1
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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: 0] [Impact Index Per Article: 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] [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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2
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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. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. 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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3
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Tabrizian P, Pero A, Schwartz M. Hepatic Resection for Hepatocellular Carcinoma. Clin Liver Dis 2025; 29:59-72. [PMID: 39608958 DOI: 10.1016/j.cld.2024.08.008] [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: 11/30/2024]
Abstract
Hepatic resection has long been considered the preferred treatment for hepatocellular carcinoma (HCC) when feasible, but its role, as well as the outcomes is evolving rapidly. This article explores the impact of the changing demographics of HCC, reviews current criteria for resection, considers the roles of liver transplantation and nonsurgical locoregional therapies vis-a-vis resection, highlights the potential of new systemic therapies (particularly immune checkpoint inhibitors) to improve outcomes, details the common complications associated with resection, and discusses recurrence of HCC after resection and its management.
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Affiliation(s)
- Parissa Tabrizian
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Adriana Pero
- Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA
| | - Myron Schwartz
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, New York, NY 10029, USA.
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4
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Tang S, Cai J, Zhou K, Mei Z, Huang D, Liu L, Yang L, Yin D, Hu L. Cu-MOFs@AuPtNPs nanozyme-based immunosorbent assay for colorimetric detection of alpha-fetoprotein. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:6443-6450. [PMID: 39225244 DOI: 10.1039/d4ay01410c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Accurate detection of tumor biomarkers in blood is crucial for diagnosing and treating tumor disease. In this study, a metal enzyme-linked immunosorbent assay (MeLISA) was fabricated for the ultrasensitive and naked-eye detection of tumor biomarker alpha-fetoprotein (AFP) in clinical serum samples. Herein, novel copper metal-organic frameworks and gold platinum nanoparticle composites (Cu-MOFs@AuPtNPs) were synthesized for the first time by an in situ method, which showed an enormous specific surface area and excellent peroxidase (POx) mimicking properties. Cu-MOFs@AuPtNPs linked with antibodies targeting AFP served as a signal nanoprobe to amplify the detection signal. Additionally, the specificity of MeLISA was significantly enhanced through a conventional antigen-antibody reaction and efficient blocking of non-specific sites with BSA. Under optimal conditions, the sandwich-type MeLISA exhibited a wide range from 0.001 to 1000 ng mL-1 (R2 = 0.997) and a low detection limit of 0.86 pg mL-1 (S/N = 3) with acceptable stability, selectivity, and reproducibility. It is noteworthy that the suggested MeLISA performed exceptionally well in detecting clinical serum samples, which were visible to the naked eye and did not require complex platforms. To sum up, the innovative MeLISA based on Cu-MOFs@AuPtNPs provides an alternative method for early cancer diagnosis, particularly in economically backward areas where simple diagnostic apparatus is extremely desirable.
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Affiliation(s)
- Sitian Tang
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Juan Cai
- Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038, PR China
| | - Kai Zhou
- Department of Spine Surgery, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China
| | - Zhu Mei
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Dongmei Huang
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Ling Liu
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Lunyu Yang
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Dan Yin
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
| | - Liyi Hu
- Department of Clinical Laboratory Medicine, The People's Hospital of Chongqing Liangjiang New Area, No. 199 Ren Xing Road, Yubei, Chongqing, 401121, PR China.
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5
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Abdelhamed W, Shousha H, El-Kassas M. Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end? LIVER RESEARCH 2024; 8:141-151. [PMID: 39957750 PMCID: PMC11771265 DOI: 10.1016/j.livres.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 08/01/2024] [Accepted: 09/05/2024] [Indexed: 01/03/2025]
Abstract
Hepatocellular carcinoma (HCC) is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality. The incidence of portal vein tumor thrombosis (PVTT) in HCC patients is 21% at one year and 46% at three years. The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades. Notably, HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT. Currently, there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT. The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C, indicating an advanced stage, and limiting treatment recommendations for these patients to systemic therapy. In recent years, there has been an increase in the availability of therapeutic options for HCC patients with PVTT. Treatment modalities include systemic therapy, transarterial chemoembolization, surgical resection, stereotactic body radiotherapy, transarterial radioembolization, and liver transplantation. An ideal therapy for each patient necessitates a multidisciplinary approach. This review article presents the latest updates in managing HCC patients with PVTT.
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Affiliation(s)
| | - Hend Shousha
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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6
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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7
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Ferraro D, Falaschi F, Nazzaro L, Vennarecci G. Impact of neoadjuvant multimodal therapy in the setting of locally advanced hepatocellular carcinoma. World J Gastroenterol 2024; 30:3452-3455. [PMID: 39091715 PMCID: PMC11290390 DOI: 10.3748/wjg.v30.i28.3452] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/28/2024] [Accepted: 07/02/2024] [Indexed: 07/24/2024] Open
Abstract
Immunotherapy and the implementation of more aggressive treatment schemes for locally advanced hepatocellular carcinomas have expanded the boundaries of curative options. Because of these advancements, patients who were once considered beyond the aim of a cure are now eligible for liver transplantation and resection.
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Affiliation(s)
- Daniele Ferraro
- Hepato-biliary and Liver Transplant Centre, Department of General Surgery and Woman’s Health, AORN Antonio Cardarelli, Naples 80131, Italy
| | - Federica Falaschi
- Hepato-biliary and Liver Transplant Centre, Department of General Surgery and Woman’s Health, AORN Antonio Cardarelli, Naples 80131, Italy
| | - Luca Nazzaro
- Hepato-biliary and Liver Transplant Centre, Department of General Surgery and Woman’s Health, AORN Antonio Cardarelli, Naples 80131, Italy
| | - Giovanni Vennarecci
- Hepato-biliary and Liver Transplant Centre, Department of General Surgery and Woman’s Health, AORN Antonio Cardarelli, Naples 80131, Italy
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8
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Chan KM, Lee WC. Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis. Biomed J 2024:100757. [PMID: 38942384 DOI: 10.1016/j.bj.2024.100757] [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: 03/18/2024] [Revised: 05/22/2024] [Accepted: 06/25/2024] [Indexed: 06/30/2024] Open
Abstract
Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan.
| | - Wei-Chen Lee
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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9
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Bhangui P. Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective? Hepatobiliary Pancreat Dis Int 2024; 23:123-128. [PMID: 37880019 DOI: 10.1016/j.hbpd.2023.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 09/27/2023] [Indexed: 10/27/2023]
Abstract
Patients with locally advanced hepatocellular cancer (HCC) and portal vein tumor thrombosis (PVTT) have a dismal prognosis since limited treatment options are available for them. In recent years, effective systemic therapy, and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy, have given some hope to prolong survival in them. This review summarized recent evidence in literature regarding the possible role of liver resection (LR) and liver transplantation (LT) in patients with locally advanced HCC and PVTT with no extrahepatic disease. Downstaging therapies have helped make curative resection or LT a reality in selected patients. This review emphasizes on the key points to focus on when considering surgery in these patients, who are usually relegated to palliative systemic therapy alone. Meticulous patient selection based on tumor biology, documented downstaging based on imaging and decrease in tumor marker levels, and an adequate waiting period to demonstrate stable disease, may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.
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Affiliation(s)
- Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Sector 38, Gurgaon, Delhi NCR 122001, India.
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10
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Horwitz JK, Agopian VG. Indication of Liver Transplant for HCC: Current Status and Future Directions. CURRENT HEPATOLOGY REPORTS 2024; 23:185-192. [DOI: 10.1007/s11901-024-00641-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/10/2024] [Indexed: 01/03/2025]
Abstract
Abstract
Purpose of Review
Liver transplantation remains the gold-standard treatment for cirrhotic patients with early stage, surgically unresectable hepatocellular carcinoma (HCC). In this review, we describe the current state of liver transplantation (LT) for HCC.
Recent Findings
We review recent advances in expanded indications for LT, diagnostics with liquid biopsy and biomarkers, and the emerging role of immunotherapy in this patient population.
Summary
Although the shortage of liver allografts necessitates a restrictive HCC selection policy, future advances in patient selection, liquid biopsy technologies and systemic therapies have the potential to improve access to liver transplantation even in patients with expanded indications, without compromising on post-transplant outcomes.
