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Gastroesophageal Reflux Disease

Gastroesophageal Reflux Disease. Rajeev Jain, MD November 27, 2006. Outline. Definition Epidemiology Pathophysiology Diagnosis Treatment Management. Definition. No gold standard Montreal Definition

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Gastroesophageal Reflux Disease

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  1. Gastroesophageal Reflux Disease Rajeev Jain, MD November 27, 2006

  2. Outline • Definition • Epidemiology • Pathophysiology • Diagnosis • Treatment • Management

  3. Definition • No gold standard • Montreal Definition • “a condition which develops when the reflux of stomach contents causes troublesome symptoms and/or complications” Vakil N, et al. Am J Gastroenterol 101(8):1900-20.2006.

  4. Classification • Endoscopy • Erosive esophagitis • Los Angeles classification • Non-erosive reflux disease (NERD) or endoscopy negative reflux disease (ENRD) • Symptoms • Esophageal • Extra-esophageal

  5. LA Grade B LA Grade A LA Grade D LA Grade C LA Classification

  6. Epidemiology • Prevalence • Symptoms in western populations • 25% monthly • 12% weekly • 5% daily • Incidence • 1.5 – 3% develop weekly GERD per yr Moayyedi P, Axon ATR. Aliment Pharmacol Ther 22(S1):11-9.2005.

  7. Risk Factors • Demographic • Age & gender not a major difference • Lifestyle & Environmental • Obesity, EtOH, & tobacco have weak associations (OR 1.5 – 2.5) 1 • H. pylori has no impact 2 • Genetic • Higher concordance in mono- than dizygotic twins 1 1. Moayyedi P & Talley NJ. Lancet 367:2086-100.2006. 2. Raghunath AS, et al. Aliment Pharmacol Ther 20:733-44.2004.

  8. Pathophysiology • Primary mechanism – impaired function of the lower esophageal sphincter (LES) • In most patients with GERD, exposure of the esophagus to refluxate is greater than normal • In a minority of patients, exposure is within normal limits; in these patients, GERD may be due to decreased mucosal resistance to refluxate

  9. Mechanisms of Acid Reflux

  10. Ineffective peristalsis Reduced salivary secretion Reduced secretion from esophageal submucosal glands Defective Esophageal Clearance

  11. Inappropriate and prolonged transient relaxations Reduction in basal LES pressure/tone LES ‘dysfunction’

  12. Hormones Secretin Cholecystokinin Glucagon Somatostatin Progesterone Foods Fat Chocolate Ethanol Peppermint Medications Substances that Decrease LES Pressure

  13. -adrenergic agonists Theophylline Anticholinergics Tricyclic antidepressants -adrenergic antagonists Diazepam Calcium channel blockers Medications that Decrease LES Pressure

  14. May trap a reservoir of gastric contents above the diaphragm, increasing reflux May compromise LES function Hiatal Hernia

  15. Pregnancy Obesity Bending Straining Coughing Tight clothes Increased Intra-abdominal Pressure

  16. May result in an increase in the volume of gastric contents available for reflux into the esophagus Exact role in GERD remains to be clarified Delayed Gastric Emptying

  17. Diagnostic Methods • History • Endoscopy • Empiric therapy • pH monitoring • Radiology

  18. History • History taking is the primary diagnostic ‘tool’ for GERD • Heartburn – sensation of discomfort or burning behind the sternum rising up to the neck • Regurgitation – effortless return of gastric contents into the pharynx • Accuracy of symptoms when compared to endoscopy as gold standard • Sensitivity 30-76% • Specificity 45-68% Moayyedi P, et al. JAMA 295:1566-76.2006.

  19. Allows direct visualization of the esophageal mucosa and biopsy if necessary Presence and severity of erosive esophagitis Detection of complications such as stricture or Barrett’s esophagus Endoscopy DeVault et al. Am J Gastroenterol 1999

  20. Advances in Endoscopy • Ultra-thin endoscopes • Transnasal or oral • No sedation • Magnification endoscopy • Capsule endoscopy

  21. Referral for Endoscopy • Chronic symptoms requiring continuous acid-suppression therapy • Persistent suspected GERD symptoms that fail to respond to acid suppression • Any new GERD patient over the age of 40 • Warning signs: • Weight loss • Anemia or Bleeding • Dysphagia

  22. Empiric TherapyPPI Test • Logical as GERD is an acid-related disorder • Normal or high-dose PPI for 1-4 wks in the diagnosis of GERD (gold standard was 24 hr ambulatory pH study) • Sensitivity 78% (95% CI 66-86%) • Specificity 54% (95% CI 44-65%) Numans ME, et al. Ann Intern Med 140:518-27.2006.

