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For unresectable advanced hepatocellular carcinoma (HCC),besides sorafenib,alternative drugs and treatment modalities are required.Clinical studies of hepatic arterial infusion chemotherapy (HAIC),transcatheter arterial chemoembolization (TACE),and system chemotherapy have shown favorable efficacy and tolerance in advanced HCC patients.In addition,the potential efficacy of sorafenib combined with focal treatment is also an interesting issue.As more therapies become available,decision-making for treating advanced HCC becomes increasingly complex.In our opinion,diverse treatment modalities should be utilized for the best interest of patients.Based on predictive biomarkers,we should develop a precise patient stratification system to select suitable candidates for each treatment modality in future studies,as is useful for improving prognosis of patients with advanced HCC.
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Objective To explore the diagnosis,treatment,risk factors and prognosis factors of postpancreaticoduodenectomy hemorrhage (PPH).Methods The retrospective case-control study was adopted.The clinical data of 703 patients who underwent pancreatoduodenectomy at Hospital 401 of the People's Liberation Army from January 2008 to July 2013 were collected.Standard pancreatoduodenectomy was carried out for the malignant tumors of the head of pancreas or ampulla,pylorus-preserving pancreatoduodenectomy was operated for the benign tumor or the duodenal papilla tumor.The corresponding treatment was adopted for PPH.The observation indicators included:(1) the surgical situation (surgical method,operation time and the volume of intraoperative blood loss),(2) diagnosis of PPH,(3) treatment of PPH,(4) univariate and multivariate analyses for the risk factors affecting the occurrence of PPH,(5) univariate and multivariate analyses for the risk factors affecting prognosis of PPH patients.The measurement data with normal distribution were represented as x ± s.The measurement data with skewed distribution were represented as M (range).The chi-square test or Fisher exact probability was used for univariate analysis.Logistic regression model was used for multivariate analysis.Results (1) The surgical situation:among 703 patients,409 patients underwent standard pancreatoduodenectomy and 294 underwent pylorus-preserving pancreatoduodenectomy,including 1 combined with right hemihepatectomy,27 with portal vein reconstruction and 2 with hepatic artery reconstruction.Pancreaticojejunostomy was applied to 658 patients using mucosa anastomosis of the pancreatic duct to jejunum and 45 patients using invagination anastomosis.Supporting tube was routinely deposed in the pancreatic duct,598 patients had internal drainage and 105 patients had external drainage.The end-to-side anastomosis between common bile duct and jejunum was used for choledochojejunostomy.The 409 patients received the gastrojejunostomy using side-to-side anastomosis of gastric part and jejunum and 294 patients using end-to-side anastomosis of duodenum and jejunum.Operation time and volume of intraoperative blood loss were (324 ± 54) minutes and (428 ± 118) mL.(2) The diagnosis of PPH:among 703 patients after pancreatoduodenectomy,62 patients had PPH,the hemorrhage reasons of 38 patients had been identified,and the hemorrhage reasons of 24 patients had not been identified (A level in 5 patients,B level in 17 patients,C level in 2 patients).① The site of hemorrhage:the hemorrhage outside the cavity were detect in 27 patients,the hemorrhage inside the cavity in 28 patients,and the hemorrhage from both outside and inside part of the cavity in 7 patients.② The time of hemorrhage:early-stage hemorrhage were detected in 5 patients and the delayed hemorrhage in 57 patients.③The volume of postoperative blood loss was (885 ± 253)mL,30 patients had mild hemorrhage and 32 patients had severe hemorrhage.④ The clinical classification of PPH:5,32 and 25 patients were detected in level A,B,C,and 19 patients combined with sentinel hemorrhage.(3) The treatment of PPH:①5 patients with PPH in A level were given clinical observation,blood volume supplement and other treatment,then the symptoms gradually turned better.② Among 32 patients with PPH in B level,15 patients became better after symptomatic and supportive treatments,6 patients received successful hemostasis after guglielmi detachable colis embolization,4 patients received successful hemostasis under gastroscopic hemostasis,7 patients received emergency exploratory laparotomy.Thirty-two patients were improved and then out of hospital after treatment,without occurrence of death.