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11
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Melehy A, Agopian V. Treating rare tumors with liver transplantation. Curr Opin Organ Transplant 2024; 29:30-36. [PMID: 37851086 DOI: 10.1097/mot.0000000000001118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2023]
Abstract
PURPOSE OF REVIEW The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS). RECENT FINDINGS Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines. SUMMARY GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
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Affiliation(s)
- Andrew Melehy
- Dumont-UCLA Transplant and Liver Cancer Centers, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles, California, USA
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12
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, 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, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie biliärer Karzinome“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e213-e282. [PMID: 38364849 DOI: 10.1055/a-2189-8567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/18/2024]
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
| | | | - 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
| | - 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
| | - 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
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - 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
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg
| | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - 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
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - 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 und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - 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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13
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Amory B, Goumard C, Laurent A, Langella S, Cherqui D, Salame E, Barbier L, Soubrane O, Farges O, Hobeika C, Kawai T, Regimbeau JM, Faitot F, Pessaux P, Truant S, Boleslawski E, Herrero A, Mabrut JY, Chiche L, Di Martino M, Rhaiem R, Schwarz L, Resende V, Calderaro J, Augustin J, Caruso S, Sommacale D, Hofmeyr S, Ferrero A, Fuks D, Vibert E, Torzilli G, Scatton O, Brustia R. Combined hepatocellular-cholangiocarcinoma compared to hepatocellular carcinoma and intrahepatic cholangiocarcinoma: Different survival, similar recurrence: Report of a large study on repurposed databases with propensity score matching. Surgery 2024; 175:413-423. [PMID: 37981553 DOI: 10.1016/j.surg.2023.09.040] [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: 07/12/2023] [Revised: 09/06/2023] [Accepted: 09/26/2023] [Indexed: 11/21/2023]
Abstract
BACKGROUND Combined hepatocholangiocarcinoma is a rare cancer with a grim prognosis composed of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma morphologic patterns in the same tumor. The aim of this multicenter, international cohort study was to compare the oncologic outcomes after surgery of combined hepatocholangiocarcinoma to hepatocellular carcinoma and intrahepatic cholangiocarcinoma. METHODS Patients treated by surgery for combined hepatocholangiocarcinoma, hepatocellular carcinoma, and intrahepatic cholangiocarcinoma from 2000 to 2021 from multicenter international databases were analyzed retrospectively. Patients with combined hepatocholangiocarcinoma (cases) were compared with 2 control groups of hepatocellular carcinoma or intrahepatic cholangiocarcinoma, sequentially matched using a propensity score based on 8 preoperative characteristics. Overall and disease-free survival were compared, and predictors of mortality and recurrence were analyzed with Cox regression after propensity score matching. RESULTS During the study period, 3,196 patients were included. Propensity score adjustment and 2 sequential matching processes produced a new cohort (n = 244) comprising 3 balanced groups was obtained (combined hepatocholangiocarcinoma = 56, intrahepatic cholangiocarcinoma = 66, and hepatocellular carcinoma = 122). Kaplan-Meier overall survival estimations at 1, 3, and 5 years were 67%, 45%, and 28% for combined hepatocholangiocarcinoma, 92%, 75%, and 55% for hepatocellular carcinoma, and 86%, 53%, and 42% for the intrahepatic cholangiocarcinoma group, respectively (P = .0014). Estimations of disease-free survival at 1, 3, and 5 years were 51%, 25%, and 17% for combined hepatocholangiocarcinoma, 63%, 35%, and 26% for the hepatocellular carcinoma group, and 51%, 31%, and 28% for the intrahepatic cholangiocarcinoma group, respectively (P = .19). Predictors of mortality were combined hepatocholangiocarcinoma subtype, metabolic syndrome, preoperative tumor markers alpha-fetoprotein and carbohydrate antigen 19-9, and satellite nodules, and recurrence was associated with satellite nodules rather than cancer subtype. CONCLUSION Despite data limitations, overall survival among patients with combined hepatocholangiocarcinoma was worse than both groups and closer intrahepatic cholangiocarcinoma, whereas disease-free survival was similar among the 3 groups. Future research on immunophenotypic profiling may hold more promise than traditional nonmodifiable clinical characteristics (as found in this study) in predicting recurrence or response to salvage treatments.
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Affiliation(s)
- Boris Amory
- Department of Digestive and Hepato-pancreatic-biliary Surgery, AP-HP, Hôpital Henri-Mondor, Paris Est Créteil University, UPEC, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Claire Goumard
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Alexis Laurent
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Serena Langella
- Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy
| | - Daniel Cherqui
- Center Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Ephrem Salame
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, University of Tours, France; FHU Support, Tours, France
| | - Louise Barbier
- Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, University of Tours, France; FHU Support, Tours, France
| | - Olivier Soubrane
- Department of Digestive, Oncological, and Metabolic Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Olivier Farges
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris, Clichy, France
| | - Christian Hobeika
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris, Clichy, France
| | - Takayuki Kawai
- Department of Surgery, Medical Research Institute, Kitano Hospital, Osaka and Graduate School of Medicine, Kyoto University, Japan
| | - Jean-Marc Regimbeau
- SSPC (Simplification of Surgical Patients Care) - Clinical Research Unit, University of Picardie Jules Verne, Amiens, France; Department of Digestive Surgery, Amiens University Medical Center, France
| | - François Faitot
- Service de Chirurgie Hépato-Biliaire et Transplantation Hépatique, Hôpital de Hautepierre, Strasbourg, France
| | - Patrick Pessaux
- Unité Chirurgie HBP, Pôle hépato-digestif Nouvel Hôpital Civil, Strasbourg, France; Institut of Viral and Liver Disease, Inserm U1110, Strasbourg, France
| | - Stéphanie Truant
- Department of Digestive Surgery and Transplantation, University Hospitals, Lille, France
| | - Emmanuel Boleslawski
- Department of Digestive Surgery and Transplantation, University Hospitals, Lille, France
| | - Astrid Herrero
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, France
| | - Jean-Yves Mabrut
- Croix Rousse University Hospital, Department of General Surgery and Liver Transplantation, Lyon, France; Cancer Research Center of Lyon, INSERM U1052, France
| | - Laurence Chiche
- Department of Hepato-Bilio-Pancreatic Surgery and Liver Transplantation, Haut Lévêque Hospital, Center Hospitalier Universitaire de Bordeaux, France; Inserm UMR 1312-Team 3 "Liver Cancers and Tumoral Invasion," Bordeaux Institute of Oncology, University of Bordeaux, France
| | - Marcello Di Martino
- HPB Unit, Department of General and Digestive Surgery, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Rami Rhaiem
- Department of Hepatobiliary, Pancreatic, and Digestive Surgery, Robert Debré University Hospital, Reims, France; University Reims Champagne-Ardenne, France
| | - Lilian Schwarz
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Rouen University Hospital, UNIROUEN, UMR 1245 INSERM, Normandie Rouen University, France
| | - Vivian Resende
- Federal University of Minas Gerais School of Medicine, Belo Horizonte, Brazil
| | - Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Jérémy Augustin
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Stefano Caruso
- Université Paris Est Créteil, INSERM, IMRB, Créteil, France; Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Pathology, Créteil, France; Inserm, U955, Team 18, Créteil, France
| | - Daniele Sommacale
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, Créteil, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France
| | - Stefan Hofmeyr
- Division of Surgery, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Ospedale Mauriziano, Torino, Italy
| | - David Fuks
- Department of Hepato-Pancreatic-Biliary and Endocrine Surgery, Hopital Cochin, Assistance Publique-Hôpitaux de Paris, France; Université Paris Cité, France
| | - Eric Vibert
- Center Hepato-Biliaire, AP-HP Paul Brousse Hospital, Paris-Saclay University, Villejuif, France
| | - Guido Torzilli
- Division of Hepatobiliary and General Surgery, Department of Surgery, Humanitas Research Hospital - IRCCS, Humanitas University, Rozzano, Milan, Italy
| | - Olivier Scatton
- Department of Hepatobiliary and Liver Transplantation Surgery, AP-HP, Hôpital Pitié Salpêtrière, CRSA, Sorbonne Université, Paris, France
| | - Raffaele Brustia
- Department of Digestive and Hepato-pancreatic-biliary Surgery, DMU CARE, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Henri Mondor, Créteil, France; Paris Est Créteil University, UPEC, France; Team "Pathophysiology and Therapy of Chronic Viral Hepatitis and Related Cancers," INSERM U955, Créteil, France; Assistance Publique-Hôpitaux de Paris, Créteil, France.
