title: Role of proton pump inhibitor on esophageal carcinogenesis and pancreatic acinar cell metaplasia development: an experimental in vivo study.
abstract: Chronic gastro-duodenal reflux in the esophagus is a major risk for intestinal metaplasia and Barrett's adenocarcinoma. A role for chronic use of proton pump inhibitor (PPI) in the increased incidence of esophageal adenocarcinoma in Western countries has been previously suggested. The aim of this work was to study the effect of chronic administration of omeprazole (a proton pump inhibitor) per os in a model of reflux induced esophageal carcinogenesis. One week after esophago-gastro-jejunostomy, 115 Sprague-Dawley rats were randomized to receive 10 mg/Kg per day of omeprazole or placebo, 5 days per week. The esophago-gastric specimens were collected 28 ± 2 weeks after randomization and analyzed in a blinded fashion. Mortality and esophageal metaplasia rates did not differ between the two groups (p = 0.99 for mortality, p = 0.36 for intestinal metaplasia and p = 0.66 for multi-layered epithelium). Gastric pancreatic acinar cell metaplasia (PACM) was more frequently observed in PPI-treated rats (p = 0.003). Severe ulcer lesions significantly prevailed in the placebo group (p = 0.03). Locally invasive esophageal epithelial neoplasia were observed in 23/39 PPI-treated versus 14/42 placebo-animals (p = 0.03). In conclusion, chronic omeprazole treatment improved the healing of esophageal ulcerative lesions. Locally invasive neoplastic lesions and PACM prevailed among PPI-treated animals. However, neither an effect on the overall mortality nor on the incidence of pre-neoplastic lesions was observed in this work.
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Dall'Olmo
authors.affiliation: ARC-NET Research Centre, University and Hospital Trust of Verona, Verona, Italy; Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy; Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dassie
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Scarpa
authors.affiliation: Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy; Venetian Institute of Molecular Medicine (VIMM), Padua, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavallin
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cagol
authors.affiliation: Endoscopy Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Pharmaceutical Chemistry and Pharmacology Department, University of Padua, Padua, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Franceschinis
authors.affiliation: Pharmaceutical Chemistry and Pharmacology Department, University of Padua, Padua, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pasut
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy; Department of Medicine (DIMED), University of Padua, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Surgery & Cancer, Imperial College of London, London, United Kingdom.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
authors.affiliation: Pharmaceutical Chemistry and Pharmacology Department, University of Padua, Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Realdon
authors.affiliation: Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D004938:Esophageal Neoplasms / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000473:pathology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054328:Proton Pump Inhibitors