Radiofrequency versus microwave ablation for hepatocellular carcinoma within the Milan criteria in challenging locations: a retrospective controlled study.

PURPOSE: The aim of this study was to compare the safety and efficacy of radiofrequency ablation (RFA) with microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria in challenging locations. METHODS: This study retrospectively investigated 201 consecutive patients with Milan criteria HCCs who underwent RFA (RFA group, n = 150) or MWA (MWA group, n = 51) between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), local tumor control, and treatment-related complications were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Median follow-up duration was 36.7 months (range: 6.2-64.0 months). Cumulative 1-, 3-, and 5-year OS rates were 97.9%, 92.3%, and 80.6% in the MWA group and 96.4%, 87.4%, and 78.2% in the RFA group, respectively, (P = 0.450). Cumulative RFS rates at 1, 3, and 5 years were 93.2%, 74.4%, and 63.7% in the MWA group and 80.3%, 57.3%, and 49.6% in the RFA group, respectively, (P = 0.097). Multivariate analyses showed that variable categories "patient age above 65 years" (P = 0.004) and "more than one tumor" (P = 0.004) were associated with overall mortality, and "patient age above 65 years" (P = 0.048) and "tumor size greater than 3 cm" (P = 0.009) were associated with inferior RFS. The incidences of major complications were not significantly different between the two groups (3.3% vs 3.9%, P = 0.843). CONCLUSIONS: RFA and MWA were associated with comparable safety and efficacy for HCC within the Milan criteria in challenging locations. Further study in a large, multi-center patient cohort is necessary to validate the results.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

Amplification of SMYD3 promotes tumorigenicity and intrahepatic metastasis of hepatocellular carcinoma via upregulation of CDK2 and MMP2.

SMYD3, a member that belongs to the SET and MYND-domain (SMYD) family, has also been proven to largely participate in gene transcription regulation and progression of several human cancers as a histone lysine methyltransferase. However, the role and significance of SMYD3 in both the clinic and progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we find that SMYD3 is increased in cirrhotic livers, and strikingly upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Subsequent analyses suggest that high expression level of SMYD3 significantly correlates with the malignant characteristics of HCC, and predicts poor prognosis in patients. Our results show that overexpression of SMYD3 increases, while silencing of SMYD3 inhibits, cell proliferation, invasiveness and tumorigenicity both in vitro and in vivo. SMYD3 also promotes intrahepatic metastasis of HCC cells. For the mechanisms, we identify that SMYD3 bound to CDK2 and MMP2 promoter and increased H3K4me3 modification at the corresponding promoters to promote gene transcription. Importantly, pharmacological targeting of SMYD3 with BCI-121 inhibitor effectively repressed the tumorigenicity of HCC cells. Finally, our results show that gene locus amplification is a cause for SMYD3 overexpression in HCC. These findings not only uncover that SMYD3 overexpression promotes the tumorigenicity and intrahepatic metastasis of HCC cell via upregulation of CDK2 and MMP2, but also suggest SMYD3 could be a practical prognosis marker or therapeutic target against the disease.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Transarterial Chemoembolization and Sorafenib Combined with Microwave Ablation for Advanced Primary Hepatocellular Carcinoma: A Preliminary Investigation of Safety and Efficacy.

PURPOSE: The aim of this study was to investigate the safety and efficacy of transarterial chemoembolization and sorafenib (TACE-S) combined with microwave ablation (TACE-S-MWA) for the treatment of patients with advanced primary hepatocellular carcinoma (HCC). METHODS: Between January 2015 and December 2018, 152 consecutive advanced HCC patients, who underwent TACE-S-MWA (MWA group, n=77) or TACE-S (Non-MWA group, n=75), were investigated. Overall survival (OS), time to progression (TTP) and safety were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Baseline patient characteristics were balanced between the two groups. MWA group was associated with a higher OS (median, 19.0 vs 13.0 months; P<0.001) and a longer TTP (median, 6.0 vs 3.0 months; P<0.001) compared with non-MWA group. Multivariate analyses showed that portal vein tumor thrombosis (PVTT) (P=0.002), duration of sorafenib (P<0.001), and MWA treatment (P=0.011) were independently associated with OS. MWA treatment strategy (P<0.001) was a significant predictor of TTP. There were no treatment-related mortalities in either group. The rates of minor complications (42.9% vs 38.7%, P=0.599) and major complications (1.29% vs 1.33%, P=0.985) in the MWA group were similar to those in the non-MWA group. CONCLUSION: TACE-S-MWA was safe and effective for advanced primary HCC. TACE-S-MWA resulted in better OS and TTP than did TACE-S for treatment of patients with advanced primary HCC.