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14
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Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, 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, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie „Diagnostik und Therapie des Hepatozellulären Karzinoms“ – Langversion 4.0. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:e67-e161. [PMID: 38195102 DOI: 10.1055/a-2189-6353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
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
| | | | - 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
| | - 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
| | - 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
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - 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
| | - 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
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - 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 und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - 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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15
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Attallah KA, Albannan MS, Farid K, Rizk SM, Fathy N. HCC-Check: A Novel Diagnostic Tool for Early Detection of Hepatocellular Carcinoma Based on Cytokeratin-1 and Epithelial Membrane Antigen: A Cross-Sectional Study. Technol Cancer Res Treat 2024; 23:15330338241234790. [PMID: 38436112 PMCID: PMC10913511 DOI: 10.1177/15330338241234790] [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: 09/28/2023] [Revised: 01/18/2024] [Accepted: 02/06/2024] [Indexed: 03/05/2024] Open
Abstract
Background: Hepatocellular carcinoma is frequently diagnosed in advanced stages, leading to a poorer prognosis. Therefore, early diagnosis and identification of biomarkers may significantly improve outcomes. Methods: This cross-sectional study enrolled 486 participants distributed among 3 groups: F1 to F3 = 184, F4 = 183, and hepatocellular carcinoma = 119. Liver fibrosis staging was performed using FibroScan, while imaging features were used for hepatocellular carcinoma detection. Epithelial membrane antigen and cytokeratin-1 levels in serum were quantified through Western blot and ELISA, respectively. Results: Patients diagnosed with hepatocellular carcinoma exhibited significantly elevated levels of epithelial membrane antigen and cytokeratin-1 compared to non-hepatocellular carcinoma patients, with a highly significant statistical difference (P < .0001). Epithelial membrane antigen demonstrated diagnostic performance with an area under the curve of 0.75, a sensitivity of 69.0%, and a specificity of 68.5%. Cytokeratin-1 for the identification of hepatocellular carcinoma showed a sensitivity of 79.0% and a specificity of 81.4%, resulting in an area under the curve of 0.87. The developed HCC-Check, which incorporates epithelial membrane antigen, cytokeratin-1, albumin, and alpha-fetoprotein, displayed a higher area under the curve of 0.95 to identify hepatocellular carcinoma, with a sensitivity of 89.8% and a specificity of 83.9%. Notably, HCC-Check values exceeding 2.57 substantially increased the likelihood of hepatocellular carcinoma, with an estimated odds ratio of 50.65, indicating a higher susceptibility to hepatocellular carcinoma development than those with lower values. The HCC-Check diagnostic test exhibited high precision in identifying patients with hepatocellular carcinoma, particularly those with small tumor sizes (<5 cm) and a single nodule, as reflected in area under the curve values of 0.92 and 0.85, respectively. HCC-Check was then applied to the validation study to test its accuracy and reproducibility, showing superior area under the curves for identifying different stages of hepatocellular carcinoma. These outcomes underscore the effectiveness of the test in the early detection of hepatocellular carcinoma. Conclusion: The HCC-Check test presents a highly accurate diagnostic method for detecting hepatocellular carcinoma in its early stages.
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Affiliation(s)
- Kareem A. Attallah
- Research and Development Department, Biotechnology Research Center, New Damietta, Egypt
- Clinical Research Department, Damietta Directorate for Health Affairs, Egyptian Ministry of Health and Population, Damietta, Egypt
| | - Mohamed S. Albannan
- Research and Development Department, Biotechnology Research Center, New Damietta, Egypt
| | - Khaled Farid
- Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Sherine M. Rizk
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Nevine Fathy
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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16
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Taouli B, Ba-Ssalamah A, Chapiro J, Chhatwal J, Fowler K, Kang TW, Knobloch G, Koh DM, Kudo M, Lee JM, Murakami T, Pinato DJ, Ringe KI, Song B, Tabrizian P, Wang J, Yoon JH, Zeng M, Zhou J, Vilgrain V. Consensus report from the 10th global forum for liver magnetic resonance imaging: multidisciplinary team discussion. Eur Radiol 2023; 33:9167-9181. [PMID: 37439935 PMCID: PMC10667403 DOI: 10.1007/s00330-023-09919-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 05/15/2023] [Accepted: 05/23/2023] [Indexed: 07/14/2023]
Abstract
The 10th Global Forum for Liver Magnetic Resonance Imaging was held in October 2021. The themes of the presentations and discussions at this Forum are described in detail in the review by Taouli et al (2023). The focus of this second manuscript developed from the Forum is on multidisciplinary tumor board perspectives in hepatocellular carcinoma (HCC) management: how to approach early-, mid-, and late-stage management from the perspectives of a liver surgeon, an interventional radiologist, and an oncologist. The manuscript also includes a panel discussion by multidisciplinary experts on three selected cases that explore challenging aspects of HCC management. CLINICAL RELEVANCE STATEMENT: This review highlights the importance of a multidisciplinary team approach in liver cancer patients and includes the perspectives of a liver surgeon, an interventional radiologist, and an oncologist, including illustrative case studies. KEY POINTS: • A liver surgeon, interventional radiologist, and oncologist presented their perspectives on the treatment of early-, mid-, and late-stage HCC. • Different perspectives on HCC management between specialties emphasize the importance of multidisciplinary tumor boards. • A multidisciplinary faculty discussed challenging aspects of HCC management, as highlighted by three case studies.
