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Clinical Applications

Nicholas Shaheen, MD, MPH; David F. Ransohoff, MD

JAMA. 2002;287:1982-1986.

ABSTRACT
Gastroesophageal reflux disease (GERD), a condition commonly encountered in the primary care setting, is a risk factor for adenocarcinoma of the esophagus. Despite the ubiquity of the complaint, considerable uncertainty exists with respect to several basic questions, including when to perform endoscopy in patients with chronic reflux symptoms and how to address the cancer risk associated with GERD. These clinical vignettes illustrate common clinical questions encountered in caring for patients with GERD, especially as they relate to the issue of cancer risk. Applying data reviewed in the companion article, we propose practical answers to common clinical situations regarding care of patients with reflux. We also present an algorithm for treatment of patients with chronic GERD symptoms.

INTRODUCTION

Jump to Section  • Top  • Introduction  • Patient 1  • Patient 2  • Patient 3  • Conclusions  • Author information  • References

Gastroesophageal reflux disease (GERD) is one of the most common problems confronted by primary care physicians.¹ The most common symptom of GERD is heartburn, but GERD may present with a variety of symptoms. Appropriate recognition and management of GERD relieves symptoms, increases quality of life, and forestalls complications of reflux disease, such as stricture formation.^2-7 A major concern of patients and physicians is the increased risk of esophageal adenocarcinoma associated with reflux symptoms.^8-10

The following cases illustrate common questions faced in caring for patients with GERD. The suggested treatment of the patients demonstrates one—but often not the only—approach to the individual's care. We have attempted to identify alternative diagnostic or therapeutic options that could be used when appropriate.

Patient 1

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A 36-year-old Asian woman complains of 8 months of intermittent rising substernal chest burning, occurring approximately 3 times a week, worse at night and after large meals. Throughout the last 3 months, she has been taking nonprescription ranitidine and initially had good symptom relief, but now she is experiencing substantial periods of discomfort. She has been reading about reflux on the Internet and is especially concerned regarding the cancer risk with reflux.

Does This Patient Have Reflux?

This individual displays many of the classic features of uncomplicated gastroesophageal reflux. The description of her discomfort, the associated exacerbating factors, and the partial response of symptoms to H₂ receptor antagonists (H₂RAs) suggest that reflux disease is the most likely diagnosis.

Given the prevalence of reflux in the population^{1, 11-12} and the typical nature of this patient's symptoms, further testing to confirm this diagnosis is not recommended.¹³ Instead, initiation of appropriate therapy can be used as a diagnostic test and a therapeutic measure.^14-15 If this patient responds to an empirical trial of proton pump inhibitors with resolution of her symptoms, the diagnosis is confirmed and no further testing is necessary. In typical reflux presentations such as this, further diagnostic testing is reserved for patients demonstrating so-called alarm symptoms, such as dysphagia, bleeding, anemia, and weight loss,¹⁶ as well as those who do not respond as expected to empirical therapy.

Should I Recommend Endoscopy to Rule Out Barrett Esophagus or Adenocarcinoma of the Esophagus?

Barrett esophagus is an endoscopically detectable metaplastic change of the lining of the esophagus so that some portion is lined with specialized columnar epithelium instead of the normal squamous epithelium (Figure 1). With respect to this patient's cancer risk, several demographic and symptomatic features argue against further invasive measures to rule out esophageal adenocarcinoma or Barrett esophagus. Although symptom severity is not a reliable predictor of the presence of Barrett esophagus, the chronicity of symptoms is.¹⁷ Individuals who are symptomatic for more than 5 years are at increased risk compared with the general public and those with symptoms of shorter duration. Additionally, epidemiologic studies show that Barrett esophagus and adenocarcinoma of the esophagus are diseases most prevalent in white men.¹⁸ With respect to esophageal adenocarcinoma, the incidence in men is 4 times that in women and is approximately 8 times as likely in whites as in other races. The incidence of esophageal adenocarcinoma increases markedly with age, making a 36-year-old unlikely to be affected. Finally, and most important, the absolute risk of adenocarcinoma in patients with uncomplicated reflux symptoms is low, and screening endoscopy has not been demonstrated to further decrease this risk. For these reasons, the yield of endoscopic screening in this patient is low and may be outweighed by the small risk of complication from upper endoscopy.^19-22

View larger version (37K): [in this window] [in a new window] Figure 1. Endoscopic Examination of Barrett Esophagus The endoscope is in the upper esophagus, looking downward to the lower esophageal sphincter. The tongues of darker salmon-colored mucosa projecting toward the endoscope represent a typical appearance of Barrett esophagus.

