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Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models
Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
Houju Memorial Hospital, Nomi, Japan, 11-71 Midorigaoka, Nomi, Ishikawa 923-1226, Japan
Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Otsu, Japan, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan
* Author to whom correspondence should be addressed.
Received: 17 May 2011; in revised form: 2 August 2011 / Accepted: 4 August 2011 / Published: 10 August 2011
Abstract: Development from chronic inflammation to Barrett’s adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett’s epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett’s adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.
Keywords: inflammation-metaplasia-adenocarcinoma sequence; Barrett’s esophagus; duodenogastroesophageal reflux; chemoprevention for esophageal adenocarcinoma; antireflux surgery; proton pump inhibitors; nonsteroidal anti-inflammatory drugs; selective cyclooxygenase-2 inhibitors; thioproline
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Fujimura, T.; Oyama, K.; Sasaki, S.; Nishijima, K.; Miyashita, T.; Ohta, T.; Miwa, K.; Hattori, T. Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models. Cancers 2011, 3, 3206-3224.
Fujimura T, Oyama K, Sasaki S, Nishijima K, Miyashita T, Ohta T, Miwa K, Hattori T. Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models. Cancers. 2011; 3(3):3206-3224.
Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Miwa, Koichi; Hattori, Takanori. 2011. "Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models." Cancers 3, no. 3: 3206-3224.