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Affiliation(s)
- Bachir Taouli
- Department of Diagnostic, Molecular, and Interventional Radiology, BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Julius Chapiro
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA
| | - Jagpreet Chhatwal
- Department of Radiology, Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kathryn Fowler
- Department of Radiology, University of California San Diego, La Jolla, CA, USA
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Gesine Knobloch
- Global Medical and Clinical Affairs and Digital Development, Radiology, Bayer Pharmaceuticals, Berlin, Germany
| | - Dow-Mu Koh
- Department of Diagnostic Radiology, Royal Marsden Hospital, Sutton, UK
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, South Korea
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - David J Pinato
- Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK; Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
| | - Kristina I Ringe
- Department of Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Parissa Tabrizian
- Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jin Wang
- Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou; Liver Disease Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, Seoul, South Korea
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Valérie Vilgrain
- Université Paris Cité and Department of Radiology, Assistance-Publique Hôpitaux de Paris, APHP Nord, Hôpital Beaujon, Clichy, France
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17
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Lai Q, De Stefano C, Emond J, Bhangui P, Ikegami T, Schaefer B, Hoppe‐Lotichius M, Mrzljak A, Ito T, Vivarelli M, Tisone G, Agnes S, Ettorre GM, Rossi M, Tsochatzis E, Lo CM, Chen C, Cillo U, Ravaioli M, Lerut JP. Development and validation of an artificial intelligence model for predicting post-transplant hepatocellular cancer recurrence. Cancer Commun (Lond) 2023; 43:1381-1385. [PMID: 37904670 PMCID: PMC10693300 DOI: 10.1002/cac2.12468] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 06/25/2023] [Accepted: 07/13/2023] [Indexed: 11/01/2023] Open
Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto ISapienza University of RomeRomeItaly
| | | | - Jean Emond
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of SurgeryWeill Cornell Medicine‐Columbia UniversityNew YorkUS
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative MedicineMedanta‐The MedicityGurgaonIndia
| | - Toru Ikegami
- Department of Surgery and ScienceKyushu UniversityFukuokaJapan
| | - Benedikt Schaefer
- Department of Medicine I, Gastroenterology, Hepatology and EndocrinologyMedical University of InnsbruckInnsbruckAustria
| | - Maria Hoppe‐Lotichius
- Klinik für Allgemein‐, Viszeral‐ und TransplantationschirurgieUniversitätsmedizin MainzMainzGermany
| | - Anna Mrzljak
- Liver Transplant CentreMerkur University of ZagrebZagrebCroatia
| | - Takashi Ito
- Division of Hepato‐Biliary‐Pancreatic and Transplant Surgery, Department of SurgeryGraduate School of MedicineKyotoJapan
| | - Marco Vivarelli
- Unit of Hepatobiliary Surgery and Transplantation, AOU Ospedali RiunitiPolytechnic University of MarcheAnconaItaly
| | - Giuseppe Tisone
- Department of Surgical Sciences and Medical Sciences University of Rome‐Tor VergataRomeItaly
| | - Salvatore Agnes
- Liver Unit, Department of SurgeryCatholic University‐Fondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly
| | | | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, AOU Policlinico Umberto ISapienza University of RomeRomeItaly
| | - Emmanuel Tsochatzis
- UCL Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver CentreRoyal Free HospitalLondonUK
| | - Chung Mau Lo
- Hong Kong University–Department of SurgeryQueen Mary Hospital, University of Hong KongHong KongP. R. China
| | - Chao‐Long Chen
- Department of SurgeryKaohsiung Chang Gung Memorial Hospital, Chang Gung University College of MedicineKaohsiung, TaiwanP. R. China
| | - Umberto Cillo
- Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
| | - Matteo Ravaioli
- Department of General Surgery and TransplantationIRCCS, Azienda Ospedaliero‐Universitaria di Bologna, Bologna UniversityBolognaItaly
| | - Jan Paul Lerut
- Institut de Recherche CliniqueUniversité catholique de LouvainBrusselsBelgium
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18
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Marrone G, Leone MS, Biolato M, Liguori A, Bianco G, Spoletini G, Gasbarrini A, Miele L, Pompili M. Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues. Cancers (Basel) 2023; 15:5593. [PMID: 38067299 PMCID: PMC10705300 DOI: 10.3390/cancers15235593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/03/2023] [Accepted: 11/18/2023] [Indexed: 01/12/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Maurizio Pompili
- Medical and Surgical Sciences Department, Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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19
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Meier RP, Kamberi S, Alvarez-Casas J, Lane BF, Bhati CS, Malik S, Twaddell W, Shetty K, Fang A, Kim HS, Maluf DG. Inferior Vena Cava Thrombectomy and Stenting as Bridge to Liver Transplantation After Radiotherapy-Induced Thrombosis. Prog Transplant 2023:15269248231212914. [PMID: 37941349 DOI: 10.1177/15269248231212914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2023]
Affiliation(s)
- Raphael Ph Meier
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Shani Kamberi
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Josue Alvarez-Casas
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Barton F Lane
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Chandra S Bhati
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Saad Malik
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - William Twaddell
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Kirti Shetty
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Adam Fang
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Hyun S Kim
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Daniel G Maluf
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
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20
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Elderkin J, Al Hallak N, Azmi AS, Aoun H, Critchfield J, Tobon M, Beal EW. Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management. Cancers (Basel) 2023; 15:5118. [PMID: 37958294 PMCID: PMC10647678 DOI: 10.3390/cancers15215118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 10/11/2023] [Accepted: 10/13/2023] [Indexed: 11/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level. Mail outreach along with navigation provision has proven to increase surveillance follow-up in patients, while provider-targeted electronic medical record reminders and compliance reports have increased provider awareness of HCC surveillance. Imaging is the primary mode of diagnosis in HCC with The Liver Imaging Reporting and Data System (LI-RADS) being a widely accepted comprehensive system that standardizes the reporting and data collection for HCC. The management of HCC is complex and requires multidisciplinary team evaluation of each patient based on their preference, the state of the disease, and the available medical and surgical interventions. Staging systems are useful in determining the appropriate intervention for HCC. Early-stage HCC is best managed by curative treatment modalities, such as liver resection, transplant, or ablation. For intermediate stages of the disease, transarterial local regional therapies can be applied. Advanced stages of the disease are treated with systemic therapies, for which there have been recent advances with new drug combinations. Previously sorafenib was the mainstay systemic treatment, but the recent introduction of atezolizumab plus bevacizumab proves to have a greater impact on overall survival. Although there is a current lack of improved outcomes in Phase III trials, neoadjuvant therapies are a potential avenue for HCC management in the future.
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Affiliation(s)
- Jessica Elderkin
- Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Najeeb Al Hallak
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Asfar S. Azmi
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
| | - Hussein Aoun
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Jeffrey Critchfield
- Department of Radiology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (H.A.); (J.C.)
| | - Miguel Tobon
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
| | - Eliza W. Beal
- Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; (N.A.H.); (A.S.A.)
- Department of Surgery, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA;
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21
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Claasen MPAW, Sneiders D, Rakké YS, Adam R, Bhoori S, Cillo U, Fondevila C, Reig M, Sapisochin G, Tabrizian P, Toso C. European Society of Organ Transplantation (ESOT) Consensus Report on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma. Transpl Int 2023; 36:11648. [PMID: 37779513 PMCID: PMC10533675 DOI: 10.3389/ti.2023.11648] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2023] [Accepted: 08/22/2023] [Indexed: 10/03/2023]
Abstract
Liver transplantation offers the best chance of cure for most patients with non-metastatic hepatocellular carcinoma (HCC). Although not all patients with HCC are eligible for liver transplantation at diagnosis, some can be downstaged using locoregional treatments such as ablation and transarterial chemoembolization. These aforementioned treatments are being applied as bridging therapies to keep patients within transplant criteria and to avoid them from dropping out of the waiting list while awaiting a liver transplant. Moreover, immunotherapy might have great potential to support downstaging and bridging therapies. To address the contemporary status of downstaging, bridging, and immunotherapy in liver transplantation for HCC, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in the treatment of HCC to review literature and to develop guidelines pertaining to this cause that were subsequently discussed and voted during the Transplant Learning Journey (TLJ) 3.0 Consensus Conference that took place in person in Prague. The findings and recommendations of the working group on Downstaging, Bridging and Immunotherapy in Liver Transplantation for Hepatocellular Carcinoma are presented in this article.
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Affiliation(s)
- Marco Petrus Adrianus Wilhelmus Claasen
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, Netherlands
- Multi-Organ Transplant Program, University Health Network (UHN), Toronto, ON, Canada
| | - Dimitri Sneiders
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - Yannick Sebastiaan Rakké
- Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, Netherlands
| | - René Adam
- Centre Hépato-Biliaire, APHP Hôpital Universitaire Paul Brousse, Université Paris-Saclay, Paris, France
| | - Sherrie Bhoori
- Hepatology, Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Umberto Cillo
- Chirurgia Generale 2, Epato-Bilio-Pancreatica e Centro Trapianto di Fegato, Azienda Ospedale Università Padova, Padova, Italy
| | | | - Maria Reig
- BCLC Group, Liver Unit, Digestive Disease Institute, Hospital Clínic, IDIBAPS CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network (UHN), Toronto, ON, Canada
| | - Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Christian Toso
- Division of Abdominal Surgery, Faculty of Medicine, University of Geneva, Geneva, Switzerland
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22
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Tustumi F, Coelho FF, de Paiva Magalhães D, Júnior SS, Jeismann VB, Fonseca GM, Kruger JAP, D'Albuquerque LAC, Herman P. Treatment of hepatocellular carcinoma with macroscopic vascular invasion: A systematic review and network meta-analysis. Transplant Rev (Orlando) 2023; 37:100763. [PMID: 37393656 DOI: 10.1016/j.trre.2023.100763] [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: 04/10/2023] [Revised: 05/11/2023] [Accepted: 05/14/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND This study aimed to evaluate the outcomes of different treatments for patients with hepatocellular carcinoma (HCC) and macroscopic vascular invasion. METHODS A systematic review and meta-analysis of comparative studies was performed to evaluate various treatment modalities for HCC with macroscopic vascular invasion, including liver resection (LR), liver transplantation (LT), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), radiotherapy (RT), radiofrequency ablation (RFA), and antineoplastic systemic therapy (AnST). RESULTS After applying the selection criteria, 31 studies were included. The surgical resection (SR) group (including LR and LT) had a similar mortality rate to the non-surgical resection (NS) group (RD = -0.01; 95% CI -0.05 to 0.03). The SR group had a higher rate of complications (RD = 0.06; 95% CI 0.00 to 0.12) but a higher 3-year overall survival (OS) rate than the NS group (RD = 0.12; 95% CI 0.05 to 0.20). The network analysis revealed that the overall survival was lower in the AnST group. LT and LR had similar survival benefits. The meta-regression suggested that SR has a greater impact on the survival of patients with impaired liver function. DISCUSSION Most likely, LT has a significant impact on long-term survival and consequently would be a better option for HCC with macroscopic vascular invasion in patients with impaired liver function. LT and LR offer a higher chance of long-term survival than NS alternatives, although LR and LR are associated with a higher risk of procedure-related complications.
