The phospholipase PNPLA7 functions as a positive indicator in human colorectal and gastric cancers.

Early diagnosis of gastrointestinal tumors remains a clinical challenge due to their insidious onset. Patatin-like phospholipase domain containing protein 7 (PNPLA7) has been shown to be associated with the occurrence and development of hepatocellular carcinoma. However, the expressions of PNPLA7 in colorectal and gastric cancers remain unclear. The online gene expression profiling interactive analysis and Kaplan-Meier Plotter databases were used for the analysis of the expression of PNPLA7 and the survival curve, respectively. The tumor tissues and their corresponding normal noncancerous tissues from colorectal cancer or gastric cancer patients were collected and quantitative real-time polymerase chain reaction assay was performed to evaluate the expression of related genes. PNPLA7 was significantly down-regulated in gastric and colorectal cancer tumor tissues compared to adjacent normal tissues. Receiver operating characteristic analysis showed that PNPLA7 could be used as a diagnostic marker for gastric and colorectal tumors. The overall survival of patients with high expression of PNPLA7 was also significantly higher than that of patients with low expression in stomach and rectum adenocarcinoma. Phospholipase PNPLA7 can be used as a positive diagnostic indicator for colorectal and gastric cancers.

Risk factor analysis and construction of prediction models of gallbladder carcinoma in patients with gallstones.

Background: Gallbladder carcinoma (GBC) is a biliary tract tumor with a high mortality rate. The objectives of this study were to explore the risk factors of GBC in patients with gallstones and to establish effective screening indicators. Methods: A total of 588 patients from medical centers in two different regions of China were included in this study and defined as the internal test samples and the external validation samples, respectively. We retrospectively reviewed the differences in clinicopathologic data of the internal test samples to find the independent risk factors that affect the occurrence of GBC. Then, we constructed three different combined predictive factors (CPFs) through the weighting method, integral system, and nomogram, respectively, and named them CPF-A, CPF-B, and CPF-C sequentially. Furthermore, we evaluated these indicators through calibration and DCA curves. The ROC curve was used to analyze their diagnostic efficiency. Finally, their diagnostic capabilities were validated in the external validation samples. Results: In the internal test samples, the results showed that five factors, namely, age (RR = 3.077, 95% CI: 1.731-5.496), size of gallstones (RR = 13.732, 95% CI: 5.937-31.762), course of gallstones (RR = 2.438, 95% CI: 1.350-4.403), CEA (RR = 9.464, 95% CI: 3.394-26.392), and CA199 (RR = 9.605, 95% CI: 4.512-20.446), were independent risk factors for GBC in patients with gallstones. Then, we established three predictive indicators: CPF-A, CPF-B, and CPF-C. These models were further validated using bootstrapping with 1,000 repetitions. Calibration and decision curve analysis showed that the three models fit well. Meanwhile, multivariate analysis showed that CPF-B and CPF-C were independent risk factors for GBC in patients with gallstones. In addition, the validation results of the external validation samples are essentially consistent with the internal test samples. Conclusion: Age (≤58.5 vs. >58.5 years), size of gallstones (≤1.95 vs. >1.95cm), course of gallstones (≤10 vs. >10 years), CEA (≤5 vs. >5 ng/ml), and CA199 (≤37 vs. >37 U/ml) are independent risk factors for GBC in patients with gallstones. When positive indicators were ≥2 among the five independent risk factors or the score of the nomogram was >82.64, the risk of GBC was high in gallstone patients.

Golgi phosphoprotein 3 promotes the proliferation of gallbladder carcinoma cells via regulation of the NLRP3 inflammasome.

Golgi phosphoprotein 3 (GOLPH3) has been demonstrated to promote tumor progression in various gastrointestinal malignancies. However, its effects in gallbladder carcinoma (GBC) remain unknown. In the present study, the expression levels of GOLPH3 and nucleotide­binding domain leucine­rich repeat and pyrin domain containing receptor 3 (NLRP3) in human GBC tissues were detected by immunohistochemistry, and the clinical data and survival of these patients were analyzed. Next, whether GOLPH3 could affect tumor proliferation via regulation of the NLRP3 inflammasome was investigated in vitro. The results demonstrated that GOLPH3 could promote GBC cell proliferation, and that it regulated protein expression levels of NLRP3, as well as Caspase­1 P10. Conversely, knockdown of NLRP3 reversed the effects of GOLPH3 overexpression on GBC cell proliferation. GOLPH3 and NLRP3 expression levels were found to be upregulated in GBC tissues and their expression was positively correlated. The expression of GOLPH3 and NLRP3 was associated with the expression of the proliferative marker Ki­67 in tissues, and associated with poor survival, tumor stage, degree of differentiation, depth of invasion, carbohydrate antigen 19­9 and C­reactive protein levels in patients with GBC. In summary, these results indicate that GOLPH3 promotes GBC cell proliferation via a NLRP3/Caspase­1 pathway. GOLPH3 and NLRP3 participate in the process of human GBC growth and may serve as a potential therapeutic targets.

