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Adenosquamous carcinoma of the pancreas (ASCP) is very rare, comprising only 1–4 % of exocrine malignancies of the pancreas. Several reports have described surgical outcomes for ASCP, but there are few reports of radiotherapy. We treated a case of ASCP with radiotherapy with 50.4 Gy in 28 fractions. The tumor disappeared completely at the end of the radiotherapy but recurred rapidly within the radiation fields, and multiple liver metastases with ascites developed 2 months after treatment, which indicated the possibly high radiosensitivity of the tumor. Initial serum levels of carcinoembryonic antigen, 8.6 ng/mL, and squamous cell-related antigen, 45.8 ng/mL, decreased to within normal limits at the end of radiation therapy, but these 2 tumor markers increased rapidly thereafter.

Background The purpose of the present study was to explore novel biomarkers that can predict the clinical outcome of patients before treatment or during vaccination. These would be useful for the selection of appropriate patients who would be expected to exhibit better treatment outcomes from vaccination, and for facilitating the development of cancer vaccine treatments. Methods From a single-arm, non-randomized, human leukocyte antigen (HLA)-A-status-blind phase II trial of a vaccine treatment using three HLA-A*2402-restricted peptides for advanced pancreatic cancer (PC), we obtained peripheral blood samples from 36 patients of an HLA-A*2402-matched group and 27 patients of an HLA-A*2402-unmatched group. Results Multivariate analysis (HR = 2.546; 95% CI = 1.138 to 5.765; p = 0.0231) and log-rank test (p = 0.0036) showed that a high expression level of programmed death-1 (PD-1) on CD4+ T cells was a negative predictive biomarker of overall survival in the HLA-A*2402-matched group . Moreover, a high expression level of PD-1 on CD4+ T cells was a negative predictor for the induction of cytotoxic T lymphocytes (p = 0.0007). After treatment, we found that the upregulation of PD-1 and T cell immunoglobulin mucin-3 (Tim-3) expression on CD4+ and CD8+ T cells was significantly associated with a poor clinical outcome in the HLA-A*2402-matched group (p = 0.0330, 0.0282, 0.0046, and 0.0068, respectively). In contrast, there was no significant difference for these factors in the HLA-A*2402-unmatched group. Conclusions Our results indicate that the upregulation of PD-1 and Tim-3 expression on CD4+ and CD8+ T cells may restrict T cell responses in advanced PC patients; therefore, combination immunotherapy with blockade of PD-1 and Tim-3 to restore T cell responses may be a potential therapeutic approach for advanced PC patients. Trial registration Clinical-Trail-Registration: UMIN000008082. Electronic supplementary material The online version of this article (doi:10.1186/s13046-017-0509-1) contains supplementary material, which is available to authorized users.

In Japan, we are now using the clinical diagnostic criteria for chronic pancreatitis (CP) that were revised in 2001 to add the findings of magnetic resonance cholangiopancreatography to the criteria compiled by the Japan Pancreas Society (JPS) in 1995. Because the current criteria are set for diagnosing advanced CP, they are unlikely to improve patients' prognoses. In addition, they seem unsuitable for current clinical practice because exocrine pancreatic function tests, which have become obsolete in Japan, are included in the diagnostic factors. For these reasons, the Research Committee on Intractable Pancreatic Diseases supported by the Ministry of Health, Labour and Welfare of Japan, the JPS and the Japanese Society of Gastroenterology have revised the criteria. The revised criteria are unique in that they contain an introduction to the concept of early CP. It is a challenge aimed at improvement of the long-term prognosis of CP patients by early diagnosis and therapeutic intervention in this disease. We need to determine and clarify the clinico-pathological outcome of early CP by a prospective long-term follow-up of the patients in this category.

Background: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer. Methods: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m−2 over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles. Results: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40–0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51–1.14); P=0.19). Conclusion: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.

Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P < 0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Although the prognosis in patients with pancreatic cancer has been poor, we recently reported unusually high response rate and survival benefit of S-1 treatment in patients with pancreatic cancer. The aim of this study was to reveal genetic background of this unique activity of S-1 against pancreatic cancer. S-1 is a novel oral fluoropyrimidine derivative consisting of Tegafur (FT) and dihydropyrimidine dehydrogenase (DPD) inhibitor (5-chloro-2,4-dihydroxypyridine; CDHP). Accordingly, intratumoral DPD mRNA expression level was measured to reveal whether the level in pancreatic cancer was different from other GI cancer and whether it was relevant to chemosensitivity.Thirty-three recurrent pancreatic cancer patients treated with S-1 were studied. We obtained 15 responders and 13 non-responders according to the change of serum CA19-9. The mRNA was extracted from paraffin-embedded surgical specimens using laser captured microdissection, and relative expression levels of each DPD/beta-actin were measured using a quantitative reverse transcription polymerase chain reaction (RT-PCR) (Taqman) system. Forty-four colorectal cancer patients and 20 gastric cancer patients treated with S-1 were enrolled as control groups. Thymidylate synthase (TS) mRNA expression levels were also measured.Intratumoral DPD mRNA expression level was significantly higher in pancreatic cancer than that in colorectal cancer (P = 0.0003; median level, 1.38 vs. 0.44) and gastric cancer (P = 0.0061; 1.38 vs. 0.82). No difference in TS mRNA expression levels was observed among cancer types. DPD expression among responded pancreatic cancer was significantly lower than non-responded. (P = 0.012, Mann-Whitney U test).Intratumoral DPD mRNA expression level in pancreatic cancer was significantly higher than the other malignancies. This result may elucidate possible reasons for the high effectiveness of S-1 in pancreatic cancer.

During rotational atherectomy (RA), the coronary atherosclerotic plaque is largely pulverized into microdebris, which may cause serious hemodynamic instability owing to significant segmental left ventricular asynergy embolization of the distal microvasculature by atheromatous debris and associated vasospasm. To evaluate the usefulness of 123I-metaiodobenzylguanidine (123I-MIBG) in the examination of microvascular embolization after RA. Nineteen patients with stable effort angina pectoris who had undergone RA were evaluated in this study. Left ventricular ejection fraction (LVEF) was determined by left ventriculography immediately before and after RA. The serum concentration of creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CPK-MB) isozyme, and cardiac troponin-T was determined after RA. 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) and 123I-MIBG scintigraphic examinations were also performed 1 day after RA. The regional defect score (RDS) was determined from 99mTc-MIBI scintigraphic findings, while early and delayed RDS, heart-to-mediastinum count ratios (H/M ratios), and washout rate (WR) were determined from 123I-MIBG scintigraphy. After RA, the left ventriculographic LVEF mildly decreased by ≤10% in ten patients (group A), but it decreased by >10% in the remaining nine patients (group B). There were no differences in baseline clinical characteristics between the two groups. The CPK, CPK-MB isozyme, troponin-T, RDS by 99mTc-MIBI, H/M ratios, and WR after RA were similar in the two groups. However, the RDSs determined from early and delayed 123I-MIBG in group A were significantly lower than those in group B (4.5 ± 3.8 vs. 13.4 ± 10.8, P < 0.05; 9.0 ± 6.3 vs. 17.7 ± 10.0, P < 0.05, respectively). Moreover, there were significant correlations between delta LVEF and troponin-T (r = 0.54, P < 0.05) and RDSs of early and delayed 123I-MIBG (r = 0.46, P < 0.05; r = 0.64, P < 0.05, respectively). These findings suggest that 123I-MIBG imaging can be used to evaluate microvascular disturbance caused by embolization by microdebris after RA.

