Editorials

Endoscopy for Barrett's Esophagus and Esophageal Adenocarcinoma

See article on page 2113.

NICHOLAS SHAHEEN, M.D., M.P.H.
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina

In this issue of American Family Physician, Shalauta and Saad1 describe endoscopic screening for Barrett's esophagus and esophageal adenocarcinoma in patients with reflux symptoms. This type of screening has been proposed in an effort to decrease the rate of death from esophageal adenocarcinoma. The concept is intuitively appealing-we know that gastroesophageal reflux disease (GERD) is associated with cancer, and we think that most cancers arise from Barrett's esophagus. Why not use endoscopy for patients with GERD to find those who have Barrett's esophagus, and then to follow those patients with Barrett's esophagus to catch curable cancers? Unfortunately, as with most issues in medicine, the application of this simple concept is fraught with problems. Several barriers exist that make endoscopic screening, as currently practiced, a flawed concept.

Too Much Reflux. Epidemiologic studies suggest that as much as 14 percent of the adult population experience reflux symptoms weekly, and 40 percent of the adult population experience reflux symptoms monthly.2,3 Even if endoscopic screening were limited to patients older than 50 years who experience weekly symptoms, more than 10 million persons in the United States would be eligible for endoscopic screening programs.4 Such a demand on a health care system already stressed in its ability to provide care is untenable.

Too Few Cancers. Although reflux is among the most common medical conditions in the United States, the cancer for which it is a risk factor, esophageal adenocarcinoma, is rare. About 50 percent of the projected 13,900 cases of esophageal cancers in the United States in 2003 were adenocarcinomas.5 Therefore, the risk of cancer to any given patient with reflux is miniscule, and has been suggested to be as low as 0.00065 to 0.00039 cases per patient with reflux annually.4 Subjecting millions of patients to upper endoscopy in an effort to find and prevent these cancers may not be worth the large expense and small rate of morbidity associated with the examinations. Although the incidence of this cancer is rising, the absolute numbers remain low.

Many Patients with Cancer Do Not Have Significant Reflux. Recent studies have demonstrated that up to 40 percent of patients who develop esophageal adenocarcinoma have no or trivial reflux symptoms.6 Presumably, if we use GERD symptoms to decide which patients will receive upper endoscopy screening, this 40 percent of patients would be excluded from screening programs and their poor outcomes would be unaffected by the availability of screening programs.

An Expensive, Unproven Screening Test. Ideally, screening tests should be cost effective, widely available, safe, and proven. Upper endoscopy is an expensive test that can be performed only by a limited number of highly trained professionals. Attempts to lessen the cost of screening examinations by using ultrathin, unsedated endoscopy are promising, but not widely available.7 Furthermore, given the current screening parameters, endoscopic complications would outnumber the cancers detected.4 Finally, no prospective studies have demonstrated that screening endoscopy lengthens life or decreases the rate of cancer mortality in patients with reflux.

A Highly Prevalent, Poorly Predictive Precursor Lesion. Barrett's esophagus is highly prevalent in the U.S. population; some estimate the prevalence to be 3 to 6 million persons.8 Although the risk of cancer is increased in patients with Barrett's esophagus, even among those patients, the estimated cancer risk is approximately 0.005 cancers per patient-year.9 In other words, the vast majority of patients with Barrett's esophagus will never develop cancer. These patients will go through periodic surveillance examinations and suffer other stigma of a chronic disease diagnosis without experiencing any benefits from the diagnosis of their Barrett's esophagus. Because we currently cannot tell which patients with Barrett's esophagus will progress to cancer, further risk stratification is impossible.

Given all of the above difficulties, it is unlikely that screening and surveillance upper endoscopy as currently practiced will do much to decrease the number of deaths from esophageal adenocarcinoma in the United States. Until we can improve risk stratification for this type of cancer among patients with reflux, scarce health care resources would best be diverted elsewhere. Screening for colorectal cancer, for instance, is an undersubscribed intervention that has proved effective in averting death from a much more common disease. It would be unfortunate if the best endoscopic test to prevent death from cancer among patients with reflux symptoms turned out to be a screening colonoscopy. Regardless, until these sizable conceptual problems with upper endoscopy screening are addressed and successfully resolved, this procedure should not gain large-scale acceptance. "Because we can" is an inadequate rationale for pursuing expensive, unproven endoscopic screening programs.

