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1
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Bi X, Zhao H, Zhao H, Li G, Wang X, Chen B, Zhang W, Che X, Huang Z, Han Y, Jiang L, Sun Y, Yang Z, Zhou J, Zhang Y, Zhu Z, Chen M, Cheng S, Cai J. Consensus of Chinese Experts on Neoadjuvant and Conversion Therapies for Hepatocellular Carcinoma: 2023 Update. Liver Cancer 2025; 14:223-238. [PMID: 40255878 PMCID: PMC12005702 DOI: 10.1159/000541249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 08/06/2024] [Indexed: 11/25/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multidisciplinary team, and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.
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Affiliation(s)
- Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital/PUMC/Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Guangming Li
- Department of Hepatobiliary Surgery, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Xiaodong Wang
- Departments of Interventional Oncology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Bo Chen
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wen Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xu Che
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Zhen Huang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Han
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Jiang
- Department of Diagnostic Imaging, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongkun Sun
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhengqiang Yang
- Department of Interventional Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianguo Zhou
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yefan Zhang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhenyu Zhu
- Department of Hepatology, Fifth Medical Center of Chinese PLA General Hospital/ Chinese PLA Medical School, Beijing, China
| | - Minshan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Shuqun Cheng
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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2
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e159-e260. [PMID: 40064172 DOI: 10.1055/a-2460-6298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Magyar CTJ, O'Kane GM, Aceituno L, Li Z, Vogel A, Bruix J, Mazzaferro V, Sapisochin G. Liver Transplantation for Hepatocellular Carcinoma: An Expanding Cornerstone of Care in the Era of Immunotherapy. J Clin Oncol 2025; 43:589-604. [PMID: 39680821 DOI: 10.1200/jco.24.00857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 09/20/2024] [Accepted: 10/19/2024] [Indexed: 12/18/2024] Open
Abstract
Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.
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Affiliation(s)
- Christian Tibor Josef Magyar
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Grainne Mary O'Kane
- University of Toronto, Toronto, ON, Canada
- St Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
| | - Laia Aceituno
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Zhihao Li
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arndt Vogel
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada
- Department of Hepatology, Gastroenterology, Endocrinology & Infectious Diseases, Hannover Medical School, Hannover, Germany
| | - Jordi Bruix
- BCLC Group, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Vincenzo Mazzaferro
- Istituto Nazionale Tumori IRCCS, Hepato Pancreatic Biliary Surgery & Liver Transplantation Unit, Milano, Italy
- Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy
| | - Gonzalo Sapisochin
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
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Sha M, Wang J, Cao J, Zou ZH, Qu XY, Xi ZF, Shen C, Tong Y, Zhang JJ, Jeong S, Xia Q. Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation. Clin Mol Hepatol 2025; 31:S285-S300. [PMID: 39159949 PMCID: PMC11925443 DOI: 10.3350/cmh.2024.0323] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 08/21/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
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Affiliation(s)
- Meng Sha
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Wang
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Cao
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-Hui Zou
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, China
| | - Xiao-ye Qu
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-feng Xi
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chuan Shen
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Tong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jian-jun Zhang
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Seogsong Jeong
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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5
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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6
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Xu E, Tabrizian P, Gutierrez J, Hoteit M, Ghaziani T, Zhou K, Parikh N, Ajmera V, Aby E, Shui A, Marino R, Martin A, Wong C, Kao K, Dave S, Florman S, Yao F, Mehta N. Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multicenter prospective cohort study. Hepatology 2025:01515467-990000000-01140. [PMID: 39808828 DOI: 10.1097/hep.0000000000001231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 12/07/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND AND AIMS Patients with HCC meeting United Network for Organ Sharing (UNOS)-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-Comers" [AC]) have been limited by small sample size and short follow-up time, prompting this analysis. APPROACH AND RESULTS Three hundred twenty-six patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate DS and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL; p =0.08), MELD (9 vs. 9; p =0.52), and Child-Pugh (A vs. A; p =0.30). Two years after the first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged ( p <0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion <10, 51% for sum 10-12, and 39% for sum >12 ( p =0.01). Yttrium-90 achieved higher DS success than transarterial chemoembolization in AC (74% vs. 65%; p <0.001). 48% of UNOS-DS and 40% of AC underwent LT ( p =0.10). Five-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%; p =0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%; p =0.02). CONCLUSIONS Despite higher HCC recurrence and lower intention-to-treat survival in AC, post-LT survival was comparable between UNOS-DS and AC. Yttrium-90 attained higher DS success than transarterial chemoembolization in AC. LT after DS is feasible in AC, though defining an upper limit in tumor burden may be necessary.
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Affiliation(s)
- Edison Xu
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Julio Gutierrez
- Center of Organ and Cell Transplantation, Department of Surgery, Scripps Green Hospital, La Jolla, California, USA
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Tara Ghaziani
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Kali Zhou
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Elizabeth Aby
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Amy Shui
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Rebecca Marino
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Allison Martin
- Center of Organ and Cell Transplantation, Department of Surgery, Scripps Green Hospital, La Jolla, California, USA
| | - Christopher Wong
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
| | - Karissa Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Shravan Dave
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Francis Yao
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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7
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Radovitch H, Le Sagere S, Cabarrou B, Maulat C, Boulard P, Farès N, Zadro C, Peron JM, Suc B, Mokrane FZ, Muscari F. Influence of the Radiological Response on Histological Necrosis and on the Survival of Patients Treated With Transarterial Chemoembolization for Hepatocellular Carcinoma Secondary to Cirrhosis on the Liver Transplantation Waiting List. Transplant Proc 2024; 56:1774-1783. [PMID: 39242311 DOI: 10.1016/j.transproceed.2024.08.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/24/2024] [Indexed: 09/09/2024]
Abstract
BACKGROUND AND AIMS Transarterial chemoembolization is the most common treatment used for HCC patients on liver transplant waiting list. The aims of this study are to evaluate the radio-histological correlation of the post-chemoembolization HCC response and its influence on overall survival (OS) and recurrence-free survival (RFS). METHODS Monocentric, retrospective study, including liver transplant patients with HCC who received chemoembolization from 2007 to 2018. The response of the hypervascular nodules was evaluated according to mRECIST, EASL. RESULTS A total of 70 patients with 122 hypervascular and 28 hypovascular HCCs were included. A complete radiological response concerned 34.3% patients. Concordance rates of hypervascular nodules (mRECIST, EASL and lipiodol uptake) with tumor necrosis ranged from 49% to 57%, with a specificity of 35% and a positive predictive value of 54%. Bilobar involvement was a predictive factor for incomplete radiological response. Major tumor necrosis was significantly correlated with the decrease in αFP level between the first CEL and liver transplantation. OS and RFS at 5 years were 64% and 60%, respectively, and 69% and 66% at complete radiological response. CONCLUSION Radiological response is significantly related to histological tumor necrosis, but with poor prediction. In case of complete radiological response, OS and RFS seem to be improved.
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Affiliation(s)
- Hugues Radovitch
- The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France
| | - Sarah Le Sagere
- Department of Radiology, Toulouse University Hospital, Toulouse, France
| | - Bastien Cabarrou
- Biostatistics & Health Data Science Unit, Institut Claudius-Regaud, IUCT-oncopole Toulouse, France
| | - Charlotte Maulat
- The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France.
| | - Paul Boulard
- The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France
| | - Nadim Farès
- Department of Digestive Oncology, Toulouse University Hospital, Toulouse, France
| | - Charline Zadro
- Department of Radiology, Toulouse University Hospital, Toulouse, France
| | - Jean-Marie Peron
- Department of Hepatology, Toulouse University Hospital, Toulouse, France
| | - Bertrand Suc
- The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France
| | | | - Fabrice Muscari
- The Digestive Surgery and Liver Transplantation Department, Toulouse University Hospital, Toulouse, France
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8
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Lerut J. Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies? Hepatobiliary Pancreat Dis Int 2024; 23:111-116. [PMID: 38195351 DOI: 10.1016/j.hbpd.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/11/2024]
Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université catholique Louvain (UCL), Avenue Hippocrate 56, 1200 Woluwe Saint Pierre, Brussels, Belgium.
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9
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Drefs M, Schoenberg MB, Börner N, Koliogiannis D, Koch DT, Schirren MJ, Andrassy J, Bazhin AV, Werner J, Guba MO. Changes of long-term survival of resection and liver transplantation in hepatocellular carcinoma throughout the years: A meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:107952. [PMID: 38237275 DOI: 10.1016/j.ejso.2024.107952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/21/2023] [Accepted: 01/03/2024] [Indexed: 03/10/2024]
Abstract
BACKGROUND Hepatocellular Carcinoma (HCC) still is one of the most detrimental malignant diseases in the world. As two curative surgical therapies exist, the discussion whether to opt for liver resection (LR) or transplantation (LT) is ongoing, especially as novel techniques to improve outcome have emerged for both. The aim of the study was to investigate how the utilization and outcome of the respective modalities changed through time. METHODS We searched Medline and PubMed for relevant publications comparing LT and LR in HCC patients during the time period from 1990 to 2022, prior to March 31, 2023. A total of 63 studies involving 19,804 patients - of whom 8178 patients received a liver graft and 11,626 underwent partial hepatectomy - were included in this meta-analysis. RESULTS LT is associated with significantly better 5-year overall survival (OS) (64.83%) and recurrence-free survival (RFS) (70.20%) than LR (OS: 50.83%, OR: 1.79, p < 0.001; RFS: 34.46%, OR: 5.32, p < 0.001). However, these differences are not as evident in short-term intervals. Older cohorts showed comparable disparities between the outcome of the respective modalities, as did newer cohorts after 2005. This might be due to the similar improvement in survival rates that were observed for both, LT (15-23%) and LR (12-20%) during the last 30 years. CONCLUSION LT still outperforms LR in the therapy of HCC in terms of long-term survival rates. Yet, LR outcome has remarkably improved which is of major importance in reference to the well-known limitations that occur in LT.
