Patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) are frequently found to be unresectable on exploration due to small distant metastasis. This study was to investigate predictors of small distant metastasis in patients with potentially resectable PDAC. Patients who underwent surgical exploration for potentially resectable PDAC from 2013 to 2014 were reviewed retrospectively and divided into two groups according to whether distant metastases were encountered on exploration. Then, univariate and multivariate logistic regression analyses were used to identify predictors of distant metastasis. A scoring system to predict distant metastasis of PDAC on exploration was constructed based on the regression coefficient of a multivariate logistic regression model. A total of 235 patients were included in this study. Mean age of the study population was 61.7 ± 10.4 years old. Upon exploration, distant metastases were found intraoperatively in 62 (26.4%) patients, while the remaining 173 were free of distant metastases. Multivariate logistic regression analysis identified that age ≤ 62 years old (p < 0.001), male sex (p = 0.011), tumor size ≥4.0 cm (p < 0.001), alanine aminotransferase level (ALT) < 125 U/L (p < 0.001), and carbohydrate antigen (CA19–9) level ≥ 385 U/mL (p < 0.001) were independent risk factors for occult distant metastasis of PDAC. A preoperative scoring system (0–8 points) for distant metastasis on exploration was constructed using these five factors. The receiver operating characteristic curves showed that the area under the curve of this score was 0.85. A score of 6 points was suggested to be the optimal cut-off value, and the sensitivity and specificity were 85% and 69%, respectively. Distant metastasis is still frequently encountered on exploration for patients with potentially resectable PDAC. Younger age, male sex, larger tumor size, low ALT level and high CA19–9 level are independent predictors of unexpected distant metastasis on exploration.
13 February 2017 in Journal of Experimental & Clinical Cancer Research
Overexpression of paternally expressed gene-10 (PEG10) is known to promote the progression of several carcinomas, however, its role in pancreatic cancer (PC) is unknown. We investigated the expression and function of PEG10 in PC. PEG10 expression and correlation with PC progression was assessed in cancerous tissues and paired non-cancerous tissues. Further, the role of PEG10 in PC cell progression and the underlying mechanisms were studied by using small interfering RNA (Si-RNA). PEG10 expression was significantly higher in cancerous tissues and correlated with PC invasion of vessels and Ki-67 expression. Si-RNA mediated PEG10 knockdown resulted in inhibition of proliferation and G0/G1 cell cycle arrest, which was mediated by p21 and p27 upregulation. A decrease in PC cell invasion and migration, mediated by ERK/MMP7 pathway, was observed in PEG10 knockdown group. Further, findings of ChIP assay suggested that E2F-1 could directly enhance the expression of PEG10 through binding to PEG10 promoter. In conclusion, PEG10 was identified as a prognostic biomarker for PC and E2F-1 induced PEG10 could promote PC cell proliferation, invasion, and metastasis.
Guidelines do not recommend resection surgery for oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, reports in small samples of selected patients suggest that surgery extends survival. Thus, this study aims to gather evidence for the benefits of cancer-directed surgery (CDS) by analyzing a national cohort and identifying prognostic factors that aid the selection of candidates for CDS or recruitment into experimental trials. Data for patients with PDAC and hepatic metastasis were extracted from the population-based Surveillance, Epidemiology, and End Results database (SEER). The bias between CDS and non-CDS groups was minimized with Propensity Score Matching (PSM), and the prognostic role of CDS was investigated by comparing Kaplan-Meier estimators and Cox proportional hazard models. A total of 12,018 patients were extracted from the database, including 259 patients who underwent CDS that were 1:1 propensity score-matched with patients who did not receive CDS. CDS appeared to significantly prolong median overall survival from 5 to 10 months. Multivariate analysis revealed chemotherapy as a protective prognostic, whilst survival was impaired by old age and tumors that were poorly differentiated (Grades III–IV). These factors can be used to select patients likely to benefit from CDS treatment, which may facilitate recruitment into randomized controlled trials.
Duodenal stump fistula is a rare but dangerous complication of gastric cancer surgery. Reinforcement of the duodenal stump was suggested as a useful method to prevent the occurrence of duodenal stump fistula. Although laparoscopic surgery has been established as a safe procedure for gastric cancer, it is acknowledged that the application of duodenal stump reinforcement is a demanding process in laparoscopic radical gastrectomy. This review aims to provide a concise description of the proposed reinforcement methods of duodenal stump after laparoscopic radical gastrectomy for gastric cancer by summarizing the relevant literature written in English. The thorough knowledge of these reinforcement techniques may help surgeons to find the most suitable reinforcement method of duodenal stump for patients.
17 January 2022 in Basic & Clinical Pharmacology & Toxicology
Pancreatic surgery is complicated by untreated fluid leakage, but no tenable techniques exist to detect and close leakage sites during surgery. A novel hydrogel called SmartPAN has been developed to meet this need and is here assessed for safety before trials on human patients. First, resazurin assays were used to test the cytotoxic effects of SmartPAN's active bromothymol blue (BTB) indicator and its solution of phosphate‐buffered saline (PBS) on normal (HPDE: human pancreatic duct epithelial) or carcinomic (FAMPAC) human pancreatic cells. Cells incubated with BTB showed no significant reduction in cell viability below threshold safety levels. However, PBS had a mild cytotoxic effect on FAMPAC cells. Second, SmartPAN's pathological effects were evaluated in vivo by applying 4‐ml SmartPAN to a porcine (Sus scrofa domesticus) model of pancreatic resection. There were no significant differences in macroscopic and microscopic pathologies between pigs treated with SmartPAN or saline. Third, measurements using HPLC‐MS/MS demonstrate that BTB does not cross into the bloodstream and was eliminated from the body within 2 days of surgery. Overall, SmartPAN appears safe in the short term and ready for first‐in‐human trials because its components are either biocompatible or quickly neutralized by dilution and drainage.