Transcript GERD
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 A LA Grade B LA Grade C LA Grade D GERD LA Classification 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 GERD Substances that Decrease LES Pressure Hormones – – – – – Secretin Cholecystokinin Glucagon Somatostatin Progesterone Foods – – – – Fat Chocolate Ethanol Peppermint Medications GERD Medications that Decrease LES Pressure -adrenergic agonists Theophylline Anticholinergics Tricyclic antidepressants -adrenergic antagonists Diazepam Calcium channel blockers GERD Hiatal Hernia May trap a reservoir of gastric contents above the diaphragm, increasing reflux May compromise LES function GERD Increased Intra-abdominal Pressure Pregnancy Obesity Bending Straining Coughing Tight clothes 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 GERD The Pyramid of Diseases Associated with GERD 0% Yes Misc Asthma ENT Prevalence of GERD Need to investigate role of acid Chest pain 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 GERD 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 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 Acid Suppression Erosive 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. GERD Acid Suppression Erosive 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. Antireflux Surgery – Procedures GERD Antireflux Surgery – use and efficacy GERD 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 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