Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the survival rate was significantly higher in patients with intermediate-and large-size HCC underwent RFA plus TACE than in those underwent RFA monotherapy; however, there was no significant difference between RFA plus TACE and RFA on survival rate for small HCC. CONCLUSION: The combination of RFA with TACE has advantages in improving overall survival rate, and pro-vides better prognosis for patients with intermediate-and large-size HCC.

Effects of hypoxia-inducible factor-1α silencing on the proliferation of CBRH-7919 hepatoma cells

AIM:To study the effects of hypoxia-inducible factor1α(HIF-1α) silencing on the proliferation of hypoxic CBRH-7919 rat hepatoma cells.METHODS:The CBRH-7919 rat hepatoma cell line was used in this study and the hypoxic model was constructed using CoCl2.The HIF-1α-specific RNAi sequences were designed according to the gene coding sequence of rat HIF-1α obtained from GeneBank.The secondary structure of the HIF-1α gene sequence was analyzed using RNA draw software.The small interfering RNA(siRNA) transfection mixture was produced by mixing the siRNA and Lipofectamine2000TM,and transfected into the hypoxic hepatoma cells.Real time reverse transcription-polymerase chain reaction(RTPCR) and Western blotting assay were used to detect the expression levels of mRNA and protein.HIF-1α and vascular endothelial growth factor(VEGF) mRNA was determined using real time RT-PCR;the protein expression levels of AKT,p-AKT,p21 and cyclinD1 were determined using Western blotting.The proliferation of hepatoma cells was observed using the methyl thiazolyl tetrazolium(MTT) assay and the bromodeoxyuridine(BrdU) incorporation cell proliferation assay.RESULTS:Under induced hypoxia,the viability of the hepatoma cells reached a minimum at 800 μmol/L CoCl2;the viability of the cells was relatively high at CoCl2 concentrations between 100 μmol/L and 200 μmol/L.Under hypoxia,the mRNA and protein expression levels of HIF-1α and VEGF were significantly higher than that of hepatoma cells that were cultured in normaxia.HIF-1α-specific RNAi sequences were successfully transfected into hepatoma cells.The transfection of specific siRNAs significantly inhibited the mRNA and protein expression levels of HIF-1α and VEGF,along with the protein expression levels of p-AKT and cyclinD1;the protein expression of p21 was significantly increased,and there was no significant difference in the expression of AKT.The MTT assay showed that the amount of hepatoma cells in S phase in the siRNA transfection group was obviously smaller than that in the control group;in the siRNA transfection group,the amount of hepatoma cells in G1 phase was more than that in the control group.The BrdU incorporation assay showed that the number of BrdU positive hepatoma cells in the siRNA transfection group was less than that in the control group.The data of the MTT assay and BrdU incorporation assay suggested that HIF-1α silencing using siRNAs significantly inhibited the proliferation of hepatoma cells.CONCLUSION:Hypoxia increases the expression of HIF-1α,and HIF-1α silencing significantly inhibits the proliferation of hypoxic CBRH-7919 rat hepatoma cells.

Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma

AIM:To analyze prognostic factors for survival after transarterial chemoembolization(TACE)combined with microwave ablation(MWA)for hepatocellular carcinoma(HCC).METHODS:Clinical data of 86 patients who underwent TACE combined with MWA between January 2006and December 2013 were retrospectively analyzed in this study.Survival curves were detected using log-rank test.Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival.All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival.P values were two-sided and P<0.05 was considered statistically significant.RESULTS:Median follow-up time was 47.6 mo,andmedian survival time of enrolled patients was 21.5 mo.The 1-,2-,3-and 5-year overall survival rates were72.1%,44.1%,31.4%and 13.9%,respectively.Tumor size(χ2=14.999,P=0.000),Barcelona Clinic Liver Cancer(BCLC)stage(χ2=29.765,P=0.000),ChildPugh class(χ2=51.820,P=0.000),portal vein tumor thrombus(PVTT)(χ2=43.086,P=0.000),arteriovenous fistula(χ2=29.791,P=0.000),MWA therapy times(χ2=12.920,P=0.002),Eastern Cooperative Oncology Group(ECOG)score(χ2=28.660,P=0.000)and targeted drug usage(χ2=10.901,P=0.001)were found to be significantly associated with overall survival by univariate analysis.Multivariate analysis identified that tumor size(95%CI:1.608-4.962,P=0.000),BCLC stage(95%CI:1.016-2.208,P=0.020),PVTT(95%CI:2.062-9.068,P=0.000),MWA therapy times(95%CI:0.402-0.745,P=0.000),ECOG score(95%CI:1.012-3.053,P=0.045)and targeted drug usage(95%CI:1.335-3.143,P=0.001)were independent prognostic factors associated with overall survival.CONCLUSION:Superior performance status,MWA treatment and targeted drug were favorable factors,and large HCC,PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.