Nicholas Shaheen, M.D., M.P.H., is assistant professor of medicine and epidemiology in the Division of Digestive Diseases and Nutrition and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill.

Address correspondence to Nicholas Shaheen, M.D., M.P.H., CB #7080, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7080. Reprints are not available from the author.

REFERENCES

1. Shalauta MD, Saad R. Barrett's esophagus. Am Fam Physician 2004;69:2113-8.

2. Nebel OT, Fornes MF, Castell DO. Symptomatic gastroesophageal reflux: incidence and precipitating factors. Am J Dig Dis 1976;21:953-6.

3. Gallup Organization. A Gallup Organization National Survey: Heartburn Across America. Princeton, N.J.: Gallup Organization, 1988.

4. Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett's esophagus, and esophageal cancer: scientific review. JAMA 2002;287:1972-81.

5. American Cancer Society. Cancer facts and figures 2003. Atlanta: American Cancer Society, 2003.

6. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999;340:825-31.

7. Zaman A, Hapke R, Sahagun G, Katon RM. Unsedated peroral endoscopy with a video ultrathin endoscope: patient acceptance, tolerance, and diagnostic accuracy. Am J Gastroenterol 1998;93: 1260-3.

8. Fennerty MB, Triadafilopoulos G. Barrett's-related esophageal adenocarcinoma: is chemoprevention a potential option? Am J Gastroenterol 2001;96: 2302-5.

9. Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS. Is there publication bias in the reporting of cancer risk in Barrett's esophagus? Gastroenterology 2000;119:333-8.

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Screening for Barrett's Esophagus

See article on page 2113.

KENNETH R. DEVAULT, M.D.
Mayo Clinic Jacksonville
Jacksonville, Florida

In Barrett's esophagus, the normal squamous lining of the distal esophagus is replaced with a metaplastic, intestinal, columnar epithelium. Barrett's esophagus represents the end stage of severe, uncontrolled gastroesophageal reflux disease (GERD). However, Barrett's esophagus also is recognized as a precursor for most cases of esophageal adenocarcinoma.1

With the recent increase in the incidence of esophageal adenocarcinoma and its association with GERD, endoscopic screening for Barrett's esophagus has been suggested in the hope of decreasing the morbidity and mortality associated with this cancer, as described by Shalauta and Saad2 in this issue of American Family Physician. While the risk of developing esophageal cancer is relatively small in the general population, the risk for a person with Barrett's esophagus is much greater.

The literature allows us to make the following assumptions with some degree of certainty: (1) 10 to 20 percent of adults in the United States have reflux; (2) about 10 percent of patients with reflux have Barrett's esophagus; and (3) about 5 to 10 percent of patients with Barrett's esophagus eventually develop cancer. Given these suppositions, the pool of patients requiring surveillance endoscopy and biopsy for Barrett's esophagus may range from 0.5 to 2 percent of the adult population.3

The diagnosis of Barrett's esophagus requires systematic biopsy of esophageal mucosa with abnormal appearance to detect the presence of specialized intestinal metaplasia. Endoscopy should not be performed for this indication without the ability and intent to obtain appropriate histologic samples of lesions. All areas that are abnormal in appearance should be sampled, and longer segments of Barrett's esophagus should be biopsied every 2 cm.

The routine biopsy of a squamocolumnar junction of normal appearance should be discouraged because intestinal metaplasia not within the esophagus does not seem to have the same premalignant potential.4 The endoscopist must carefully document the location of the biopsies and clearly communicate this information to the pathologist.

