Operatively induced chronic reflux in rats: A suitable model for studying esophageal carcinogenesis?

Abstract

Despite pathophysiologic differences with humans, the rat model of esophagoduodenostomy reproduces accurately histologic and molecular lesions in the carcinogenetic sequence of BE and allowed us to identify novel, tumor-associated proteins that may be potential biomarkers and new therapeutic targets in EA.

Preclinical models for the study of Barrett's carcinogenesis

“…Gronnier et al . later confirmed these results . However, they also identified Brunner's glands within the columnar lined esophageal segment.…”

“…The results suggested that bile was the key injurious factor and that gastric secretions alone had little effect. Despite key anatomical and histological differences between the murine and human esophagus, such as the presence of a keratinized squamous epithelium within the esophagus, an SCJ located within the forestomach, and the absence of esophageal submucosal glands (ESMGs), this paper served to popularize the murine model and formed the basis from which several later surgical reflux models were generated …”

“…However, they also identified Brunner's glands within the columnar lined esophageal segment. Because these glands normally reside within the submucosa of the first part of the duodenum, this raised the possibility that duodenal tissue may have been mechanically introduced into the distal esophagus, suggesting that both mechanisms may be occurring . Buskens et al .…”

“…Despite key anatomical and histological differences between the murine and human esophagus, such as the presence of a keratinized squamous epithelium within the esophagus, an SCJ located within the forestomach, and the absence of esophageal submucosal glands (ESMGs), 15 this paper served to popularize the murine model and formed the basis from which several later surgical reflux models were generated. [28][29][30][31][32][33][34][35] Once the association between the CLE and EAC became apparent, research shifted from investigating reflux esophagitis to the more clinically important metaplasia-dysplasia-carcinoma sequence. Given the complexities involved in such a disease process and its long natural time course, researchers have gone to great efforts to generate a suitable animal model.…”

“…To extrapolate the results from animal models to the human disease process, it is essential that models undergo rigorous validation. 30 Unfortunately, the results from multiple studies aiming to validate the surgically induced reflux model have varied, leaving two fundamental issues unresolved. The first issue is whether the CLE seen within the model is truly metaplastic or simply is the migration of epithelial cells from below the anastomosis.…”