Meta-analysis of radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>There is no clear consensus on the better therapy [radiofrequency ablation (RFA) versus hepatic resection (HR)] for small hepatocellular carcinoma (HCC) eligible for surgical treatments. This study is a meta-analysis of the available evidence.</p> <p>Methods</p> <p>Systematic review and meta-analysis of trials comparing RFA with HR for small HCC published from 1997 to 2009 in PubMed and Medline. Pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or random effects model.</p> <p>Results</p> <p>One randomized controlled trial, and 9 nonrandomized controlled trials studies were included in this analysis. These studies included a total of 1411 patients: 744 treated with RFA and 667 treated with HR. The overall survival was significantly higher in patients treated with HR than in those treated with RFA at 3 years (OR: 0.56, 95% CI: 0.44-0.71), and at 5 year (OR: 0.60, 95% CI: 0.36-1.01). RFA has a higher rates of local intrahepatic recurrence compared to HR (OR: 4.50, 95% CI: 2.45-8.27). In the HR group the 1, 3, and 5 years disease -free survival rates were significantly better than in the HR-treated patients (respectively: OR: 0.54, 95% CI: 0.35-0.84; OR: 0.44, 95% CI: 0.28-0.68; OR: 0.64, 95% CI: 0.42-0.99). The postoperative morbidity was higher with HR (OR: 0.29, 95% CI: 0.13-0.65), but no significant differences were found concerning mortality. For tumors ≤ 3 cm HR did not differ significantly from RFA for survival, as reported in three NRCTs .</p> <p>Conclusions</p> <p>HR was superior to RFA in the treatment of patients with small HCC eligible for surgical treatments, particularly for tumors > 3 cm. However, the findings have to be carefully interpreted due to the lower level of evidence.</p

Association between HLA-DRB1 alleles polymorphism and hepatocellular carcinoma: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>HLA-DRB1 allele polymorphisms have been reported to be associated with hepatocellular carcinoma susceptibility, but the results of these previous studies have been inconsistent. The purpose of the present study was to explore whether specific HLA-DRB1 alleles (DRB1*07, DRB1*12, DRB1*15) confer susceptibility to hepatocellular carcinoma.</p> <p>Methods</p> <p>Case-control studies on HLA-DRB1 alleles association with HCC were searched up to January 2010 through a systematic review of the literature. The odds ratios (ORs) of HLA-DRB1 allele distributions in patients with hepatocellular carcinoma were analyzed against healthy controls. The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity.</p> <p>Results</p> <p>Eight case-control studies were included in the final analysis. Among the 3 HLA-DRB1 alleles studied, DRB1*07 and DRB1*12 were significantly associated with the risk of HCC in the whole populations (OR = 1.65, 95% CI: 1.08-2.51, P = 0.02 and OR = 1.59, 95% CI: 1.09-2.32, P = 0.02, respectively). No significant association was established for DRB1*15 allele with HCC in the whole populations. Subgroup analysis by ethnicity showed that DRB1*07, DRB1*12 and DRB1*15 alleles significantly increased the risk of hepatocellular carcinoma in Asians (OR = 2.10, 95% CI: 1.06-4.14, P = 0.03; OR = 1.73, 95% CI: 1.17-2.57, P = 0.006 and <b><it>OR </it></b>= 2.88, <it><b>95%CI: 1</b></it>.77-4.69, P <<it><b>0.001</b></it>, respectively).</p> <p>Conclusion</p> <p>These results support the hypothesis that specific HLA-DRB1 alleles might influence the susceptibility of hepatocellular carcinoma. Large, multi-ethnic confirmatory and well designed studies are needed to determine the host genetic determinants of hepatocellular carcinoma.</p

Stereotactic body radiation therapy with or without transarterial chemoembolization for patients with primary hepatocellular carcinoma: preliminary analysis

