Acknowledgments

We acknowledge the support provided by the UC Davis Health System National Board of Advisors Vision grant awarded to M.C. Disclosure: The authors declare no confict of interest.
The current definition for Barrett’s esophagus (BE) proposed by the American Gastroenterological Association (AGA) is “the condition in which any extent of metaplastic Cisplatin columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus (1)”. Three types of columnar epithelium are seen in the setting of BE: (I) gastric-fundic type, (II) cardia-type, Inhibitors,research,lifescience,medical and (III) intestinal-type including goblet cells. However, Inhibitors,research,lifescience,medical only the last type has been clearly linked to an increased risk of malignant progression, with a reported annual risk of esophageal adenocarcinoma (EAC) of about 0.5% per year in patients with intestinal metaplasia of the esophagus (1-3). For this reason both the AGA and the American College of Gastroenterology Inhibitors,research,lifescience,medical (ACG) currently recommend that although columnar-type mucosa can be recognized during endoscopy, the

presence of intestinal metaplasia must be confirmed by biopsy before rendering a diagnosis of BE (1,4). Controversies regarding intestinal metaplasia The American definition is used in most parts of the world, however, Great Britain and Japan allow the diagnosis of BE to be assigned if only cardiac-type metaplasia is seen on biopsy (5,6). While some advocate the universal adoption Inhibitors,research,lifescience,medical of the less stringent criteria (7), the evidence to do so is controversial. Gatenbyet al. and Keltyet al. each conducted studies that showed a similar risk of EAC in patients having columnar metaplasia of the esophagus with and without goblet cells (8,9). In contrast, two large population studies from Northern Ireland showed a clear increased risk of cancer when intestinal metaplasia was present versus when only columnar cell change was identified (10,11). A study by

Takuboet al. which examined the mucosa Inhibitors,research,lifescience,medical adjacent to EAC treated with endoscopic mucosal resection found that most (>70%) were bordered by cardiac-type mucosa rather than intestinal-type mucosa and that 56% had no intestinal-type mucosa in any areas of the resection specimens. They concluded that there is a relationship between much EAC and cardiac-type mucosa and that a background of intestinal metaplasia may not be a necessary pre-requisite to EAC (6). Two similar studies by Chandrasoma and colleagues had different findings. The first, which examined esophagogastrectomy specimens resected due to adenocarcinoma, showed cardiac mucosa adjacent to all tumors but also showed residual intestinal metaplasia in 65% of cases overall and in 100% of intramucosal tumors as well as those less than 1 cm in diameter (12).