1. Gastroesophageal Reflux Disease: Beyond Heartburn Annette Y. Kwon, M.D. Edward W. Holt, M.D. October 1, 2011

2. Gastroesophageal Reflux Disease The scope of the problemThe scope of the problem What is the working definition?What is the working definition? What is the pathophysiology?What is the pathophysiology? What is laryngopharyngeal reflux?What is laryngopharyngeal reflux? What is the current diagnostic strategy?What is the current diagnostic strategy? What is a rational treatment strategy?What is a rational treatment strategy?

3. Gastroesophageal Reflux Disease Most common GI diagnosis for outpatient visitsMost common GI diagnosis for outpatient visits 14-20% of adults affected in US14-20% of adults affected in US Rising incidence of esophageal adenocarcinoma with 8000 incidence in 2004 (2-6 fold increase in 20 yrs)Rising incidence of esophageal adenocarcinoma with 8000 incidence in 2004 (2-6 fold increase in 20 yrs)

4. GERD: Montreal Definition A condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complicationsA condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications –> 2 heartburn episodes/week –Adversely affect an individual’s well being From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

5. GERD: Complications Kahrilas P. N Engl J Med 2008;359:1700-1707

6. Montreal Classification of GERD From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.

7. Montreal Classification of GERD

8. Pathogenesis of GERD Impaired Esophageal Clearance Decreased Salivation Impaired Tissue Resistance Decreased LES Resting Tone Delayed Gastric Emptying Bile Reflux Hiatal Hernia LES Duodenum

9. Paradox in GERD: Imperfect correlation between symptoms and endoscopic features Barrett’s esophagus Esophagitis Cases (%) 16/1000 (1.6%) 155/1000 (15.5%) % with GERD symptoms 40%33% From Ronikainen J et al. Gastroenterology 2005;129:1825-31.

10. Paradox in GERD: Imperfect correlation between symptoms and esophageal adenocarcinoma Typical GERD symptoms in only 60% of patients with cancer 453/589 patients with cancer had Barrett’s on pathology 23/63 with prior EGD had prior Barrett’s diagnosis Laryngopharyngeal reflux (LPR) symptoms more common than GERD symptoms in patients with cancer

11. Diagnosis

12. GERD Diagnostic Approach ACG Guidelines If history typical for uncomplicated GERD, initial trial of empiric therapy (including lifestyle modification) is appropriateIf history typical for uncomplicated GERD, initial trial of empiric therapy (including lifestyle modification) is appropriate DeVault KD et al. Am J Gastroenterol 2005;100:190-200.

13. Role of Endoscopy in Management of GERD: ASGE Guidelines Role of Endoscopy in Management of GERD: ASGE Guidelines GERD despite therapyGERD despite therapy DysphagiaDysphagia OdynophagiaOdynophagia GI bleeding/anemiaGI bleeding/anemia Mass, stricture or ulcer on imaging studyMass, stricture or ulcer on imaging study Recurrent symptoms after antireflux surgeryRecurrent symptoms after antireflux surgery From Gastrointest Endosc 2007;66:219-24.

14. Role of Endoscopy in Management of GERD: ASGE Guidelines Role of Endoscopy in Management of GERD: ASGE Guidelines Screening for Barrett’s:Screening for Barrett’s: –controversial with no clinically proven decrease in mortality with screening and surveillance programs Persistent vomitingPersistent vomiting Suspected extraesophageal GERDSuspected extraesophageal GERD From Gastrointest Endosc 2007;66:219-24.

15. Alternative Diagnosis in GERD Coronary artery diseaseCoronary artery disease GallstonesGallstones Gastric /esophageal cancerGastric /esophageal cancer Peptic ulcer diseasePeptic ulcer disease Esophageal motility disordersEsophageal motility disorders Pill induced esophagitisPill induced esophagitis Eosinophilic esophagitisEosinophilic esophagitis From Kahrilas PJ. N Engl J Med 2008;359:1700-7.

