Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.
A systematic review was conducted in compliance with PRISMA statement standards to identify all studies reporting outcomes of laparoscopic resection of benign or malignant lesions located in caudate lobe of liver. Pooled outcome data were calculated using random-effects models. A total of 196 patients from 12 studies were included. Mean operative time, volume of intraoperative blood loss, and length of hospital stay were 225 minutes (95% confidence interval [CI], 181-269 minutes), 134 mL (95% CI, 85-184 mL), and 7 days (95% CI, 5-9 days), respectively. The pooled risk of need for intraoperative transfusion was 2% (95% CI, 0%-5%). It was 3% (95% CI, 1%-6%) for conversion to open surgery, 6% (95% CI, 0%-19%) for need for intra-abdominal drain, 1% (95% CI, 0%-3%) for postoperative mortality, 2% (95% CI, 0%-4%) for biliary leakage, 2% (95% CI, 0%-4%) for intra-abdominal abscess, 1% (95% CI, 0%-4%) for biliary stenosis, 1% (95% CI, 0%-3%) for postoperative bleeding, 1% (95% CI, 0%-4%) for pancreatic fistula, 2% (95% CI, 1%-5%) for pulmonary complications, 1% (95% CI, 0%-4%) for paralytic ileus, and 1% (95% CI, 0%-4%) for need for reoperation. Although the available evidence is limited, the findings of the current study might be utilized for hypothesis synthesis in future studies. They can be used to inform surgeons and patients about estimated risks of perioperative complications until a higher level of evidence is available.
Aims to compare the outcomes of iatrogenic gallbladder perforation versus no gallbladder perforation in patients undergoing laparoscopic cholecystectomy. Methods In compliance with PRISMA statement standards, electronic databases were searched to identify all studies comparing the outcomes of iatrogenic gallbladder perforation versus no gallbladder perforation in patients undergoing laparoscopic cholecystectomy. The outcome of interest included surgical site infection (SSI), postoperative collection, operative time and length of hospital stay. Random effects modelling was applied to calculate pooled outcome data. The certainty of evidence was assessed using GRADE system. Results A total of 5366 patients from 11 studies were included. Analysis of 5366 patients from 11 observational studies suggested that iatrogenic gallbladder perforation during laparoscopic cholecystectomy does not increase the risk of SSI (OR 1.48, 95% CI 0.57–3.86, P=0.42) and postoperative collection (RD 0.00, 95%CI -0.00–0.01, P=0.41) but may result in longer operative time (MD 10.28, 95% CI 7.40–13.16, P <0.00001) and length of hospital stay (MD 0.51, 95%CI 0.15–0.87, P=0.005). The results remained consistent through sensitivity analyses. The quality of available evidence was judged to be moderate and the GRADE certainty of the evidence was judged to be high. Conclusions Relatively robust evidence with high level of certainty suggests that iatrogenic gallbladder perforation during laparoscopic cholecystectomy may not increase the risk of SSI and postoperative collection but may result in longer operative time and length of hospital stay. Whether prompt retrieval of spilled stones, adequate peritoneal irrigation, and intraoperative use of prophylactic antibiotic contribute to the above findings remains unknown.
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