Gastroesophageal Reflux Disease (GERD) and Barrett s Esophagus (BE) Hashem El-Serag, M.D., M.P.H. Dan L. Duncan Professor of Medicine Chief, Gastroenterology and Hepatology Baylor College of Medicine Houston, Texas
Prevalence of GERD Population-based studies of at least 1-2 episodes per week El-Serag HB et al. Gut 2013
Erosive esophagitis (10-30%) Esophageal stricture with chronic erosive esophagitis (1-2%) Barrett s esophagus (1-12%) Esophageal adenocarcinoma with Barrett s esophagus (0.5% per year)
Barrett s is the Precursor of Adenocarcinoma Non-Dysplastic BE Low-Grade Dysplasia Adenocarcinoma High-Grade Dysplasia
Risk factors for Barrett s esophagus/adenocarcinoma Definite factor associated with increased risk Chronic GERD symptoms Older age Possible factors associated with increased risk Tobacco smoking Family history of BE or adenocarcinoma Male sex White race / Caucasian ethnicity
Variations along the Spectrum of GERD Erosive Esophagitis Barrett s Esophageal adenocarcinoma GERD Symptoms Men Western countries Whites Women Eastern countries Non- Whites
Obesity and Hazardous Waist
Transient LES relaxation (TLESR) Nucleus ambiguus Nucleus tractus solitarius Dorsal vagal nucleus Respiratory center Phrenic nucleus Phrenic nerve Vagus nerve Diaphragm LES Distension of proximal stomach
Pathophysiology of GERD oesophageal hypersensitivity impaired peristalsis hiatus hernia weak LOS Obesity TLOSRs increased pressure gradient acid pocket delayed gastric emptying excessive acid secretion
Large Amount of Visceral Abdominal Fat Increases Risk of Erosive Esophagitis and Barrett s Esophagus 173 BE cases, 343 colonoscopy controls and 172 endoscopy controls BE esp 3 cm twice as likely to be in the highest tertile of VAT to SAT ratio El-Serag HB et al. Gut 2013
Does it Make epidemiological Sense? Both obesity and GERD are increasing in parallel Abdominal obesity more likely Men more than women Caucasians more than African Americans
Helicobacter pylori (Hp) and the Risk of Esophageal Disease GERD symptoms: no consistent association with Hp or Hp treatment Esophageal erosions Weak inverse association with Hp BE and esophageal adenocarcinoma Consistent inverse association 25-50% lower likelihood of Hp in the presence of BE or EA
The Trends GERD GERD is a global problem that has high prevalence, and an increasing incidence GERD is a risk factor for Barrett s esophagus and esophageal adenocarcinoma Remarkable variations related region, gender and race Stories behind the Trends Increasing obesity Increasing chronic GERD Declining H. pylori
GERD Management
Lifestyle Changes Weight loss Elevation of head end of bed Small frequent meals Avoid eating before bedtime Over the Counter Meds Antacid Histamine receptor antagonists
Antisecretory Therapy of Esophagitis Therapeutic gain (% greater than placebo) 100 90 80 70 60 50 40 30 20 10 0 0 10 20 30 40 50 60 70 80 90 100 Placebo Response (%) Antacid qid Nizatidine 150mg bid Nizatidine 300mg bid Nizatidine 300mg bid Cimetidine 400mg bid Cimetidine 300mg qid Famotidine 20mg bid Ranitidine 150mg qid Ranitidine 150mg bid Omeprazole 20-40mg qd Lansoprazole 30mg qd Rabeprazole 20mg qd Pantoprazole 40mg qd Severe Disease severity Updated from: Kahrilas PJ, JAMA 1996;276:983 Mild
PPI efficacy for potential manifestations of GERD Estimates based on available RCT data Esophagitis healing Mild Severe Heartburn relief Esophagitis NERD Regurgitation relief Chest pain (50% relief) GERD (+ph) GERD (-ph) Chronic cough (improved) GERD (+ph) GERD (-ph) Hoarseness (improved) GERD (-) Placebo Therapeutic gain 0% 100% 25% 50% 75% Modified from Kahrilas PJ, et al. Gut 2012;61:1501
Which PPI should you use? Eenie, Meenie, Minie, Moe!!
PPIs may decrease the risk of esophageal cancer in patients with BE PPI use was associated with 70% reduction in risk of EAC and/or BE-HGD in patients with BE Prolonged PPIs use may have side effects Iron malabsorption Bone density loss (and fractures) Low magnesium Low B12 Increased C difficile? Pneumonia, spontaneous bacterial peritonitis Singh S et al. Gut 2013
Esophageal ph monitoring Catheter Capsule 5 cm LES 6 cm SCJ
Esophageal ph monitoring Esophageal acid exposure % of time with ph < 4 Temporal association between symptom episodes and reflux events symptom episodes 08 10 12 14 16 18 20 22 24 02 04 06 08
Esophageal ph monitoring identifies 4 groups These patients will not respond to any form of antireflux therapy ph monitoring excessive acid exposure positive symptom assocation Symptomatic GERD excessive acid exposure negative symptom association GERD, but symptoms not caused by acid reflux physiological acid exposure positive symptom association Symptomatic GERD Hypersensitive esophagus physiological acid exposure negative symptom association No GERD, functional
Impedance monitoring detects all reflux episodes, acid and nonacid reflux ph 7 4 1 Non-acid reflux 60 seconds ph 5.4
Perception Perception modulators tested in GERD: acupuncture citalopram
Effect of citalopram on symptoms in patients with hypersensitive esophagus N=75 Viazis N et al. Am J Gastroenterol 2011; 1662-1167
Barrett s Classification and Management Non-dysplastic IM Surveillance every 3 years Detect progression to dysplasia or cancer LGD (low-grade dysplasia) Surveillance every 6-12 months Detect progression to HGD or cancer HGD (high-grade dysplasia) Surveillance every 3 months EMR and ablation: options at select institutions Esophagectomy
Management Summary Treatment Life style changes Antacids Gaviscon Histamine receptor antagonists Life style modifications Acid suppression (PPI) BE PPI Ablation for BE with dysplasia Endoscopic resection for BE with dysplasia or early cancer