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Barrett Esophagus
Eric Ji-Yuan Mao, MD
Harlan G. Rich, MD, FACP, AGAF
image BASICS
  • Metaplasia of the distal esophageal mucosa from native stratified squamous epithelium to abnormal columnar (intestinalized) epithelium, likely as a consequence of chronic GERD
  • Predisposes to the development of adenocarcinoma of the esophagus
  • Predominant age: >50 years
  • May occur in children (rare <5 years)
  • 10-15% of patients undergoing endoscopy for evaluation of reflux symptoms (1)
  • Esophageal adenocarcinoma incidence is rising in the United States (1,2). From 1975 to 2001, there was nearly a 6-fold increase from 4 to 23 cases per million person-years.
  • Attributed to changes in smoking and obesity rather than reclassification or overdiagnosis
  • Difficult to ascertain because of different populations studied, varying definitions, and asymptomatic cases
  • As many as 1.5 to 2.0 million adults in the United States (extrapolated from a 1.6% prevalence in Swedish general population) (1)
  • Chronic gastric reflux injures the esophageal mucosa, triggering columnar metaplasia. Refluxed bile acids likely induce differentiation in gastroesophageal junction (GEJ) cells.
  • Columnar cells in the esophagus have higher malignant potential than squamous cells. Activation of CDX2 gene and overexpression of HER2/neu (ERBB2) oncogene promotes carcinogenesis.
  • Elevated levels of COX-2, a mediator of inflammation and regulator of epithelial cell growth, are associated with Barrett esophagus (2).
  • Classic progression: normal epithelium → esophagitis → metaplasia (Barrett esophagus) → dysplasia (low-or high-grade) → adenocarcinoma
  • Familial predisposition to GERD and Barrett esophagus and multiple genetic markers have been identified.
  • Acquired genetic changes lead to adenocarcinoma and are being investigated as biomarkers for risk stratification and early detection.
  • Chronic reflux (>5 years)
  • Hiatal hernia
  • Age >50
  • Male gender
  • White ethnicity—incidence in white males is much higher than white women and African American men
  • Smoking history
  • Intra-abdominal obesity
  • Family history with at least one first-degree relative with Barrett esophagus or esophageal adenocarcinoma
Weight loss, smoking cessation, robust dietary intake of fruits and vegetables, and moderate wine consumption may decrease risk of Barrett esophagus and lower progression to esophageal cancer (3)[C].
GERD, obesity, hiatal hernia
No abnormal findings on physical exam are specific for Barrett esophagus. Perform a general physical examination including vital signs, oral examination, cardiopulmonary examination, abdominal examination, and lymph node examination.
  • Erosive esophagitis
  • GERD
Endoscopy with multiple biopsies for histologic examination are required to diagnose Barrett esophagus.
  • Gastric fundic-type epithelium on pathology does not have clear malignant significance and may reflect sampling error.
  • Specialized intestinal metaplasia at the GEJ: cancer risk difficult to assess with varying definitions of GEJ landmarks
Initial Tests (lab, imaging)
  • Helicobacter pylori testing is not indicated. Metaanalyses show an inverse relationship between H. pylori infections and Barrett esophagus, which may be related to decreased acid production (5)[C].
  • No biomarkers are currently effective for diagnosis; many are under investigation for risk stratification (1),(3)[B].
Diagnostic Procedures/Other
  • Endoscopy: visual identification of columnar epithelium (reddish, velvety appearance) replacing the squamous lining of the distal esophagus
  • Disease extent: Long-segment (≥3 cm) versus short-segment (<3 cm)
  • The Prague C (circumference) and M (maximum extent) criteria is a consensus-driven grading system used to describe Barrett esophagus using landmarks of the squamocolumnar junction, GEJ, extent of circumferential columnar lining, and extent of proximal extension of columnar mucosa.
    • White light endoscopy (preferably high resolution) is the standard for diagnosis. Advanced imaging techniques, such as narrow band imaging (NBI) and confocal laser endomicroscopy, may help identify dysplasia but are preliminary (1)[A].
