mg, or SC GLM 100mg at baseline (Wk0) and OUTCOMES FOLLOWING INFLIXIMAB THERAPY
q4wks through Wk52. The primary endpoint was clinical response through Wk54 J. Ruel1,*, J.-F. Colombel2, B. Cohen2
(CCR). Clinical remission, mucosal healing, corticosteroid use, and IBDQ out- 1
Gastroenterology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke,
comes and fecal markers at Wk54 among CCR versus non-CCR were assessed. Canada, 2Gastroenterology, Icahn School of Medicine at Mount Sinai, New York,
All sub-analyses are based on patients randomized at Wk0 of maintenance United States
(n 456). Contact E-mail Address: benjamin.cohen@mssm.edu
RESULTS: On all of the selected endpoints evaluated, CCR patients had better
results when compared with non-CCR patients (Table). Among patients receiv- INTRODUCTION: Crohns disease (CD) may be complicated by a sealed-off
ing corticosteroids at baseline, a greater proportion of CCR patients were not perforation that results in the development of an abscess typically located next to
receiving corticosteroids at Wk54 versus non-CCR patients. Greater proportions adjacent loops of bowel. Traditional treatment has been antibiotics, surgical or
of CCR patients were also in clinical remission versus non-CCR patients. CT-guided drainage of drainable collections, bowel rest, and, ultimately, in some
Additionally, mean decreases in fecal lactoferrin and fecal calprotectin at patients, resection of the affected bowel segment. Most gastroenterologists avoid
Wk54 from Wk0 of maintenance were greater for CCR patients compared immune suppression in this setting because of the potential for disseminated and
with non-CCR patients. Data between the GLM groups were similar and thus systemic infection. Data regarding use of anti-tumor necrosis factor (TNF) in this
were pooled in the table. situation are scarce. The aim of this study was to examine outcomes for patients
with CD who developed an abdominal abscess that was subsequently treated
with infliximab without initial drainage in order to evaluate its safety and efficacy
in a larger number of patients than previously reported.
AIMS & METHODS: We retrospectively reviewed the records of all CD patients
attending the Mount Sinai Medical Center in New York City, between 2000 and
2013, with an intra-abdominal abscess who were treated with infliximab in order
to evaluate its safety and efficacy.
RESULTS: There were 18 patients with CD complicated by an intra-abdominal
collection treated with antibiotics and infliximab at our center between 2000 and
2013. The median age was 25.5 (18-46) years and eleven patients were males.
Seventeen patients had ileal disease. Fourteen patients developed an intra-
abdominal abscess (size ranging from 1.1 cm to 7.9 cm) and four had a phlegmon
only. In addition to anti-TNF therapy, all patients were treated with broad-
spectrum antibiotics. No complications following infliximab therapy were
reported including sustained fever or sepsis. None required a surgical drainage
but four patients required abscess drainage by interventional radiology. Eight
patients underwent surgery within 6 months after initiating anti-TNF therapy.
CONCLUSION: Penetrating CD complicated by intra-abdominal abscess for-
mation may be safely and effectively managed with a combination of antibiotics
and infliximab therapy without drainage. Prospective trials are required to con-
firm these findings.
Disclosure of Interest: J. Ruel: None declared, J.-F. Colombel Consultancy for:
Janssen and Abbvie, B. Cohen Lecture fee(s) from: Abbvie
United European Gastroenterology Journal 2(5S) A377
activity was assessed using Harvey-Bradshaw index for CD and partial-Mayo-
P0893 HIGH SERUM CRP PREDICTS FASTER CLEARANCE OF
score for UC. In patients treated with anti-TNF all parameters were reevaluated
INFLIXIMAB AND POOR OUTCOME IN MODERATE-SEVERE
6 weeks later. Data are presented as Median/25thpercentile/75thpercentile.
ULCERATIVE COLITIS
RESULTS: Patients with active IBD showed significantly reduced parameters in
J.F. Brandse1,*, G.R. van den Brink1, D.van der Kleij2, T. Rispens3, K. Bloem3, their PFT. Tiffeneau index-values (FEV1%) were significantly reduced in IBD
Y. Ashruf1, J.M. Jansen4, M. Lowenberg1, C. Ponsioen1, R.A. Mathot5, patients with active disease (78,9/73,7/85,1) compared to controls (86/81,8/88,3;
G.R. DHaens1 p 0.001) and IBD patients in remission (84,5/81,2/89,4; p 0.0002). No differ-
1
Department of Gastroenterology & Hepatology, Academic Medical Center, ence was found between IBD patients in remission and controls (p40.05).
