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      Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma: Current state of the art

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          Abstract

          Transarterial chemoembolization (TACE) represents the current gold standard for hepatocellular carcinoma (HCC) patients in intermediate stage. Conventional TACE (cTACE) is performed with the injection of an emulsion of a chemotherapeutic drug with lipiodol into the artery feeding the tumoral nodules, followed by embolization of the same vessel to obtain a synergistic effect of drug cytotoxic activity and ischemia. Aim of this review is to summarize the main characteristics of drug-eluting beads (DEB)-TACE and the clinical results reported so far in the literature. A literature search was conducted using PubMed until June 2017. In order to overcome the drawbacks of cTACE, namely lack of standardization and unpredictability of outcomes, non-absorbable embolic microspheres charged with cytotoxic agents (DEBs) have been developed. DEBs are able to simultaneously exert both the therapeutic components of TACE, either drug-carrier function and embolization, unlike cTACE in which applying the embolic agent is a second moment after drug injection. This way, risk of systemic drug release is minimal due to both high-affinity carrier activity of DEBs and absence of a time interval between injection and embolization. However, despite promising results of preliminary studies, clear evidence of superiority of DEB-TACE over cTACE is still lacking. A number of novel technical devices are actually in development in the field of loco-regional treatments for HCC, but only a few of them have entered the clinical arena. In absence of well-designed randomized-controlled trials, the decision on whether use DEB-TACE or cTACE is still controversial.

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          Most cited references64

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          Heterogeneity of Patients with Intermediate (BCLC B) Hepatocellular Carcinoma: Proposal for a Subclassification to Facilitate Treatment Decisions

          The intermediate stage of hepatocellular carcinoma (HCC) comprises a highly heterogeneous patient population and therefore poses unique challenges for therapeutic management, different from the early and advanced stages. Patients classified as having intermediate HCC by the Barcelona Clinic Liver Cancer (BCLC) staging system present with varying tumor burden and liver function. Transarterial chemoembolization (TACE) is currently recommended as the standard of care in this setting, but there is considerable variation in the clinical benefit patients derive from this treatment.In April 2012, a panel of experts convened to discuss unresolved issues surrounding the application of current guidelines when managing patients with intermediate HCC. The meeting explored the applicability of a subclassification system for intermediate HCC patients to tailor therapeutic interventions based on the evidence available to date and expert opinion. The present report summarizes the proposal of the expert panel: four substages of intermediate HCC patients, B1 to B4. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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            Evolving strategies for the management of intermediate-stage hepatocellular carcinoma: available evidence and expert opinion on the use of transarterial chemoembolization.

            Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options. Results of an extensive literature review into the treatment of unresectable HCC with TACE were combined with our own clinical experience to identify factors that may predict survival after TACE. We also report contraindications to TACE and propose a treatment algorithm for the repetition of TACE. In addition, we have constructed a number of expert opinions that may be used as a guide to help physicians make treatment decisions for their patients with intermediate-stage HCC. The data included in the literature review related almost exclusively to conventional TACE, rather than to TACE with drug-eluting beads. Therefore, the findings and conclusions of the literature review are only applicable to the treatment of HCC with conventional TACE. Treating physicians may want to consider other treatment options for patients with intermediate-stage HCC who are not suitable for or do not respond to TACE. By distinguishing those patients who represent good candidates for TACE from those where little or no benefit might be expected, it may be possible to make better use of current treatment options and improve outcomes for patients. Copyright © 2010. Published by Elsevier Ltd.
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              Survival of patients with hepatocellular carcinoma treated by transarterial chemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design.

              Transarterial chemoembolisation (TACE) improves survival of properly selected patients with hepatocellular carcinoma (HCC). Drug eluting beads (DEB) provide a calibrated and homogenous procedure while increasing efficacy. Outcome data applying this technology is lacking, and this is instrumental for clinical decision-making and for trial design. We evaluated the survival of HCC patients treated with DEB-TACE following a strict selection (preserved liver function, absence of symptoms, extrahepatic spread or vascular invasion). We registered baseline characteristics, the development of treatment-related adverse events, and the overall survival of all HCC patients treated by DEB-TACE from February 2004 to June 2010. One hundred and four patients were treated with DEB-TACE. All but one were cirrhotic, 62.5% HCV+, 95% Child-Pugh A, 41 BCLC-A and 63 BCLC-B. Causes of DEB-TACE treatment in BCLC-A patients were: 35 unfeasible ablation, and six post-treatment recurrences. After a median follow-up of 24.5 months, 38 patients had died, two patients had received transplantation and 24 had received sorafenib because of untreatable tumour progression. Median survival of the cohort was 48.6 months (95% CI: 36.9-61.2), while it was 54.2 months in BCLC stage A and 47.7 months in stage B. Median survival after censoring follow-up at time of transplant/sorafenib was 47.7 (95%CI: 37.9-57.5) months. These data validate the safety of DEB-TACE and show that the survival expectancy applying current selection criteria and technique is better than that previously reported. A 50% survival at 4 years should be considered when suggesting treatment for patients fitting into controversial scenarios such as expanded criteria for transplantation/resection for multifocal HCC. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                14 January 2018
                14 January 2018
                : 24
                : 2
                : 161-169
                Affiliations
                Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia 71122, Italy. antonio.facciorusso@ 123456virgilio.it
                Author notes

                Author contributions: Facciorusso A designed the study and wrote the paper.

                Correspondence to: Antonio Facciorusso, MD, PhD, Assistant Professor, Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Viale L.Pinto 1, Foggia 71100, Italy. antonio.facciorusso@ 123456virgilio.it

                Telephone: +39-88-1732154 Fax: +39-88-1732135

                Article
                jWJG.v24.i2.pg161
                10.3748/wjg.v24.i2.161
                5768935
                29375202
                a07d88a7-00b3-4343-995c-5afcf5b9111c
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 26 October 2017
                : 16 December 2017
                : 20 December 2017
                Categories
                Minireviews

                embolization,doxorubicin,conventional,hepatocarcinoma,liver cancer,survival

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