Non-Ulcer Dyspepsia: what is it? What can we do with these patients? Overview. Dyspepsia Definition. Functional Dyspepsia. Dyspepsia the Basics

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1 Non-Ulcer : what is it? What can we do with these patients? Temporal Changes and Geographic Variations in Developing Peptic Ulcer Disease Gastric Cancer 1900 Eamonn M M Quigley MD FACG Alimentary Pharmabiotic Centre National University of Ireland, Cork ACG Postgraduate Course 2010 San Antonio Texas October 16 th and 17 th 2010 Developed IBS GERD Functional 2010 Overview Definition: Rome III Interpreting symptoms Role of H pylori Assessment Therapy and future directions Definition Not a disease but a symptom, or symptom complex A medical term arrived at following interpretation of a patient s symptom(s) What symptoms to include? Pain vs discomfort Satiety vs satiation Fullness vs bloating Nausea and vomiting Heartburn Location? Epigastric Upper abdomen Central Association? Bowel movement Some are very non-specific How well do these translate? the Basics Common, affecting up to 29% in the community Veldhuyzen van Zanten, et al Associated with various personal and environmental risk factors Tobacco Alcohol NSAID s Significant impact on QOL + personal and societal costs Functional One or more of: 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 Criteria fulfilled for the last three months with symptom onset at least six months prior to diagnosis Rome III 1

2 Functional Canadian Definition Post-prandial Distress Syndrome Bothersome post-prandial fullness Occurring after ordinary-sized meals Early satiation with regular meal At least several times a week May Coexist Epigastric Pain Syndrome At least once a week Intermittent Not generalized or in chest Not IBS-like Not biliary Rome III a symptom complex of epigastric pain or discomfort thought to originate in the upper gastrointestinal tract, and it may include any of the following symptoms: heartburn, acid regurgitation, excessive burping/belching, increased abdominal bloating, nausea, feeling of abnormal or slow digestion, or early satiety Veldhuyzen van Zanten, et al Rome III Differentiates FD from GERD: the pain may be of a burning quality but without a retrosternal component Differentiates FD from IBS: not relieved by defecation or the passage of flatus Canadian Definition a symptom complex of epigastric pain or discomfort thought to originate in the upper gastrointestinal tract, and it may include any of the following symptoms: heartburn, acid INCLUSIVE regurgitation, excessive burping/belching, increased abdominal bloating, nausea, feeling of abnormal or slow digestion, or early satiety Veldhuyzen van Zanten, et al How common is functional dyspepsia? 1033 inhabitants of 2 Italian villages had symptom evaluation, EGD and 13 C-urea breath test 156 (15.1%) had dyspepsia 114 (11%) had FD 77 (67.5%) had meal-related symptoms Abstract 44 Herrick et al. Does Functional exist in the Community? A clinical trial experience 55 (48.2%) had epigastric pain 18 (15.8%) had both Unemployment (OR 5.80), divorce (OR 2.76), smoking (OR 1.74), and IBS (OR3.38) associated with FD. Zagari, et al, 2010 The Symptom Trap Poorly predictive of pathology Limited value of alarm symptoms Unhelpful in predicting response to therapy With the exception of heartburn (the great contaminant!) 2

3 Can History Distinguish between Organic and Functional? Diagnosis LR+ LR- Organic Peptic Ulcer Esophagitis Moayyeddi et al, 2006 Alarm features in the diagnosis of upper GI malignancy 15 studies, 57,363 patients, 458 (.8%) had cancer Sensitivity of alarm symptoms: 0-83% Specificity 40-98% Clinical diagnosis made by a physician Very specific (range, 97%-98%) Not very sensitive (range, 11%-53%) Vakil et al, 2006 Can History Distinguish between Organic and Functional? Diagnosis LR+ LR- AF Patients with AF (n) Diagnostic accuracy of alarm features in predicting upper GI malignancy in 102,265 Chinese patients Cancer in patients with AF (n) Patients without AF (n) Cancer in patients without AF (n) Sensitivity Specificity PPV NPV Organic Peptic Ulcer Esophagitis Moayyeddi et al, 2006 Dysphagia % 97.8% 37.8% 96.9% Weight loss % 97.5% 14.4% 96.0% GI bleeding % 95.3% 7.8% 95.9% Vomiting % 95.9% 5.8% 95.8% Total % 96.6% Bai et al, Gut 2010 Can History Distinguish between Organic and Functional? Diagnosis LR+ LR- Organic Peptic Ulcer Esophagitis Moayyeddi et al, 2006 Critical clinical issues in definition Investigated vs uninvestigated GERD in or out? Noh et al, 2010 IBS in or out? OR for IBS in dyspepsia = 8! Ford et al,

