Experimental columnar metaplasia in the canine oesophagus

Abstract

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

“…8,9 The origin and pathological progression of BE and the contribution of gastroesophageal reflux in the disease process have been extensively studied in animal models. 1,[10][11][12][13] The metaplastic process of BE appears to be a protective adaptation 14 or a regenerative healing mechanism. 15 It is hypothesized that 'pleuripotent cells' from the native esophageal stratified squamous epithelium or ductal epithelium of the esophageal submucosal glands may give rise to the specialized columnar epithelium.…”

Development of Barrett's Esophagus Soon after Total Gastrectomy

“…In animal studies, bile reflux alone did not cause columnar re-epithelialization in one study, 5 but in other study, esophago-jejunostomy on rats induced glandular metaplasia.…”

“…3,4 Animal studies also have shown that excision of esophageal mucosa in conjunction with reflux of either acid alone or acid and bile results in re-epithelialization of the esophagus with primarily columnar epithelium, whereas excision of the esophageal mucosa alone results in re-epithelialization primarily with squamous epithelium. 5 The roles of duodenal secretions, as an individual or as the potential synergistic, in the pathophysiology of BE remains unclear due to the limited and conflicting data available. In human, reflux of duodenal contents is increased in BE compared with age-matched controls and GERD patients without BE.…”

Review Article; Duodeno-Gastro-Esophageal Reflux Combined and Isolated

“…AMJ the metaplasia-dysplasia-carcinoma sequence (Gillen et al, 1988a;Attwood et al, 1992;Miwa et al, 1995;Nishijima et al, 2004;Kivilaakso et al, 1980;Fujimura, 1991;Clark et al, 1994;DeMeester et al, 1987;DeMeester and Ireland, 1997;Di Marco et al, 1990;Fein et al, 2000a;2000b;Fujikawa et al, 1994;Gerlach et al, 1997;Harmon et al, 1978;Hofmann et al, 1969;Hofmann and Mysels, 1992;Hossain et al, 1988;Isozaki et al, 1995;Kauer and Stein, 2002;Kauer, 2005;Kivilaakso et al, 1981;Segalin et al, 1994;Lillemoe et al, 1983;Miwa et al, 1992b;Smallwood and Hoffman, 1976;Theisen et al, 2003;Ireland et al, 1996). Manifold et al (2000a) studied the role of omeprazole in gastric carcinogenesis induced by duodeno-gastric reflux.…”

“…Bile acids, pancreatic enzymes and intestinal enzymes can all result in gastrointestinal mucosal injury in vitro and in vivo (Jolly et al, 2004;Stein et al, 1999;Tibbling et al, 2002). There is adequate information on the toxicity of bile acids to the colonic mucosa (Owen et al, 1984;Turjman and Nair, 1981), hepatocytes (Scholmerich et al, 1984) and gastric mucosa (Gillen et al, 1988a;Gadacz and Zuidema, 1978), but less relating to their toxicity to esophageal mucosa (Gillen et al, 1988a;1988b;Lagergren et al, 1999;Kauer et al, 1997;1995a;Attwood et al, 1992). Whereas some authors consider Duodeno-Gastric Reflux (DGR) a physiological event (Schindlbeck et al, 1987), others believe that excessive DGR can damage the gastric Science Publications AMJ mucosa (Stern et al, 1984).…”