GERD
| UPDATE ON DIAGNOSIS AND MANAGEMENT OF GERD—Kenneth R. DeVault, MD, Professor of Medicine and
Chair, Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Jacksonville, FL
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| Diagnosis: definition of gastroesophageal reflux disease (GERD)—chronic symptoms or mucosal damage produced
by abnormal reflux of gastric contents into esophagus; symptom surveys suggest GERD occurs in 10% to 50% of population
and continues to increase (by conservative definition, 10% to 15% of population suffers from GERD); endoscopic
examination—in most patients with GERD, reveals normal esophagus or Barrett’s esophagus (patients with long-term
symptoms); esophagitis not commonly seen with endoscopy because most patients already on therapy; in community,
erosive esophagitis found in those with heartburn who are not on therapy; extraesophageal signs and symptoms—
laryngitis; sinusitis; other throat symptoms; asthma; chronic cough; interstitial fibrosis; noncardiac chest pain; dental
erosions; halitosis; patients referred to gastroenterologists with extraesophageal signs and symptoms who have not responded
to proton pump inhibitor (PPI) therapy
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| Pathogenesis of GERD: much of pathogenesis surrounds gastroesophageal (GE) junction; hiatal hernia important in
more severe forms of GERD; lower esophageal sphincter (LES) pressure low, infrequently without hiatal hernia; transient
LES relaxation more commonly problem; esophageal clearance problems (aging issue); tissue resistance (impaired
by alcohol); decreased salivation (aging factor); delayed gastric emptying (rare); bile reflux (rare); GERD considered
motility problem, not due to excess acid secretion
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| Lifestyle: not dominant factor in pathogenesis of erosive esophagitis, but potentially important in symptomatic GERD;
more research needed to determine how lifestyle factors affect patients; potential factors include smoking, and certain
foods, drinks, and medications
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| Incidence of GERD: not common in people <40 yr of age, but increases with age and peaks at 60 to 70 yr of age; disease
also increases in severity with age; study—12,000 patients with severe heartburn and patients with erosive esophagitis
(Los Angeles [LA] grade C and D); proportion of patients with severe erosive esophagitis increased with age (one-
third of 70-yr-old patients had LA grade C or D on endoscopy); findings do not correlate with practice because most patients
who come for endoscopy already on PPIs; take-home message—when patients present at older age, take into account
patients likely to have severe esophagitis or Barrett’s esophagus
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| Supraesophageal reflux disease: 2 mechanisms—aspiration; distention of esophagus using air, acid, or other substance
causes bronchoconstriction and bradycardia; aspiration—primary mechanism in majority of patients; potentially
produces laryngitis, ear, nose, and throat (ENT) symptoms, and pulmonary fibrosis (aggressively attack reflux in patients
with lung transplants); asthma—75% of patients with asthma report heartburn (pH monitoring provides similar results);
patients with asthma (or altered physiology, eg, lung transplant) have increase in negative intrathoracic pressure, leading
to acid reflux into chest and worsening pulmonary symptoms; difficult to demonstrate change in pulmonary function tests
with treatment of GERD, even when symptoms improve; chronic cough—study found that 86% of incidences of difficult-to-control
chronic cough potentially explained by postnasal drip (PND), asthma, and GERD; chronic cough clinic at
speakers’ hospital includes pH testing, methacholine challenge testing, amd trial of PND therapy (improvement seen with
this therapy); study—71 patients (history and physical examination; chest x-ray; methacholine challenge) given daily diary
to record symptoms; 48 of 71 patients proved to have another cause of chronic cough; 18 patients had inadequate
symptoms; patients who got PND therapy improved; 23 patients got pH testing (17 had positive test); 35% of those with
positive pH test responded; overall, low response rate in this study; speaker orders chest x-ray, methacholine challenge
test, and high-resolution computed tomography (CT; in some patients) before work-up for GERD
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| Stress: study of patients who had undergone major stress vs no major stress looked at severity of GERD symptoms and
found that overall, starting at time of major stress, symptoms more severe than in patients without stress; symptom severity
not back to baseline 4 mo out from stressor; stress increases frequency and severity of GERD symptoms (eg, after 9/
11 in New York and after hurricane Katrina), but does not cause GERD through change in motility; change in eating habits
with stress (mainly overeating) may produce GERD; stress probably does not increase GERD, but increases perception
of GERD; weight gain—study showed GERD symptoms (new and old) increased with weight gain; data show
waist circumference more important than true weight gain
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| More on diagnosis: empiric therapy reasonable practice; endoscopy—indicated in patients with alarm symptoms (dysphagia,
weight loss, and bleeding) and to rule out Barrett’s esophagus; questionable whether indicated in patients with refractory
symptoms; eosinophilic esophagitis—common in patients with difficult-to-understand dysphagia; endoscopic
