Assessment of risk factors and development and validation of an early prediction model for mortality in patients with severe traumatic liver injury / 中华创伤杂志

Objective:To investigate the risk factors associated with mortality in patients with severe traumatic liver injury (TLI) and to establish and validate an early prediction model for mortality.Methods:A retrospective cohort study was conducted to analyze the clinical data of 273 patients with severe TLI admitted to the ICU from the medical information mart for the intensive care-IV (MIMIC-IV) database. The cohort consisted of 176 males and 97 females, with age ranging from 18 to 83 years [35.6 years(25.7,57.5)years]. The patients were divided into two groups based on in-hospital mortality: the survival group (253 patients, 92.7%) and the death group (20 patients, 7.3%). The two groups were compared with regards to gender, age, cause and type of injury, treatment method, massive blood transfusion, comorbidities as well as vital signs and laboratory tests measured within 24 hours of ICU admission. Univariate analysis was used to screen for risk factors associated with mortality in severe TLI patients. Independent risk factors for mortality were determined using multivariate Logistic regression analysis. Lasso regression was used to screen for predictors of mortality, and a nomogram prognostic model was then established through a multivariate Logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the discrimination of the model, while the Hosmer-Lemeshow goodness-of-fit test and calibration curve were used to evaluate the calibration of the model. The model′s clinical applicability was evaluated through decision curve analysis (DCA). Internal validation was performed by the 200 Bootstrap samples, and external validation was performed by using 163 patients with severe TLI from the emergency ICU collaborative research database (eICU-CRD). Finally, the predictive efficacy of the nomogram model was compared to other trauma or severity scores.Results:Univariate analysis showed that the age, cause of injury, massive blood transfusion, chronic liver disease and laboratory tests measured within 24 hours of ICU admission, including temperature, systolic blood pressure, diastolic blood pressure, mean arterial pressure, shock index, platelets, red blood cell distribution width (RDW), mean red blood cell hemoglobin concentration (MCHC), blood glucose, blood urea nitrogen, creatinine, anion gap, bicarbonate, prothrombin time (PT), activated partial thromboplastin time (APTT) and international normalized ratio (INR) were associated with the mortality of severe TLI patients ( P<0.05 or 0.01). Multivariate Logistic regression analysis revealed that age ( OR=1.08, 95% CI 1.03, 1.12, P<0.01), body temperature <36 ℃ ( OR=8.00, 95% CI 2.17, 29.53, P<0.01), shock index ( OR=9.59, 95% CI 1.76, 52.18, P<0.01) and anion gap ( OR=1.32, 95% CI 1.15, 1.53, P<0.01) were significantly associated with mortality in severe TLI patients. Lasso regression analysis selected 7 predictors, including age, body temperature<36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT. Based on these 7 predictors, a nomogram prediction model was developed. The AUC of the nomogram for predicting mortality was 0.96 (95% CI 0.94, 0.99), and the Hosmer-Lemeshow goodness-of-fit test indicated a good fit ( P>0.05). The calibration curve demonstrated excellent consistency between the predicted and actual probabilities, and DCA demonstrated that the model had good clinical net benefit at all risk threshold probability ranges. Internal validation confirmed the stability of the model ( AUC=0.96, 95% CI 0.92, 0.98), and external validation demonstrated good generalization ability ( AUC=0.95, 95% CI 0.91, 0.98). Moreover, the nomogram exhibited superior predictive efficacy compared with injury severity score (ISS), revised trauma score (RTS), trauma injury severity score (TRISS), sequential organ failure score (SOFA), acute physiological score III (APS III), Logistic organ dysfunction score (LODS), Oxford acute severity of illness score (OASIS) and simplified acute physiological score II (SAPS II). Conclusions:Age, body temperature <36 ℃, shock index and anion gap are independent risk factors for mortality in severe TLI patients. A nomogram prognosis model based on 7 predictors, namely age, body temperature <36 ℃, shock index, anion gap, chronic liver disease, creatinine and APTT exhibits good predictive efficacy and robustness, and is contributive to accurately assess the risk of mortality in severe TLI patients at an early stage.

Influence of vitamin D deficiency on fibrosis-4 index and disease severity in patients with nonalcoholic steatohepatitis / 临床肝胆病杂志

Objective To investigate the influence of vitamin D deficiency on nonalcoholic steatohepatitis (NASH). Methods The patients with NASH who were hospitalized in Department of Infectious Diseases, The First Hospital of Changsha, from January 2020 to October 2021 were enrolled, and according to the serum level of 1, 25(OH) 2 D 3 , they were divided into group A with 1, 25(OH) 2 D 3 deficiency ( 30 ng/mL). The three groups were compared in terms of the serum levels of 1, 25(OH) 2 D 3 , alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), total cholesterol (TC), triglyceride (TG), interleukin-18 (IL-18), and interleukin-37 (IL-37) and liver pathological grade, and fibrosis-4 (FIB-4) index was calculated. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A Pearson correlation analysis was also performed. Results A total of 120 NASH patients were enrolled, with 40 patients in each group. Compared with group A, groups B and C had significant increases in the levels of 1, 25(OH) 2 D 3 and IL-37 and significant reductions in FIB-4 index and the levels of ALT, AST, TBil, TC, TG, and IL-18 (all P < 0.05). Compared with group B, group C had significant increases in the levels of 1, 25(OH) 2 D 3 and IL-37 and significant reductions in FIB-4 index and the levels of ALT, AST, TC, TG, and IL-18 (all P < 0.05). The correlation analysis showed that 1, 25(OH) 2 D 3 was negatively correlated with ALT ( r =-0.84, P < 0.001), AST ( r =-0.77, P < 0.001), TBil ( r =-0.32, P < 0.001), TC ( r =-0.45, P < 0.001), TG ( r =-0.42, P < 0.001), IL-18 ( r =-0.40, P < 0.001), and FIB-4 index ( r =-0.62, P < 0.001), and it was positively correlated with IL-37 ( r =0.59, P < 0.001). Compared with group A, groups B and C had significant reductions in the proportion of patients with severe steatosis ( χ 2 =51.46, P < 0.001), bridging fibrosis and early liver cirrhosis ( χ 2 =36.59, P < 0.001), or bridging necrosis and large-scale necrosis ( χ 2 =37.28, P < 0.001). Light microscopy showed that group A had extensive ballooning degeneration of hepatocytes, a large number of lipid droplets (mainly macrovesicular lipid droplets), disordered arrangement of the liver plate, lymphocyte infiltration, and focal bridging fibrosis; group B mainly had spotted focal necrosis, periportal fibrosis, lipid droplets with various sizes, a small amount of neutrophil infiltration, and ballooning degeneration of some hepatocytes; group C had ballooning degeneration of a small number of hepatocytes, focal perisinusoidal fibrosis, a small number of lesions with spotted focal necrosis, and a small number of lipid droplets in the cytoplasm of hepatocytes. Conclusion The degree of liver injury and fibrosis increases with the reduction in vitamin D level, and vitamin D measurement helps to evaluate the progression of NASH.

