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J.Jpn. Surg. Soc.. 119(3): 259-265, 2018

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1) Department of Gastroenterological Surgery, Kanazawa University Hospital
2) Toyama City Hospital
3) Cancer Research Institute of Kanazawa University
4) Houju Memorial Hospital
5) Department of Surgery, Johns Hopkins University

Tomoharu Miyashita1)5), Takashi Fujimura2), Masanobu Oshima3), Ryohei Takei1), Daisuke Matsui1), Shozo Sasaki2), Katsunobu Oyama1), Koji Nishijima1), Koichi Miwa4), John W. Harmon5), Tetsuo Ohta1)

Esophageal squamous cell carcinoma used to be the dominant type of esophageal malignancy in Asia, including Japan. However, esophageal adenocarcinoma (EADC) has been rapidly increasing in Western countries during the past half-century, especially among Caucasian men. The rapid increase in EADC has occurred in parallel with an increased prevalence of gastroesophageal reflux disease (GERD) and its major determinant, obesity. It is expected that EADC will also increase among Japanese along with the increase in GERD patients. Our prior studies suggested that duodenal content reflux from GERD induces the inflammation-mediated progression from hyperplasia to metaplasia and then to EADC. We further investigated the sequential development of EADC with the use of an established surgical rat model. The present paper describes the impact of the inflammation-metaplasia-adenocarcinoma (IMA) sequence and chemoprevention in this clinically relevant rat reflux model. We found that duodenal reflux plays an important role in the inflammation-induced transformation of the esophageal mucosa to EADC and that the IMA sequence is important in the progression and development of EADC. Carcinogenesis can be prevented with chemopreventive agents such as proton pump inhibitors, etc. These results must be validated in clinical trials.

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