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1
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Borucki K, Brunner T, Caspari R, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Gebert J, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, Fougère CL, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Ott J, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ringe K, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schütte K, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Trojan J, van Thiel I, Utzig M, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wenzel G, Wildner D, Wörns MA, Galle P, Malek N. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:e82-e158. [PMID: 39919781 DOI: 10.1055/a-2460-6347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2025]
Affiliation(s)
- Sabrina Groß
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Michael Bitzer
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Jörg Albert
- Katharinenhospital, Klinik für Allgemeine Innere Medizin, Gastroenterologie, Hepatologie, Infektiologie und Pneumologie, Stuttgart
| | - Susanne Blödt
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | | | - Katrin Borucki
- Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Klinische Chemie und Pathobiochemie
| | - Thomas Brunner
- Universitätsklinik für Strahlentherapie-Radioonkologie, Medizinische Universität Graz
| | - Reiner Caspari
- Klinik Niederrhein Erkrankungen des Stoffwechsels der Verdauungsorgane und Tumorerkrankungen, Bad Neuenahr-Ahrweiler
| | | | | | - Markus Follmann
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | | | - Cihan Gani
- Klinik für Radioonkologie, Universitätsklinikum Tübingen
| | - Jamila Gebert
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Andreas Geier
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
| | - Eleni Gkika
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg
| | - Martin Götz
- Medizinische Klinik IV - Gastroenterologie/Onkologie, Klinikverbund Südwest, Böblingen
| | - Thomas Helmberger
- Institut für Radiologie, Neuroradiologie und minimal invasive Therapie, München Klinik Bogenhausen
| | - Ralf-Thorsten Hoffmann
- Institut und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Dresden
| | - Peter Huppert
- Radiologisches Zentrum, Max Grundig Klinik, Bühlerhöhe
| | - David Krug
- Strahlentherapie Campus Kiel, Universitätsklinikum Schleswig-Holstein
| | - Christian La Fougère
- Nuklearmedizin und Klinische Molekulare Bildgebung, Eberhard-Karls Universität, Tübingen
| | - Hauke Lang
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Johannes Gutenberg-Universität, Mainz
| | - Thomas Langer
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Philipp Lenz
- Zentrale Einrichtung Palliativmedizin, Universitätsklinikum Münster
| | - Tom Lüdde
- Medizinische Klinik für Gastroenterologie, Hepatologie und Infektiologie, Universitätsklinikum Düsseldorf
| | - Andreas Mahnken
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Marburg
| | - Silvio Nadalin
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Eberhard-Karls Universität, Tübingen
| | | | - Monika Nothacker
- Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Berlin
| | - Johann Ockenga
- Medizinische Klinik II, Gesundheit Nord, Klinikverbund Bremen
| | - Karl Oldhafer
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Asklepios Klinik Barmbek
| | - Julia Ott
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
| | - Philipp Paprottka
- Sektion für Interventionelle Radiologie, Klinikum rechts der Isar, Technische Universität München
| | - Philippe Pereira
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, SLK-Klinken Heilbronn
| | - Thorsten Persigehl
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln
| | - Ruben Plentz
- Digestive Diseases and Nutrition, Gastroenterology, University of Kentucky
| | - Jürgen Pohl
- Abteilung für Gastroenterologie, Asklepios Klinik Altona
| | | | - Peter Reimer
- Institut für Diagnostische und Interventionelle Radiologie, Städtisches Klinikum Karlsruhe
| | | | - Kristina Ringe
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | - Elke Roeb
- Medizinische Klinik II Pneumologie, Nephrologie und Gastroenterologie, Universitätsklinikum Gießen
| | - Jörn Rüssel
- Medizinische Klinik IV Hämatologie und Onkologie, Universitätsklinikum Halle (Saale)
| | - Barbara Schellhaas
- Medizinische Klinik I Gastroenterologie, Pneumologie und Endokrinologie, Friedrich-Alexander-Universität, Erlangen
| | - Peter Schirmacher
- Allgemeine Pathologie und pathologische Anatomie, Universitätsklinikum Heidelberg
| | | | - Irene Schmid
- Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital, LMU München
| | - Kerstin Schütte
- Klinik für Innere Medizin und Gastroenterologie, Niels-Stensen-Kliniken, Marienhospital Osnabrück
| | - Andreas Schuler
- Medizinische Klinik, Gastroenterologie, Alb-Fils-Kliniken, Geislingen an der Steige
| | - Daniel Seehofer
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig
| | - Marianne Sinn
- II. Medizinische Klinik und Poliklinik (Onkologie, Hämatologie, Knochenmarktransplantation mit Abteilung für Pneumologie), Universitätsklinikum Hamburg-Eppendorf