  23. Allows investigation of: the amount and timing of reflux the correlation between reflux and symptoms the effect of therapy on reflux In general, most useful in: endoscopy-negative patients patients with chest pain or pulmonary/upper respiratory symptoms patients with refractory symptoms pH Monitoring

  24. pH Monitoring • 24 hr pH monitoring • single best test • 50-60% will have abnormalities • new device: • BRAVO probe • 48 hr monitoring

  25. pH Monitoring

  26. Now considered to be of very limited practical value in the diagnosis of GERD1 May be helpful in the detection of subtle strictures and hiatal hernias in patients with dysphagia May be helpful in identifying pathologies unrelated to GERD Barium Esophagram • 1Dent et al. Gut 1999

  27. The Pyramid of Diseases Associated with GERD 0% Yes Misc Asthma ENT Need to investigate role of acid Prevalence of GERD Chest pain Non-erosive reflux disease Erosive esophagitis 100% No Richter. Am J Gastroenterol 2000

  28. Esophageal Barrett’s esophagus adenocarcinoma stricture ulceration bleeding Extra-esophageal asthma reflux laryngitis vocal cord ulcers subglottic stenosis tracheal stenosis Complications of GERD

  29. Esophageal stricture

  30. Barrett’s Esophagus

  31. Barrett’s Esophagus Clinical Significance • Premalignant lesion for esophageal adenocarcinoma • Patients with Barrett’s esophagus may be 30–60 times more likely to develop this cancer than the general population1 • The reported incidence of Barrett’s esophagus is rising 1Lagergren et al. New Engl J Med 1999

  32. The Risk of Esophageal Adenocarcinoma Increases with: • Frequency of reflux symptoms • OR 16.7 with > 3/wk • Duration of reflux symptoms • OR 16.4 with greater than 20 yrs • Severity of reflux symptoms • OR 20 with most severe score Lagergren et al. N Engl J Med 1999

  33. Treatment

  34. Treatment Options • Lifestyle measures • Pharmacological therapy • Initial therapy • Maintenance therapy • Antireflux surgery • Endoscopic techniques

  35. Lifestyle Measures • Raise the head of the bed, or lie on left side • Decrease fat intake • Avoid certain foods • Avoid lying down for 3 hours after eating • Stop smoking • Lose weight if appropriate

  36. Caffeinated products Peppermint Fatty foods Chocolate Spicy foods Citrus fruits and juices Tomato-based products Alcohol Aggravating Dietary Factors

  37. Pharmacological Therapy • Antacids • Prokinetics • Acid suppression • Histamine 2-receptor antagonists (H2RAs) • Proton pump inhibitors (PPIs)

  38. Acid SuppressionErosive Esophagitis – Initial Therapy • H2RA v placebo (4-8 wks of therapy) • 18 trials, 2134 patients • NNT 5 (95% CI, 3-22) • PPI v placebo • 5 trials, 635 patients • NNT 2 (95% CI, 1.4-2.5) • PPI v H2RA • 26 trials, 4064 patients • NNT 3 (95% CI, 2.8-3.6) Khan M, et al. Cochrane Database Syst Rev.2006.

  39. Acid SuppressionErosive Esophagitis – Maintenance Therapy • 80% relapse after 6-12 months off therapy • PPI v H2RA • 10 trials, 1583 patients, 24-52 wks of therapy • Relapse rate • 22% in PPI group • 58% in H2RA group • NNT 2.5 (95% CI, 2.0-3.4) Donnellan C, et al. Cochrane Database Syst Rev.4:2004.

  40. Antireflux Surgery – Procedures

  41. Antireflux Surgery – use and efficacy • Antireflux surgery is an option as maintenance therapy for patients with well documented GERD1 • The efficacy of antireflux surgery is similar to that of chronic PPI therapy2 • The outcome of surgery is highly dependent on the skill and experience of the surgeon2 • 1DeVault et al. Am J Gastroenterol 1999 • 2Dent et al. Gut 1999

  42. Endoscopic Therapy • Three FDA approved techniques • Stretta: radiofrequency therapy to LES • EndoCinch: endoscopic gastroplication • Enteryx: 8% ethylene vinyl alcohol copolymer

  43. Endoscopic Gastroplication

  44. ManagementGoals • Provide complete relief from heartburn and other symptoms • Heal underlying erosive esophagitis • Treat or prevent complications • Prevent recurrence

  45. Management • Clinical diagnosis • Endoscopy in pts with alarm symptoms • PPI once daily taken 30 min before breakfast for 4-8 weeks • If symptoms resolve, consider on-demand therapy or step down • Relapse is common

  46. Management • If symptoms persist despite daily PPI • Nonadherence • Inadequate dosing or timing • Nocturnal acid breakthrough • Rare • Zollinger-Ellison syndrome • Drug resistance • Surgery – right patient and right surgeon

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