Download as PPT, PDF, TXT or read online from Scribd
Download as ppt, pdf, or txt
You are on page 1/ 83
Gastroesophageal
Reflux Disease Gary W. Falk, M.D., M.S. Professor of Medicine Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Department of Gastroenterology & Hepatology Taussig Cancer Center USA Disclosures • Grant support • Consultant • NIDDK • Astra Zeneca • NCI • Nycomed • Astra Zeneca • Olympus • Takeda • Ethicon • Given imaging Gastroesophageal Reflux Disease • What are current working definitions? • What is pathophysiology of GERD • What is the current diagnostic strategy? • What is a rational treatment strategy? Gastroesophageal Reflux Disease • What are current working definitions? • What is pathophysiology of GERD • What is the current diagnostic strategy? • What is a rational treatment strategy? GERD: Montreal Definition • A 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.
Montreal Classification of GERD
From Vakil N et al. Am J Gastroenterol 2006;101:1900-20.
Montreal GERD Consensus Conference: Atypical Symptoms • GERD & extraesophageal symptoms are associated • Extraesophageal symptoms rarely occur in absence of typical GERD symptoms • Extraesophageal symptoms typically multifactorial • Data substantiating beneficial effect of treatment weak From Vakil N et al. Am J Gastroenterol 2006;101:1900-20. Gastroesophageal Reflux Disease • What are current working definitions? • What is pathophysiology of GERD • What is the current diagnostic strategy? • What is a rational treatment strategy? Pathogenesis of GERD Decreased Salivation LES Impaired Tissue Resistance Impaired Esophageal Clearance Hiatal Hernia
Decreased LES Resting Tone
Duodenum
Delayed Gastric Emptying
Bile Reflux Different Reflux Mechanisms With Hiatal Hernia 100 Patients Without Hiatal Hernia (n = 10) Patients With Hiatal Hernia (n = 12) Reflux Episodes (%)
80 * 60
40 * † 20
0 TLESRs Low LESP Strain + Low LESP
*P<0.001. †P0.005.
From van Herwaarden et al. Gastroenterology. 2000;119:1439-1446.
Relationship Between BMI & TLESr
From Wu JC et al. Gastroenterology 2007;132:883-9.
Gastroesophageal Pressure Gradients & GERD
From de Vries DR et al. Am J Gastroenterol 2008;103:1349-54.
Duration of Esophageal Acid and Bile Exposure Affects GERD Severity Total Time pH <4 and Bilirubin 0.14 (%)
13 From Vaezi and Richter. Gastroenterology. 1996;111:1192-1199. Gastroesophageal Reflux Disease • What are current working definitions? • What is pathophysiology of GERD • What is the current diagnostic strategy? • What is a rational treatment strategy? GERD Diagnosis
• There is no single diagnostic gold standard for GERD GERD Diagnosis: Menu • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance Clarifying Patient Symptoms: Heartburn • Patients do not reliably interpret the word “heartburn” • For symptom evaluation, “a burning feeling rising from the stomach or lower chest up toward the neck” is more reliable than “heartburn” Carlsson et al. Scand J Gastroenterol. 1998;33:1023-1029. Alternative Diagnosis in GERD • Coronary artery disease • Gallstones • Gastric /esophageal cancer • Peptic ulcer disease • Esophageal motility disorders • Pill induced esophagitis • Eosinophilic esophagitis From Kahrilas PJ. N Engl J Med 2008;359:1700-7. GERD Diagnosis • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance GERD Diagnostic Approach ACG Guidelines
• If history typical for uncomplicated
GERD, initial trial of empiric therapy (including lifestyle modification) appropriate
From DeVault KD et al. Am J Gastroenterol 2005;100:190-200.
Meta-Analysis of PPI Trials as a Diagnostic Test for GERD Comparator Sensitivity Specificity (95% CI) (95% CI)
24-hr pH 0.78 0.54
(0.66-0.86) (0.44-0.65)
EGD 0.68 0.46
(0.56-0.79) (0.34-0.59)
From Numans ME et al. Ann Intern Med 2004;140:518-27.
