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- 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
- Esophageal adenocarcinoma incidence is rising in the United States (1). From 1975 to 2001, there was ~6-fold increase, from 4 to 23 cases/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)
Etiology and Pathophysiology
- 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 (BE) (1).
- Classic progression: normal epithelium → esophagitis → metaplasia (BE) → dysplasia (low- or high-grade) → adenocarcinoma
- Familial predisposition to GERD and BE with 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 years
- 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—at least one first-degree relative with BE or esophageal adenocarcinoma
Commonly Associated Conditions
GERD, obesity, hiatal hernia