Research advances of exosome miRNA-mediated drug-resistance in pancreatic cancer / 中华消化外科杂志

In recent years, many researchs have found that microRNA (miRNAs) has differential expression in pancreatic tissues, pancreatic cancer cells and drug-resistant pancreatic cancer cells, and miRNAs can change the sensitivity of pancreatic cancer cells to chemotherapy drugs by acting on downstream target genes.The molecular mechanism of drug resistance in tumors is complex. In the drug-resistance of pancreatic cancer, miRNAs can mediate drug resistance in pancreatic cancer cells by affecting epithelial-mesenchymal transformation, DNA damage and repair, downstream signaling pathways, non-coding RNA, related coding genes, pancreatic cancer stem cells and other mechanisms. Therefore, the investigation of drug resistance mechanism and related miRNAs in pancreatic cancer will help to find new anti-drug resistance treatment methods. The authors summarize exosome miRNAs invloved in regulating chemoresistance in pancreatic cancer, in order to provide theoretical support for clinical treatment and find new targeted therapy of pancreatic cancer.

Ibrutinib inhibits mesenchymal stem cells-mediated drug resistance in diffuse large B-cell lymphoma / 中华血液学杂志

Objective@#To explore the mechanism of ibrutinib on drug resistance diffuse large B-cell lymphoma (DLBCL) cells.@*Methods@#DLBCL cell line was cultured with mesenchymal stem cells (MSC) , and DLBCL cells which migrated and adhered to MSC under microscope was counted. The secretion of CXCL12 by MSC were measured by ELISA. The expression of CXCR4 on DLBCL cells were measured by flow cytometry, HBL-1 cells were transfected with a CXCR4-lentivector. An Annexin Ⅴ-binding assay was used to detect the induction of apoptosis. Clonogenic growth of DLBCL cells was evaluated on MethoCult media. Ibrutinib was injected into NOD/SCID mice, tumor growth was assessed via caliper measurements every 3 days.@*Results@#MSC promoted migration and adhesion of DLBCL cells to MSC. Ibrutinib inhibited migration and adhesion of DLBCL cells to MSC in a dose-dependent manner (P<0.05) . CXCL12 secreted by MSC and CXCR4 expressed on DLBCL cells could induce each other, which upgraded the levels of secretion and expression. Ibrutinib could inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL-1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004) and expression of CXCR4 (P<0.05) . When co-cultured with MSC, the ratio of HBL-1 cells apoptosis in the group of control, mitoxantrone, ibrutinib, mitoxantrone+ibrutinib were respectively 15.1%, 17.5%, 23.5%, 58.7%. After transfected with a CXCR4-lentivector and overexpressed CXCR4, the ratios of HBL-1 cells apoptosis were 14.2%, 16.1%, 22.5%, 38.3% respectively. The ratio of DLBCL cells apoptosis induced by mitoxantrone was lower when co-cultured with MSC (P<0.05) . But with the addition of ibrutinib, the ratio of apoptosis was increaed and it was similar to cultivation without MSC, which suggested ibrutinib could inhibit drug-resistance induced by MSC. But after transfected with a CXCR4-lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis was significantly lower when co-cultured with MSC which demonstrated that ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4. MSC enhanced lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. The number of colonies of control, MSC, Ibrutinib, MSC+Ibrutinib were 113±5, 205±4, 62±9, 123±3 (2.5×103/well, ±s) , respectively. The tumor volume of NOD/SCID mice were respectively 6 500, 17 000, 4 000, 10 000 mm3. Ibrutinib inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vitro.@*Conclusion@#Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of CXCR4 and inhibited MSC-mediated drug resistance. Ibrutinib also inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. These results provided a scientific rationality for relapsed/refractory DLBCL treatment with ibrutinib.

Clinical Study of Xiezhuo Zhubi Decoction Combined with Etoricoxib in Treating Acute Gout Arthritis / 广州中医药大学学报

Objective To observe the clinical efficacy of Xiezhuo Zhubi Decoction combined with Etoricoxib for the treatment of acute gout arthritis.Methods Seventy acute gout arthritis patients were randomly divided into treatment group and control group,35 cases in each group.Based on the fundamental treatment,the control group were given oral use of Etoricoxib and the treatment group was treated with Xiezhuo Zhubi Decoction combined with Etoricoxib.The treatment for both group lasted for 7 days.Before and after treatment,the changes of blood uric acid,C-reactive protein and erythrocyte sedimentation rate in both groups were observed.After treatment,the clinical efficacy was evaluated,and the toxic and adverse effects were also monitored.Results (1) In the treatment group,the total effective rate was 91.4％;in the control group,the total effective rate was 71.4％.There were significant differences between the two groups(P ＜ 0.05).(2) After treatment,blood uric acid,C-reactive protein and blood sedimentation rate were much improved in both groups (P ＜ 0.05 compared with those before treatment),and the treatment group had better effect on improving blood uric acid and C-reactive protein(P ＜ 0.05).(3) The control group had 3 cases of nausea,while no adverse reactions occurred in the treatment group.Conclusion Xiezhuo Zhubi Decoction combined with Etoricoxib is effective for the treatment of acute gout arthritis,and its effects on relieving clinical symptoms and decreasing blood uric acid and erythrocyte sedimentation rate are better than Etoricoxib alone.

Effect analysis of laparoscopy-assisted and open D2 radical gastrectomy for gastric cancer / 中华消化外科杂志

Objective To compare the effect of laparoscopy-assisted gastrectomy (LAG) and open D2 radical gastrectomy (OG) for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 117 patients who underwent D2 radical gastrectomy at the Guangdong General Hospital from January 2014 to December 2014 were collected.Of 117 patients,60 undergoing LAG and 57 undergoing OG were respectively allocated into the LAG group and OG group.Total gastrectomy,distal subtotal gastrectomy and proximal subtotal gastrectomy were performed according to the location of the tumor.The perigastric lymph nodes dissection was performed according to the Japanese " Gastric cancer treatment protocol" (the 14th edition).Eligible patients received the adjuvant chemotherapy of XELOX regimen according to the Guideline published by National Comprehensive Cancer Network (NCCN).Observation indicators:(1) comparison of intra-and postoperative recovery between groups;(2) stratified analysis of number of lymph node dissected;(3) relationship among surgical method,number of lymph node dissected and postoperative complication;(4) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect the postoperative adjuvant chemotherapy,tumor-free survival and tumor recurrence or metastasis up to December 2016.Measurement data with normal distribution were represented as (x)± s and comparison between groups was analyzed using the independent-sample t test.Count data were analyzed using the chi-square test or Fisher exact probability.The relationship between number of lymph node dissected and postoperative complication was done using the Logistic regression model.Results (1) Comparison of intra-and post-operative recovery between groups:all the patients completed the operation successfully.Volume of intraoperative blood loss,time to postoperative anal exsufflation and duration of postoperative hospital stay were (113±36) mL,(4.3±2.1) days,(9.7±2.9) days in the LAG group and (209 ± 77) mL,(5.3 ± 2.2) days,(11.2 ± 3.9) days in the OG group,respectively,with statistically significant differences between groups (t =6.850,-2.604,-2.405,P＜0.05).Number of lymph node dissected,numbers of patients with overall complication,incisional infection,intestinal obstruction,digestive tract fistula,intra-abdominal bleeding,cardiovascular accident,pulmonary infection,urinary tract infection and death within postoperative 30 days were respectively 31±7,6,1,0,4,0,0,1,0,0 in the LAG group and 34±6,12,0,1,2,2,1,4,1,1 in the OG group,with no statistically significant difference between groups (t=0.177,x2=2.743,0.126,0.563,0.837,P＞0.05).All the patients with complications received symptomatic treatment,1 patient with abdominal bleeding in the OG group died and other patients recovered smoothly.(2) Stratified analysis of number of lymph node dissected:number of lymph node dissected in patients with total gastrectomy,distal subtotal gastrectomy and proximal subtotal gastrectomy were 35±8,29±5,27±4 in the LAG group and 34± 5,34±6,29±6 in the OG group,respectively,with no statistically significant difference between groups (t =0.846,1.052,0.934,P＞0.05).Number of lymph node dissected in patients with stage Ⅰ,Ⅱ and Ⅲ of TNM staging were respectively 31±5,32±9,31±6 in the LAG group and 34±7,32±4,35±6 in the OG group,with no statistically significant difference between groups (t =0.494,1.657,0.136,P＞0.05).(3) Relationship among surgical method,number of lymph node dissected and postoperative complication:surgical method (LAG and OG) and number of lymph node dissected were used as the independent variable and postoperative complication between groups was used as the dependent variable,the Logistic regression model showed that surgical method and number of lymph node dissected were not related factors affecting the postoperative complication (OR =1.062,2.049,95％ confidence interval:0.998-1.140,0.695-6.042,P＞0.05).(4) Follow-up and survival:108 of 117 patients (54 in each group) were followed up for 2-35 months,with a median time of 28 months.During the follow-up,numbers of patients undergoing postoperative adjuvant chemotherapy,with tumor-free survival and with tumor recurrence were 45,43,10 in the LAG group and 42,42,10 in the OG group,respectively,with no statistically significant difference in the tumor-free survival and tumor recurrence between groups (x2 =0.055,0.002,P＞0.05).Conclusion Laparoscopy-assisted D2 radical gastrectomy is safe and feasible,which equivalent to clinical effect of open radical gastrectomy,meanwhile,it also can reduce volume of intraoperative blood loss and duration of postoperative hospital stay,and accelerate recovery of postoperative gastrointestinal function.

Protective effect of peroxisome proliferator receptor γcoactivator-1αon hepatic ischemia-reperfusion injury / 重庆医学

Objective To investigate the protective effect of peroxisome proliferator receptor γcoactivator (PGC)-1αon he-patic ischemia-reperfusion injury .Methods The rat model of hepatic ischemia-reperfusion injury was established .The expression of PGC-1αwas detected by Western blot after 12 hours of reperfusion .The changes of reactive oxygen species(ROS) ,ATP level and serum liver enzyme activity were measured ,and the liver function was evaluated .On the other hand ,PGC-1α lentiviral overexpres-sion vector was constructed and transfected in rat before ischemia-reperfusion .After ischemia-reperfusion ,the expression of PGC-1α,liver ROS ,ATP level were measured by Western blot to explore the protective role of PGC-1αin liver ischemia reperfusion inju-ry .Results The expression of PGC-1α in ischemia-reperfusion liver was significantly lower than that in the control group (P<0 .05) .The level of ROS[(325 .4 ± 70 .9)RLU vs .(108 .5 ± 25 .2)RLU ,P<0 .05] ,the ALT activity in serum [(367 .8 ± 82 .7)U/L vs .(98 .7 ± 16 .8 )U/L ,P<0 .05]in ischemia-reperfusion liver were increased than that in the control group ,whereas liver ATP production was reduced[(6 .1 ± 3 .7)pmol vs .(19 .8 ± 3 .1)pmol ,P<0 .05)] .The expression of PGC-1αin the liver was significantly up-regulated by PGC-1αlentiviral overexpression vector (57 .3 ± 21 .3) U/L vs .(311 .2 ± 25 .8) U/L ,P<0 .05) ,down-regulated ROS[(98 .7 ± 18 .9)RLU vs .(300 .2 ± 45 .6)RLU ,P< 0 .05] and serum glutamic-pyruvic transaminase[(105 .3 ± 21 .3)U/L vs . (311 .2 ± 25 .8)U/L ,P<0 .05)] ,and increased liver ATP production [(17 .3 ± 3 .1)pmol vs .(5 .8 ± 2 .0)pmol ,P<0 .05]in contrast to non-transfected rats .Conclusion PGC-1αcontributes to protect liver ischemia reperfusion injury .

Prognostic factors resulting in the perioperative liver failure and death for the hepatocellular carcinoma patients with or without cirrhosis / 中华消化外科杂志

Objective To investigate the risk factors resulting in the perioperative liver failure and death for the HBV-associated hepatocellular carcinoma (HCC) patients with or without cirrhosis.Methods The method of retrospective case-control study was performed.The clinicopathological data of 1 083 HCC patients with positive HBsAg who received curative liver resection at the Southwest Hospital from January 2008 to December 2012 were collected.According to the absence or presence of cirrhosis,the HCC patients with positive HBsAg were divided into the 2 groups,including the cirrhosis group (633 patients) and the non-cirrhosis group (450patients).The intraoperative conditions (operation time,volume of intraoperative blood loss,rate of blood transfusion,rate of pringle maneuver) and postoperative conditions (incidence of perioperative complications,duration of postoperative hospital stay,perioperative mortality) of HCC patients were observed.The gender,age,alanine transaminase (ALT),aspartate transaminase (AST),albumin (Alb),total bilirubin (TBil),platelet (PLT),Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,pringle maneuver,extent of liver resection,number of tumors,tumor diameter,tumor thrombus and liver cirrhosis were enrolled and prognostic factors resulting in perioperative liver failure and death for the HCC patients were explored.Measurement data with skewed distribution were presented as M (range) and comparison between the 2 groups was analyzed using Mann-Whitney U test.Count data were presented as counts (percentage) and comparison between the 2 groups was analyzed using chi-square test or Fisher exact probability.Univariate analysis was performed by chi-square test and multivariate analysis was performed by Logistic regression model (forward).Results (1) The intraoperative conditions:the volume of intraoperative blood loss were 500 mL (range,30-7 000 mL) in the cirrhosis group and 400 mL (range,50-8 000 mL) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-2.209,P ＜ 0.05).The operation time,rate of blood transfusion and rate of pringle maneuver were 250 minutes (range,82-715 minutes),29.86％ (189/633),62.24％ (394/633) in the cirrhosis group and 242 minutes (range,85-738 minutes),27.11％ (122/450),66.67％ (300/450) in the non-cirrhosis group,respectively,with no statistical differences between the 2 groups (Z =-1.212,x2 =0.969,2.236,P ＞0.05).(2) The postoperative conditions:the incidence of perioperative complications was 30.49％(193/633) in the cirrhosis group and 21.11％ (95/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2 =11.851,P ＜ 0.05).The incidence of lung infection,abdominal infection and liver failure were 6.48％ (41/633),2.69％ (17/633),5.53％ (35/633) in the cirrhosis group and 3.56％ (16/450),0.89％ (4/450),1.33％ (6/450) in the non-cirrhosis group,respectively,with statistically significant differences between the 2 groups (x2 =4.502,4.465,12.713,P ＜ 0.05).The duration of postoperative hospital stay was 15 days (range,0-70 days) in the cirrhosis group and 14 days (range,0-71 days) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (Z =-3.448,P ＜ 0.05).The perioperative mortality was 5.85％ (37/633) in the cirrhosis group and 2.44％ (11/450) in the non-cirrhosis group,with a statistically significant difference between the 2 groups (x2=7.181,P ＜ 0.05).(3)Results of risk factors affecting perioperative liver failure:①results of univariate analysis showed that age,AST,Alb,Child-Pugh classification,operation time,volume of intraoperative blood loss,blood transfusion,extent of liver resection,tumor diameter,liver cirrhosis with positive HBsAg were associated with perioperative liver failure in HCC patients (x2=5.013,7.979,8.855,16.968,14.148,9.764,18.511,11.749,5.534,12.713,P＜0.05);age,AST,Alb,Child-Pugh classification,operation time,blood transfusion,extent of liver resection and tumor diameter were associated with perioperative liver failure in the cirrhosis group (x2=5.877,5.380,11.087,13.672,8.849,13.170,12.418,5.805,P ＜ 0.05);volume of intraoperative blood loss was associated with perioperative liver failure in the non-cirrhosis group (P ＜ 0.05).②Results of multivariate analysis showed that age≥60 years,Child-Pugh class B,operation time ＞ 360 minutes,blood transfusion,extent of liver resection ≥3 segments and liver cirrhosis were independent risk factors affecting perioperative liver failure in HCC patients with positive HBsAg [OR =2.285,2.716,2.315,2.159,2.459,4.322;95％ confidence interval (CI):1.081-4.831,1.100-6.706,1.064-5.038,1.068-4.362,1.264-9.786,1.763-10.598,P＜0.05];Alb ＜38 g/L,Child-Pugh class B,blood transfusion and extent of liver resection ≥ 3 segments were independent risk factors affecting perioperative liver failure in the cirrhosis group (OR =2.231,2.857,2.186,2.927,95％ CI:1.038-4.795,1.095-7.451,1.045-4.576,1.426-6.008,P ＜ 0.05);volume of intraoperative blood loss ＞ 1 200 mL was an independent risk factor affecting perioperative liver failure in the non-cirrhosis group (OR =15.077,95％CI:2.695-84.353,P ＜ 0.05).(4) Risk factors affecting perioperative death:①results of univariate analysis showed that gender,Alb,TBil,Child-Pugh classification,blood transfusion,extent of liver resection,tumor diameter,tumor thrombus and liver cirrhosis were associated with perioperative death in HCC patients with positive H BsAg (x2=4.462,8.783,4.212,4.869,7.189,11.745,6.837,4.323,7.181,P ＜0.05);Alb,extent of liver resection and tumor diameter were associated with perioperative death in the cirrhosis group (x2=12.173,12.793,10.981,P ＜ 0.05);blood transfusion and tumor thrombus were associated with perioperative death in the non-cirrhosis group (x2 =5.836,6.417,P ＜ 0.05).② Results of multivariate analysis showed that Alb ＜38 g/L,extent of liver resection ≥ 3 segments and liver cirrhosis were independent risk factors affecting perioperative death in HCC patients with positive HBsAg (OR =2.560,2.657,2.567,95％ CI:1.382-4.742,1.471-4.800,1.283-5.134,P ＜ 0.05);Alb ＜ 38 g/L,extent of liver resection ≥ 3 segments and tumor diameter≥5 cm were independent risk factors affecting perioperative death in the cirrhosis group (OR =3.003,2.533,3.060,95％ CI:1.495-6.034,1.251-5.128,1.135-8.251,P＜0.05);blood transfusion and tumor thrombus were independent risk factors affecting perioperative death in the non-cirrhosis group (OR =3.755,4.036,95％ CI:1.047-13.467,1.126-14.469,P ＜ 0.05).Conclusions Liver cirrhosis is an independent risk factor for perioperative liver failure and death in HCC patients with positive HBsAg.The risk of perioperative liver failure and death in HCC patients with cirrhosis is significantly higher than that in HCC patients without cirrhosis,and there is a difference in the risk factors for perioperative liver failure and death.

Effects of the phosphoinostitide-3'-kinase delta inhibitor, CAL-101, in combination with Bortezomib on mantle lymophma cells and exploration of its related mechanism / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma.</p><p><b>METHODS</b>MTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups.</p><p><b>RESULTS</b>CAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated.</p><p><b>CONCLUSIONS</b>The combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.</p>

Inhibitory effects of the phosphoinostitide-3'-kinase delta inhibitor CAL-101 on Raji and SUDHL-10 lymphoma cells and its relative mechanism / 中国肿瘤临床

Objective:To detect the inhibitory effects of CAL-101, a selective inhibitor of phosphoinostitide-3'-kinase delta (PI3Kδ), on Burkitt's lymphoma cell line Raji and diffused large B-cell lymphoma cell line SUDHL-10 and elucidate its relative mechanism. Methods:Raji and SUDHL-10 cells were treated with various concentrations of CAL-101. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the inhibitory effect of CAL-101 on lymphoma cells, and cell apoptosis was measured by Annexin V/PI and DAPI staining. Migration assays were performed with transwell to detect the migration of lymphoma cells derived from the stromal cell line HK. Western blot was used to detect the phosphorylation status of the ERK pathway. MTT and CalcuSyn software analyses were preformed to detect whether or not combining CAL-101 with bortezomib induces synergistic cytoxicity. Results:CAL-101 at con-centrations of 5, 10, 15, and 20μmol/L inhibited cell proliferation in a dose-dependent manner. The proliferation rates of the Raji cells treated with 5, 10, 15, and 20μmol/L for 48 h were 29.17%± 1.23%, 38.15%± 1.51%, 46.46%± 1.78%, and 55.8%± 2.01%, respec-tively, which were significantly higher (P<0.05) than that of the control group (1.15% ± 0.02%). Similar results were found in the SUDHL-10 cells after treatment with CAL-101 (P<0.05). CAL-101 also exerted an apoptotic effect on the lymphoma cells. The apop-totic rates of the Raji cells treated with CAL-101 for 21 h were 22.69%± 3.83%and 49.96%± 7.36%, respectively, which were signifi-cantly higher (P<0.05) than that of the control group (5.23%± 2.04%). Similar results were found in the SUDHL-10 cells (P<0.05). Treatment with 5 and 10 μmol/L CAL-101 dose-dependently inhibited the migration activity of lymphoma cells to stromal cells (P<0.05). Western blot analysis showed that the expression level of ERK phosphorylation protein was significantly downregulated in the cells treated with CAL-101. A synergistic effect between CAL-101 and bortezomib was verified. That is, these two drugs can signifi-cantly inhibit the proliferation of lymphoma cells with CI values less than 1. Conclusion:The PI3Kδ-specific inhibitor CAL-101 sup-pressed the proliferation of Raji and SUDHL-10 cells, induced apoptosis, and inhibited stromal cell-derived migration. This inhibitory effect may be induced by blocking the ERK pathway. Overall, our study indicated that CAL-101 is a novel and potential agent in the therapeutic strategy against aggressive B-cell lymphoma.

Comparison of clinical efficacy of hepatectomy via anterior approach and conventional approach for the treatment of giant liver cancer: a Meta analysis / 中华消化外科杂志

Objective To systematically compare the clinical efficacy of hepatectomy via anterior approach and the conventional approach for the treatment of giant liver cancer.Methods The database including Cochrane library,PubMed,Web of Knowledge,EMBASE,China National Knowledge Infrastructure (CNKI),Chinese Medical Current Contents(CMCC),Wanfang database were searched with the key words of原发性肝癌,转移性肝癌,手术,肝切除术,前入路,绕肝提拉法,传统入路,hepatocellular carcinoma,metastatic liver cancer,HCC,surgery,liver resection,hepatectomy,hepatic resection,anterior approach,conventional approach and liver hanging maneuver between the database establishment and December 2013.Chinese and English literatures on major hepatectomy via anterior approach and conventional approach for the treatment of giant liver cancer were retrieved,and data were analyzed by 2 independent researchers.Meta analysis was carried out using the software of Review Manager 5.1.2.The count data were analyzed using the odds ratio (OR).The quantitative data were analyzed by the weighted mean difference (WMD),and were presented by 95％ confidence interval (95％ CI).Results Thirteen literatures with 1 287 giant liver cancer patients were retrieved,including 603 patients receiving hepatectomy via anterior approach and 684 via conventional approach.Three literatures were enrolled in the randomly controlled studies,one had high risk of bias and the other 2 had low risk of bias.Ten literatures were enrolled in the non-randomly controlled studies with the mean score of 7 (range,5-9).The results of Meta analysis showed that hepatectomy via anterior approach could reduce the volume of intraoperative blood loss (MD =-349.39,95％ CI:-636.90--61.81,P ＜ 0.05),the blood transmission rate (OR =0.41,95％ CI:0.24-0.72,P ＜ 0.05),the operation time (MD =-40.81,95 ％ CI:-57.81--23.80,P ＜ 0.05),the mean time of hospital stay (MD =-4.52,95 ％ CI:-8.36--0.69,P ＜ 0.05) and the postoperative mortality and incidence of postoperative complications (OR =0.32,0.68,95 ％ CI:0.16-0.62,0.53-0.88,P ＜ 0.05) when compared with the conventional approach,further more,hepatectomy via the anterior approach could reduce the postoperative recurrence of giant liver cancer and had higher overall 1-and 3-year survival rates (OR =0.45,2.72,4.47,95％ CI:0.29-0.69,1.59-4.66,2.61-7.63,P ＜ 0.05).Conclusion The safety of hepatectomy via anterior approach is similar to that of the conventional approach,while the short-and long-term efficacy are superior to those of the conventional approach.