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Affiliation(s)
- Moritz Drefs
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany.
| | - Markus B Schoenberg
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Faculty of Medicine, LMU Munich, Germany; Medical Centers Gollierplatz and Nymphenburg, Munich, Germany
| | - Nikolaus Börner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Dionysios Koliogiannis
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Dominik T Koch
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Malte J Schirren
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Joachim Andrassy
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany
| | - Alexandr V Bazhin
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Faculty of Medicine, LMU Munich, Germany; Bavarian Cancer Research Center (BZKF), Munich, Germany
| | - Markus O Guba
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, Germany; Transplantation Center Munich, LMU University Hospital, LMU Munich, Germany
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10
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Schwenk L, Rauchfuß F, Ali-Deeb A, Dondorf F, Rohland O, Ardelt M, Settmacher U. [Individualized curative treatment for malignant diseases through liver transplantation]. CHIRURGIE (HEIDELBERG, GERMANY) 2024; 95:122-128. [PMID: 37847311 DOI: 10.1007/s00104-023-01973-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 09/22/2023] [Indexed: 10/18/2023]
Abstract
BACKGROUND For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions. OBJECTIVE This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies. RESULTS AND CONCLUSION Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.
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Affiliation(s)
- Laura Schwenk
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland.
| | - Falk Rauchfuß
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Aladdin Ali-Deeb
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Felix Dondorf
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Oliver Rohland
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Michael Ardelt
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein‑, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Deutschland
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11
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Minozzi S, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments. Dig Liver Dis 2024; 56:223-234. [PMID: 38030455 DOI: 10.1016/j.dld.2023.10.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova- Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Silvia Minozzi
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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12
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Wu X, Kwong A, Heller M, Lokken RP, Fidelman N, Mehta N. Cost-effectiveness analysis of interventional liver-directed therapies for downstaging of HCC before liver transplant. Liver Transpl 2024; 30:151-159. [PMID: 37639286 DOI: 10.1097/lvt.0000000000000249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/20/2023] [Indexed: 08/29/2023]
Abstract
Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are the 2 most used modalities for patients with HCC while awaiting liver transplant. The purpose of this study is to perform a cost-effectiveness analysis comparing TACE and TARE for downstaging (DS) patients with HCC. A cost-effectiveness analysis was performed comparing TACE and TARE in DS HCC over a 5-year time horizon from a payer's perspective. The clinical course, including those who achieved successful DS leading to liver transplant and those who failed DS with possible disease progression, was obtained from the United Network for Organ Sharing. Costs and effectiveness were measured in US dollars and quality-adjusted life years (QALYs). Probabilistic and deterministic sensitivity analyses were performed. TARE achieved a higher effectiveness of 2.51 QALY (TACE: 2.29 QALY) at a higher cost of $172,162 (TACE: $159,706), with the incremental cost-effectiveness ratio of $55,964/QALY, making TARE the more cost-effective strategy. The difference in outcome was equivalent to 104 days (nearly 3.5 months) in compensated cirrhosis state. Probabilistic sensitivity analyses showed that TARE was more cost-effective in 91.69% of 10,000 Monte Carlo simulations. TARE was more effective if greater than 48.2% of patients who received TACE or TARE were successfully downstaged (base case: 74.6% from the pooled analysis of multiple published cohorts). TARE became more cost-effective when the cost of TACE exceeded $4,831 (base case: $12,722) or when the cost of TARE was lower than $43,542 (base case: $30,609). Subgroup analyses identified TARE to be the more cost-effective strategy if the TARE cohort required 1 fewer locoregional therapy than the TACE cohort. TARE is the more cost-effective DS strategy for patients with HCC exceeding Milan criteria compared to TACE.
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Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
| | - Allison Kwong
- Department of Gastroenterology & Hepatology, Stanford University, Stanford, California, USA
| | - Michael Heller
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
| | - R Peter Lokken
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
| | - Nicholas Fidelman
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, USA
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, San Francisco, California, USA
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He X, Xu S, Tang L, Ling S, Wei X, Xu X. Insights into the history and tendency of liver transplantation for liver cancer: a bibliometric-based visual analysis. Int J Surg 2024; 110:406-418. [PMID: 37800536 PMCID: PMC10793788 DOI: 10.1097/js9.0000000000000806] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/18/2023] [Indexed: 10/07/2023]
Abstract
Research on liver transplantation (LT) for liver cancer has gained increasing attention. This paper has comprehensively described the current status, hotspots and trends in this field. A total of 2991 relevant articles from 1 January 1963 to 28 February 2023 were obtained from the Web of Science Core Collection. VOSviewer and CiteSpace software were utilized as bibliometric tools to analyze and visualize knowledge mapping. Between 1963 and 2023, the number of papers in the area of LT for liver cancer increased continuously. A total of 70 countries/regions, 2303 institutions and 14 840 researchers have published research articles, with the United States and China being the two most productive countries. Our bibliometric-based visual analysis revealed the expansion of LT indications for liver cancer and the prevention/treatment of cancer recurrence as ongoing research hotspots over the past decades. Meanwhile, emerging studies also focus on downstaging/bridging treatments before LT and the long-term survival of LT recipient, in particular the precise application of immunosuppressants.
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Affiliation(s)
- Xinyu He
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Shengjun Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Linsong Tang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
| | - Sunbin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xuyong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China
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14
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Yilma M, Mehta N. Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma. Surg Oncol Clin N Am 2024; 33:133-142. [PMID: 37945139 DOI: 10.1016/j.soc.2023.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Liver transplantation continues to be the optimal treatment for hepatocellular carcinoma (HCC). Given the limited organ supply, patient selection for liver transplant must carefully balance tumor progression with risk of recurrence posttransplant. There are several pretransplant selection criteria that incorporate biomarkers as well as imaging modality to risk-stratify patients as we continue to look for the optimal transplant cutoff for patients with HCC, which should be transplant-center specific, and account for organ availability and dynamic response to locoregional therapy.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA; National Clinician Scholars Program, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA. https://twitter.com/mignoteyilmaMD
| | - Neil Mehta
- Department of Medicine, University of California San Francisco, Connie Frank Transplant Center, 400 Parnassus Avenue 7th Floor, San Francisco, CA 94143, USA.
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Zamora-Olaya JM, Aparicio-Serrano A, Amado Torres V, Poyato González A, Montero JL, Barrera Baena P, Sánchez Frías M, Ciria Bru R, Briceño Delgado J, De la Mata M, Rodríguez-Perálvarez M. Changes in the Liver Transplant Waiting List after Expanding to the 'Up-to-Seven' Criteria for Hepatocellular Carcinoma. J Pers Med 2023; 13:1670. [PMID: 38138897 PMCID: PMC10744381 DOI: 10.3390/jpm13121670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 11/19/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
We aimed to assess changes in the composition of the waiting list for liver transplantation (LT) after expanding from Milan to "up-to-seven" criteria in patients with hepatocellular carcinoma (HCC). A consecutive cohort of 255 LT candidates was stratified in a pre-expansion era (2016-2018; n = 149) and a post-expansion era (2019-2021; n = 106). The most frequent indication for LT was HCC in both groups (47.7% vs. 43.4%; p = 0.5). The proportion of patients exceeding the Milan criteria in the explanted liver was nearly doubled after expansion (12.5% vs. 21.1%; p = 0.25). Expanding criteria had no effect in drop-out (12.3% vs. 20.4%; p = 0.23) or microvascular invasion rates (37.8% vs. 38.7%; p = 0.93). The length on the waiting list did not increase after the expansion (172 days [IQR 74-282] vs. 118 days [IQR 67-251]; p = 0.135) and was even shortened in the post-expansion HCC subcohort (181 days [IQR 125-232] vs. 116 days [IQR 74-224]; p = 0.04). Tumor recurrence rates were reduced in the post-expansion cohort (15.4% vs. 0%; p = 0.012). In conclusion, expanding from Milan to up-to-seven criteria for LT in patients with HCC had no meaningful impact on the waiting list length and composition, thus offering the opportunity for the adoption of more liberal policies in the future.
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Affiliation(s)
- Javier Manuel Zamora-Olaya
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
| | - Ana Aparicio-Serrano
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
| | - Víctor Amado Torres
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
| | - Antonio Poyato González
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain
| | - José Luis Montero
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain
| | - Pilar Barrera Baena
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain
| | | | - Rubén Ciria Bru
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- Division of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Javier Briceño Delgado
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- Division of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain
| | - Manuel Rodríguez-Perálvarez
- Division of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (J.M.Z.-O.); (A.A.-S.); (V.A.T.); (A.P.G.); (J.L.M.); (P.B.B.); (M.D.l.M.)
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), 14004 Córdoba, Spain; (R.C.B.); (J.B.D.)
- CIBER of Hepatic and Digestive Diseases (CIBEREHD), 28029 Madrid, Spain
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16
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Huo H, Wang X, Xu S, Niu X, Cheng L, Yuan Z, Huo S, Fang P. Transarterial chemoembolization plus camrelizumab is an effective and tolerable bridging therapy for patients with intermediate‑stage hepatocellular carcinoma: A pilot study. Oncol Lett 2023; 26:465. [PMID: 37780547 PMCID: PMC10534277 DOI: 10.3892/ol.2023.14052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 07/24/2023] [Indexed: 10/03/2023] Open
Abstract
Transarterial chemoembolization (TACE) has been reported to synergize with camrelizumab in the treatment of hepatocellular carcinoma (HCC). The present study aimed to explore the potential of TACE and camrelizumab as a bridging therapy prior to surgery for patients with HCC. For this purpose, 11 patients with HCC with intermediate stage disease [classified by China Liver Cancer (CNLC) staging] who received TACE combined with camrelizumab as a bridging therapy prior to surgery were enrolled in this study. The treatment response was evaluated at 2 weeks following TACE therapy and following camrelizumab treatment. The relapse-free survival (RFS) and overall survival (OS) of the patients were calculated. The objective response and disease control rates were 72.7 and 100.0% following TACE treatment, and were 100.0 and 100.0% following camrelizumab treatment, respectively. The α-fetoprotein levels gradually decreased following TACE, camrelizumab treatment and surgical resection (all P<0.05). Of note, the CNLC stage decreased following treatment (P=0.007) and the downstaging success rate was 63.6%. In terms of survival profiles, the mean RFS (95% CI) was 14.1 (11.7-16.5) months and the 1-year RFS rate was 77.9±14.1%. Furthermore, the mean OS (95% CI) was 15.0 (13.2-16.8) months and the 1-year OS rate was 80.0±17.9%. Successful downstaging was associated with RFS (P=0.041), but not OS (P=0.221). With regard to safety, 6 (54.5%) patients experienced reactive cutaneous capillary endothelial proliferation, 5 (45.5%) patients reported pain and 4 (36.4%) patients had a fever. On the whole, the present study demonstrated that TACE plus camrelizumab may be an effective and safe strategy that has potential for use as a bridging strategy prior to surgery in patients with intermediate-stage HCC.
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Affiliation(s)
- Haoran Huo
- Department of General Surgery, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Xiaoying Wang
- Department of Nephrology, Affiliated Hospital of Hebei University of Engineering, Handan, Hebei 056002, P.R. China
| | - Shan Xu
- Department of Gastroenterology, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Xiaotong Niu
- Department of Gastroenterology, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Limin Cheng
- Department of Gastroenterology, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Zengjiang Yuan
- Department of General Surgery, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Shuang Huo
- Department of General Surgery, Handan Central Hospital, Handan, Hebei 056000, P.R. China
| | - Pingping Fang
- Department of Neurology, Handan Central Hospital, Handan, Hebei 056000, P.R. China
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Natarajan B, Tabrizian P, Hoteit M, Frenette C, Parikh N, Ghaziani T, Dhanasekaran R, Guy J, Shui A, Florman S, Yao FY, Mehta N. Downstaging hepatocellular carcinoma before liver transplantation: A multicenter analysis of the "all-comers" protocol in the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) consortium. Am J Transplant 2023; 23:1771-1780. [PMID: 37532179 PMCID: PMC10998692 DOI: 10.1016/j.ajt.2023.07.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/27/2023] [Accepted: 07/27/2023] [Indexed: 08/04/2023]
Abstract
Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for "all-comers" (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.
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Affiliation(s)
- Brahma Natarajan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Catherine Frenette
- Center for Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Tara Ghaziani
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA
| | - Renu Dhanasekaran
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA
| | - Jennifer Guy
- Department of Transplantation, California Pacific Medical Center, San Francisco, California, USA
| | - Amy Shui
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA.
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18
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Wu X, Lokken RP, Mehta N. Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy? JHEP Rep 2023; 5:100781. [PMID: 37456674 PMCID: PMC10339255 DOI: 10.1016/j.jhepr.2023.100781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/30/2023] [Indexed: 07/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.
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Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Ryan Peter Lokken
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, San Francisco, CA, USA
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Pommergaard HC. Prognostic biomarkers in and selection of surgical patients with hepatocellular carcinoma. APMIS 2023; 131 Suppl 146:1-39. [PMID: 37186326 DOI: 10.1111/apm.13309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
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Bauschke A, Altendorf-Hofmann A, Brückner L, Drescher R, Freesmeyer M, Settmacher U. Impact of metabolic indices of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on post transplantation recurrence of hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:1401-1410. [PMID: 35451699 PMCID: PMC10020288 DOI: 10.1007/s00432-022-04009-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 04/02/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors. METHODS This retrospective study analyzes 103 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates. RESULTS Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, "up-to-seven" out tumors, grade 3 tumors, α- fetoprotein level >400 ng/ml and lesions > 5cm in diameter. Factors with statistically significant influence on the 10- year overall survival in the univariate analysis were Milan, up-to-seven" criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, "up-to-seven" criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significant. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates. CONCLUSIONS Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma. If we focus on preoperative findings, such as tumor size, tumor number and AFP value adding the information given by TLR of 18F-FDG PET/CT allows to estimate the risk of tumor recurrence more accurate than the established classifications Milan and UTS. Therefore, it may add valuable information to other preoperative findings, such as tumor size, tumor number and AFP level.
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Affiliation(s)
- Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany.
| | - Annelore Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Lukas Brückner
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Robert Drescher
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Martin Freesmeyer
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
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21
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Wu X, Heller M, Kwong A, Fidelman N, Mehta N. Cost-Effectiveness Analysis of Interventional Liver-Directed Therapies for a Single, Small Hepatocellular Carcinoma in Liver Transplant Candidates. J Vasc Interv Radiol 2023:S1051-0443(23)00170-7. [PMID: 36804296 DOI: 10.1016/j.jvir.2023.02.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 02/01/2023] [Accepted: 02/12/2023] [Indexed: 02/18/2023] Open
Abstract
PURPOSE To assess the cost effectiveness of 3 main locoregional therapies (LRTs) (transarterial chemoembolization [TACE], transarterial radioembolization [TARE], and percutaneous ablation) as bridging therapy. MATERIALS AND METHODS A cost-effectiveness analysis was performed comparing the 3 LRTs for patients with a single hepatocellular carcinoma (HCC) with a diameter of 3 cm or less over a 5-year time horizon from a payer's perspective. The clinical courses, including transplantation, decompensation resulting in delisting, and the need for a second LRT, were based on data from the United Network for Organ Sharing (2016-2019). Costs and effectiveness were measured in U.S. dollars and quality-adjusted life-years, respectively. Probabilistic and deterministic sensitivity analyses were performed. RESULTS A total of 2,594, 1,576, and 903 patients underwent TACE, ablation, and TARE, respectively. Ablation was the dominant strategy, with the lowest expected cost and highest effectiveness. The probabilistic sensitivity analysis demonstrated that ablation was the most cost-effective strategy in 93.9% of simulations. A subgroup analysis was performed for different wait times, with ablation remaining the most cost-effective strategy. The sensitivity analysis showed that ablation was most effective if the risk of waitlist dropout was less than 2.00% and the rate of transplantation was more than 15.1% quarterly. TARE was most effective if the risk of dropout was less than 1.19% and the rate of transplantation was more than 24.0%. TACE was most effective if the risk of dropout was less than 1.01% and the rate of transplantation was more than 45.7%. Ablation remained the most cost-effective modality until its procedural cost was more than $34,843. CONCLUSIONS Ablation is the most cost-effective bridging strategy for patients with a single, small (≤3 cm) HCC prior to liver transplantation. The conclusion remained robust in multiple sensitivity analyses.
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Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, Stanford University, San Francisco, California
| | - Michael Heller
- Department of Radiology and Biomedical Imaging, Stanford University, San Francisco, California
| | - Allison Kwong
- Department of Gastroenterology & Hepatology, Stanford University, San Francisco, California
| | - Nicholas Fidelman
- Department of Radiology and Biomedical Imaging, Stanford University, San Francisco, California
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, Stanford University, San Francisco, California.
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22
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Minoux K, Lassailly G, Ningarhari M, Lubret H, El Amrani M, Canva V, Truant S, Mathurin P, Louvet A, Lebuffe G, Goria O, Nguyen-Khac E, Boleslawski E, Dharancy S. Neo-Adjuvant Use of Sorafenib for Hepatocellular Carcinoma Awaiting Liver Transplantation. Transpl Int 2022; 35:10569. [PMID: 36438781 PMCID: PMC9681796 DOI: 10.3389/ti.2022.10569] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 10/21/2022] [Indexed: 12/01/2023]
Abstract
Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical and biological evaluation was performed every month. Radiological tumor response evaluation was realized every 3 months on the waiting list and every 6 months after LT. Among 327 patients listed for HCC, 62 (19%) were treated with Sorafenib. Sorafenib was initiated for HCC progression after loco-regional therapy (LRT) in 50% of cases and for impossibility of LRT in 50% of cases. The mean duration of treatment was 6 months. Thirty six patients (58%) dropped-out for tumor progression and 26 (42%) patients were transplanted. The 5-year overall and recurrent-free survival after LT was 77% and 48% respectively. Patients treated for impossibility of LRT had acceptable 5-year intention-to-treat overall and post-LT survivals. Conversely, patients treated for HCC progression presented high dropout rate and low intention-to-treat survival. Our results suggest that it is very questionable in terms of utility that patients treated for HCC progression should even be kept listed once the tumor progression has been observed.
