An Evidence An Evidence--based Approach based Approach

to the Diagnostic of to the Diagnostic of

Uninvestigated Dyspepsia Uninvestigated Dyspepsia
in the Primary Care Settings in the Primary Care Settings
MUHAMMAD BEGAWAN BESTARI MUHAMMAD BEGAWAN BESTARI
Division of Division of Gastroenterohepatology Gastroenterohepatology
Department of Internal Medicine Department of Internal Medicine
Medical School Medical School Padjadjaran Padjadjaran University University
Hasan Hasan Sadikin Sadikin General Hospital General Hospital
BANDUNG BANDUNG
Talley, J Clin Gastroenterol 2001; 32: 28693.
Locke, Ballieres Clin Gastroenterol 1998; 12: 43542.
Par, Can J Gastroenterol 1999; 13: 64754.
van Bommel et al., Postgrad Med J 2001; 77: 51418.
Talley et al., BMJ 2001; 323: 12947.
1525% of the general population experience
dyspepsia within a 12-month period
Much more common than peptic ulcer
Up to 5% of primary care visits are due to
dyspepsia
Most patients have no detectable abnormality on
radiological upper GI series or endoscopy
Endoscopy findings and symptoms do not correlate
Dyspepsia: Dyspepsia:
the size of the problem the size of the problem
Dyspepsia: Dyspepsia:
the size of the problem the size of the problem
ORGANIC
UNINVESTIGATED
FUNCTIONAL
(or idiopathic)
(use of the term non-ulcer
is discouraged)
INVESTIGATED
Talley et al., Gut 1999; 45(Suppl II): II3742.
Dyspepsia covers a range of symptoms Dyspepsia covers a range of symptoms Dyspepsia covers a range of symptoms Dyspepsia covers a range of symptoms
DYSPEPSIA
PAIN OR DISCOMFORT
centred in upper abdomen
IBS GERD
Pain or discomfort occurring Pain or discomfort occurring
centred in the upper abdomen centred in the upper abdomen
Talley et al., Gut 1999; 45(Suppl II): II3742.
Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S259.
Definition of dyspepsia (Rome II) Definition of dyspepsia (Rome II) Definition of dyspepsia (Rome II) Definition of dyspepsia (Rome II)
Gastritis Gastritis
Peptic ulcer Peptic ulcer
disease disease
(Includes (Includes
NSAID NSAID--induced induced
ulcers) ulcers)
Duodenitis Duodenitis
Duodenal ulcer Duodenal ulcer
Acid reflux Acid reflux
Oesophagitis Oesophagitis
Strictures Strictures
Barretts Barretts
oesophagus oesophagus
Oesophageal Oesophageal
adenocarcinoma adenocarcinoma
Normal Normal
Gastritis/duodenitis Gastritis/duodenitis
Reflux esophagitis Reflux esophagitis
Cancer Cancer
Peptic ulcer disease Peptic ulcer disease
33.6% 33.6%
23.9% 23.9%
2% 2%
19.9% 19.9%
20.8% 20.8%
Richter 1991 Richter 1991
51
(24%)
36
(17%)
27
(13%)
21
(10%)
11
(5%)
7 (3%)
10
(5%)
Ulcer Ulcer--like like
dyspepsia dyspepsia
Dysmotility Dysmotility--like like
dyspepsia dyspepsia
Reflux Reflux--like like
dyspepsia dyspepsia
Unspecified Unspecified
dyspepsia dyspepsia
n=50 (23%) n=50 (23%)
Talley et al 1992
Functional Dyspepsia (Rome I) Functional Dyspepsia (Rome I) Functional Dyspepsia (Rome I) Functional Dyspepsia (Rome I)
Twelve weeks or more (within the last 12 Twelve weeks or more (within the last 12
months) of persistent or recurrent dyspepsia months) of persistent or recurrent dyspepsia
and evidence that organic disease likely to and evidence that organic disease likely to
explain the symptoms is absent explain the symptoms is absent
(including at upper endoscopy) (including at upper endoscopy)
Definition of Functional Dyspepsia Definition of Functional Dyspepsia
(Rome II) (Rome II)
Definition of Functional Dyspepsia Definition of Functional Dyspepsia
(Rome II) (Rome II)
Talley et al., Gut 1999; 45(Suppl II): II3742.
Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S259.
Dyspepsia subgroups Dyspepsia subgroups
Ulcer Ulcer--like (predominantly pain) like (predominantly pain)
Dysmotility Dysmotility--like (predominantly discomfort) like (predominantly discomfort)
Unspecified (non Unspecified (non--specific, no predominant symptom) specific, no predominant symptom)
