GERD UPDATE
From Update 2005: Gastroenterology and Hepatology for the Primary Care Physician, sponsored by the David
Geffen School of Medicine at the University of California, Los Angeles
| THE SCOPE AND LIMITS OF PPIS: HEARTBURN AND BEYOND —Bennett E. Roth, MD, Professor of Medicine, and
Chief of Clinical Affairs, Division of Digestive Disease, David Geffen School of Medicine at the University of California,
Los Angeles
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| Gastroesophageal reflux disease (GERD): periodic relaxation of gastroesophageal sphincter occurs more frequently in
patients with pathologic reflux; hiatal hernias can exacerbate GERD by restricting gastric emptying and increasing pressure
in sphincter; other factors include suboptimal peristalsis, insufficient secretion of saliva and bicarbonate, incomplete
gastric emptying, and gastroparesis associated with diabetes; activities that can increase intra-abdominal pressure include
abdominal exercises (eg, sit-ups) and lifting weights
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| Presentation and treatment: heartburn most common presentation of GERD; history of heartburn and response to medications
often sufficient for diagnosis; medical treatment largely depends on severity and frequency of symptoms
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| Proton pump inhibitors (PPIs): have replaced histamine-2 (H2 ) blockers in management of chronic reflux disease; treatment
failures—partial response; relapse of symptoms; complete lack of response to treatment; partial response—
problems may include incomplete relief of symptoms, nocturnal breakthrough, and nonacidic (bland) regurgitation
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| Treatment errors: timing of dose—action of PPIs dependent on activation of proton pump (ie, ineffective when taken
before bed on empty stomach); patients generally advised to take PPI before breakfast (preferred) or dinner; effect of
other medications—drugs with anticholinergic activity (eg, tricyclic antidepressants, diazepam) affect gastric emptying;
some drugs (eg, theophylline) cause relaxation of lower esophageal sphincter (LES); some drugs that can injure
esophagus and make it more sensitive to reflux (pill-induced esophagitis) include tetracycline, quinidine, potassium, iron,
bisphosphonates, and, possibly, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin
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| Lifestyle issues: lying down after eating—full stomach induces secretion of acid; horizontal position allows reflux into
esophagus; diet—caffeine stimulates secretion of acid; fatty foods may delay gastric emptying; some foods (eg, chocolate,
onion, garlic) may relax LES; acidic foods can irritate inflamed or sensitive esophagus and aggravate symptoms of
reflux; carbonated beverages may exacerbate symptoms (likely related to increase in belching); obesity—although data
from pH studies do not implicate obesity as contributing factor, obese individuals tend to eat large quantities, eat often
(including before going to bed), and eat fatty foods, all of which contribute to reflux; associated with increased risk for
esophageal cancer; smoking—although not proven to exacerbate reflux, increases risk for esophageal cancer
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| Dosage: 25% to 30% of patients need increasing doses of PPIs; possible explanations include high production of acid and
compromised absorption of medication; bid schedule of standard dose superior to taking doubled dose once daily; additional
increases in dose have no significant effect; comparison of PPIs—all available PPIs have similar effects on secretion
of acid; differences in pharmacodynamics not clinically relevant; although erosive esophagitis may heal more
quickly with esomeprazole compared to other PPIs, end results do not differ
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| Nocturnal breakthrough: if unexplained by timing of evening meal, consider adding H2 -blocker at night; effect—
intragastric pH may drop significantly at night; H2 -blockers initially eliminate nighttime drop but effect diminishes after
2 wk; PPI dosing—if patient on once-daily dosing, add second dose before dinner; other options—consider elevating
head of bed, especially if patient complains of nonacidic reflux (high index of suspicion for large hiatal hernia or incompetent
sphincter)
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| Reflux-induced hypersensitivity: study found lower pain thresholds (as evoked by presence of acid in lower esophagus)
in patients with GERD; pain thresholds increased once reflux treated; chronic reflux may sensitize esophagus and increase
occurrence of chest pain and other symptoms
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| Relapse: stopping medication often results in return of symptoms; recent additions of medications (for other medical problems)
or marked weight gain may affect reflux
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| Step-down therapy: patients may switch from PPI to H2 -blockers once symptoms controlled, but H2 -blockers insufficient
to control symptoms in 50% of patients
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| Nonresponders: switching to different PPI unlikely to help; diagnosis of GERD possibly incorrect; endoscopic examination
