Abstracts
2000 Digestive Disease Week

# 2296 Hypergastrinemia Induced by Proton Pump Inhibitor (PPI) Causes Pancreatic Growth But Does NOT Promote Pancreatic Carcinogenesis.
Mc Donald M. Jerome, Daniel S. Longnecker, Ravi Moonka, Linda Robinson, Richard H. Bell, Lebanon, NH, Seattle, WA, Tacoma, WA

INTRODUCTION: Receptors for the peptide hormone gastrin have been described on adenocarcinomas arising in several digestive organs, including colon, stomach, esophagus, and pancreas. We have previously described the expression of gastrin receptors on pancreatic adenocarcinomas in the rat, despite the fact that such receptors are not present in normal rat pancreas ( J Surg Res 63: 105-109, 1996). The widespread chronic use of drugs like PPI’s and H2-receptor blockers, which raise serum gastrin levels, leads to concern about the effect of chronic hypergastrinemia on susceptibility to cancer. We evaluated the risk of chronic PPI administration in the aforementioned rat model of pancreatic cancer. METHODS: 120 male Lewis rats received injections of the pancreatic carcinogen azaserine (30 mg/kg bw) at age 19 and 26 days. After weaning, all animals were maintained on a purified defined diet. 12 months following azaserine, animals were randomized to receive either the PPI lansoprazole (30 mg/kg bw) or vehicle by daily gavage for six months. All surviving animals were sacrificed at 18 months of age. At the time of sacrifice, blood was drawn for serum gastrin determination and the pancreas was weighed and removed for histological examination. RESULTS: 112 of 120 animals (93%) survived until planned sacrifice at 18 months. PPI administration raised serum gastrin levels significantly (269 ± 10 vs. 129 ± 7 pg/ml, p<0.0001) and to levels similar to those in humans on PPI treatment. The ratio of pancreatic weight:body weight was significantly increased in PPItreated animals (3.11 ± 0.08 vs. 2.80 ± 0.08 mg/g). The number of azaserine- induced neoplasms per animal are shown in the table below: CONCLUSIONS: Chronic PPI therapy increased serum gastrin levels and increased pancreatic weight relative to body weight, but did not enhance tumor development. This study does not support a carcinogenic risk of long-term PPI therapy. Supported by a Merit Review Award from the Dept. of Veterans Affairs