caa a22 4500 445796707 CHVBK 20180317145127.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s10620-010-1465-1 doi (NATIONALLICENCE)springer-10.1007/s10620-010-1465-1 Rabeprazole Impedes the Development of Reflux-Induced Esophageal Cancer in a Surgical Rat Model [Elektronische Daten] [Tomoharu Miyashita, Furhawn Shah, Guy Marti, Jiaai Wang, Pramod Bonde, Michael Gibson, Tetsuo Ohta, Elizabeth Montgomery, Mark Duncan, John Harmon] Background: The role of proton pump inhibitors in Barrett's metaplasia and esophageal adenocarcinoma has been an area of controversy. Aims: We evaluated the effectiveness of the proton pump inhibitor rabeprazole as a chemoprevention agent in a surgical rat reflux model of esophageal cancer. Methods: The rat reflux model was created by performing a jejuno-esophagostomy on Sprague-Dawley rats. The surgery promoted the reflux of gastro-duodenal contents into the esophagus. Rabeprazole sodium (Eisai, Tokyo, Japan) was dissolved in 0.9% physiological saline to a desired concentration of 1.5% (W/V). Beginning 4weeks post-surgery, all animals were administered either 0.2ml per 100g body weight injections of rabeprazole or equivalent injections of saline 3days per week into the subcutaneous tissue of the back. Forty animals were killed 40weeks after surgery and their esophagi were examined. Of these, 23 were included in the control group, while the remaining 17 were subjected to rabeprazole. Results: While 74% (17/23) of the controls developed esophageal cancer, animals administered rabeprazole had an incidence of cancer of 29% (5/17) (p<0.05, Fisher's exact test). Barrett's metaplasia was found on 100% (23/23) of the rats in the placebo group, but there was a protective effect in the rabeprazole group with 65% (11/17) of the rats displaying signs of Barrett's metaplasia (p<0.05, Fisher's exact test). All of the rats developed proliferative hyperplasia. Conclusions: Rabeprazole protected against the development of esophageal cancer in a clinically relevant surgical reflux model. Rabeprazole warrants further investigation for potential clinical use as a chemoprevention agent. Springer Science+Business Media, LLC, 2010 Esophageal carcinoma nationallicence Barrett's metaplasia nationallicence Cancer prevention nationallicence Proton pump inhibition nationallicence COX-2 : Cyclo-oxygenase 2 nationallicence GERD : Gastroesophageal reflux disease nationallicence H&E : Hematoxylin and Eosin nationallicence PBS : Phosphate buffered saline nationallicence PPI : Proton pump inhibitor nationallicence Miyashita Tomoharu Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Shah Furhawn Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Marti Guy Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Wang Jiaai Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Bonde Pramod Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Gibson Michael Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aut Ohta Tetsuo Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan aut Montgomery Elizabeth Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aut Duncan Mark Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Harmon John Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/5(2011-05-01), 1309-1314 0163-2116 56:5<1309 2011 56 10620 https://doi.org/10.1007/s10620-010-1465-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-010-1465-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Miyashita Tomoharu Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Shah Furhawn Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Marti Guy Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Wang Jiaai Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Bonde Pramod Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Gibson Michael Department of Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Ohta Tetsuo Department of Gastroenterological Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan aut NATIONALLICENCE 700 1- Montgomery Elizabeth Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Duncan Mark Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 700 1- Harmon John Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224, Baltimore, Maryland, USA aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/5(2011-05-01), 1309-1314 0163-2116 56:5<1309 2011 56 10620 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer