Serum HIF-1α and VEGF Levels Pre-and Post-TACE in Patients with Primary Liver Cancer

Objective To investigate the expression levels of serum hypoxia inducible factor 1 alpha(HIF-1α) and vascular endothelial growth factor(VEGF) pre-and post-transcatheter arterial chemoembolization(TACE) in patients with primary liver cancer(PLC),and correlations between prognosis factors and serum HIF-1α as well as VEGF levels.Methods Forty consecutive patients fulfilling diagnostic criteria for PLC undergoing TACE from March 2008 to May 2009 were enrolled into the study.The serum HIF-1α and VEGF levels of PLC patients pre-and 1 day,1 week,1 month post-TACE were analyzed using ELISA,and compared with that of 20 healthy volunteers.Patients were divided into complete response(CR) and partial response(PR),stable disease(SD),progressive disease(PD) groups according to the therapeutic efficacy.Pearson correlation was used to analyze the correlation between different clinical variables and serum HIF-1α and VEGF levels before TACE,and correlation between serum HIF-1α and VEGF levels was also evaluated.Results The expression levels of serum HIF-1α and VEGF in PLC patients were 154.94±83.29 and 264.00±148.10 pg/mL pre-TACE,and both of them were significantly higher than those in control group(23.84±8.15 and 69.78±21.42 pg/mL,all P<0.01).One day after TACE,both serum HIF-1α(570.64± 230.87 pg/mL) and VEGF levels(362.07±102.25 pg/mL) reached the peak values(all P<0.01).One week post-TACE,expression levels of them were decreased(198.62±92.11 and 283.52±145.46 pg/mL respectively),but still significantly higher than those before TACE(all P<0.01).The levels of both HIF-1α(133.96±57.02 vs.255.74±123.44 pg/mL) and VEGF(150.96±84.89 vs.368.95±161.90 pg/mL) in CR group 1 month post-TACE were significantly lower than those in PR+SD+PD group(all P<0.01).The level of serum HIF-1α was positively correlated with serum VEGF level(r=0.42,P<0.001).Both serum HIF-1α and VEGF levels were observed to be correlated with portal vein tumor thrombi(P<0.05) and metastasis(P<0.05).

Prealbumin is predictive for postoperative liver insufficiency in patients undergoing liver resection

AIM:To investigate the risk factors for postoperative liver insufficiency in patients with Child-Pugh class A liver function undergoing liver resection.METHODS:A total of 427 consecutive patients undergoing partial hepatectomy from October 2007 to April 2011 at a single center(Department of Hepatic SurgeryⅠ,Eastern Hepatobiliary Surgery Hospital,Shanghai,China) were included in the study.All the patients had preoperative liver function of Child-Pugh class A and were diagnosed as having primary liver cancer by postoperative histopathology.Surgery was performed by the same team and hepatic resection was carried out by a clamp crushing method.A clamp/unclamp time of 15 min/5 min was adopted for hepatic inflow occlusion.Patients' records of demographic variables,intraoperative parameters,pathological findings and laboratory test results were reviewed.Postoperative liver insufficiency and failure were defined as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,clinically apparent ascites,prolonged coagulopathy requiring frozen fresh plasma,and/or hepatic encephalopathy.The incidence of postoperative liver insufficiency or liver failure was observed and the attributing risk factors were analyzed.A multivariate analysis was conducted to determine the independent predictive factors.RESULTS:Among the 427 patients,there were 362 males and 65 females,with a mean age of 51.1 ± 10.4 years.Most patients(86.4%) had a background of viral hepatitis and 234(54.8%) patients had liver cirrhosis.Indications for partial hepatectomy included hepatocellular carcinoma(391 patients),intrahepatic cholangiocarcinoma(31 patients) and a combination of both(5 patients).Hepatic resections of ≤ 3 and ≥ 4 liver segments were performed in 358(83.8%) and 69(16.2%) patients,respectively.Seventeen(4.0%) patients developed liver insufficiency after hepatectomy,of whom 10 patients manifested as prolonged hyperbilirubinemia unrelated to biliary obstruction or leak,6 patients had clinically apparent ascites and prolonged coagulopathy,1 patient had hepatic encephalopathy and died on day 21 after surgery.On univariate analysis,age ≥ 60 years and prealbumin < 170 mg/dL were found to be significantly correlated with postoperative liver insufficiency(P = 0.045 and P = 0.009,respectively).There was no statistical difference in postoperative liver insufficiency between patients with or without hepatitis,liver cirrhosis and esophagogastric varices.Intraoperative parameters(type of resection,inflow blood occlusion time,blood loss and blood transfusion) and laboratory test results were not associated with postoperative liver insufficiency either.Age ≥ 60 years and prealbumin < 170 mg/dL were selected on multivariate analysis,and only prealbumin < 170 mg/dL remained predictive(hazard ratio,3.192;95%CI:1.185-8.601,P = 0.022).CONCLUSION:Prealbumin serum level is a predictive factor for postoperative liver insufficiency in patients with liver function of Child-Pugh class A undergoing hepatectomy.Since prealbumin is a good marker of nutritional status,the improved nutritional status may decrease the incidence of liver insufficiency.

