Pancreatic ductal adenocarcinoma is among the top 10 causes of death from cancer in industrialized countries. In comparison with other gastrointestinal malignancies, pancreatic cancer is one of the tumors most resistant to chemotherapy. An important mechanism of tumor multidrug resistance is increased drug efflux mediated by several transporters of the ABC superfamily. Especially BCRP (ABCG2), MDR1 P-glycoprotein (ABCB1) and members of the MRP (ABCC) family are important in mediating drug resistance. The MRP family consists of 9 members (MRP1-MRP9) with MRP1-MRP6 being best characterized with respect to protein localization and substrate selectivity. Here, we quantified the mRNA expression of BCRP and of all MRP family members in normal human pancreas and pancreatic carcinoma and analyzed the mRNA level of the transporters most abundantly expressed in pancreatic tissue, BCRP, MRP1, MRP3, MRP4 and MRP5, in 37 tissue samples. In addition, we determined the localization of the 4 MRP proteins in normal human pancreas and in pancreatic carcinoma. The expression of BCRP, MRP1 and MRP4 mRNA did not correlate with tumor stage or grading. On the other hand, the expression of MRP3 mRNA was upregulated in pancreatic carcinoma samples and was correlated with tumor grading. The MRP5 mRNA level was significantly higher in pancreatic carcinoma tissue compared to normal pancreatic tissue. These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer. ' 2005 Wiley-Liss, Inc.Key words: multidrug resistance protein; pancreatic carcinoma; ABCC family; MRP Pancreatic cancer is the 4th to 5th leading cause of cancerrelated death in most Western industrialized countries 1 with an average survival after diagnosis of 3 to 6 months. In Europe, it is the 8th most common cancer with approximately 74,000 newly diagnosed cases per year. 2 In spite of impressive advances in the field of diagnostic imaging of the pancreas, the availability of numerous tumor markers and an aggressive therapeutic approach, the prognosis of pancreatic carcinoma continues to be poor, with less than 5% surviving beyond 5 years. Surgical resection is possible in up to 40% of the patients with localized disease, but even in this group of patients, prognosis is relatively poor. 3,4 Most treatment failures are due to local recurrence, hepatic metastases or both and occur within 1 to 2 years after surgery. 5,6 Adjuvant therapy may improve long-term survival 7-10 but its routine use is not universal 9 because the results of randomized trials have been inconclusive. 8 In case of nonresectable pancreatic carcinomas infiltrating the retroperitoneal plexi or the superior mesenteric artery, chemotherapy might be the option of choice for the treatment. Until now, much impact on survival has not been achieved regarding the different chemotherapies, with maximum median survival times lying between 4 and 9 months ...

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Postoperative irradiation with wIRA can improve normal postoperative wound healing and may reduce costs in gastrointestinal surgery.

Hypothesis: Antecolic duodenojejunostomy prevents delayed gastric emptying (DGE) after a pyloruspreserving Whipple (ppW) procedure better than retrocolic duodenojejunostomy. Design: A single operation team's experience with antecolic and retrocolic duodenojejunostomy in ppW is analyzed on a prospective database using univariate and multivariate models. Setting: Tertiary referral center that focuses on pancreatic diseases.