examination shows linear furrows, mucosal rings, and white plaques; take biopsy from mid-esophagus and request absolute
eosinophil count (20 eosinophils per high-powered field required for diagnosis); potential reason for endoscopy in
patient with refractory symptoms; 24-hr pH monitoring—most accurate test for measuring acid; enables documentation
of symptom correlation; useful when diagnosis unclear; limited by discomfort; algorithm for refractory GERD—
endoscopy, biopsy, and leave catheter-free pH monitoring system behind (ideally off therapy); data show potential utility
while on PPI for patients with refractory GERD; impedance monitoring—transnasal device (difficult); allows analysis
of acid and nonacid reflux events; clinical importance of nonacid reflux unclear; if doing transnasal intraesophageal pH
monitoring on therapy, speaker suggests having gastric and esophageal monitoring port to allow correlation of events in
stomach and esophagus; barium esophagography—provides minimal information in reflux, except for work-up of
large hiatal hernia; good test for dysphagia
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| Treatment: lifestyle modifications—recognition and modification of eating trigger foods, losing weight, elevating head
of bed, and avoiding eating just before bedtime; rarely effective as monotherapy; PPIs—control acid reflux quickly and
better than H2 -blockers or placebo; data show that in 2 wk, 66% of patients have healed esophagitis and control of symptoms
(more severe patients take longer); 10% to 25% of patients remain in remission off therapy for 6 mo; PPIs most effective
drugs for maintenance therapy; initial grade of esophagitis predicts maintenance of healed erosive esophagitis;
“on-demand” therapy—short course (1 or 2 wk) when symptoms occur; study of prn use of esomeprazole vs placebo in
patients with nonerosive reflux disease showed 85% of patients taking prn PPIs willing to continue this regimen; approved
in Europe but not in United States; long-term use of PPIs—typically considered safe; study that showed increased
odds ratio (OR) for community acquired pneumonia criticized; study showed minor increase in OR for hip
fracture with long-term use of PPIs
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| Surgery: data show predictors of successful surgery include young patient, with heartburn and regurgitation, and successful
on acid-suppression therapy; avoid surgery in older patients, those with atypical symptoms, and those who did not improve
on PPIs; similar outcomes seen after 5 yr in patients randomized to surgery or titrated PPIs; outcomes at 7 yr
showed statistical superiority in favor of surgery, but consensus that surgery and PPIs equivalent long-term therapy;
complications—operation performed on patient without documented reflux disease (only symptoms); dysphagia (1 in
10 patients); bloating and gas problems (≈60% of patients); diarrhea (mainly due to dumping syndrome; well controlled);
recurrent reflux; indication for surgery—pulmonary damage from GERD
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| LONG-TERM MANAGEMENT OF GERD—Joel E. Richter, MD, Richard L. Evans Professor of Medicine, and Chair,
Department of Medicine, Section of Gastroenterology, Temple University School of Medicine, Philadelphia, PA
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| Lifestyle modifications: tobacco, alcohol, chocolate, and high-fat meals decrease LES pressure, but no evidence of
treatment efficacy; elevation of head of bed and left lateral decubitus position useful for patients with nocturnal symptoms;
weight loss improves acid reflux profiles and symptoms; study—50,000 nurses followed for 20 yr showed marked
increase in GERD symptoms with increase in body mass index (BMI); patients who lost weight or had low BMI had
fewer reflux symptoms
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| Burden of GERD treatment: approximately $14 billion in expenditures for GERD in United States in 2004 (60%
spent on drug therapy)
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| Predictors of esophageal mucosal improvement: Veterans Affairs (VA) study—showed factors most important
in predicting improvement included PPIs and H2 -blockers; in patients with esophagitis who are not doing well, think
about nonsteroidal anti-inflammatory drug (NSAID) use or abuse; regardless of regimen, most patients do well (in 8-yr
follow-up, only ≈11% of patients worsened)
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| PPI efficacy: Cochrane reviews—for healing esophagitis, in PPI vs placebo, number needed to treat (NNT) 2; in PPI vs
H2 -blockers, NNT 3; PPIs superior to placebo and H2 -blockers in endoscopy-negative and undiagnosed GERD; for remission
of esophagitis of 6 to 12 mo, NNT 2.5 for PPIs; meta-analysis—10 studies; ≈15,000 patients; looked at efficacy
of esomeprazole vs other PPIs in erosive esophagitis (LA grades A, B, C, and D); average overall risk reduction (ARR)
4% (NNT ≈25, with PPIs equal in effectiveness); ARR 14% in LA grade C and 8% in LA grade D
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| PPIs and complications: PPIs effective in treating some complications of GERD; peptic strictures—study showed
resolution of esophagitis and strictures 3 to 6 mo after treatment with PPIs and esophageal dilation in patients with dysphagia,
peptic esophagitis and early stricture disease; study (2006) looking at incidence of peptic strictures in United Kingdom
(UK) showed decrease of ≈50% from 1994 to 2000 (correlates with increase in use of PPIs); Schatzki’s rings—not