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Affiliation(s)
- Francisco Tustumi
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Fabricio Ferreira Coelho
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Daniel de Paiva Magalhães
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Sérgio Silveira Júnior
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Vagner Birk Jeismann
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Gilton Marques Fonseca
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Jaime Arthur Pirola Kruger
- Instituto do Câncer do Estado de São Paulo (ICESP), Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Luiz Augusto Carneiro D'Albuquerque
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Paulo Herman
- Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clinicas (HCFMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
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23
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Soin A, Lesurtel M, Bhangui P, Cocchi L, Bouattour M, Clavien PA. Are patients with hepatocellular carcinoma and portal vein tumour thrombosis candidates for liver transplantation? J Hepatol 2023; 78:1124-1129. [PMID: 37208099 DOI: 10.1016/j.jhep.2023.03.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 03/27/2023] [Indexed: 05/21/2023]
Abstract
In this debate, the authors consider whether patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis are candidates for liver transplantation (LT). The argument for LT in this context is based on the premise that, following successful downstaging treatment, LT confers a much greater clinical benefit in terms of survival outcomes than the available alternative (palliative systemic therapy). A major argument against relates to limitations in the quality of evidence for LT in this setting - in relation to study design, as well as heterogeneity in patient characteristics and downstaging protocols. While acknowledging the superior outcomes offered by LT for patients with portal vein tumour thrombosis, the counterargument is that expected survival in such patients is still below accepted thresholds for LT and, indeed, the levels achieved for other patients who receive transplants beyond the Milan criteria. Based on the available evidence, it seems too early for consensus guidelines to recommend such an approach, however, it is hoped that with higher quality evidence and standardised downstaging protocols, LT may soon be more widely indicated, including for this population with high unmet clinical need.
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Affiliation(s)
- Arvinder Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Mickaël Lesurtel
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Lorenzo Cocchi
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Mohamed Bouattour
- Department of Hepatology, APHP Beaujon Hospital, University of Paris Cité, 100, Bd General Leclerc, 92110 Clichy, France
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24
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Bitzer M, Groß S, Albert J, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Kautz A, Krug D, Fougère CL, Lang H, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. S3-Leitlinie Diagnostik und Therapie biliärer Karzinome – Langversion. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:e92-e156. [PMID: 37040776 DOI: 10.1055/a-2026-1240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/13/2023]
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
| | | | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | | | - 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
| | - 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 Transplantationschrirugie, Eberhard-Karls Universität, Tübingen
| | | | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - 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
- Klinik für Innere Medizin, Gesundheit Nord, Klinikverbund Bremen
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | | | - 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
| | - 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
| | - Reina Tholen
- Deutscher Bundesverband für Physiotherapie (ZVK) e. V
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Arndt Vogel
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover
| | - 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 und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - 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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Abstract
This is a review of current practices and upcoming developments regarding hepatocellular carcinoma (HCC). This includes a contemporary review of the diagnosis, staging, and treatment of HCC. Furthermore, the authors provide a review of certain ongoing trials and future directions of various treatment modalities for HCC.
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Liver transplantation and portal vein tumour thrombus: futile enterprise? Curr Opin Organ Transplant 2022; 27:312-319. [PMID: 36354257 DOI: 10.1097/mot.0000000000000997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE OF REVIEW To summarize recent evidence in literature regarding liver transplantation in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT) with no extrahepatic disease. In addition, in this review, we have tried to highlight the advances in downstaging with ablative therapies that have made liver transplantation a possibility, and also the key points to focus on when considering liver transplantation in these patients with locally advanced HCC. RECENT FINDINGS Advances in the understanding of technicalities and effectiveness of ablative therapies, including transarterial chemoembolization, stereotactic body radiotherapy and transarterial radioembolization on PVTT have helped successfully downstage patients with HCC and PVTT to within transplant criteria. This provides the opportunity to offer a curative liver transplantation in these patients who are generally managed with systemic or palliative therapy alone with dismal prognosis. Meticulous patient selection based on tumour biology, documented downstaging based on imaging and decrease in tumour marker levels, an adequate waiting period to demonstrate stable disease, liver transplantation with some technical modifications, and a modified immunosuppression protocol may offer long-term survival in a select group of patients treated with initial downstaging therapies in an intention to treat strategy. SUMMARY In patients with HCC, presence of PVTT is generally considered the end of the road by many. A multidisciplinary approach combining ablation and a curative liver transplantation may offer the best hope of long-term survival in a select group of patients with favourable tumour biology. Although promising, current evidence is limited, and future studies with larger number of patients, and longer follow-up may pave the way for an elaborate selection algorithm to choose the ideal candidates for such a curative strategy in patients with locally advanced HCC with PVTT.
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The impact of biological features for a better prediction of posttransplant hepatocellular cancer recurrence. Curr Opin Organ Transplant 2022; 27:305-311. [PMID: 36354256 DOI: 10.1097/mot.0000000000000955] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW Morphological criteria (i.e., Milan Criteria) have been considered for a long time to be the best tool for selecting patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT). In the last ten years, a refinement of the selection criteria has been observed, with the introduction of biological tumor characteristics enabling to enlarge the number of potential transplant candidates and to select LT candidates with a lower risk of posttransplant recurrence. RECENT FINDINGS Several biological tumor aspects have been explored and validated in international cohorts to expand the ability to predict patients at high risk for recurrence. Alpha-fetoprotein, radiological response to locoregional treatments, and other more recently proposed markers have been principally explored. Moreover, more complex statistical approaches (i.e., deep learning) have been advocated to explore the nonlinear intercorrelations between the investigated features. SUMMARY The addition of biological aspects to morphology has improved the ability to discriminate among high- and low-risk patients for recurrence. New prognostic algorithms based on the more sophisticated artificial intelligence approach are further improving the capability to select LT candidates with HCC.
