|
1
|
Bitzer M, Groß S, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e159-e260. [PMID: 40064172 DOI: 10.1055/a-2460-6298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2025]
Affiliation(s)
- Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
2
|
Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| |
Collapse
|
|
3
|
Xu E, Tabrizian P, Gutierrez J, Hoteit M, Ghaziani T, Zhou K, Parikh N, Ajmera V, Aby E, Shui A, Marino R, Martin A, Wong C, Kao K, Dave S, Florman S, Yao F, Mehta N. Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multicenter prospective cohort study. Hepatology 2025:01515467-990000000-01140. [PMID: 39808828 DOI: 10.1097/hep.0000000000001231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 12/07/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND AND AIMS Patients with HCC meeting United Network for Organ Sharing (UNOS)-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-Comers" [AC]) have been limited by small sample size and short follow-up time, prompting this analysis. APPROACH AND RESULTS Three hundred twenty-six patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed. Competing risk analysis and Kaplan-Meier method were used to evaluate DS and LT outcomes, and Fine-and-Gray and Cox models were used to identify predictors of outcomes. AC and UNOS-DS had similar median alpha-fetoprotein (15 vs. 12 ng/mL; p =0.08), MELD (9 vs. 9; p =0.52), and Child-Pugh (A vs. A; p =0.30). Two years after the first local regional therapy, 82% of UNOS-DS and 66% of AC were successfully downstaged ( p <0.001). In AC, DS rates were 72% for tumor number plus diameter of largest lesion <10, 51% for sum 10-12, and 39% for sum >12 ( p =0.01). Yttrium-90 achieved higher DS success than transarterial chemoembolization in AC (74% vs. 65%; p <0.001). 48% of UNOS-DS and 40% of AC underwent LT ( p =0.10). Five-year post-LT survival was similar between UNOS-DS and AC (74% vs. 72%; p =0.77), although 5-year post-LT recurrence was higher in AC (30% vs. 14%; p =0.02). CONCLUSIONS Despite higher HCC recurrence and lower intention-to-treat survival in AC, post-LT survival was comparable between UNOS-DS and AC. Yttrium-90 attained higher DS success than transarterial chemoembolization in AC. LT after DS is feasible in AC, though defining an upper limit in tumor burden may be necessary.
Collapse
Affiliation(s)
- Edison Xu
- Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Julio Gutierrez
- Center of Organ and Cell Transplantation, Department of Surgery, Scripps Green Hospital, La Jolla, California, USA
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Tara Ghaziani
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University, Palo Alto, California, USA
| | - Kali Zhou
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Veeral Ajmera
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Elizabeth Aby
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA
| | - Amy Shui
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Rebecca Marino
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Allison Martin
- Center of Organ and Cell Transplantation, Department of Surgery, Scripps Green Hospital, La Jolla, California, USA
| | - Christopher Wong
- Division of Gastrointestinal and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, California, USA
| | - Karissa Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Shravan Dave
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Diego, San Diego, California, USA
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Francis Yao
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Neil Mehta
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| |
Collapse
|
|
4
|
Chen JJ, Jin ZC, Zhong BY, Fan W, Zhang WH, Luo B, Wang YQ, Teng GJ, Zhu HD. Locoregional therapies for hepatocellular carcinoma: The current status and future perspectives. United European Gastroenterol J 2024; 12:226-239. [PMID: 38372444 PMCID: PMC10954431 DOI: 10.1002/ueg2.12554] [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: 06/29/2023] [Accepted: 01/07/2024] [Indexed: 02/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related mortality. Locoregional therapies (LRTs) play a crucial role in HCC management and are selectively adopted in real-world practice across various stages. Choosing the best form of LRTs depends on technical aspects, patient clinical status and tumour characteristics. Previous studies have consistently highlighted the efficacy of combining LRTs with molecular targeted agents in HCC treatment. Recent studies propose that integrating LRTs with immune checkpoint inhibitors and molecular targeted agents could provide substantial therapeutic benefits, a notion underpinned by both basic and clinical evidence. This review summarised the current landscape of LRTs in HCC and discussed the anticipated outcomes of combinations with immunotherapy regimens.
Collapse
Affiliation(s)
- Jian-Jian Chen
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Zhi-Cheng Jin
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
| | - Wenzhe Fan
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei-Hua Zhang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Biao Luo
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Yu-Qing Wang
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Gao-Jun Teng
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Hai-Dong Zhu
- Department of Radiology, Center of Interventional Radiology & Vascular Surgery, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| |
Collapse
|
|
5
|
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. [Not Available]. 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
| |
Collapse
|
|
6
|
Natarajan B, Tabrizian P, Hoteit M, Frenette C, Parikh N, Ghaziani T, Dhanasekaran R, Guy J, Shui A, Florman S, Yao FY, Mehta N. Downstaging hepatocellular carcinoma before liver transplantation: A multicenter analysis of the "all-comers" protocol in the Multicenter Evaluation of Reduction in Tumor Size before Liver Transplantation (MERITS-LT) consortium. Am J Transplant 2023; 23:1771-1780. [PMID: 37532179 PMCID: PMC10998692 DOI: 10.1016/j.ajt.2023.07.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 06/27/2023] [Accepted: 07/27/2023] [Indexed: 08/04/2023]
Abstract
Patients with hepatocellular carcinoma meeting united network for organ sharing (UNOS)-downstaging (DS) criteria have excellent liver transplantation (LT) outcomes after DS. However, outcomes for "all-comers" (AC) patients with tumors initially exceeding UNOS-DS are poorly understood. Patients meeting AC (n = 82) or UNOS-DS (n = 229) at 7 LT centers in 4 UNOS regions were prospectively followed from 2015-2020. AC patients had a lower probability of successful DS (67% vs 83% within 12 months; P < .001). The 3-year survival was 69% for UNOS-DS vs 58% for AC (P = .05) and reduced to 30% in patients with Child-Pugh B/C cirrhosis or alpha-fetoprotein (AFP) ≥ 500. Five-year LT probability was 42% for AC vs 74% in UNOS-DS (P = .10). Thirty-eight percent were understaged on explant, with the increasing sum of the largest tumor diameter plus the number of lesions before LT (odds ratio 1.3; P = .01) and AFP ≥ 20 (odds ratio 5.9; P = .005) associated with understaging. Post-LT 3-year survival was 91% for AC vs 81% for UNOS-DS (P = .67). In this first prospective multiregional study of AC patients from the multicenter evaluation of reduction in tumor size before liver transplantation (MERITS-LT) consortium, we observed a 65% probability of successful DS. Three-year survival in AC was nearly 60%, though AC with Child-Pugh B/C or AFP ≥ 500 had poor survival. Explant pathology and 3-year post-LT outcomes were similar between cohorts, suggesting that LT is a reasonable goal in selected AC patients.
Collapse
Affiliation(s)
- Brahma Natarajan
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Parissa Tabrizian
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Maarouf Hoteit
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Catherine Frenette
- Center for Organ and Cell Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Neehar Parikh
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Tara Ghaziani
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA
| | - Renu Dhanasekaran
- Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA
| | - Jennifer Guy
- Department of Transplantation, California Pacific Medical Center, San Francisco, California, USA
| | - Amy Shui
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Sander Florman
- Department of Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA.
| |
Collapse
|
|
7
|
Wu X, Lokken RP, Mehta N. Optimal treatment for small HCC (<3 cm): Resection, liver transplantation, or locoregional therapy? JHEP Rep 2023; 5:100781. [PMID: 37456674 PMCID: PMC10339255 DOI: 10.1016/j.jhepr.2023.100781] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/30/2023] [Indexed: 07/18/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains the most common form of liver cancer, accounting for 90% of all primary liver cancers. Up to 30% of HCC cases could be small (2-3 cm in diameter) at the time of diagnosis with advances in imaging techniques and surveillance programmes. Treating patients with early-stage HCC can be complex and often requires interdisciplinary care, owing to the wide and increasing variety of treatment options, which include liver resection, liver transplantation, and various locoregional therapies offered by interventional radiology and radiation oncology. Decisions regarding the optimal management strategy for a patient involve many considerations, including patient- and tumour-specific characteristics, as well as socioeconomic factors. In this review, we aim to comprehensively summarise the commonly used therapies for single, small HCC (<3 cm), with a focus on the impact of tumour size (<2 cm vs. 2-3 cm), as well as a brief discussion on the cost-effectiveness of the different treatment options.