At least 3 months, with onset at least 6 months At least 3 months, with onset at least 6 months
previously, of 1 or more of the following: previously, of 1 or more of the following:
Definition of Functional Dyspepsia Definition of Functional Dyspepsia
(Rome II (Rome IIII))
Definition of Functional Dyspepsia Definition of Functional Dyspepsia
(Rome II (Rome IIII))
Bothersome postprandial fullness Bothersome postprandial fullness
And And
No evidence of structural disease No evidence of structural disease
(including at upper endoscopy) (including at upper endoscopy)
that is likely to explain the symptoms that is likely to explain the symptoms
Early satiation Early satiation
Epigastric pain Epigastric pain
Epigastric burning Epigastric burning
Functional dyspepsia: Functional dyspepsia:
an exclusion diagnosis an exclusion diagnosis
Patient with new onset or recurrent Patient with new onset or recurrent
dyspeptic symptoms in whom no dyspeptic symptoms in whom no
investigation have been conducted investigation have been conducted
and no specific diagnosis for and no specific diagnosis for
the current symptoms exist the current symptoms exist
Uninvestigated Dyspepsia Uninvestigated Dyspepsia Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Sander et al., CMAJ 2000; 162 (Suppl): S123
Uninvestigateddyspepsia
All symptomatic patients,
regardless of whether a cause
has been sought
Functional dyspepsia
Symptomatic patients in whom
an organic cause has been
sought and excluded
Talley Talley et al et al., ., Gut Gut 1999; 1999; 45( 45(Suppl II): II37 Suppl II): II3742. 42.
Uninvestigated dyspepsia Uninvestigated dyspepsia
vs vs functional dyspepsia functional dyspepsia
Uninvestigated dyspepsia Uninvestigated dyspepsia
vs vs functional dyspepsia functional dyspepsia
Management of Management of
uninvestigated dyspepsia uninvestigated dyspepsia
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Sander et al., CMAJ 2000; 162 (Suppl): S123
Consider: Consider:
Recommendation Recommendation
Exclude other possible causes of the dyspeptic symptoms Exclude other possible causes of the dyspeptic symptoms
with thorough history with thorough history--taking and physical examination taking and physical examination
(grade C recommendation, consensus) (grade C recommendation, consensus)
cardiac and cardiac and hepatobiliary hepatobiliary sources sources
medication medication--induced symptoms induced symptoms
possible dietary indiscretion possible dietary indiscretion
lifestyle or other causes lifestyle or other causes
No
YES
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Investigate Investigate
(endoscopy recommended) (endoscopy recommended)
(B)
Age >50 or alarm features?
- Vomiting
- Bleeding anemia
- Abdominal mass/
unexplained weight loss
- Dysphagi a
Sander et al., CMAJ 2000; 162 (Suppl): S123
Prompt investigation is recommended for patients Prompt investigation is recommended for patients over 50 years of age over 50 years of age
with uninvestigated dyspepsia and for any patient presenting with with uninvestigated dyspepsia and for any patient presenting with alarm alarm
features features
Endoscopy is the recommended method of investigation for patients Endoscopy is the recommended method of investigation for patients
with uninvestigated dyspepsia who are over 50 years of age or who have with uninvestigated dyspepsia who are over 50 years of age or who have
alarm features alarm features
Recommendation Recommendation
Alarm features:
(grade B recommendation, level III evidence) (grade B recommendation, level III evidence)
(grade A recommendation, level II evidence) (grade A recommendation, level II evidence)
persistent vomiting
evidence of gastrointestinal bleeding or anemia
presence of an abdominal mass
unexplained weight loss
dysphagia
Older patients and with alarm features Older patients and with alarm features
America America
> 50 years > 50 years
> 55 years > 55 years

