IntroductionRadiofrequency 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 methodsIn 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.ResultsIt 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.ConclusionBased 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.

ObjectiveTo 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 MethodsA 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.ResultsA 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.ConclusionsWhen 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.

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.

Background: Transcatheter arterial chemoembolization (TACE) is one of the local therapies most commonly used to treat intermediate-stage or advanced-stage hepatocellular carcinoma (HCC). However, the clinical benefits of PA-TACE (postoperative adjuvant TACE) for improving prognosis (progress-free survival [PFS] or overall survival [OS]) of low-risk HCC patients with R0-stage HCC after hepatectomy were not very clear. Methods: From January 2005 to December 2012, 180 patients who underwent hepatectomy for HCC treatment were enrolled in this study, and the follow-up of these patients was ended in December 2017. Among these patients, 102 patients were performed PA-TACE 1 month later after R0 hepatectomy and 78 patients without adjuvant TACE after R0 hepatectomy. Survival analysis was calculated using the Kaplan–Meier statistical method. Differences between survival curves of different groups were tested using the univariate log-rank test. Multivariate Cox model was used to search for independent prognostic factors for progression or death and to acquire the adjusted HR. Results: PA-TACE significantly improved the survival of HCC patients received surgical resection. The PFS (progress-free survival) of PA-TACE group (median PFS 52.0 months; 95% CI: 14.0–90.0) was significantly longer than the control group (median PFS 11.1 months; 95% CI: [7.9–14.3]; log-rank P <0.001); and the OS (in PA-TACE group (median OS 90.7 months; 95% CI: 84.4–97.0 months) was also much longer than that of control group (median OS 54.4 months; 95% CI: 38.2–70.6 months; log-rank p <0.001). Moreover, the benefits of PA-TACE are greater for low-risk patients than high-risk patients. Conclusion: In patients with HCC, PA-TACE can significantly prolong progression-free survival and long-term OS. For low-risk patients, the benefits might be greater.

AIMIn 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.METHODSLogistic 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.RESULTSArtificial 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.CONCLUSIONMulti-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.

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