Expression of Bcl-2 gene and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the expression of Bcl-2 mRNA and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Real time quantitative PCR was used to determine the expression of Bcl-2 mRNA in 40 PGI-DLBCL patients and 17 healthy controls. The association of Bcl-2 expression with clinicopathological features and prognosis of the patients was analyzed.</p><p><b>RESULTS</b>The expression level of Bcl-2 mRNA in PGI-DLBCL patients was 1.03 ± 0.93, significantly higher than that of the controls (0.41 ± 0.21) (P < 0.05). The expression of Bcl-2 mRNA in stage IIE-IV patients (1.28 ± 1.01) was significantly higher than that in the stage I-II2 patients (0.62 ± 0.61) (P < 0.05). The expression of Bcl-2 mRNA in patients with international prognostic index (IPI) score >2 (1.95 ± 1.27) was significantly higher than those with IPI score ≤ 2 (0.86 ± 0.75)(P < 0.05). The expression of Bcl-2 mRNA in patients with complete remission (CR) (0.71 ± 0.58) was significantly lower vs. 2.42 ± 0.91 in patients with no CR (P < 0.05). Univariate analysis indicated that β2-MG, IPI score>2, the Lugano staging, and Bcl-2 mRNA expression were associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Multivariate analysis indicated that IPI score>2 was independently associated with OS (P < 0.05), and both IPI score >2 and Bcl-2 mRNA expression were independently associated with PFS (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of Bcl-2 mRNA in the tumor tissue of PGI-DLBCL patients is significantly higher than that in controls. PGI-DLBCL patients with higher expression of Bcl-2 have a poor chemotherapy response and inferior prognosis. IPI score >2 and higher expression of Bcl-2 mRNA are independent poor prognostic factors for PFS in PGI-DLBCL patients.</p>

In vitro synergistic effect of arsenic trioxide with conventional or new drugs on the proliferation of cutaneous T cell lymphoma cells Hut-78 and Hut-102 / 中国肿瘤临床

Objective:To investigate the in vitro effect of arsenic trioxide (As2O3) alone and in combination with dexamethasone (DXM), etoposide (VP-16), methotrexate (MTX), bortezomib (BTZ), and suberoylanilide hydroxamic acid (SAHA) on the growth of human cutaneous T cell lymphoma (CTCL) cells Hut-78 and Hut-102. Methods:Hut-78 and Hut-102 cells were cultured with different concentrations of As2O3, DXM, VP-16, MTX, BTZ, and SAHA alone and As2O3 in combination with DXM, VP-16, MTX, BTZ, or SAHA for 48 h. The effects of the different samples on Hut-78 and Hut-102 cell proliferation were determined by MTT assay. Analyses using CalcuSyn software were performed to determine whether the combination of As2O3 with DXM, VP-16, MTX, BTZ, or SAHA in-duced synergistic cytoxicity. Results:As2O3, DXM, VP-16, MTX, BTZ, and SAHA alone significantly inhibited the growth of Hut-78 and Hut-102 cells in a dose-dependent manner, with a 50%inhibiting concentration of 5μmol/L, 500μg/mL, 2.5μg/mL, 1μg/mL, 10μmol/L, and 2.5μmol/L individually after 48 h of culture. As2O3 with DXM, VP-16, MTX, BTZ, or SAHA showed remarkable antitu-mor efficacy compared with that of individual applications. Conclusion:As2O3 alone or combined with DXM, VP-16, MTX, BTZ, or SAHA significantly inhibited Hut-78 and Hut-102 cell growth in vitro. This study demonstrated that As2O3 with DXM, VP-16, MTX, BTZ, or SAHA presents synergistic antitumor effects on CTCL cells and may be an optimal regimen in clinical trials of CTCL.

Clinical efficacy of radiofrequency ablation for the treatment of metastatic hepatic carcinoma / 中华消化外科杂志

Objective To investigate the clinical efficacy of radiofrequency ablation for the treatment of metastatic hepatic carcinoma.Methods The clinical data of 87 patients with metastasis hepatic carcinoma who received radiofrequency ablation (RFA) at the Southwest Hospital from January 2004 to December 2008 were retrospectively analyzed.Of the 87 patients,34 were with liver metastasis from colonic cancer,33 with liver metastasis from rectal cancer,12 with liver metastasis from pancreatic cancer,and 8 with liver metastasis from gastric cancer.The survival of the patients was analyzed by life score and kamofsky performance status (KPS)scale.Patients were followed up via phone call and out-patient examination.Ultrasonography,computed tomography,liver function and tumor markers test were done every month within postoperative 6 months,and every 2 months at 6 months later.The follow-up was ended in Novermber 2013.All data were analyzed using chi-square test or rank sum test.The survival curve was drawn by Kaplan-Meier method,and the survival rate was compared using the Log-rank test.Results Of the 87 patients,84 were successfully treated by RFA,and 3 patients gave up RFA because of unbearable pain (2 patients with colonic cancer and 1 with gastric cancer).A total of 129 metastatic lesions were detected in the 84 patients,and 107 metastatic lesions were ablated after single RFA,with the success rate of 82.95％ (107/129).The other 22 lesions were ablated after a second RFA.The mean duration of hospital stay was (10.7 ± 2.3) days (range,4-29 days).Before operation,the life quality was excellent in 60.7％ (51/84) of patients,good in 22.6％ (19/84) of patients,fair in 10.7％ (9/84) of patients,and poor in 6.0％ (5/84) of patients.The candition of 63.1％ (53/84) of patients was improved,29.8％ (25/84) of patients was stable,and 7.1％ (6/84) of patients was deteriorated.At postoperative month 6,the life quality was excellent in 78.2％ (54/69) of patients,good in 11.6％ (8/69) of patients,fair in 5.8％ (4/69) of patients,and poor in 4.4％ (3/69) of patients.The condition of 73.9％ (51/69) of patients was improved,21.7％ (15/69) of patients was stable,and 4.4％ (3/69) of patients was deteriorated.There were significant differences in the life score and KPS scale between patients before and after operation (x2 =29.760,17.140,P ＜ 0.05).All patients were followed up for 6-60 months.The 1-,3-,5-year survival rates of patients with liver metastasis from colonic cancer after RFA treatment were 68.8％,21.9％ and 6.3％,and the median survival time was 21.5 months.The 1,3,5-year survival rates of patients with liver metastasis from rectal cancer after RFA were 66.7％,27.3％,12.1％,and the median survival time was 19.5 months.The 1-,3-,5-year survival rates of patients with liver metastasis from pancreatic cancer after RFA treatment were 41.7％,0 and 0,and the median survival time was 8.5 months.The 1-,3-,5-year survival rates of patients with liver metastasis from gastric cancer after RFA treatment were 71.4％,14.3％ and 0,and the median survival time was 16.5 months.The survival rates of patients with liver metastasis from pancreatic cancer and gastric cancer were significantly lower than those with liver metastasis from colorectal cancer after RFA (x2 =9.169,P ＜ 0.05).Conclusion The efficacy of RFA for selected patients with liver metastasis from digestive tract tumors is satisfactory.

