Huaming Wang

Multicenter randomized controlled trial of percutaneous cryoablation versus radiofrequency ablation in hepatocellular carcinoma

Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child‐Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment‐naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1‐, 3‐, and 5‐year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1‐, 3‐, and 5‐year tumor‐free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child‐Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). Conclusion: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5‐year survival rates. (Hepatology 2015;61:1579–1590)

The Efficacy of Radiofrequency Ablation Combined with Transcatheter Arterial Chemoembolization for Primary Hepatocellular Carcinoma in a Cohort of 487 Patients

Although diagnostic methods, surgical techniques, and perioperative care have undergone significant advancement over the past decades, the prognosis of primary hepatocellular carcinoma (HCC) remains discouraged because of the high postoperative recurrence rate and high cancer mortality. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is a recently developed means for the treatment of HCC. In this study, we analyzed the efficacy of RFA plus TACE in 487 cases of HCC in our institution. We observed that the 1-, 2-, 3-, 4- and 5-year rates of overall survival rates after RFA and TACE treatment were 97.5% (475/487), 89.4% (277/310), 84.2% (181/215), 80.4% (150/186) and 78.7% (141/177), respectively. We did not find that age or tumor location (the caudate group or non-caudate group) plays a role in this cohort. However, we have identified that tumor recurrent status, the number of tumors, albumin (ALB), prothrombin time (PT) and platelet count (PLT) were significantly associated with poor overall survival in HCC patients receiving RFA combined with TACE. Interestingly, tumor size did not significantly impact overall survival, indicating that RFA combined with TACE for HCC treatment has the same efficiency for different sizes of tumors. Our results provide evidence for the rationale for using combined RFA and TACE in the treatment of primary HCC.

What is the best combination treatment with transarterial chemoembolization of unresectable hepatocellular carcinoma? a systematic review and network meta-analysis

Objective To assess the comparative efficacy and safety of combination treatment with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify what is the best combination treatment with TACE. Materials and Methods A network meta-analysis was used to identify evidence from relevant randomized controlled trials. We searched databases for publications up to June 2017. The prespecified primary efficacy outcomes were treatment response and 6-month to 3-year overall survival (OS), while the secondary efficacy outcomes were 1- and 2-year disease-free survival (DFS); safety outcomes were advance effects of combination treatment. We conducted pairwise meta-analyses using a random-effects model and then performed random-effects network meta-analyses. Results A total of 48 trials were eligible (50 analyses), involving 5627 patients and 19 treatment arms. In comparison with other types of combination therapy arms, network meta-analysis disclosed that TACE + three-dimensional conformal radiotherapy, TACE + percutaneous ethanol injection, TACE + percutaneous microwave coagulation therapy, TACE + percutaneous acetic acid injection, and TACE + sorafenib were the more effective methods in treatment response, 6-month to 3-year OS, and 1–2 year DFS; the adverse effects of TACE + sorafenib were serious. The study was registered with PROSPERO, number CRD42017071102. Conclusions When considering the efficacy, combination therapy with TACE seemed to offer clear advantages for patients with unresectable HCC. TACE + Three-dimensional conformal radiotherapy, TACE + Percutaneous ethanol injection, TACE + Percutaneous microwave coagulation therapy, and TACE + Percutaneous acetic acid injection are likely the best options to consider in the application of combination treatment.

A new apatinib microcrystal formulation enhances the effect of radiofrequency ablation treatment on hepatocellular carcinoma

Introduction Radiofrequency ablation (RFA) is the foremost treatment option for advanced hepatocellular carcinoma (HCC), however, rapid and aggressive recurrence of HCC often occurs after RFA due to epithelial–mesenchymal transition process. Although combination of RFA with sorafenib, a molecular targeted agent, could attenuate the recurrence of HCC, application of this molecular targeted agent poses a heavy medical burden and oral administration of sorafenib also brings severe side effects. Materials and methods In this study, we prepared an apatinib microcrystal formulation (Apa-MS) that sustainably releases apatinib, a novel molecular targeted agent, for advanced HCC treatment. We injected apatinib solution or Apa-MS into subcutaneous HCC tumors. Results It was found that Apa-MS exhibited slow apatinib release in vivo and in turn inhibited the epithelial–mesenchymal transition of HCC cells for extended time. Moreover, in rodent HCC model, Apa-MS enhanced the antitumor effect of RFA treatment. Conclusion Based on these results, we conclude that Apa-MS, a slow releasing system of apatinib, allows apatinib to remain effective in tumor tissues for a long time and could enhance the antitumor effect of RFA on HCC.