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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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Lai Q, Viveiros A, Iesari S, Vitale A, Mennini G, Onali S, Hoppe-Lotichius M, Colasanti M, Manzia TM, Mocchegiani F, Spoletini G, Agnes S, Vivarelli M, Tisone G, Ettorre GM, Mittler J, Tsochatzis E, Rossi M, Cillo U, Schaefer B, Lerut JP. Prognostic Factors for 10-Year Survival in Patients With Hepatocellular Cancer Receiving Liver Transplantation. Front Oncol 2022; 12:877107. [PMID: 35574299 PMCID: PMC9093683 DOI: 10.3389/fonc.2022.877107] [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: 02/16/2022] [Accepted: 03/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background Long-term survival after liver transplantation (LT) for hepatocellular cancer (HCC) continues to increase along with the modification of inclusion criteria. This study aimed at identifying risk factors for 5- and 10-year overall and HCC-specific death after LT. Methods A total of 1,854 HCC transplant recipients from 10 European centers during the period 1987-2015 were analyzed. The population was divided in three eras, defined by landmark changes in HCC transplantability indications. Multivariable logistic regression analyses were used to evaluate the significance of independent risk factors for survival. Results Five- and 10-year overall survival (OS) rates were 68.1% and 54.4%, respectively. Two-hundred forty-two patients (13.1%) had HCC recurrence. Five- and 10-year recurrence rates were 16.2% and 20.3%. HCC-related deaths peaked at 2 years after LT (51.1% of all HCC-related deaths) and decreased to a high 30.8% in the interval of 6 to 10 years after LT. The risk factors for 10-year OS were macrovascular invasion (OR = 2.71; P = 0.001), poor grading (OR = 1.56; P = 0.001), HCV status (OR = 1.39; P = 0.001), diameter of the target lesion (OR = 1.09; P = 0.001), AFP slope (OR = 1.63; P = 0.006), and patient age (OR = 0.99; P = 0.01). The risk factor for 10-year HCC-related death were AFP slope (OR = 4.95; P < 0.0001), microvascular (OR = 2.13; P < 0.0001) and macrovascular invasion (OR = 2.32; P = 0.01), poor tumor grading (OR = 1.95; P = 0.001), total number of neo-adjuvant therapies (OR = 1.11; P = 0.001), diameter of the target lesion (OR = 1.11; P = 0.002), and patient age (OR = 0.97; P = 0.001). When analyzing survival rates in function of LT era, a progressive improvement of the results was observed, with patients transplanted during the period 2007-2015 showing 5- and 10-year death rates of 26.8% and 38.9% (vs. 1987-1996, P < 0.0001; vs. 1997-2006, P = 0.005). Conclusions LT generates long-term overall and disease-free survival rates superior to all other oncologic treatments of HCC. The role of LT in the modern treatment of HCC becomes even more valued when the follow-up period reaches at least 10 years. The results of LT continue to improve even when prudently widening the inclusion criteria for transplantation. Despite the incidence of HCC recurrence is highest during the first 5 years post-transplant, one-third of them occur later, indicating the importance of a life-long follow-up of these patients.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza, Rome, Italy
| | - Andre Viveiros
- Department of Medicine I, Innsbruck University, Innsbruck, Austria
| | - Samuele Iesari
- Institut de Recherche Expérimental et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, Padua University, Padua, Italy
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, Sapienza, Rome, Italy
| | - Simona Onali
- UCL Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
| | - Maria Hoppe-Lotichius
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz University, Mainz, Germany
| | - Marco Colasanti
- Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy
| | | | - Federico Mocchegiani
- Unit of Hepatobiliary Surgery and Transplantation, Marche Polytechnic University, Ancona, Italy
| | - Gabriele Spoletini
- Catholic University - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Salvatore Agnes
- Catholic University - Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Marco Vivarelli
- Unit of Hepatobiliary Surgery and Transplantation, Marche Polytechnic University, Ancona, Italy
| | - Giuseppe Tisone
- Department of Transplant Surgery, PTV University, Rome, Italy
| | - Giuseppe M. Ettorre
- Division of General Surgery and Liver Transplantation, San Camillo Hospital, Rome, Italy
| | - Jens Mittler
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Mainz University, Mainz, Germany
| | - Emmanuel Tsochatzis
- UCL Institute for Liver and Digestive Health and Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Sapienza, Rome, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, Padua University, Padua, Italy
| | | | - Jan P. Lerut
- Institut de Recherche Expérimental et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium
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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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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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Lozanovski VJ, Ramouz A, Aminizadeh E, Al-Saegh SAH, Khajeh E, Probst H, Picardi S, Rupp C, Chang DH, Probst P, Mehrabi A. Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis. BJS Open 2022; 6:6536147. [PMID: 35211739 PMCID: PMC8874238 DOI: 10.1093/bjsopen/zrab130] [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: 08/16/2021] [Revised: 10/27/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Heike Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Susanne Picardi
- Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Rupp
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany.,Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - De-Hua Chang
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany.,Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany.,Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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Biolato M, Galasso T, Marrone G, Miele L, Grieco A. Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation. Cancers (Basel) 2021; 13:cancers13246337. [PMID: 34944957 PMCID: PMC8699392 DOI: 10.3390/cancers13246337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022] Open
Abstract
Simple Summary Currently, most transplant centres worldwide accept patients with hepatocellular carcinoma who underwent successful downstaging. Concurrently, the effectiveness of radiological and systemic therapies used for the downstaging of hepatocellular carcinoma are increasing. It is now more frequently observed that candidates for liver transplantation have an excellent response to downstaging, even if the baseline stage was well beyond the transplantable tumour. Downstaged patients have a higher risk of dropout from the waiting list and post-transplant recurrence if not transplanted in a short time. Since an increasing number of downstaged patients affects the waitlist dynamics, the definition of upper limits of downstaging is becoming a crucial issue. In this narrative review, we summarise current evidence on the downstaging of hepatocellular carcinoma for liver transplantation, including downstaging of patients with macrovascular invasion or extrahepatic metastasis at presentation and employment of the new systemic treatments for hepatocellular carcinoma. Abstract In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60–70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to “extended” downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
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Affiliation(s)
- Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Tiziano Galasso
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Luca Miele
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
- Correspondence:
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Alim A, Karataş C. Prognostic Factors of Liver Transplantation for HCC: Comparative Literature Review. J Gastrointest Cancer 2021; 52:1223-1231. [PMID: 34882291 DOI: 10.1007/s12029-021-00730-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE The aim of the review study is investigation of the prognostic factors of the liver transplantation for hepatocellular carcinoma. METHODS A literature review has been made, especially in countries where dominantly living donor liver transplantation is performed, such as Turkey. Liver transplantation from deceased donor and from living donor has been evaluated about as advantages and disadvantages, and their effects on prognosis have been compared. In addition, hepatocellular carcinoma series of Koç University Liver Transplantation center has been presented. RESULTS Liver transplantation is still the best treatment option with 5-year 50% survival rate for hepatocellular carcinoma even in patient who has locally advanced tumor. The patient's survival is not only an important issue but also the living donor's safety is controversial particularly when expectation of recipient's 5-year survival is below 50% due to donor complication. CONCLUSION Detailed preoperative examination, appropriate patient selection, and timing of surgery are seen the most important issues in liver transplant's patients with hepatocellular carcinoma.
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Affiliation(s)
- Altan Alim
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey.
| | - Cihan Karataş
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey
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Serenari M, Cappelli A, Cucchetti A, Mosconi C, Strigari L, Monari F, Ravaioli M, Rizzini EL, Fanti S, Golfieri R, Cescon M. Deceased Donor Liver Transplantation After Radioembolization for Hepatocellular Carcinoma and Portal Vein Tumoral Thrombosis: A Pilot Study. Liver Transpl 2021; 27:1758-1766. [PMID: 34355489 PMCID: PMC9290139 DOI: 10.1002/lt.26257] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 07/12/2021] [Accepted: 07/22/2021] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) with portal vein tumoral thrombosis (PVTT) represents a major concern especially in the field of deceased donor liver transplantation (DDLT). However, when receiving transarterial radioembolization (TARE), a considerable percentage of such patients are able to achieve a radiologic complete response with adequate survival rates. In this pilot prospective study, we evaluated the effect of TARE in downstaging HCC patients with PVTT to meet criteria for DDLT. Between May 2013 and November 2016, patients were evaluated to be enrolled into our "Superdownstaging" protocol. Patients received yttrium-90 TARE and were enlisted for DDLT in case of complete and sustained (6 months) radiological response. Patients with tumor thrombus in the main trunk and/or in the contralateral portal vein branch were excluded. TARE was effective in downstaging and receiving DDLT in 5/17 patients (29.4%). The 5-year overall survival was significantly higher in patients who underwent DDLT compared with those who were not transplanted (60.0% versus 0.0%, P = 0.03). Three out of 5 patients developed recurrence within 1 year after LT. The current series showed a clear survival gain in those patients who were able to receive DDLT after TARE but careful selection for DDLT is however advised.