Transcatheter hepatic arterial infusion chemotherapy vs sorafenib in the treatment of patients with hepatocellular carcinoma of Barcelona Clinic Liver Cancer stage C: a meta-analysis of Asian population.

OBJECTIVE: To compare the clinical efficacy and safety of transcatheter hepatic arterial infusion chemotherapy (HAIC) with those of sorafenib in the treatment of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C. METHODS: Potentially relevant studies comparing the clinical efficacy and safety of HAIC with those of sorafenib were searched using Medline, PubMed, Embase, Cochrane Library, and Chinese databases (Wanfang Data and China National Knowledge Infrastructure). Overall survival rate (OSR), tumor response rate, disease control rate (DCR), and serious adverse events (SAEs) were compared and analyzed. Pooled ORs with 95% CIs were calculated using either the fixed-effects model or the random-effects model. All statistical analyses were conducted using Review Manager (version 5.3) from the Cochrane Collaboration. RESULTS: A total of 1,264 patients were included in this meta-analysis. The results of this study showed that HAIC was associated with significantly higher 1-, 2-, and 3-year OSRs than sorafenib (OR 1.88, 95% CI1-year: [1.27-2.78], P1-year=0.002; OR 2.15, 95% CI2-year: [1.06-4.37], P2-year=0.03; OR 7.90, 95% CI3-year: [2.12-29.42], P3-year=0.002). Compared to sorafenib, HAIC was associated with superior complete response (CR), partial response (PR), and objective response rate (ORR) (OR 3.90, 95% CICR: [1.89-8.03], P CR =0.0002; OR 3.47, 95% CIPR: [2.31-5.24], P PR <0.00001; OR 3.02, 95% CIOR: [2.05-4.45], P OR <0.0001). There was no statistically significant difference between HAIC and sorafenib in stable disease (SD), progressive disease (PD), DCR, and SAEs (OR 0.86, 95% CISD: [0.51-1.45], P SD =0.56; OR 0.62, 95% CIPD: [0.35-1.11], P PD =0.11; OR 0.53, 95% CISAE: [0.14-1.92], P SAE =0.33). CONCLUSION: This study showed that HAIC was associated with better efficacy than sorafenib in terms of OSR and tumor response. Therefore, HAIC can be considered as an alternative treatment option for patients with HCCs of BCLC stage C.

Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization Therapy Versus Surgical Resection for Hepatocellular Carcinoma within the Milan Criteria: A Meta-Analysis.

Objective: To meta-analytically compare combined transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA) and surgical resection (SR) for the treatment of hepatocellular carcinoma (HCC) within the Milan criteria. Materials and Methods: PubMed, Medline, Embase, and Cochrane Library were searched for studies comparing these two therapies that were published between January 2006 and August 2017. Overall survival rate (OS), recurrence-free survival rate (RFS), major complications and the average length of hospital stay were compared between these two therapies. Meta-analytic pooled odds ratio (OR) was calculated using TACE plus RFA as the base category. Results: Seven case-control studies and one randomized trial were identified. Meta-analytic results revealed that, compared with SR, TACE plus RFA had significantly higher 1-year OS (OR for survival = 0.50, p = 0.009) and lower major complications (OR = 1.88, p = 0.02) after therapy. Three studies reported on the length of hospital stay. The average length ± standard deviation reported in individual studies for SR and TACE plus RFA groups was 19.8 ± 8.4 days and 7.4 ± 2.2 days, respectively; 18.7 ± 4.9 days and 11.5 ± 6.9 days, respectively; and 16.6 ± 6.7 days and 8.5 ± 4.1 days, respectively (p < 0.0001 for all studies). Three or 5-year OS and 1-, 3-, or 5-year RFS did not significantly differ between the two therapies. Conclusion: Combined TACE plus RFA may be an alternative to SR for the treatment of patients with HCC within Milan the criteria. Non-randomized design in most of the original studies was a limitation.