③ Among 25 patients with PPH in C level,4 patients received successful hemostasis after guglielmi detachable colis embolization,17 patients received hemostasis by emergency exploratory laparotomy,4 patients with undiscovered bleeding points received the treatment of fluid infusion,blood volume supplement and antacid.Among 25 patients after corresponding treatment,10 patients were improved and 15 patients were dead.(4) The result of univariate analysis showed that the combined hypertension,vascular resection and reconstruction,postoperative pancreatic leakage and postoperative intraabdominal infection were risk factors affecting the occurrence of PPH (x2 =4.950,5.300,7.568,5.505,P ＜ 0.05).The results of multivariate analysis showed that the combined pancreatic leakage and postoperative intraabdominal infection were independent risk factors affecting the occurrence of PPH [OR =2.761,2.216,95％ confidence interval (CI):1.389-5.489,1.198-4.101,P ＜ 0.05].(5) The risk factors affecting the prognosis of PPH patients:the results of univariate analysis showed that postoperative sentinel hemorrhage,postoperative pancreatic leakage,site,degree and level of hemorrhage were risk factors affecting the prognosis of PPH patients (x2 =8.022,4.448,11.853,18.551,28.285,P ＜ 0.05).The results of multivariate analysis showed that postoperative sentinel hemorrhage and site of hemorrhage (outside and inside part of the cavity) were independent risk factors affecting the prognosis of PPH patients (OR =5.550,0.233,95％ CI:1.595-19.314,0.086-0.635,P ＜ 0.05).Conclusions Pancreatic leakage and intraabdominal infection are independent risk factors after pancreatoduodenectomy.The treatment effect of the early-stage hemorrhage is better than that of the delayed hemorrhage,and angiographic embolization is the first choice of diagnosis and treatment for the delayed hemorrhage.Sentinel hemorrhage could result from aneurysm or continuous arterial hemorrhage of vascular erosion,it is the independent risk factor affecting the death of hemorrhage after pancreatoduodenectomy.
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Objective To examine the role of c-Src activation in hepatitis B virus X (HBx) protein induced epithelial-mesenchymal transition (EMT) in liver cancer.Methods SMMC-7721 liver cancer cells were transfected with HBx gene to induce EMT and the activated c-Src expression was evaluated by Western blot.Both the morphological changes and the epithelial and mesenchymal markers expression (real-time PCR,western blot and immunocytochemistry) of HBx-transfected SMMC-7721 cell treated by c-Src kinase inhibitor PP2 and negative control PP3 were observed and compared,respectively.Results The activated c-Src expression in HBx gene transfected SMMC-7721 cells was significantly increased compared to that in mock transfected cells,c-Src kinase inhibitor PP2 could enable the HBx-transfected SMMC-7721 cells to transmit from spindle-like shape to original epithelial morphology.Western blot and immunocytochemistry confirmed that the expression of epithelial markers and mesenchymal markers almost returned to the levels of parental cells,indicating the mesenchymal-epithelial transition.Conclusions c-Src activation plays a key role in the process of EMT induced by HBx protein in SMMC-7721 cells.
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Objectives To analyze the expression of fibroblast growth factor-19(FGF-19) in hepatocellular carcinoma ( HCC) and adjacent tissues , and to investigate its clinical significance .Methods A total of 209 HCC patients who had undergone radical resection operations at Hospital 401 between January 2003 and December 2009 were chosen as samples . Immunohistochemistry method was employed to examine the expression level of FGF-19 in HCC and adjacent tissues .The relationship between FGF-19 protein expressions and clinicopathological features was analyzed by the chi -square test or Fisher exact probability .A survival curve was drawn using the Kaplan-Meier method and the Cox model was used to analyze factors that influenced survival .Results The rate of high expression of FGF-19 was 66.1% (138/209) in HCC, which was significantly higher than 46.9%(98/209) in adjacent tissues (P<0.05).The high expression of FGF-19 was related to the tumor capsule and tumor boundary (P<0.05).The overall survival in high expression of FGF-19 group was signifi-cantly lower than that in low expression group (P<0.05).Conclusion FGF-19 plays an important role in the carcinogen-esis and development of HCC , and a high expression of FGF-19 might be closely related to survival time of postoperative patients.FGF-19 might be a potential prognosis prediction factor for HCC .