Current management of Barrett esophagus and esophageal adenocarcinoma
Release date: November 1, 2019
Expiration date: October 31, 2020
Estimated time of completion: 1 hour
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ABSTRACT
Barrett esophagus is found in 5% to 15% of patients with gastroesophageal reflux disease and is a precursor of esophageal adenocarcinoma, yet the condition often goes undiagnosed. Patients with reflux disease who are male, over age 50, or white, and who smoke or have central obesity or a family history of Barrett esophagus or esophageal adenocarcinoma, should undergo initial screening endoscopy and, if no dysplasia is noted, surveillance endoscopy every 3 to 5 years. Dysplasia is treated with endoscopic eradication by ablation, resection, or both. Chemoprotective agents are being studied to prevent progression to dysplasia in Barrett esophagus. The authors discuss current recommendations for screening and management.
KEY POINTS
- Screening is recommended for patients with long-standing reflux symptoms (> 5 years) and 1 or more key risk factors: male sex, age over 50, white race, central obesity, and history of smoking.
- In Barrett esophagus without dysplasia, surveillance endoscopy is recommended every 3 to 5 years to detect dysplasia and early esophageal adenocarcinoma.
- The recommended treatment of dysplasia is endoscopic eradication followed by surveillance endoscopy.
SURVEILLANCE: WHAT’S INVOLVED, WHAT’S AVAILABLE
Surveillance in Barrett esophagus aims to detect premalignant changes or early-stage adenocarcinoma to provide longer survival and lower cancer-related mortality. Recent evidence suggests that patients with esophageal adenocarcinoma that is diagnosed in a Barrett esophagus surveillance program have an earlier stage of disease and therefore a survival benefit.22
Patient education is essential
Before enrolling a patient in a surveillance program, the clinician should explain the risks, benefits, and limitations, the importance of periodic endoscopy, and the possible eventual need for endoscopic therapy or surgery.
The endoscopic procedure
Surveillance involves examination by high-definition white-light endoscopy, with random 4-quadrant biopsies every 2 cm (or every 1 cm in patients with a history of dysplasia) and biopsy of any mucosal irregularity (nodule, ulcer, or other visible lesion). The degree of dysplasia determines the frequency of follow-up surveillance intervals and the need for endoscopic eradication therapy, as presented in professional society guidelines (Table 1).4,23,24
Advanced methods for detecting dysplasia
Newer endoscopic surveillance techniques include dye-based chromoendoscopy, narrow-band imaging, confocal laser endomicroscopy, volumetric laser endomicroscopy, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis. All these techniques are used to increase the detection of dysplasia. Of these, dye-based chromoendoscopy, narrow-band imaging, and confocal laser endomicroscopy meet current criteria of the American Society for Gastrointestinal Endoscopy for preservation and incorporation of valuable endoscopic innovations.23
MANAGEMENT OF NONDYSPLASTIC BARRETT ESOPHAGUS
A proton pump inhibitor (PPI) is recommended to control reflux symptoms in patients with nondysplastic Barrett esophagus. But it is important to counsel patients on additional ways to protect against esophageal adenocarcinoma, such as:
- Low to moderate alcohol consumption
- Regular physical activity
- Increased dietary intake of fruits, vegetables, folate, fiber, beta-carotene, and vitamin C
- Weight control
- Smoking cessation.25
Surveillance endoscopy with 4-quadrant biopsies at 2-cm intervals is recommended every 3 to 5 years (Table 1).
DOES CHEMOPREVENTION HAVE A ROLE?
Chemoprevention is an exciting area of research in preventing progression to adenocarcinoma in patients with Barrett esophagus. Various drugs such as aspirin, other nonsteroidal anti-inflammatory drugs (NSAIDs), PPIs, metformin, and statins have been studied.
Aspirin
Aspirin has been shown to prevent development of Barrett esophagus in patients with reflux disease,26 but more studies are needed to validate those findings.
PPIs
Gastroesophageal reflux disease is a primary risk factor for esophageal adenocarcinoma, and gastric acid suppression with PPIs reduces cancer risk. PPI therapy is associated with a 71% decrease in the risk of high-grade dysplasia and adenocarcinoma in patients with Barrett esophagus (OR 0.29, 95% CI 0.12–0.79).27 Long-term therapy (> 2 to 3 years) has a higher protective effect (adjusted OR 0.45, 95% CI 0.19–1.06) than short-term therapy (< 2 to 3 years) (adjusted OR 1.09, 95% CI 0.47–2.56).27
NSAIDs
NSAIDs, including aspirin, have been associated with decreased risk of colon, stomach, lung, breast, and esophageal cancer due to their potential to inhibit cyclooxygenase 2 (COX-2) enzymes.
A meta-analysis demonstrated that aspirin and NSAIDs led to a 32% reduction in the risk of adenocarcinoma (OR 0.68, 95% CI 0.56–0.83). The benefit was even greater if the drug was taken daily or more frequently (OR 0.56, 95% CI 0.43–0.73, P < .001) or was taken for 10 or more years (OR 0.63, 95% CI 0.45–0.90, P = .04).28
PPI plus aspirin
The best evidence for the role of PPIs and aspirin in reducing the risk of dysplasia comes from the Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia Trial.29 This randomized, controlled trial compared 4 regimens consisting of esomeprazole (a PPI) in either a high dose (40 mg twice daily) or a low dose (20 mg once daily) plus either aspirin (300 or 320 mg per day) or no aspirin in 2,557 patients with Barrett esophagus. The composite end point was the time to all-cause mortality, adenocarcinoma, or high-grade dysplasia.
At a median follow-up of 8.9 years, the combination of high-dose esomeprazole plus aspirin had the strongest effect compared with low-dose esomeprazole without aspirin (time ratio 1.59, 95% CI 1.14–2.23, P = .0068). The number needed to treat was 34 for esomeprazole and 43 for aspirin.29
Based on these data, we can conclude that aspirin and PPIs can prevent dysplasia and all-cause mortality in Barrett esophagus.
Metformin: No evidence of benefit
Metformin was studied as a protective agent against obesity-associated cancers including esophageal adenocarcinoma, as it reduces insulin levels.
In a randomized controlled trial30 in 74 patients with Barrett esophagus, metformin (starting at 500 mg daily, increasing to 2,000 mg/day by week 4) was compared with placebo. At 12 weeks, the percent change in esophageal levels of the biomarker pS6K1—an intracellular mediator of insulin and insulin-like growth factor activation in Barrett epithelium—did not differ significantly between the 2 groups (1.4% with metformin vs −14.7% with placebo; 1-sided P = .80). This suggested that metformin did not significantly alter proliferation or apoptosis in Barrett epithelium, despite reducing serum insulin levels and insulin resistance. Thus, metformin did not demonstrate a chemoprotective effect in preventing the progression of Barrett esophagus to adenocarcinoma.