Collapse
Affiliation(s)
- Xiao Wu
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Ryan Peter Lokken
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Neil Mehta
- Department of General Hepatology and Liver Transplantation, University of California, San Francisco, CA, USA
| |
Collapse
|
|
8
|
Cesario S, Genovesi V, Salani F, Vasile E, Fornaro L, Vivaldi C, Masi G. Evolving Landscape in Liver Transplantation for Hepatocellular Carcinoma: From Stage Migration to Immunotherapy Revolution. Life (Basel) 2023; 13:1562. [PMID: 37511937 PMCID: PMC10382048 DOI: 10.3390/life13071562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/30/2023] [Accepted: 07/10/2023] [Indexed: 07/30/2023] Open
Abstract
Liver transplantation (LT) represents the primary curative option for HCC. Despite the extension of transplantation criteria and conversion with down-staging loco-regional treatments, transplantation is not always possible. The introduction of new standards of care in advanced HCC including a combination of immune checkpoint inhibitor-based therapies led to an improvement in response rates and could represent a promising strategy for down-staging the tumor burden. In this review, we identify reports and series, comprising a total of 43 patients who received immune checkpoint inhibitors as bridging or down-staging therapies prior to LT. Overall, treated patients registered an objective response rate of 21%, and 14 patients were reduced within the Milan criteria. Graft rejection was reported in seven patients, resulting in the death of four patients; in the remaining cases, LT was performed safely after immunotherapy. Further investigations are required to define the duration of immune checkpoint inhibitors, their minimum washout period and the LT long-term safety of this strategy. Some randomized clinical trials including immunotherapy combinations, loco-regional treatment and/or tyrosine kinase inhibitors are ongoing and will likely determine the appropriateness of immune checkpoint inhibitors' administration before LT.
Collapse
Affiliation(s)
- Silvia Cesario
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Virginia Genovesi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Francesca Salani
- Institute of Interdisciplinary Research "Health Science", Scuola Superiore Sant'Anna, Piazza Martiri della Libertà 33, 56124 Pisa, Italy
| | - Enrico Vasile
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Lorenzo Fornaro
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
| | - Caterina Vivaldi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| | - Gianluca Masi
- Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, 56126 Pisa, Italy
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy
| |
Collapse
|
|
9
|
Bauschke A, Altendorf-Hofmann A, Brückner L, Drescher R, Freesmeyer M, Settmacher U. Impact of metabolic indices of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on post transplantation recurrence of hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:1401-1410. [PMID: 35451699 PMCID: PMC10020288 DOI: 10.1007/s00432-022-04009-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 04/02/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors. METHODS This retrospective study analyzes 103 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates. RESULTS Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, "up-to-seven" out tumors, grade 3 tumors, α- fetoprotein level >400 ng/ml and lesions > 5cm in diameter. Factors with statistically significant influence on the 10- year overall survival in the univariate analysis were Milan, up-to-seven" criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, "up-to-seven" criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significant. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates. CONCLUSIONS Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma. If we focus on preoperative findings, such as tumor size, tumor number and AFP value adding the information given by TLR of 18F-FDG PET/CT allows to estimate the risk of tumor recurrence more accurate than the established classifications Milan and UTS. Therefore, it may add valuable information to other preoperative findings, such as tumor size, tumor number and AFP level.
Collapse
Affiliation(s)
- Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany.
| | - Annelore Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Lukas Brückner
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Robert Drescher
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Martin Freesmeyer
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| |
Collapse
|
|
10
|
Minoux K, Lassailly G, Ningarhari M, Lubret H, El Amrani M, Canva V, Truant S, Mathurin P, Louvet A, Lebuffe G, Goria O, Nguyen-Khac E, Boleslawski E, Dharancy S. Neo-Adjuvant Use of Sorafenib for Hepatocellular Carcinoma Awaiting Liver Transplantation. Transpl Int 2022; 35:10569. [PMID: 36438781 PMCID: PMC9681796 DOI: 10.3389/ti.2022.10569] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 10/21/2022] [Indexed: 12/01/2023]
Abstract
Data on efficacy and safety of sorafenib in a neoadjuvant setting for HCC awaiting liver transplantation (LT) are heterogeneous and scarce. We aimed to investigate the trajectory of patients treated with sorafenib while awaiting LT. All patients listed for HCC and treated with sorafenib were included in a monocentric observational study. A clinical and biological evaluation was performed every month. Radiological tumor response evaluation was realized every 3 months on the waiting list and every 6 months after LT. Among 327 patients listed for HCC, 62 (19%) were treated with Sorafenib. Sorafenib was initiated for HCC progression after loco-regional therapy (LRT) in 50% of cases and for impossibility of LRT in 50% of cases. The mean duration of treatment was 6 months. Thirty six patients (58%) dropped-out for tumor progression and 26 (42%) patients were transplanted. The 5-year overall and recurrent-free survival after LT was 77% and 48% respectively. Patients treated for impossibility of LRT had acceptable 5-year intention-to-treat overall and post-LT survivals. Conversely, patients treated for HCC progression presented high dropout rate and low intention-to-treat survival. Our results suggest that it is very questionable in terms of utility that patients treated for HCC progression should even be kept listed once the tumor progression has been observed.
Collapse
Affiliation(s)
- Kate Minoux
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Guillaume Lassailly
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Massih Ningarhari
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Henri Lubret
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Medhi El Amrani
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Valérie Canva
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Stéphanie Truant
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Philippe Mathurin
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Alexandre Louvet
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| | - Gilles Lebuffe
- CHU Lille, Department of Anesthesiology, Resuscitation, and Critical Care Anesthesiology, University of Lille, Lille, France
| | - Odile Goria
- CHU Rouen, Department of Hepatogastroenterology, Hôpital Charles Nicolle, Rouen, France
| | - Eric Nguyen-Khac
- CHU Amiens-Picardie, Hôpital Sud, Department of Hepatogastroenterology, Amiens, France
- CHU Amiens, Centre Universitaire de Recherche en Santé (CURS), Université de Picardie-Jules-Verne (UPJV), Groupe de Recherche sur l’alcool et les Pharmacodépendances (GRAP), Inserm U1247, Amiens, France
| | - Emmanuel Boleslawski
- CHU Lille, Department of Digestive Surgery and Transplantation, University of Lille, Lille, France
| | - Sebastien Dharancy
- CHU Lille, Department of Hepatogastroenterology, Lille, France
- INSERM U995, University of Lille, Lille, France
| |
Collapse
|
|
11
|
Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
Collapse
Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| |
Collapse
|
|
12
|
Manjunatha N, Ganduri V, Rajasekaran K, Duraiyarasan S, Adefuye M. Transarterial Chemoembolization and Unresectable Hepatocellular Carcinoma: A Narrative Review. Cureus 2022; 14:e28439. [PMID: 36176866 PMCID: PMC9509692 DOI: 10.7759/cureus.28439] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor, and even with the breakthrough in preventive strategies, and new diagnostic and treatment modalities, incidence and fatality rates continue to climb. Patients with HCC are most commonly diagnosed in the later stage, where the disease has already advanced, making it impossible to undertake potentially curative surgery. Transarterial chemoembolization (TACE) is a locoregional therapy regarded as a first-line treatment in patients with intermediate-stage HCC (Barcelona clinical liver cancer {BCLC}-B). TACE is a minimally invasive and non-surgical procedure that combines local chemotherapeutic drug administration with embolization to treat HCC. It helps limit tumor growth, preserve liver function, and increase overall and progression-free survival in patients with intermediate-stage HCC. This article has reviewed the efficacy, survival, limitations, and overall benefit of TACE in patients with unresectable HCC. This article has also discussed the effectiveness of TACE for neoadjuvant chemoembolization and the use of TACE with combination therapies.
Collapse
Affiliation(s)
- Nisha Manjunatha
- Research, Our Lady of Fatima University College of Medicine, Metro Manila, PHL
| | | | | | | | - Mayowa Adefuye
- Research, University of Ibadan College of Medicine, Ibadan, NGA
| |
Collapse
|
|
13
|
Radiofrequency ablation versus trans-arterial chemoembolization in patients with HCC awaiting liver transplant: an analysis of the Scientific Registry of Transplant Recipients. J Vasc Interv Radiol 2022; 33:1222-1229.e1. [PMID: 35777619 DOI: 10.1016/j.jvir.2022.06.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 04/21/2022] [Accepted: 06/21/2022] [Indexed: 11/22/2022] Open
Abstract
PURPOSE To evaluate differences in waitlist mortality/dropout for liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency ablation (RFA) versus trans-arterial chemoembolization (TACE). MATERIAL AND METHODS From 2004-2013, 11,824 patients in the Scientific Registry of Transplant Recipients (SRTR) with HCC who underwent RFA or TACE. Patients were followed until December 31, 2019 or 5 years, whichever came first and stratified by Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality/dropout were performed with adjusted hazard ratios (asHR, reference group RFA). Regression models were adjusted for age, race, sex, calculated Model for End Stage Liver Disease (cMELD) score, tumor size, and number. RESULTS There was no difference in waitlist mortality/dropout for patients outside Milan criteria (N = 1,226) between TACE (19.2%) compared to RFA (19.0%) (asHR 0.91; 95% CI 0.79-1.03). There was also no difference for patients inside Milan criteria (N = 10,598) in waitlist mortality/dropout (TACE 13.4% vs. RFA 12.9%) (asHR 1.29; 95% CI 0.79-2.09). Subgroup analysis within Milan criteria demonstrated no evidence of difference in TACE compared to RFA in patients with single tumor ≤3 cm (asHR 0.92; 95% CI 0.77-1.10), single tumor > 3 cm (asHR 1.03; 95% CI 0.79-1.34), or with > 1 tumor (asHR 0.89; 95% CI 0.72-1.09). CONCLUSION Using national registry data, no difference was found in waitlist mortality/dropout for transplant candidates with HCC who received TACE vs. RFA.
