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An Evidence-based Approach
      to the Management of
 Uninvestigated Dyspepsia
  in the Primary Care Settings:
             an update
Dyspepsia:
       the size of the problem

15–25% 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


                                   Talley, J Clin Gastroenterol 2001; 32: 286–93.
                            Locke, Ballieres Clin Gastroenterol 1998; 12: 435–42.
                                    Paré, Can J Gastroenterol 1999; 13: 647–54.
                            van Bommel et al., Postgrad Med J 2001; 77: 514–18.
                                            Talley et al., BMJ 2001; 323: 1294–7.
Dyspepsia covers a range of symptoms



                      DYSPEPSIA
  GERD          PAIN OR DISCOMFORT                         IBS
                centred in upper abdomen




     UNINVESTIGATED                   INVESTIGATED

                                                    FUNCTIONAL
                            ORGANIC                  (or idiopathic)
                                              (use of the term ‘non-ulcer’
                                                      is discouraged)




                                           Talley et al., Gut 1999; 45(Suppl II): II37–42.
Definition of dyspepsia (Rome II)



 Pain or discomfort occurring
centred in the upper abdomen

                                       Talley et al., Gut 1999; 45(Suppl II): II37–42.
              Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
Gastritis
                  Peptic ulcer disease
                       (Includes NSAID-induced ulcers)




                  Acid reflux
                   Oesophagitis
                     Strictures
                     Barrett’s
                  oesophagus
                   Oesophageal
                 adenocarcinoma




    Duodenitis
Duodenal ulcer
Reflux esophagitis
          Normal
                                23.9%
                       33.6%
                                        2% Cancer

                                19.9%
                        20.8%
                                        Peptic ulcer disease
Gastritis/duodenitis

                                                    Richter 1991
Functional Dyspepsia (Rome I)

                                      Dysmotility-like
                           21      11   dyspepsia
    Ulcer-like           (10%)   (5%)
    dyspepsia
                             27
                   51      (13%)     7 (3%)
                 (24%)

                           36
                         (17%)      10
                                   (5%)
Unspecified
 dyspepsia                              Reflux-like
                                        dyspepsia
n=50 (23%)
                                               Talley et al 1992
Definition of Functional Dyspepsia (Rome II)

    Twelve weeks or more (within the last 12
   months) of persistent or recurrent dyspepsia
   and evidence that organic disease likely to
      explain the symptoms is absent
        (including at upper endoscopy)

                         Dyspepsia subgroups
    ●   Ulcer-like (predominantly pain)
    ●   Dysmotility-like (predominantly discomfort)
    ●   Unspecified (non-specific, no predominant symptom)

                                                       Talley et al., Gut 1999; 45(Suppl II): II37–42.
                              Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
Definition of Functional Dyspepsia
               (Rome III)

At least 3 months, with onset at least 6 months
previously, of 1 or more of the following:

• Bothersome postprandial fullness
• Early satiation
• Epigastric pain
• Epigastric burning
                And
• No evidence of structural disease (including at upper
endoscopy) that is likely to explain the symptoms
Functional dyspepsia:
an exclusion diagnosis
Uninvestigated Dyspepsia


Patient with new onset or recurrent
 dyspeptic symptoms in whom no
investigation have been conducted
and no specific diagnosis for   the
      current symptoms exist

                     Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Uninvestigated dyspepsia
     vs functional dyspepsia

  Uninvestigated dyspepsia
      ●   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 et al., Gut 1999; 45(Suppl II): II37–42.
Management of
uninvestigated dyspepsia
Uninvestigated Dyspepsia                          Consider :
                                                                - Cardiac
                                                             - Hepatobiliary
                              (A)             YES
                                                          - Medication-induced
                    Other possible causes ?               - Dietary indiscretion
                                                                  - Other
                                                          Treat as appropriate




First Visit




                                                    Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Recommendation

Exclude other possible causes of the dyspeptic symptoms with
      thorough history-taking and physical examination

                 Consider:
    cardiac and hepatobiliary sources
      medication-induced symptoms
       possible dietary indiscretion
       lifestyle or other causes


                        (grade C recommendation, consensus)
Uninvestigated Dyspepsia                               Consider :
                                                                     - Cardiac
                                                                  - Hepatobiliary
                                 (A)               YES
                                                               - Medication-induced
                    Other possible causes ?                    - Dietary indiscretion
                                         No                            - Other
                                   (B)
                      Age >50 or alarm features?               Treat as appropriate
                               - Vomiting
                          - Bleeding anemia        YES
                         - Abdominal mass/                          Investigate
                        unexplained weight loss
                             - Dysphagia
                                                             (endoscopy recommended)
First Visit




                                                         Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Older patients and with alarm features
   
   


          America > 45 years
          Canada > 50 years
          Indonesia > 55 years
          Cancer is a rare cause of dyspeptic symptoms
          <2%
Dispepsia
 
     Diagnostic test: endoscopy or radiography?


      Radiography : 70 %
      Endoscopy : 96 %




             Dooley et al., Ann Intern Med 1984;
                         101: 538-45
Specialist management of
 uninvestigated dyspepsia


Endoscopy with biopsies
           and

   treat accordingly!