2
Sanquin Diagnostic Services, 3Sanquin Research, Sanquin Laboratories, Parameters of peripheral airway obstruction (MEF 75-25%) showed comparable
4
Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis, changes (MEF75: IBDactive vs. controls p 0.01; IBDactive vs. IBDremission
5
Pharmacy, Academic Medical Center, Amsterdam, Netherlands p 0.002). Clinically significant peripheral airway obstruction was seen in
Contact E-mail Address: j.f.brandse@amc.uva.nl 19.1%, obstructive dysfunction in 12.8% and restrictive dysfunction in 2.1%
of IBD patients with an active disease (IBDremission: 4.6%/2.3%/6.9%;
INTRODUCTION: Insufficient serum concentrations have been suggested as a Control: 5%/0%/0%). Patients treated with anti-TNF showed a significant
cause of lack of response to infliximab (IFX) in Ulcerative Colitis (UC) and may improvement of obstructive parameters (p 0.003 FEV1%) compared to base-
be associated with a high inflammatory load. Early pharmacokinetics (PK) of line levels.
IFX related to inflammatory markers and response to induction therapy have CONCLUSION: IBD patients with active disease showed significant abnormal-
been poorly studied. ities in their obstructive PFT-parameters in comparison to healthy controls and
AIMS & METHODS: We studied the PK of IFX induction therapy and mar- IBD patients in remission. Anti-inflammatory therapy with anti-TNF improves
kers/predictors for response in patients with moderate-to-severe UC (endoscopy obstructive abnormalities. Pulmonary obstruction and chronic broncho-pulmon-
Mayo 2 or 3) in a multicenter prospective study. Serum IFX concentrations and ary inflammation might be the cause of reduced exercise levels during active
antibodies to IFX (Radioimmunoassay, Sanquin Laboratories, Amsterdam), disease and may be overlooked in the majority of patients. Further studies are
serum CRP and albumin and fecal samples (for calprotectin and IFX concentra- necessary to determine whether chronic obstruction should be treated and
tions) were collected at 10 serial time points during the first 6 weeks of therapy. whether it contributes to the observed mortality from lung problems in IBD.
Endoscopic response was defined as improvement by at least 1 Mayo point at Disclosure of Interest: None declared
week 6-8.
RESULTS: Twenty patients were included, all but one receiving IFX according
to standard induction regime (5mg/kg at week 0.2,6). 11/19 patients showed P0895 THE EFFECT OF ANTI-TNF TREATMENT ON FISTULAS IN
endoscopic improvement. The median IFX serum concentration at week 6 was CROHNS DISEASE: A SYSTEMATIC REVIEW AND META-
2.9 (0.01-5.8) ug/ml for endoscopic non-responders versus 8.1 (3.0-13.7) ug/ml for ANALYSIS
responders (p 0.03). Serum IFX7ug/ml at week 6 was defined as a predictive J. De Groof1,*, S. Sahami2, C. Lucas3, C. Ponsioen4, W. Bemelman2, C. Buskens2
cut-off (OR:18.67, 95%CI 1.56-223.1, p 0.02) for endoscopic non-response. 1
Department of Surgery and Gastroenterology & Hepatology, 2Department of
The presence of antibodies to IFX at week 6 (n 4) was associated with a 2.93 Surgery, 3Department of Epidemiology, Biostatistics & Bioinformatics,
fold increased clearance of the drug. Fecal IFX concentrations at day 1 were 4.1 4
Department of Gastroenterology & Hepatology, Academic Medical Centre,
(1.3-20.1) ug/ml in non-responders compared to 1.3 (0-5.8) ug/ml for responders Amsterdam, Netherlands
(P[GD1] 0.10). Median area under the curve (AUC), IFX concentration versus Contact E-mail Address: e.j.degroof@amc.uva.nl
time, was 1229 mg/L/day in the endoscopic non-responders compared to 1352
mg/L/day for the responders (p 0.65). Patients with a baseline CRP450mg/l INTRODUCTION: Peri-anal fistulas are an incapacitating complication of
had a significantly smaller AUC than those below 50mg/l (578 vs. 1361 mg/L/ Crohns disease affecting approximately 25% of patients in population-based
day, p 0.001), with IFX clearance 1.63 fold increased (P50.001, multivariate estimates. Since the introduction of anti-TNF agents (infliximab and adalimu-
analysis). mab), the treatment for Crohns fistulas has changed from almost exclusively
CONCLUSION: Ulcerative Colitis patients with a high baseline serum CRP surgical to placing a much larger emphasis on medical therapy.
have increased clearance and lower serum IFX concentrations during IFX induc- AIMS & METHODS: The purpose of this systematic review is to provide an
tion therapy, predicting poor outcome as early as week 6. These patients can be overview of the literature evaluating the success rate of perianal fistula treatment
selected for more intensive induction regimens. with anti-TNF. PubMed, Embase and Biosis were searched. Randomized con-
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie, Takeda, G. trolled trials on the effect of anti-TNF treatment on Crohns perianal fistulas
van den Brink Financial support for research from: Abbott laboratories, Crucell were included. Studies assessing perianal fistulas in children, rectovaginal fistulas
and Ferring Pharmaceuticals, Lecture fee(s) from: Abbott laboratories, Merck and costs were excluded. The primary outcome of interest was complete fistula
Sharp & Dohme and Ferring Pharmaceuticals, Consultancy for: Abbott labora- closure with partial closure as a secondary outcome parameter. A subgroup
tories, D. van der Kleij: None declared, T. Rispens: None declared, K. Bloem: analysis for complete fistula closure was performed based on studies with a
None declared, Y. Ashruf: None declared, J. Jansen Lecture fee(s) from: MSD en follow-up longer than 4 weeks.
