Impact of inflammation-metaplasia-adenocarcinoma sequence and prevention in surgical rat models

• Published in: Digestion Vol. 87; no. 1; p. 6
• Main Authors: Miyashita, Tomoharu, Shah, Furhawn A, Miwa, Koichi, Sasaki, Shozo, Nishijima, Koji, Oyama, Katsunobu, Ninomiya, Itasu, Fushida, Sachio, Fujimura, Takashi, Hattori, Takanori, Harmon, John W, Ohta, Tetsuo
• Format: Journal Article
• Language: English
• Published: Switzerland 2013
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacology; 2-Pyridinylmethylsulfinylbenzimidazoles - therapeutic use; Adenocarcinoma - pathology; Adenocarcinoma - physiopathology; Adenocarcinoma - prevention & control; Animals; Disease Models, Animal; Disease Progression; Duodenum - physiopathology; Epithelium - pathology; Esophageal Neoplasms - pathology; Esophageal Neoplasms - physiopathology; Esophageal Neoplasms - prevention & control; Esophagus - pathology; Metaplasia; Proton Pump Inhibitors - pharmacology; Proton Pump Inhibitors - therapeutic use; Rabeprazole; Rats
• ISSN: 1421-9867
• DOI: 10.1159/000343896

The incidence of esophageal cancer continues to rise in the Western world. Prior studies have suggested that gastroduodenal content reflux from gastroesophageal reflux disease induces the inflammation-mediated progression from hyperplasia to metaplasia, and to adenocarcinoma. We further investigated the sequential development of esophageal adenocarcinoma (EADC) with the use of an established surgical rat model. The present paper will describe the impact of the inflammation-metaplasia-adenocarcinoma sequence and chemoprevention in surgical rat models. A clinically relevant rat reflux model was used to investigate the cause of carcinogenesis, the sequential development of adenocarcinoma and chemoprevention with the use of a proton pump inhibitor. We found that duodenal reflux plays an important role in the inflammation-induced transformation of esophageal mucosa to adenocarcinoma. We were able to inhibit this transformation with rabeprazole, a proton pump inhibitor. Duodenal reflux promotes inflammation in the esophagus. The inflammation-metaplasia-adenocarcinoma sequence is important in the progression and development of EADC. Carcinogenesis can be prevented with chemoprevention agents such as rabeprazole. These results will need to be validated in clinical trials.