Diagnostic Testing in GERD
• Avert misdiagnosis
• Identify complications
• Evaluate treatment failures
From Kahrilas PJ. N Engl J Med 2008;359:1700-7.
GERD Diagnosis • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance Barium Esophagram • Especially sensitive in evaluating dysphagia • In pre- and postoperative evaluations, identifies: • Normal or impaired esophageal emptying • Normal or impaired motility • Presence and type of hiatal hernia • Distal stricture or mucosal ring • Presence of gastroesophageal reflux • Main deficiency is insensitivity for erosive esophagitis & Barrett’s esophagus GERD Diagnosis • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance Role of Endoscopy in Management of GERD: ASGE Guidelines • GERD despite therapy • Dysphagia • Odynophagia • GI bleeding/anemia • Mass, stricture or ulcer on imaging study • Recurrent symptoms after antireflux surgery
From Gastrointest Endosc 2007;66:219-24.
Role of Endoscopy in Management of GERD: ASGE Guidelines
Reflux symptoms/mucosal breaks not visible in standard video endoscopy
Symptoms Do Not Predict the Presence of Erosive Esophagitis Heartburn Grade Mild Moderate Severe
32% 68% EE NERD (n = 316) (n = 677)
Prevalence of Erosive Esophagitis
From Venables et al. Scand J Gastroenterol. 1997;32:965-973.
LA Classification of Esophagitis
From Nayar DS et al. Gastrointest Endosc 2004;60:253-7.
Screening for Barrett’s Esophagus: Guidelines ACG AGA BSG 2008 2005 2005 GERD Individualize Maybe No symptoms
No GERD No No No symptoms Prevalence of Barrett’s Esophagus in VA GERD Patients at Initial EGD
• 378 GERD patients
• Barrett’s esophagus in 13.2% • LSBE-36% • SSBE-64%
From Westhoff B et al. Gastrointest Endosc 2005;61:226-31.
Barrett’s Esophagus On Repeat Endoscopy Within 5 Years According To Finding At Baseline: CORI Project
From Rodriguez S et al. Am J Gastroenterol 2008;103:1892-7.
Symptomatic GERD As A Risk Factor For Esophageal Adenocarcinoma Absence of heartburn, regurgitation or both > once weekly 100
80
60 % 40
20
0 Controls Esophageal Cardia Ca Esophageal Adenoca Squamous Cell Ca
From Lagergren J et al. NEJM 1999;340:825-31.
Prevalence of Barrett’s Esophagus in General Population of Sweden BE LSBE SSBE No BE (> 2cm) (< 2cm) Cases 16 5 11 984 (%) (1.6%) (0.5%) (1.1%) (98.4%) % with 56.3% 80.0% 45.5% 39.7% GERD symptoms % with 25.0% 60.0% 9.1% 15.4% esophagitis From Ronikainen J et al. Gastroenterology 2005;129:1825-31. Screening for Barrett’s Esophagus: Problems • Relatively few cases of esophageal adenocarcinoma • High prevalence of GERD • No prior GERD symptoms in 40% of adenocarcinoma patients • EGD & pathology diagnostic inconsistencies Screening for Barrett’s Esophagus: Problems
• Cost/risk of endoscopy • Lack of noninvasive alternatives • Lack of predictors to increase yield of screening • Unproven Screening Of Barrett’s Esophagus: Problems
• Risks of screening: • False positives • Patient anxiety • Unnecessary follow-up exams • Life insurance premiums Esophageal Capsule Endoscopy for The Diagnosis of Barrett’s Esophagus
From Sharma P et al. Am J Gastroenterol 2008;103:525-32.
Esophageal Capsule Endoscopy for The Diagnosis of Barrett’s Esophagus
From Sharma P et al. Am J Gastroenterol 2008;103:525-32.