Which patients with GERD should have upper endoscopy? Heartburn and regurgitation are fairly specific symptoms of GERD, and most patients with GERD can be managed empirically without endoscopy. Endoscopy is indicated to evaluate the so-called alarm symptoms (i.e., dysphagia, odynophagia, bleeding, and weight loss) and to screen for Barrett's esophagus.5 The epidemiology of Barrett's esophagus is not completely understood, but the risk seems to be higher in patients with long-term symptoms, especially white men. Some researchers have suggested a one-time screening endoscopy in all patients with chronic GERD, while others have limited this screening recommendation to patients older than 40 to 50 years who have had GERD symptoms for at least five years. All authorities would prefer long-term, evidence-based data on which to base clinical recommendations; however, these data will not be available for many years.

Currently, clinical practice should be based on the imperfect data that are available. The original American College of Gastroenterology Practice Guidelines of the Diagnosis Surveillance and Therapy of Barrett's Esophagus6 recommended that patients with long-standing GERD symptoms, particularly patients 50 years or older, have upper endoscopy to detect Barrett's esophagus. The more recent guideline was a bit more vague but continued to advocate for screening endoscopy in patients with chronic GERD symptoms.7

Where does this leave us when trying to determine which patients to screen for Bar-rett's esophagus? A patient younger than 40 years with mild, infrequent symptoms may be managed without endoscopy. We must remember that we have no data showing that symptom-driven treatment prevents the development of Barrett's esophagus and, therefore, even these patients eventually may require screening as they age and their duration of acid exposure increases. Most patients with heartburn who are older than 40 to 50 years have chronic symptoms, and it is not unreasonable to screen them (especially white men), regardless of the severity of their symptoms. Patients who initially present with chronic symptoms (i.e., more than five years) and those who have been followed for several years with reflux symptoms might be included in this group.

Furthermore, patients older than 65 years with new-onset GERD symptoms probably should have early endoscopy because their symptoms are less specific and mucosal disease often is more severe in this age group.8 Finally, there is no need to withhold therapy while waiting for endoscopy. Although not proved in clinical trials, treating a patient before endoscopy is performed may increase the ability of the endoscopist to recognize Barrett's esophagus and may decrease the risk of a biopsy showing false dysplasia that is actually caused by acid-induced inflammation.

Aggressive use of endoscopy would mean that most patients with GERD would be scoped eventually, which would put economic pressure on the health care system. We can help in limiting the cost of this approach by avoiding inappropriate repeated screening in patients who have already had negative endoscopy results. Most clinicians think that once Barrett's esophagus has been excluded with a single endoscopy, the risk of that patient subsequently developing Barrett's esophagus is low enough to exclude further screening (probably in the patient's lifetime). Adhering to current guidelines that have expanded the screening interval for nondysplastic Barrett's esophagus to three years also is important.6 The cost savings from appropriate use of surveillance would help to offset the cost of screening a larger segment of the population, just as has been advocated in colon cancer screening.

Kenneth R. DeVault, M.D., is professor of medicine at Mayo Clinic Jacksonville, Jacksonville, Fla.

Address correspondence to Kenneth R. DeVault, M.D., Mayo Clinic Jacksonville, 4300 San Pablo Rd., Jacksonville, FL 32224. Reprints are not available from the author.

REFERENCES

1. Spechler SJ, Goyal RK. The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology 1996;110:614-21.

2. Shalauta MD, Saad R. Barrett's esophagus. Am Fam Physician 2004;69:2113-8.

3. DeVault KR. Epidemiology and significance of Barrett's esophagus. Dig Dis 2000-2001;18:195-202.

4. Sharma P, Weston AP, Morales T, Topalovski M, Mayo MS, Sampliner RE. Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia. Gut 2000; 46:9-13.

5. DeVault KR, Castell DO. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1999;94:1434-42.

6. Sampliner RE. Practice guidelines on the diagnosis, surveillance and therapy of Barrett's esophagus. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1998;93:1028-32.

7. Sampliner RE, for the Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus. Am J Gastroenterol 2002;97:1888-95.

8. Richter JE. Gastroesophageal reflux disease in the older patient: presentation, treatment, and complications. Am J Gastroenterol 2000;95:368-73.

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