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.

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.

Clinical significance of stanniocalcin expression in tissue and serum of gastric cancer patients.

PURPOSE: Stanniocalcin (STC) has been recognized as a potential biomarker in a variety of cancers. The aim of this study was to examine STC1 and STC2 expression in tumor and serum samples from gastric cancer (GC) patients. METHODS: A total of 83 GC patients treated with radical resection were enrolled in this study. Immunohistochemistry was used to detect STC protein expression in paired tumor and adjacent normal tissues. Serum STC levels were determined by enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristics (ROC) curve was constructed to describe diagnostic specificity and sensitivity. RESULTS: Both of STC1 and STC2 protein expression were upregulated in GC tissues compared with that in normal ones. Moreover, the high/moderate of STC1 protein was significantly associated with lymph metastasis, clinical stage and adverse 3-year progression-free survival (PFS). In addition, serum STC1 and STC2 expression in GC patients were much higher than that in patients with benign gastric disease, which decreased at postoperative 7-10 days. The sensitivity of serum STC protein also showed superiority over CEA and CA19-9. CONCLUSIONS: STC upregulation plays an important role in GC development, and serum STC1 and STC2 might function as promising tumor markers for GC diagnosis and prognosis.

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.

Overexpression of phosphorylated 4E-binding protein 1 predicts lymph node metastasis and poor prognosis of Chinese patients with hilar cholangiocarcinoma.

Previous studies have confirmed the role of phosphorylated form of 4E-binding protein 1 (p-4E-BP1) as a good candidate tumor biomarker. The aim of this study was to investigate p-4E-BP1 expression status in hilar cholangiocarcinoma (HCCA) specimens and to clarify its clinical significance. Tissue microarray containing tumor specimens obtained from 61 patients with HCCA were constructed. p-4E-BP1 was investigated by immunohistochemical studies. High/moderate expression p-4E-BP1 was observed in 57.4% (35/61) primary cancer specimens. Overexpression of p-4E-BP1 protein was associated with poor differentiation and regional lymph node metastasis. Survival analysis and Cox proportional hazards model revealed that p-4E-BP1 overexpression was an independent factor in predicting recurrence-free survival and overall survival for HCCA patients, apart from tumor invasion and complete resection. P-4E-BP1 was highly expressed in HCCA. Overexpressed p-4E-BP1 might be a novel biomarker to predict the clinical outcome of patients with resected HCCA.

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.

Role of elevated liver transaminase levels in the diagnosis of liver injury after blunt abdominal trauma.

The liver is the second most commonly injured organ following blunt abdominal trauma. The stable patient with minimal physical findings with a history of blunt abdominal trauma presents a challenge for diagnosis of liver injury. This study was conducted to determine the usefulness of hepatic transaminases in predicting the presence of liver injury and its severity following blunt abdominal trauma. In this retrospective study, we included all patients who had sustained blunt abdominal injury and were treated at our institution between January 2008 and December 2010. The grading of the liver injury was verified using CT scans or surgical findings. One hundred and eighty-two patients with blunt abdominal trauma underwent the required blood tests and were included in the study. Using receiver operating characteristic (ROC) curve assessment, optimum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (GGT) thresholds were determined to be >57 U/l, 113 U/l, 595 U/l and 50 U/l. ALT >57 U/l (OR, 66.1; P<0.001) and AST >113 U/l (OR, 30.6; P<0.001) were strongly associated with the presence of liver injuries. This association was also observed in patients with elevated LDH >595 U/l (OR, 3.8; P<0.001) and GGT >50 U/l (OR, 3.0; P<0.05). None of the laboratory tests were related to the severity of the liver injuries. In patients with blunt abdominal trauma, abnormal hepatic transaminase levels are associated with liver injuries. Patients with ALT >57 U/l and AST >113 U/l are strongly associated with liver injury and require further imaging studies and close management.

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.