Clinical biology of the Barrett's metaplasia, dysplasia to carcinoma sequence

Barrett's esophagus is a complication of gastroesophageal reflux disease and a manifestation of chronic injury to the esophageal tissue. It is characterized by the presence of intestinal mucosa in an esophagus lined by cardia-type mucosa, alternatively described as a columnar-lined esophagus with intestinal metaplasia or Barrett's mucosa. When present., the abnormal mucosa confers a more than 30-125 fold risk of progression to esophageal adenocarcinoma, which emerges at a rate of about 1-2 cancers per 100 patient years of follow-up [1-3]. Perhaps a more meaningful statement is that a middle age individual who develops Barrett's esophagus has a risk of developing adenocarcinoma of the esophagus during his lifetime of 10-15%. Current dogma states that Barrett's esophagus developed quickly to its full extent with little subsequent increase in length [4]. This was based on data from patients with long segments of Barrett's mucosa within the tubular esophagus, i.e., > 3 cm. It is now accepted that intestinal metaplasia occurs in segments of cardia-type mucosa that are < 3 cm in length and can even occur in extremely small segments of cardia-type mucosa located just beyond the squamous epithelium of an endoscopically normal appearing gastroesophageal junction [5,6]. There is a controversy over the implication of these findings. Some hypothesize that intestinal metaplasia of the cardia, short segment Barrett's, and long segment Barrett's are similar, but are separate distinct entities. Others state that they represent a continuum that progresses from intestinal metaplasia of the cardia to long segment Barrett's esophagus. In the latter, the process begins with a temporary loss of lower esophageal sphincter competence due to gastric distention (7]. This results in increased esophageal exposure to gastric juice and injury to the esophageal squamous mucosa, which leads to the emergence of cardiac mucosa. A by-product of this inflammatory process is shortening and eventually loss of the lower esophageal sphincter., allowing more gastric juice to reflux and more cardiac mucosa to form. Under appropriate conditions. cardiac mucosa is intestinalized and becomes Barrett's esophagus.