MEIS-1 level in unresectable hepatocellular carcinoma can predict the post-treatment outcomes of radiofrequency ablation

Radiofrequency ablation (RFA) is a local-ablative therapy for unresectable hepatocellular carcinoma (HCC). At present, there is no predictive marker for RFA treatment outcomes. This work aimed to valuate myeloid ecotropic viral integration site 1 (MEIS-1) in predicting post-RFA treatment outcomes of unresectable HCC patients. The time to progression (TTP) and overall survival (OS) of 81 HCC patients who received RFA treatment were measured. The protein level of MEIS-1 in tumor specimens was measured by western blot. The role of MEIS-1 in RFA-treating HCC in vivo growth nude mouse model was examined via PET/CT imaging. Higher level of MEIS-1 in tumor tissue is associated with better RFA treatment outcomes. The median TTP was 9.0 (95% confidence interval [CI]: 6.8–11.3) months in patients with high MEIS-1 expression (n = 43) versus 6.0 (95% CI: 4.6–7.4) months in patients with low MEIS-1 expression (n = 38). Moreover, in rodent HCC model we found overexpression of MEIS-1 enhanced the anti-tumor effect of RFA treatment. We conclude that high level of MEIS-1 expression predicts better RFA treatment outcome in HCC.

Enhanced Therapeutic Efficacy of Combined Use of Sorafenib and Transcatheter Arterial Chemoembolization for Treatment of Advanced Hepatocellular Carcinoma

OBJECTIVE Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients. METHODS Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival. RESULTS Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase ≥5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival. CONCLUSIONS Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.

Multi-parameter gene expression profiling of peripheral blood for early detection of hepatocellular carcinoma

AIM In our previous study, we have built a nine-gene (GPC3, HGF, ANXA1, FOS, SPAG9, HSPA1B, CXCR4, PFN1, and CALR) expression detection system based on the GeXP system. Based on peripheral blood and GeXP, we aimed to analyze the results of genes expression by different multi-parameter analysis methods and build a diagnostic model to classify hepatocellular carcinoma (HCC) patients and healthy people. METHODS Logistic regression analysis, discriminant analysis, classification tree analysis, and artificial neural network were used for the multi-parameter gene expression analysis method. One hundred and three patients with early HCC and 54 age-matched healthy normal controls were used to build a diagnostic model. Fifty-two patients with early HCC and 34 healthy people were used for validation. The area under the curve, sensitivity, and specificity were used as diagnostic indicators. RESULTS Artificial neural network of the total nine genes had the best diagnostic value, and the AUC, sensitivity, and specificity were 0.943, 98%, and 85%, respectively. At last, 52 HCC patients and 34 healthy normal controls were used for validation. The sensitivity and specificity were 96% and 86%, respectively. CONCLUSION Multi-parameter analysis methods may increase the diagnostic value compared to single factor analysis and they may be a trend of the clinical diagnosis in the future.

The "Vessel through Strait" Sign is a Signature Radiological Sign for the Diagnosis of Left Hepatic Artery Variation.

An aberrant artery (AA) can frequently be observed coursing through the fissure for the ligamentum venosum (FLV) which was termed the “vessel through strait” sign (VTSS) by us. Fundamental data including the incidence, anatomical composition and clinical significance of VTSS and the AAs composing VTSS are still lacking. We sought to give a systematic demonstration on this issue in the present study. VTSS was respectively analyzed in 2,275 patients and was observed in 357 of them. Interestingly, 319 (89.4%) out of the 357 patients exhibiting VTSS were proved to have left hepatic artery variation (LHAV) (247 with replaced left hepatic artery, 64 with accessory left hepatic artery and 8 with variant common hepatic artery). We therefore hypothesized that VTSS could be a sign that strongly associated with LHAV and could be used for its diagnosis. In the following validating analysis, VTSS gained a sensitivity of 96.3% and a specificity of 98.3% for the diagnosis of LHAV in another bicenter cohort consisted of 1,329 patients. In conclusion, VTSS is a signature radiological sign of LHAV which could be used as an easy and specific method for the diagnosis of LHAV.