1. Dyspepsia Cengiz Pata Department of Gastroenterology Yeditepe University, Istanbul

2. The Case 40 year old female 6 months of intermittent epigastric burning with occasional nausea but no vomiting Denies weight loss Eating does not change her symptoms She denies any changes in her bowel habits

3. The Case PMH: HTN SH: denies tobacco, EtOH, or IVDA FH: DM, HTN Meds: HCTZ All: NKDA Exam: Unremarkable except moderate epigastric tenderness

4. What is Dyspepsia? Epigastric pain IndigestionFullness Early satiety BloatingBelchingNauseaRetching

5. What is Not Dyspepsia? Heartburn –Almost always a sign of GERD and not included in evaluation/guidelines of dyspepsia.

6. Defining Dyspepsia (AGA) Chronic or recurrent pain or discomfort centered in the upper abdomen Patients with predominant or frequent (>1/wk) heartburn or acid regurgitation are considered to have GERD until proven otherwise and are not considered to have dyspepsia

7. Why is Dyspepsia Important? Prevalence is 25% - 40% per year Accounts for 5% of all PCP referrals Accounts for 50% of gastroenterologists workload $2 Billion is spent on acid-suppressing drugs each year in the US

8. Differential Diagnosis Functional Dyspepsia (60%) PUD (25%) GERD Biliary Pain Chronic Abdominal Wall Pain Gastric CA Esophageal CA Other Abdominal Malignancy GastroparesisPancreatitis Carbohydrate Malabsorption Meds (NSAIDS, Narcotics, etc.) Infiltrative Diseases Metabolic Disturbances Hepatoma Ischemic Bowel Disease Systemic Disorders Parasites

9. Making the Diagnosis Can the clinical history distinguish between organic and functional dyspepsia? Moayyedi et al., JAMA 2006; 295: 1566-1576 –Rational clinical exam series –Meta-analysis of 15 studies evaluating clinicians and computer models in using symptoms and physical exam findings in diagnosing the cause of dyspepsia Dyspepsia defined as any upper GI symptoms

10. AGA Guidelines – Step 1

11. AGA Guidelines – Step 2 Alarm Symptoms: –Weight loss –Progressive dysphagia –Recurrent vomiting –Evidence of GI bleed –Family history of malignancy

12. AGA Guidelines – Step 3

13. AGA Guidelines – Step 4

14. Functional Dyspepsia Diagnostic Criteria (Rome II): –At least 12 weeks, which need not be consecutive, in the preceding 12 months of: 1) Persistent or recurrent dyspepsia 2) No evidence of organic disease that is likely to explain symptoms; and 3) No evidence that dyspepsia is exclusively relieved by defecation or associated with onset of a change in stool frequency or form (not irritable bowel).

15. Diagnostic methods for H. pylori Diagnostic method Histology Main indication Diagnosis Sensitivity (%) 90 Specificity (%) 90 Culture H. pylori antibiotic sensitivities 80-9095 Rapid urease test Endoscopy room diagnosis 90 SerologyScreening and diagnosis 90 Urea breath test To confirm eradication 95100

16. The principle of the urease test NH 2 C O + 2H 2 O + H + 2NH 4 + + HCO 3 - Urease UreaCLOtest pH change

17. The principle of the 13 C- or 14 C-urea breath test Reproduced with permission from Mr Phil Johnson, Bureau of Stable Isotope Analysis, Brentford, UK.

18. Functional Dyspepsia Rome III- similar to Rome II but now FD is broken down into two subgroups based on a complex of symptom features: 1)Postprandial distress syndrome 2)Epigastric pain syndrome

19. Pathophysiology of FD Increased gastric acid H. pylori infection GI dysmotility (antral hypocontractility) Decreased perception threshold Autonomic dysfunction Decreased gastric accommodation Gastric myoelectric activity Psychological factors

20. Pharmacological Treatment of FD Cochrane Meta-analyses (versus placebo): –PPIs (RRR 13%, CI 4% - 20%) –Prokinetics (RRR 33%, CI 18% - 45%) Cisapride, Domperidone, Metaclopramide, Tegaserod May be affected by publication bias –H2RAs (RRR 23%, CI 8% - 35%) –Bismuth salts (RRR 40%, CI –3% - 65%) –Antacids (RRR –2%, CI –36% - 24%) –Sucralfate (RRR 29%, CI –40% - 64%) –H. pylori eradication (RRR 10%, CI 6% - 14%)

21. Pharmacological Treatment of FD Itopride – Dopamine D2 antagonist with acetylcholinesterase inhibitory actions –Stimulates gastric motility –Often used for FD in Japan Holtmann G. et al. A Placebo-Controlled Trial of Itopride in Functional Dyspepsia. NEJM. 2006; 354: 832-840 –Patients with Rome II diagnosis of FD –Pts recruited from private physicians (PCPs?) and one tertiary care center

22. Pharmacological Treatment of FD

23. Psychological Treatment for FD 4 trials have evaluated CBT, hypnotherapy, or psychotherapy All show statistically improvement at 1 year Cochrane Meta-analysis- insufficient evidence as all trials likely underpowered

24. Guidelines for use of antibiotic therapy in patients with Helicobacter pylori infection

25. Treatment regimens for eradication of Helicobacter pylori

26. Therapeutic options clarithromycin 2 x 250 - 500mg metronidazole 2 x 400 - 500mg amoxycillin 2 x 1000mg PPI X 2 eradication rate 90% eradication rate >80% _ < _ <

27. Treatment failures

29. Approach to the Management of Patients with FD (Rome II) Make a positive clinical diagnosis as early as possible Determine why the patient having chronic symptoms has presented on this occasion, and allay any unwarranted fears that the patient may have Do not over-investigate: an empiric therapeutic trial may be appropriate initially especially in the younger patient in the absence of risk factors for serious organic disease After the evaluation, reassure the patient regarding the absence of serious disease and reinforce the diagnosis represents a recognized entity Explain the pathogenesis of the dyspepsia symptoms as far as possible Psychological factors may contribute to the morbidity of the disorder; these issues should be explored and counseling offered

30. Approach to the Management of Patients with FD (Rome II) Advise the patient to avoid possible precipitating factors where appropriate Inquire if the patient would like medication for their problem- not all patients will Follow up with the patient at least once to determine natural history or treatment response Do not repeat investigations based on symptoms alone. Diagnostic studies should depend on new or objective findings Some patients with severe symptoms or multisystem complaints may benefit from counseling Referral to a specialist in motility disorders and/or formal psychological, psychiatric, and/or eating disorder evaluation may be indicated for some patients

31. References American Gastroenterological Association Medical Position Statement: Evaluation of dyspepsia. Gastroenterology. 2005; 129: 1753-1755 Bytzer P. et al. Dyspepsia. Annals of Internal Medicine. 2001; 134: 815-822 Drossman D. et al. Rome II: The functional gastrointestinal disorders, Degnon Associates, 2000 Holtmann G. et al. A Placebo-Controlled Trial of Itopride in Functional Dyspepsia. NEJM. 2006; 354: 832-840 Moayyedi P. et al. Can the clinical history distinguish between organic and functional dyspepsia? JAMA. 2006; 295: 1566-1576 Moayyedi P. et al. Pharmacological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews 2006, Issue 4. Moayyedia P. et al. Eradication of Helicobacter pylori for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews 2006, Issue 2. Soo S. et al. Psychological interventions for non-ulcer dyspepsia. Cochrane Database of Systematic Reviews 2005, Issue 2.