<p>Abstract</p> <p>Background</p> <p>The objectives of this retrospective study was to evaluate the efficacy of stereotactic body radiation therapy (SBRT) for small non-resectable hepatocellular carcinoma (HCC) and SBRT combined with transarterial chemoembolization (TACE) for advanced HCC with portal vein tumor thrombosis (PVTT).</p> <p>Methods</p> <p>Thirty one patients with HCC who were treated with SBRT were used for the study. We studied 32 HCC lesions, where 23 lesions (22 patients) were treated targeting small non-resectable primary HCC, and 9 lesions (9 patients) targeting PVTT using the Cyberknife. All the 9 patients targeting PVTT received TACE for the advanced HCC. Tumor volume was 3.6–57.3 cc (median, 25.2 cc) and SBRT dose was 30–39 Gy (median, 36 Gy) in 3 fractions for consecutive days for 70–85% of the planned target volume.</p> <p>Results</p> <p>The median follow up was 10.5 months. The overall response rate was 71.9% [small HCC: 82.6% (19/23), advanced HCC with PVTT: 44.4% (4/9)], with the complete and partial response rates of 31.3% [small HCC: 26.1% (6/23), advanced HCC with PVTT: 11.1% (1/9)], and 50.0% [small HCC: 56.5% (13/23), advanced HCC with PVTT: 33.3% (3/9)], respectively. The median survival period of small HCC and advanced HCC with PVTT patients was 12 months and 8 months, respectively. No patient experienced Grade 4 toxicity.</p> <p>Conclusion</p> <p>SBRT for small HCC and SBRT combined with TACE for advanced HCC with PVTT showed feasible treatment modalities with minimal side effects in selected patients with primary HCC.</p

Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

<p>Abstract</p> <p>Background</p> <p>To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>The <it>Aurora B </it>and <it>Aurora A </it>mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the <it>p53 </it>and <it>β-catenin </it>genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of <it>p53 </it>and exon 3 of <it>β-catenin</it>. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines.</p> <p>Results</p> <p><it>Aurora B </it>was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of <it>Aurora B </it>was associated with <it>Aurora A </it>overexpression (<it>P </it>= 0.0003) and <it>p53 </it>mutation (<it>P </it>= 0.002) and was inversely associated with <it>β</it>-<it>catenin </it>mutation (<it>P </it>= 0.002). <it>Aurora B </it>overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that <it>Aurora B </it>overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of <it>p53 </it>and <it>β</it>-<it>catenin</it>. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis.</p> <p>Conclusion</p> <p><it>Aurora B </it>overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment.</p

Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation

<p>Abstract</p> <p>Background</p> <p>The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy.</p> <p>Methods</p> <p>Rat Novikoff hepatoma cells were injected percutaneously into the liver lobes of Sprague-Dawley rats under the guidance of high resolution ultrasound. The implantation rate and the correlation between dissected and ultrasound-measured tumor sizes were evaluated. A similar induction procedure was performed by means of laparotomy in a different group of rats. Pairs of tumor measurement were compared by ultrasound and computerized tomography scan. Rats with a successful establishment of the tumor were divided into the treatment (7-day low-dose epirubicin) group and the control group. The tumor sizes were non-invasively monitored by the same ultrasound machine. Blood and tumor tissues from tumor-bearing rats were examined by biochemical and histological analysis respectively.</p> <p>Results</p> <p>Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic hepatocellular carcinoma in 60.4% (55/91) of the Sprague-Dawley rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (<it>P </it>< 0.00001). The rate of tumor induction by ultrasound-guided implantation was comparable to that of laparotomy (55/91, 60.4% vs. 39/52, 75%) and no significant difference in sizes of tumor was noted between the two groups. There was a significant correlation in tumor size measurement by ultrasound and computerized tomography scan. In tumor-bearing rats, short-term and low-dose epirubicin chemotherapy caused a significant reduction in tumor growth, and was found to be associated with enhanced apoptosis and attenuated proliferation as well as a decrease in the microvessel density in tumors.</p> <p>Conclusions</p> <p>Ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic hepatocellular carcinoma in Sprague-Dawley rats. Short-term and low-dose epirubicin chemotherapy had perturbed tumor progression by inducing apoptosis and neovascularization blockade.</p