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Background and Aim: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive biology and poor prognosis even after resection. Long term survival is very rare and cannot be reliably predicted. Experimental data suggest an important role of epithelialmesenchymal transition (EMT) in invasion and metastasis of PDAC. Tumor budding is regarded as the morphologic correlate of local invasion and cancer cell dissemination. The aim of this study was to evaluate the biologic and prognostic implications of EMT and tumor budding in PDAC of the pancreatic head. Methods: Patients were identified from a prospectively maintained database and baseline, operative, histopathologic and follow-up data extracted. Serial tissue slices stained for Pan-Cytokeratin (PCK) served for analysis of tumor budding, and E-Cadherin (ECad), Beta-Catenin (BCat) and Vimentin (VIM) staining for analysis of EMT. Baseline, operative, standard pathology and immunohistochemical parameters were evaluated for prediction of long term survival (>= 30 months) in uniand multivariate analysis. Results: Intraand intertumoral patterns of EMT marker expression and tumor budding provide evidence of partial EMT induction at the tumor-host interface. Lymph node ratio (LNR) and E-Cadherin expression in tumor buds were independent predictors of long term survival in multivariate analysis. Conclusions: Detailed immunohistochemic assessment confirms a relationship between EMT and tumor budding at the tumorhost interface. A small group of patients with favorable prognosis can be identified by combined assessment of LNR and EMT in tumor buds.

Background: The efficacy of AGC varies among individuals and the resulting survival rates are still unsatisfactory. Objective: The aim of this study was to investigate predictive value of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotid reductase submit 1 (RRM1) expression for advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Methods: Intratumoral hENT1 and RRM1 expression was investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (including 68 with AGC, and 59 without AGC). Impact of hENT1 and RRM1 expression on diseasefree survival (DFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: High intratumoral hENT1 and RRM1 expression was observed in 86 (68%) and 67 (53%) patients, respectively. Univariate analysis of data from 68 patients with AGC revealed that high hENT1 and low RRM1 expression were significantly associated with longer DFS (hENT1, P = 0.005; RRM1, P = 0.015) and longer OS (hENT1, P = 0.036; RRM1, P = 0.035). In multivariate analysis, moderately or poorly differentiation, (P = 0.007), low hENT1expression (P = 0.044) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor DFS, and moderately or poorly differentiation, (P = 0.045), lymph node metastasis, (P = 0.011) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor OS. In contrast, hENT1 and RRM1 expression did not correlate with DFS and OS in 58 patients without AGC. Conclusions: Intratumoral hENT1 and RRM1 expression predicts survival of advanced cholangiocarcinoma patients treated with AGC.

Introduction: Pancreatoduodenectomy (PD) has become a standard operation with low mortality in high-volume centers, however perioperative morbidity remains substantial, mainly due to postoperative pancreatic fistula (POPF). Development of preoperative protective measures is hampered by a lack of strictly preoperative risk stratification. Predictive power of single parameters can be enhanced by optimally weighed combination of risk factors in an artificial neuronal network (ANN). Methods: A panel of clinical and radiological parameters were assessed retrospectively from patients with pancreatoduodenectomy in our institution and risk factors analysis for the endpoint POPF (clinically relevant Grade B/C of ISGPS definition) were identified. Preoperatively available parameters were used for prediction of a high risk pancreas in an ANN. Internal validation of the thereby identified risk group was performed by testing for POPF and other relevant complications. Results A total of 471 patients with PD operated from 2001 to 2012 were included. Out of twelve clinical and radiological risk factors for POPF B/C, the most powerful was a soft pancreas. When an ANN was trained to predict a soft high-risk pancreas, correct prediction was achieved in 83% in the test group. Patients predicted to have a high-risk pancreas had a significantly higher rate of POPF and severe complications compared to the low-risk group (POPF B/C (38% vs 8%, p=0.000), intraabdominal abscess (23% vs 10%, p=0.000), severe complications (26% vs 13%, p=0.003), severe postpancreatectomy hemorrhage (18% vs 6%, p=0.012)), as well as a five-fold elevated mortality (5% vs 1%, p=0.034). Conclusion Clinical and radiological parameters combined in an ANNmodel can correctly predict a high-risk pancreas and severe complications already before the operation.

Background: Given that the life expectancy is increasingly becoming longer, safety and efficacy of pancreaticoduodenectomy for periampullary cancers in elderly patients is a great clinical concern. Over the last decademany reports have described outcome of pancreaticoduodenectomy in elderly patients, but the results are still inconsistent. Methods: From a database of all the patients with periampullary cancers undergoing pancreaticoduodenectomy between 2001 and 2009, the patients over 80 years were identified. Perioperative characteristics, postoperative complications, mortality, and a long-term survival were retrospectively compared between the patients aged 80 and older, and the patients younger than 80 years. Results: Among a total of 561 patients undergoing pancreaticoduodenectomy, 22 patients (3.9%) were over 80 years. The pathological diagnosis in the elderly patients consisted of as follows; pancreatic cancer (n=8), bile duct cancer (n=5), ampullary neoplasm (n=5), intraductal papillary mucinous neoplasm (n=3), and gallbladder cancer (n=1). The elderly patients had a higher ASA score (P=0.02) than the younger patients, but there was no significant difference in operative time (455 vs 520 minutes; P=0.08), and blood loss (654 vs 838 ml; P=0.38). The mortality rate was 4.5% in the elderly patients and 0.9% in the younger patients, though the difference was not statistically significant (p=0.106). Although the incidence of postoperative pancreatic fistula and delayed gastric emptying were similar between the two groups, that of intraabdominal abscess, intraabdominal hemorrhage, pneumonia and ascites in the elderly patients (22.7%, 18.2%, 9.1% and 4.5%, respectively) were higher than in the younger patients (6.9%, 2.2%, 0.6% and 0.2%, respectively). The rate of grade IIIa or higher complication (Clavien-Dindo classification) was 27.3% in the elderly patients and 6.3% in the younger patients (P=0.008). There was no significant difference in overall survival between the two groups. Among the elderly patients, the median survival for those with pancreatic cancer was significantly shorter than that with non-pancreatic cancer. (P=0.003) Conclusions: Pancreaticoduodenectomy in patients aged 80 and older should be indicated carefully, because of the higher incidence of the severe postoperative complications. Pancreaticoduodenectomy for pancreatic cancer in elderly patients could not provide a satisfactory outcome in terms of a long-term survival compared with that for nonpancreatic cancers.