Background Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC. However, almost all of those studies used primary tumor tissues. Methods In this study, we employed a single-cell RNA sequencing technology to profile the transcriptomes of individual cells from dissociated primary tumors or metastatic biopsies obtained from patients with PDAC. Unsupervised clustering analysis as well as a new supervised classification algorithm, SuperCT, was used to identify the different cell types within the tumor tissues. The expression signatures of the different cell types were then compared between primary tumors and metastatic biopsies. The expressions of the cell type-specific signature genes were also correlated with patient survival using public datasets. Results Our single-cell RNA sequencing analysis revealed distinct cell types in primary and metastatic PDAC tissues including tumor cells, endothelial cells, cancer-associated fibroblasts (CAFs), and immune cells. The cancer cells showed high inter-patient heterogeneity, whereas the stromal cells were more homogenous across patients. Immune infiltration varies significantly from patient to patient with majority of the immune cells being macrophages and exhausted lymphocytes. We found that the tumor cellular composition was an important factor in defining the PDAC subtypes. Furthermore, the expression levels of cell type-specific markers for EMT+ cancer cells, activated CAFs, and endothelial cells significantly associated with patient survival. Conclusions Taken together, our work identifies significant heterogeneity in cellular compositions of PDAC tumors and between primary tumors and metastatic lesions. Furthermore, the cellular composition was an important factor in defining PDAC subtypes and significantly correlated with patient outcome. These findings provide valuable insights on the PDAC microenvironment and could potentially inform the management of PDAC patients.

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.

827 patients with gastric cancer underwent 236 robotic and 591 laparoscopic radical gastrectomies with curative intent. The patients' data were prospectively collected and retrospectively analyzed. Main Outcome Measures:We performed a comparative analysis between the robotic surgery group and laparoscopic surgery group for preoperative patient characteristics, intraoperative factors, and postoperative morbidity and mortality.Results: The robotic group was younger than the laparoscopic group, but other preoperative patient charac-teristics did not differ. The mean operative time for the robotic group (219.5 minutes) was on average 49 minutes longer than the laparoscopic group (170.7 minutes) (P Ͻ .001), while mean blood loss was significantly less in the robotic group (91.6 mL vs 147.9 mL; P=.002). The robotic group had mortality of 0.4% and morbidity of 11.0%, comparable with those of the laparoscopic group (P Ͼ .05). The number of lymph nodes retrieved per level was adequate in both groups and did not differ significantly. Robotic D1ϩ␣ (n = 5), D1ϩ␤ (n=126), and D2 (n=105) dissections retrieved 27.2, 36.7, and 42.4 mean numbers of lymph nodes, respectively. Except for 3 cases in the laparoscopic group, all specimens had negative margins.Conclusions: Our largest comparative study demonstrates robotic gastrectomy to have better short-term and comparable oncologic outcomes compared with laparoscopic gastrectomy. A robotic approach to gastric cancer is a promising alternative to laparoscopic surgery.

Oncolytic virotherapy of tumors has shown promising results in both preclinical and clinical studies. Here, we investigated the therapeutic efficacy of a replicationcompetent vaccinia virus, GLV-1h68, against human pancreatic carcinomas in cell cultures and in nude mice. We found that GLV-1h68 was able to infect, replicate in, and lyse tumor cells in vitro. Virus-mediated marker gene expressions were readily detected. Moreover, s.c. PANC-1 pancreatic tumor xenografts were effectively treated by a single i.v. dose of GLV-1h68. Cancer killing was achieved with minimal toxicity. Viral titer analyses in homogenized organs and PANC-1 tumors showed that the mutant virus resides almost exclusively in the tumors and not in healthy organs. Except mild spleen enlargements, no histopathology changes were observed in any other organs 2 months after virus injection. Surprisingly, s.c. MIA PaCa-2 pancreatic tumors were treated with similar efficiency as PANC-1 tumors, although they differ significantly in sensitivity to viral lysis in cell cultures. When GLV-1h68 oncolytic viral therapy was used together with cisplatin or gemcitabine to treat PANC-1 tumors, the combination therapy resulted in enhanced and accelerated therapeutic results compared with the virus treatment alone. Profiling of proteins related to immune response revealed a significant proinflammatory immune response and marked activation of innate immunity in virus-colonized tumors. In conclusion, the GLV-1h68 strain showed outstanding therapeutic effects and a documented safety profile in mice, with great promise for future clinical development.