congenital; study of 30 patients with no obvious esophagitis randomized to PPI and dilation vs placebo and dilation; followed
over 2 yr; majority of patients treated with placebo relapsed; speaker treats patients with Schatzki’s rings with PPI
and dilation, and they seldom need further dilation
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| Atypical manifestations of GERD: noncardiac chest pain (NCCP)—acid reflux determined etiology in many patients
with NCCP; meta-analysis showed NNT 3 (PPIs); asthma—data do not support efficacy of antireflux therapy for
pulmonary and laryngeal problems associated with GERD; Cochrane database concluded that “In asthmatic subjects with
GERD, there is no overall improvement in asthma following treatment for GERD. Subgroups of patients may gain benefit,
but it appears difficult to predict responders.”
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| Complications of PPIs: fundic polyps—question of malignant potential; study showed risk for fundic polyps in patients
on PPIs increased over time (OR 3.8 at >5 yr), but progression to malignancy rare; community acquired pneumonia
(CAP)—study showed increase in patients on PPIs and H2 -blockers, with significant dose response for PPIs; enteric
infections—study results similar to those for CAP; increase related to decreased acid and double dosing; speaker proponent
of giving as little PPI as necessary and potentially on prn basis; hip fracture—study showed risk linked to duration
of PPI therapy; increased OR dose-dependent; reason for finding unknown; take-home message—long-term use of PPIs
associated with some risk
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| New drug therapies: goal to develop therapy to inhibit or decrease transient LES relaxation (TLESR); total ablation
problematic because patient then unable to belch, vent, and might have difficulty swallowing; baclofen—study showed
decrease in episodes of TLESR and amount of postprandial reflux; side-effect profile problematic, eg, decrease in seizure
threshold; speaker starts with 5 mg and increases to 20 mg bid to tid; used in patients with nonacid reflux
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| Endoscopic treatment: good concept; patients included in studies were those easiest to treat with PPIs, ie, those with
frequent heartburn who got better on PPIs or H2 -blockers, no or mild esophagitis, and no or small hiatal hernia; Stretta
procedure and endoscopic full-thickness plication still under investigation; endoscopic full-thickness plication—study
showed that at 3 mo, in patients who got true plication (vs sham), GERD questionnaires improved, PPI use decreased significantly,
amount of acid exposure decreased significantly (from 10% to 7%), but LES pressure did not change; no evidence
of healing of esophagitis; complications included one pneumomediastinum; problems with therapies—
durability; deaths (5); American Gastroenterological Association (AGA) position statement—“current data suggest
that there are no definite indications for endoscopic therapy for GERD at this time”
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| Laparoscopic antireflux surgery: principles—reduce hiatal hernia; restore intra-abdominal esophagus; approximate
diaphragmatic crurae; perform fundoplication; all important in combination because they increase LES pressure and
interfere in LES relaxation; abstract showed antireflux surgery peaked in 2000 and decreased by 27% in 2003;
indications—patients with typical or atypical GERD symptoms who respond to PPIs but want surgery (desire for permanent
cure; patient preference; intolerance to PPIs); failed medical therapy because of persistent volume reflux (heartburn
better with PPIs, but taste of food remains after eating or when lying down; low valve pressure; hiatal hernia;
delayed gastric emptying in many); recurrent peptic strictures in young patients; patients with respiratory complications;
study—large group of patients randomized to omeprazole or open Nissen fundoplication; 7-yr data show surgery superior
to medical therapy; complications included dysphagia (≈10%); increased rectal flatus (50%-60%); impairment in
ability to belch (15%- 29%); variable data on antireflux surgery in patients with strictures; little data from procedure done
in community; study of laparoscopic fundoplication in United States community (2003)—151 patients, of whom 80
responded to questionnaire; 28 surgeons in 17 hospitals; mean follow-up 20 mo; 61% satisfied with operation; 32% back
on medication; 67% had new complaints; 11% required esophageal dilation for dysphagia; 7% required another operation;
study (VA system)—>3000 patients; 30-day follow-up; 45 procedures per hospital; redo-fundoplication rate 2.5%;
death 0.8%; approximately one-half of patients back on medication at 5-yr follow-up; durability—repair can break
down, or wear out; contributing factors include isometric exercise, heavy lifting, weight gain, and eating disorders; learning
curve for surgeon performing procedure; primary patterns of failure—fundoplication herniates into chest (most
common; presents with dysphagia and chest pain); slipped Nissen fundoplication (second most common); paraesophageal
hernia (presents with dysphagia and chest pain, not heartburn); fundoplication placed too low (patients present with
abdominal pain and chest pain, not heartburn); unrecognized esophageal shortening common denominator in all of these;
operation should be performed by highly skilled surgeons
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Suggested Reading
Artis J et al: Empirical therapy for symptomatic gastroesophageal reflux isease in primary are: determinants of fficacy.