> 45 years > 45 years

Canada Canada
Indonesia Indonesia

Cancer is a rare cause of dyspeptic symptoms Cancer is a rare cause of dyspeptic symptoms
< 2 % < 2 %
Diagnostic test: endoscopy or radiography? Diagnostic test: endoscopy or radiography?
Radiography :
96 %

70 %
Endoscopy :
Dooley Dooley et al. et al., , Ann Intern Med Ann Intern Med 1984; 101: 538 1984; 101: 538--45 45
(C)
NSAID and/or
Regular ASA
Use?
NSAID Management
No
NO
YES
YES
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Investigate Investigate
(endoscopy recommended) (endoscopy recommended)
(B)
Age >50 or alarm features?
- Vomiting
- Bleeding anemia
- Abdominal mass/
unexplained weight loss
- Dysphagi a
Sander et al., CMAJ 2000; 162 (Suppl): S123
Patients with uninvestigated dyspepsia Patients with uninvestigated dyspepsia
who are regular users of NSAIDS who are regular users of NSAIDS
(including ASA) should be identified, (including ASA) should be identified,
and if there are no alarm features, and if there are no alarm features,
they can be managed without initial endoscopy they can be managed without initial endoscopy
Recommendation Recommendation
(grade C recommendation, consensus) (grade C recommendation, consensus)
Patients who use NSAIDs Patients who use NSAIDs
Hp infection is the most common cause of
peptic ulcers

NSAIDs are responsible for most

Hp-negative ulcers
(C)
NSAID and/or
Regular ASA
Use?
(D)
Is dominant symptom
heartburn and/or
regurgitation ?
NSAID Management
Treat as reflux
No
NO
NO
YES
YES
YES
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Investigate Investigate
(endoscopy recommended) (endoscopy recommended)
(B)
Age >50 or alarm features?
- Vomiting
- Bleeding anemia
- Abdominal mass/
unexplained weight loss
- Dysphagi a
Sander et al., CMAJ 2000; 162 (Suppl): S123
Patients with dominant symptom of heartburn Patients with dominant symptom of heartburn
or acid regurgitation, or both or acid regurgitation, or both
Heartburn (89 %) or acid regurgitation (95 %) have Heartburn (89 %) or acid regurgitation (95 %) have
high specificity for GERD high specificity for GERD

Most GERD patients do not have macroscopic Most GERD patients do not have macroscopic
esophagitis esophagitis
Initial treatment can be started based on Initial treatment can be started based on
symptoms of reflux in primary care symptoms of reflux in primary care
Endoscopy is not a useful diagnostic Endoscopy is not a useful diagnostic gold standard gold standard for for
GERD, nor 24 GERD, nor 24--hour pH monitoring hour pH monitoring

A reliable interpretation of the term heartburn is A reliable interpretation of the term heartburn is
key for the diagnosis of GERD key for the diagnosis of GERD
The effectiveness of lifestyle modifications and antacids for the treatment The effectiveness of lifestyle modifications and antacids for the treatment
of GERD is not proven. Patient with mild GERD symptoms may derive of GERD is not proven. Patient with mild GERD symptoms may derive
benefit from these treatment benefit from these treatment
Treatment recommendations for patients with a dominant symptom of
heartburn or acid regurgitation, or both, are as follows :
(a) PPI
(b) H
2
RA
(c) Prokinetic agent
(grade C recommendation, consensus) (grade C recommendation, consensus)
(grade C recommendation, consensus) (grade C recommendation, consensus)
Patients should be reassessed after 4 weeks of therapy
(grade A recommendation, level I evidence) (grade A recommendation, level I evidence)
Recommendation Recommendation
(C)
NSAID and/or
Regular ASA
Use?
(D)
Is dominant symptom
heartburn and/or
Regurgitation ?
NSAID Management
Treat as reflux
Treat as Hp positive
No
NO
NO
NO
YES
YES
YES
YES
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Investigate Investigate
(endoscopy recommended) (endoscopy recommended)
(B)
Age >50 or alarm features?
- Vomiting
- Bleeding anemia
- Abdominal mass/
unexplained weight loss
- Dysphagi a
(E)
Hp test positive?
1. UBT
2. Serology
Hp Hp test and treat strategy test and treat strategy
Hp infection is associated with
- duodenal ulcer 90 95 %
- gastric ulcer 60 80 %
- gastric cancer
Option for the treatment of younger patients w/o alarm features: Option for the treatment of younger patients w/o alarm features:
Uncertainty as to whether Hp plays a role in
dyspepsia in the absence of ulcers