           Talley et al., BMJ 2001; 323: 1294–7
Recommendation
   Prompt investigation is recommended for patients over 50 years of age
   with uninvestigated dyspepsia and for any patient presenting with alarm
                                   features
                         Alarm features:
                     persistent vomiting
         evidence of gastrointestinal bleeding or anemia
                 presence of an abdominal mass
                   unexplained weight loss
                        dysphagia

                      (grade B recommendation, level III evidence)

     Endoscopy is the recommended method of investigation for patients
with uninvestigated dyspepsia who are over 50 years of age or who have alarm
                                  features
                     (grade A recommendation, level II evidence)
Uninvestigated Dyspepsia                               Consider :
                                                                     - Cardiac
                                                                  - Hepatobiliary
                                 (A)               YES
                                                               - Medication-induced
                    Other possible causes ?                    - Dietary indiscretion
                                         No                            - Other
                                   (B)
                      Age >50 or alarm features?               Treat as appropriate
                               - Vomiting
                          - Bleeding anemia        YES
                         - Abdominal mass/                          Investigate
                        unexplained weight loss
                             - Dysphagia
                                                             (endoscopy recommended)
First Visit
                                           NO

                           (C)
                                                   YES
                       NSAID and/or
                       Regular ASA                          NSAID Management
                          Use?




                                                         Sander et al., CMAJ 2000; 162 (Suppl): S1–23

   Patients who use NSAIDs

    Hp infection is the most common cause of
                    peptic ulcers






        NSAIDs are responsible for most
             Hp-negative ulcers
Recommendation

      Patients with uninvestigated dyspepsia
         who are regular users of NSAIDS
       (including ASA) should be identified,
         and if there are no alarm features,
they can be managed without initial endoscopy


                  (grade C recommendation, consensus)
NSAID and/or
       reguler ASA use



                               YES
  Can NSAID/ASA
                                     Stop therapy
   be stopped?

                                                             YES
                NO
                               Patient improved?                        End



Treat or investigate                 NO
a. PPI
b. Cytoprotective agent
c. High-dose H2-RA
d. Switch to COX-2 inhibitor

                                          Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Recommendation
                    If possible, NSAID use should be stopped
                    and the patient’s response monitored

                        (grade C recommendation, level III evidence)
    If NSAIDs cannot be stopped the choice is to treat or investigate

Treatment recommendations for patients aged 50 years or less who
present with uninvestigated dyspepsia, who no alarm features and
who need to use NSAIDs (including ASA) are as follows:
• PPI
• Cytoprotective agent
• High-dose H2–RA therapy
(d) Consider switch to COX-2 inhibitor

                               (grade C recommendation, consensus)
Uninvestigated Dyspepsia                               Consider :
                                                                     - Cardiac
                                                                  - Hepatobiliary
                                 (A)               YES
                                                               - Medication-induced
                    Other possible causes ?                    - Dietary indiscretion
                                         No                            - Other
                                   (B)
                      Age >50 or alarm features?               Treat as appropriate
                               - Vomiting
                          - Bleeding anemia        YES
                         - Abdominal mass/                          Investigate
                        unexplained weight loss
                             - Dysphagia
                                                             (endoscopy recommended)
First Visit
                                           NO

                           (C)
                                                   YES
                       NSAID and/or
                       Regular ASA                          NSAID Management
                          Use?

                                       NO



                               (D)                 YES
                      Is dominant symptom
                         heartburn and/or                   Treat as reflux
                          regurgitation ?




                                                         Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Patients with dominant symptom of heartburn
             or acid regurgitation, or both




      Heartburn (89 %) or acid regurgitation (95 %) have
                    high specificity for GERD
    Initial treatment can be started based on symptoms
                   of reflux in primary care






     Most GERD patients do not have macroscopic
                    esophagitis
    Endoscopy is not a useful diagnostic gold standard for
            GERD, nor 24-hour pH monitoring






    A reliable interpretation of the term heartburn is key
                  for the diagnosis of GERD
Recommendation
  Patients aged 50 years or less with uninvestigated dyspepsia
  and dominant symptoms of heartburn or acid regurgitation,
         or both should be diagnosed as having GERD
                  and be treated accordingly

 Rather than using the term “heartburn”, describing the
sensation of “a burning feeling rising from your stomach
    or lower chest toward your neck” increases the
             diagnostic accuracy for GERD


                    (grade B recommendation, level II-2 evidence)
Reflux mini-management schema

  Dominant symptom heartburn and/or regurgitation

      Treat
      a. PPI
      b. H2-RA
      c. Prokinetic
      Reassess at 4 weeks


             Symptoms
                                   YES
             Resolved?
                     NO
Treat
- If not on PPI, switch to PPI x 4-8 weeks
- If on PPI, double dose x 4-8 weeks or
       consider investigation


             Symptoms              YES                  Stop therapy (if symptoms recur,
             resolved?                                       repeat original therapy)
                     NO
             Investigate                            Sander et al., CMAJ 2000; 162 (Suppl): S1–23