Digestion 76:207, 2007; Bajbouj M et al: Combined pH-metry/impedance monitoring increases the diagnostic yield in
patients with atypical gastroesophageal reflux symptoms. Digestion 76:223, 2007; Chandra KM, Harding SM:
Therapy Insight: treatment of gastroesophageal reflux in adults with chronic cough. Nat Clin Pract Gastroenterol Hepatol
4:604, 2007; Garcia Rodriguez LA et al: Use of acid-suppressing drugs and the risk of bacterial gastroenteritis.
Clin Gastroenterol Hepatol 5:1418, 2007; Gulmez SE et al: Use of proton pump inhibitors and the risk of community-
acquired pneumonia: a population-based case-control study. Arch Intern Med 14:950, 2007; Hauben M et al: Association
between gastric acid suppressants and Clostridium Difficile colitis and community-acquired pneumonia: analysis using
pharmacovigilance tools. Int J Infect Dis 11:417, 2007; Katz Z: Medical therapy for gastroesophageal reflux diseases in
2007. Rev Gastroenterol Disord 7:193, 2007; Kelly JJ et al: Laparoscopic Nissen fundoplication: clinical outcomes at
10 years. J Am Coll Surg 205:570, 2007; Leonard J et al: Systematic review of the risk of enteric infection inpatients
taking acid suppression. Am J Gastroenterol 102:2047, 2007; Manning BJ et al: Laparoscopic Nissen fundoplication:
predicting outcome from peri-operative evaluation. Ir J Med Sci 175:55, 2006; Mumad RR, Pascricha PJ: Review:
om-demand maintenance therapy with proton pump inhibitors is as effective as continuous therapy for nonerosive GERD.
ACP J Club 147:69, 2007; Tonini M et al: Potential Options to Optimize Therapy of Gastroesophageal Reflux Disease
with Proton Pump Inhibitors. Digestion 76:171, 2007; Tygat GN et al: New algorithm for the treatment of gastro-oesophageal
reflux disease. Aliment Pharmacol Ther 27:249, 2008.
Educational Objectives
| The goal of this program is to improve diagnosis and management of gastroesophageal reflux disease (GERD). After
hearing and assimilating this program, the clinician will be better able to:
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 | 1. Discuss the incidence of GERD.
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| 2. Describe the extraesophageal signs and symptoms of GERD.
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| 3. Explain how to diagnose GERD.
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| 4. Describe treatment options for GERD.
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| 5. Discuss potential complications associated with treatment options for GERD.
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Faculty Disclosure
In adherence with ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal
conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in
health care and not a proprietary business or commercial interest. For this program, the following has been disclosed:
Dr. DeVault is a consultant for AstraZeneca and TAP Pharmaceuticals. Dr. Richter and the planning committee reported
nothing to disclose.
Acknowledgements
Dr. DeVault was recorded at the 17th Annual GI Symposium, held November 3, 2007, in New Brunswick, NJ, and
sponsored by the University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Division
of Gastroenterology/Hepatology. Dr. Richter was recorded at the 8th Annual Update in Gastroenterology, held
October 26-28, 2007, in La Quinta, CA, and sponsored by Cedars-Sinai Medical Center, Division of Gastroenterology.
The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of
this program.
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