Abbott, Consultancy for: Ferring Pharmaceuticals, Schering Plough, Abbvie, RESULTS: Four studies comparing placebo with anti-TNF therapy regimens
and Pfizer, M. Lowenberg Lecture fee(s) from: Abbott, Dr. Falk, Ferring, were included in the meta-analysis: one study on infliximab (ACCENT study)
MSD and Tramedico, C. Ponsioen Financial support for research from: and three studies analysing adalimumab (CLASSIC, CHARM and GAIN trial).
Schering Plough, Falk Pharma, Tramedico, Abbott Inc., and Glaxo Smith All patients with fistulising disease were included in the trials (peri-anal, entero-
Klin, Lecture fee(s) from: Schering Plough, Falk Pharma, Tramedico, Abbott cutaneous and entero-enteral fistulas). In total, 179 patients were treated with
Inc., and Glaxo Smith Kline, Consultancy for: Schering Plough, Falk Pharma, anti-TNF medication whereas 109 patients received placebo. All studies assessed
Tramedico, Abbott Inc., and Glaxo Smith Kline, R. Mathot: None declared, G. complete closures rates and three studies reported partial closure rates. The mean
DHaens Financial support for research from: Abbott Inc, Jansen Biologics, follow-up time was 13 weeks (range 4-26). In the anti-TNF group, 54 of 179
Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: Abbott (30%) patients responded to treatment with complete fistula closure, whereas
Inc, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire, Consultancy for: complete healing was seen in 13 of 109 (12%) patients in the placebo group.
Abbott Laboratories, Actogenix, Centocor, Cosmo, Engene, Ferring Partial fistula closure was seen in 48 of 109 (44%) patients in the anti-TNF
Pharmaceuticals, GlaxoSmithKline, Jansen Biologics, Millenium treatment group and in 15 of 62 (24%) patients in the placebo group. There
Pharmaceuticals, MSD, Novonordisk, PDL Biopharma, Pfizer, SetPoint, was no significant difference in complete or partial closure rates between the
Shire, Takeda, Teva, UCB two groups (RD 0.12, -0.06-0.30, I2 74% and 0.09, 95% CI -0.23-0.41, I2 78%,
respectively). The subgroup analysis showed a significant advantage for complete
fistula closure with anti-TNF in the two trials with follow-up longer than 4 weeks
P0894 PULMONARY INVOLVEMENT AND THE EFFECT OF TNF- (ACCENT: 46% versus 13%, p 0.003 and CHARM: 30% versus 13%,
ALPHA-INHIBITORS ON PULMONARY FUNCTION IN IBD- p 0.03) when compared to the placebo group.
PATIENTS CONCLUSION: Meta-analysis of 4 randomized controlled trials did not show a
J. Bethge1,*, M. Ellrichmann1, C. Conrad1, S. Nikolaus1, R. Noth2, D. Schuldt1, significant advantage for (partial) fistula closure with anti-TNF treatment as
S. Zeissig1, S. Schreiber1,2 compared to placebo. However, subgroup analysis showed an advantage of
1
Medical Department I, Gastroenterology, 2Medical Department I, Pulmonology, anti-TNF treatment on complete fistula closure rates in the two trials with a
University Medical Center, Schleswig Holstein, Campus Kiel, Kiel, Germany follow-up longer than 4 weeks.
Contact E-mail Address: jbethge@1med.uni-kiel.de Disclosure of Interest: None declared
n
mortality from respiratory diseases was observed in patients with ulcerative coli- 1,*
J.A. D. M. Jalandoon , I.H. Y. cua 2
w
tis. This may be due to an overlap between genetic causes in IBD and various 1
Gastroenterology, Institute of digestive and liver disease, St. lukes medical centre,
chronic inflammatory lung diseases. Therefore, pulmonary involvement may be
overlooked in IBD patients.
AIMS & METHODS: The aim of this prospective study was to assess pulmon-
2
i t h ra
gastroenterology, st lukes medical center, quezon city, Philippines
d
Contact E-mail Address: doyangelie@yahoo.com
ary-function-abnormalities in IBD patients in comparison to healthy controls
and investigate the effect of TNF-a-inhibitors on pulmonary-function-test
(PFT). 90 consecutive patients with IBD (51 Crohns disease (CD), 39 UC)
were included. 47 patients were in remission and 43 had active disease. Out of
these, 25 patients were seen for initiating anti-TNF therapy. 40 matched healthy
W
INTRODUCTION: Significance.