Appropriate treatment for this patient consists of counseling about the pathophysiology of reflux and a review of conservative measures sometimes helpful in avoiding reflux symptoms. These conservative measures, listed in BOX 1, may decrease distal esophageal acid exposures.^23-25 Additionally, adding a pharmacological intervention would be reasonable. Because the patient has had an incomplete symptomatic response to H₂RAs, therapy with a proton pump inhibitor could be initiated at standard daily dosing. Alternatively, in this patient, increasing the dose of H₂RA as an initial step is also acceptable. A discussion of the risk factors and demographics of esophageal adenocarcinoma and the risks and benefits of endoscopic screening should help the patient understand why this measure is not recommended in her situation. Finally, close follow-up to ensure response of symptoms to therapy and to allow the tapering of pharmacological therapy to the lowest dose at which the patient is symptom free should be arranged. Figure 2 demonstrates a suggested algorithm for the use of endoscopy and pharmacological therapy for patients with classic reflux symptoms. This figure demonstrates a step-down approach to pharmacological therapy, starting with a proton pump inhibitor and decreasing acid suppression to the lowest dosage of either proton pump inhibitor or, preferably, H₂RA that keeps the subject symptom free. Step-up approaches, starting with H₂RAs and intensifying therapy as necessary, are also acceptable in patients who have not tried H₂RA before evaluation.

View larger version (64K): [in this window] [in a new window] Figure 2. Algorithm for Initial Evaluation and Treatment of Patients With Gastroesophageal Reflux Disease Symptoms This diagram illustrates a step-down approach, initiating therapy with a proton pump inhibitor, as might be used for patient 1. Initial therapy with H2 receptor antagonists in patients not previously receiving these medications is also acceptable (a step-up approach).

Box 1. Conservative Measures in Reflux Disease Elevate the head of the bed on 15-cm blocks. Avoid eating within 4 hours before sleep. Avoid eating large meals and chocolate. Avoid consuming caffeinated products. Avoid peppermint. Avoid fatty foods. Quit smoking. Lose weight if overweight. RETURN TO TEXT

Patient 2

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A 65-year-old white man visits your office for follow-up for chronic reflux symptoms. He had an endoscopy 3 years ago, at which time 5 cm of Barrett mucosa without dysplasia was discovered. He otherwise is well, with no weight loss or dysphagia. He has been receiving therapy with a proton pump inhibitor daily for the last 6 years and is worried about the long-term effects of these medications on his system.

Are There Adverse Effects of Long-term Proton Pump Inhibition?

When omeprazole, the first proton pump inhibitor, was introduced into the US market, there was concern that the potency of the drug and the increase in serum gastrin levels associated with its use might lead to the development of gastrinomas. Now, despite the ubiquitous nature of these agents and more than 15 years of experience with them, no increased cancer risk associated with proton pump inhibitor use has been demonstrated. The drugs appear to be safe, even when taken long-term and at doses higher than those initially approved for the healing of erosive esophagitis.²⁶ Routine monitoring of serum gastrin levels is not recommended and may, in fact, cause the physician and patient some distress if they are checked, because they are often elevated in those undergoing therapy.^27-29

What Is the Appropriate Follow-up for This Patient's Barrett Esophagus?

Because of the dearth of data supporting surveillance endoscopy in Barrett esophagus, any consideration of enrolling a patient in an endoscopic surveillance program should be preceded by a frank discussion of the risks and benefits of surveillance. At the end of this discussion, the patient should understand the rationale behind endoscopic surveillance (to detect cancer in a preclinical and potentially more curable stage), the absolute risk of esophageal adenocarcinoma (approximately 1 in 200-300 patient-years),^30-32 the risk of serial upper endoscopy (1 major complication in approximately 1000 procedures),¹⁹ the treatment options if dysplasia occurs within the Barrett esophagus (esophagectomy, closer surveillance to detect early cancer,³³ and enrollment in an experimental ablative protocol),³⁴ and the lack of endoscopic-surveillance evidence showing a survival benefit in those with Barrett esophagus. If after this discussion the patient opts for enrollment in an endoscopic surveillance program, referral to a gastroenterologist or surgeon for upper endoscopy with biopsies is warranted.³⁴

Patient 3

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A 36-year-old man presents for follow-up of 2 years of reflux disease. His condition, made manifest by substernal chest burning, is well controlled by twice-daily proton pump inhibitors, for which he pays out of pocket. He wonders how long he will have to take these medications and whether there are other treatment options for him. He has heard that cancer can be associated with reflux, and his neighbor recently underwent a surgical antireflux procedure. He wonders if this procedure would protect him from cancer.

