MANAGMENT OF BARRETT'S ESOPHAGUS

December 31, 2009 — Strategies and recommendations for diagnosing and managing Barrett's esophagus are presented in a review published in the December 24 issue of the New England Journal of Medicine.

"Barrett's esophagus is a premalignant lesion detected in the majority of patients with esophageal and gastroesophageal adenocarcinoma — cancers that are associated with a low rate of survival (5-year survival rate, 15 to 20%)," writes Prateek Sharma, MD, from the Veterans Affairs Medical Center and University of Kansas School of Medicine in Kansas City. "The risk of esophageal adenocarcinoma is 30 to 40 times as high among patients with Barrett's esophagus as among patients without this condition. The progression of Barrett's esophagus may involve the development of low-grade dysplasia and high-grade dysplasia before the eventual development of cancer."

In the United States, the incidence of esophageal adenocarcinoma has been increasing. Although the prevalence of Barrett's esophagus in the general US population is unknown, Barrett's esophagus is diagnosed at endoscopy in approximately 10% to 15% of patients referred for this test. In 1 report of endoscopic screening in patients without chronic reflux symptoms, the prevalence of Barrett's esophagus was 5.6%.

Based on extrapolation from a population-based study in Sweden, 1.5 to 2.0 million adults in the United States may have Barrett's esophagus. Risk factors for Barrett's esophagus include older age, male sex, white race, reflux symptoms, and obesity, whereas drinking red wine, infection with Helicobacter pylori, and black race may be protective.

Some gastroenterology societies recommend endoscopic screening for Barrett's esophagus in patients with symptoms of chronic reflux, but such screening is controversial because the absolute risk for esophageal adenocarcinoma is low in these patients; Barrett's esophagus may develop without chronic reflux symptoms; and there is no evidence that endoscopic screening lowers mortality rate from esophageal adenocarcinoma.

Barrett's esophagus is diagnosed by endoscopy and graded with use of the Prague circumference and maximum (C and M) criteria, which is a standardized, validated system based on the circumferential and maximal extent of the columnar-lined esophagus. Mucosal biopsy specimens from the columnar segment are used to identify metaplastic or neoplastic epithelium. Sites for biopsy should include any visible mucosal abnormalities as well as a systematic 4-quadrant biopsy protocol, with specimens obtained every 2 cm along the extent of the Barrett's esophagus.

Clinicians should counsel patients with Barrett's esophagus that they are at increased risk for the development of esophageal adenocarcinoma but that this risk is low. Based on recent evidence, this risk is approximately 0.5% per year, or from 0.6% to 1.6% per year in patients with low-grade dysplasia. Most patients with low-grade dysplasia identified endoscopically no longer have evidence of dysplasia on the next endoscopic examination. In patients with high-grade dysplasia, however, the risk for the development of esophageal adenocarcinoma is high (approximately 6.6 cases per 100 patient-years).

Most patients with Barrett's esophagus should undergo endoscopic surveillance with detailed inspection and systematic biopsies. When making clinical decisions, however, the clinician should consider patient age, comorbid conditions, and life expectancy, recognizing the lack of proof that such surveillance lowers mortality rates because of esophageal adenocarcinoma.

Frequency of surveillance can probably be reduced to once every 3 years in patients with nondysplastic Barrett's esophagus who have at least 2 endoscopic examinations with no evidence of disease progression. Annual surveillance is typically recommended for patients with low-grade dysplasia in whom an advanced lesion has been ruled out.

Enhanced optical imaging techniques may improve the efficiency and accuracy of endoscopic surveillance, although head-to-head comparisons with standard endoscopy are generally lacking. Enhanced techniques that may be promising include narrow-band imaging (electronic chromoendoscopy) and confocal laser endomicroscopy.

To manage reflux symptoms and heal erosive esophagitis in patients with Barrett's esophagus, use of proton-pump inhibitors for acid suppression and/or surgery to correct reflux may be helpful. However, evidence to date has not proved that these treatments are associated with a lower risk for neoplastic progression.

"Indications for antireflux surgery in patients with Barrett's esophagus are the same as those in patients with chronic reflux (e.g., a lack of response to or an inability to tolerate proton-pump inhibitors); the presence of Barrett's esophagus should not be viewed as an indication for antireflux surgery," Dr. Sharma writes. "The primary goal of both treatment with proton-pump inhibitors and surgery is symptom control; 24-hour pH monitoring to document normalization of exposure to esophageal acid is not routinely recommended."

Endoscopic treatment or surgical resection should be considered in patients with high-grade dysplasia. Because of high risk for progression and high prevalence of coexisting adenocarcinoma, esophagectomy is generally recommended.

Neoplastic lesions associated with Barrett's esophagus should be removed by mucosal ablative techniques, which may include photodynamic eradication therapy, radiofrequency ablation, cryoablation, or argon plasma coagulation. Eradication therapy is associated with a complication rate of 10% to 15%, with adverse effects including chest pain, odynophagia, strictures, perforation, and bleeding.

"Among patients with esophageal adenocarcinoma, endoscopic eradication therapy should be considered only for those with mucosal disease, in whom the rate of lymph-node metastasis is extremely low (≤3%); once the cancer invades the submucosa, the risk of lymph-node metastasis at diagnosis increases to 20 to 25%," Dr. Sharma writes. "Endoscopic eradication therapy is not currently recommended in patients with nondysplastic Barrett's esophagus. Because of the overall low risk of esophageal adenocarcinoma among patients with Barrett's esophagus, if the procedure is confirmed to be preventive, the estimated number of patients who would need to be treated to prevent one case of esophageal adenocarcinoma would be 250 or more."

The American College of Gastroenterology, the American Society for Gastrointestinal Endoscopy, the British Society of Gastroenterology, the French Society of Digestive Endoscopy, and the Society for Surgery of the Alimentary Tract have published guidelines for the management of Barrett's esophagus, which are generally consistent with the clinical recommendations offered in this review article.

"Given the low overall risk of neoplastic progression of Barrett's esophagus, there is an interest in biomarkers that might identify persons at particular risk for the development of cancer," Dr. Sharma concludes. "Among biomarkers reported to be predictive of neoplastic progression are abnormalities in the tumor-suppressor genes CDKN2A (which encodes the cyclin-dependent kinase inhibitor p16INK4a) and TP53 (which encodes tumor protein p53), and the presence of tetraploidy or aneuploidy in epithelial cells. However, data are needed from large prospective studies to confirm the predictive value of these and other markers, and they are not currently used in routine clinical management."

Dr. Sharma has received consulting fees from AstraZeneca, Santarus, and Takeda and grant support from Given Imaging, Barrx Medical, Olympus, Cogentus, Mauna Kea Technologies, and Takeda.

N Engl J Med. 2009;361:2548-2556.