4 Definitions Dictate Outcome! ENDOSCOPY Hp Serology INVESTIGATED DYSPEPSIA UN-INVESTIGATED Sum score (% of baseline) ELAN: -Sum-Score eradication no eradication Difference: 9% p = Baseline 2 weeks 1 year Organic Functional Malfertheiner P et al, 2003 Role of Hp Assessment and Diagnosis Uninvestigated dyspepsia: Significant role for Hp through D.U. G.U. Cancer and MALToma Test-and treat strategies will work! What about functional (non-ulcer) dyspepsia? Who to investigate? All patients Certain age/demographic groups Alarm symptoms How? Hp testing EGD Therapeutic test Hp eradication for dyspepsia: Cochrane Review Study Relative Risk (95% CI) % Weight Blum 0.92 (0.81,1.03) 14.9 McColl 0.85 (0.77,0.93) 16.3 Koelz 0.95 (0.81,1.11) 8.2 Talley(Orchid) 0.97 (0.85,1.11) 12.3 Talley(USA) 1.07 (0.86,1.34) 8.4 Miwa 0.91 (0.70,1.18) 3.6 Malfertheiner 0.88 (0.77,0.99) 22.3 Varannes 0.83 (0.68,1.00) 10.0 Froehlich 0.86 (0.60,1.24) 4.0 Total (95% CI) 0.91 (0.86,0.96) p< Heterogenity χ 2 = 7.1 (df=8) p= Eradication better Placebo better Moayyedi et al, 2001 Approaches to Test-and-Treat scope-and-treat Treat empirically eradication acid suppression prokinetic Investigate; then treat accordingly 4

5 Approaches to Functional Test-and-Treat Investigate gastric emptying tests, EGG, drink test, etc Treat empirically, or on the basis of symptom predominance (PPI, 5HT-1 agonist, visceral analgesic, etc) DYSPEPSIA High Background Rates for Hp Gastric cancer Alarm features Low Rates of Hp and cancer No alarm features HEARTBURN PAIN INVESTIGATE Empiric PPI Treat as IBS Test-and-Treat vs Empiric PPI in Primary Care Differences in quality adjusted life years, costs, and symptom scores at 12 months Difference in SF-LDQ from baseline (all participants) Test and treat No with symptoms at 12 months 217/265* (82%) Difference in SF-LDQ from baseline (epigastric pain predominant patients) (n=245) Difference in SF-LDQ from baseline (heartburn predominant patients) (n=203) Proton pump inhibitor Difference (95% CI) ( 0.8 to 1.8) 229/276* (83%) 1.1% ( 5.4 to 7.6) ( 1.2 to 2.9) ( 1.3 to 3.2) Mean costs ( ) ( 44 to 53) New ideas Eosinophilia Post-infectious FD Persistent inflammation Prokinetics Fundic relaxants tandospirone Delaney et a, BMJ 2008 Who will not respond to Acid suppression? Female Early satiety, post-prandial discomfort Epigastric pain Nausea No reflux symptoms DYSPEPSIA SYMPTOMS Remember Itopride! Phase II Phase III Study absolutely flat! Holtmann et al, NEJM

6 Summary is a symptom or symptom complex susceptible to the pitfalls of symptom interpretation its definition, though, controversial, is critical in determining outcomes As organic causes of dyspepsia recede, NERD, IBS and FD loom ever larger Unlike GERD and IBS, FD is not well defined FD commonly overlaps with GERD and IBS and its separation from them is somewhat arbitrary In FD, pathophysiological correlations with symptoms have been poor and it has been a minefield for new therapies 6