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Affiliation(s)
- Matteo Serenari
- General Surgery and Transplant UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant'Orsola‐Malpighi HospitalBolognaItaly
| | - Alberta Cappelli
- Department of RadiologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
| | - Alessandro Cucchetti
- Department of Medical and Surgical SciencesAlma Mater StudiorumUniversity of BolognaBolognaItaly
| | - Cristina Mosconi
- General Surgery and Transplant UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant'Orsola‐Malpighi HospitalBolognaItaly
| | - Lidia Strigari
- Department of Medical PhysicsIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
| | - Fabio Monari
- Division of Radiation OncologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
| | - Matteo Ravaioli
- General Surgery and Transplant UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant'Orsola‐Malpighi HospitalBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater StudiorumUniversity of BolognaBolognaItaly
| | - Elisa Lodi Rizzini
- Division of Radiation OncologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
| | - Stefano Fanti
- Nuclear Medicine UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
- Department of Experimental, Diagnostic and Specialty MedicineAlma Mater StudiorumUniversity of BolognaBolognaItaly
| | - Rita Golfieri
- Department of RadiologyIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant’Orsola‐Malpighi HospitalBolognaItaly
| | - Matteo Cescon
- General Surgery and Transplant UnitIRCCS Azienda Ospedaliero‐Universitaria di BolognaSant'Orsola‐Malpighi HospitalBolognaItaly
- Department of Medical and Surgical SciencesAlma Mater StudiorumUniversity of BolognaBolognaItaly
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36
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Mehta N, Yao FY. Liver Transplantation After Downstaging of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus Using Yttrium-90 Radioembolization: Pipe Dream or Reality? Liver Transpl 2021; 27:1706-1708. [PMID: 34529890 DOI: 10.1002/lt.26302] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 09/09/2021] [Indexed: 01/13/2023]
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California San Francisco, San Francisco, CA
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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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Luo F, Li M, Ding J, Zheng S. The Progress in the Treatment of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus. Front Oncol 2021; 11:635731. [PMID: 34631513 PMCID: PMC8496502 DOI: 10.3389/fonc.2021.635731] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 09/08/2021] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of most prevalent cancer and is a serious healthcare issue worldwide. Portal vein tumor thrombus (PVTT) is a frequent complication and remains as the blockage in the treatment of HCC with high recurrence rate and poor prognosis. There is still no global consensus or standard guideline on the management of HCC with PVTT. In western countries, Sorafenib and Lenvatinib are recommended as the first-line treatment options for HCC patients with PVTT where this condition is now regarded as BCLC Stage C regardless of PVTT types. However, there is growing evidence that supports the close relationship of the extent of PVTT to the prognosis of HCC. Besides the targeted therapy, more aggressive treatment modalities have been proposed and practiced in the clinic which may improve the prognosis of HCC patients with PVTT and prolong the patients’ survival time, such as transarterial chemoembolization, radiotherapy, hepatic resection, liver transplantation, and various combination therapies. Herein, we aim to review and summarize the advances in the treatment of HCC with PVTT.
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Affiliation(s)
- Fangzhou Luo
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.,Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Mengxia Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.,Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Jun Ding
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,School of Medicine, Zhejiang University, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.,Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, China.,Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences, Hangzhou, China.,Key Laboratory of Organ Transplantation, Research Center for Diagnosis and Treatment of Hepatobiliary Diseases, Hangzhou, China
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Glantzounis GK, Karampa A, Peristeri DV, Pappas-Gogos G, Tepelenis K, Tzimas P, Cyrochristos DJ. Recent advances in the surgical management of hepatocellular carcinoma. Ann Gastroenterol 2021; 34:453-465. [PMID: 34276183 PMCID: PMC8276352 DOI: 10.20524/aog.2021.0632] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/19/2021] [Indexed: 02/07/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, despite effective antiviral treatment for hepatitis B (HBV) and C virus infection and the application of preventive measures such as vaccination at birth against HBV infection. This is mainly due to the increase in metabolic syndrome and its hepatic components, nonalcoholic fatty liver disease and steatohepatitis. Liver resection and transplantation are the main treatment options, offering long-term survival and potential cure. In this review, the recent advances in the surgical management of HCC are presented. More specifically, the role of liver resection in the intermediate and advanced stages, according to the Barcelona Clinic Liver Cancer classification, is analyzed. In addition, the roles of minimally invasive surgery and of living-related liver transplantation in the management of patients with HCC are discussed. Finally, recent data on the role of molecular markers in the early diagnosis and recurrence of HCC are presented. The management of HCC is complex, as there are several options for each stage of the disease. In order for, each patient to get the maximum benefit, an individualized approach is suggested, in specialized liver units, where cases are discussed in multidisciplinary tumor boards.
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Affiliation(s)
- Georgios K. Glantzounis
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Anastasia Karampa
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Dimitra V. Peristeri
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - George Pappas-Gogos
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Kostas Tepelenis
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
| | - Petros Tzimas
- Department of Anesthesiology (Petros Tzimas), University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios J. Cyrochristos
- HPB Unit, Department of Surgery (Georgios K. Glantzounis, Anastasia Karampa, Dimitra V. Peristeri, George Pappas-Gogos, Kostas Tepelenis, Dimitrios J. Cyrochristos)
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Bhatti ABH, Naqvi W, Khan NY, Zia HH, Dar FS, Khan ZA, Rana A. Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion. J Cancer Res Clin Oncol 2021; 148:245-253. [PMID: 34117916 PMCID: PMC8752562 DOI: 10.1007/s00432-021-03665-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/13/2021] [Indexed: 02/05/2023]
Abstract
Background The indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI). Methods We reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27). Results The median follow was 28 (10.6–42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003). Conclusion With inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria. Supplementary Information The online version contains supplementary material available at 10.1007/s00432-021-03665-9.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan. .,Department of Surgery, Shifa Tameer-e-Millat University Islamabad, Islamabad, Pakistan.
| | - Wajih Naqvi
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Nusrat Yar Khan
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Faisal Saud Dar
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Zahid Amin Khan
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Atif Rana
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
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Qin JM. Conversion therapy for primary liver cancer: Indications and selective strategies. Shijie Huaren Xiaohua Zazhi 2021; 29:501-510. [DOI: 10.11569/wcjd.v29.i10.501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer has an insidious onset and no specific symptoms at early stage. Most patients are in the middle or advanced stage when diagnosed, and only 20%-40% of patients meet the criteria for radical resection. At present, surgical resection is still the main radical treatment for primary liver cancer, but factors such as liver function decompensation, too large tumor volume, too small future liver remnant, intrahepatic multiple metastasis, tumor thrombus invading the large vessels or bile duct, and distant metastasis limit the application of surgical resection or liver transplantation. In recent years, with the advances of basic research of primary liver cancer, the development of surgical techniques and equipment, as well as the development of new molecular targeted drugs and immunotherapy drugs, a part of unresectable patients with primary liver cancer can receive conversion therapy to improve liver function, minimize tumor volume, minimize or inactivate tumor thrombus, and increase the residual liver volume. Following conversion therapy, patients with primary liver cancer can undergo surgical resection or liver transplantation, which greatly improve the therapeutic efficacy and patient survival.
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Affiliation(s)
- Jian-Min Qin
- Department of General Surgery, the Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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42
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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43
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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: 9] [Impact Index Per Article: 2.3] [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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44
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Vernuccio F, Porrello G, Cannella R, Vernuccio L, Midiri M, Giannitrapani L, Soresi M, Brancatelli G. Benign and malignant mimickers of infiltrative hepatocellular carcinoma: tips and tricks for differential diagnosis on CT and MRI. Clin Imaging 2020; 70:33-45. [PMID: 33120287 DOI: 10.1016/j.clinimag.2020.10.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 09/23/2020] [Accepted: 10/07/2020] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) may have an infiltrative appearance in about 8-20% of cases. Infiltrative HCC can be a challenging diagnosis and it is associated with the worst overall survival among HCC patients. Infiltrative HCC is characterized by the spread of multiple minute nodules throughout the liver, without a dominant one, ultimately resulting into macrovascular invasion. On CT and MRI, infiltrative HCC appears as an ill-defined, large mass, with variable degree of enhancement, and satellite neoplastic nodules in up to 52% of patients. On MRI, it may show restriction on diffusion weighted imaging, hyperintensity on T2- and hypointensity on T1-weighted images, and, if hepatobiliary agent is used, hypointensity on hepatobiliary phase. Infiltrative HCC must be differentiated from other liver diseases, such as focal confluent fibrosis, steatosis, amyloidosis, vascular disorders of the liver, cholangiocarcinoma, and diffuse metastatic disease. In cirrhotic patients, the identification of vascular tumor invasion of the portal vein and its differentiation from bland thrombosis is of utmost importance for patient management. On contrast enhanced CT and MRI, portal vein tumor thrombosis appears as an enhancing thrombus within the portal vein, close to the main tumor and results into vein enlargement. The aim of this pictorial review is to show CT and MRI features that allow the diagnosis of infiltrative HCC and portal vein tumor thrombosis. A particular point of interest includes the tips and tricks for differential diagnosis with potential mimickers of infiltrative HCC.
