Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon cancer cell line SW480 for apoptosis induction.

The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.

Treatment of gallbladder stone with common bile duct stones in the laparoscopic era.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) for stone can be carried out by either laparoscopic transcystic stone extraction (LTSE) or laparoscopic choledochotomy (LC). It remains unknown as to which approach is optimal for management of gallbladder stone with common bile duct stones (CBDS) in Chinese patients. METHODS: From May 2000 to February 2009, we prospective treated 346 consecutive patients with gallbladder stones and CBDS with laparoscopic cholecystectomy and LCBDE. Intraoperative findings, postoperative complications, postoperative hospital stay and costs were analyzed. RESULTS: Because of LCBDE failure,16 cases (4.6%) required open surgery. Of 330 successful LCBDE-treated patients, 237 underwent LTSE and 93 required LC. No mortality occurred in either group. The bile duct stone clearance rate was similar in both groups. Patients in the LTSE group were significantly younger and had fewer complications with smaller, fewer stones, shorter operative time and postoperative hospital stays, and lower costs, compared to those in the LC group. Compared with patients with T-tube insertion, patients in the LC group with primary closure had shorter operative time, shorter postoperative hospital stay, and lower costs. CONCLUSIONS: In cases requiring LCBDE, LTSE should be the first choice, whereas LC may be restricted to large, multiple stones. LC with primary closure without external drainage of the CBDS is as effective and safe as the T-tube insertion approach.

Primary closure after laparoscopic common bile duct exploration versus T-tube.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is now one of the main methods for treating choledocholithiasis accompanied with cholelithiasis. The objective of our study was to assess the safety and effectiveness of laparoscopic primary closure for the treatment of common bile duct (CBD) stones compared with T-tube drainage. METHODS: Patients who underwent CBD stones were studied prospectively from 2002-2012 in a single center. A total of 194 patients were randomly assigned to group A (LCBDE with primary closure) with 101 cases and group B (LCBDE with T-tube drainage) with 93 cases. Intraoperative cholangiography and choledochoscopy were performed in all patients. Patient demographics, intraoperative findings, postoperative stay, complications, and hospital expenses were recorded and analyzed. RESULTS: There was no mortality in the two groups. Four patients (3.96%) of group A were converted to open surgery, and three patients (3.23%) in group B. The mean operating time was much shorter in group A than in group B (102.6 ± 15.2 min versus 128.6 ± 20.4 min, P < 0.05). The length of postoperative hospital stay was longer in group B (4.9 ± 3.2 d) than in group A (3.2 ± 2.1 d). The hospital expenses were significantly lower in group A. Three patients experienced postoperative complications, which were related to the usage of the T-tube in group B. The incidences of overall postoperative complications were insignificantly lower in group A. CONCLUSIONS: Laparoscopic primary closure of CBD is safe and effective for the management of CBD stones, and can be performed routinely as an alternative to T-tube drainage.

Meta-analysis of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization alone for hepatocellular carcinoma.

This meta-analysis was conducted to compare transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) with TACE alone for hepatocellular carcinoma. We searched MEDLINE, EMBASE and CENTRAL for all relative randomized controlled trials (RCTs) and retrospective studies until October 31 2016. Tumor response, recurrence-free survival, overall survival and postoperative complications were the major evaluation indices. Review Manager (version 5.3) was used to analyze the data. Dichotomous data was calculated by odds ratio (OR) with 95% confidence intervals (CI). There were 1 RCT and 10 retrospective studies with 928 patients in this meta-analysis: 412 patients with TACE plus RFA and 516 patients with TACE alone. Compared with TACE alone group, TACE plus RFA group attained higher tumor response rates (OR = 6.08, 95% CI = 4.00 to 9.26, P < 0.00001), achieved longer recurrence-free survival rates (ORRFS = 3.78, 95% CI: 2.38 to 6.02, P < 0.00001) and overall survival rates (OR1-year = 3.92, 95% CI = 2.41-6.39, P < 0.00001; OR3-year = 2.56; 95% CI = 1.81-3.60; P < 0.00001; OR5-year = 2.78; 95% CI = 1.77-4.38; P < 0.0001). Serious postoperative complications were not observed, although complications were higher in TACE plus RFA group than that in TACE alone group (OR = 2.74, 95% CI = 1.07 to 7.07, P = 0.04). In conclusion, the use of TACE plus RFA for intermediate stage hepatocellular carcinoma can attain higher tumor response rates and improve survival rates than TACE alone.