16. Physiological Testing Helpful in Selected Patients Identify subtle motility disorders (esophageal manometry) Demonstrate abnormal exposure to esophageal acid in absence of esophagitis (ambulatory pH monitoring) Quantifying exposure to acid and reflux events regardless of acidic content to assess correlations with symptoms (combined impedance-pH monitoring)

17. Laryngopharyngeal Reflux (LPR) LPR results when stomach contents reflux into the posterior pharynx and cause symptoms 4-10% of ENT visits are GERD related Significant association with hoarseness Difference with GERD –Injury threshold lower –Weak acids, weak bases or neutral substances can cause significant injury –Rarely have erosive esophagitis

18. LPR: Reflux Symptoms Index Within the last month, how did the following probems affect you? –Hoarseness or problem with your voice –Clearing your throat –Excess throat mucus or postnasal drip –Difficulty swallowing food, liquids, or pills –Coughing after you ate or after lying down Hammer. Dig Dis 2009;27:14-17

19. LPR: Reflux Symptoms Index –Breathing difficulties or choking episodes –Troublesome or annoying cough –Sensation of something sticking in your throat or a lump in your throat –Heartburn, chest pain, indigestion or stomach acid coming up Rate of 0 to 5 by patients for each question Score of >13 suggestive of LPR

20. Treatment

21. AGA GERD Practice Guidelines: Lifestyle Modifications Weight loss should be recommended in all patientsWeight loss should be recommended in all patients Lifestyle modifications should be tailored to individual circumstancesLifestyle modifications should be tailored to individual circumstances –Elevate HOB if nocturnal symptoms –Avoid precipitating foods Broad lifestyle changes for all (vs. selected) not recommendedBroad lifestyle changes for all (vs. selected) not recommended From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.

22. Weight Loss & GERD “Our current treatment goals should move away from allowing our patients to eat through their PPI therapy….” From Pandolfino J. Am J Gastroenterol 2008;103:1355-7.

23. AGA GERD Practice Guidelines: Medication PPIH2RAPlacebo Esophagitis83%52%8% Heartburn40%15% No major differences in efficacy among various PPIs Twice standard dose modestly effective but significant (NNT 25) Khan M et al. Cochrane Database Sys Rev 2007;2:CD003244

24. Patients in symptomatic remission (%) 100 80 60 40 20 0 0123456 Time after cessation of therapy (months Time after cessation of therapy (months) No mucosal breaks LA Grade A LA Grade B LA Grade C GERD Is a Chronic Condition Likely to Relapse From Lundell LR, et al. Gut. 1999;45:172-180 From Lundell LR, et al. Gut. 1999;45:172-180.

25. Adverse Events With Up to 1 Year of Esomeprazole Treatment Adverse Event % Patients (N=807) Headache10.3 Diarrhea9.4 Abdominal pain 9.3 Nausea6.1 Back pain 5.9 From Maton PN et al. Drug Safety 2001;24:625-35

26. Safety Profile of PPIs Recent epidemiologic associationsRecent epidemiologic associations –C. difficile 2x –Bacterial gastroenteritis 1.5x –Hip fracture 1.4x in age >50 –Plavix interaction…resolved… PregnancyPregnancy –Omeprazole category C but rest of PPI and H2RA are category B

27. GERD Treatment Algorithm: Initial Work Up LPR requires higher doses for 3 months

28. GERD Treatment Algorithm: Initial Work Up High recurrence rate when therapy discontinued

29. GERD Treatment Algorithm

30. Summary GERD currently classified by Montreal systemGERD currently classified by Montreal system –Esophageal –Extraesophageal (LPR) Diagnostic testingDiagnostic testing –Empiric treatment in uncomplicated cases with typical symptoms –Endoscopy

31. Summary Diagnostic sequence:Diagnostic sequence: –Endoscopy –Manometry –pH studies Role of screening for Barrett’s esophagus remains controversialRole of screening for Barrett’s esophagus remains controversial

32. Summary PPIs are cornerstone of therapyPPIs are cornerstone of therapy –Goal of therapy: lowest dose to control symptoms Lifestyle changes should be used selectivelyLifestyle changes should be used selectively Antireflux surgery reserved for nocturnal regurgitation & PPI intoleranceAntireflux surgery reserved for nocturnal regurgitation & PPI intolerance

33. Thank you!