Budesonide MMX, a novel drug developed for the treatment of ulcerative colitis
using multi-matrix system. The effects on remission of disease would help to form
recommendations for efficacy and safety profile. Most of these trials conducted
have relatively small size, limited data and a meta-analysis for this drug could
controls were included. Pulmonary function was evaluated using the Medical have stronger conclusion.
Research Council (MRC) dyspnea index and a standardized spirometry. IBD
A378 United European Gastroenterology Journal 2(5S)
AIMS & METHODS: Manual search through MEDLINE & PUBMED using (IBD). Among various adverse events during anti-TNF therapy, skin lesions
ulcerative colitis and Budesonide MMX were merged yielding 9 studies. Six such as psoriasis or eczema could be a reason for discontinuation of anti-TNF
studies were shown which was limited to human. Excluded were two reviews and therapy.
a comment. Three multicenter, randomized, placebo-controlled trials were AIMS & METHODS: We aimed to identify the risk factors for skin lesion
included & Cochrane Review Manager Software Version 5 was used. occurrence and compared the cumulative incidence of skin lesions in relation
RESULTS: There was a significant remission of symptoms in patients using the to concomitant use of azathioprine/6-mercaptopurine during being treated with
combined Budesonide MMX 9 & 6 mg with a p-value of 0.02. Sensitivity analysis anti-TNF agents in IBD patients. Methods: Between June 2002 and July 2013,
using Budesonide MMX 9 mg is effective in the remission compared to 500 patients (404 Crohns disease and 96 ulcerative colitis) were treated with anti-
Budesonide 6 mg alone and placebo with p-value 0.0005 at 95% confidence TNF at Asan Medical Center. Among them, new skin lesions occurred in 47 IBD
ra w n
interval. Adverse effects showed no significant difference between Budesonide
MMX group and the placebo group with a p value of 0.71.
CONCLUSION: Budesonide MMX, on clinical improvement, is beneficial in
patients at the department of dermatology. We retrospectively reviewed the
medical records. To identify risk factors for skin lesions, we compared 47 patients
with skin lesions to 443 patients without any skin disease or history.
t h d
assessing the response to treatment in remission of symptoms. The adverse effects
Wi
have no significant difference with placebo thus further study is needed to assess
the safety profile of the drug.
REFERENCES
RESULTS: The incidence of skin lesions during anti TNF therapy was 9.4%.
The skin lesions were listed in Table 1. Face was the most common involved site
(n 21, 45%), followed by trunk (n 18, 38%) and upper extremities (n 18,
38%). Thirty three (70%) patients were treated with topical steroids with or
DHaens GR, et al. Clinical trial: preliminary efficacy and safety study of a new without antihistamine and showed good response. Four subjects (9%) discon-
budesonide-MMX 9 mg extended-release tablets in patients with active left-sided tinued anti-TNF because of eczematiform (n 2), psoriasiform (n 1), linear
ulcerative colitis. J Crohns Colitis 2010; 4: 153-160. IgA dermatosis (n 1). On univariate analysis, skin lesion occurred more in
Sandborn WJ, et al. Once-daily budesonide MMX extended-release tablets female (HR: 1.794, 95% CI: 1.011-3.181, p 0.046) than in male. Also, combined
induce remission in patients with mild to moderate ulcerative colitis: results use of azathioprine/6-mecaptopurine was associated with decreased risk of the
from the CORE I study. Gastroenterology 2012; 143: 1218-1226. occurrence of skin lesions (HR: 0.452, 95% CI: 0.251-0.814, p 0.008). However,
Travis SPL, et al. Once-daily budesonide MMX in active, mild-to-moderate only combined use of azathioprine/6-mercaptopurine (HR: 0.437, 95% CI: 0.242-
ulcerative colitis: results from the randomised CORE II study. Gut Br J Med 0.790, p 0.006) decreased the risk of occurrence for skin lesions on multivariate
2013; 0: 1-9. analysis. Thus, we compared the cumulative incidence of skin lesions according
Sandborn WJ, et al. MMX multi matrix system mesalazine for the induction of to the use of azathioprine/6-mercaptopurine. Combined use of azathioprine/6-
remission in patients with mild-to-moderate ulcerative colitis: a combined ana- mercaptopurine at the time of starting anti-TNF agents tended to be lower
lysis of two randomized, double-blind, placebo-controlled trials. Aliment cumulative incidence of skin lesions (p 0.009 by log rank test) during follow-
Pharmacol Ther 2007; 26: 205215. up period.