-- trial of empiric ( trial of empiric (antisecretory antisecretory or or prokinetic prokinetic))

-- diagnostic evaluation diagnostic evaluation
-- non invasive testing for non invasive testing for Hp Hp
followed by eradication therapy for patients w/ (+) followed by eradication therapy for patients w/ (+)ve ve results results
-- non invasive testing for non invasive testing for Hp Hp
followed by endoscopy for patients w/ (+) followed by endoscopy for patients w/ (+)ve ve results results
A test A test--and and--treat strategy for uninvestigated dyspepsia treat strategy for uninvestigated dyspepsia
in younger patient (aged 50 years or less) in younger patient (aged 50 years or less)
who have no alarm features is recommended who have no alarm features is recommended
Recommendation Recommendation
(grade B recommendation, level I evidence) (grade B recommendation, level I evidence)
Testing for Testing for Hp Hp infection infection
Infection can be detected by: Infection can be detected by:
-- invasive (endoscopy based) invasive (endoscopy based)
-- non invasive (UBT non invasive (UBT, HPSA , HPSAor serologic or serologic
testing) testing)

Serologic testing cannot be used to determine cure Serologic testing cannot be used to determine cure
as the as the IgG IgG antibodies remain detected for a long antibodies remain detected for a long
time after eradication time after eradication
UBT UBT has a high (+) has a high (+)ve ve and ( and (--))ve ve predictive value predictive value
(both > 90 %) (both > 90 %)
Noninvasive methods are recommended Noninvasive methods are recommended
for the detection of for the detection of H. pylori H. pylori in patient aged 50 years or less in patient aged 50 years or less
with uninvestigated dyspepsia who have no alarm features with uninvestigated dyspepsia who have no alarm features
Recommendation Recommendation
(grade B recommendation, level II (grade B recommendation, level II--2 evidence) 2 evidence)
Hp stool antigen Hp stool antigen is the preferred test is the preferred test
No more serology No more serology
Recommendation Recommendation
((AGA guidelines from 2005 AGA guidelines from 2005))
Stool Stool aantigen ntigen iis s tthe he rrecommended ecommended ttest est
TTest with est with stool stool antigen antigen before before prescribing prescribing PPPI PIss
do not have alarm symptoms do not have alarm symptoms
have not been using NSAIDS have not been using NSAIDS
who are not > 55 who are not > 55 yrs yrs
(C)
NSAID and/or
Regular ASA
Use?
(D)
Is dominant symptom
heartburn and/or
Regurgitation ?
NSAID Management
Treat as reflux
Treat as Hp positive
Treat as Hp Negative
No
NO
NO
NO
NO
YES
YES
YES
YES
YES
First Visit
(A)
Other possible causes ?
Consider : Consider :
-- Cardiac Cardiac
-- Hepatobiliary Hepatobiliary
-- Medication Medication--induced induced
-- Dietary indiscretion Dietary indiscretion
-- Other Other
Treat as appropriate Treat as appropriate
Uninvestigated Dyspepsia Uninvestigated Dyspepsia
Investigate Investigate
(endoscopy recommended) (endoscopy recommended)
(B)
Age >50 or alarm features?
- Vomiting
- Bleeding anemia
- Abdominal mass/
unexplained weight loss
- Dysphagi a
(E)
Hp test positive?
1. UBT
2. Serology
Sander et al., CMAJ 2000; 162 (Suppl): S123
