Barrett's disease: pathophysiology of metaplasia and adenocarcinoma

Peptic ulceration arising in the lower esophagus lined by columnar epithelium was described in detail by Tileston in 1906. Although this concept was challenged in 1950 by Barrett, experimental and clinical evidence has now conclusively demonstrated that Barrett's metaplasia is an acquired condition and is a consequence of chronic reflux of gastric or duodenal contents or both. Current concepts suggest that unknown trophic factors present in these secretions stimulate proliferation of multipotential reserve cells located in the esophageal submucosal glands resulting in columnar metaplasia of the normal squamous epithelium with subsequent potential for malignant degeneration. Today, numerous patients are affected by reflux esophagitis, a lesser number by Barrett's metaplasia, and a smaller but ever-enlarging group by adenocarcinoma. Although high-grade dysplasia is considered a precursor to invasive adenocarcinoma, detection of this abnormal mucosa remains controversial and currently requires esophagoscopy with biopsy. Epithelial markers, such as increased activity of mucosal ornithine decarboxylase, sulfomucin production, nuclear DNA aneuploidy, and recently molecular analysis, have also been proposed to identify those paitents at increased risk for malignant degeneration. As more is learned about the pathogenesis of Barrett's disease, perhaps these cancers can ultimately be prevented.