  • Systematic biopsies from endoscopy showing columnar epithelium confirm the diagnosis:
    • Seattle protocol: four-quadrant biopsies at regular intervals with additional biopsies of visible mucosal irregularities; more time-consuming but higher diagnostic yield than random biopsies (3)[A]
    • Capsule endoscopy is still developing and has lower sensitivity than conventional endoscopy (6)[B].
Test Interpretation
  • Specialized intestinal metaplasia (also called specialized columnar epithelium) is diagnostic: Benign Barrett esophagus diagnosis is established by a single pathologist report (4)[C].
  • Diagnosis of dysplasia (and grade) should be confirmed by two specialist gastrointestinal pathologists before treatment (4)[C].
  • Cardia-type columnar epithelium may predispose to malignancy (unclear risk); International Consensus Group currently recommends defining Barrett esophagus by the presence of columnar mucosa in the esophagus with modifier of whether intestinal metaplasia is present. (4)[C].
  • The goal of medical therapy is to control GERD to reduce esophagitis.
  • Therapy usually does not result in reversal of Barrett esophagus but may decrease risk of progression to cancer (1,2)[A],(6,7)[B].
First Line
  • Unlike the stepwise management of GERD without evidence of Barrett esophagus, patients with Barrett esophagus and GERD symptoms should be treated initially with a once-daily PPI.
  • PPIs should be dosed 30 minutes before a meal (ideally, the first meal of the day).
  • Chemoprevention of neoplastic progression is under active investigation.
  • Case-controlled studies have shown that aspirin, and NSAIDs may prevent progression to esophageal cancer due to COX-2 inhibition:
    • COX-2 selective inhibitor celecoxib use not shown to affect progression of Barrett dysplasia to adenocarcinoma (2)[A].
    • Use of aspirin and a PPI for chemoprevention of esophageal cancer is under investigation (1,2,3).
    • Consider low-dose aspirin in patients with Barrett esophagus who also have risk factors for cardiovascular disease (2)[C].
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  • Statins, alone or in combination with aspirin or NSAIDs, appear to be effective in chemoprevention but are not yet routinely recommended (3)[B],(8)[A].
Second Line
If once-daily PPI does not control symptoms, move to twice-daily dosing (6)[A].
  • Initiate PPI therapy prior to endoscopy to reduce reactive esophagitis/atypia (6)[C].
  • Refer patients considering esophagectomy to a high-volume institution.
  • Endoscopic eradication is any combination of endoscopic mucosal resection (EMR), photodynamic therapy (PDT), and radiofrequency ablation (RFA) to eliminate all Barrett epithelium.
  • EMR: eradication rate 86-100%, excision to submucosa, allows staging, preferred for visible irregularities
  • PDT: eradication rate 77-100% but strictures in 40%
  • RFA: eradication rate 54-90%, comparable efficacy to PDT, fewer adverse effects
  • Focal EMR combined with RFA of other areas is considered most effective eradication therapy (3)[B].
  • Additional studies are still required before cryotherapy and other ablative procedures can be recommended.
  • Barrett esophagus with visible lesions:
    • EMR with ablation if high-grade dysplasia or intramucosal cancer detected (4)[C]
  • Low-grade dysplasia: Treatment is controversial.
    • Offer treatment such as RFA for low-grade dysplasia and high-risk features (multifocality, long segment length, persistence) (4)[C]. Endoscopic eradication may prevent progression to high-grade dysplasia or esophageal adenocarcinoma (3)[B],(9)[A].
  • Endoscopic eradication therapy is recommended for High-grade dysplasia, without or with very limited submucosal invasion (stage T1SM1 or lower by endoscopic ultrasound) (1,2,6)[B].
Antireflux surgery such as fundoplication may control GERD symptoms but are not convincingly shown to reverse Barrett esophagus, decrease risk of cancer, or be superior to medical therapy (1,2)[A],(6)[B].
A prospective study of 339 men and women with Barrett esophagus found those taking either a multivitamin, vitamin C, or vitamin E once a day were less likely to develop esophageal adenocarcinoma (10)[B].
Geriatric Considerations
Surveillance or no treatment may be preferable to endoscopic eradication therapy or esophagectomy in patients who are poor operative candidates.
