Gastric cancer with peritoneal dissemination has poor clinical prognosis because of the presence of rich stromal fibrosis and acquired drug resistance. Recently, Angiotensin II type I receptor blockers such as candesartan have attracted attention for their potential anti-fibrotic activity. We examined whether candesartan could attenuate tumor proliferation and fibrosis through the interaction between gastric cancer cell line (MKN45) cells and human peritoneal mesothelial cells. Candesartan significantly reduced TGF-β1 expression and epithelial-to-mesenchymal transition-like change, while tumor proliferation and stromal fibrosis were impaired. Targeting the Angiotensin II signaling pathway may therefore be an efficient strategy for treatment of tumor proliferation and fibrosis.

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Abstract. Background Sepsis is a clinical syndrome of systemic inflammatory responses arising from an infectious process with a presumed or known focus (1, 2). Severe sepsis, defined as sepsis with acute organ dysfunction, is associated with high morbidity and mortality rates (3). Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis (4, 5). Sepsis-induced multiple organ failure (MOF) has numerous causes, such as various types of shock, adult respiratory distress syndrome (ARDS), and disseminated intravascular coagulation (DIC) (6). Gando et al. (7) reported that DIC is frequently associated with systemic inflammatory response syndrome (SIRS; 83%) and that such patients have a high mortality rate (63%). Ogura et al. (4) evaluated coagulation activity, organ dysfunction, and SIRS in critically-ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. In critically-ill patients with thrombocytopenia, they found that coagulopathy and organ dysfunction progressed with a significant mutual correlation, depending on the increase in SIRS scores. Thus, SIRSassociated coagulopathy may play a critical role in inducing organ dysfunction after severe insult. 1051This article is freely accessible online.Correspondence to: Tomoharu Miyashita,

The effectiveness of preoperative (neoadjuvant) chemotherapy (NAC) for resectable pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study retrospectively evaluated the efficacy of NAC with gemcitabine (GEM)-based regimens or GEM monotherapy for resectable PDAC. Between 2006 and 2015, NAC with GEM was performed in 52 cases (head 31, and body and tail 21) and compared with 34 resection-only cases serving as controls (head 20, and body and tail 14). According to the Response Evaluation Criteria In Solid Tumors guidelines, the treatment effect was a partial response in 5 cases, stable disease in 45 cases, and progressive disease in 2 cases. Maximum standardized uptake values and carbohydrate antigen (CA19-9) values were significantly reduced after preoperative chemotherapy. Using the Evans grading system, the treatment effect was grade I in 31 patients, grade IIa in 8, and grade IIb in 3 cases. There were significant differences in the overall survival rate between the NAC and control groups, only in the patients with node-positive pancreatic head cancer. Significantly higher CA19-9 values in peripheral blood and higher lymph node metastasis and plexus invasion rates were observed in early-recurring cases within a year. The preoperative CA 19-9 cutoff value as an early recurrence risk factor was calculated as 30 U/ml in the NAC group and 88 U/ml in the control group. NAC with GEM prolonged survival in patients with node-positive pancreatic head cancer. High CA19-9 values before operation, lymph node metastases and plexus invasion were risk factors for early tumor recurrence after surgery. Preoperative chemotherapy would be necessary for resectable pancreatic head cancer as lymph node metastasis was observed in >60% with resectable PDAC. Moreover, if normalization of CA19-9 values is not achieved with NAC, extension of preoperative chemotherapy should be considered as for borderline resectable PDAC cases.

Abstract. Background: In this study, the effects of neoadjuvant chemotherapy (NAC) on cancer-associated fibroblasts (CAFs