Liver: Hepatocellular Cancer
2177
An Evidence-Based Strategy for HCC Surveillance after Liver
Transplantationv
Uchida K.1, Levi D.M.1, Nishida S.1, Selvaggi G.1, Tekin A.1, Fan J.1,
Hibi T.1, Dohi T.1, El Hinnawi A.1, Ruiz P.1, Tzakis A.G.1
1
University of Miami / Jackson Memorial Hospital, Miami Transplant
Institute, Miami, United States
Background: Liver transplantation (LT) has been accepted as the
treatment of choice for early, unresectable hepatocellular carcinoma
(HCC) in cirrhotic patients. Still, HCC recurrence after transplant remains
a serious problem. Currently, there are no evidence-based guidelines for
post-transplant surveillance for HCC recurrence. In this study we review
our experience with LT for HCC and determine the characteristics and
patterns of recurrence. Our purpose is to generate a surveillance strategy
for HCC recurrence after LT.
Methods: We retrospectively reviewed our experience with LT for HCC,
focusing on those patients that experienced HCC recurrence. The setting
was a single, high volume center in the US operating under the MELD
allocation system. The risk factors that predicted recurrence and the
incidence of recurrence were determined. Data regarding the timing
and first site of recurrence, alpha-fetoprotein (AFP) level, treatment,
and survival after the diagnosis of recurrent HCC were collected and
analyzed. With this information we propose surveillance guidelines.
Results: Between March 2002 and December 2010, 275 adults
underwent primary LT for cirrhosis and HCC including 53 with incidental
tumors. The 5 year recurrence-free survival for the cohort was 83.4%.
At a median follow-up of 44.0 months, 42 patients developed recurrent
HCC for an actual recurrence rate of 15.2%. The factors most predictive
of HCC recurrence included an elevated peak AFP prior to transplant
(>50 ng/ml) and unfavorable explant pathology (poorly differentiated
tumors and/or presence of lymphovascular invasion-LVI). Nine (21%)
patients that recurred had none of these factors while 5 (11.9%) of
patients that recurred originally had incidental tumors. The median time to
recurrence was 20.5 months (n=42), with the presence of LVI predicting
earlier recurrence (median 7.5 months, n=24). Nineteen patients (46%)
experienced recurrence more than 2 years after LT. The site of first
recurrence was the lung (38%) followed by the liver (33%). Serum AFP
was elevated (>50 ng/ml) at the time of recurrence diagnosis in 26
patients (61.9%). Median survival after recurrence was 10.0 months; 11
patients are currently alive with recurrent HCC. Patients with recurrent
tumors able to undergo resection or loco-regional therapy experienced
improved survival.
Conclusions: These data suggest that surveillance for HCC recurrence
after LT is warranted, including patients thought to be at low risk
for recurrence. Surveillance imaging should include the chest and
abdomen. Surveillance should be more rigorous for those patients that
had HCC with LVI, especially during the first year after LT. The duration
of surveillance for HCC recurrence should extend at least 4 years. AFP
is a useful adjunct for surveillance. Early detection of HCC recurrence
may allow for aggressive treatment and improved survival.
636 Supplement to Transplantation November 27, 2012, Volume 94 Number 10S
2278
Transarterial Chemoembolization before Liver Transplantation
in Patients with Hepatocellular Carcinoma - a Single Center
Experience
Liese J.1, Moench C.1, Schreckenbach T.1, Sarrazin C.M.2, Zeuzem
S.2, Zangos S.3, Vogl T.3, Bechstein W.O.1, Ulrich F.1
1
Johann Wolfgang Goethe Universität Frankfurt, Klinik für Allgemein-
und Visceralchirurgie, Frankfurt am Main, Germany, 2Johann Wolfgang
Goethe Universität Frankfurt, Medizinische Klinik I, Gastroenterologie
und Hepatologie, Frankfurt am Main, Germany, 3Johann Wolfgang
Goethe Universität Frankfurt, Institut für Diagnostische und
Interventionelle Radiologie, Frankfurt am Main, Germany
Transarterial chemoembolisation (TACE) is the most common bridging
therapy to prevent tumour progress of hepatocellular carcinoma (HCC) on
the waiting list for orthotopic liver transplantation (OLT), although there is
no clear evidence for its therapeutic success. In earlier studies, TACE is
discussed as risk factor for biliary complications after hepatic resection.
In a retrospective single center study we included all patients with a TACE
bridging therapy for HCC one year after receiving liver transplantation
(observation period January 2008 until Dezember 2011) .
Beside demographic data, we analysed the course and complication rates
during TACE bridging and after transplantation as well as the correlation
of imaging and histopathology. The mean time on the waiting list was
349 days. During this period we performed 60 liver transplantations in
46 men and 14 women with HCC in liver cirrhosis who had received
TACE as a bridging therapy. Our patients received a mean number
of 4 TACE sessions before transplantation. 47 patients demonstrated
a stable disease, while 13 patients showed a tumour regression
concerning radiologic follow-up. Complications associated with TACE
therapy occurred in 21% of all TACE treatments. In 13 patients the
histological examination showed a complete tumour necrosis without
viable tumour. In 6 patient tumour size and spread within the liver was
underestimated. Seven (11.7%) patients developed a recurrent HCC after
liver transplantation. 17 of our patients died after transplantation due to
sepsis, multiorgan or graft failure or due to other malignant diseases.
The number of TACE sessions and the evaluation of RECIST criteria
as well as the underlying liver disease did not have an influence on the
1-year patient survival.
There was no hint for a higher rate of biliary complications after OLT in
patients who received preoperative TACE compared to a group of patients
with OLT without preoperative TACE.
The results of our study show that TACE is an effective bridging therapy
for a high percentage of patients with HCC in the era of MELD allocation
which offers a low rate of TACE-associated morbidity. A still unresolved
problem is the radiologic underestimation of the tumour stage.
2359
Regulatory T Cells Favor Human Cancer Development by
Suppressing Anti-Tumor Immunity in Primary and Metastatic
Liver Malignancies
Pedroza-Gonzalez A.1, Verhoef C.2, IJzermans J.N.2, Peppelenbosch
M.P.1, Kwekkeboom J.1, Janssen H.L.1, Sprengers D.1
1
Erasmus MC-University Medical Centre, Gastroenterology and
Hepatology, Rotterdam, Netherlands, 2Erasmus MC-University
Medical Centre, Surgery, Rotterdam, Netherlands
The mechanisms that enable liver cancer to escape elimination by the
immune system remain unclear, but their elucidation may provide novel
therapeutic interventions. Here we report that in both hepatocellular
carcinoma (HCC) and in liver metastases from colorectal cancer (LM-
CRC) CD4+CD25+Foxp3+ regulatory T cells (Treg) accumulate in the
tumor milieu. These tumor-associated Treg are activated, express high
levels of GITR and ICOS, and are more potent suppressors of tumor-
specific CD4+ T cell responses compared to circulating Treg. Especially
in LM-CRC, there is good evidence for local proliferation of Treg at the
cancer site. Soluble GITR ligand (GITRL) induces a decrease in the
suppression mediated by the activated tumor-infiltrating Treg and restores
the proliferative capacity and cytokine production by CD4+ T cells. Our
results thus show that tumor-associated Tregs are critical for immune
evasion in liver cancer and we propose that GITRL constitutes rational
treatment for this disease.