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Affiliation(s)
- Kate Minoux
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Guillaume Lassailly
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Massih Ningarhari
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Henri Lubret
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Medhi El Amrani
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Valérie Canva
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Stéphanie Truant
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Philippe Mathurin
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Alexandre Louvet
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Gilles Lebuffe
- CHU Lille, Department of Anesthesiology, Resuscitation, and Critical Care Anesthesiology, University of Lille, Lille, France
| | - Odile Goria
- CHU Rouen, Department of Hepatogastroenterology, Hôpital Charles Nicolle, Rouen, France
| | - Eric Nguyen-Khac
- CHU Amiens-Picardie, Hôpital Sud, Department of Hepatogastroenterology, Amiens, France
- CHU Amiens, Centre Universitaire de Recherche en Santé (CURS), Université de Picardie-Jules-Verne (UPJV), Groupe de Recherche sur l’alcool et les Pharmacodépendances (GRAP), Inserm U1247, Amiens, France
| | - Emmanuel Boleslawski
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Sebastien Dharancy
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
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23
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Di Martino M, Vitale A, Ferraro D, Maniscalco M, Pisaniello D, Arenga G, Falaschi F, Terrone A, Iacomino A, Galeota Lanza A, Esposito C, Cillo U, Vennarecci G. Downstaging Therapies for Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation: A Systematic Review and Meta-Analysis on Intention-to-Treat Outcomes. Cancers (Basel) 2022; 14:5102. [PMID: 36291885 PMCID: PMC9600776 DOI: 10.3390/cancers14205102] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45−2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91−2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26−11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15−8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted.
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Affiliation(s)
- Marcello Di Martino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Daniele Ferraro
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Marilisa Maniscalco
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Donatella Pisaniello
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Giuseppe Arenga
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Federica Falaschi
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alfonso Terrone
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Iacomino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | | | - Ciro Esposito
- Liver Intesive Care Unit, Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Giovanni Vennarecci
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
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24
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Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
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25
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Filipec Kanižaj T, Dinjar Kujundžić P, Ostojić A, Mijić M, Sertić Milić H, Mijić A, Mateljak M, Martinčević D, Radetić E, Vidjak V, Kocman B, Mikolašević I. Liver transplantation in hepatocellular carcinoma - should we perform downstaging? Croat Med J 2022; 63:317-325. [PMID: 36046928 PMCID: PMC9468736 DOI: 10.3325/cmj.2022.63.317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 07/01/2022] [Indexed: 11/30/2022] Open
Abstract
AIM To compare the long-term outcomes between liver transplant (LT) recipients with hepatocellular carcinoma (HCC) who were downstaged with transarterial-chemoembolization (TACE) to the Milan criteria (MC) and those initially meeting the MC. METHODS This retrospective study enrolled 198 patients with HCC: 38 were downstaged and 160 patients initially met the MC. Post-LT survival and HCC recurrence-free survival were evaluated. We assessed the association of death and HCC recurrence with TACE, baseline (age, sex, disease etiology, Model of End-stage Liver Disease, tumor number and the sum of maximum tumor diameters, waiting time, alpha-fetoprotein level) and explant characteristics (tumor number and the sum of maximum tumor diameters, micro- and macrovascular invasion). RESULTS The recipient survival rates one, three, and five years after LT were 88.2%, 80.1%, and 75.9%, respectively. HCC recurrence-free probabilities were 92.3%, 87.9%, and 85%, respectively. The outcomes were comparable between the groups. In multivariate analysis, the number of tumors on the explant, age, and tumor recurrence were independent risk factors for death. Only the sum of maximum tumor diameters on the explant was an independent risk factor for HCC recurrence. CONCLUSIONS Patients successfully downstaged with TACE to the MC can achieve post-LT recipient and HCC recurrence-free survival comparable with patients initially within the MC. Good response to TACE as a criterion for LT may be a method of selecting patients with favorable biological characteristics.
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Affiliation(s)
- Tajana Filipec Kanižaj
- Tajana Filipec Kanižaj, Department of Gastroenterology, Merkur University Hospital, Zajčeva 19, 10000 Zagreb, Croatia,
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26
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Su TH, Hsu SJ, Kao JH. Paradigm shift in the treatment options of hepatocellular carcinoma. Liver Int 2022; 42:2067-2079. [PMID: 34515412 DOI: 10.1111/liv.15052] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Hepatocellular carcinoma (HCC) is prevalent worldwide with suboptimal therapeutic outcomes. The advancement of therapeutic options and the development of new systemic therapies expand the armamentarium to tackle HCC. Treatment options should be provided based on the hierarchy of efficacy in a multidisciplinary perspective, instead of the traditional stage-guided scheme. In advanced HCC, lenvatinib has a comparable efficacy as sorafenib for the first-line therapy of HCC; while regorafenib, cabozantinib, and ramucirumab have been approved as second-line therapy after the failure of sorafenib. Immune checkpoint inhibitor therapy prolongs response rate and survival and enables long-term cure. Atezolizumab plus bevacizumab is superior to sorafenib as the first-line therapy for advanced HCC. Several emerging regimens by the combination of various systemic therapies are currently under clinical trials. Systemic therapy may be used in the neoadjuvant, adjuvant or even as initial therapy for intermediate-stage HCC. The paradigm shift of HCC treatment will improve patient outcomes.
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Affiliation(s)
- Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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27
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Piñero F, Thompson M, Boin I, Chagas A, Quiñonez E, Bermúdez C, Vilatobá M, Santos L, Anders M, Hoyos Duque S, Soares Lima A, Menendez J, Padilla M, Poniachik J, Zapata R, Maraschio M, Chong Menéndez R, Muñoz L, Arufe D, Figueroa R, Perales SR, Maccali C, Vergara Sandoval R, McCormack L, Varón A, Marciano S, Mattera J, Carrilho F, Silva M. Performance of pre-transplant criteria in prediction of hepatocellular carcinoma progression and waitlist dropout. Liver Int 2022; 42:1879-1890. [PMID: 35304813 DOI: 10.1111/liv.15223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Revised: 02/08/2022] [Accepted: 02/25/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIM Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout because of tumour progression. The aim of this study was to compare the alpha-foetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. METHODS A multicentre cohort study was conducted in 20 Latin American transplant centres, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumour characteristics, and patterns of progression were recorded at time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and model's discrimination was compared estimating Harrell's adapted c-statistics. RESULTS HCC dropout rate was significantly higher in patients beyond (24% [95% CI 16-28]) compared to those within Milan criteria (8% [95% IC 5%-12%]; p < .0001), with a SHR of 3.01 [95% CI 2.03-4.47]), adjusted for waiting list time and bridging therapies (c-index 0.63 [95% CI 0.57; 0.69). HCC dropout rates were higher in patients with AFP scores >2 (adjusted SHR of 3.17 [CI 2.13-4.71]), c-index of 0.71 (95% CI 0.65-0.77; p = .09 vs Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout (SHR 1.68 [95% CI 1.08-2.61]). CONCLUSIONS Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.
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Affiliation(s)
- Federico Piñero
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
- Hospital Universitario Austral, University, School of Medicine, Buenos Aires, Argentina
| | - Marcos Thompson
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Ilka Boin
- Hospital das Clínicas UNICAMP Campinas, Sao Paulo, Brazil
| | - Aline Chagas
- Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil
| | | | - Carla Bermúdez
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Mario Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, Mexico
| | | | | | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe & Gastroenterology group from the University of Antioquia, Medellín, Colombia
| | - Agnaldo Soares Lima
- Hospital das Clinicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | - Martín Padilla
- Universidad Nacional de San Marcos, Hospital Guillermo Almenara, Lima, Peru
| | | | - Rodrigo Zapata
- Clínica Alemana, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile
| | | | | | - Linda Muñoz
- Hospital Universitario "Dr. José E. González", Monterrey, Mexico
| | - Diego Arufe
- Sanatorio Sagrado Corazón, Buenos Aires, Argentina
| | | | | | - Claudia Maccali
- Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil
| | | | | | | | | | | | - Flair Carrilho
- Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas Department of Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil
| | - Marcelo Silva
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
- Hospital Universitario Austral, University, School of Medicine, Buenos Aires, Argentina
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28
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Ilmer M, Guba MO. Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection. Cancers (Basel) 2022; 14:cancers14112662. [PMID: 35681642 PMCID: PMC9179475 DOI: 10.3390/cancers14112662] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 05/10/2022] [Accepted: 05/19/2022] [Indexed: 02/04/2023] Open
Abstract
While liver transplantation was initially considered as a curative treatment modality only for hepatocellular carcinoma, the indication has been increasingly extended to other tumor entities over recent years, most recently to the treatment of non-resectable colorectal liver metastases. Although oncologic outcomes after liver transplantation (LT) are consistently good, organ shortage forces stringent selection of suitable candidates. Dynamic criteria based on tumor biology fulfill the prerequisite of an individual oncological prediction better than traditional morphometric criteria based on tumor burden. The availability of specific (neo-)adjuvant therapies and customized modern immunosuppression may further contribute to favorable post-transplantation outcomes on the one hand and simultaneously open the path to LT as a curative option for advanced stages of tumor patients. Herein, we provide an overview of the oncological LT indications, the selection process, and expected oncological outcome after LT.