Capsule Endoscopy for Barrett’s Esophagus Screening • Currently not cost effective based on modeling studies • Broad adoption as screening technology questionable • Unclear benefits compared to conventional EGD • Significant improvements in technology needed to alter assessments From Hur C. Clin Gastroenterol Hepatol 2007;5:307-9. GERD Diagnosis • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance AGA Esophageal GERD Practice Guidelines: Manometry • GERD despite therapy • Negative endoscopy • Goals: • LES location • Peristaltic function preoperatively • Detection of subtle motility abnormalities • High resolution manometry superior to conventional manometry for achalasia variants & distal esophageal spasm From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91. Contour Plot Topographic Analysis of Esophageal Motility in Achalasia.
GI Motility online (May 2006) | doi:10.1038/gimo22
GERD Diagnosis • Empiric trial • Barium esophagram • Endoscopy • Manometry • pH testing • Impedance AGA Esophageal GERD Practice Guidelines: Reflux Monitoring • Failure to respond to PPI • Negative EGD • No major manometric abnormality • Wireless pH studies superior for detection of abnormal acid exposure • Studies should be done off therapy From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91. 24-Hour Esophageal pH Monitoring • Most accurate test for measuring pattern, frequency, and duration of reflux episodes • Documents correlation between reflux episodes and symptoms • Sensitivity (77-100%) • Normal in 25% of esophagitis! • Specificity 85-100% • Most useful when diagnosis still unclear
Dent et al. Gut. 1999;44(suppl 2):S1-S16.
Impedance pH Catheter
From Smout A. Aliment Pharmacol Ther 2007;26(Suppl2):7-12.
Gastroesophageal Reflux Monitoring: The Porto Conference
• Combined pH and impedance:
• Best detection of all reflux events • Best evaluation of antireflux barrier
• Consider impedance pH for
persistent symptoms despite therapy
From Sifrim D et al. Gut 2004;53:1024-31.
AGA GERD Practice Guidelines: Diagnostic Testing Sequence
1. Endoscopy
2. Manometry
3. pH testing
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
Gastroesophageal Reflux Disease • What are current working definitions? • What is pathophysiology of GERD • What is the current diagnostic strategy? • What is a rational treatment strategy? AGA GERD Practice Guidelines: Lifestyle Modifications • Weight loss should be recommended in all patients (B) • Lifestyle modificatons should be tailored to individual circumstances (B) • Elevate HOB if nocturnal symptoms • Avoid precipitating foods • Broad lifestyle changes for all (vs. selected) not recommended From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91. Systematic Review of Effect of Lifestyle Intervention on GERD Parameters
From Kaltenbach T et al. Arch Intern Med 2006;166:965-71.
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.
Short Term (1-12 Week) Treatment of GERD Symptoms Or Endoscopy Negative GERD Treatment Heartburn 95% CI Remission RR Empiric Therapy Group PPI vs. placebo 0.37 0.32-0.44 H2RA vs. placebo 0.77 0.60-0.99 PPI vs. H2RA 0.66 0.60-0.73 Endoscopy Negative Reflux Group PPI vs. placebo 0.69 0.62-0.78 H2RA vs. placebo 0.84 0.74-0.95 PPI vs. H2RA 0.78 0.62-0.97 From Van Pinxteren B et al. Cochrane Database of Systematic Reviews 2006:3:CD002095. Esomeprazole Vs Other PPIs: Erosive Esophagitis Healing @ 8 Weeks
From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.
Esomeprazole Vs Other PPIs: GERD Symptom Relief @ 4 Weeks
From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.
Esomeprazole Vs Other PPIs: NNT For LA Grade Esophagitis
From Gralnek I et al. Clin Gastroenterol Hepatol 2006;4:1452-8.
GERD Is a Chronic Condition Likely to Relapse Patients in symptomatic remission (%)
100 No mucosal breaks
LA Grade A 80 LA Grade B
LA Grade C 60
40
20
0 0 1 2 3 4 5 6 Time after cessation of therapy (months) From Lundell LR, et al. Gut. 1999;45:172-180. Step Down Management of GERD in a Primary Care Setting
From Inadomi JM et al. Gastroenterology 2001;121:1095-1100.
