The clinical significance of preoperative serum fibrinogen levels and platelet counts in patients with gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma (GBC) was the most common malignancy of biliary tract. Patients with malignancies frequently present with activated coagulation pathways, which might potentially related to tumor progression and prognosis. The purpose of the study was to investigate the clinical significance of preoperative serum fibrinogen levels and platelet counts in GBC patients. METHODS: The preoperative fasting serum fibrinogen levels and platelet counts of 58 patients with GBC were measured by AUV2700 automatic biochemical analyzer, as well as 60 patients with cholesterol polyps and 60 healthy volunteers. Kaplan-Meier survival analysis was applied to show the correction between fibrinogen levels and outcome after surgery. RESULTS: The fibrinogen levels of patients with GBC were significantly higher than healthy gallbladder and cholesterol polyp of gallbladder (p < 0.001 and p < 0.001, respectively). In GBC, fibrinogen levels were associated with tumor depth (p = 0.001), lymph node metastasis (p = 0.002), distant metastasis (p < 0.001) and Tumor Node Metastasis (TNM) stage (p < 0.001). The levels in TNM stage IV disease were significantly higher than stage III or stage I + II disease (p = 0.048 and p < 0.001, respectively), and in TNM stage III disease were significantly higher than stage I + II disease (p = 0.002). Furthermore, the overall survival was better in low fibrinogen level group than in high fibrinogen level group (p < 0.001). However, thrombocytosis was not significantly associated with overall survivals (p > 0.05) in multivariate analysis. CONCLUSIONS: The preoperative serum fibrinogen levels and platelet counts might be reliable biomarkers for the occurance of disease, tumor depth, lymph node metastasis, distant metastasis and advanced TNM stage in patients with GBC. The serum fibrinogen levels might be a prognostic factor to predict outcome for GBC patients suffering from surgery treatment. Anticoagulation therapy might be considered to control cancer progression in future studies.

CD276 Promotes Vasculogenic Mimicry Formation in Hepatocellular Carcinoma via the PI3K/AKT/MMPs Pathway.

PURPOSE: CD276 protein expression and vasculogenic mimicry (VM) formation are associated with the poor prognosis of hepatocellular carcinoma (HCC) patients. Although both the effects of CD276 and VM formation involve the activation of matrix metalloproteinases, and their relationship has not yet been explored. The following study investigated the effect of CD276 expression on VM formation and the potential mechanisms. MATERIALS AND METHODS: CD276 expression and VM were examined in commercial tissue microarrays by immunohistochemistry and CD31/PAS double staining. Tumor cell proliferation, invasion, migration and, tube formation were detected in vitro after transfecting HCC cell lines with an shRNA lentiviral vector against CD276. The expression of MMP14, MMP2, VE-cadherin, E-cadherin, and vimentin and MMPs activation was detected by Western blot, immunofluorescence and gelatin zymography assay. In addition, an orthotopic xenograft model of HCC cells was established in vivo, after which VM was detected, along with its marker molecules. RESULTS: CD276 expression was associated with VM and poor prognosis in HCC patients. RNA interference of CD276 reduced tumor cell proliferation, invasion, migration, and VM formation in vitro and in vivo. Furthermore, CD276 knockdown up-regulated the expression of E-cadherin but inhibited the phosphorylation of AKT, the expression of MMP14, MMP2, VE-cadherin, vimentin and the activation of MMP2 and MMP9 in HCC cell lines. CONCLUSION: CD276 may promote VM formation by activating the PI3K/AKT/MMPs pathway and inducing the EMT process in HCC. CD276 may serve as a promising candidate for the anti-VM treatment of HCC.

Risk Factors for Cholangiocarcinoma After Initial Hepatectomy for Intrahepatic Stones.