Collapse
|
|
14
|
Couillard AB, Knott EA, Zlevor AM, Mezrich JD, Cristescu MM, Agarwal P, Ziemlewicz TJ, Longhurst C, Lubner MG, Hinshaw JL, Said A, Laeseke PF, Lucey MR, Rice JP, Foley D, Al-Adra D, Lee FT. Microwave ablation as bridging to liver transplant for patients with hepatocellular carcinoma: a single-center retrospective analysis. J Vasc Interv Radiol 2022; 33:1045-1053. [PMID: 35667580 DOI: 10.1016/j.jvir.2022.05.019] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 05/03/2022] [Accepted: 05/27/2022] [Indexed: 11/28/2022] Open
Abstract
PURPOSE To evaluate the efficacy and safety of microwave (MW) ablation as first-line locoregional therapy (LRT) for bridging patients with hepatocellular carcinoma (HCC) to liver transplant. MATERIALS AND METHODS This retrospective study evaluated 88 patients who received percutaneous MW ablation for 141 tumors as first-line LRT for HCC and listed for liver transplantation at a single medical center between 2011 and 2019. Overall survival rate status-post liver transplant, waitlist retention and disease progression were evaluated using Kaplan-Meier techniques. RESULTS Of 88 patients (72M, 16F, mean age 60 years, MELD=11.2) listed for transplant, median waitlist time was 9.4 months (IQR: 5.5 - 18.9). Seventy-one patients (80.7%) received transplant after median wait time of 8.5 months. Seventeen patients (19.3%) were removed from the waitlist, four (4.5%) due to tumors outside of the Milan criteria (HCC-specific dropout). No difference in tumor size or AFP was seen in transplanted vs. non-transplanted patients at time of ablation (2.1 vs. 2.1 cm and 34.4 vs. 34.7 ng/mL for transplanted vs. non-transplanted, respectively, p>0.05). Five of 88 patients (5.1%) experienced adverse events after ablation; however, all recovered. There were no cases of tract seeding. The local tumor progression (LTP) rate was 7.2%. The overall survival status-post liver transplant at 5-years was 76.7% and the disease-specific survival after LT was 89.6% with a median follow-up of 61 months for all patients. CONCLUSION MW ablation appears to be safe and effective for bridging patients with HCC to liver transplant without waitlist removal from seeding, adverse events, or local tumor progression.
Collapse
Affiliation(s)
| | - Emily A Knott
- University of Wisconsin-Madison: Department of Radiology
| | - Annie M Zlevor
- University of Wisconsin-Madison: Department of Radiology
| | | | | | | | | | - Colin Longhurst
- Department of Carbone Cancer Center; Department of Biostatistics and Medical Informatics
| | | | - J Louis Hinshaw
- University of Wisconsin-Madison: Department of Radiology; Department of Urology
| | | | - Paul F Laeseke
- University of Wisconsin-Madison: Department of Radiology
| | | | | | | | | | - Fred T Lee
- University of Wisconsin-Madison: Department of Radiology; Department of Urology; Department of Biomedical Engineering.
| |
Collapse
|
|
15
|
Núñez KG, Sandow T, Fort D, Hibino M, Wright P, Cohen AJ, Thevenot PT. PD-1 expression in hepatocellular carcinoma predicts liver-directed therapy response and bridge-to-transplant survival. Cancer Immunol Immunother 2022; 71:1453-1465. [PMID: 34689234 PMCID: PMC9122885 DOI: 10.1007/s00262-021-03087-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 10/05/2021] [Indexed: 10/25/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) patients undergo liver-directed therapy (LDT) to control tumor burden while awaiting liver transplantation with response impacting waitlist survival. In this study, we investigate the link between absolute lymphocyte count (ALC) and PD-1 expression with response to LDT and bridge-to-transplant survival. METHODS Treatment-naïve HCC patients (n = 86) undergoing LDT were enrolled at a single center from August 2016-March 2020. Response to LDT was determined using mRECIST. Blood samples were collected on the day of LDT and at follow-up. Cells were analyzed for phenotype by flow cytometry. Outcomes were liver transplantation or tumor progression. RESULTS Incomplete response to initial LDT was associated with tumor progression precluding liver transplantation (OR: 7.6, 1.7 - 33.3, P < 0.001). Univariate analysis of baseline T cell phenotypes revealed ALC (OR: 0.44, 0.24-0.85, P = 0.009) as well as intermediate expression of PD-1 on CD4 (OR: 3.3, 1.03-10.3, P = 0.034) and CD8 T cells (OR: 3.0, 0.99-8.8 P = 0.043) associated with incomplete response to LDT. Elevations in PD-1 expression were associated with increased risk of bridge-to-transplant tumor progression (HR: 3.2, 1.2-9.4). In patients successfully bridged to liver transplantation, pre-treatment peripheral PD-1 profile was associated with advanced tumor staging (P < 0.005) with 2/4 of patients with elevations in PD-1 having T3-T4 TNM staging compared to 0 with low PD-1 expression. CONCLUSION Low lymphocyte count or elevated expression of the PD-1 checkpoint inhibitor is associated with incomplete response to LDT and increased risk of bridge-to-transplant tumor progression. Patients with impaired T cell homeostasis may benefit from PD-1 immunotherapy to improve response to LDT and improve bridge-to-transplant outcomes.
Collapse
Affiliation(s)
- Kelley G Núñez
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, 1520 Jefferson Highway, USA
| | - Tyler Sandow
- Interventional Radiology, Ochsner Clinic Foundation, New Orleans, LA, 1514 Jefferson Highway, USA
| | - Daniel Fort
- Centers for Outcomes and Health Services Research, Ochsner Clinic Foundation, New Orleans, LA, 1514 Jefferson Highway, USA
| | - Mina Hibino
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, 1520 Jefferson Highway, USA
| | - Paige Wright
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, 1520 Jefferson Highway, USA
| | - Ari J Cohen
- Multi-Organ Transplant Institute, Ochsner Clinic Foundation, New Orleans, LA, 1514 Jefferson Highway, USA
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - Paul T Thevenot
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, 1520 Jefferson Highway, USA.
| |
Collapse
|
|
16
|
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
| |
Collapse
|
|
17
|
Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
Collapse
|
|
18
|
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:zrab130. [PMID: 35211739 PMCID: PMC8874238 DOI: 10.1093/bjsopen/zrab130] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [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.
Collapse
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
| |
Collapse
|
|
19
|
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.
Collapse
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.)
| |
Collapse
|
|
20
|
Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
Collapse
Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| |
Collapse
|
|
21
|
Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review. J Clin Med 2021; 10:jcm10173932. [PMID: 34501381 PMCID: PMC8432180 DOI: 10.3390/jcm10173932] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 08/22/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023] Open
Abstract
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.
Collapse
|
|
22
|
da Fonseca L, Carrilho FJ. Expanding TACTICS trial into a different setting in hepatocellular carcinoma. Ann Hepatol 2021; 19:230-231. [PMID: 32139261 DOI: 10.1016/j.aohep.2020.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 02/04/2023]
Abstract
Systemic treatment for hepatocellular carcinoma (HCC) is recommended for patients with advanced stage and for those who progressed on locoregional modalities. The first agent approved for advanced HCC was sorafenib, and it remains one of the cornerstones of systemic treatment. In the past years, immunotherapy has shown promising results and has been incorporated into the treatment armamentarium. The rates of recurrence and progression after locoregional therapies are significant, what highlights the need to explore systemic agents for preventing or delaying these negative outcomes. Recently, sorafenib was shown to benefit patients with unresectable HCC under transarterial chemoembolization (TACE) by delaying tumor progression and prolonging time to vascular invasion and extrahepatic spread. Although this result was reported in patients with intermediate stage, it provides background to test the strategy of combining systemic treatment plus TACE as a bridge therapy to HCC patients awaiting liver transplantation, for which the risk of dropout due to tumor progression impairs the possibility of cure.