   Management of patients with GERD

           Five treatment possibilities for GERD
                   - lifestyle modification
                           - antacids
                            - H2RAs
                          - prokinetic
                             - PPIs






    Review of lifestyle modification and antacids concluded
       that definitive evidence of efficacy is unavailable

     Milder symptoms of GERD may derive benefit from
                   lifestyle modification
Recommendation

The effectiveness of lifestyle modifications and antacids for the treatment
 of GERD is not proven. Patient with mild GERD symptoms may derive
                        benefit from these treatment

                               (grade C recommendation, consensus)

Treatment recommendations for patients with a dominant symptom of
      heartburn or acid regurgitation, or both, are as follows :
                               • PPI
                           (a) H2 – RA
                       (b) Prokinetic agent
                        (grade A recommendation, level I evidence)

Patients should be reassessed after 4 weeks of therapy

                               (grade C recommendation, consensus)
Uninvestigated Dyspepsia                           Consider :
                                                                 - Cardiac
                                                              - Hepatobiliary
                                 (A)               YES
                                                           - Medication-induced
                    Other possible causes ?                - Dietary indiscretion
                                         No                        - Other
                                   (B)
                      Age >50 or alarm features?           Treat as appropriate
                               - Vomiting
                          - Bleeding anemia        YES
                         - Abdominal mass/                      Investigate
                        unexplained weight loss
                             - Dysphagia
                                                         (endoscopy recommended)
First Visit
                                           NO

                           (C)
                                                   YES
                       NSAID and/or
                       Regular ASA                       NSAID Management
                          Use?

                                       NO



                               (D)                 YES
                      Is dominant symptom
                         heartburn and/or                Treat as reflux
                          Regurgitation ?


                                       NO

                                 (E)
                                                   YES
                          Hp test positive?
                               1. UBT                    Treat as Hp positive
                            2. Serology
Hp test and treat strategy
            Hp infection is associated with
             - duodenal ulcer 90 – 95 %
               - gastric ulcer 60 – 80 %
                      - gastric cancer
        Uncertainty as to whether Hp plays a role in
           dyspepsia in the absence of ulcers

    Option for the treatment of younger patients w/o alarm features:
               - trial of empiric (antisecretory or prokinetic)
                            - diagnostic evaluation
                         - non invasive testing for Hp
      followed by eradication therapy for patients w/ (+)ve results
                         - non invasive testing for Hp
          followed by endoscopy for patients w/ (+)ve results
Recommendation


A test-and-treat strategy for uninvestigated dyspepsia
      in younger patient (aged 50 years or less)
   who have no alarm features is recommended




               (grade B recommendation, level I evidence)

   Testing for Hp infection

             Infection can be detected by:
             - invasive (endoscopy based)
       - non invasive (UBT, HPSA or serologic
                         testing)
     Serologic testing cannot be used to determine cure
      as the IgG antibodies remain detected for a long
                     time after eradication






        UBT has a high (+)ve and (-)ve predictive value
                        (both > 95 %)
          Gisbert et al. Aliment Pharmacol Ther 2004;20:1001–17
Recommendation

           Noninvasive methods are recommended
for the detection of H. pylori in patient aged 50 years or less
  with uninvestigated dyspepsia who have no alarm features

            Hp stool antigen is the preferred test




                 (grade B recommendation, level II-2 evidence)
Recommendation

             No more serology
   Stool antigen is the recommended test
  Test with stool antigen before prescribing
                       PPIs
 do not have alarm symptoms
 have not been using NSAIDS
 who are not > 55 yrs
                         (AGA guidelines from 2005)
H. Pylori positive mini-management schema

             Patient Hp positive

Eradicate Hp:
a. PPI + AC or MC or
   RBC + AC or MC (bid x 7 days)
b. Alternative first line therapy
c. PPI + BMT (bid x 14 days)
(advise patient to return 4 weeks after
treatment if symptoms recur or persist)


                                          YES
                   Symptoms                                    No further therapy
             resolved at follow up?                             or investigation
                            NO

      Confirm Hp eradication by UBT
        or histology (not serology)

                                          YES
               Hp eradicated?                                  Treat as Hp negative

                            NO

        Switch regimen and retreat
         or refer for investigation
                                                 Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Hp eradication therapy
           (a) First line therapy
      PPI + AC or PPI + MC (bid for 7 days)
    or ranitidine bismuth citrate + AC or MC
     • Alternative first-line therapy
•   PPI + BMT (14-day quadruple regimen)
                      PPI (bid)
                B (4x2 tablets/day)
                 M (4x250 mg/day)
                 T (4x500 mg/day)
    PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg
                        A = Amoxicillin 1000 mg
                  B = Bismuth subsalicylate (2 tablets)
          C = Clarithromycin 250 (or 500 mg if treatment failure)
     M = Metronidazole 500 mg (250 mg in BMT combination therapy)
                        T = Tetracyclin 500 mg