of esophagus often normal in patients with uncomplicated reflux disease; patients with nonerosive esophageal reflux
disease (NERD) may have true reflux, functional disorders, or motor disorders (eg, achalasia)
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| Associated disorders: extraesophageal symptoms of reflux include pharyngitis, sinusitis, laryngitis, hoarseness, sensation
of globus or sticking, asthma, cough, sleep disturbances, and chest pain; 40% to 90% of patients with extraesophageal
symptoms do not have classic symptoms of reflux (ie, heartburn); pulmonary symptoms—microaspiration of acid
and/or pepsin may result in bronchospasm, laryngitis, or cough; bronchospasm may prevent acid from entering lungs;
chest pain—once cardiac causes excluded, GERD accounts for 40% to 50% of complaints; other symptoms of reflux
often not present; objective testing—endoscopy usually normal; pH testing may show reflux but cannot establish relation
to pain
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 | Therapeutic trials: sensitive and specific test for evaluating relationship between reflux and symptoms; high doses of
omeprazole (2 doses before breakfast; 1 dose before dinner) for 7 days; note—if symptoms intermittent, longer trial
often necessary; once patient responds to therapy, reduce dosage to maintenance level
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| Chronic cough: GERD third most common cause (after asthma and postnasal drip); cough increases intra-abdominal pressure,
potentially aggravating GERD symptoms; cough associated with GERD most often upright and nonproductive; most patients
do not complain of other symptoms that indicate GERD; increased index of suspicion—nonsmokers, who do not
take angiotensin-converting enzyme (ACE) inhibitors and have normal findings on chest radiograph (asthma present or
absent)
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| Laryngeal symptoms: chronic sore throat, hoarseness, or throat-clearing (patient may complain of sensation of globus);
55% of patients with unresponsive hoarseness have abnormal pH studies; as many as 60% of patients with chronic sore
throats have GERD; examination of larynx may reveal abnormalities (eg, swollen arytenoids or inflammation and
plaques on vocal cords), but findings not specific to GERD
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| Note about therapeutic trials: patients with extraesophageal symptoms respond more slowly than those with classic
symptoms of GERD (course of several months sometimes required to assess response)
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| Asthma: as many as 80% of patients with adult-onset asthma have GERD as contributing factor; adult-onset asthma and
refractory asthma increase index of suspicion for GERD
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| Sleep disorders: patients typically do not arouse with mild reflux; acid then remains in lower esophagus, causing injury
and sensitization; salivation and secretion of bicarbonate decrease during sleep, decreasing ability to neutralize acid; patients
swallow less frequently while asleep, reducing clearance of esophagus; reflux affects sleep, causing patients to experience
daytime somnolence and to have difficulty concentrating; relationship between sleep apnea and reflux not upheld in recent
study
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| Diagnostic testing: barium swallow—beneficial if achalasia or large hiatal hernia suspected; helps distinguish paraesophageal
hernia from sliding hernia; endoscopy—60% to 70% of patients have normal findings; esophageal
manometry—usually normal; valuable for assessing function of esophagus when considering surgery; pH testing—
75% to 80% accuracy; false negative results may occur because patients often alter diet and behavior during test; therapeutic
trial—most sensitive for assessing reflux, especially in patients with extraesophageal symptoms
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| SURGICAL THERAPY —Mary Maish, MD, Assistant Professor of Surgery, Division of Thoracic Surgery, and Surgical
Director, Center for Esophageal Disorders, David Geffen School of Medicine at the University of California, Los Angeles
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| GERD and cancer: medical therapy relieves many symptoms of GERD, but some may persist and cause disease to
progress to Barrett’s esophagus or cancer; incidence of esophageal adenocarcinoma (but not squamous cell carcinoma)
has increased since introduction of PPIs and H2 -blockers; although causal relationship not established, concern exists; antireflux
therapy—in spite of resolution of symptoms, disease may progress; PPIs do not address problem with LES
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| Pathophysiology: if LES does not sit beneath diaphragm, even with normal pressure, reflux may occur; sphincter may
weaken with exercise, obesity, age, and some systemic diseases; in patient with hiatal hernia, sphincter often displaced
into thoracic cavity where negative pressure prevents proper functioning
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| Diagnostic testing: important to confirm presence of reflux disease before surgery; barium swallow—allows visualization
of esophagus and stomach; identifies anatomic and functional problems that may affect decision for surgery or affect
technique; endoscopy—aids evaluation of mucosa (including collection of biopsies); allows dilation of strictures that
