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      Survival analysis of 230 patients with unresectable hepatocellular carcinoma treated with bland transarterial embolization

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          Abstract

          Locoregional therapies for hepatocellular carcinoma (HCC) include endovascular treatments such as chemoembolization (TACE) and bland embolization (TAE). TACE is the most adopted technique, despite a lack of definitive evidence of superiority over TAE, which is less costly and better tolerated due to the absence of chemotherapy. However, few studies have reported data on TAE monotherapy for unresectable HCC. We report our results in a cohort of 230 patients with unresectable HCC treated with TAE (TAE with 40-100micron microparticles, TAE with microparticles plus n-butyl-2-cyanoacrylate, TAE with Lipiodol) over the course of seven years. Thirty-seven patients (14%) were down-staged during observation and also received a percutaneous ablation. We observed 1-, 2-, 3-, 4- and 5-year rates of 84,8%, 58,7%, 38,3%, 28,3%, and 18,7%. Patients who also received percutaneous treatment performed best. Our results broaden the body of evidence for the use of TAE in advanced HCC.

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          Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment

          Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate.
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            Use of Lipiodol as a drug-delivery system for transcatheter arterial chemoembolization of hepatocellular carcinoma: a review.

            Hepatocellular carcinoma (HCC) remains a major public health problem. Transarterial chemoembolization (TACE) is recognized as the standard of care for patients with unresectable, asymptomatic, noninvasive and multinodular HCC. This procedure is based on percutaneous administration of a cytotoxic drug emulsified with Lipiodol followed by embolization of the tumour-feeding arteries. The standard procedure involves Lipiodol, an oily contrast medium which consists of a mixture of long-chain di-iodinated ethyl esters of poppy seed fatty acids. The aim of this review is to discuss the physical properties, tumour uptake behaviour and drug delivery effects of Lipiodol, the parameters influencing tumour uptake and future prospects. Lipiodol has a unique place in TACE as it combines three specific characteristics: drug delivery, transient and plastic embolization and radiopacity properties. Substantial heterogeneity in the physicochemical characteristics of Lipiodol/cytotoxic agent emulsions might reduce the efficacy of this procedure and justifies the current interest in Lipiodol for drug delivery. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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              Transcatheter embolization therapy in liver cancer: an update of clinical evidences.

              Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol(®) (Lipiodol(®) Ultra Fluid(®), Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem(®) (CeloNova Biosciences Inc., USA), DC-Beads(®) (BTG, UK) and HepaSphere(®) (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres(®) (Sirtex Medical Limited, Australia) and TheraSphere(®) (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: SoftwareRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Methodology
                Role: SupervisionRole: ValidationRole: Visualization
                Role: InvestigationRole: Validation
                Role: SupervisionRole: Validation
                Role: SupervisionRole: ValidationRole: Visualization
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 January 2020
                2020
                : 15
                : 1
                : e0227711
                Affiliations
                [1 ] Department of Diagnostic and Interventional Radiology, Humanitas Clinical and Research Hospital IRCCS, Rozzano, Milan, Italy
                [2 ] Training School in Radiology, Humanitas University, Pieve Emanuele, Milan, Italy
                [3 ] Department of Internal Medicine - Hepatology, Humanitas Clinical and Research Hospital IRCCS, Rozzano, Milan, Italy
                [4 ] Department of Surgery - Hepatobiliary and General Surgery, Humanitas Clinical and Research Hospital IRCCS, Rozzano, Milan, Italy
                Texas A&M University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-1889-8798
                Article
                PONE-D-19-28248
                10.1371/journal.pone.0227711
                6959584
                31935255
                a4aa2637-46eb-4c0c-a392-1f1a37b7e7a8
                © 2020 Lanza et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 October 2019
                : 24 December 2019
                Page count
                Figures: 5, Tables: 4, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Hepatocellular Carcinoma
                Medicine and Health Sciences
                Gastroenterology and Hepatology
                Liver Diseases
                Hepatocellular Carcinoma
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                Surgical and Invasive Medical Procedures
                Research and Analysis Methods
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                Mathematical and Statistical Techniques
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