                                               Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Recommendation
Eradication therapies recommended for patients
with uninvestigated dyspepsia who are found
to be H. pylori positive are as follow:
• PPI + AC or MC,
        or ranitidine bismuth citrate + AC or MC
• Alternative first-line therapy
(c) PPI + BMT
          PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg
          A = Amoxicillin 1000 mg
          B = Bismuth subsalicylate (2 tablets)
          C = Clarithromycin 250 (or 500 mg if treatment failure)
          M = Metronidazole 500 mg (250 mg in BMT combination therapy)
          T = Tetracyclin 500 mg




                           (grade A recommendation, level I evidence)
A meta-analysis of short versus long therapy
         with a PPI, clarithromycin
  and either metronidazole or amoxicillin
          for treating Hpinfection

               A meta-analysis of 13 studies:
  Eradication rate for 14-day therapy vs 10-day therapy
 was 81% (95% CI, 77%–85%) vs 72% (95% CI, 68%–76%)

 The eradication rate for 10-day therapy vs 7-day therapy:
   83% (95% CI, 75%–89%) vs 80% (95% CI, 71%–86%)


           Calvet et al. Aliment Pharmacol Ther 2000;14:603–609
Meta-analysis:
duration of first-line PPI-based triple therapy
     for Helicobacter pylori eradication



    Extending triple therapy beyond 7 days
  is unlikely to be a clinically useful strategy




             Fuccio et al. Ann Intern Med. 2007;147(8):553-62
Pantoprazole based therapies in HP eradication:
     a systematic review and meta-analysis


  Pantoprazole achieves similar cure rates to
    those of omeprazole and lansoprazole
     when co-prescribed with antibiotics


                       Eur J Gastroenterol. 2004;16: 89-99   
Uninvestigated Dyspepsia                             Consider :
                                                                         - Cardiac
                                                                      - Hepatobiliary
                                         (A)               YES
                                                                   - Medication-induced
                          Other possible causes ?                  - Dietary indiscretion
                                                 No                        - Other
                                           (B)
                              Age >50 or alarm features?           Treat as appropriate
                                       - Vomiting
                                  - Bleeding anemia        YES
                                 - Abdominal mass/                      Investigate
                                unexplained weight loss
                                     - Dysphagia
                                                                 (endoscopy recommended)
      First Visit
                                                   NO

                                   (C)
                                                           YES
                               NSAID and/or
                                                                 NSAID Management
                               Regular ASA
                                  Use?

                                               NO



                                       (D)                 YES
                              Is dominant symptom
                                 heartburn and/or                Treat as reflux
                                  Regurgitation ?


                                               NO


                         NO
                                         (E)
                                                           YES
Treat as Hp Negative              Hp test positive?
                                                                 Treat as Hp positive
                                       1. UBT
                                    2. Serology                    Sander et al., CMAJ 2000; 162 (Suppl): S1–23
H. Pylori negative mini-management schema

       Patient Hp negative

     Treat x 4 weeks
     a. PPI
     b. H2-RA
     c. Prokinetic

                                  YES
            Symptoms
            resolved?

                    NO

              Modify therapy
(increase dose or switch to another therapy)


                                  YES
            Symptoms
            resolved?                                         Stop
                    NO
                                                            therapy
  Reassess or investigate/refer
                                               Sander et al., CMAJ 2000; 162 (Suppl): S1–23
Recommendation

    There is good evidence that antacids are ineffective
for functional dyspepsia, and they are not recommended
       for the treatment of uninvestigated dyspepsia
  in patients subsequently found to be H. Pylori negative




                 (grade B recommendation, level I evidence)
Recommendation

Treatment recommendation for patients who present
with uninvestigated dyspepsia and who subsequently
have negative results of testing for H. Pylori are as follows:
(a) PPI
(b) H2-RA
(c) Prokinetic agent

                       (grade B recommendation, level I evidence)
Summaries

    Clinical management tool consists of 5 key steps in
     the evaluation of patients with uninvestigated
     dyspepsia
       The tool includes 4 mini-management schemata


    The tool is practical, easy to use, explicit and concise,
     and it reflects the realities of the primary care setting


    Adoption of this tool will optimize the treatment of
     patients with dyspepsia, improve quality of care and be
     cost-effective
PRIMARY MANAGEMENT OF NEW ONSET
               UNINVESTIGATED DYSPEPSIA IN INDONESIA

  EXCLUDE BY HISTORY :                                   IF < 2 – 4 WKS.
                               DYSPEPSIA           DIETARY ADVICE, OBSERVE
      BILLIARY PAIN,
IRRITABLE BOWEL, REFLUX                             REVIEW CURRENT MEDS.