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Affiliation(s)
- Matthias Ilmer
- Department of General, Visceral and Transplantation Surgery, Hospital of the University of Munich, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany;
- German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Transplantation Center Munich, Ludwig-Maximilians-University Munich, Campus Grosshadern, 81377 Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
- Correspondence:
| | - Markus Otto Guba
- Department of General, Visceral and Transplantation Surgery, Hospital of the University of Munich, Ludwig-Maximilians-University (LMU), 81377 Munich, Germany;
- Transplantation Center Munich, Ludwig-Maximilians-University Munich, Campus Grosshadern, 81377 Munich, Germany
- Liver Center Munich, Ludwig-Maximilians-University Munich, 81377 Munich, Germany
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29
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Benkö T, König J, Theysohn JM, Schotten C, Saner FH, Treckmann J, Radunz S. Bridging treatment prior to liver transplantation for hepatocellular carcinoma: radioembolization or transarterial chemoembolization? Eur J Med Res 2022; 27:74. [PMID: 35619164 PMCID: PMC9134704 DOI: 10.1186/s40001-022-00708-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 05/16/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND In hepatocellular carcinoma (HCC) patients, intraarterial therapies are regularly employed as a bridge to liver transplantation to prevent tumor progression during waiting time. Objective of this study was to compare HCC recurrence after liver transplantation following TACE or radioembolization bridging treatment. METHODS We retrospectively analyzed prospectively collected data on 131 consecutive HCC patients who underwent liver transplantation between January 2007 and December 2017 at our liver transplant center (radioembolization n = 44, TACE n = 87). Multivariable logistic regression and cox proportional hazard regression models were used to evaluate factors associated with tumor recurrence and post-transplant survival. RESULTS Between groups, patients were comparable with regards to age and gender. In the radioembolization group, Milan criteria for HCC were met significantly less frequently (20.5% vs. 65.5%, p < 0.0001). Patients in the radioembolization group required significantly fewer intraarterial treatments (1 [1-2] vs. 1 [1-7], p = 0.0007). On explant specimen, tumor differentiation, microvascular invasion and tumor necrosis were comparable between the groups. HCC recurrence and overall survival were similar between the groups. Multivariable analysis detected increasing recipient age, male gender, complete tumor necrosis and absence of microvascular invasion being independently associated with decreased odds for HCC recurrence. Increasing model of end-stage liver disease (MELD) score and tumor recurrence were independently associated with increased odds of post-transplant death. CONCLUSIONS Intraarterial bridging treatment leading to tumor necrosis may not only prevent waitlist drop-out but also facilitate long-term successful liver transplantation in HCC patients. Both radioembolization and TACE represent potent treatment strategies.
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Affiliation(s)
- Tamás Benkö
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Julia König
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jens M Theysohn
- Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
| | - Clemens Schotten
- Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany
| | - Fuat H Saner
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Jürgen Treckmann
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany
| | - Sonia Radunz
- Department of General, Visceral and Transplant Surgery, University Hospital Essen, Essen, Germany.
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30
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Kwong AJ, Ghaziani TT, Yao F, Sze D, Mannalithara A, Mehta N. National Trends and Waitlist Outcomes of Locoregional Therapy Among Liver Transplant Candidates With Hepatocellular Carcinoma in the United States. Clin Gastroenterol Hepatol 2022; 20:1142-1150.e4. [PMID: 34358718 DOI: 10.1016/j.cgh.2021.07.048] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 07/07/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Policy changes in the United States have lengthened overall waiting times for patients with hepatocellular carcinoma (HCC). We investigated temporal trends in utilization of locoregional therapy (LRT) and associated waitlist outcomes among liver transplant (LT) candidates in the United States. METHODS Data for primary adult LT candidates listed from 2003 to 2018 who received HCC exception were extracted from the Organ Procurement and Transplantation Network database. Explant histology was examined, and multivariable competing risk analysis was used to evaluate the association between LRT type and waitlist dropout. RESULTS There were 31,609 eligible patients with at least 1 approved HCC exception, and 34,610 treatments among 24,145 LT candidates. The proportion with at least 1 LRT recorded increased from 42.3% in 2003 to 92.4% in 2018. Chemoembolization remains the most frequent type, followed by thermal ablation, with a notable increase in radioembolization from 3% in 2013 to 19% in 2018. An increased incidence of LRT was observed among patients with tumor burden beyond Milan criteria, higher α-fetoprotein level, and more compensated liver disease. Receipt of any type of LRT was associated with a lower risk of waitlist dropout; there was no significant difference by number of LRTs. In inverse probability of treatment weighting-adjusted analysis, radioembolization or ablation as the first LRT was associated with a reduced risk of waitlist dropout compared with chemoembolization. CONCLUSIONS In a large nationwide cohort of LT candidates with HCC, LRT, and in particular radioembolization, increasingly was used to bridge to LT. Patients with greater tumor burden and those with more compensated liver disease received more treatments while awaiting LT. Bridging LRT was associated with a lower risk of waitlist dropout.
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Affiliation(s)
- Allison J Kwong
- Division of Gastroenterology and Hepatology, Stanford, California
| | - T Tara Ghaziani
- Division of Gastroenterology and Hepatology, Stanford, California
| | - Francis Yao
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California
| | - Daniel Sze
- Division of Interventional Radiology, Stanford University, Stanford, California
| | | | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, San Francisco, California.
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31
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Seehofer D, Petrowsky H, Schneeberger S, Vibert E, Ricke J, Sapisochin G, Nault JC, Berg T. Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation—Adjusting the Odds? Transpl Int 2022; 35:10333. [PMID: 35529597 PMCID: PMC9069348 DOI: 10.3389/ti.2022.10333] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022]
Abstract
Background and Aims: Morphometric features such as the Milan criteria serve as standard criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Since it has been recognized that these criteria are too restrictive and do not adequately display the tumor biology, additional selection parameters are emerging. Methods: Concise review of the current literature on patient selection for downstaging and LT for HCC outside the Milan criteria. Results: The major task in patients outside the Milan criteria is the need for higher granularity with patient selection, since the benefit through LT is not uniform. The recent literature clearly shows that beneath tumor size and number, additional selection parameters are useful in the process of patient selection for and during downstaging. For initial patient selection, the alpha fetoprotein (AFP) level adds additional information to the size and number of HCC nodules concerning the chance of successful downstaging and LT. This effect is quantifiable using newer selection tools like the WE (West-Eastern) downstaging criteria or the Metroticket 2.0 criteria. Also an initial PET-scan and/or tumor biopsy can be helpful, especially in the high risk group of patients outside the University of California San Francisco (UCSF) criteria. After this entry selection, the clinical course during downstaging procedures concerning the tumor and the AFP response is of paramount importance and serves as an additional final selection tool. Conclusion: Selection criteria for liver transplantation in HCC patients are becoming more and more sophisticated, but are still imperfect. The implementation of molecular knowledge will hopefully support a more specific risk prediction for HCC patients in the future, but do not provide a profound basis for clinical decision-making at present.
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Affiliation(s)
- Daniel Seehofer
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital, Leipzig, Germany
- *Correspondence: Daniel Seehofer,
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zürich, Zurich, Switzerland
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eric Vibert
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France
| | - Jens Ricke
- Department of Radiology, LMU Munich, Munich, Germany
| | - Gonzalo Sapisochin
- Ajmera Transplant Program and HPB Surgical Oncology, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Jean-Charles Nault
- Service d’Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Université Paris Nord, Paris, France
- INSERM UMR 1138 Functional Genomics of Solid Tumors Laboratory, Paris, France
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
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32
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Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
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Shimamura T, Goto R, Watanabe M, Kawamura N, Takada Y. Liver Transplantation for Hepatocellular Carcinoma: How Should We Improve the Thresholds? Cancers (Basel) 2022; 14:cancers14020419. [PMID: 35053580 PMCID: PMC8773688 DOI: 10.3390/cancers14020419] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/06/2022] [Accepted: 01/10/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary The ideal treatment for hepatocellular carcinoma (HCC) is liver transplantation (LT), which both eliminates the HCC and cures the diseased liver. Once considered an experimental treatment with dismal survival rates, LT for HCC entered a new era with the establishment of the Milan criteria over 20 years ago. However, over the last two decades, the Milan criteria, which are based on tumor morphology, have come under intense scrutiny and are now largely regarded as too restrictive, and limit the access of transplantation for many patients who would otherwise achieve good clinical outcomes. The liver transplant community has been making every effort to reach a goal of establishing more reliable selection criteria. This article addresses how the criteria have been extended, as well as the concept of pre-transplant down-staging to maximize the eligibility. Abstract Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related mortality, and liver transplantation is the ideal treatment for this disease. The Milan criteria provided the opportunity for HCC patients to undergo LT with favorable outcomes and have been the international gold standard and benchmark. With the accumulation of data, however, the Milan criteria are not regarded as too restrictive. After the implementation of the Milan criteria, many extended criteria have been proposed, which increases the limitations regarding the morphological tumor burden, and incorporates the tumor’s biological behavior using surrogate markers. The paradigm for the patient selection for LT appears to be shifting from morphologic criteria to a combination of biologic, histologic, and morphologic criteria, and to the establishment of a model for predicting post-transplant recurrence and outcomes. This review article aims to characterize the various patient selection criteria for LT, with reference to several surrogate markers for the biological behavior of HCC (e.g., AFP, PIVKA-II, NLR, 18F-FDG PET/CT, liquid biopsy), and the response to locoregional therapy. Furthermore, the allocation rules in each country and the present evidence on the role of down-staging large tumors are addressed.