Expression of S100A4 in pancreatic carcinoma and its significance / 中华内分泌外科杂志

Objective To investigate the expression of calcium-binding protein S100A4 in pancreatic carcinoma and its clinical significannce.Methods Immunohistochemistry EliVisionTM Plus method was used to examine the expression of S100A4 in 70 surgical specimens of primary pancreatic carcinoma and 15 patients with noncarcinoma pancreatic tissues.The correlation between the expression of S100A4 and the clinicopathological parameters was analyzed.Results S100A4 was positive in 52(52/70,74.3％) specimens of primary pancreatic carcinoma according to immunohistochemistry detection.No expression of S100A4 in adjacent noncarcinoma pancreatic tissues was detected.The expression of S100A4 did not correlated with gender,age or tumor site while it was significantly correlated with tumor size,grade of differentiation,TNM stages,lymph node metastasis and survival.Disease-free survival and overall survival of the negative group were significantly longer than the positive group.The difference had statistical significance.Conclusion The study shows that over expression of S100A4 protein is closely related with clinicopathological parameters of pancreatic cancer patients,indicating poor prognosis for pancreatic cancer patients.

Application of radiofrequency ablation in liver resection for hepatic cancer / 中华消化外科杂志

Objective To compare the effects of radiofrequency ablation and clamp crushing resection on intraoperative blood loss and postoperative complications.Methods The clinical data of 130 patients with hepatic cancer who were admitted to the Southwest Hospital from January 2011 to June 2012 were retrospectively analyzed.Sixty-five patients who received radiofrequency ablation were in the radiofrequency ablation group; the clinical data of 65 hepatic cancer patients with similar tumor size,position and Child-Pugh scores who received traditional clamp crushing resection were selected from the data base,and they were in the clamp crushing resection group.The intra-and postoperative clinical data of the 2 groups were statistically analyzed.The measurement data were presented in the format of median plus range,and were analyzed using the analysis of variance; the enumeration data were analyzed using chi-square test,when the number of patients was under 10,the Fisher exact probability was used for analysis.Results The time for liver resection and hepatic inflow occlusion in the radiofrequency ablation group were 28 minutes (range,12-55 minutes) and 10 minutes (range,0-15 minutes),which were significantly shorter than 45 minutes (range,25-92 minutes) and 15 minutes (range,10-32 minutes) in the clamp crushing resection group (F =10.35,9.05,P ＜0.05).The volumes of intraoperative blood loss and blood transfusion were 150 ml (range,50-350 ml) and 0 ml in the radiofrequency ablation group,which were significantly lesser than 450 ml (range,250-2500 ml) and 550 ml (range,0-2000 ml) in the clamp crushing resection group (F =15.86,P ＜ 0.05).The number of patients who did not receive blood transfusion in the radiofrequency ablation group was 65,which was significantly greater than 48 in the clamp crushing resection group (x2 =19.58,P ＜ 0.05).The levels of aspartic transaminase (AST) and total bilirubin (TBil) at postoperative day 3 and 7,prothrombin time (PT) at postoperative day 3,Clavien classification of surgical complications,duration of hospital stay were 302 U/L (range,89-823 U/L),54 U/L (range,16-325 U/L),37 μmol/L(range,18-112 μmol/L),24 μmol/L (range,9-66 μmol/L),15 s (range,11-20 s),22％ (14/65),12 days (range,8-36 days) in the radiofrequency ablation group,and 253 U/L (range,63-876 U/L),62 U/L(range,22-376 U/L),41 μmol/L (range,19-105 μmol/L),25 μmol/L (range,11-59 μmol/L),14 s (range,11-21 s),26％ (17/65) and 13 days (range,9-35 days) in the clamp crushing resection group.There were no significant differences in the 7 indexes between the radiofrequency ablation group and the clamp crushing resection group (F=2.59,1.93,3.96,1.58,2.35,x2 =0.381,F=1.58,P＞0.05).The incidence of complications of the radiofrequency ablation group was 17％ (11/65),which was significantly lower than 52％ (34/65) of the clamp crushing resection group (x2 =17.38,P ＜ 0.05).The number of patients who had postoperative bleeding in the radiofrequency ablation group was 2,which was significantly lesser than 22 patients in the clamp crushing resection group.Eight patients in the radiofrequency ablation group had encapsulated effusion,and 5 of them need drainage.Two patients in the clamp crushing resection group had hepatic insufficiency.Two patients in the radiofrequency ablation group had hemoglobinuria.Conclusion Compared with clamp crushing resection,radiofrequency ablation has advantages of less blood loss and safer manipulation.

Continuous occlusion of hepatic artery for prevention of blood loss in partial hepatectomy for ruptured hepatocellular carcinoma / 中华消化外科杂志

Objective To investigate the value of continuous occlusion of hepatic artery proper to intermittent Pringle maneuver in partial hepatectomy for ruptured hepatocellular carcinoma(HCC).Methods The clinical data of 36 patients(test group)who received partial hepatectomy for ruptured HCC by adding continuous occlusion of hepatic artery proper to intermittent Pringle maneuver at the Southwest Hospital were retrospectively analyzed.Thirty-six patients(control group)who received intermittent Pringle maneuver only were selected as the control.All data were analyzed using the chi-square test,Fisher exact probability and analysis of variance.Results The mean hepatic artery occlusion time of the test group was 58 minutes(range,36-98 minutes).The median blood loss of the test group was 400 ml,which was significantly less than 750 ml of the control group(F =16.47,P ＜ 0.05);78%(28/36)of patients in the test group did not receive blood transfusion,which was significantly more than 53%(19/36)of the control group(x2 =6.01,P ＜0.05).The levels of postoperative serumaspartate transaminase and total bilirubin of the 2 groups were peaked at postoperative day 2 and then decreased to the normal level 1 week later.There were no significant differences in the incidences and levels of complications between the 2 groups(x2 = 1.83,0.89,P ＞ 0.05).Conclusion The addition of continuous occlusion of hepatic artery proper to intermittent Pringle maneuver significantly reduces intraoperative blood loss and doesn't bring any adverse effects to hepatic function for partial hepatectomy in patients with ruptured HCC when compared with intermittent Pringle maneuver alone.