Collapse
Affiliation(s)
- Leonardo da Fonseca
- Sao Paulo Clínicas Liver Cancer Group - Hospital das Clínicas Complex, Instituto do Cancer do Estado de São Paulo, University of São Paulo School of Medicine, Brazil.
| | - Flair José Carrilho
- Sao Paulo Clínicas Liver Cancer Group - Hospital das Clínicas Complex, Instituto do Cancer do Estado de São Paulo, University of São Paulo School of Medicine, Brazil
| |
Collapse
|
|
23
|
Minici R, Ammendola M, Manti F, Siciliano MA, Giglio E, Minici M, Melina M, Currò G, Laganà D. Safety and Efficacy of Degradable Starch Microspheres Transcatheter Arterial Chemoembolization as a Bridging Therapy in Patients with Early Stage Hepatocellular Carcinoma and Child-Pugh Stage B Eligible for Liver Transplant. Front Pharmacol 2021; 12:634084. [PMID: 33897421 PMCID: PMC8062923 DOI: 10.3389/fphar.2021.634084] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 02/19/2021] [Indexed: 12/12/2022] Open
Abstract
In patients with early-stage hepatocellular carcinoma, awaiting liver transplantation, current guidelines by AASLD and ESMO recommend a bridging therapy with a loco-regional treatment to prevent progression outside transplantation criteria. The standard of care in delaying disease progression has been recognized to be the transarterial chemoembolization. Permanent occlusion of tumor feeding vessels has effects on tumour stromal microenvironment by inducing intra- and intercellular signaling processes counteracting hypoxia, such as the release of vascular endothelial growth factor, a promoter of neoangiogenesis, tumour proliferation and metastatic growth. Among chemoembolization interventions, TACE with degradable starch microspheres represents an alternative to conventional cTACE and DEB-TACE and it minimizes detrimental effects on tumour stromal microenvironment, guaranteeing a transient occlusion of tumour feeding arteries and avoiding VEGF overexpression.Between January 2015 and September 2020, 54 consecutive patients with early-stage hepatocellular carcinoma and Child-Pugh stage B, who had undergone DSM-TACE as a bridging therapy while awaiting liver transplantation, were eligible for the study. A total of 154 DSM-TACE was performed, with a mean number of 2.85 procedures per patient. 18 patients (33.3%) succeeded in achieving liver transplantation, with a mean waiting time-to-transplantation of 11.7 months. The cumulative rates of patients still active on the WL at 6 months were about 91 and 93% when considering overall drop-out and tumour-specific drop-out respectively. Overall survival was about 96% at 6 months and 92% at 12 months. 17 patients experienced adverse events after the chemoembolizations. For patients with HCC in the transplant waiting list and within the Child-Pugh B stage, life expectancy may be dominated by the liver dysfunction, rather than by the tumour progression itself. In this population subset, the choice of LRT is critical because LRT itself could become a dangerous tool that is likely to precipitate liver dysfunction to an extent that survival is shortened rather than prolonged. Hence, the current study demonstrates that DSM-TACE is not far from being an ideal LRT, because it has an excellent safety profile, maintaining an efficacy that guarantees a clear advantage on the dropout rate with respect to the non-operative strategy, thus justifying its use.
Collapse
Affiliation(s)
- Roberto Minici
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Michele Ammendola
- Digestive Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Francesco Manti
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Maria Anna Siciliano
- Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Enrica Giglio
- Medical Oncology Unit, University Hospital-Marche Polytechnic University, Ancona, Italy
| | - Marco Minici
- National Research Council (Cnr), Institute for High Performance Computing and Networking (ICAR), Rende, Italy
| | - Marica Melina
- Department of Medical and Surgical Sciences, Sant’Orsola Malpighi Hospital, Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Giuseppe Currò
- General Surgery Unit, Science of Health Department, Magna Graecia University, Catanzaro, Italy
| | - Domenico Laganà
- Radiology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| |
Collapse
|
|
24
|
Kwong A, Mehta N. Expanding the Limits of Liver Transplantation for Hepatocellular Carcinoma: Is There a Limit? Clin Liver Dis 2021; 25:19-33. [PMID: 33978578 DOI: 10.1016/j.cld.2020.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation is a treatment option for hepatocellular carcinoma within Milan criteria. With careful selection practices, patients with larger tumors can do well with successful downstaging followed by liver transplantation and should not be excluded based on tumor size or number alone. When considering expanded criteria for hepatocellular carcinoma, however, survival outcomes after liver transplantation should be comparable with patients without hepatocellular carcinoma. Surrogate measures of tumor biology, such as α-fetoprotein, other biomarkers, and dynamic tumor behavior including response to locoregional therapy can aid in risk stratification of patients before liver transplantation.
Collapse
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.
| |
Collapse
|
|
25
|
Downstaging to Liver Transplant: Success Involves Choosing the Right Patient. Clin Liver Dis 2020; 24:665-679. [PMID: 33012452 DOI: 10.1016/j.cld.2020.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.
Collapse
|
|
26
|
Chang Y, Jeong SW, Young Jang J, Jae Kim Y. Recent Updates of Transarterial Chemoembolilzation in Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:E8165. [PMID: 33142892 PMCID: PMC7662786 DOI: 10.3390/ijms21218165] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Revised: 10/28/2020] [Accepted: 10/28/2020] [Indexed: 12/24/2022] Open
Abstract
Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.
Collapse
Affiliation(s)
- Young Chang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Soung Won Jeong
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Jae Young Jang
- Department of Internal Medicine, Digestive Disease Center, Institute for Digestive Research, Soonchunhyang University College of Medicine, Seoul 04401, Korea; (Y.C.); (J.Y.J.)
| | - Yong Jae Kim
- Department of Radiology, Soonchunhyang University College of Medicine, Seoul 04401, Korea;
| |
Collapse
|
|
27
|
Ziogas IA, Hickman LA, Matsuoka LK, Izzy M, Montenovo MI, Rega SA, Feurer ID, Alexopoulos SP. Comparison of Wait-List Mortality Between Cholangiocarcinoma and Hepatocellular Carcinoma Liver Transplant Candidates. Liver Transpl 2020; 26:1112-1120. [PMID: 32475062 DOI: 10.1002/lt.25807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Revised: 04/28/2020] [Accepted: 05/17/2020] [Indexed: 12/13/2022]
Abstract
Despite the divergent disease biology of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC), wait-list prioritization is identical for both diagnoses. We compared wait-list and posttransplant outcomes between CCA and HCC liver transplantation patients with Model for End-Stage Liver Disease exceptions using Scientific Registry of Transplant Recipients data. The 408 CCA candidates listed between 2003 and mid-2017 were matched to 2 HCC cohorts by listing date (±2 months, n = 816) and by Organ Procurement and Transplantation Network (OPTN) region and date (±6 months, n = 408). Cumulative incidence competing risk regression examined the effects of diagnosis, OPTN region, and center-level CCA listing volume on wait-list removal due to death/being too ill (dropout). Cox models evaluated the effects of diagnosis, OPTN region, center-level CCA volume, and waiting time on graft failure among deceased donor liver transplantation (DDLT) recipients. After adjusting for OPTN region and CCA listing volume (all P ≥ 0.07), both HCC cohorts had a reduced likelihood of wait-list dropout compared with CCA candidates (HCC with period matching only: subdistribution hazard ratio [SHR] = 0.63; 95% CI, 0.43-0.93; P = 0.02 and HCC with OPTN region and period matching: SHR = 0.60; 95% CI, 0.41-0.87; P = 0.007). The cumulative incidence rates of wait-list dropout at 6 and 12 months were 13.2% (95% CI, 10.0%-17.0%) and 23.9% (95% CI, 20.0%-29.0%) for CCA candidates, 7.3% (95% CI, 5.0%-10.0%) and 12.7% (95% CI, 10.0%-17.0%) for HCC candidates with region and listing date matching, and 7.1% (95% CI, 5.0%-9.0%) and 12.6% (95% CI, 10.0%-15.0%) for HCC candidates with listing date matching only. Additionally, HCC DDLT recipients had a 57% reduced risk of graft failure compared with CCA recipients (P < 0.001). Waiting time was unrelated to graft failure (P = 0.57), and there was no waiting time by diagnosis cohort interaction effect (P = 0.47). When identically prioritized, LT candidates with CCA have increased wait-list dropout compared with those with HCC. More granular data are necessary to discern ways to mitigate this wait-list disadvantage and improve survival for patients with CCA.
Collapse
Affiliation(s)
- Ioannis A Ziogas
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Laura A Hickman
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Lea K Matsuoka
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Manhal Izzy
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN
| | - Martin I Montenovo
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| | - Scott A Rega
- Vanderbilt Transplant Center, Vanderbilt University Medical Center, Nashville, TN
| | - Irene D Feurer
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
- Vanderbilt Transplant Center, Vanderbilt University Medical Center, Nashville, TN
| | - Sophoclis P Alexopoulos
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Vanderbilt University Medical Center, Nashville, TN
| |
Collapse
|
|
28
|
Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, Durand F, Ijzermans J, Polak W, Zheng S, Roberts JP, Sapisochin G, Hibi T, Kwan NM, Ghobrial M, Soin A. Liver Transplantation for Hepatocellular Carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1136-1142. [PMID: 32217938 DOI: 10.1097/tp.0000000000003174] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) offers excellent long-term outcome for certain patients with hepatocellular carcinoma (HCC), with a push to not simply rely on tumor size and number. Selection criteria should also consider tumor biology (including alpha-fetoprotein), probability of waitlist and post-LT survival (ie, transplant benefit), organ availability, and waitlist composition. These criteria may be expanded for live donor LT (LDLT) compared to deceased donor LT though this should not adversely affect the double equipoise in LDLT, namely ensuring both acceptable recipient outcomes and donor safety. HCC patients with compensated liver disease and minimal tumor burden have low urgency for LT, especially after local-regional therapy with complete response, and do not appear to derive the same benefit from LT as other waitlist candidates. These guidelines were developed to assist in selecting appropriate HCC patients for both deceased donor LT and LDLT.