The present study was undertaken to evaluate the prevalence of pancreatic and biliary tract tumors in pancreas divisum (PD).A retrospective single-center study was performed, and a total of 118 cases of complete PD and 7850 cases of fused pancreas were identified among the 8537 consecutive new endoscopic retrograde cholangiopancreatography (ERCP) examinations performed between 1980 and 2002. The prevalence of pancreatic cancer (PCA), intraductal papillary mucinous neoplasms (IPMNs), other pancreatic tumors, and biliary tract cancer in the patients with PD and the patients with a fused pancreas were compared.The prevalence of the pancreatic tumors in the PD patients was: PCA, 10%; IPMN, 5.1%; other pancreatic tumors, 2.5%. The prevalence of pancreatic tumors in the patients with a fused pancreas was: PCA, 4.8%; IPMN, 2.6%; and other pancreatic tumors, 1.1%. The prevalence of PCA was significantly higher in the patients with PD than in those with a fused pancreas (P = 0.008; OR, 2.24). The percentages of PD patients with PCA who had pancreatic-type pain and a serum pancreatic enzyme elevation were significantly higher than among the PD patients without PCA. The prevalence of biliary tract cancer was 0.8% in the PD group and 5.3% in the fused pancreas group, and it was significantly lower in PD than in fused pancreas (P = 0.031).The results of this study showed a significantly higher prevalence of PCA in PD than in fused pancreas. We concluded that patients with PD, especially patients presenting with pancreatic-type pain and pancreatic enzyme elevation, should be carefully followed up because of the risk of developing PCA.

Intrahepatic cholangiocarcinoma (ICC) with lymph node (LN) metastasis is generally associated with a poor prognosis. However, we treated ICC with LN metastasis successfully by surgery and postoperative immunotherapy in a 59-year-old woman. The immunotherapy consisted of CD3-activated T cells and tumor lysate- or peptide-pulsed dendritic cells. Pathological examination confirmed a diagnosis of moderately differentiated adenocarcinoma with LN metastasis and portal vein invasion. The patient has been alive without recurrence for 3 years 6 months since her operation.

In 40 patients with tumor size (TS)1 pancreatic cancer with a TS of 2 cm or less, the tumor was classified as without direct extrapancreatic invasion in 11 patients (t1a, group) and as with direct extrapancreatic invasion in 29 patients (t2t3 group). Ultrasonography (US) and endoscopic retrograde cholangio-pancreatography (ERCP) were useful for the diagnosis, with accuracy rates of 80% and 75%, respectively, in the t1a group and 78% and 75% in the t2t3 group. The accuracy rate of preoperative integrated imaging diagnosis was 83% in the t2t3 group but only 55% in the t1a group. All of the t2t3 patients were stage III or higher and 18% of the t1a patients had lymph node metastasis, indicating the need for extended radical operation in TS1 pancreatic cancer. Because standard operation is indicated when the preoperative diagnosis is not pancreatic cancer, accurate preoperative diagnosis is very important. The rate of curative resection and the 5-year survival rate were 100% and 56%, respectively, in the t1a group and there were two 5-year survivors. The rate of non-curative resection and the 5-year survival rate were 31% and 35%, respectively, in the t2t3 group and there were three 5-year survivors. In the light of these findings, it is therefore important to make an accurate diagnosis of t1a pancreatic cancer of TS1 pancreatic cancer without direct extrapancreatic invasion. As liver metastasis was frequently observed in both the t1a and t2t3 groups, the establishment of effective measures to inhibit liver metastasis is considered urgent to improve the result of TS1 pancreatic cancer surgery.

The results of duodenum-preserving total resection of the head of the pancreas (DpTRHP) in 20 patients were compared with the results of pylorus-preserving pancreatico-duodenostomy (PpPD), a procedure in conventional use for the treatment of benign diseases, in 19 patients. The mean operative time for DpTRHP was 4.5±0.9 h, this being not significantly different from that for PpPD, whereas the mean intraoperative blood loss with DpTRHP (825±508ml) was significantly less than that with PpPD (1382±798 ml) (P