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declare that they have no competing interests. Authors’ contributions Before submission, all authors read and approved the final manuscript. Among the authors, LYX designed the study, while JR collected the materials, performed all experiments, and drafted the manuscript. LJY conducted the statistical analysis and GQ accomplished construction of tissue microarray blocks. ZXL participated in the

instruction of the experiment, while ST revised the manuscript critically to ensure important intellectual content. WJJ and LYX read and reviewed the sections, while, LJB and DQY performed follow-up observations on all patients. SBC provided the study concept and participated in its design and coordination.”
“Background Unresectable pancreatic cancer is known to have a poor prognosis, with most patients dying within several months of diagnosis. However, recent progress in chemotherapy using gemcitabine (GEM) for this disease RAD001 cell line has improved patient survival. A number of phase III clinical trials have been performed to determine the GEM regimens that lead to the greatest increases in survival compared with GEM monotherapy. To date, only one regimen has been shown

to yield significantly longer survival periods than GEM alone in phase III studies: GEM with erlotinib, an epidermal growth factor receptor (EGFR)-targeting agent [1]. S-1 is an oral fluoropyrimidine derivative that contains tegafur (a 5-FU prodrug) and a reversible competitive dihydropyrimidine dehydrogenase (DPD) inhibitor, 5-chloro-2,4-dihydrogenase (CDHP). As DPD is a rate-limiting enzyme that degrades 5-FU, Astemizole CDHP is expected to enhance the cytotoxicity of 5-FU by prolonging high 5-FU concentrations in blood and tumor tissues [2]. In Japan, S-1 has been clinically used as a first-line chemotherapeutic agent for pancreatic cancer since being approved for national health insurance coverage in 2006. A phase II study of S-1 for 40 patients with metastatic pancreatic cancers resulted in the response rate of 37.5% and the overall survival time of 9.2 months [3]. As the efficacy of S-1 monotherapy against pancreatic cancer is not satisfactory, numerous studies using S-1 combined with GEM have been conducted. Two phase I studies and two phase II studies of the combination therapy showed promising efficacy and acceptable adverse events [4–7].