Collapse
Affiliation(s)
- Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Francis Y Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Vincenzo Mazzaferro
- Department of Surgery, GI Surgery and Liver Transplantation, Istituto Nazionale Tumori, Milan, Italy
| | - Christian Toso
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Francois Durand
- Service d'Hépatologie & Réanimation Hépatodigestive, Université Paris VII Hôpital Beaujon, Paris, France
| | - Jan Ijzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wojciech Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - John P Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Taizo Hibi
- Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nancy Man Kwan
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Mark Ghobrial
- J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Avi Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| |
Collapse
|
|
29
|
Bauschke A, Altendorf-Hofmann A, Ardelt M, Kissler H, Tautenhahn HM, Settmacher U. Impact of successful local ablative bridging therapy prior to liver transplantation on long-term survival in patients with hepatocellular carcinoma in cirrhosis. J Cancer Res Clin Oncol 2020; 146:1819-1827. [PMID: 32356179 PMCID: PMC7256027 DOI: 10.1007/s00432-020-03215-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Accepted: 04/08/2020] [Indexed: 12/13/2022]
Abstract
Background It has been shown that local ablative procedures enable downsizing, reduce drop-out from the waiting list and improve prognosis after liver transplantation. It is still unclear whether a response to the local ablative therapy is due to a favorable tumor biology or if a real benefit in tumor stabilization exists, particularly in complete pathological response. Method Data of 163 HCC patients who underwent liver transplantation were extracted from our prospectively maintained registry. We analyzed the tumor load, pre-transplant α-fetoprotein levels, child stage aside the application and success of local ablative therapies as bridging procedures before transplantation. Results 87 patients received multiple and/or combined local therapies. In 20 cases, this resulted in a complete remission of the tumor as observed in the explant histology. The other 76 patients underwent no bridging procedure. The observed 5- and 10-year survival rates for patients with bridging were 67% and 47% and without bridging 56% and 46%, respectively. Tumor-related 10-year survival showed a statistically significant difference between both groups (81% versus 59%). In the multivariate analyses bridging, number of lesions and α-fetoprotein level showed an independent statistically significant influence on tumor-related survival in these patients. Conclusions Successful local ablative therapy before liver transplantation is an independent statistically significant factor in long-term tumor-related survival for patients with HCC in cirrhosis and reduces tumor recurrences.
Collapse
Affiliation(s)
- Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany.
| | - Annelore Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - Michael Ardelt
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - Herman Kissler
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - Hans-Michael Tautenhahn
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 101, 07740, Jena, Germany
| |
Collapse
|
|
30
|
Mehta N, Dodge JL, Grab JD, Yao FY. National Experience on Down-Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha-Fetoprotein, and Wait Time. Hepatology 2020; 71:943-954. [PMID: 31344273 PMCID: PMC8722406 DOI: 10.1002/hep.30879] [Citation(s) in RCA: 94] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 07/18/2019] [Indexed: 01/04/2023]
Abstract
BACKGROUND AND AIMS United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down-staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down-staging by comparing two down-staging groups with (1) tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria and (2) "all-comers" (AC-DS) with initial tumor burden beyond UNOS-DS criteria versus patients always within Milan. APPROACH AND RESULTS This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n = 3,276), UNOS-DS (n = 422), and AC-DS (n = 121). Median time to LT was 12.8 months in long wait regions, 6.5 months in mid wait regions (MWR), and 2.6 months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC-DS versus 16.9% of UNOS-DS and 14.4% of Milan (P = 0.002). Kaplan-Meier 3-year post-LT survival was 83.2% for Milan, 79.1% for UNOS-DS (P = 0.17 vs. Milan), and 71.4% for AC-DS (P = 0.04 vs. Milan). Within down-staging groups, risk of post-LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P = 0.005) and with alpha-fetoprotein (AFP) ≥ 100 ng/mL at LT (HR, 2.4; P = 0.009). The 3-year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS-DS, and 16.7% for AC-DS (P < 0.001). In down-staging groups, AFP ≥ 100 (HR, 2.6; P = 0.02) was the only independent predictor of HCC recurrence. CONCLUSIONS Our results validated UNOS-DS criteria based on comparable 3-year survival between UNOS-DS and Milan groups. Additional refinements based on AFP and wait time may further improve post-LT outcomes in down-staging groups, especially given that reported 3-year recurrence was higher than in those always within Milan criteria.
Collapse
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Joshua D. Grab
- Division of Transplant Surgery, Department of Surgery, 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
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| |
Collapse
|
|
31
|
Cools KS, Moon AM, Burke LM, McGinty KA, Strassle PD, Gerber DA. Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma. Liver Transpl 2020; 26:203-214. [PMID: 31677319 PMCID: PMC6980979 DOI: 10.1002/lt.25673] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 10/26/2019] [Indexed: 12/17/2022]
Abstract
Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.
Collapse
Affiliation(s)
- Katherine S. Cools
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Andrew M. Moon
- Division of Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Lauren M.B. Burke
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Katrina A. McGinty
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Paula D. Strassle
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Department of Epidemiology, University of North Carolina School of Public Health
| | - David A. Gerber
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC
| |
Collapse
|
|
32
|
Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
Collapse
Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| |
Collapse
|
|
33
|
Wu TH, Wang YC, Cheng CH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC. Outcomes associated with the intention of loco-regional therapy prior to living donor liver transplantation for hepatocellular carcinoma. World J Gastrointest Surg 2020; 12:17-27. [PMID: 31984121 PMCID: PMC6943093 DOI: 10.4240/wjgs.v12.i1.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 11/06/2019] [Accepted: 11/28/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Loco-regional therapy for hepatocellular carcinoma (HCC) during the period awaiting liver transplantation (LT) appears to be a logical approach to reduce the risk of tumor progression and dropout in the waitlist. Living donor LT (LDLT) offers a flexible timing for transplantation providing timeframe for well preparation of transplantation. AIM To investigate outcomes in relation to the intention of pre-transplantation loco-regional therapy in LDLT for HCC patients. METHODS A total of 308 consecutive patients undergoing LDLTs for HCC between August 2004 and December 2018 were retrospectively analyzed. Patients were grouped according to the intention of loco-regional therapy prior to LT, and outcomes of patients were analyzed and compared between groups. RESULTS Overall, 38 patients (12.3%) were detected with HCC recurrence during the follow-up period after LDLT. Patients who were radiologically beyond the University of California at San Francisco criteria and received loco-regional therapy as down-staging therapy had significant inferior outcomes to other groups for both recurrence-free survival (RFS, P < 0.0005) and overall survival (P = 0.046). Moreover, patients with defined profound tumor necrosis (TN) by loco-regional therapy had a superior RFS (5-year of 93.8%) as compared with others (P = 0.010). CONCLUSION LDLT features a flexible timely transplantation for patient with HCC. However, the loco-regional therapy prior to LDLT does not seem to provide benefit unless a certain effect in terms of profound TN is noted.
Collapse
Affiliation(s)
- Tsung-Han Wu
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Yu-Chao Wang
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Chih-Hsien Cheng
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33305, Taiwan
| | - 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 33305, Taiwan
- Department of Organs Transplantation Institute, Chang Gung University College of Medicine, Taoyun 33305, 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 33305, Taiwan
| |
Collapse
|
|
34
|
|
|
35
|
Lipiodol retention pattern after TACE for HCC is a predictor for local progression in lesions with complete response. Cancer Imaging 2019; 19:75. [PMID: 31730491 PMCID: PMC6858631 DOI: 10.1186/s40644-019-0260-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 11/05/2019] [Indexed: 12/23/2022] Open
Abstract
Background To evaluate the predictive value of the lipiodol retention pattern for local progression of HCC with a complete response (CR) on CT according to mRECIST criteria after a first session of conventional chemoembolization (cTACE). Methods From January 2014 to May 2016 all consecutive patients undergoing a first cTACE session for HCC were identified. Inclusion criteria were the presence of ≤3 HCCs and available pre- and post-cTACE CT. Tumor response was classified according to mRECIST criteria. The analysis focused on tumors with a CR. The lipiodol retention pattern in these tumors was classified as complete (C-Lip, covering the entire tumor volume), or incomplete (I-Lip). Local progression was defined as the reappearance of areas of enhancement on arterial-phase images with washout on portal/delayed phase images within 2 cm from treated tumors on follow-up CT. Results The final population included 50 patients with 82 HCCs. A total of 46 (56%) HCCs were classified with a CR, including 16 (35%) with I-Lip, and 30 (65%) with C-Lip. After a median follow-up of 14 months (3.2–35.9 months), 15/16 (94%) and 10/30 (30%) of I-Lip and C-Lip HCCs showed local progression on CT, respectively (p < 0.001), with no significant difference in the time to progression (mean 11.1 ± 2 vs. 13.4 ± 3 months for I-Lip and C-Lip, respectively p = 0.51). Conclusions HCCs with incomplete lipiodol retention after a first cTACE session have a high risk of local progression even when there is a CR according to mRECIST, and should be considered to be incompletely treated.