Prognostic Factors for Survival After Transarterial Chemoembolization Combined with Sorafenib in the Treatment of BCLC Stage B and C Hepatocellular Carcinomas.

RATIONALE AND OBJECTIVE: The objective of this study was to analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with sorafenib for hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stages B and C. MATERIALS AND METHODS: Clinical data of 198 patients with BCLC stage B and C HCCs who underwent TACE combined with sorafenib between June 2012 and January 2017 were retrospectively collected and analyzed. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 11 prognostic factors potentially 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: By the end of this study, the median follow-up duration was 43.6 months. The median overall survival (OS) of the patients was 21.0 months (95% confidence interval [CI]: 16.94-25.05), and the 1-, 2-, 3- and 5-year OS rates were 72%, 43%, 28%, and 4%, respectively. Tumor size (χ2 = 33.607, P < 0.0001), tumor number (χ2 = 4.084, P = 0.043), Child-Pugh class (χ2 = 33.187, P < 0.0001), BCLC stage (χ2 = 50.224, P < 0.0001), portal vein tumor thrombus (χ2 = 88.905, P < 0.0001), Eastern Cooperative Oncology Group (ECOG) performance status (χ2 = 98.007, P < 0.0001), extrahepatic spread (χ2 = 34.980, P < 0.0001), TACE times (χ2 = 8.350, P = 0.015), and sorafenib treatment strategy (χ2 = 81.593, P < 0.0001) were found to be significantly associated with OS by univariate analysis. Multivariate analysis showed that BCLC stage (95% CI: 1.133-3.982, P = 0.019), extrahepatic spread (95% CI: 1.136-2.774, P = 0.012), and sorafenib treatment duration (95% CI: 0.352-0.574, P = 0.000) were independent prognostic factors associated with OS. There were no serious treatment-related adverse events. CONCLUSIONS: This study showed that extrahepatic spread was a risk factor, and sorafenib treatment and superior BCLC stage were protective factors. Therefore, the study indicated that TACE combined with sorafenib was an effective and safe treatment for patients with BCLC stage B HCC without extrahepatic spread.

Drug-eluting bead transarterial chemoembolization in the treatment for unresectable soft tissue sarcoma refractory to systemic chemotherapy: a preliminary evaluation of efficacy and safety.

PURPOSE: To preliminarily evaluate the clinical efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) for unresectable soft tissue sarcoma refractory to systemic chemotherapy. METHODS: Ten patients with refractory sarcoma who underwent DEB-TACE therapy between January 2015 and January 2017 were identified. Clinical information and radiological data were retrospectively collected to analyze tumor response, overall survival (OS), progression-free survival and adverse events (AEs). Tumor response to DEB-TACE was assessed with modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. RESULTS: All DEB-TACE procedures were successfully performed for ten patients with 15 tumor lesions. The median follow-up duration was 19 months and the median survival time was 21 months (range 11-30 months). The 1- and 2-year OS rate was 90 and 30%, respectively. According to the guidance of mRECIST, complete response, partial response, stable disease and progressive disease were noted in zero (0%), three (30%), four (40%) and three (30%) patients, respectively. The disease control rate and objective response rate was 70 and 30%, respectively. There were no serious AEs in patients after DEB-TACE. CONCLUSIONS: Our data showed that DEB-TACE was effective and safe for patients with soft tissue sarcoma. Therefore, DEB-TACE can be considered as an alternative treatment option for unresectable soft tissue sarcoma refractory to conventionally systemic chemotherapy.