| | - Andreas Stengel
- Innere Medizin VI - Psychosomatische Medizin und Psychotherapie, Eberhard-Karls Universität, Tübingen
| | | | | | | | - Anne Taubert
- Klinische Sozialarbeit, Universitätsklinikum Heidelberg
| | - Jörg Trojan
- Medizinische Klinik 1: Gastroenterologie und Hepatologie, Pneumologie und Allergologie, Endokrinologie und Diabetologie sowie Ernährungsmedizin, Goethe-Universität, Frankfurt
| | | | - Martin Utzig
- Abteilung Zertifizierung, Deutsche Krebsgesellschaft e.V., Berlin
| | - Arndt Vogel
- Institute of Medical Science, University of Toronto
| | - Thomas Vogl
- Institut für Diagnostische und Interventionelle Radiologie, Goethe-Universität, Frankfurt
| | - Frank Wacker
- Institut für Diagnostische und Interventionelle Radiologie, Medizinische Hochschule Hannover
| | | | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie, Medizinische Hochschule Hannover
| | - Henning Wege
- Klinik für Allgemeine Innere Medizin, Onkologie/Hämatologie, Gastroenterologie und Infektiologie, Klinikum Esslingen
| | - Gregor Wenzel
- Office des Leitlinienprogrammes Onkologie, Deutsche Krebsgesellschaft e.V., Berlin
| | - Dane Wildner
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Standort Lauf
| | - Marcus-Alexander Wörns
- Klinik für Gastroenterologie, Hämatologie und internistische Onkologie und Endokrinologie, Klinikum Dortmund
| | - Peter Galle
- 1. Medizinische Klinik und Poliklinik, Gastroenterologie, Hepatologie, Nephrologie, Rheumatologie, Infektiologie, Johannes Gutenberg-Universität, Mainz
| | - Nisar Malek
- Abteilung für Gastroenterologie, Gastrointestinale Onkologie, Hepatologie, Infektiologie und Geriatrie, Eberhard-Karls Universität, Tübingen
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Alnagar A, Zakeri N, Koilias K, Faulkes RE, Brown R, Cain O, Perera MTPR, Roberts KJ, Sanabria-Mateos R, Bartlett DC, Ma YT, Sivakumar S, Shetty S, Shah T, Dasari BVM. SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation. World J Transplant 2024; 14:95849. [PMID: 39295983 PMCID: PMC11317860 DOI: 10.5500/wjt.v14.i3.95849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/28/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.
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Affiliation(s)
- Amr Alnagar
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nekisa Zakeri
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Konstantinos Koilias
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rosemary E Faulkes
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Owen Cain
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - M Thamara P R Perera
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rebeca Sanabria-Mateos
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shivan Sivakumar
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shishir Shetty
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Bobby V M Dasari
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
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3
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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4
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Wehrle CJ, Raj R, Maspero M, Satish S, Eghtesad B, Pita A, Kim J, Khalil M, Calderon E, Orabi D, Zervos B, Modaresi Esfeh J, Whitsett Linganna M, Diago-Uso T, Fujiki M, Quintini C, Kwon CD, Miller C, Pinna A, Aucejo F, Hashimoto K, Schlegel A. Risk assessment in liver transplantation for hepatocellular carcinoma: long-term follow-up of a two-centre experience. Int J Surg 2024; 110:2818-2831. [PMID: 38241354 PMCID: PMC11093438 DOI: 10.1097/js9.0000000000001104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 01/08/2024] [Indexed: 01/21/2024]
Abstract
BACKGROUND Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC), but there are ongoing debates regarding outcomes and selection. This study examines the experience of LT for HCC at a high-volume centre. METHODS A prospectively maintained database was used to identify HCC patients undergoing LT from 2000 to 2020 with more than or equal to 3-years follow-up. Data were obtained from the centre database and electronic medical records. The Metroticket 2.0 HCC-specific 5-year survival scale was calculated for each patient. Kaplan-Meier and Cox-regression analyses were employed assessing survival between groups based on Metroticket score and individual donor and recipient risk factors. RESULTS Five hundred sixty-nine patients met criteria. Median follow-up was 96.2 months (8.12 years; interquartile range 59.9-147.8). Three-year recurrence-free (RFS) and overall survival (OS) were 88.6% ( n =504) and 86.6% ( n =493). Five-year RFS and OS were 78.9% ( n =449) and 79.1% ( n =450). Median Metroticket 2.0 score was 0.9 (interquartile range 0.9-0.95). Tumour size greater than 3 cm ( P =0.012), increasing tumour number on imaging ( P =0.001) and explant pathology ( P <0.001) was associated with recurrence. Transplant within Milan ( P <0.001) or UCSF criteria ( P <0.001) had lower recurrence rates. Increasing alpha-fetoprotein (AFP)-values were associated with more HCC recurrence ( P <0.001) and reduced OS ( P =0.008). Chemoembolization was predictive of recurrence in the overall population ( P =0.043) and in those outside-Milan criteria ( P =0.038). A receiver-operator curve using Metroticket 2.0 identified an optimal cut-off of projected survival greater than or equal to 87.5% for predicting recurrence. This cut-off was able to predict RFS ( P <0.001) in the total cohort and predict both, RFS ( P =0.007) and OS ( P =0.016) outside Milan. Receipt of donation after brain death (DBD) grafts (55/478, 13%) or living-donor grafts (3/22, 13.6%) experienced better survival rates compared to donation after cardiac death (DCD) grafts ( n =15/58, 25.6%, P =0.009). Donor age was associated with a higher HCC recurrence ( P =0.006). Both total ischaemia time (TIT) greater than 6hours ( P =0.016) and increasing TIT correlated with higher HCC recurrence ( P =0.027). The use of DCD grafts for outside-Milan candidates was associated with increased recurrence ( P =0.039) and reduced survival ( P =0.033). CONCLUSION This large two-centre analysis confirms favourable outcomes after LT for HCC. Tumour size and number, pre-transplant AFP, and Milan criteria remain important recipient HCC-risk factors. A higher donor risk (i.e. donor age, DCD grafts, ischaemia time) was associated with poorer outcomes.
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Affiliation(s)
- Chase J. Wehrle
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Roma Raj
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Marianna Maspero
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Sangeeta Satish
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Bijan Eghtesad
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Alejandro Pita
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Jaekeun Kim
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Mazhar Khalil
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Esteban Calderon
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Danny Orabi
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Bobby Zervos
- Cleveland Clinic Weston Hospital, Department of Liver Transplantation, Weston, FL, USA
| | | | | | - Teresa Diago-Uso
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Masato Fujiki
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Cristiano Quintini
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Choon David Kwon
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Charles Miller
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Antonio Pinna
- Cleveland Clinic Weston Hospital, Department of Liver Transplantation, Weston, FL, USA
| | - Federico Aucejo
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Koji Hashimoto
- Transplantation Center, Department of Surgery, Digestive Disease Institute
| | - Andrea Schlegel
- Transplantation Center, Department of Surgery, Digestive Disease Institute
- Department of Immunology, Lerner Research Institute, Cleveland Clinic, OH
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5
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Gonvers S, Martins-Filho SN, Hirayama A, Calderaro J, Phillips R, Uldry E, Demartines N, Melloul E, Park YN, Paradis V, Thung SN, Alves V, Sempoux C, Labgaa I. Macroscopic Characterization of Hepatocellular Carcinoma: An Underexploited Source of Prognostic Factors. J Hepatocell Carcinoma 2024; 11:707-719. [PMID: 38605975 PMCID: PMC11007400 DOI: 10.2147/jhc.s447848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/29/2024] [Indexed: 04/13/2024] Open
Abstract
The macroscopic appearance of a tumor such as hepatocellular carcinoma (HCC) may be defined as its phenotype which is de facto dictated by its genotype. Therefore, macroscopic characteristics of HCC are unlikely random but rather reflect genomic traits of cancer, presumably acting as a valuable source of information that can be retrieved and exploited to infer prognosis. This review aims to provide a comprehensive overview of the available data on the prognostic value of macroscopic characterization in HCC. A total of 57 studies meeting eligible criteria were identified, including patients undergoing liver resection (LR; 47 studies, 83%) or liver transplant (LT; 9 studies, 16%). The following macroscopic variables were investigated: tumor size (n = 42 studies), number of nodules (n = 28), vascular invasion (n = 24), bile duct invasion (n = 6), growth pattern (n = 15), resection margin (n = 11), tumor location (n = 6), capsule (n = 2) and satellite (n = 1). Although the selected studies provided insightful data with notable prognostic performances, a lack of standardization and substantial gaps were noted in the report and the analysis of gross findings. This topic remains incompletely covered. While the available studies underscored the value of macroscopic variables in HCC prognostication, important lacks were also observed. Macroscopic characterization of HCC is likely an underexploited source of prognostic factors that must be actively explored by future multidisciplinary research.