Collapse
|
|
36
|
Sinha J, Mehta N, Dodge JL, Poltavskiy E, Roberts J, Yao F. Are There Upper Limits in Tumor Burden for Down-Staging of Hepatocellular Carcinoma to Liver Transplant? Analysis of the All-Comers Protocol. Hepatology 2019; 70:1185-1196. [PMID: 30779440 DOI: 10.1002/hep.30570] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 02/10/2019] [Indexed: 12/18/2022]
Abstract
Patients with hepatocellular carcinoma (HCC) within the University of California, San Francisco down-staging (UCSF-DS) criteria (one lesion > 5 cm and ≤ 8 cm; two to three lesions each ≤ 5 cm; or four to five lesions each ≤ 3 cm with total tumor diameter ≤ 8 cm) who achieved successful down-staging (DS) to Milan criteria had similar outcomes after liver transplantation (LT) compared with HCC initially meeting the Milan criteria. Nevertheless, little is known about the outcome of DS in patients with initial tumor burden exceeding the UCSF-DS criteria, defined as "all-comers" (AC). We compared the intention-to-treat (ITT) outcomes of DS in 74 patients in the AC group and 133 patients in the UCSF-DS group. Successful DS to Milan was observed in 64.8% of the AC group versus 84.2% of the UCSF-DS group (P < 0.001). The sum of tumor number and largest tumor diameter was significantly associated with successful DS (hazard ratio [HR] 0.87, P < 0.05). The cumulative probability of dropout within 1 year and 3 years was 53.5% and 80.0%, respectively, for AC versus 25.0% and 36.1%, respectively, for UCSF-DS (P < 0.0001). Factors predicting dropout included sum of tumor number and largest tumor diameter greater than 8 (HR 1.79, P = 0.049) and Child class B and C (HR 2.54, P = 0.001). The AC group also had a significantly lower liver transplant (LT) rate (13.5% versus 59.0%, P < 0.001). ITT survival at 1 year and 5 years was 77.4% and 21.1%, respectively, in AC versus 85.5% and 56.0%, respectively, in UCSF-DS (P < 0.001). Three of 10 patients in the AC group who underwent LT developed HCC recurrence. Conclusion: We observed a significantly lower LT probability and inferior ITT survival with DS in the AC group versus the UCSF-DS group. Our results suggest that an upper limit in tumor burden exists beyond which successful LT after DS becomes an unrealistic goal.
Collapse
Affiliation(s)
- Jasmine Sinha
- School of Medicine, University of California, San Francisco, CA
| | - Neil Mehta
- School of Medicine, University of California, San Francisco, CA
| | - Jennifer L Dodge
- Department of Surgery, University of California, San Francisco, CA
| | | | - John Roberts
- Department of Surgery, University of California, San Francisco, CA
| | - Francis Yao
- School of Medicine, University of California, San Francisco, CA.,Department of Surgery, University of California, San Francisco, CA
| |
Collapse
|
|
37
|
Kim DG, Lee JG, Joo DJ, Kim SI, Kim MS. Favourable outcome of pathologic downstaging by locoregional treatment for hepatocellular carcinoma in liver transplantation. Sci Rep 2019; 9:10386. [PMID: 31316165 PMCID: PMC6637173 DOI: 10.1038/s41598-019-46871-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 06/27/2019] [Indexed: 02/07/2023] Open
Abstract
No distinct guidelines are available regarding the effect of pretransplant locoregional treatment (LRT) in hepatocellular carcinoma (HCC) staging system. The aim of this study was to investigate the prognosis of pathologic downstaging (PDS) by the exclusion of total necrosis after liver transplantation. We conducted a study of 326 HCC patients who underwent liver transplantation between September 2005 and December 2016. Two hundred twenty-two patients received pretransplant LRT and 102 patients did not. Among the former group, 74 (33.0%) achieved PDS while 150 (67.0%) showed unchanged T stage after the exclusion of total necrosis. Five-year HCC recurrent free survival (RFS) of PDS group (85.1%) was similar to that of the no LRT group (88.8%) but higher than that of the non-PDS group (68.9%; P < 0.001). Based on T stage adjusted with total necrosis and PDS status, RFS was similar in the PDS T1 (82.4%) and non-PDS T1 (86.5%) groups. Non-PDS T2 cancers had worse outcome regardless of the Milan (P = 0.982) or University of California San Francisco criteria (P = 0.466). On preoperative examination, parameters like less than 1 viable tumor, less than 1 cm of tumor size, and less than 20 ng/mL of serum alpha fetoprotein were associated with PDS. This study showed that PDS by LRT was associated with favorable outcome in HCC patients after liver transplantation.
Collapse
Affiliation(s)
- Deok Gie Kim
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea. .,The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
| |
Collapse
|
|
38
|
Uemura T, Kirichenko A, Bunker M, Vincent M, Machado L, Thai N. Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation. World J Surg 2019; 43:886-893. [PMID: 30361748 DOI: 10.1007/s00268-018-4829-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx. PATIENTS AND METHODS Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40-50 Gy delivered in 4-6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT. RESULTS Median size of original tumors was 3.2 cm (2.0-8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0-3.2) in the explanted livers (p < 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx. CONCLUSION SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.
Collapse
Affiliation(s)
- Tadahiro Uemura
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA.
| | | | - Mark Bunker
- Pathology, Allegheny General Hospital, Pittsburgh, USA
| | - Molly Vincent
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| | - Lorenzo Machado
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| | - Ngoc Thai
- Department of Surgery, Abdominal Transplantation and Hepato-Biliary Surgery, Allegheny General Hospital, Pittsburgh, PA, 15212, USA
| |
Collapse
|
|
39
|
Schmitz S, Lurje G, Ulmer F, Andert A, Bruners P, Schulze-Hagen M, Neumann U, Schoening W. Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation. Hepatobiliary Pancreat Dis Int 2019; 18:228-236. [PMID: 30718181 DOI: 10.1016/j.hbpd.2019.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/15/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation remains the main curative treatment option for hepatocellular carcinoma (HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points (exceptional MELD, exMELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional (neoadjuvant) treatment (LRT) is used. For patients unlikely to timely receive an organ via primary allocation, "extended critera donor (ECD) organs" are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. METHODS Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42 (84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients (82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. RESULTS One- and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached (P = 0.487). LRT had no impact on overall survival (P = 0.629). Median waiting time was shorter if no LRT was performed (4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival (P = 0.663). CONCLUSIONS Patients with an expected waiting time to transplantation of >6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.
Collapse
Affiliation(s)
- Sophia Schmitz
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Georg Lurje
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Florian Ulmer
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Anne Andert
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Philipp Bruners
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Maximilian Schulze-Hagen
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Ulf Neumann
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, Netherlands
| | - Wenzel Schoening
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Charité - University Medicine at Berlin, Germany.
| |
Collapse
|
|
40
|
Sandow T, Pavlus J, Field D, Lacayo E, Cohen E, Lynskey G, Caridi T, Buckley D, Cardella J, Kallakury B, Spies J, Kim AY. Bridging Hepatocellular Carcinoma to Transplant: Transarterial Chemoembolization Response, Tumor Biology, and Recurrence after Transplantation in a 12-Year Transplant Cohort. J Vasc Interv Radiol 2019; 30:995-1003. [PMID: 31109853 DOI: 10.1016/j.jvir.2018.12.736] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 12/09/2018] [Accepted: 12/18/2018] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate tumor response to transarterial chemoembolization as well as biologic characteristics of the tumor as predictors of recurrence after transplantation in patients with hepatocellular carcinoma (HCC) who were bridged or down-staged to liver transplantation. MATERIALS AND METHODS An institutional review board-approved, Health Insurance Portability and Accountability Act-compliant, single-institution retrospective analysis was performed on all patients with HCC who were treated with the use of conventional transarterial chemoembolization or transarterial chemoembolization with drug-eluting embolics (DEE) over a 12-year period and who subsequently underwent liver transplantation (n = 142). Treatment response was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) imaging criteria and then correlated with tumor characteristics and recurrence. Of the 142 patients followed after transplantation, 127 had imaging after transarterial chemoembolization but before transplantation. Imaging response and post-transplantation recurrence were correlated with patient demographics, liver function, and tumor morphology. HCC recurred in 9 patients (mean time from transplantation, 526 days). Recurrence was analyzed with the use of univariate and multivariate statistics. Kaplan-Meier recurrence-free survival curves were calculated based on immediate imaging response before transplantation with the use of the log-rank test. RESULTS Before transplantation, 57% of patients (72/127) demonstrated complete response (CR) and 24% (31/127) showed partial response (PR). Complete pathologic necrosis occurred in 54% (39/72) of CR patients and 20% (6/31) of PR patients. Poor treatment response, defined as stable disease (SD) or progressive disease (PD), occurred in 18% of patients (24/127) before transplantation and was present in 67% of cases of recurrence (6/9; P < .001). Post-transplantation recurrence was present in 1.4% of patients (1/71) with CR and in 6.5% of patients (2/31) with PR. In patients with SD after transarterial chemoembolization, HCC recurred in 18.8% of transplant patients (3/16) and in 43% of patients (3/7) with PD. Larger pretreatment tumor size (P = .05), higher Child-Pugh score (P = .002), higher tumor grade at explantation (P = .04), and lymphovascular invasion at explantation (P = .008) also were associated with increased incidence of post-transplantation recurrence. CONCLUSIONS Poor tumor response to transarterial chemoembolization before transplantation identifies patients at increased risk for post-transplantation recurrence.