     AGE > 55 YRS                                      AGE > 55 YRS
WITHOUT ALARM FEATURES
                                                 WITH ALARM FEATURES :

                                                   SEVERE VOMITING
                                                  FEVER
  TREATMENT TRIAL : 2 WKS       SUCCESS           HEMATEMESIS / MELENA
     ANTACIDS
     ANTISECRETORY                               ICTERUS
                                                  ↓ BW
     PROKINETICS                                 NSAIDs
                               FOLLOW UP          STRONG FEAR OF SERIOUS DIS.
      FAILURE OR
     EARLY RELAPSE                                FAMILY HISTORY : GASTRIC CA.
                               RELAPSE

  SEROLOGIC Hp TESTING                          SPECIALIST REFFERAL :
                                                 GASTROENTEROLOGIST

    NEG.      POS.                               INTERNAL MED./PED. WITH
                                                   ENDOSCOPIC FACILITIES

                 FINAL EVALUATION AFTER 8 WKS
                         > 3 X RELAPSE

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Dispepsia

  • 1. An Evidence-based Approach to the Management of Uninvestigated Dyspepsia in the Primary Care Settings: an update
  • 2. Dyspepsia: the size of the problem 15–25% 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 Talley, J Clin Gastroenterol 2001; 32: 286–93. Locke, Ballieres Clin Gastroenterol 1998; 12: 435–42. Paré, Can J Gastroenterol 1999; 13: 647–54. van Bommel et al., Postgrad Med J 2001; 77: 514–18. Talley et al., BMJ 2001; 323: 1294–7.
  • 3. Dyspepsia covers a range of symptoms DYSPEPSIA GERD PAIN OR DISCOMFORT IBS centred in upper abdomen UNINVESTIGATED INVESTIGATED FUNCTIONAL ORGANIC (or idiopathic) (use of the term ‘non-ulcer’ is discouraged) Talley et al., Gut 1999; 45(Suppl II): II37–42.
  • 4. Definition of dyspepsia (Rome II) Pain or discomfort occurring centred in the upper abdomen Talley et al., Gut 1999; 45(Suppl II): II37–42. Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
  • 5. Gastritis Peptic ulcer disease (Includes NSAID-induced ulcers) Acid reflux Oesophagitis Strictures Barrett’s oesophagus Oesophageal adenocarcinoma Duodenitis Duodenal ulcer
  • 6. Reflux esophagitis Normal 23.9% 33.6% 2% Cancer 19.9% 20.8% Peptic ulcer disease Gastritis/duodenitis Richter 1991
  • 7. Functional Dyspepsia (Rome I) Dysmotility-like 21 11 dyspepsia Ulcer-like (10%) (5%) dyspepsia 27 51 (13%) 7 (3%) (24%) 36 (17%) 10 (5%) Unspecified dyspepsia Reflux-like dyspepsia n=50 (23%) Talley et al 1992
  • 8. Definition of Functional Dyspepsia (Rome II) Twelve weeks or more (within the last 12 months) of persistent or recurrent dyspepsia and evidence that organic disease likely to explain the symptoms is absent (including at upper endoscopy) Dyspepsia subgroups ● Ulcer-like (predominantly pain) ● Dysmotility-like (predominantly discomfort) ● Unspecified (non-specific, no predominant symptom) Talley et al., Gut 1999; 45(Suppl II): II37–42. Malfertheiner, Eur J Gastroenterol Hepatol 1999; 11(Suppl 1): S25–9.
  • 9. Definition of Functional Dyspepsia (Rome III) At least 3 months, with onset at least 6 months previously, of 1 or more of the following: • Bothersome postprandial fullness • Early satiation • Epigastric pain • Epigastric burning And • No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms
  • 11. Uninvestigated Dyspepsia Patient with new onset or recurrent dyspeptic symptoms in whom no investigation have been conducted and no specific diagnosis for the current symptoms exist Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 12. Uninvestigated dyspepsia vs functional dyspepsia Uninvestigated dyspepsia ● 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 et al., Gut 1999; 45(Suppl II): II37–42.
  • 14. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion - Other Treat as appropriate First Visit Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 15. Recommendation Exclude other possible causes of the dyspeptic symptoms with thorough history-taking and physical examination Consider: cardiac and hepatobiliary sources  medication-induced symptoms  possible dietary indiscretion  lifestyle or other causes (grade C recommendation, consensus)
  • 16. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion No - Other (B) Age >50 or alarm features? Treat as appropriate - Vomiting - Bleeding anemia YES - Abdominal mass/ Investigate unexplained weight loss - Dysphagia (endoscopy recommended) First Visit Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 17. Older patients and with alarm features         America > 45 years Canada > 50 years Indonesia > 55 years Cancer is a rare cause of dyspeptic symptoms <2%
  • 19.     Diagnostic test: endoscopy or radiography? Radiography : 70 % Endoscopy : 96 % Dooley et al., Ann Intern Med 1984; 101: 538-45
  • 20. Specialist management of uninvestigated dyspepsia Endoscopy with biopsies and treat accordingly! Talley et al., BMJ 2001; 323: 1294–7
  • 21. Recommendation Prompt investigation is recommended for patients over 50 years of age with uninvestigated dyspepsia and for any patient presenting with alarm features Alarm features: persistent vomiting evidence of gastrointestinal bleeding or anemia  presence of an abdominal mass unexplained weight loss dysphagia (grade B recommendation, level III evidence) Endoscopy is the recommended method of investigation for patients with uninvestigated dyspepsia who are over 50 years of age or who have alarm features (grade A recommendation, level II evidence)