What Is the Natural History of Treated and Untreated Reflux Disease?

Longitudinal studies of reflux disease demonstrate that, for most patients, the condition is chronic.^{26, 35-36} Furthermore, in most of those who develop erosive esophagitis, maintenance therapy will be necessary after healing to avoid recurrence of esophagitis.^{26, 37} However, many patients requiring proton pump inhibitors to heal mucosal disease can continue taking H₂RAs. Therefore, in individuals with erosive disease, an 8-week course of proton pump inhibitors to heal mucosal lesions may be followed by an attempt to continue giving the patient H₂RAs. In reflux patients who again become symptomatic while receiving H₂RAs, long-term maintenance therapy with proton pump inhibitors may be initiated. In addition to good relief of symptoms and high healing rates of erosive esophagitis, proton pump inhibitor treatment effectively delays the development of peptic strictures in patients with a history of strictures.^{7, 38} However, medical therapy has not been demonstrated to avert the development of Barrett esophagus or decrease the risk of cancer in individuals with long-term reflux symptoms.

Does a Surgical Antireflux Procedure Decrease the Risk of Cancer in Individuals With Long-term Reflux Symptoms?

Although a surgical antireflux procedure is a safe and effective treatment for GERD in appropriately selected patients, it should not be pursued to decrease the risk of cancer in patients with reflux symptoms. Although the risk of mortality from a laparoscopic antireflux procedure is low (approximately 0.2%),^39-41 it is still likely higher than the lifetime risk of death from adenocarcinoma in patients with chronic reflux disease because of the rareness of this cancer in the GERD population. Also, although it is intuitive to expect that decreasing exposure of the esophagus to gastric acid might halt the development of neoplasia, no data suggest that surgical antireflux procedures decrease the already low risk of esophageal adenocarcinoma among patients with GERD. The limited data that do exist suggest that surgical antireflux procedures do not decrease the cancer risk in subjects with GERD.^{8, 42-43} Whether surgical antireflux procedures decrease the incidence of cancer in the subgroup with Barrett esophagus is a debated and unsettled issue. However, for patients with typical reflux symptoms, cancer prevention should not be the impetus for a surgical antireflux procedure.

CONCLUSIONS

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Despite the commonness of GERD, it is often undiagnosed or undertreated in practice. In patients with classic substernal chest burning, further diagnostic testing is usually unnecessary, and empiric therapy with antisecretory medications may be instituted. Testing is appropriate for individuals who display alarm symptoms and those who do not respond as expected to therapy. The cancer risk in patients with GERD is low, and screening endoscopy has not been demonstrated to be effective in decreasing cancer incidence or increasing life expectancy. Potent anti-acid medications, such as proton pump inhibitors, make total relief of symptoms attainable in most patients. Long-term therapy with proton pump inhibitors may be necessary and, given the available evidence, appears safe and well tolerated. Surgical antireflux procedures are effective in appropriately chosen patients but should not be pursued solely in an attempt to decrease the already low risk of esophageal cancer in those with reflux.

Several other resources for physicians and patients to learn more about the evaluation and management of gastroesophageal reflux disease are available on the Internet (BOX 2).

Box 2. Resources For Patients American College of Gastroenterology's Web site, available at: http://www.acg.gi.org/acg-dev/patientinfo/frame_gerd.html National Institutes of Health's information page, available at: http://www.niddk.nih.gov/health/digest/pubs/heartbrn/heartbrn.htm Mayo Clinic's heartburn information site, available at: http://www.mayoclinic.com/findinformation/diseasesandconditions/invoke.cfm?id=DS00095 National Library of Medicine's online tutorial, available at: http://www.nlm.nih.gov/medlineplus/tutorials/gerd/id159101.html For Physicians American College of Gastroenterology's physician forum on GERD, available at: http://www.acg.gi.org/phyforum/gifocus/2evi.html American College of Gastroenterology's guidelines for the diagnosis and treatment of GERD, available at: http://www-east.elsevier.com/ajg/issues/9406/ajg1123fla.htm RETURN TO TEXT

AUTHOR INFORMATION

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Funding/Support: This research was supported in part by National Institutes of Health grant K23DK59311-01.

Corresponding Author and Reprints: Nicholas Shaheen, MD, MPH, CB#7080, UNC-CH, Chapel Hill, NC 27599-7080 (e-mail: nshaheen{at}med.unc.edu).

Author Affiliations: Division of Digestive Diseases and Nutrition, the Center for Esophageal Diseases and Swallowing, and the Center For Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill.

REFERENCES

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Scientific Review and Clinical Applications Section Editor: Wendy Levinson, MD, Contributing Editor.

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