Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett’s esophagus and esophageal adenocarcinoma

Abstract

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.

D-002 Ameliorates Histological Changes in Rats with Bile Reflux-Induced Esophagitis

“…[31,32] The thickness of esophageal epithelium was measured randomly in 10 areas per animal. Also, leukocytes were counted in ten random areas of the esophageal mucosa, with higher magnification (400 X).…”

Positive correlation of image analysis by mini-endoscopy with micro-PET scan and histology in rats after esophagoduodenal anastomosis

“…A 4-mm enterotomy was made 1 cm distal to the pylorus on the antimesenteric border. The distal esophagus was then anastomosed to the duodenal enterotomy with mucosal-to-mucosal opposition [3]. The animals were weighed weekly.…”

“…Several small animal surgical models have been used to study the natural history of this disease process and identify mechanisms of damage and devise-protective strategies [2][3][4][5][6]. Lu et al [1] performed sequential endoscopic exams on a rat model of esophageal reflux and found that endoscopic pathology correlated with histologic changes.…”

Acid-induced COX-2 expression and prostaglandin E2 production via activation of ERK1/2 and p38 MAPK in cultured feline esophageal smooth muscle cells

“…Esophageal reflux is a common condition that affects both children and adults, but failure to treat cases of repeated esophageal reflux may result in chronic esophagitis, aspiration pneumonia, esophageal strictures and Barrett's esophagus (Biancani et al, 1997;Li and Martin, 2007). Reflux esophagitis (RE) is a multifactorial disease influenced by transient lower esophageal sphincter relaxation, speed of esophageal clearance, and mucosal resistance, and often associated with lower esophageal sphincter pressure (Bell et al, 1992).…”