SeminarBarrett's metaplasia
Section snippets
Oesophageal stem cells
Barrett's metaplasia consists of a simple columnar epithelium that is folded to form glandular invaginations in the mucosa. Cells that are shed from the epithelial surface into the lumen are replaced from below by new cells as a result of stem-cell division. Stem cells can self-renew (clonogenic) and produce indefinite numbers of differentiated progeny. These progeny, termed transit amplifying cells or daughter cells, can undergo a finite number of divisions, but each time they divide they lose
Clonal expansion
After the initial selection or generation of a metaplastic stem cell, clonal expansion takes place, which depends on the control of stem-cell number per gland. The number of stem cells is usually highly controlled so that the production of new cells does not upset homoeostatic balance. However, knowledge of stem-cell biology in the intestine has shown that any abnormality in stem-cell division causes extreme alterations in glandular organisation, structure, and function (figure 2).22 Usually
Role of bile acids
Gastro-oesophageal reflux of acid and bile are the predominant initiating factors in Barrett's metaplasia, although the precise mechanism of cytotoxicity is unclear. Partly regressed metaplastic mucosa might be induced by ablation of acid (and bile) reflux with either proton pump inhibitors or antireflux surgery.32 However, a series of in-vitro experiments showed that intermittent exposure to acid causes epithelial changes, which could be interpreted as selecting poorly differentiated cells
Mucosal inflammmation
Mixed inflammatory cell infiltrate is a common feature of acid and bile damage to the native oesophageal mucosa, especially around the stem-cell rich areas of the basal mucosal compartment and papillae.41, 42 This infiltrate is initially composed of acute inflammatory cells. Subsequently T lymphocytes become more numerous, especially in tissues in which metaplastic foci develop.42 Once duodenal gastro-oesophageal reflux disease is corrected by powerful acid suppressing drugs Barrett's
Conclusion
The process of initiation, clonal expansion, and aberrant epithelial biology explains not only why cancer evolution is a multistage process but also why there is a long lag phase between initiation of metaplastic change and cancer development. A combination of aberrant biology, site of origin, and resistance to environmentally induced apoptosis could explain the heterogeneity and malignant potential of metaplastic cells. We suggest that during the initiation phase of Barrett's metaplasia, there
References (67)
- et al.
Prevalence of columnar-lined (Barrett's) oesophagus
Gastroenterology
(1990) - et al.
Barrett's esophagus: it's prevalence and association with adenocarcinoma in patients with symptoms of gastroesphageal reflux
Am J Surg
(1985) - et al.
Barrett's esophagus: age, prevalence and extent of columnar epithelium
Gastroenterology
(1992) - et al.
Familial aggregation of gastroesophageal reflux in patients with Barrett's esophagus and esophageal adenocarcinoma
Gastroenterology
(1997) - et al.
Prospective evaluation of the prevalence of gastric Helicobacter pylori infection in patients with GERD, Barrett's esophagus, Barrett's dysplasia, and Barrett's adenocarcinoma
Am J Gastroenterol
(2000) The role of gastric carditis in metaplasia and neoplasia at the gastro-oesophageal junction
Gastroenterology
(1999)- et al.
Differentation and proliferation in Barrett's esophagus and the effects of acid suppression
Gastroenterology
(1999) - et al.
Duodeno-gastric reflux: relationship to pH and importance in Barrett's esophagus
Gastroenterology
(1994) - et al.
Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: ex vivo induction by bile salts and acid exposure
Gastroenterology
(2000) - et al.
Inflammation and intestinal metaplasia of the gastric cardia: the role of gastroesophageal reflux and H pylori infection
Gastroenterology
(1998)