Adverse Events With Up to 1 Year of Esomeprazole Treatment Adverse Event % Patients (N=807) Headache 10.3 Diarrhea 9.4 Abdominal pain 9.3 Nausea 6.1 Back pain 5.9
From Maton PN et al. Drug Safety 2001;24:625-35
Safety Profile of PPIs • Recent epidemiologic associations • C. difficile • Aspiration pneumonia • Hip fracture • Fundic gland polyps Long-term Acid Suppression and Risk of Hip Fracture Average Daily dose > 1.75 PPI < 1.75
> 1.75 H2RA < 1.75
0 1 2 3 4
Adjusted Odds Ratio
Study cohort included 79% women, mean age 77 yo, with high baseline risk for hip fracture Adjusted OR > 1 year on acid suppression. Yang Y-X, et al. JAMA. 296;2947-2953. AGA GERD Practice Guidelines: PPI Safety • Inadequate evidence to mandate: • Bone density studies • Calcium supplementation • H. pylori screening • Good medical practice to screen & treat the elderly for osteoporosis
From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91.
Pharmacologic Therapy of GERD: Not Recommended
• Nocturnal H2 blocker • Not supported by clinical endpoints • Rapid tachyphylaxis • Metoclopramide monotherapy or adjunctive therapy
From Kahrilas PJ. Gastroenterology 2008;135:1383-91.
Possible Causes For Failure of PPI Therapy • Compliance • Improper dosing time • Weakly acidic reflux • Visceral hypersensitivity • Psychologic comorbidities • Concomitant functional bowel disease • Delayed gastric emptying • Eosinophilic esophagitis From Fass R. Clin Gastroenterol Hepatol 2008;6:393-400. PPI Instructions By Primary Care Physicians
From Chey WD et al. Am J Gastroenterol 2005;100:1237-42.
Eosinophilic Esophagitis: Endoscopy
From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.
Histologic Features of Eosinophilic Esophagitis
From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.
Prevalence & Predictive Factors of Eosinophilic Esophagitis in Adults
• 33/222 (15%) with midesophageal
biopsies had EoE • 10/102 (9.8%) with normal EGD had EoE • 8/21 (38%) with endoscopic features of EoE had EoE!
From Prasad GA et al. Am J Gastroenterol 2007;102:2627-32.
Eosinophilic Esophagitis: Number of Biopsies Needed for Diagnosis With Different Diagnostic Criteria
From Gonsalves N et al. Gastrointest Endosc 2006;64:313-9.
RCT of Laparoscopic Antireflux Surgery Vs. Esomeprazole for GERD
N = 80. *Some patients reported more than 1 reason. Vakil et al. Am J Med. 2003;114:1-5. Risks of Antireflux Surgery
From Vakil N. Aliment Pharmacol Ther 2007;25:1365-72.
Annual Number of Antireflux Operations Performed in USA
From Finks JF et al. Surg Endosc 2006;20:1698-1701.
Systematic Review of Surgical Vs. Medical Therapy of Barrett’s Esophagus: Cancer Incidence
From Chang EY et al. Ann Surg 2007;246:11-21.
AGA GERD Practice Guidelines: Surgery • Patients with esophagitis who are well maintained on medical therapy have nothing to gain from surgery • Incur added risk • Should be advised against surgery • Patients likely to benefit from surgery: • PPI intolerance • Persistent symptoms especially regurgitation From Kahrilas PJ et al. Gastroenterology 2008;135:1383-91. Indications for Antireflux Surgery: A Systematic Review
• Requirements for surgery
• Experienced surgeon • Fit patient • Prior response to PPI
From Moayyedi P et al. Lancet 2006;367:2086-2100.
Summary • GERD currently classified by Montreal system • Esophageal • Extraesophageal • Diagnostic testing • Avert misdiagnosis • Identify complications • Evaluate treatment failures Summary • Diagnostic sequence: • Endoscopy • Manometry • pH studies • Role of screening for Barrett’s esophagus remains controversial Summary • PPIs are cornerstone of therapy • Avoid metoclopramide and nocturnal H2RAs • Goal of therapy: lowest dose to control symptoms • Lifestyle changes should be used selectively • Antireflux surgery reserved for nocturnal regurgitation & PPI intolerance