  • 22. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion No - Other (B) Age >50 or alarm features? Treat as appropriate - Vomiting - Bleeding anemia YES - Abdominal mass/ Investigate unexplained weight loss - Dysphagia (endoscopy recommended) First Visit NO (C) YES NSAID and/or Regular ASA NSAID Management Use? Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 23.   Patients who use NSAIDs Hp infection is the most common cause of peptic ulcers   NSAIDs are responsible for most Hp-negative ulcers
  • 24. Recommendation Patients with uninvestigated dyspepsia who are regular users of NSAIDS (including ASA) should be identified, and if there are no alarm features, they can be managed without initial endoscopy (grade C recommendation, consensus)
  • 25. NSAID and/or reguler ASA use YES Can NSAID/ASA Stop therapy be stopped? YES NO Patient improved? End Treat or investigate NO a. PPI b. Cytoprotective agent c. High-dose H2-RA d. Switch to COX-2 inhibitor Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 26. Recommendation If possible, NSAID use should be stopped and the patient’s response monitored (grade C recommendation, level III evidence) If NSAIDs cannot be stopped the choice is to treat or investigate Treatment recommendations for patients aged 50 years or less who present with uninvestigated dyspepsia, who no alarm features and who need to use NSAIDs (including ASA) are as follows: • PPI • Cytoprotective agent • High-dose H2–RA therapy (d) Consider switch to COX-2 inhibitor (grade C recommendation, consensus)
  • 27. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion No - Other (B) Age >50 or alarm features? Treat as appropriate - Vomiting - Bleeding anemia YES - Abdominal mass/ Investigate unexplained weight loss - Dysphagia (endoscopy recommended) First Visit NO (C) YES NSAID and/or Regular ASA NSAID Management Use? NO (D) YES Is dominant symptom heartburn and/or Treat as reflux regurgitation ? Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 28. Patients with dominant symptom of heartburn or acid regurgitation, or both   Heartburn (89 %) or acid regurgitation (95 %) have high specificity for GERD Initial treatment can be started based on symptoms of reflux in primary care   Most GERD patients do not have macroscopic esophagitis Endoscopy is not a useful diagnostic gold standard for GERD, nor 24-hour pH monitoring   A reliable interpretation of the term heartburn is key for the diagnosis of GERD
  • 29. Recommendation Patients aged 50 years or less with uninvestigated dyspepsia and dominant symptoms of heartburn or acid regurgitation, or both should be diagnosed as having GERD and be treated accordingly Rather than using the term “heartburn”, describing the sensation of “a burning feeling rising from your stomach or lower chest toward your neck” increases the diagnostic accuracy for GERD (grade B recommendation, level II-2 evidence)
  • 30. Reflux mini-management schema Dominant symptom heartburn and/or regurgitation Treat a. PPI b. H2-RA c. Prokinetic Reassess at 4 weeks Symptoms YES Resolved? NO Treat - If not on PPI, switch to PPI x 4-8 weeks - If on PPI, double dose x 4-8 weeks or consider investigation Symptoms YES Stop therapy (if symptoms recur, resolved? repeat original therapy) NO Investigate Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 31.   Management of patients with GERD Five treatment possibilities for GERD - lifestyle modification - antacids - H2RAs - prokinetic - PPIs   Review of lifestyle modification and antacids concluded that definitive evidence of efficacy is unavailable Milder symptoms of GERD may derive benefit from lifestyle modification
  • 32. Recommendation The effectiveness of lifestyle modifications and antacids for the treatment of GERD is not proven. Patient with mild GERD symptoms may derive benefit from these treatment (grade C recommendation, consensus) Treatment recommendations for patients with a dominant symptom of heartburn or acid regurgitation, or both, are as follows : • PPI (a) H2 – RA (b) Prokinetic agent (grade A recommendation, level I evidence) Patients should be reassessed after 4 weeks of therapy (grade C recommendation, consensus)
  • 33. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion No - Other (B) Age >50 or alarm features? Treat as appropriate - Vomiting - Bleeding anemia YES - Abdominal mass/ Investigate unexplained weight loss - Dysphagia (endoscopy recommended) First Visit NO (C) YES NSAID and/or Regular ASA NSAID Management Use? NO (D) YES Is dominant symptom heartburn and/or Treat as reflux Regurgitation ? NO (E) YES Hp test positive? 1. UBT Treat as Hp positive 2. Serology
  • 34. Hp test and treat strategy  Hp infection is associated with - duodenal ulcer 90 – 95 % - gastric ulcer 60 – 80 % - gastric cancer Uncertainty as to whether Hp plays a role in dyspepsia in the absence of ulcers  Option for the treatment of younger patients w/o alarm features: - trial of empiric (antisecretory or prokinetic) - diagnostic evaluation - non invasive testing for Hp followed by eradication therapy for patients w/ (+)ve results - non invasive testing for Hp followed by endoscopy for patients w/ (+)ve results
  • 35. Recommendation A test-and-treat strategy for uninvestigated dyspepsia in younger patient (aged 50 years or less) who have no alarm features is recommended (grade B recommendation, level I evidence)
  • 36.   Testing for Hp infection Infection can be detected by: - invasive (endoscopy based) - non invasive (UBT, HPSA or serologic testing) Serologic testing cannot be used to determine cure as the IgG antibodies remain detected for a long time after eradication   UBT has a high (+)ve and (-)ve predictive value (both > 95 %) Gisbert et al. Aliment Pharmacol Ther 2004;20:1001–17