BACKGROUND: Aggressive hepatectomy is effective in treating intrahepatic stones and may minimize the deleterious consequences of subsequent cholangiocarcinoma (S-CCA). The risk factors of S-CCA after different methods of hepatectomy may vary with the resection scope of stone-affected segments. METHODS: We reviewed the records of 981 patients of primary intrahepatic stones with elective hepatectomy from January 2000 to December 2010. The clinical characteristics of patients in the S-CCA group (n = 55) and the control group (n = 926) were compared. The uniformity between extent of liver resection (ELR) with stone-affected segments (SAS) was segmented into 2 varieties: ELR = SAS with ELR < SAS according to the different hepatic resection scopes. Cox regression model with forward selection was used to identify the risk factors of S-CCA. RESULTS: In the univariate analysis, significant differences were observed between the S-CCA and control groups concerning stone location (unilateral 43.6 and 65.2 %, bilateral 56.4 and 34.8 %), residual stones (32.7 and 11.6 %), hepaticojejunostomy (43.6 and 30.9 %), and uniformity between ELR with SAS (ELR = SAS 20.0 and 42.6 %, ELR < SAS 80.0 and 57.4 %). Residual stones [hazard ratio (HR) 2.101, P = 0.016], hepaticojejunostomy (HR 1.837, P = 0.026) and uniformity between ELR and SAS (HR 2.442, P = 0.013) were independent prognostic factors for S-CCA by a Cox regression analysis with forward selection. In the subsection of ELR = SAS group, the 5- and 10-year postoperative tumor occurrence rates of unilateral and bilateral stones group were 0.9 versus 1.9 % and 3.0 versus 4.1 %, respectively (P = 0.663, log-rank). In the other subsection of ELR < SAS group, the 5- and 10-year postoperative tumor occurrence rates of unilateral and bilateral stones group were 3.4 versus 3.9 % and 6.8 versus 13.2 %, respectively (P = 0.047, log-rank), and the 5- and 10-year postoperative tumor occurrence rates of residual stones and non-residual stones group were 5.8 versus 3.0 % and 16.0 versus 7.9 %, respectively (P = 0.015, log-rank). CONCLUSIONS: Patients who underwent aggressive hepatectomy and had ELR = SAS had better outcomes than those with ELR < SAS. In the patients with ELR = SAS, the S-CCA rates of unilateral and bilateral stones were low and comparable. However, patients with ELR < SAS and bilateral intrahepatic or residual stones should be monitored more carefully for high-risk factors of S-CCA.

Serum vascular endothelial growth factors C and D as forecast tools for patients with gallbladder carcinoma.

Gallbladder carcinoma (GBC) is the most common cancer of the biliary tract. Lymph node metastasis (LNM) is the major diffusion route of GBC and is a prognosis factor. The aim of study was to assess the potential of the serum VEGF-C and VEGF-D (sVEGF-C/D) levels to predict the presence of LNM and the survival of GBC patients. The preoperative sVEGF-C/D levels of 31 patients with GBC, 10 patients with cholesterol polyps, and 10 healthy volunteers were measured by enzyme-linked immunoadsorbent assay (ELISA). The sVEGF-C/D levels of patients with GBC were significantly higher than those of people with healthy gallbladders (p < 0.001 and p = 0.001, respectively) and cholesterol polyp (p = 0.032 and p = 0.004, respectively). In GBC, the sVEGF-C levels were associated with LNM (p = 0.011), distant metastasis (p = 0.018), and stage (p = 0.045), but the sVEGF-D levels had a significant association with the tumor depth (p = 0.001), LNM (p = 0.001), distant metastasis (p = 0.047), and stage (p = 0.002). The sVEGF-C/D diagnostic values for the presence of GBC were sensitivity of 71.0 and 74.2 % and specificity of 80.0 and 85.0 %, respectively. With respect to the diagnosis of LNM, the diagnostic values of sVEGF-C/D were as follows: sensitivity 81.2 and 87.5 % and specificity 73.3 and 80.0 %, respectively. The mean survival time with high sVEGF-C was significantly shorter than that with low sVEGF-C (p < 0.001), which was also true for low sVEGF-D (p = 0.032). The preoperative sVEGF-C/D levels might be reliable biomarkers for the presence of disease and LNM in patients with GBC. The sVEGF-C/D levels may be prognosis factors that can predict a poor outcome for GBC patients.