Importance Hyperthermic intraperitoneal chemotherapy (HIPEC) has been employed within various multimodality strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis. Objective To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness at different stages of peritoneal disease progression. Data Sources Medline and Embase databases between January 1, 1985, and June 1, 2016. Study Selection Randomized control trials (RTC) and high-quality nonrandomized control trials (NRCTs) selected on a validated tool (Methodological Index for Nonrandomized Studies) comparing HIPEC and standard oncological management for the treatment of advanced stage gastric cancer with and without peritoneal carcinomatosis were considered. Data Extraction and Synthesis A random-effects network meta-analysis. Main Outcomes and Measures The primary outcomes were overall survival and disease recurrence. Secondary outcomes were overall complications, type of complications, and sites of recurrence. Results A total of 11 RCTs and 21 NRCTs (2520 patients) were included. For patients without the presence of peritoneal carcinomatosis (PC), the overall survival rates between the HIPEC and control groups at 3 or 5 years resulted in favor of the HIPEC group (RR=0.82, P=0.01). No difference in the 3-year overall survival (RR=0.99, P=0.85) in but a prolonged median survival of 4 months in favor of the HIPEC group (WMD=4.04, P<0.001) was seen in patients with PC. HIPEC was associated with significantly higher risk of complications for both patients with PC (RR=2.15, P<0.01) and without (RR=2.17, P<0.01). This increased risk in the HIPEC group was related to systemic drugs toxicity. Anastomotic leakage rates were found to be similar between groups. Conclusions and Relevance Our study demonstrates a survival advantage of the use of HIPEC as a prophylactic strategy and suggests that patients whose disease burden is limited to positive cytology and limited nodal involvement may benefit the most from HIPEC. For patients with extensive carcinomatosis, the completeness of cytoreductive surgery is a critical prognostic factor for survival. Future RCTs should better define patient selection criteria.

Purpose To assess the clinical and pathological significance of mast cell infiltration in human pancreatic cancer and evaluate crosstalk between mast cells and cancer cells in vitro. Experimental Design Immunohistochemistry for tryptase was performed on 53 pancreatic cancer specimens. Mast cell counts were correlated with clinical variables and survival. Serum tryptase activity from cancer patients was compared to patients with benign pancreatic disease. In vitro, the effect of pancreatic cancer conditioned media on mast cell migration was assessed. The effect of conditioned media from the human mast cell line, LAD-2, on cancer and normal ductal cell proliferation was assessed by thymidine incorporation. Matrigel invasion assays were used to evaluate the effect of mast cell conditioned media on cancer cell invasion in the presence and absence of a matrix metalloproteinase inhibitor, GM6001. Results Mast cell infiltration was significantly increased in pancreatic cancer compared to normal pancreatic tissue [11.4±6.7vs.2.0±1.4(p<0.001)]. Increased infiltrating mast cells correlated with higher grade tumors (p<0.0001) and worse survival. Patients with pancreatic cancer had elevated serum tryptase activity (p<0.05). In vitro, AsPC1 and PANC-1 cells induced mast cell migration. Mast cell conditioned media induced pancreatic cancer cell migration, proliferation and invasion but had no effect on normal ductal cells. Furthermore, the effect of mast cells on cancer cell invasion was in large part MMP-dependent. Conclusions Tumor infiltrating mast cells are associated with worse prognosis in pancreatic cancer. In vitro, the interaction between mast cells and pancreatic cancer cells promote tumor growth and invasion.

Our results demonstrate that the flavonoid apigenin decreases glucose uptake and downregulates the GLUT-1 glucose transporter in human pancreatic cancer cells. In addition, the inhibitory effects of apigenin and the PI3K inhibitors on GLUT-1 are similar, indicating that the PI3K/Akt pathway is involved in mediating apigenin's effects on downstream targets such as GLUT-1.

Functional CD8+ T cells in human tumors play a clear role in clinical prognosis and response to immunotherapeutic interventions. PD-1 expression in T cells involved in chronic infections and tumors such as melanoma often correlates with a state of T-cell exhaustion. Here we interrogate CD8+ tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8+ TILs retain robust capacity for production of effector cytokines and degranulation capacity. In contrast, melanoma CD8+ TILs display dramatic reduction of cytokine production and degranulation capacity. We show that CD8+ TILs from human breast tumors can potently kill cancer cells via bi-specific antibodies. Our data demonstrate that CD8+ TILs in human breast tumors retain polyfunctionality, despite PD-1 expression, and suggest that they may be harnessed for effective immunotherapies.