Transarterial embolization combined with RNA interference targeting hypoxia-inducible factor-1α for hepatocellular carcinoma: a preliminary study of rat model.

PURPOSE: To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery. The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting assays, respectively. RESULTS: In vitro experiment, the specific HIF-1α-siRNA was proved to inhibit expression levels of HIF-1α and vascular endothelial growth factor (VEGF) effectively. In animal study, real-time RT-PCR assay showed the average relative mRNA expressions of HIF-1α were 0.31 ± 0.01, 0.65 ± 0.03, 0.46 ± 0.005, and 1.00 ± 0.00 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Western blotting assay showed the average relative protein expressions of HIF-1α were 0.13 ± 0.02, 0.87 ± 0.02, 0.39 ± 0.02, and 1.02 ± 0.01 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Compared with control, TAE, and siRNA groups, TAE + siRNA can significantly inhibit protein expressions of HIF-1α and VEGF (P HIF-1α < 0.001; P VEGF < 0.001). Overall survival of rats underwent TAE + siRNA was significantly longer than that of rats treated with TAE monotherapy (P = 0.001). CONCLUSION: This animal study showed TAE combined with HIF-1α-RNAi could significantly improve efficacy of TAE in treating HCC by inhibiting expressions of HIF-1α and VEGF after TAE treatment.

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 2006 and 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, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ(2) = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ(2) = 29.765, P = 0.000), Child-Pugh class (χ(2) = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ(2) = 43.086, P = 0.000), arterio-venous fistula (χ(2) = 29.791, P = 0.000), MWA therapy times (χ(2) = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ(2) = 28.660, P = 0.000) and targeted drug usage (χ(2) = 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.

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 December 2013, 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 from 34- 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.

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 PubMed, 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 (OR(1-year) = 1.38, 95%CI(1-year): 1.05-1.82; OR(2-year) = 2.88, 95%CI(2-year): 1.18-7.05; OR(3-year) = 2.15, 95%CI(3-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.

Percutaneous ablation therapy versus surgical resection in the treatment for early-stage hepatocellular carcinoma: a meta-analysis of 21,494 patients.

PURPOSE: To compare comprehensively the benefits of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) with those of surgical resection (SR) in early-stage hepatocellular carcinoma (HCC). METHODS: The potentially relevant studies comparing the efficacy and safety of RFA and/or PEI with those of SR were searched using the databases such as PubMed, MEDLINE, Embase and Chinese databases (CNKI and Wanfang data). Overall survival rate, recurrence-free survival rate and complications were compared and analyzed. Pooled odds ratios with 95 % confidence intervals (95 % CIs) were calculated using either the fixed-effects model or random-effects model. All statistic analyses were conducted using the Review Manager (version 5.1.) from the Cochrane Collaboration. RESULTS: Our analysis showed that the overall survival rate in patients treated with SR was significantly higher than that of percutaneous ablation therapy (PAT) [SR vs. PAT: 95 % confidence interval (95 % CI)2-year 0.46-0.89, P = 0.009; 95 % CI3-year 0.57-0.83, P < 0.0001; 95 % CI5-year 0.45-0.46, P < 0.0001]. SR was associated with significantly higher recurrence-free survival rate compared with PAT (SR vs. PAT: 95 % CI1-year 0.51-0.90, P = 0.008; 95 % CI2-year 0.41-0.78, P = 0.0004; 95 % CI3-year 0.38-0.77, P = 0.0006; 95 % CI5-year 0.33-0.61, P < 0.0001). SR resulted in longer survival than PAT in HCCs no larger than 3 cm. PAT was associated with less complications compared with SR (PAT vs. SR: 95 % CI 0.14-0.76, P = 0.01). CONCLUSIONS: Although SR was associated with more complications, SR was superior to RFA and PEI for treatment of patients with early-stage HCC.