Collapse
Affiliation(s)
- Tyler Sandow
- Department of Radiology, Ochsner Health System, New Orleans, Louisiana
| | - John Pavlus
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - David Field
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Eduardo Lacayo
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Emil Cohen
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - George Lynskey
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Theresa Caridi
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Donna Buckley
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - John Cardella
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Bhaskar Kallakury
- Department of Pathology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - James Spies
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007
| | - Alexander Y Kim
- Department of Radiology, Medstar Georgetown University Hospital, 3800 Reservoir Rd, Washington, DC 20007.
| |
Collapse
|
|
41
|
Abstract
Liver transplantation is the definitive treatment for patients with end-stage liver disease. Liver transplantation is also the optimal treatment for patients with hepatocellular carcinoma (HCC), especially in the setting of chronic liver disease. Unfortunately, due to the worldwide shortage of organs, this treatment is not available for all patients with HCC. Strict selection criteria have been developed in order to obtain optimal results. A surgical perspective of the preoperative selection, perioperative management, and postoperative care of patients is reviewed in depth and provides an overview for obtaining optimal long-term results from liver transplantation for HCC. With rigorous selection and patient management, excellent long-term outcomes can be obtained with liver transplantation for patients with HCC.
Collapse
|
|
42
|
Lee DD, Samoylova M, Mehta N, Musto KR, Roberts JP, Yao FY, Harnois DM. The mRECIST Classification Provides Insight into Tumor Biology for Patients With Hepatocellular Carcinoma Awaiting Liver Transplantation. Liver Transpl 2019; 25:228-241. [PMID: 30198150 DOI: 10.1002/lt.25333] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Accepted: 08/27/2018] [Indexed: 02/07/2023]
Abstract
With recent changes in United Network for Organ Sharing policy, patients in the United States with hepatocellular carcinoma (HCC) are likely to spend more time on the liver transplantation (LT) waiting list. The increasing wait time will allow for an opportunity to assess tumor biology prior to LT. Modified Response Evaluation Criteria in Solid Tumors (mRECIST) paradigm provides such a framework for this assessment, and yet little is understood of its utility as it would apply for patients listed for LT in the United States. Through a collaboration between the University of California, San Francisco, and the Mayo Clinic, Jacksonville, Florida, the experience of 772 patients listed for LT were retrospectively reviewed to study the impact of immediate mRECIST classification following locoregional therapy (LRT) on pre- and post-LT outcomes. Patients who had progression of disease (PD; n = 72), failed to respond to LRT (n = 89) at any time point, or did not achieve radiologic complete response (CR; n = 224) were all at significant risk for wait-list dropout (odds ratio [OR] = 12.11, 4.81, and 2.48; respectively). CR identified a cohort of patients who were at a reduced risk for wait-list dropout. However, 24.9% eventually required further intervention while waiting for transplant, and as many as 82.4% were found to have residual HCC on explant pathology. Failure to respond to LRT was associated with increased risk for recurrence (OR = 3.00) more so than PD (OR = 1.36), suggesting that despite PD, patients who eventually can respond to LRT may represent favorable candidates for LT. In conclusion, for patients awaiting LT, the mRECIST assessment provides critical guidance for patient management. Although PD portends a poor prognosis, our findings suggest that further aggressive LRT should be pursued because a response to LRT may yield acceptable results for patients awaiting LT as well as after LT.
Collapse
Affiliation(s)
- David D Lee
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - Mariya Samoylova
- General Surgery Residency, Department of Surgery, Duke University School of Medicine, Durham, NC.,Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Neil Mehta
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Kaitlyn R Musto
- Department of Transplantation, Mayo Clinic, Jacksonville, FL
| | - John P Roberts
- Divisions of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y Yao
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | | |
Collapse
|
|
43
|
Raoul JL, Forner A, Bolondi L, Cheung TT, Kloeckner R, de Baere T. Updated use of TACE for hepatocellular carcinoma treatment: How and when to use it based on clinical evidence. Cancer Treat Rev 2018; 72:28-36. [PMID: 30447470 DOI: 10.1016/j.ctrv.2018.11.002] [Citation(s) in RCA: 408] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 11/09/2018] [Accepted: 11/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, representing the sixth leading cause of cancer and the third leading cause of cancer-related mortality. Patient stratification and treatment allocation are based on tumor stage, liver function, and performance status. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate stage HCC, including those with large or multinodular HCC, well-preserved liver function, and no cancer-related symptoms or evidence of vascular invasion or extrahepatic spread. Two TACE techniques have been used since 2004, conventional TACE (cTACE) and TACE with drug-eluting beads (DEB-TACE). cTACE was evidenced first to treat intermediate stage HCC patients. It combines the transcatheter delivery of chemotherapy using Lipiodol-based emulsion plus an embolizing agent to achieve strong cytotoxic and ischemic effects. Drug-eluting beads (DEBs) were developed in order to slowly release chemotherapeutic agents, and to increase ischemia intensity and duration. Recent advances allow TACE treatment of both early stage patients (i.e. those with a solitary nodule or up to 3 nodules under 3 cm) and some advanced stage patients. Here we review recent clinical evidence related to TACE treatment of patients with early, intermediate, and advanced stage HCC. Based on the 2014 TACE algorithm of Raoul et al., this international expert panel proposes an updated TACE algorithm and provides insights into TACE use for patients at any HCC stage.
Collapse
Affiliation(s)
- Jean-Luc Raoul
- Digestive Oncology, Institut de Cancérologie de l'Ouest, Boulevard Professeur Jacques Monod, 44805 Nantes-Saint Herblain, France.
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, IDIBAPS, Hospital Clínic, University of Barcelona, Calle Villaroel 170, 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Avenida Monforte de Lemos, 28029 Madrid, Spain.
| | - Luigi Bolondi
- Unit of Internal Medicine, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Zamboni 33, 40126 Bologna, Italy.
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road 102, Hong Kong Special Administrative Region
| | - Roman Kloeckner
- Department of Diagnostic and Interventional Radiology, Johannes Gutenberg-University Medical Centre, Langenbeckstraße 1, 55131 Mainz, Germany.
| | - Thierry de Baere
- Gustave Roussy-Cancer Campus, rue Edouard-Vaillant 114, 94 805 Villejuif Cedex, France.
| |
Collapse
|
|
44
|
Werner JD, Frangakis C, Ruck JM, Hong K, Philosophe B, Cameron AM, Saberi B, Gurakar A, Georgiades C. Neoadjuvant Transarterial Chemoembolization Improves Survival After Liver Transplant in Patients With Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2018; 17:638-643. [PMID: 30251938 DOI: 10.6002/ect.2018.0017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Our aims were to determine whether transarterial chemoembolization before liver transplant for hepatocellular carcinoma improves posttransplant survival and whether patients downstaged by transarterial chemoembolization within Milan criteria have a posttransplant survival benefit. MATERIALS AND METHODS In this retrospective analysis of prospectively collected data, survival rates of 87 patients treated with and 68 patients not treated with transarterial chemoembolization before liver transplant were compared using 2-sample t tests and multivariate Cox regression. We also compared posttransplant survival of patients within Milan criteria versus those downstaged after transarterial chemoembolization. We controlled for disease severity by assessing, among other variables, tumor diameter before and at transplant and alpha-fetoprotein levels before transplant and transarterial chemoembolization. RESULTS Overall 1-, 3-, and 5-year survival rates were 84%, 71%, and 63%, respectively. These rates were 91%, 78%, and 73% for patients who received and 76%, 63%, and 54% for patients who did not receive transarterial chemoembolization. Hazard ratios were 0.56 for having versus not having transarterial chemoembolization (P = .04), 1.06 for total tumor diameter on explantation (P = .01), 1.5 for largest tumor > 3 cm (P = .15), and 2.9 for pretransplant alpha-fetoprotein > 659 ng/mL (P = .006). A higher end-stage liver disease score correlated with poorer overall survival (hazard ratio = 1.53; P < .001). Laboratory values, lipiodol uptake, imaging response, and downstaging into Milan criteria were not correlated with survival. CONCLUSIONS Patients with hepatocellular carcinoma who were treated with neoadjuvant transarterial chemoembolization had better survival rates posttransplant than those not treated with transarterial chemoembolization. A high pretransplant alpha-fetoprotein level was negatively correlated with survival. Patients downstaged to Milan criteria after transarterial chemoembolization fared equally well versus those who met Milan criteria initially. Pretreatment with transarterial chemoembolization was positively correlated with survival posttransplant, with patients having a 44% reduction in posttransplant mortality.