Disclosure of Interest: None declared Multivariate analysis of factors associated with skin lesion occurred during treat-
ment of anti-TNF agents in patients with inflammatory bowel disease
For this simulation, the mean decrease in costs was similar when testing a popu- INTRODUCTION: Infliximab (IFX) trough levels (TLI) vary greatly between
lation of 3 000 or 10 000 patients. At 5 years the mean decreased costs were 12 inflammatory bowel disease (IBD) patients. This variability is relevant because
899 (95% CI:11820 - 13977) for 3 000 patients and 13 130 euros (95% CI:12535 - there is a relationship between IFX concentration and clinical response.
13725) for 10 000 patients. After a stochastic sensitivity analysis (30 simulations AIMS & METHODS: Main objective: estimate individual pharmacokinetic
with random choice of transition probabilities and a bootstrap analysis), these parameters and predict trough IFX levels. Secondary objective: evaluate the
results were comparable with a decreased costs at 5 years for each patient using association between IFX exposure and covariates that could modify trough
tests with a 95CI [13 251,74 E - 13 565,05 E]. The impact of the direct cost of test levels.
is not significant and our results were similar using cost of test of 2.000 euros. (a) Observational and prospective study of patients on IFX treatment from July
CONCLUSION: A test-based strategy is associated with major cost savings 2013 to March 2014. TLI and antibodies toward infliximab (ATI) were measured
among Crohns disease patients treated with anti-TNF strategy. These findings by ELISA at steady-state. Variables recorded: demographic, disease location C-
should be taken into account to guide decision making in clinical practice and reactive protein levels (CRP), serum albumin concentrations (SAC), immunomo-
also by French healthcare system. dulatory treatment (IMM) and smoking. Individual pharmacokinetic parameters
REFERENCES were estimated and TLI were predicted using population PK modelling
Velayos T, et al. Clinical Gastroenterol Hepatol 2013; 11: 654-666. (Nonmem 7.2).
Steenholdt C, et al. Gut in press. RESULTS: 55 patients (49% women) were included. 93 TLI and ATI were
Disclosure of Interest: X. Roblin Lecture fee(s) from: Theradiag, MSD, Abbvie, measured. Mean age: 43 yr (18-75); weight: 74 kg (IC95%: 71-77.5). Diagnose:
M. Lamure: None declared, A. Attar: None declared, B. Savarieau: None 58.5% CD and 41.5% UC. 70 % received IMM. 27% patients were under
declared, P. brunel: None declared, G. Duru: None declared, L. Peyrin intensified IFX doses. Mean CRP: 6.45 mg/L (IC95%: 4.56-8.35), mean SAC:
Biroulet Financial support for research from: MSD, Lecture fee(s) from: Abbvie 4.70 g/dL (IC95% 2.55-6.84).
Mean TLI: 3.34 mg/L (CD: 3.62. UC: 2.49) (IC95%:2.66-4.02). TLI: 53: 56 %
and 3-7: 31.2%. ATI status: 4.3% of patients tested positive. All patients who
P0900 LONG-TERM OUTCOME IN PATIENTS WITH CHRONIC developed ATI had undetectable trough levels. 68.5% of patients with trough
ACTIVE ULCERATIVE COLITIS STARTED ON INFLIXIMAB: A levels53 were in remission. Mean estimated peak levels: 114.35 mg/L (IC95%:
RETROSPECTIVE SWEDISH MULTICENTER STUDY 107.37-121.305); mean estimated AUC: 27105.77 mg/h/L (IC95%: 24835-
L. Angelison1,*, S. Almer2, A. Bajor3, J. Bjork2, M. Eberhardsson2, A. Eriksson3, 29376.54).
O. Grip4, P. Hammarlund5, U. Hindorf4, P. Karling6, M. Thorn7, J. Torp8, Fasanmade et al (2011) population PK model for CD was used in both CD and
E. Hertervig4 UC patients. Mean predicted TLI: 3.1 mg/L (IC 95%: 2.49-3.69). Bias 5.55%
1
Department of Medicine, Helsingborg Hospital, Helsingborg, 2Department of (IC95 %: -7.98-(-3.129)) and precision 10.4% (IC95 %: 8.85-11.95). Fasanmade
Gastroenterology, Stockholm University Hospital, Stockholm, 3Department of et al (2009) population PK model for UC was not precise enough.
Gastroenterology, Sahlgrenska University Hospital, Gothenburg, 4Department of Individual estimated PK parameters (mean): central clearance (Cl) 5.65 ml/kg/
Gastroenterology, Skane university Hospital, Lund/Malmo, 5Department of day (IC95%: 5.13-6.16), volume of distribution (central) (Vd) 50.59 ml/kg
Medicine, Angelholm Hospital, Angelholm, 6Department of Gastroenterology, (IC95%: 49.97-51.21), half-life (t1/2): 11.7 days (IC95%: 10.7 -12.7). Population
Umea University Hospital, Umea, 7Department of Gastroenterology, Uppsala PK parameters: Cl 5.42 ml/kg/day, Vd 52.4 ml/kg. Difference between individual
University Hospital, Uppsala, 8Department of Medicine, Kristianstad Hospital, and population PK parameters: 4% in Cl and 3.4% in Vd. Comparison of
Kristianstad, Sweden exposures achieved showed that patients with positive ATI, SAC5 3.9 g/dL,
Contact E-mail Address: leif.angelison@skane.se non receiving IMM and smokers had significant lower trough IFX levels,
higher Cl and lower t1/2. Patients with PCR46 mg/L and ileo-colonic CD had
INTRODUCTION: Infliximab has been shown to be effective in acute severe lower IFX levels.