could affect surgical outcome; motility study—primarily for assessment of peristalsis (eg, distinguishing reflux from
achalasia); pH study—good sensitivity for identifying reflux; PPIs and H2 -blockers must be discontinued 2 wk before
study (return of symptoms provides additional evidence of reflux)
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| Surgical treatment: surgical candidates—patients with large hiatal hernias or uncontrolled extraesophageal symptoms
at risk for progression of disease; goal—to restore barrier to reflux; LES—adequate length (2 cm), of which 1 cm located
within abdomen, required for competence
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| Surgical approach: strictures or large (nonreducing) hiatal hernias may interfere with repositioning of esophagus and neces
sitate transthoracic approach; approach (thoracic or abdominal) not affected by fundoplication procedure; procedures—
Nissen fundoplication best option for patients with normal motility; gastric fundus wrapped around lower esophagus;
other procedures include Belsey fundoplication, Collis gastroplasty, and Toupet fundoplication
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| Laparoscopy: generally preferred over open procedures, unless patient has history of extensive surgery; general
procedure—5 ports (5-mm incisions) made for camera and instrumentation; bougie used to dilate esophagus before
wrapping fundus
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| Efficacy: restores barrier to reflux in 90% of patients (antisecretory medications no longer needed); prevents progression of
disease, including esophagitis (which can lead to functional problems) and Barrett’s esophagus (which increases risk for
esophageal adenocarcinoma)
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| ENDOSCOPIC THERAPY —Brennan Speigel, MD, Assistant Professor of Medicine, David Geffen School of Medicine at
the University of California, Los Angeles
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| Published studies: in last 2 yr, >60 review articles on endoscopic therapies published in peer-reviewed journals; other
published studies include 10 uncontrolled case series and only 1 fully published randomized controlled trial
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| Role in treatment of GERD: limitations of PPIs—barrier to reflux not restored; nighttime breakthrough of symptoms
may continue; rebound hypersecretion may occur when PPIs discontinued; 20% of patients do not respond;
fundoplication—invasive; up to 30% of patients experience bloating, nausea, and other symptoms after surgery; >50%
of patients require PPIs after surgery; high cost
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| Arguments against endoscopic therapy: PPIs effective for most patients (many function well with antacids alone); patients
typically continue to require PPIs after procedure; long-term data show efficacy of surgery in appropriate patients;
endoscopic procedures expensive
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| Stretta procedure: radiofrequency ablation; well-tolerated outpatient endoscopic procedure; takes 45 min and costs $1000 to
$3000; temperature-controlled radiofrequency energy delivered through catheter; balloon at end of catheter expands at
gastroesophageal junction; 4-mm needles around equator of balloon deploy energy into mucosa and superficial submucosa,
resulting in a series of circumferential burns above and below junction; scarring and shrinkage of junction creates
barrier to acid reflux; possible mechanisms—may increase thickness of LES; may injure nerves, reducing incidence of
transient LES relaxations (TLESRs; important mechanism in GERD); concern—damaged nerves may not transmit pain
sensations even when acid present (ie, reflux unaffected, but patient insensitive to pain); animal models—show improvements
in gastric emptying after procedure (mechanism unknown); contraindications—large hiatal hernia (patients
with hiatal hernias >2 cm ineligible for endoluminal therapies); severe erosive esophagitis
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| Study: randomized sham-controlled trial of 64 patients with GERD followed for 6 mo; patients in treatment group had
average increase in health-related quality of life score of 6 points (clinically significant); GERD symptoms improved
by 50% in 30% of treated patients; treatment did not affect daily use of PPIs or esophageal pH; conclusions—
although some improvements in symptoms occurred, function of gastroesophageal junction may remain compromised
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| Complications: rare, but include perforation (occasionally fatal)
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| Conclusions: although GERD may progress to Barrett’s esophagus, patient lifespan unaffected; according to American
College of Gastroenterology, treatment aim to control symptoms, not to save lives; procedures with risk for mortality
have limited role; more controlled studies and long-term data required before endoscopic therapies replace other methods
of treating GERD
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Educational Objectives
| The goal of this activity is to review important issues in the 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 pathophysiology of acid reflux and factors that contribute to GERD.