  • Surveillance (to detect high-grade dysplasia or early carcinoma), while controversial, is recommended in patients with histologically confirmed Barrett-especially for those in high-risk groups.
  • Surveillance intervals depend on the grade of dysplasia (3)[C].
  • No dysplasia: 3 to 5 years
    • Discontinue surveillance if life expectancy is ≤5 years (4)[C].
  • Low-grade dysplasia: 6 to 12 months
    • Routine surveillance if patients have confirmed absence of low-grade dysplasia after two consecutive endoscopies (4)[C]
  • Indefinite for dysplasia: within 1 year
    • Increase acid suppression (4)[C].
  • High-grade dysplasia without eradication therapy: 3 months
Avoid foods that can trigger reflux: caffeine, alcohol, chocolate, peppermint, carbonated drinks, garlic, onions, spicy foods, fatty foods, citrus, and tomato-based products.
  • Lifestyle modifications: smoking cessation, weight loss, avoid supine position after meals, avoid tight-fitting clothes, elevate head of bed
  • No evidence that treating GERD reverses Barrett esophagus or prevents esophageal cancer.
Annual incidence of esophageal cancer in patients with Barrett esophagus is ≤0.33% per year (2,3)[B]:
  • Low-grade dysplasia: may be transient; cancer risk 0.5-0.6% per year
  • High-grade dysplasia: cancer risk 5-7% per year
1. Sharma P. Clinical practice. Barrett's esophagus. N Engl J Med. 2009;361(26):2548-2556.
2. Spechler SJ, Sharma P, Souza RF, et al. American Gastroenterological Association technical review on the management of Barrett's esophagus. Gastroenterology. 2011;140(3):e18-e52.
3. Spechler SJ, Sharma P, Souza RF, et al. American Gastroenterological Association medical position statement on the management of Barrett's esophagus. Gastroenterology. 2011;140(3):1084-1091.
4. Bennett C, Moayyedi P, Corley DA, et al. BOB CAT: a large-scale review and delphi consensus for management of Barrett's esophagus with no dysplasia, indefinite for, or low-grade dysplasia. Am J Gastroenterol. 2015;110(5):662-682.
5. Fischbach LA, Nordenstedt H, Kramer JR, et al. The association between Barrett's esophagus and Helicobacter pylori infection: a meta-analysis. Helicobacter. 2012;17(3):163-175.
6. Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol. 2008;103(3):788-797.
7. Singh S, Garg SK, Singh PP, et al. Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis. Gut. 2014;63(8):1229-1237.
8. Kastelein F, Spaander MC, Biermann K, et al. Nonsteroidal anti-inflammatory drugs and statins have chemopreventative effects in patients with Barrett's esophagus. Gastroenterology. 2011;141(6):2000-2008.
9. Phoa KN, van Vilsteren FG, Weusten BL, et al. Radiofrequency ablation vs endoscopic surveillance for patients with Barrett esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014;311(12):1209-1217.
10. Dong LM, Kristal AR, Peters U, et al. Dietary supplement use and risk of neoplastic progression in esophageal adenocarcinoma: a prospective study. Nutr Cancer. 2008;60(1):39-48.
Additional Reading
  • Dunbar KB, Spechler SJ. Controversies in Barrett esophagus. Mayo Clin Proc. 2014;89(7):973-984.
  • Zimmerman TG. Common questions about Barrett esophagus. Am Fam Physician. 2014;89(2):92-98.
  • K22.70 Barrett's esophagus without dysplasia
  • K22.719 Barrett's esophagus with dysplasia, unspecified
  • K22.710 Barrett's esophagus with low grade dysplasia
Clinical Pearls
  • The incidence of esophageal carcinoma is rising faster than any other major malignancy. Barrett esophagus is a known precursor.
  • Highest incidence is among white males >50 years.
  • Endoscopic eradication therapy is preferred for high-grade dysplasia with or without submucosal invasion.
  • Esophagectomy offers definitive therapy: Consider for all patients with high-grade dysplasia; preferred for patients with submucosal invasion.
  • Promising areas for future research include the use of biomarkers for risk stratification, chemoprevention of neoplastic progression, capsule endoscopy for screening and the use of vitamins and antioxidants for prevention and treatment.