  • 37. Recommendation Noninvasive methods are recommended for the detection of H. pylori in patient aged 50 years or less with uninvestigated dyspepsia who have no alarm features Hp stool antigen is the preferred test (grade B recommendation, level II-2 evidence)
  • 38. Recommendation  No more serology  Stool antigen is the recommended test  Test with stool antigen before prescribing PPIs  do not have alarm symptoms  have not been using NSAIDS  who are not > 55 yrs (AGA guidelines from 2005)
  • 39. H. Pylori positive mini-management schema Patient Hp positive Eradicate Hp: a. PPI + AC or MC or RBC + AC or MC (bid x 7 days) b. Alternative first line therapy c. PPI + BMT (bid x 14 days) (advise patient to return 4 weeks after treatment if symptoms recur or persist) YES Symptoms No further therapy resolved at follow up? or investigation NO Confirm Hp eradication by UBT or histology (not serology) YES Hp eradicated? Treat as Hp negative NO Switch regimen and retreat or refer for investigation Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 40. Hp eradication therapy (a) First line therapy PPI + AC or PPI + MC (bid for 7 days) or ranitidine bismuth citrate + AC or MC • Alternative first-line therapy • PPI + BMT (14-day quadruple regimen) PPI (bid) B (4x2 tablets/day) M (4x250 mg/day) T (4x500 mg/day) PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg A = Amoxicillin 1000 mg B = Bismuth subsalicylate (2 tablets) C = Clarithromycin 250 (or 500 mg if treatment failure) M = Metronidazole 500 mg (250 mg in BMT combination therapy) T = Tetracyclin 500 mg Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 41. Recommendation Eradication therapies recommended for patients with uninvestigated dyspepsia who are found to be H. pylori positive are as follow: • PPI + AC or MC, or ranitidine bismuth citrate + AC or MC • Alternative first-line therapy (c) PPI + BMT PPI = Lansoprazole 30 mg; Omeprazole 20 mg; Pantoprazole 40 mg A = Amoxicillin 1000 mg B = Bismuth subsalicylate (2 tablets) C = Clarithromycin 250 (or 500 mg if treatment failure) M = Metronidazole 500 mg (250 mg in BMT combination therapy) T = Tetracyclin 500 mg (grade A recommendation, level I evidence)
  • 42. A meta-analysis of short versus long therapy with a PPI, clarithromycin and either metronidazole or amoxicillin for treating Hpinfection A meta-analysis of 13 studies: Eradication rate for 14-day therapy vs 10-day therapy was 81% (95% CI, 77%–85%) vs 72% (95% CI, 68%–76%) The eradication rate for 10-day therapy vs 7-day therapy: 83% (95% CI, 75%–89%) vs 80% (95% CI, 71%–86%) Calvet et al. Aliment Pharmacol Ther 2000;14:603–609
  • 43. Meta-analysis: duration of first-line PPI-based triple therapy for Helicobacter pylori eradication Extending triple therapy beyond 7 days is unlikely to be a clinically useful strategy Fuccio et al. Ann Intern Med. 2007;147(8):553-62
  • 44. Pantoprazole based therapies in HP eradication: a systematic review and meta-analysis Pantoprazole achieves similar cure rates to those of omeprazole and lansoprazole when co-prescribed with antibiotics Eur J Gastroenterol. 2004;16: 89-99   
  • 45. Uninvestigated Dyspepsia Consider : - Cardiac - Hepatobiliary (A) YES - Medication-induced Other possible causes ? - Dietary indiscretion No - Other (B) Age >50 or alarm features? Treat as appropriate - Vomiting - Bleeding anemia YES - Abdominal mass/ Investigate unexplained weight loss - Dysphagia (endoscopy recommended) First Visit NO (C) YES NSAID and/or NSAID Management Regular ASA Use? NO (D) YES Is dominant symptom heartburn and/or Treat as reflux Regurgitation ? NO NO (E) YES Treat as Hp Negative Hp test positive? Treat as Hp positive 1. UBT 2. Serology Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 46. H. Pylori negative mini-management schema Patient Hp negative Treat x 4 weeks a. PPI b. H2-RA c. Prokinetic YES Symptoms resolved? NO Modify therapy (increase dose or switch to another therapy) YES Symptoms resolved? Stop NO therapy Reassess or investigate/refer Sander et al., CMAJ 2000; 162 (Suppl): S1–23
  • 47. Recommendation There is good evidence that antacids are ineffective for functional dyspepsia, and they are not recommended for the treatment of uninvestigated dyspepsia in patients subsequently found to be H. Pylori negative (grade B recommendation, level I evidence)
  • 48. Recommendation Treatment recommendation for patients who present with uninvestigated dyspepsia and who subsequently have negative results of testing for H. Pylori are as follows: (a) PPI (b) H2-RA (c) Prokinetic agent (grade B recommendation, level I evidence)
  • 49. Summaries  Clinical management tool consists of 5 key steps in the evaluation of patients with uninvestigated dyspepsia The tool includes 4 mini-management schemata  The tool is practical, easy to use, explicit and concise, and it reflects the realities of the primary care setting  Adoption of this tool will optimize the treatment of patients with dyspepsia, improve quality of care and be cost-effective
  • 50. PRIMARY MANAGEMENT OF NEW ONSET UNINVESTIGATED DYSPEPSIA IN INDONESIA EXCLUDE BY HISTORY : IF < 2 – 4 WKS. DYSPEPSIA DIETARY ADVICE, OBSERVE BILLIARY PAIN, IRRITABLE BOWEL, REFLUX REVIEW CURRENT MEDS. AGE > 55 YRS AGE > 55 YRS WITHOUT ALARM FEATURES WITH ALARM FEATURES :  SEVERE VOMITING  FEVER TREATMENT TRIAL : 2 WKS SUCCESS  HEMATEMESIS / MELENA  ANTACIDS  ANTISECRETORY  ICTERUS  ↓ BW  PROKINETICS  NSAIDs FOLLOW UP  STRONG FEAR OF SERIOUS DIS. FAILURE OR EARLY RELAPSE  FAMILY HISTORY : GASTRIC CA. RELAPSE SEROLOGIC Hp TESTING SPECIALIST REFFERAL :  GASTROENTEROLOGIST NEG. POS.  INTERNAL MED./PED. WITH ENDOSCOPIC FACILITIES FINAL EVALUATION AFTER 8 WKS > 3 X RELAPSE