Clinical study of FOLFOX4 regimen for patients of advanced hepatocellular carcinoma

Objective:The aim of our study was to observe the efficiency and toxicity of oxaliplatin (L-OHP) combined with CF/5-FU in patients with advanced primary hepatocellular carcinoma.Methods:Twenty patients with advanced primary hepatocellular carcinoma had recurrence/metastasis after multiple courses of TACE (cisplatin and epirubicin,etc.).All patients were treated with FOLFOX4 regimen of the combination of oxaliplatin and leucovorin and 5-fluorouracil.Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred.The efficiency was evaluated according to RECIST criteria,and toxicities according to American National Cancer Institute Common Toxicity Criteria (NCI CTC),respectively.Results:Twenty patients were assessable for the objective efficiency and for toxicity.No patient achieved complete response (CR),4 patients were partial response (PR),8 patients were stable disease (SD),8 patients were disease progression (PD);Time to tumor progression (TTP) of the patients ranged from 1.5 to 4.8 months,median TTP was 2.2 months;Overall survival (OS) of the patients ranged from 3 to 10.2 months,median OS was 5 months.The 2 patients' serum AFP level decreasing.Sixteen patients relieved the symptoms obviously,stabilized or raised up Karnofsky Score.The toxicities were mainly grade I-II arrest of bone marrow (50%),mild neurotoxicity (30%) and mild reaction of gastrointestinal tract (40%).Conclusion:FOLFOX4 regimen is effective and safe for patients with advanced primary hepatocellular carcinoma.It can be worthy of further clinical investigation.

EFFICACY OF URSODEOXYCHOLIC ACID IN TREATMENT OF ISCHEMIA-REPERFUSION INJURY IN LIVER TRANSPLANTATION

Objective To investigate the efficacy of ursodeoxycholic acid in treatment of ischemia-reperfusion injury （IRI） in liver transplantation. Methods Eighty liver transplantation adult recipients were preoperatively enrolled and randomized into the ursodeoxycholic acid （ UDCA ） （42 cases） and control （ 38 cases ） groups between May 2005 and June 2006. The two groups were statistically compared in liver biochemical parameters on post- transplant d 1, 7, 14, and 21. Rates of severe IRI-induced liver graft dysfunction, acute cellular rejection （ ACR ） episode, drug-induced hepatotoxicity, viral hepatitis, and recurrence of primary liver disease were measured within 3 weeks post-transplantation; and rates of vascular, biliary complications, and death were also measured within 3 months post-transplantation. Results In the UDCA group, serum levels of alanine aminotransferase （ ALT） on post-transplant d 7, 14, and 21 were significantly lower than those in the control group （ P = 0. 002,0. 030, 0. 049, respectively）. Compared with the control group, serum levels of aspartate aminotransferase （ AST） and y-Glutamyltranspeptidase （ GGT） on d 7 were also lower in the UDCA group （ P =0. 012 and 0. 025）. The cases of severe IRI- induced liver graft dysfunction in the UDCA group were significantly fewer than those in the control group （ 17. 5% vs. 26.3%, P =0. 048）. There were no significant differences in rates of ACR episode, histological Banff grading, or drug-induced hepatotoxicity within 3 weeks post-transplantation as well as rates of vascular, biliary complications, and death within 3 months post-transplantation between the two groups. We did not find any case of viral hepatitis or recurrence of primary liver disease in the study. Conclusion UDCA treatment can improve graft IRI early after liver transplantation. It significantly decreased serum ALT level and incidence of severe IRl-induced liver dysfunction within post-transplant 3 weeks. Cytoprection of hepatocytes by UDCA was more outstanding than that of bile duct when cold ischemia time was beneath 12 h. Vascular and biliary complications within 3 months post-transplantation can not be affected by UDCA administration in the study.

Pattern characteristics in patients with primary liver cancer in different clinical stages

OBJECTIVE： To explore the characteristics of prima- ry liver cancer in terms of Traditional Chinese Medi-cine （TCM） by analyzing the variations of the patterns along with the clinical stages. METHODS： The patients who were hospitalized in the Changhai Hospital of Traditional Chinese Medi- cine dated from March 1999 to December 2008 were included in this retrospective study. The patients were grouped according to their cancer stag- es, and their patterns were judged and quantified according to the ＂Standard diagnosis and quantitative criteria of the common patterns in primary liv-er cancer＂ formulated by the Changhai Hospital of Traditional Chinese Medicine. Statistics methods included ANOVA and nonparametric test, among others.RESULTS： The data of the 398 newly diagnosed patients showed that Qi Stagnation, Blood Stasis, and Dampness patterns were more frequent than the other basic patterns with relatively high scores; patterns of Liver Qi Stagnation, Liver Blood Stasis, and Dampness Heat were more than the other complex patterns and scored relatively high. Scores of Dampness and Liver Qi Stagnation patterns varied among the groups at different stages and the differences were statistically significant （PDampeness= 0.002, PLiver Qi Stagnation ： 0.020）. The highest scores of Damp- ness pattern and Liver Qi Stagnation pattern corresponded with Stage Ⅲ b, and Stage Ⅲ a, respectively. Dampness pattern frequency was higher （P = 0.001） in the Stage Ⅲb group than in other groups.CONCLUSION： Pattern characteristics in patients with primary liver cancer of different clinical stages might manifest in the variations of the Dampness pattern along the process of the disease and the major pathogenic factor of primary liver cancer might be Dampness.