Collapse
Affiliation(s)
- John D Werner
- From the Division of Vascular and Interventional Radiology, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Smolock AR, Cristescu MM, Hinshaw A, Woo KM, Wells SA, Ziemlewicz TJ, Lubner MG, Dalvie PS, Louis Hinshaw J, Brace CL, Ozkan OS, Lee FT, Laeseke P. Combination transarterial chemoembolization and microwave ablation improves local tumor control for 3- to 5-cm hepatocellular carcinoma when compared with transarterial chemoembolization alone. Abdom Radiol (NY) 2018; 43:2497-2504. [PMID: 29450606 DOI: 10.1007/s00261-018-1464-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE To compare transarterial chemoembolization (TACE) monotherapy to combination TACE and microwave ablation (MWA) for local control of 3- to 5-cm hepatocellular carcinoma (HCC). METHODS Patients with HCC between 3 and 5 cm treated with TACE monotherapy or combination TACE + MWA at a single institution between 2007 and 2016 were retrospectively reviewed. Twenty-four HCCs (median diameter 3.8 cm) in 16 patients (13 males; median age 64 years) were treated using TACE monotherapy. Combination TACE + MWA was used to treat 23 HCCs (median diameter 4.2 cm) in 22 patients (18 males; median age 61 years). Microwave ablation was performed at a target time of two weeks following TACE. Individual tumors were followed by serial contrast-enhanced CT or MR. Response to treatment was evaluated on a tumor-by-tumor basis using mRECIST criteria with the primary outcome being local tumor progression (LTP). Data were analyzed using Fisher's exact test for categorical variables and Wilcoxon rank sum test for continuous variables. Time to LTP was estimated with the Kaplan-Meier method. RESULTS Relative to TACE monotherapy, TACE + MWA provided a trend toward both a lower rate of LTP (34.8% vs. 62.5%, p = 0.11) and a higher complete response rate (65.2% vs. 37.5%; p = 0.12). Time to LTP (22.3 months vs. 4.2 months; p = 0.001) was significantly longer in the TACE + MWA group compared to TACE monotherapy. CONCLUSIONS Combination therapy with TACE and microwave ablation improves local control and increases time to LTP for 3-5 cm HCC.
Collapse
Affiliation(s)
- Amanda R Smolock
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Mircea M Cristescu
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Audrey Hinshaw
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Kaitlin M Woo
- Departments of Biostatistics and Medical Informatics, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Shane A Wells
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Timothy J Ziemlewicz
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Meghan G Lubner
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Prasad S Dalvie
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - J Louis Hinshaw
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Christopher L Brace
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
- Departments of Biomedical Engineering, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
- Departments of Medical Physics, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Orhan S Ozkan
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Fred T Lee
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
- Departments of Biomedical Engineering, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA
| | - Paul Laeseke
- Departments of Radiology, University of Wisconsin Hospital and Clinics, 600 Highland Ave., MC 3252, Madison, WI, 53792, USA.
| |
Collapse
|
|
46
|
Pavel MC, Fuster J. Expansion of the hepatocellular carcinoma Milan criteria in liver transplantation: Future directions. World J Gastroenterol 2018; 24:3626-3636. [PMID: 30166858 PMCID: PMC6113720 DOI: 10.3748/wjg.v24.i32.3626] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 06/24/2018] [Accepted: 06/30/2018] [Indexed: 02/06/2023] Open
Abstract
Milan criteria are currently the benchmark related to liver transplantation (LT) for hepatocellular carcinoma. However, several groups have proposed different expanded criteria with acceptable results. In this article, we review the current status of LT beyond the Milan criteria in three different scenarios-expanded criteria with cadaveric LT, downstaging to Milan criteria before LT, and expansion in the context of adult living donor LT. The review focuses on three main questions: what would the impact of the expansion beyond Milan criteria be on the patients on the waiting list; whether the dichotomous criteria (yes/no) currently used are appropriate for LT or continuous survival estimations, such as the one of “Metroticket” and whether it should enter into the clinical practice; and, whether the use of living donor LT in the context of expansion beyond Milan criteria is justified.
Collapse
Affiliation(s)
- Mihai-Calin Pavel
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, Digestive and Metabolic Diseases Institute, Hospital Clínic, University of Barcelona, Barcelona, Catalonia 08036, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit, Department of Surgery, Digestive and Metabolic Diseases Institute, Hospital Clínic, University of Barcelona, Barcelona, Catalonia 08036, Spain
- Barcelona-Clínic Liver Cancer Group (BCLC), Liver Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBEREHD, Universitat de Barcelona, Barcelona, Catalonia 08036, Spain
| |
Collapse
|
|
47
|
Cho CW, Choi GS, Kim JM, Kwon CHD, Kim DJ, Joh JW. Clinical usefulness of transarterial chemoembolization response prior to liver transplantation as predictor of optimal timing for living donor liver transplantation. Ann Surg Treat Res 2018; 95:111-120. [PMID: 30079328 PMCID: PMC6073044 DOI: 10.4174/astr.2018.95.2.111] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 11/22/2017] [Accepted: 12/05/2017] [Indexed: 12/13/2022] Open
Abstract
Purpose Response to preoperative transarterial chemoembolization (TACE) has been recommended as a biological selection criterion for liver transplantation (LT). The aim of our study was to identify optimal timing of living donor liver transplantation (LDLT) after TACE based on the TACE response. Methods We performed a retrospective study to assess recurrence in 128 hepatocellular carcinoma (HCC) patients who underwent LDLT following sequential TACE from January 2002 to March 2015 at a single institute. Cox proportional hazard models and Kaplan-Meier analysis were utilized to estimate HCC recurrence and find optimal timing for LDLT. Results Seventy-three and 61 patients were divided as the responder and nonresponder, respectively. Multivariate analysis showed independent pre-liver transplantation (pre-LT) predictors of recurrence were larger sized tumor (>3 cm, P = 0.024), nonresponse to TACE (P = 0.031), vascular invasion (P = 0.002), and extrahepatic nodal involvement (P = 0.001). In the 3-month time difference between last pre-LT TACE and LDLT subgroup, TACE responders showed significantly higher adjusted hazard ratio (aHR) of recurrence free survival (aHR, 6.284; P = 0.007), cancer specific survival (aHR, 7.033; P = 0.016), and overall survival (aHR, 7.055; P = 0.005). Moreover, for overall patients and responder groups, the significant time difference between last pre-LT TACE and LDLT was 2 months in the minimum P-value approach. Conclusion In selected patients who showed good response to pre-LT TACE, a shorter time interval between TACE and LDLT may be associated with higher recurrence free survival, cancer specific survival, and overall survival.
Collapse
Affiliation(s)
- Chan Woo Cho
- Department of Surgery, Yeungnam University College of Medicine, Daegu, Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Doo Jin Kim
- Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
48
|
Sangiovanni A, Colombo M. Bridging to liver transplantation patients with a hepatocellular carcinoma within Milan criteria: how worth is it? Hepatobiliary Surg Nutr 2018; 7:202-205. [PMID: 30046574 DOI: 10.21037/hbsn.2018.03.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, CRC "AM e A Migliavacca" Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy
| | - Massimo Colombo
- Department of Medicine, Humanitas Clinical and Research Center, Humanitas Hospital, Rozzano, Italy
| |
Collapse
|
|
49
|
Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
Collapse
Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
| |
Collapse
|
|
50
|
Ma KW, Chan ACY, She BWH, Chok KSH, Cheung TT, Dai JWC, Fung JYY, Lo CM. Changing Paradigm in the Surgical Management of Hepatocellular Carcinoma With Salvage Transplantation. Transplant Proc 2018; 50:1087-1093. [PMID: 29731072 DOI: 10.1016/j.transproceed.2018.01.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 01/22/2018] [Indexed: 01/06/2023]
Abstract
OBJECTIVE The objective of this study was to compare the long-term outcomes of primary and salvage liver transplantation for patients with hepatocellular carcinoma (HCC). METHOD This was a 10-year retrospective analysis in a tertiary referral center. RESULTS There were 184 patients recruited (primary liver transplantation [pLT]:salvage liver transplantation [sLT], 143:41). The median follow-up time was 79 months. Operation time was shorter in the pLT group than the sLT group (661 ± 164 minutes vs 754 ± 206 minutes; P = .01) and the blood loss was 3749 mL and 3545 mL for pLT and sLT, respectively (P = .735). The reoperation rate was 5.6% and 4.9%, respectively (P = 1.0). The 5-year overall and disease-free survival rates from the time of transplantation for pLT and sLT were 84.1% versus 70.2% (P = .01) and 82.2% versus 65.8% (P = .01), respectively. The 5-year overall survival rate from the time of primary treatment for sLT was 80.3% (P = .1). Subgroup analysis of sLT showed that young age (50 vs 56 year old; P = .004) was the only factor associated with poor overall survival. Young age (P = .004) and microvascular permeation (P = .008) in the recurrent tumor were associated with HCC recurrence. Young age stands out to be the only independent factor associated with HCC recurrence. CONCLUSION sLT is the treatment of choice for patients with recurrent HCC in regions of graft shortage.
Collapse
Affiliation(s)
- K W Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - A C Y Chan
- Department of Surgery, The University of Hong Kong, Hong Kong, China.
| | - B W H She
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - K S H Chok
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - T T Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - J W C Dai
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - J Y Y Fung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - C M Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| |
Collapse
|