Notes de l'éditeur

  1. Dyspepsia – whatever the cause – is common in the general population, and is more common than peptic ulcers. Dyspepsia affects up to a quarter of the population in a 12-month period. Up to 5% of primary care consultations are due to dyspepsia.
  2. The pain of dyspepsia overlaps with that of GORD and irritable bowel syndrome (IBS). Functional dyspepsia is a diagnosis that can only be made after investigation to exclude an organic cause. It is not necessary to investigate all patients with dyspepsia. Use of the term ‘non-ulcer’ dyspepsia is now discouraged.
  3. According to Rome II criteria, dyspepsia is any pain or discomfort occurring in the upper abdomen. Dyspepsia is further divided into subgroups on the basis of the predominant symptom (ulcer-like, dysmotility-like and non-specific) rather than symptom clusters. While proposed for research purposes, these dyspepsia subgroups are not particularly useful in clinical practice in providing clues to the underlying disease, and therefore, remain contentious.
  4. All of the diseases on this slide are related to inappropriate amounts of acid/levels of acid secretion in the various regions of the upper gastrointestinal (GI) tract. These are the primary areas dealt with in this slide kit.
  5. Patients with dyspepsia may have underlying organic lesions Among patients diagnosed as having dyspepsia, 60–80% may have underlying organic lesions. Reflux esophagitis is frequently the most common such lesion, occurring in up to 1 in 4 dyspeptic patients. 23-25 In a group of 3667 primary care patients in the UK with a clinical diagnosis of dyspepsia, over 60% were subsequently diagnosed endoscopically as having an organic lesion, and over 20% of the dyspeptic patients had reflux esophagitis 25 . However, given the prevalence of dyspepsia, it is not feasible to refer all patients for endoscopy, and the physician has to make a decision on who should be treated empirically and who should receive further investigation.
  6. Dyspepsia has been classified into subgroups based on medical history Dyspeptic patients have been divided into clinical subgroups based on their medical history to try to match symptoms with pathophysiological disturbances and thus enable rational prescribing. The subgroups include those with ulcer-like (typical ulcer symptoms), reflux-like (retrosternal and concomitant upper abdominal symptoms), dysmotility-like (symptoms suggestive of gastric stasis) and unspecified (those whose symptoms cannot be classified) dyspepsia 5 . For any individual patient, however, the symptom pattern may change over time 21 . In addition, considerable overlap exists between the subgroups and few patients exhibit symptoms exclusive to one particular group 3, 22 . For example, in an endoscopy-based study of patients diagnosed with dyspepsia, the prevalence of peptic ulcer disease was found to be similar among patients regardless of whether they had reflux-like (11%), ulcer-like (9%) or dysmotility-like dyspepsia (7%) 22 .
  7. Functional dyspepsia is a diagnosis that can only be made after investigation. Patients with functional dyspepsia (non-organic dyspepsia) have undergone investigation, such as upper GI barium series or upper GI endoscopy, at which time an ulcer (an organic cause of the pain/discomfort) has not been observed. It is not necessary to investigate all patients with dyspepsia, but it is important to take a careful history to rule out the more obvious serious differential diagnoses.
  8. Specialist investigation usually takes place after one or more therapeutic trials with antisecretory agents have been carried out in general practice. Endoscopy and biopsy is used to rule out possible organic causes for the pain.