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| 2. Diagnose patients with GERD, including those presenting with extraesophageal symptoms.
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| 3. Medically treat patients with GERD and identify possible reasons for treatment failures.
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| 4. Discuss surgical therapies for patients with GERD and identify surgical candidates.
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| 5. Discuss role of endoscopic therapies for GERD.
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Discussed on This Program
Diazepam [Diastat, Diazepam Intensol, Valium]
Esomeprazole magnesium [Nexium]
Omeprazole [Prilosec, Prilosec OTC, Rapinex]
Quinidine gluconate
Tetracycline HCl [Sumycin 𣝢’, Sumycin 𣡜’, Sumycin Syrup])
Theophylline (several trade names)
Suggested Reading
Ahmed T, Vaezi MF: The role of pH monitoring in extraesophageal gastroesophageal reflux disease. Gastrointest Endosc
Clin N Am 15:319, 2005; Caos A, et al: Long-term prevention of erosive or ulcerative gastro-oesophageal reflux disease
relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5-year study in the United States. Aliment Pharmacol
Ther 22:193, 2005; Chen YK: Endoscopic approaches to the treatment of gastroesophageal reflux disease. Curr Opin
Gastroenterol 21:595, 2005; Darling G, Deschamps C: Technical controversies in fundoplication surgery. Thorac Surg
Clin 15:437, 2005; Johnson DA, et al: A comparison of esomeprazole and lansoprazole for control of intragastric pH in
patients with symptoms of gastro-oesophageal reflux disease. Aliment Pharmacol Ther 22:129, 2005; Katz PO: State of
the art: extraesophageal manifestations of gastroesophageal reflux disease. Rev Gastroenterol Disord 5:126, 2005; Oda
K, et al: Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor. Dig Dis Sci
50:1921, 2005; Pessaux P, et al: Laparoscopic antireflux surgery: five-year results and beyond in 1340 patients. Arch Surg
140:946, 2005; Pilotto A, et al: Recent advances in the treatment of GERD in the elderly: focus on proton pump inhibitors.
Int J Clin Pract 59:1204, 2004; Richter JE: New investigational therapies for gastroesophageal reflux disease. Thorac
Surg Clin 15:377, 2005; Rothstein RI, Dukowicz AC: Endoscopic therapy for gastroesophageal reflux disease. Surg
Clin North Am 85:949, 2005; Scholten T, et al: On-demand therapy with pantoprazole 20 mg as effective long-term management
of reflux disease in patients with mild GERD: The ORION Trial. Digestion 72:76, 2005; Talley NJ, Vakil N:
Guidelines for the management of dyspepsia. Am J Gastroenterol 100:2324, 2005; Watson TJ, Peters JH: Lower esophageal
sphincter injections for the treatment of gastroesophageal reflux disease. Thorac Surg Clin 15:405, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Drs. Roth, Maish, and Speigel were recorded in Beverly Hills, California, at Gastroenterology and Hepatology for
the Primary Care Physician, sponsored by Division of Digestive Diseases and the Office of Continuing Medical Education
of the David Geffen School of Medicine at the University of California, Los Angeles, and held February 19,
2005. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of
this program.
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