ulcerative colitis (UC) reducing the risk of colectomy. The ACT studies proved CONCLUSION: High interindividual variability in IFX PK and trough levels
efficacy for IFX in patients with a more chronic type of UC, However, long-term exists in IBD patients. The influence of IMM, SAC, smoking and inflammation
data on clinical outcome of anti-TNF therapy are scarce. We assessed long-term on infliximab clearance suggests that individual adjustment of infliximab doses
outcome in patients with chronic UC started on IFX. according to disease activity may be useful in IBD.
AIMS & METHODS: METHODS: Retrospective data capture from local regis- REFERENCES
tries at 9 Swedish IBD centers from November 2004 to December 2011. Inclusion Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic properties of
criteria were: a) IFX treatment on an ambulatory basis. b) age 18 years, c) 8 infliximab in children and adults with Crohns disesase: a retrospective analysis
weeks or more on continuous steroid use or more than 12 weeks during the last 6 of data from 2 phase III clinical trials. Clin Ther 2011; 33: 946-964.
months, d) steroid intolerance, e) insufficient response to, or intolerance to thio- Disclosure of Interest: None declared
purine therapy. Patients were eligible if followed at least 12 months or until
colectomy.
RESULTS: 243 patients (145 males, 98 females) were included; median age 26.3 P0902 MESENCHYMAL STEM CELL TREATMENT DOES NOT
years (8-71.7) at diagnosis and a median disease duration of 5.0 years (0.2-39.5 INCREASE COLITIS-ASSOCIATED COLON CANCER RISK
years). 114/243 patients (47%) were on steroids and 116/243 (48%) were on L.R. Lopetuso1,*, F. Scaldaferri1, V. Petito1, A. Puglisi1, S. Vetrano2,
concomitant thiopurines, 25/243 (10%) started a thiopurine together with IFX M.E. Caristo3, V. Arena4, V. Cufino4, A. Sgambato4, A. Gasbarrini1
at inclusion and 90/243 (37%) patients had a previous thiopurine exposure. 1
INTERNAL MEDICINE, GASTROENTEROLOGY DIVISION, CATHOLIC
Median follow-up was 3.3 years (0.1 8.9 years) during which a median of 6 UNIVERSITY OF ROME, Rome, 2Division of Gastroenterology, Humanitas
(1-41) infusions were given. At 12 months 114/243 (46.9%) patients were in Clinical and Research Center, Rozzano, Milan, 3Experimental Center,
steroid-free remission and 46/243 (18.9%) had a steroid-free response. Lack of CATHOLIC UNIVERSITY OF ROME, 4Pathology, CATHOLIC
response was noted in 39/243 (16%) and 32/243 (13.2%) underwent colectomy. UNIVERSITY OF ROME, Rome, Italy, Rome, Italy
The corresponding figures at a median follow-up of 3.3 years were steroid-free Contact E-mail Address: lopetusoloris@libero.it
remission: 114/243 (46.9%), steroid-free response 31/243 (12.8%), no response
14/243 (5.8%) while 75/243 (30.9%) had undergone colectomy. Of non-respon- INTRODUCTION: Mesenchymal stem cells (MSCs) are potent immune regula-
ders at 1 year, 21/39 (53.8%) had a colectomy during follow-up compared to 22/ tors, proposed for local and systemic use in human IBD. Recent studies reported
172 (13%) patients with response or remission at 12 months. At last follow-up, 44 that MSCs can promote tumorigenesis, warning their use in clinical condition
patients were on IFX maintenance treatment with a median of 24 (11-54) infu- associated to increased cancer risk, such as IBD.
sions. The remaining 199 patients had a first course of IFX treatment with a AIMS & METHODS: To evaluate the cancer risk associated to the therapeutic
median of 4 (1-41) infusions, 41 patients had a second course with a median of 5 effect of MSCs in murine model of colon cancer associated to chronic colitis.