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, recurrence-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 χ(2) and I(2) 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 was used; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted using 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 significantly higher overall survival rate (OR1-year = 2.96, 95%CI: 1.84-7.74, P < 0.001; OR2-year = 3.72, 95%CI: 1.24-11.16, P = 0.02; OR3-year = 2.65, 95%CI: 1.81-3.86, P < 0.001) and recurrence-free survival rate (OR3-year = 3.00, 95%CI: 1.75-5.13, P < 0.001; OR5-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 provides 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 factor-1α (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 Lipofectamine2000(TM), and transfected into the hypoxic hepatoma cells. Real time reverse transcription-polymerase chain reaction (RT-PCR) 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.

Transarterial chemoembolization combined with percutaneous radiofrequency ablation versus TACE and PRFA monotherapy in the treatment for hepatocellular carcinoma: a meta-analysis.

PURPOSE: This meta-analysis was designed to compare the effectiveness of the combination of transarterial chemoembolization (TACE) and percutaneous radiofrequency ablation (PRFA) with that of TACE and PRFA monotherapy in hepatocellular carcinoma (HCC). METHODS: Randomized controlled trials were searched using various databases, and six studies were revealed on comparing TACE plus PRFA with TACE and/or PRFA alone for the treatment for HCC. Overall survival rate and recurrence-free survival rate were analyzed and compared. All statistic analyses were conducted using Review Manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Meta-analysis data revealed that TACE plus PRFA had significantly better effectiveness on 1- and 3-year overall survival rate(odds ratio [OR] 1-year = 4.61, 95 % confidence interval [95 % CI] 2.26-9.42, P < 0.0001; OR 3-year = 2.79, 95 % CI 1.69-4.61, P < 0.0001) and 3-year recurrence-free survival rate ([OR] 3-year = 3.00, [95 % CI] 1.75-5.13, P < 0.0001) than that of TACE and/or PRFA alone treatment. There was no significant difference between the combined therapy and monotherapy on 1-year recurrence-free survival rate ([OR] 1-year = 1.55, [95 % CI] 0.91-2.65, P = 0.11). CONCLUSIONS: The data of our study indicate that the combination of TACE and PRFA has better effectiveness than that of TACE and PRFA monotherapy in the treatment for patients with HCC.

Large primary hepatocellular carcinoma: transarterial chemoembolization monotherapy versus combined transarterial chemoembolization-percutaneous microwave coagulation therapy.

BACKGROUND AND AIM: To evaluate the clinical benefits of transarterial chemoembolization (TACE) monotherapy or TACE combined with percutaneous microwave coagulation therapy (PMCT) and the long-term survival rate of patients with large primary hepatocellular carcinoma (HCC) treated with these techniques. METHODS: This is a retrospective study involving 136 patients with unresectable large HCC (189 tumor nodules, ≥ 5.0 cm in diameter) admitted to Sun Yat-Sen University Memorial Hospital (Guangzhou, China) between January 2004 and December 2011. The median follow-up time was 41 months (range, 6-96 months). Of these patients, 80 patients received TACE monotherapy and 56 patients received TACE combined with PMCT. The median interval between treatments and overall survival (OS) were hierarchically analyzed using log-rank tests. RESULTS: All patients successfully underwent TACE alone or TACE with PMCT with no serious complications. The median survival time was 13 months (range, 3-84 months) for the TACE group and 25 months (range, 7-96 months) for the TACE-PMCT group. The 1-year, 3-year, and 5-year OS rates were 62.5%, 17.5%, and 5.0% in the TACE group, respectively. In contrast, in the TACE-PMCT group, the 1-year, 3-year, and 5-year OS rates were 87.5%, 50.0%, and 10.0%, respectively. This difference was statistically significant between the groups (P < 0.001). CONCLUSIONS: TACE combined with PMCT had advantages in prolonging OS with satisfying time to progression and improving liver function in patients with large unresectable HCC. The results suggest that further prospective studies are required to confirm the findings of this study.