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Affiliation(s)
- Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, N-14, W-5, Kita-ku, Sapporo 060-8648, Hokkaido, Japan
- Correspondence:
| | - Ryoichi Goto
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan;
| | - Masaaki Watanabe
- Department of Transplant Surgery, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan; (M.W.); (N.K.)
| | - Norio Kawamura
- Department of Transplant Surgery, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-ku, Sapporo 060-8638, Hokkaido, Japan; (M.W.); (N.K.)
| | - Yasutsugu Takada
- Department of HBP and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon 791-0295, Ehime, Japan;
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34
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Sun Z, Shi Z, Xin Y, Zhao S, Jiang H, Wang D, Zhang L, Wang Z, Dai Y, Jiang H. Artificial Intelligent Multi-Modal Point-of-Care System for Predicting Response of Transarterial Chemoembolization in Hepatocellular Carcinoma. Front Bioeng Biotechnol 2021; 9:761548. [PMID: 34869272 PMCID: PMC8634755 DOI: 10.3389/fbioe.2021.761548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/22/2021] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks the second most lethal tumor globally and is the fourth leading cause of cancer-related death worldwide. Unfortunately, HCC is commonly at intermediate tumor stage or advanced tumor stage, in which only some palliative treatment can be used to offer a limited overall survival. Due to the high heterogeneity of the genetic, molecular, and histological levels, HCC makes the prediction of preoperative transarterial chemoembolization (TACE) efficacy and the development of personalized regimens challenging. In this study, a new multi-modal point-of-care system is employed to predict the response of TACE in HCC by a concept of integrating multi-modal large-scale data of clinical index and computed tomography (CT) images. This multi-modal point-of-care predicting system opens new possibilities for predicting the response of TACE treatment and can help clinicians select the optimal patients with HCC who can benefit from the interventional therapy.
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Affiliation(s)
- Zhongqi Sun
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhongxing Shi
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanjie Xin
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Sheng Zhao
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hao Jiang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dandan Wang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Linhan Zhang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ziao Wang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanmei Dai
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huijie Jiang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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Crocetti L, Bozzi E, Scalise P, Bargellini I, Lorenzoni G, Ghinolfi D, Campani D, Balzano E, De Simone P, Cioni R. Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation. Cancers (Basel) 2021; 13:5558. [PMID: 34771720 PMCID: PMC8583584 DOI: 10.3390/cancers13215558] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/27/2021] [Accepted: 11/03/2021] [Indexed: 02/08/2023] Open
Abstract
Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.
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Affiliation(s)
- Laura Crocetti
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
| | - Elena Bozzi
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Paola Scalise
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Irene Bargellini
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Giulia Lorenzoni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
| | - Davide Ghinolfi
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Daniela Campani
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Pathology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy
| | - Emanuele Balzano
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Paolo De Simone
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, 56126 Pisa, Italy; (D.C.); (P.D.S.)
- Division of Hepatobiliary Surgery and Liver Transplantation, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (D.G.); (E.B.)
| | - Roberto Cioni
- Division of Interventional Radiology, Azienda Ospedaliero Universitaria Pisana, 56126 Pisa, Italy; (E.B.); (P.S.); (I.B.); (G.L.); (R.C.)
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Mehta N, Frenette C, Tabrizian P, Hoteit M, Guy J, Parikh N, Ghaziani TT, Dhanasekaran R, Dodge JL, Natarajan B, Holzner ML, Frankul L, Chan W, Fobar A, Florman S, Yao FY. Downstaging Outcomes for Hepatocellular Carcinoma: Results From the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) Consortium. Gastroenterology 2021; 161:1502-1512. [PMID: 34331914 PMCID: PMC8545832 DOI: 10.1053/j.gastro.2021.07.033] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 05/30/2021] [Accepted: 07/20/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND & AIMS United Network of Organ Sharing (UNOS) has adopted uniform criteria for downstaging (UNOS-DS) of hepatocellular carcinoma (HCC) before liver transplantation (LT), but the downstaging success rate and intention-to-treat outcomes across broad geographic regions are unknown. METHODS In this first multiregional study (7 centers, 4 UNOS regions), 209 consecutive patients with HCC undergoing downstaging based on UNOS-DS criteria were prospectively evaluated from 2016 to 2019. RESULTS Probability of successful downstaging to Milan criteria and dropout at 2 years from the initial downstaging procedure was 87.7% and 37.3%, respectively. Pretreatment with lectin-reactive α-fetoprotein ≥10% (hazard ratio, 3.7; P = .02) was associated with increased dropout risk. When chemoembolization (n = 132) and yttrium-90 radioembolization (n = 62) were compared as the initial downstaging treatment, there were no differences in Modified Response Evaluation Criteria In Solid Tumors response, probability of or time to successful downstaging, waiting list dropout, or LT. Probability of LT at 3 years was 46.6% after a median of 17.2 months. In the explant, 17.5% had vascular invasion, and 42.8% exceeded Milan criteria (understaging). The only factor associated with understaging was the sum of the number of lesions plus largest tumor diameter on the last pre-LT imaging, and the odds of understaging increased by 35% per 1-unit increase in this sum. Post-LT survival at 2 years was 95%, and HCC recurrence occurred in 7.9%. CONCLUSION In this first prospective multiregional study based on UNOS-DS criteria, we observed a successful downstaging rate of >80% and similar efficacy of chemoembolization and yttrium-90 radioembolization as the initial downstaging treatment. A high rate of tumor understaging was observed despite excellent 2-year post-LT survival of 95%. Additional LRT to reduce viable tumor burden may reduce tumor understaging.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California.
| | | | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jennifer Guy
- Department of Transplantation, California Pacific Medical Center
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - T. Tara Ghaziani
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California
| | - Renu Dhanasekaran
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Brahma Natarajan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Matthew L. Holzner
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York
| | - Leana Frankul
- Center for Organ and Cell Transplantation, Scripps Green Hospital
| | - Wesley Chan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Austin Fobar
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco,Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
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Hwang S, Song GW, Ahn CS, Kim KH, Moon DB, Ha TY, Jung DH, Park GC, Yoon YI, Lee SG. Quantitative Prognostic Prediction Using ADV Score for Hepatocellular Carcinoma Following Living Donor Liver Transplantation. J Gastrointest Surg 2021; 25:2503-2515. [PMID: 33532981 DOI: 10.1007/s11605-021-04939-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/18/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND We assessed the prognostic impact of the ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting hepatocellular carcinoma (HCC) recurrence and patient survival after living donor liver transplantation (LDLT). METHODS This study included 843 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. These cases were divided into treatment-naïve (TN, n = 256]) and pretransplant-treated (PT, n = 587 [69.6%]) groups. RESULTS There were weak or nearly no correlations among AFP, DCP, and TV. There existed high correlations between the pretransplant and explant findings regarding tumor number, size, and ADV score. Right lobe grafts were implanted in 760 (90.2%) patients. HCC recurrence and all-cause patient death occurred in 182 (15.9%) and 126 (15.0%) respectively during the follow-up period for 75.6 ± 35.5 months. The 5-year tumor recurrence (TR) and overall patient survival (OS) rates were 21.5% and 86.2%, respectively. The PT group showed higher TR (p < 0.001) and lower OS rates (p < 0.001). TR and OS were closely correlated with both pretransplant and explant ADV scores in the TN and PT groups. The ADV score enabled further prognostic stratification of the patients within and beyond the Milan, UCSF, and Asan Medical Center criteria. Compared with the 7 pre-existing selection criteria, ADV score with a cutoff of 5log showed the highest prognostic contrast regarding TR and OS. CONCLUSIONS Our prognostic prediction model using ADV scores is an integrated quantitative surrogate biomarker for posttransplant prognosis in HCC patients and can provide reliable information that assists the decision-making for LDLT.
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Affiliation(s)
- Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea.
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma. Cancer Immunol Immunother 2021; 71:1103-1113. [PMID: 34585256 PMCID: PMC9015997 DOI: 10.1007/s00262-021-03061-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 09/16/2021] [Indexed: 01/13/2023]
Abstract
Background Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients. Methods Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567). Results The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells. Conclusions In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood. Trial Registration DRKS00013567 Supplementary Information The online version contains supplementary material available at 10.1007/s00262-021-03061-9.
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Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review. J Clin Med 2021; 10:jcm10173932. [PMID: 34501381 PMCID: PMC8432180 DOI: 10.3390/jcm10173932] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 08/22/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023] Open
Abstract
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.
