Pathophysiology

Barrett’s esophagus is an acquired condition resulting from severe esophageal mucosal injury. However, it still remains unclear why some patients with gastroesophageal reflux disease develop Barretts esophagus whereas others do not. Duration and extent of acid exposure, genetic susceptibility, environmental factors and reflux of duodenogastric contents may all play a role in this regard.

Barretts esophagus is clearly associated with severe gastroesophageal reflux disease. Studies consistently show that distal esophageal acid exposure, both day and night, is greater in patients with Barretts esophagus than in patients with uncomplicated reflux disease. Excessive reflux of duodenogastric contents may also contribute to the development of this disease and its complications. A variety of other motility abnormalities of the esophagus have been described in Barretts esophagus. These include prolonged esophageal transit, low LES pressures, and peristaltic dysfunction of the esophagus. Barrett’s patients also have hernias that are longer and hiatal openings that are wider than controls with or without esophagitis.

Patients with short segment Barrett’s esophagus (< 3 cm in length) may have a variety of abnormalities intermediate to those of long segment Barrett’s patients and normal controls. Short segment Barrett’s esophagus patients are characterized by a LES pressure lower than controls but higher than long segment Barrett’s esophagus. Distal acid exposure time is greater than controls but less than that in long segment Barrett’s esophagus. Furthermore, recent data suggest that the length of Barrett’s esophagus correlates with duration of acid exposure. Bile reflux may be less important in these patients than in individuals with long-segment Barrett’s esophagus.

The development of Barretts esophagus requires injury to the esophageal mucosa accompanied by an abnormal environment of epithelial repair. Epidemiologic data suggest that once injury occurs, Barretts esophagus develops to its full extent fairly rapidly with little subsequent change in length. The mechanism whereby injury triggers metaplasia, and why this occurs in some but not all individuals is unknown. The cell of origin remains unclear; candidates include esophageal glandular cells, heterotopic gastric mucosa, or abnormal differentiation of a primordial stem cell in the esophagus.

An exciting new area of investigation of Barrett’s esophagus is the role of cylooxygenase (COX)-2 expression, which is involved in chronic inflammation and epithelial cell growth and is known to be increased in a variety of gastrointestinal malignancies. COX-2 expression increases progressively in Barrett’s metaplasia, dysplasia and adenocarcinoma, all of which are greater than that encountered in normal esophageal squamous or duodenal columnar epithelium. Furthermore, ex vivo organ culture experiments found that COX-2 expression was increased by exposure to pulses of either bile salts or acid but not to the combination of the two. These findings provide a potential rationale for chemoprevention strategies in Barrett’s esophagus that examine COX-2 inhibitors and profound suppression of acid and bile.