(1-29) infusions, 9 patients a third course with a median of 5 (1-14) infusions and MSCs were isolated from adipose tissue of C57BL/6 mice, and analyzed for
one patient a fourth course with 4 infusions. The main reasons for stopping IFX MSCs markers and for adipocyte and osteogenic differentiation. An MTT
at the first course was remission in 32%, loss of response 28%, non-response assay was used to explore the direct effects of MSCs on tumor intestinal epithelial
18% and adverse events 10%. Overall 62 (25,5%) patients were switched to cells proliferation and vitality. CT26 cells were incubated with TNF-a for 48 h
adalimumab. and then exposed to the surnatant of TNF-alfa pre- treated AMSC. C57BL/6
CONCLUSION: Anti-TNF is an efficacious long-term treatment in chronic mice were injected intraperitoneally with azoxymethane (AOM) and exposed to 3
active UC with 47% of patients in steroid-free remission at 12 months and weekly cycles of 2.5% DSS.1 million of MSCs were injected intra-peritoneally at
sustained at 3.3 years. 66% had at least a clinically significant steroid-free day 3 of each DSS cycle, control (CT) mice received saline. Body weight, occult
response at 12 months with a slight decrease to 60% at 3.3 years. In contrast, blood test and stool consistency were used to calculate the Disease Activity Index
non-response at 12 months was associated with a high risk of subsequent (DAI). Mice were sacrificed at week 10 and colon was analyzed macroscopically
colectomy. and microscopically for number of cancer and degree of inflammation. Nude
Disclosure of Interest: None declared mice were subcutaneously engrafted respectively with murine (CT26) or human
A380 United European Gastroenterology Journal 2(5S)
(HCT116) tumor cells lines alone or in combination with MSCs to evaluate their AIMS & METHODS: Our aim was to evaluate the clinical efficacy of ADA in
role in tumor cell growth. CT nude mice received MSCs alone. steroid-dependent UC patients.
RESULTS: MSCs differentiated into adipocytes and osteocytes, and expressed We designed an open-label, retrospective, consecutive, and multicentre study.
low levels of CD31, CD34, LIN and cKIT markers, and highlevels of SCA-1, Inclusion criteria were patients over 18 years old with UC and ECCO criteria
CD44 and CD106. MSCs proliferation was increased when stimulated with TNF. of steroid-dependency: Patients who are either unable to reduce corticosteroids
Their surnatant leaded to a not significant reduction of CT26 growth. MSCs below the equivalent of prednisolone 10 mg/day within three months of starting
injection significantly reduced DAI in treated mice vs. CT. MSCs treated mice corticosteroids, without recurrent active disease or who have a relapse within
showed lower body weight loss and better survival rate. Treated mice had a not three months of stopping corticosteroids. All patients received ADA treatment
significant reduced rate of colon cancer development vs. CT. In nude mice, there for induction (160/80 mg) at weeks 0 and 2 and 40 mg every 2 weeks thereafter. In
was no significant difference in tumor size between groups. No lesions were the event of loss of response patients received higher doses of ADA. The main
found in CT mice. endpoint evaluated was clinical remission without steroids during all the treat-
CONCLUSION: MSCs did not increase cancer risk in this colitis model and did ment. Clinical response, mucosal healing and varying levels of C-reactive protein
not affect the progression of pre-existing tumor lesions. MSCs exerted an (CRP) and calprotectine were also evaluated. Results are shown in percentages;
immune-modulatory effect in vivo, by decreasing the severity of colitis in associations were analyzed by Cox regression whenever appropriate.
mouse, suggesting that their anti-inflammatory effects may contra-balance RESULTS: 37 steroid-dependent UC patients were treated with ADA: 67%
their pro-carcinogenetic potential, even in pre-cancer condition such as chronic female, mean years since UC diagnosis being 11 years, 40% presenting extrain-
colitis. Further analyses are required to define mechanisms of action underlying testinal manifestations and 65% with extensive colitis (E3). 12 patients (32%)
these findings. were na ve to anti-TNF and 25 (68%) had previously received infliximab. Mean
Disclosure of Interest: None declared follow-up was 25.9 months. 83% received concomitant treatment with immuno-
suppressive drugs. 43% needed higher doses of ADA treatment due to loss of
response. After induction 35% of patients were in remission and after 12 months.
P0903 INCREASED FREQUENCY OF ENDOSCOPIC MUCOSAL 40% of patients were in remission without steroids. The mean partial mayo score
HEALING AND REDUCED INTESTINAL RESECTION IN was 6.89 basal, 3.13 at month 6 and 2.33 at month 12 (p50.001). Mucosal
PATIENTS WITH SEVERE IBD BY LONGTERM AZATHIOPRINE healing was achieved in 48% of patients. Mean calprotectine decreased from
THERAPY, BUT NEGATIVELY AFFECTED BY MALE GENDER 563 basal to 218 at month 6 (p50.05) and to 61 at month 12. CRP decreased
M. Basaranoglu1, M. Yuksel1,*, M. Kaplan1, N. Suna1, A.E. Demirbag1, from 19.13 to 6.13 at month 12 (p50.001). Only 3 patients (8%) needed a
O. Coskun1, Y. Akpinar1, M. Yalinkilic1, Y. Ozin1, F. Saygili1, E. Kayacetin1 colectomy during the first year. We did not observe any association between
1
Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey concomitant treatment with immunosuppressive drugs and response to ADA,
Contact E-mail Address: metin_basaranoglu@yahoo.com but after Cox regression patients with need of intensification with ADA
(HR 48.1 95%IC:1.46-1589.1; p 0.03) and with previous IFX (HR 12.8;
INTRODUCTION: Currently, safety and economic issues have increasingly 95%CI: 2.24-73.54, p 0.004) had a lower remission rates.
