Gastroesophageal Reflux Disease R. Jain

Gastroesophageal Reflux Disease Rajeev Jain, MD November 27, 2006 GERD Outline Definition  Epidemiology Pathophysiology Diagnosis Treatment  Management GERD 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. GERD Classification  Endoscopy – Erosive esophagitis  Los Angeles classification – Non-erosive reflux disease (NERD) or endoscopy negative reflux disease (ENRD)  Symptoms – Esophageal – Extra-esophageal LA Grade C LA Grade A LA Classification LA Grade D LA Grade B GERD GERD 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. GERD 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. GERD 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 GERD Mechanisms of Acid Reflux Defective Esophageal Clearance Ineffective peristalsis Reduced salivary secretion Reduced secretion from esophageal submucosal glands GERD GERD LES ‘dysfunction’ Inappropriate and prolonged transient relaxations Reduction in basal LES pressure/tone Substances that Decrease LES Pressure Hormones – – – – – Secretin Cholecystokinin Glucagon Somatostatin Progesterone GERD Foods – – – – Fat Chocolate Ethanol Peppermint Medications Medications that Decrease LES Pressure -adrenergic agonists Theophylline Anticholinergics Tricyclic antidepressants -adrenergic antagonists Diazepam Calcium channel blockers GERD GERD Hiatal Hernia May trap a reservoir of gastric contents above the diaphragm, increasing reflux May compromise LES function Increased Intra-abdominal Pressure Pregnancy Obesity Bending Straining Coughing Tight clothes GERD GERD Delayed Gastric Emptying 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 GERD Diagnostic Methods History Endoscopy Empiric therapy pH monitoring Radiology GERD 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. GERD Endoscopy 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 DeVault et al. Am J Gastroenterol 1999 GERD Advances in Endoscopy Ultra-thin endoscopes – Transnasal or oral – No sedation Magnification endoscopy Capsule endoscopy GERD Referral for Endoscopy  Chronic symptoms requiring continuous acidsuppression 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 GERD Empiric Therapy PPI 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. GERD pH Monitoring  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 GERD pH Monitoring 24 hr pH monitoring – single best test – 50-60% will have abnormalities – new device: BRAVO probe 48 hr monitoring GERD pH Monitoring GERD Barium Esophagram 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 1Dent et al. Gut 1999 The Pyramid of Diseases Associated with GERD 0% Misc Asthma Yes GERD ENT Prevalence of GERD Chest pain Need to investigate role of acid Non-erosive reflux disease Erosive esophagitis 100% No Richter. Am J Gastroenterol 2000 GERD Complications of GERD Esophageal –Barrett‟s esophagus –adenocarcinoma –stricture –ulceration –bleeding Extraesophageal –asthma –reflux laryngitis –vocal cord ulcers –subglottic stenosis –tracheal stenosis GERD Esophageal stricture Barrett’s Esophagus GERD Barrett’s Esophagus Clinical Significance GERD 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 The Risk of Esophageal Adenocarcinoma Increases with:  Frequency of reflux symptoms – OR 16.7 with > 3/wk GERD  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 Treatment GERD Treatment Options Lifestyle measures Pharmacological therapy –Initial therapy –Maintenance therapy Antireflux surgery Endoscopic techniques GERD 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 GERD Aggravating Dietary Factors Caffeinated products Peppermint Fatty foods Chocolate Spicy foods Citrus fruits and juices Tomato-based products Alcohol GERD Pharmacological Therapy Antacids Prokinetics Acid suppression –Histamine 2-receptor antagonists (H2RAs) –Proton pump inhibitors (PPIs) GERD Erosive Esophagitis – Initial Therapy  H2RA v placebo (4-8 wks of therapy) – 18 trials, 2134 patients – NNT 5 (95% CI, 3-22) Acid Suppression  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. GERD Erosive Esophagitis – Maintenance Therapy Acid Suppression 80% relapse after 6-12 months off therapy PPI v H2RA – 10 trials, 1583 patients, 24-52 wks of therapy – Relapse rate – NNT 2.5 (95% CI, 2.0-3.4) Donnellan C, et al. Cochrane Database Syst Rev.4:2004. 22% in PPI group 58% in H2RA group Antireflux Surgery – Procedures GERD 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 GERD et al. Am J Gastroenterol 1999 2Dent et al. Gut 1999 GERD Endoscopic Therapy Three FDA approved techniques –Stretta: radiofrequency therapy to LES –EndoCinch: endoscopic gastroplication –Enteryx: 8% ethylene vinyl alcohol copolymer GERD Endoscopic Gastroplication GERD Management Goals Provide complete relief from heartburn and other symptoms Heal underlying erosive esophagitis Treat or prevent complications Prevent recurrence GERD 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 ondemand therapy or step down Relapse is common GERD 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