There is good evidence that antacids are ineffective There is good evidence that antacids are ineffective
for functional dyspepsia, and they are not recommended for functional dyspepsia, and they are not recommended
for the treatment of uninvestigated dyspepsia for the treatment of uninvestigated dyspepsia
in patients subsequently found to be in patients subsequently found to be H. Pylori H. Pylori negative negative
Recommendation Recommendation
(grade B recommendation, level I evidence) (grade B recommendation, level I evidence)
SSPECIALIST PECIALIST RREFFERAL EFFERAL ::
PPRIMARY RIMARY MMANAGEMENT ANAGEMENT OF OF NNEW EWOONSET NSET
UUNINVESTIGATED NINVESTIGATED DDYSPEPSIA YSPEPSIA IN IN IINDONESIA NDONESIA
IIFF <2 <2 4 W 4 WKS KS..
DDIETARY IETARY AADVICE DVICE, O , OBSERVE BSERVE
RREVIEW EVIEWCCURRENT URRENT MMEDS EDS..
EEXCLUDE BY XCLUDE BY HHISTORY ISTORY ::
BBILLIARY ILLIARY PPAIN AIN, ,
IIRRITABLE RRITABLE BBOWEL OWEL, R , REFLUX EFLUX
FFAILURE AILURE OR OR
EEARLY ARLY RRELAPSE ELAPSE
FFINAL INAL EEVALUATION VALUATIONAAFTER FTER 8 W 8 WKS KS
>3 X R >3 X RELAPSE ELAPSE
RRELAPSE ELAPSE
FFOLLOW OLLOWUUPP
SSUCCESS UCCESS
PPOS OS..
AAGE GE >55 Y >55 YRS RS
WITH WITH AALARM LARM FFEATURES EATURES ::
NNEG EG..
SSEROLOGIC EROLOGIC Hp T Hp TESTING ESTING
AANTACIDS NTACIDS
AANTISECRETORY NTISECRETORY
PPROKINETICS ROKINETICS
GGASTROENTEROLOGIST ASTROENTEROLOGIST
IINTERNAL NTERNAL MMED. ED./P /PED. WITH ED. WITH
EENDOSCOPIC NDOSCOPIC FFACILITIES ACILITIES
TTREATMENT REATMENT TTRIAL RIAL : 2 W : 2 WKS KS
AGE <55 Y AGE <55 YRS RS
WWITHOUT ITHOUTAALARM LARM FFEATURES EATURES
DYSPEPSIA DYSPEPSIA
FFEVER EVER
HHEMATEMESIS / EMATEMESIS / MMELENA ELENA
J AUNDICE J AUNDICE
BW BW
NSAIDs NSAIDs
SSTRONG TRONG FFEAR EAR OF OF SSERIOUS ERIOUS DDIS IS. .
FFAMILY AMILY HHISTORY : ISTORY : GGASTRIC ASTRIC CCA. A.
SSEVERE EVERE VVOMITING OMITING
EERADICATION RADICATION TTHERAPY HERAPY
RREEVALUATE EEVALUATE : E : ENDOSC NDOSC.,PA, Hp C .,PA, Hp CULTURE ULTURE
RREEVALUATE : EEVALUATE : EENDOSC., NDOSC.,PA PA, , CLO CLO
CLO ( CLO (), PA ( ), PA ())
QQUADRUPLE UADRUPLE TTREATMENT REATMENT
MMANAGEMENT ANAGEMENT OF OF DDYSPEPSIA YSPEPSIA IN IN RREFFERAL EFFERAL CCENTER ENTER
FFROM ROM AALGORHYTM LGORHYTM 11 UGI E UGI ENDOSCOPY NDOSCOPY
CLO ( CLO (), PA ( ), PA ()) CLO ( CLO (), PA ( ), PA ())
CLO ( CLO (), PA ( ), PA ())
NNOO EERADICATION RADICATION
EEMPIRIC MPIRIC TTREATMENT REATMENT
FFIND IND OOTHER THER CCAUSES AUSES
SSUCCESS UCCESS FFAILURE AILURE
FFAILURE AILURE
Hp E Hp ERADICATION RADICATION AACCORDING CCORDING
TO TO THE THE RRESISTANCY ESISTANCY TTEST EST
DYSPEPSIA DYSPEPSIA
CLO T CLO TEST EST, PA , PA
EEVALUATION VALUATION 4 W 4 WKS KS. .
AAFTER FTER EERADICATION RADICATION
Note : Note :
CCASE ASE SSELECTION ELECTION ::
1. Strongly recommended : 1. Strongly recommended :
DU DU
GU GU
Post resection of early gastric Ca Post resection of early gastric Ca
MALT lymphoma MALT lymphoma
2. Recommended : 2. Recommended :
Ulcer Ulcer--like dyspepsia like dyspepsia
Severe chronic gastritis Severe chronic gastritis
NSAIDs gastritis NSAIDs gastritis
Severe erosive gastritis Severe erosive gastritis
Hypertrophic gastritis Hypertrophic gastritis
CCASE ASE SSELECTION ELECTION
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