raised concerns about the long term use of biologics as maintenance therapies. CONCLUSION: Adalimumab can be effective for clinical remission without
AIMS & METHODS: To evaluate the role of azathioprine (AZA) on mucosal steroids and mucosal healing in steroid-dependent UC. Previous IFX or need
healing in patients with inflammatory bowel disease (IBD). Two thousand seven of intensification are predictive factors of poorer efficacy.
hundred patients with IBD were evaluated from January 1995 to April 2014. The Disclosure of Interest: None declared
searching criteria were as follows: (1) endoscopic records before the AZA and
during the AZA therapy; (2) AZA na ve patients with severe IBD. The data
included patients and disease demographics and the efEcacy of AZA. Patients P0905 ONE HOUR INFLIXIMAB INFUSIONS DO NOT AFFECT
with a minimum duration of 4 months of AZA were included in this study. ANTIBODIES ANTI-INFLIXIMAB AND TROUGH LEVELS IN IBD
RESULTS: A total of 120 patients treated with AZA for IBD were enrolled. PATIENTS
AZA therapy reduced the number of the surgical interventions in patients with M. Marzo1,*, A. Armuzzi1, B. Tolusso2, D. Pugliese1, C. Felice1, G. Andrisani1,
IBD* (*: p50.05). Male gender had a negative impact on the efficacy of AZA O. Nardone1, F. Pizzolante1, G. Mocci1, S. Canestri2, E. Gremese2,
therapy*. IBD patients with responce were older than the nonresponder*. There G. Ferraccioli2, A. Papa1, G. Rapaccini1, L. Guidi1
was no difference between the operated CD patients and nonoperated for the 1
IBD Unit, 2Reumatology Unit, Complesso Integrato Columbus, Catholic
AZA responce rates (32% vs 34%, p4 0.05 respectively). Then, 33 AZA non- University, Rome, Italy
responder patients with CD were put on biologics. Responce rate was 30%. Of Contact E-mail Address: manuelamarzo@gmail.com
the nonresponders, intestinal resection performed in 35% .
INTRODUCTION: Infliximab therapy in patients with inflammatory bowel dis-
mucosal ease (IBD) requires intravenous administration in over 2 hours, with a further 1
healing hour of post-infusion observation. Recent studies demonstrated the safety and
number by AZA Nonresponce % the tolerance of a shortened 1-hour infusion in IBD patients under scheduled
maintenance infliximab treatment. We report our experience in order to evaluate
Patients with IBD 120 37 % 63% if repeated 1-hour infliximab infusions could affect the antibodies to infliximab
(ATI) and the infliximab trough levels (TL).
UC 38%(45p) 42% 58% AIMS & METHODS: This was a prospective cohort study on patients with IBD
CD 62%(75p) 33% 67% receiving infliximab with shortened 1-hour infusions. All patients were treated
Male 60% 25% 67%* with scheduled maintenance infliximab therapy, after at least 5 well tolerated 2-
Operated after AZA 13% 4.5% 18.4* hours infusions before enrolment. For each patient we recorded diagnosis, vital
signs. All patients were routinely premedicated with 20 mg i.v. methylpredniso-
AZA used (months) 31.524.7 (4-113) 31.225.7 (4-90) 31.624.3 (4-113) lone and oral antihistaminics. We analyzed serum samples collected before start-
Age at IBD 36.812.3 (11-72) 38.112.3 (17-58) 36.112.3 (11-72) * ing the first shortened infusion and after one year of maintenance scheduled
diagnose (years) infliximab treatment for ATI and TL by a commercial ELISA kit according to
Period (AZA 39.852.5 (0-264) 5669 (0-264) 3037 (0-204) the manufacturer instructions (DRG Diagnostics GmbH, Marburg, Germany).
started-IBD All samples were analyzed simultaneously at the end of the collection period.
diagnosed (months) Statistical analysis was performed by Wilcoxon test for paired samples and
Fishers exact test.
RESULTS: Fifty-seven IBD patients (28 Crohns Disease, 29 Ulcerative Colitis)
were treated at our IBD Outpatient clinic with 1-hour infliximab infusion pro-
CONCLUSION: In this study, we showed that AZA therapy increased endo- tocol: out of them 24 (42%) at the dose of 10 mg/kg and 18 (31.6%) with a
scopic mucosal healing rates and decreased the frequency of the surgical inter- shortened interval of 6 weeks. Eleven patients (19.3%) were on concomitant
ventions in AZA na ve patients with severe IBD. We believe that there is still immunosuppressants. In total, 396 maintenance 1-hour infli