Mesenchymal stem cells promote pancreatic adenocarcinoma cells invasion by transforming growth factor-ß1 induced epithelial-mesenchymal transition.

Mesenchymal stem cells (MSCs) could be ideal delivery vehicles for antitumor biological agents in pancreatic adenocarcinoma (PA). While the role of MSCs in tumor growth is elusive. Inflammation is an important feature of PA. In this study, we reported that MSCs pre-stimulated with the combination of TNF-α and IFN-γ promote PA cells invasion. The invasion of PA cell lines were evaluate by wound healing assay and transwell assay in vitro and liver metastasis in nude mice. We observed MSCs pre-stimulated with the combination of TNF-α and IFN-γ promoted PA cells invasion in vitro and in vivo. Consistent with MSCs promoting PA cells invasion, PA cells were found undergo epithelial-mesenchymal transition (EMT). We demonstrated that MSCs pre-stimulated with both of TNF-α and IFN-γ provoked expression transforming growth factor-ß1 (TGF-ß1). MSCs promoting EMT-mediated PA cells invasion could be reversed by short interfering RNA of TGF-ß1. Our results suggest that MSCs could promote PA cells invasion in inflammation microenvironment and should be cautious as delivery vehicles in molecular target therapy.

A 10-year experience with hepatic trauma in a Chinese level one trauma center.

OBJECTIVES: To analyze strategies of operative management (OM) and non-operative management (NOM), mortality, and morbidity of hepatic trauma patients. METHODS: We retrospectively reviewed 296 consecutive patients with hepatic trauma at the Department of Hepatobiliary Surgery, 101st Hospital of PLA, Wuxi, Jiangsu, China a single level one trauma center between January 2003 and December 2012. Data on demographics, mechanism of trauma, American Association for the Surgery of Trauma grade, initial management, and outcome were collected for this study. RESULTS: A total of 101 (34%) patients were of low-grade, while 195 (66%) were of high-grade. Hepatic trauma with associated injury of other organs was noted in 205 (69.3%) patients. The initial management was OM for 119 (40.2%) and NOM for 177 (59.8%), 12 patients later required laparotomy. Surgical intervention included perihepatic packing in 6, liver parenchyma suturing in 29, liver parenchyma suturing and hemostasis in 50, segmental resection in 19, and right hepatectomy in 2. The overall mortality rate was 9.1%, and the mortality rate of 8.4% was due to hepatic injuries. CONCLUSION: All hemodynamically stable patients can be managed by NOM with excellent results, while high-grade hepatic injuries require OM due to hemodynamic instability, or concomitant injuries.

Risk factors affecting conversion in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy is the gold standard in the treatment for cholelithiasis, but there are still some patients requiring conversion to open cholecystectomy for several factors. The objective of this study was to evaluate preoperative risk factors for conversion from laparoscopic to open cholecystectomy. METHODS: One thousand two hundred and sixty-five laparoscopic cholecystectomies were carried out from January 2005 to January 2006 in our hospital. Preoperative clinical, laboratory and radiographic parameters of these patients were kept prospectively and analysed retrospectively. RESULTS: Conversion to open cholecystectomy was needed in 94 patients (7.4%). The main reason for conversion was inability to safely display and identify anatomical structures of Calot's triangle correctly secondary to severe inflammation or dense adhesions, Multivariate analysis identified male sex, with Murphy's sign positive, gall bladder wall thickness > 4 mm and previous upper abdominal surgery as independent predictors of conversion rate to laparotomy. CONCLUSION: Preoperative risk factors evaluated by the present study confirm the likelihood of conversion. Recognition of these factors was important for understanding the characteristics of patients at a higher risk of conversion. Identifying risk factors will help the surgeon to plan and counsel the patients and introduce new policies.