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      Multidisciplinary approach for post-liver transplant recurrence of hepatocellular carcinoma: A proposed management algorithm

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          Abstract

          A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy (SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligo-recurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a pre-requisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Phenotypic analysis of antigen-specific T lymphocytes.

            Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.
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              Oligometastases.

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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
                7 December 2018
                7 December 2018
                : 24
                : 45
                : 5081-5094
                Affiliations
                Department of Surgery, Queen Mary Hospital, Hong Kong, China
                Department of Surgery and State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China. chok6275@ 123456hku.hk
                Author notes

                Author contributions: Chok KSH proposed the study; Au KP and Chok KSH conducted the literature review and wrote up the manuscript.

                Correspondence author to: Kenneth Siu Ho Chok, FRCS (Ed), Associate Professor, Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China. chok6275@ 123456hku.hk

                Telephone: +86-852-22553025 Fax: +86-852-28165284

                Article
                jWJG.v24.i45.pg5081
                10.3748/wjg.v24.i45.5081
                6288653
                30568386
                e42b3d0a-410b-4ea9-84ec-0e1daeb146a0
                ©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
                : 1 September 2018
                : 21 October 2018
                : 7 November 2018
                Categories
                Minireviews

                hepatocellular carcinoma,recurrence,liver transplantation

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