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Affiliation(s)
- Federica Vernuccio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy; University Paris Diderot, Sorbonne Paris Cité, Paris, France; I.R.C.C.S. Centro Neurolesi Bonino Pulejo, Contrada Casazza, SS113, 98124 Messina, Italy; Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University Hospital of Palermo, Via del Vespro 129, 90127 Palermo, Italy.
| | - Giorgia Porrello
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University Hospital of Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Roberto Cannella
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy; Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University Hospital of Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Laura Vernuccio
- U.O.C. Geriatria e Lungodegenza, AOUP University Hospital Palermo, CDCD Geriatria, Palermo, Italy
| | - Massimo Midiri
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University Hospital of Palermo, Via del Vespro 129, 90127 Palermo, Italy
| | - Lydia Giannitrapani
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maurizio Soresi
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Giuseppe Brancatelli
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (BIND), University Hospital of Palermo, Via del Vespro 129, 90127 Palermo, Italy
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45
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Levi Sandri GB, Berardi G, Giannelli V, Ettorre GM. Primary role of radioembolization as a downstaging strategy in patients with macrovascular invasion prior to liver transplantation. Transpl Int 2020; 33:1833-1834. [PMID: 32935365 DOI: 10.1111/tri.13746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
| | - Giammauro Berardi
- Division of General Surgery and Liver Transplantation, S. Camillo Hospital, Rome, Italy.,Liver and Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy
| | - Valerio Giannelli
- Liver and Transplant Unit, San Camillo Forlanini Hospital, Rome, Italy
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46
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Moeckli B, Ivanics T, Claasen M, Toso C, Sapisochin G. Recent developments and ongoing trials in transplant oncology. Liver Int 2020; 40:2326-2344. [PMID: 33021344 DOI: 10.1111/liv.14621] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Revised: 07/17/2020] [Accepted: 07/21/2020] [Indexed: 12/17/2022]
Abstract
Over the past two decades since the introduction of the Milan criteria, the field of transplant oncology has undergone a rapid development with a rising proportion of liver transplantations being performed for oncological indications. For many patients with liver tumours, transplantation represents the only chance for cure. However, many challenges remain, such as the adequate patient selection, management of post-transplant recurrence and refinement of neoadjuvant treatment protocols. This review provides an overview of the current state of the art of liver transplantation for oncological indications such as hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastasis and metastatic neuroendocrine tumours. We also summarize the ongoing research and explore future trends. Clinical trials are currently studying new diagnostic modalities, innovative pharmacological treatments, novel surgical techniques, downstaging regimens and new indications for liver transplantation. These emerging results will continue to shape the field of transplant oncology and provide us with the necessary tools to better select, treat and follow patients with liver tumours qualifying for liver transplantation.
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Affiliation(s)
- Beat Moeckli
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Tommy Ivanics
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Marco Claasen
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Christian Toso
- Department of Visceral and Transplantation Surgery, University of Geneva Hospitals, Geneva, Switzerland
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.,Division of General Surgery, University Health Network, Toronto, ON, Canada
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47
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Finotti M, Vitale A, Volk M, Cillo U. A 2020 update on liver transplant for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:885-900. [PMID: 32662680 DOI: 10.1080/17474124.2020.1791704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma is the most frequent liver tumor and is associated with chronic liver disease in 90% of cases. In selected cases, liver transplantation represents an effective therapy with excellent overall survival. AREA COVERED Since the introduction of Milan criteria in 1996, numerous alternative selection systems to LT for HCC patients have been proposed. Debate remains about how best to select HCC patients for transplant and how to prioritize them on the waiting list. EXPERT OPINION The selection of the best scoring system to propose in the context of LT for HCC is far to be identified. In this review, we analyze and categorize the various selection systems, assessing their roles in the different decisional phases.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health , Loma Linda, California, USA
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
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48
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Masior Ł, Grąt M. Exploring new pathways in the treatment of hepatocellular cancer. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:980. [PMID: 32953780 PMCID: PMC7475451 DOI: 10.21037/atm-20-3629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Affiliation(s)
- Łukasz Masior
- Department of General, Vascular and Oncological Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
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49
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Halazun KJ, Sapisochin G, von Ahrens D, Agopian VG, Tabrizian P. Predictors of outcome after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria. Int J Surg 2020; 82S:61-69. [PMID: 32707331 DOI: 10.1016/j.ijsu.2020.07.029] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 07/07/2020] [Accepted: 07/08/2020] [Indexed: 12/16/2022]
Abstract
The Milan criteria have been the cornerstone of selection policies for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT) globally for over two decades. Many groups have proposed the transplantation of patients with larger and more numerous tumors achieving comparable results. Many of these use radiologic morphometric criteria as surrogates for explant pathology to predict outcomes. Several other indices have been developed both within and beyond Milan incorporating biological indices as well as dynamic markers of response to pre-transplant locoregional treatments and waiting time. These have allowed for successful expansion of transplant selection criteria without compromising outcomes with limited organ supplies. In this review we will discuss the predictors of outcome in patients beyond Milan criteria.
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Affiliation(s)
- K J Halazun
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medicine, 525 East 68th, F-763, New York, NY, 10065, USA; Center for Liver Disease and Transplantation, Columbia University Medical Center, NY Presbyterian Hospital, 622 West 168th St, PH14-101, New York, NY, 10032, USA.
| | - G Sapisochin
- Center for Liver Disease and Transplantation, Columbia University Medical Center, NY Presbyterian Hospital, 622 West 168th St, PH14-101, New York, NY, 10032, USA; Multi-Organ Transplant, Division of General Surgery, Toronto General Hospital, University of Toronto, 585 University Avenue Toronto, ON, M5G 2N2, Canada.
| | - D von Ahrens
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medicine, 525 East 68th, F-763, New York, NY, 10065, USA.
| | - V G Agopian
- Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Los Angeles, CA, 90095, USA.
| | - P Tabrizian
- Department of Transplantation, Recanati/Miller Transplantation Institute, 5 East 98th St. Mount Sinai Medical Center, New York, 10029, USA.
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50
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Yang Z, Luo FZ, Wang S, Lerut J, Zhuang L, Li QY, Xu X, Zheng SS. Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis: Preliminary experience. Hepatobiliary Pancreat Dis Int 2020; 19:229-234. [PMID: 32303439 DOI: 10.1016/j.hbpd.2020.03.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 03/23/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND Portal vein tumor thrombosis (PVTT) is regarded as a contraindication for liver transplantation (LT) in hepatocellular carcinoma (HCC). However, some of these patients may have a favorable prognosis after LT. In this study, we evaluated the biological behavior of HCC with PVTT using tumor biomarker (alpha-fetoprotein, AFP) and 18F-FDG positron emission tomography (tumor standard uptake value) to identify a subset of patients who may be suitable for LT. METHODS Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed. Different pre-transplant prognostic factors were identified by univariate and multivariate analyses. PVTT status was identified following Vp classification (Vp1-Vp4). RESULTS Three-year recurrence-free survival and overall survival rates were 40% and 65.4% in Vp2-Vp3 PVTT patients, 21.4% and 30.6% in Vp4 PVTT patients (P < 0.05). Total tumor diameter >8 cm, pre-transplant AFP level >1000 ng/mL and intrahepatic tumor maximal standard uptake value (SUVmax-tumor >5) were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients. Low risk patients were defined as total tumor diameter ≤8 cm; or if total tumor diameter more than 8 cm, with both pre-transplant AFP level less than 1000 ng/mL and intrahepatic tumor SUVmax less than 5, simultaneously. Twenty-two Vp2-3 PVTT HCC patients (46.8%) were identified as low risk patients, and their 3-year recurrence-free and overall survival rates were 67.6% and 95.2%, respectively. CONCLUSIONS Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18F-FDG SUVmax might be suitable for LT.
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Affiliation(s)
- Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China; Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China
| | - Fang-Zhou Luo
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuo Wang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Jan Lerut
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium
| | - Li Zhuang
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Qi-Yong Li
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China
| | - Xiao Xu
- Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou, China; Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; National Clinical Research Center of Infectious Diseases, Hangzhou, China.
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