PURPOSE: Following a pancreatoduodenectomy, atrophy of the distal pancreas commonly occurs. It has been demonstrated that gastrin stimulates the regeneration of the pancreas in animals. This study was undertaken to determine whether gastrin has a similar effect in humans and in particular, whether it prevents the atrophy of the distal pancreas after a pylorus preserving pancreatoduodenectomy (PPPD). METHODS: Between March 1999 and May 2000, a randomized prospective study was performed in 56 patients who underwent PPPD for periampullary neoplasms. The patients were allocated to either a lansoprazole group (LG) or a control group (CG). The LG members were given oral lansoprazole (30 mg/day) over 12 weeks postoperatively to induce hypergastrinemia. During the study period, 19 patients were excluded for various reasons. Therefore, a total of 37 patients (LG: n=18; CG: n=19) were eligible for this study. The volume of the distal pancreas was determined using thin sectioned spiral CT data, the nutritional status, the endocrine (insulin level, glucose tolerance test) and exocrine function (stool elastase) of the pancreas. In addition, the serum gastrin level were measured prior to the operation and 3 months after the operation. The two groups were clinically comparable. RESULTS: The serum gastrin level was higher in the LG (P<0.05). In this group, the mean volume of the distal pancreas was reduced by 10% (63,954 mm3+/-57,069 mm3) after PPPD, whereas severe pancreatic atrophy occurred in the CG (71,446 mm3+/-39,753 mm3) (P<0.01). The postoperativeinsulin and stool elastase levels were higher in the LG than in the CG (insulin: 21.1milliunit/ml vs 6.9milliunit/ml; elastase: 59 microgram/g vs 23microgram/g). CONCLUSION: Induced hypergastrinemia prevents pancreatic atrophy after PPPD. This is probably because of the stimulated regenerative activity of the pancreas by gastrin. This has never been previously demonstrated in humans.