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Talakić E, Janek E, Mikalauskas S, Schemmer P. Liver Transplantation in Malignancies: A Comprehensive and Systematic Review on Oncological Outcome. Visc Med 2021; 37:302-314. [PMID: 34540947 PMCID: PMC8406343 DOI: 10.1159/000517328] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/20/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Liver transplantation (LT) is today's standard treatment for both end-stage liver disease and tumors; however, suitable grafts for LT are a scarce resource and outcome after LT is highly dependent on its underlying indication. Thus, patients must be carefully selected to optimize the number of life years gained per graft. This comprehensive and systematic review critically reflects the most recently published oncological outcome data after LT in malignancies based on the preoperative radiological findings. METHODS A systematic literature search was conducted to detect preferentially most recent high-volume series or large database analysis on oncological outcomes after LT for both primary liver cancer and liver metastases between January 1, 2019, and November 14, 2020. A comprehensive review on the radiological assessment of the reviewed liver malignancies is included and its preoperative value for an outcome-driven indication reflected. RESULTS Twenty most recent high-volume or relevant studies including a total number of 2,521 patients were identified including 4, 4, 4, 4, 3, and 1 publications on oncological outcome after LT for hepatocellular carcinoma, cholangiocellular carcinoma, hepatic epitheloid hemangioendothelioma, hepatoblastoma, and both metastatic neuroendocrine tumors and colorectal cancer, respectively. The overall survival is comparable to patients without tumors if patients with malignancies are well selected for LT; however, this is highly dependent on tumor entity, tumor stage, and both neoadjuvant and concomitant treatment. DISCUSSION/CONCLUSION LT is a promising option for better survival in patients with malignant liver tumors in selected patients; however, the indication must be critically discussed prior to LT in every single case in the context of organ shortage.
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Affiliation(s)
- Emina Talakić
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Elmar Janek
- Division of General Radiology, Department of Radiology, Medical University Graz (MUG), Graz, Austria
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
| | - Saulius Mikalauskas
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
| | - Peter Schemmer
- Transplant Center Graz, Medical University Graz (MUG), Graz, Austria
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University Graz (MUG), Graz, Austria
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Hwang S, Moon DB, Kim KH, Ahn CS, Song GW, Jung DH, Park GC, Lee SG. Prognostic Accuracy of the ADV Score Following Resection of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis. J Gastrointest Surg 2021; 25:1745-1759. [PMID: 32948961 DOI: 10.1007/s11605-020-04800-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 09/06/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND We assessed the prognostic accuracy of ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) following resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS This was a retrospective observational study. This study included 147 patients who underwent hepatic resection for HCC with PVTT. They were followed up for ≥ 66 months or until patient death. RESULTS The grades of PVTT were Vp1 in 121 (14.3%), Vp2 in 41 (27.9%), Vp3 in 71 (48.3%), and Vp4 in14 (9.5%) cases. Preoperative HCC treatment was performed in 48 (32.7%) patients. R0 and R1 resections were performed in 119 (81.0%) and 28 (19.0%) cases, respectively. The 5-year tumor recurrence, HCC-specific survival, and post-recurrence survival rates were 79.2%, 43.5%, and 25.4%, respectively. Neither PVTT grade nor history of preoperative HCC treatment was a significant prognostic indicator. Stratification in accordance with ADV scores of 1log- and 3log-intervals resulted in high prognostic accuracy in predicting tumor recurrence and patient survival. Following cluster analysis, the cutoff for ADV score was determined at 9log and was more prognostically significant in terms of tumor recurrence and patient survival than surgical curability or microvascular invasion. Further comparisons revealed that prognostic prediction with an ADV score cutoff at 9log was more accurate than that using the Eastern Hepatobiliary Surgery Hospital-PVTT score. CONCLUSIONS ADV score is an integrated surrogate biomarker for post-resection prognosis in HCC with PVTT. Our prognostic prediction model using ADV scores provides reliable post-resection prognosis for patients with various grades of these tumors.
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Affiliation(s)
- Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
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Dirican A, Karakas S. What Should Be the Rules for Downstaging for Hepatocellular Carcinoma? J Gastrointest Cancer 2021; 51:1148-1151. [PMID: 32839945 DOI: 10.1007/s12029-020-00490-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Liver transplantation remains the main curative treatment method for hepatocellular carcinoma. There are several criteria for hepatocellular carcinoma to be eligible for liver transplantation, and it depends on main transplantation centers worldwide. Locoregional treatments and downstaging protocols are used for either to achieve these criteria or to prevent drop outs on the transplant waiting lists. But who can benefit from these bridging therapies effectively for the main purpose of curative treatment? Main contraindications are known for locoregional treatments like cirrhosis or low hepatic function, total main portal vein occlusion, and extrahepatic metastasis. HCCs, which are confined to liver but have high tumor burden, remains the main controversial issue. AIM On this aspect, we reviewed the literature for downstaging protocols for hepatocellular carcinoma with their effect on survival and recurrence rates after liver transplantation. CONCLUSION Although candidates for downstaging is still controversial, with the absence of main contraindications, LRT can be applied to selected HCCs, which have a certain degree of tumor burden.
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Affiliation(s)
- Abuzer Dirican
- Faculty of Medicine, Department of Surgery, Institute of Liver Transplantation, Inonu University, 44280, Malatya, Turkey
| | - Serdar Karakas
- Faculty of Medicine, Department of Surgery, Institute of Liver Transplantation, Inonu University, 44280, Malatya, Turkey.
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Frankul L, Frenette C. Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy. J Clin Transl Hepatol 2021; 9:220-226. [PMID: 34007804 PMCID: PMC8111105 DOI: 10.14218/jcth.2020.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 10/04/2020] [Accepted: 03/04/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
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Affiliation(s)
| | - Catherine Frenette
- Correspondence to: Catherine Frenette, Scripps Center for Organ Transplant, Scripps Clinic/Green Hospital, 10666 N. Torrey Pines Rd N200, La Jolla, CA 92037, USA. ORCID: https://orcid.org/0000-0002-2245-8173 Tel: +1-858-554-4310, Fax: +1-858-554-3009, E-mail:
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45
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Renner P, Da Silva T, Schnitzbauer AA, Verloh N, Schlitt HJ, Geissler EK. Hepatocellular carcinoma progression during bridging before liver transplantation. BJS Open 2021; 5:6220251. [PMID: 33839747 PMCID: PMC8038254 DOI: 10.1093/bjsopen/zrab005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 01/13/2021] [Indexed: 12/18/2022] Open
Abstract
Background Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P < 0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P = 0.030). Conclusion Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival. Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.
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Affiliation(s)
- P Renner
- Department of Surgery, University Medical Centre Regensburg, Regensburg, Germany.,Department of Surgery, Robert-Bosch Hospital, Stuttgart, Germany
| | - T Da Silva
- Department of Surgery, University Medical Centre Regensburg, Regensburg, Germany
| | - A A Schnitzbauer
- Department for General, Visceral and Transplant Surgery, University Hospital Frankfurt, Goethe-University, Frankfurt, Germany
| | - N Verloh
- Department of Radiology, University Medical Centre Regensburg, Regensburg, Germany
| | - H J Schlitt
- Department of Surgery, University Medical Centre Regensburg, Regensburg, Germany
| | - E K Geissler
- Department of Surgery, University Medical Centre Regensburg, Regensburg, Germany.,Division of Personalized Tumor Therapy, Fraunhofer Institute for Experimental Medicine and Toxicology, Regensburg, Germany
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Schoenberg MB, Ehmer U, Umgelter A, Bucher JN, Koch DT, Börner N, Nieß H, Denk G, De Toni EN, Seidensticker M, Andrassy J, Angele MK, Werner J, Guba MO. Liver transplantation versus watchful waiting in hepatocellular carcinoma patients with complete response to bridging therapy - a retrospective observational study. Transpl Int 2021; 34:465-473. [PMID: 33368655 DOI: 10.1111/tri.13808] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 08/04/2020] [Accepted: 12/22/2020] [Indexed: 12/13/2022]
Abstract
Bridging therapy to prevent progression on the waiting list can result in a sustained complete response (sCR). In some patients, the liver transplantation (LT) risk might exceed those of tumor recurrence. We thus evaluated whether a watchful waiting (CR-WW) strategy could be a feasible alternative to transplantation (CR-LT). We performed a retrospective analysis of overall survival (OS) and recurrence-free survival (RFS) of patients with a sCR (CR > 6 months). Permitted bridging included thermoablation, resection, and combinations of either with transarterial chemoembolization. Patients were divided into the intended treatment strategies CR-WW and CR-LT. 39 (18.40%) sCR patients from 212 were investigated. 22 patients were treated with a CR-LT and 17 patients a CR-WW strategy. Five-year RFS was lower in the CR-WW than in the CR-LT group [53.3% (22.1%; 77.0%) and 84.0% (57.6%; 94.7%)]. 29.4% (5/17) CR-WW patients received salvage transplantation because of recurrence. OS (5-year) was 83.9% [56.8%; 94.7%] after LT and 75.4% [39.8%; 91.7%] after WW. Our analysis shows that the intuitive decision made by our patients in agreement with their treating physicians for a watchful waiting strategy in sCR can be justified. Applied on a larger scale, this strategy could help to reduce the pressure on the donor pool.
