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      Trans-arterial chemoembolization combined with Jinlong capsule for advanced hepatocellular carcinoma: a PRISMA-compliant meta-analysis in a Chinese population

      review-article
      a , b , c
      Pharmaceutical Biology
      Taylor & Francis
      Traditional Chinese medicine, efficacy, safety, immune function, systematic review

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          Abstract

          Context

          Jinlong capsule (JLC) is an animal-derived traditional Chinese medical preparation for advanced hepatocellular carcinoma (HCC). However, its clinical efficacy is still not well investigated.

          Objective

          This study summarizes the efficacy and safety of JLC combined with trans-arterial chemoembolization (TACE) for patients with HCC.

          Methods

          The databases PubMed, Cochrane Library, Web of Science, EMBASE, Medline, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database and Chinese Biological Medicine Database were systematically searched from the date of their inception until February 2020. Jinlong capsule, trans-arterial chemoembolization, and hepatocellular carcinoma were the key terms searched. Randomized controlled trials and high-quality prospective cohort trials comparing the combined use of JLC and TACE versus TACE for HCC were included. Data were pooled using random or fixed effect models depending on heterogeneity.

          Results

          Data from 19 articles with 1,725 HCC patients were analysed. Compared with TACE treatment alone, the combination of TACE and JLC significantly prolonged patients’ 6–36 month overall survival ( p < 0.05), and markedly improved the overall response rate (RR = 1.37, 95% CI = 1.24–1.52, p < 0.00001) and disease control rate (RR = 1.11, 95% CI = 1.06–1.17, p < 0.0001) of patients. The liver function, quality of life, and immune function of patients were significantly improved; the partial adverse events related to TACE were also effectively relieved after the combination treatment.

          Conclusion

          This meta-analysis suggests that the combination of TACE and JLC is more effective in the treatment of HCC than treatment with TACE alone.

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          Most cited references36

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          Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

          Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I 2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R 2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I 2, which we call . We also provide a multivariate H 2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I 2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd.
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            The trim-and-fill method for publication bias: practical guidelines and recommendations based on a large database of meta-analyses

            Abstract Publication bias is a type of systematic error when synthesizing evidence that cannot represent the underlying truth. Clinical studies with favorable results are more likely published and thus exaggerate the synthesized evidence in meta-analyses. The trim-and-fill method is a popular tool to detect and adjust for publication bias. Simulation studies have been performed to assess this method, but they may not fully represent realistic settings about publication bias. Based on real-world meta-analyses, this article provides practical guidelines and recommendations for using the trim-and-fill method. We used a worked illustrative example to demonstrate the idea of the trim-and-fill method, and we reviewed three estimators (R 0, L 0, and Q 0) for imputing missing studies. A resampling method was proposed to calculate P values for all 3 estimators. We also summarized available meta-analysis software programs for implementing the trim-and-fill method. Moreover, we applied the method to 29,932 meta-analyses from the Cochrane Database of Systematic Reviews, and empirically evaluated its overall performance. We carefully explored potential issues occurred in our analysis. The estimators L 0 and Q 0 detected at least one missing study in more meta-analyses than R 0, while Q 0 often imputed more missing studies than L 0. After adding imputed missing studies, the significance of heterogeneity and overall effect sizes changed in many meta-analyses. All estimators generally converged fast. However, L 0 and Q 0 failed to converge in a few meta-analyses that contained studies with identical effect sizes. Also, P values produced by different estimators could yield different conclusions of publication bias significance. Outliers and the pre-specified direction of missing studies could have influential impact on the trim-and-fill results. Meta-analysts are recommended to perform the trim-and-fill method with great caution when using meta-analysis software programs. Some default settings (e.g., the choice of estimators and the direction of missing studies) in the programs may not be optimal for a certain meta-analysis; they should be determined on a case-by-case basis. Sensitivity analyses are encouraged to examine effects of different estimators and outlying studies. Also, the trim-and-fill estimator should be routinely reported in meta-analyses, because the results depend highly on it.
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              Transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): the role of angiogenesis and invasiveness.

              Although transcatheter arterial chemoembolization (TACE) is effective in hepatocellular carcinoma (HCC), it is not considered a curative procedure. Among the factors potentially interfering with its effectiveness is a hypothetical neoangiogenic reaction due to ischemia. In our study, we evaluated the changes in the levels of two angiogenic factors (vascular endothelial growth factor [VEGF] and basic fibroblast growth factor [b-FGF]) and one parameter of invasiveness (urokinase-type plasminogen activator [uPA]) in patients treated with TACE. Three blood samples were provided from 71 HCC patients undergoing TACE: before TACE (t0), after 3 days (t1), and after 4 wk, when they had spiral computed tomography (sCT) scanning (t2). The referring radiologists blindly evaluated tumor burden and vascularization at t0 and residual activity at t2. The choice of TACE as treatment was based on the American Association for the Study of Liver Diseases (AASLD) guidelines. Complete response at sCT was recorded in 27% of patients; mean survival was 35 months (confidence interval [CI] 31-40) and the 4-yr survival was 57%. VEGF levels were significantly correlated with the number of nodes and were higher in nonresponders at t2 (P = 0.01); below-median VEGF levels predicted a longer survival (P = 0.008). b-FGF correlated with VEGF, tumor size, vascularization, and residual activity, showing a borderline correlation with survival. uPA correlated with tumor size and VEGF. VEGF was singled out in the Cox multivariate analysis as an independent predictor of survival. When TACE is not totally effective, it may induce a significant neoangiogenetic reaction, as suggested by an increase in VEGF and b-FGF following treatment; this affects patient survival. VEGF emerges as the most reliable prognostic parameter, so it could be measured for judging TACE efficacy. Finally, antiangiogenic drugs may be indicated in TACE-treated HCC.
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                Author and article information

                Journal
                Pharm Biol
                Pharm Biol
                Pharmaceutical Biology
                Taylor & Francis
                1388-0209
                1744-5116
                7 August 2020
                2020
                : 58
                : 1
                : 771-784
                Affiliations
                [a ]Department of Hepatobiliary Surgery, Liaocheng People’s Hospital , Liaocheng, China
                [b ]Department of Oncology, Liaocheng People’s Hospital , Liaocheng, China
                [c ]Department of Gastroenterology, Liaocheng People’s Hospital , Liaocheng, China
                Author notes

                Supplemental data for this article can be accessed here .

                CONTACT Huimin Tao huimtxh@ 123456126.com Department of Gastroenterology, Liaocheng People’s Hospital , Dongchang West Road, No. 67, Liaocheng, Shandong Province252000, China.
                Author information
                https://orcid.org/0000-0002-0816-4152
                Article
                1799040
                10.1080/13880209.2020.1799040
                7470052
                32767901
                2012f413-9a9b-4fa4-881f-454eb8612d4c
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 10, Tables: 3, Pages: 14, Words: 6464
                Categories
                Review
                Review

                traditional chinese medicine,efficacy,safety,immune function,systematic review

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