Mini-clamp crushing combined with saline-linked diathermy in hepatectomy for giant hepatocellular carcinoma / 中华消化外科杂志

Objective To evaluate the efficacy of mini-clamp crushing combined with saline-linked diathermy in hepatectomy for giant hepatocellular carcinoma(HCC).Methods The clinical data of 58 patients with giant HCC(diameter≥10 cm)who received hepatectomy with the mini-clamp crushing technique(miniclamp crushing group)at the Southwest Hospital from April 2006 to December 2009 were retrospectively analysed.According to the tumor size,location and Child classification,the clinical data of 58 patients with similar parameters and received hepatectomy with traditional clamp crushing technique(control group)were selected from the database to conduct the matched case-control study.All the peri-and postoperative data were compared and analysed via one-way ANOVA,chi-square test and Fisher's exact test.Results The median blood loss and transfusion of control group were 850 ml and 650 ml,which were significantly higher than 400 ml and 550 ml of mini-clamp crushing group(F=16.23,5.63,P＜0.05).Twenty-four patients in control group needed blood transfusion,which was significantly larger than 6 of mini-clamp crushing group(χ~2=14.57,P＜0.05).The median time for parenchymal transection and portal triad clamping of control group were 45 minutes and 16 minutes,which were significantly shorter than 86 minutes and 35 minutes of mini-clamp crushing group(F=12.76,11.23,P＜0.05).The numbers of patients in control group who had complications and blood loss were 43 and 28,which were significantly larger than 13 and 8 of mini-clamp crushing group(χ~2=18.69,16.11,P＜0.05).The numbers of patients who had bile leakage,encapsulated effusion of the liver cut face and hepatic insufficiency were 8,5 and 2 in control group,and were 2,3,0 in mini-clamp crushing group,with no significant difference(χ~2=3.04,0.54,2.04,P＞0.05).Conclusion Mini-clamp crushing combined with saline-linked diathermy for the treatment of g4ant HCC is mone effective and available than traditional clamp crushing in terms of reducing blood loss and complications.

Influence of hepatic ischemia-reperfusion injury induced by Pringle maneuver on the prognosis of hepatocellular carcinoma patients after hepatectomy / 中华消化外科杂志

Objective To evaluate the influence of hepatic ischemia-repeffusion injury (HIRI) induced by Pringle maneuver on the prognosis of hepatoceUular carcinoma (HCC) patients after hepatectomy. Methods The chnical data of 315 HCC patients who had been admitted to Southwest Hospital from January 2004 to December 2008 were retrospectively analyzed. The 194 patients who received Pringle maneuver during hepatectomy were in the HIRI group. The control group was composed of 121 patients without portal triad clamping. The pre- and peri-operative characteristics and the prognosis of the patients were analyzed by t test, chi-square test, Kaplan-Meier survival curve, Log-rank test and Cox regression model analysis. Results Patients in the HIRI group were significantly younger than those in control group (median age, 49 vs 59) (X2 =4. 12, P < 0.05). There were 108 patients (55.7%) with large HCC (diameter > 5 cm) in the HIRI group, while the number of patients with large HCC in the control group was 83 (68.6%), with statistical difference between the 2 groups (X2=4. 12, P <0.05). The serum levels of aspartate aminotransferase on postoperative day 3 and day 7 were 255 U/L and 112 U/L, which were significantly higher than 128 U/L and 35 U/L in the control group (X2 =4.57, 5.89, P <0.05). The level of total bilirubin on postoperative day 3 was 56 U/L in the HIRI group, which was significantly higher than 39 U/L in the control group (X2=4.79, P <0.05). The disease-free survival rate and cumulative survival rate in the HIRI group were significantly lower than those in the control group (X2 = 5.93, 8. 32, P < 0. 05). Perioperative blood loss, diameter of tumor, portal triad clamping and portal vein invasion were independent factors influencing the diseasefree survival rate. Conclusions HIRI induced by Pringle maneuver significantly decreases the disease-free survival rate and cumulative survival rate of HCC patients after hepatectomy.

Influence of cholangiocardnoma cells on endothelial cells in a co-culture system / 中华消化外科杂志

Objective To study the influence of cholangiocarcinoma cells on endothelial cells in a co-culture system. Methods A co-culture system of eholangioeareinoma cell line QBC939> and endothelial cells was established in vitro (co-culture group). Endothelial cells were cultured individually during the same time (control group). The mixed supematant of cholangiecareinoma cells and endothelial cells was in the mixed group. Light microscopy and transmission electron micrescopy were used to observe the morphology of the endothelial cells. Changes in expression of ppI25FAK, MMP-2, MMP-9 and uPA of the endothelial cells were detected by mmunofluorescence, and the activities of MMP-2 and MMP-9 were detected by gelatin zymography. All the data were analyzed by paired t test. Results The intercellular space between endothelial cells in co-cuhure group was wider than in the control group. The expression of pp125FAK, MMP-2, MMP-9 and uPA was 394 ±51,455±82, 377±48,422±55 in control group, and was 1096±128,931±72,815±76,801±56 in the eo-euhure group. The difference between the 2 groups had statistical significance (t = 6.53,4.32, 3.61,3.45, P < 0. 05). The values of gray-scale scanning of MMP-2 and MMP-9 in the mixed group were 240.2±15.2 and 2.4±0.8, respectively. The values of gray-scale scanning of MMP-2 and MMP-9 in the co-culture group were significantly increased, they were 687.4 ± 43.6 and 150.9 ± 13.2, respectively (t = 4.89, 5.43, P < 0.05). Conclusions The intercellular space between endothelial ceils and the expression of the proteolytie enzymes are increased after co-culturing endothelial cells with eholangiocarcinoma cells. Proteolytie enzymes may be involved in the process of degradation of subendothelial matrix, and promotes the metastasis of cholangiocarcinoma.