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Affiliation(s)
- Markus Bo Schoenberg
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Ursula Ehmer
- Medical Department II, Technical University of Munich, Munich, Germany
| | - Andreas Umgelter
- Medical Department II, Technical University of Munich, Munich, Germany.,Interdisciplinary Emergency Room, Vivantes Humboldt Hospital, Berlin, Germany
| | - Julian Nikolaus Bucher
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Dominik Thomas Koch
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Nikolaus Börner
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Hanno Nieß
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Gerald Denk
- Department of Medicine II, LMU Munich, University Hospital, Munich, Germany.,Transplantation Center Munich, Ludwig-Maximilians-University, Munich, Germany
| | | | - Max Seidensticker
- Department of Radiology, Ludwig-Maximilians-University, Munich, Germany
| | - Joachim Andrassy
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Martin Kurt Angele
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Jens Werner
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany
| | - Markus Otto Guba
- Department of General-, Visceral-, and Transplantation Surgery, Ludwig-Maximilians-University, Munich, Germany.,Transplantation Center Munich, Ludwig-Maximilians-University, Munich, Germany
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Kwong A, Mehta N. Expanding the Limits of Liver Transplantation for Hepatocellular Carcinoma: Is There a Limit? Clin Liver Dis 2021; 25:19-33. [PMID: 33978578 DOI: 10.1016/j.cld.2020.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation is a treatment option for hepatocellular carcinoma within Milan criteria. With careful selection practices, patients with larger tumors can do well with successful downstaging followed by liver transplantation and should not be excluded based on tumor size or number alone. When considering expanded criteria for hepatocellular carcinoma, however, survival outcomes after liver transplantation should be comparable with patients without hepatocellular carcinoma. Surrogate measures of tumor biology, such as α-fetoprotein, other biomarkers, and dynamic tumor behavior including response to locoregional therapy can aid in risk stratification of patients before liver transplantation.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University, 420 Broadway Street, 3rd Floor, Redwood City, CA 94063, USA
| | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, 513 Parnassus Avenue, S-357, San Francisco, CA 94143, USA.
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48
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Piñero F, Anders M, Boin IF, Chagas A, Quiñonez E, Marciano S, Vilatobá M, Santos L, Hoyos Duque S, Lima AS, Menendez J, Padilla M, Poniachik J, Zapata R, Soza A, Maraschio M, Chong Menéndez R, Muñoz L, Arufe D, Figueroa R, de Ataide EC, Maccali C, Vergara Sandoval R, Bermudez C, Podesta LG, McCormack L, Varón A, Gadano A, Mattera J, Villamil F, Rubinstein F, Carrilho F, Silva M. Liver transplantation for hepatocellular carcinoma: impact of expansion criteria in a multicenter cohort study from a high waitlist mortality region. Transpl Int 2021; 34:97-109. [PMID: 33040420 DOI: 10.1111/tri.13767] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Revised: 08/25/2020] [Accepted: 10/06/2020] [Indexed: 01/16/2023]
Abstract
This study aimed to compare liver transplantation (LT) outcomes and evaluate the potential rise in numbers of LT candidates with hepatocellular carcinoma (HCC) of different allocation policies in a high waitlist mortality region. Three policies were applied in two Latin American cohorts (1085 HCC transplanted patients and 917 listed patients for HCC): (i) Milan criteria with expansion according to UCSF downstaging (UCSF-DS), (ii) the AFP score, and (iii) restrictive policy or Double Eligibility Criteria (DEC; within Milan + AFP score ≤2). Increase in HCC patient numbers was evaluated in an Argentinian prospective validation set (INCUCAI; NCT03775863). Expansion criteria in policy A showed that UCSF-DS [28.4% (CI 12.8-56.2)] or "all-comers" [32.9% (CI 11.9-71.3)] had higher 5-year recurrence rates compared to Milan, with 10.9% increase in HCC patients for LT. The policy B showed lower recurrence rates for AFP scores ≤2 points, even expanding beyond Milan criteria, with a 3.3% increase. Patients within DEC had lower 5-year recurrence rates compared with those beyond DEC [13.3% (CI 10.1-17.3) vs 24.2% (CI 17.4-33.1; P = 0.0006], without significant HCC expansion. In conclusion, although the application of a stricter policy may optimize the selection process, this restrictive policy may lead to ethical concerns in organ allocation (NCT03775863).
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Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Margarita Anders
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
- Hospital Alemán, Buenos Aires, Argentina
| | - Ilka F Boin
- Hospital das Clínicas UNICAMP Campinas, Sao Paulo, Brazil
| | - Aline Chagas
- Hospital das Clínicas University of São Paulo School of Medicine, São Paulo, Brazil
| | | | | | - Mario Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, México
| | | | - Sergio Hoyos Duque
- Grupo de Gastrohepatología, Hospital Pablo Tobón Uribe, Universidad de Antioquia, Medellin, Colombia
| | | | | | | | | | - Rodrigo Zapata
- Clínica Alemana, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile
| | - Alejandro Soza
- Hospital Clínico, Universidad Católica de Chile, Santiago, Chile
| | | | | | - Linda Muñoz
- Hospital Universitario "Dr. José E. González", Monterrey, Mexico
| | - Diego Arufe
- Sanatorio Sagrado Corazón, Buenos Aires, Argentina
| | | | | | - Claudia Maccali
- Hospital das Clínicas University of São Paulo School of Medicine, São Paulo, Brazil
| | | | - Carla Bermudez
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | | | - Adriana Varón
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Tlalpan, México
| | | | - Juan Mattera
- Hospital das Clínicas University of São Paulo School of Medicine, São Paulo, Brazil
| | - Federico Villamil
- Hospital El Cruce, Florencio Varela, Argentina
- Hospital Británico, Buenos Aires, Argentina
| | - Fernando Rubinstein
- Instituto de Efectividad Clínica y Sanitaria (IECS), Buenos Aires, Argentina
| | - Flair Carrilho
- Hospital das Clínicas University of São Paulo School of Medicine, São Paulo, Brazil
| | - Marcelo Silva
- Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
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Role of Locoregional Therapies in Patients With Hepatocellular Cancer Awaiting Liver Transplantation. Am J Gastroenterol 2021; 116:57-67. [PMID: 33110015 DOI: 10.14309/ajg.0000000000000999] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
Hepatocellular cancer (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related deaths. The United Network for Organ Sharing has its own staging criteria for organ allocation, which is a modification of tumor-node-metastasis staging of American Joint Committee on Cancer. For the purpose of clarity, United Network for Organ Sharing staging will be described as uT1, uT2 (Milan criteria), and uT3 (eligible for downstaging) in this review. For those with unresectable HCC or those with advanced liver disease and HCC but within the Milan criteria, liver transplantation is the treatment of choice. Because of prolonged waiting period on the liver transplant list in many parts of the world for deceased donor liver transplantation, there is a serious risk of dropout from the liver transplant list because of tumor progression. For those patients, locoregional therapies might need to be considered, and moreover, there is circumstantial evidence to suggest that tumor progression after locoregional therapies might be a surrogate marker of unfavorable tumor biology. There is no consensus on the role or type of locoregional therapies in the management of patients with uT1 and uT2 eligible for liver transplant and of those with lesions larger than uT2 but eligible for downstaging protocol (uT3 lesions). In this review, we examine the role of locoregional therapies in these patients stratified by staging and propose treatment options based on the current evidence of tumor progression rates while awaiting liver transplantation and tumor recurrence rates after liver transplantation.
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Lee S, Kim KW, Song GW, Kwon JH, Hwang S, Kim KH, Ahn CS, Moon DB, Park GC, Lee SG. The Real Impact of Bridging or Downstaging on Survival Outcomes after Liver Transplantation for Hepatocellular Carcinoma. Liver Cancer 2020; 9:721-733. [PMID: 33442541 PMCID: PMC7768098 DOI: 10.1159/000507887] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 04/14/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION There is no consensus regarding selection criteria on liver transplantation (LT) for hepatocellular carcinoma (HCC), especially for living donor liver transplantation, although emerging evidence has been found for the effectiveness of bridging or downstaging. OBJECTIVE We evaluated the long-term outcomes of patients who underwent LT with or without bridging or downstaging for HCC. METHODS This retrospective study included 896 LT recipients with HCC between June 2005 and May 2015. Recurrence-free survival (RFS), overall survival (OS), and their associated factors were evaluated. RESULTS The 5-year RFS in the full cohort of 896 patients was 82.4%, and the OS was 85.3%. In patients with initial Organ Procurement and Transplantation Network (OPTN) T1 and T2, the 5-year RFS and OS did not significantly differ between LT groups with and without bridging (all p ≥ 0.05). The 5-year RFS and OS of OPTN T3 patients with successful downstaging were not significantly different from those of patients with OPTN T2 with primary LT (p = 0.070 and p = 0.185), but were significantly higher than in patients with OPTN T3 with downstaging failure and initial OPTN T1 or T2 with progression (all p < 0.001). In the multivariate analysis, last alpha-fetoprotein before LT ≥70 ng/mL (hazard ratio [HR]: 1.77, p = 0.001; HR: 1.72, p = 0.004), pretransplant HCC status exceeding the Milan criteria (HR: 5.12, p < 0.001; HR: 3.31, p < 0.001), and positron emission tomography positivity (HR: 2.57, p < 0.001; HR: 2.57, p < 0.001) were independent predictors for worse RFS and OS. CONCLUSIONS The impact of bridging therapy on survival outcomes is limited in patients with early-stage HCC, whereas OPTN T1 or T2 with progression provides worse prognosis. OPTN T3 should undergo LT after successful downstaging, and OPTN T3 with successful downstaging allows for acceptable long-term posttransplant outcomes.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Won Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,*Kyoung Won Kim, Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology 88, Olympic-Ro 43-Gil, Seoul 05505 (Republic of Korea),
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,**Gi-Won Song, Asan Medical Center, University of Ulsan College of Medicine, Department of Radiology 88, Olympic-Ro 43-Gil, Seoul 05505 (Republic of Korea),
| | - Jae Hyun Kwon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ki-Hun Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chul-Soo Ahn
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Deok-Bog Moon
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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