Conventional transarterial chemoembolization vs microsphere embolization in hepatocellular carcinoma:A meta-analysis

AIM:To compare conventional transarterial chemoembolization(c-TACE)with microsphere embolization in hepatocellular carcinoma(HCC).METHODS:We searched Pub Med,Medline,Embase and the Cochrane Library for trials assessing the efficacy and safety of c-TACE in comparison with those of yttrium-90 microsphere or drug-eluting bead embolization from January 2004 to December 2013.Overall survival rate(OSR),tumor response[complete response,partial response(PR),stable disease(SD),progressive disease(PD)],α-fetoprotein(AFP)response,progression rate and complications were compared and analyzed.Pooled ORs with 95%CI were calculated using either the fixed-effects model or random-effects model.All statistical analyses were conducted using the Review Manager(version 5.1.)from the Cochrane collaboration.RESULTS:Thirteen trials were identified,including a total of 1834 patients;1233 were treated with c-TACE,377 underwent yttrium-90 microsphere embolization and 224 underwent drug-eluting bead embolization.The meta-analysis with either the random-effects model or fixed-effects model indicated that microsphere embolization was associated with significantly higher OSRs compared with those of c-TACE(OR1-year=1.38,95%CI1-year:1.05-1.82;OR2-year=2.88,95%CI2-year:1.18-7.05;OR3-year=2.15,95%CI3-year:1.18-3.91).The complete tumor response rates of patients who underwent microspheres embolization were significantly higher than those of patients treated with c-TACE(OR=2.19,95%CI:1.31-3.64).The tumor progression rate after microsphere embolization was markedly lower than that after c-TACE(OR=0.56,95%CI:0.39-0.81).There was no significant difference between microsphere embolization and c-TACE in PR(OR=0.73,95%CI:0.47-1.15),SD(OR=1.07,95%CI:0.79-1.44),PD(OR=0.75,95%CI:0.33-1.68),AFP response(OR=1.38,95%CI:0.64-2.94)and complications(OR=0.68,95%CI:0.46-1.00).CONCLUSION:Our analysis indicated that microsphere embolization was associated with superior survival and treatment response in comparison with c-TACE in the treatment of patients with HCC.

Interventional digital subtraction angiography for small bowel gastrointestinal stromal tumors with bleeding

AIM:To retrospectively evaluate the diagnostic efficacy of interventional digital subtraction angiography(DSA)for bleeding small bowel gastrointestinal stromal tumors(GISTs).METHODS:Between January 2006 and December2013,small bowel tumors in 25 consecutive patients undergoing emergency interventional DSA were histopathologically confirmed as GIST after surgical resection.The medical records of these patients and the effects of interventional DSA and the presentation and management of the condition were retrospectively reviewed.RESULTS:Of the 25 patients with an age range from34-to 70-year-old(mean:54±12 years),8 were male and 17 were female.Obscure gastrointestinal bleeding,including tarry or bloody stool and intermittent melena,was observed in all cases,and one case also involved hematemesis.Nineteen patients required acute blood transfusion.There were a total of 28 small bowel tumors detected by DSA.Among these,20 were located in the jejunum and 8 were located in the ileum.The DSA characteristics of the GISTs included a hypervascular mass of well-defined,homogeneous enhancement and early developed draining veins.One case involved a complication of intussusception of the small intestine that was discovered during surgery.No pseudoaneurysms,arteriovenous malformations or fistulae,or arterial rupture were observed.The completely excised size was approximately 1.20 to 5.50 cm(mean:3.05±1.25 cm)in maximum diameter based on measurements after the resection.There were ulcerations(n=8),erosions(n=10),hyperemia and edema(n=10)on the intra-luminal side of the tumors.Eight tumors in patients with a large amount of blood loss were treated with transcatheter arterial embolization with gelfoam particles during interventional DSA.CONCLUSION:Emergency interventional DSA is a useful imaging option for locating and diagnosing small bowel GISTs in patients with bleeding,and is an effective treatment modality.