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Affiliation(s)
- Stéphanie Gonvers
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | | | - André Hirayama
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Julien Calderaro
- Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, Val-de-Marne, France
| | - Rebecca Phillips
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Emilie Uldry
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emmanuel Melloul
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Young Nyun Park
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Valérie Paradis
- Department of Pathology, APHP, Beaujon University Hospital, Clichy, France
| | - Swan N Thung
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Venancio Alves
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Christine Sempoux
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
- Department of Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Ismail Labgaa
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
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6
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Groß S, Bitzer M, Albert J, Blödt S, Boda-Heggemann J, Brunner T, Caspari R, De Toni E, Dombrowski F, Evert M, Follmann M, Freudenberger P, Gani C, Geier A, Gkika E, Götz M, Helmberger T, Hoffmann RT, Huppert P, Krug D, La Fougère C, Lang H, Langer T, Lenz P, Lüdde T, Mahnken A, Nadalin S, Nguyen HHP, Nothacker M, Ockenga J, Oldhafer K, Paprottka P, Pereira P, Persigehl T, Plentz R, Pohl J, Recken H, Reimer P, Riemer J, Ritterbusch U, Roeb E, Rüssel J, Schellhaas B, Schirmacher P, Schlitt HJ, Schmid I, Schuler A, Seehofer D, Sinn M, Stengel A, Steubesand N, Stoll C, Tannapfel A, Taubert A, Tholen R, Trojan J, van Thiel I, Vogel A, Vogl T, Wacker F, Waidmann O, Wedemeyer H, Wege H, Wildner D, Wörns MA, Galle P, Malek N. [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
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7
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Ishii M, Ibuki S, Morinaga J, Shimata K, Hirukawa K, Isono K, Honda M, Sugawara Y, Inomata Y, Hibi T. Elevated Alfa-Fetoprotein and Des-Gamma-Carboxy Prothrombin Levels Predict Poor Outcomes After Liver Transplantation for Hepatocellular Carcinoma Beyond the Japan Criteria. Transplant Proc 2023; 55:606-612. [PMID: 37005157 DOI: 10.1016/j.transproceed.2023.02.047] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 02/24/2023] [Indexed: 04/03/2023]
Abstract
AIM The Japan criteria (Milan criteria + 5-5-500 rule) was established recently to select cirrhotic patients with hepatocellular carcinoma for liver transplantation. We evaluated factors associated with poor prognosis after liver transplantation and investigated whether a further extension of the criteria would be worthwhile. METHODS We retrospectively analyzed 86 patients who underwent liver transplantation for hepatocellular carcinoma at Kumamoto University Hospital since 2004; 69 patients (80.2%) met the Japan criteria (the JCIN group), and 17 patients (19.8%) did not (the JCOUT group). RESULTS The 5-year cancer-specific survival rates of the JCIN group (92.2%) were significantly better than that of the JCOUT group (39.2%; P < .001). In univariable analysis, alfa-fetoprotein and des-gamma-carboxy prothrombin were significant independent factors associated with cancer-specific survival rates. According to the receiver operating characteristic curves, the cutoff values of alfa-fetoprotein and des-gamma-carboxy prothrombin that predicted hepatocellular carcinoma recurrence after liver transplantation were 756 ng/mL and 1976 mAU/mL, respectively. The JCOUT group was divided into 2 subgroups according to alfa-fetoprotein and des-gamma-carboxy prothrombin: low risk (alfa-fetoprotein level <756 ng/mL and des-gamma-carboxy prothrombin level <1976 mAU/mL) and high risk (alfa-fetoprotein level ≥756 ng/mL and/or des-gamma-carboxy prothrombin level ≥1976 mAU/mL). The 5-year cancer-specific survival rate in the low-risk group (67.5%) was significantly better than that in the high-risk group (0%; P < .001). CONCLUSIONS Alfa-fetoprotein levels of <756 ng/mL and des-gamma-carboxy prothrombin levels of <1976 mAU/mL may help identify cirrhotic patients with hepatocellular carcinoma who do not meet the Japan criteria but still benefit from liver transplantation.
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8
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Ali MAM, Harmsen WS, Morsy KH, Galal GMK, Therneau TM, Roberts LR. Prognostic utility of systemic inflammatory markers and chronic hepatitis C virus infection status in hepatocellular carcinoma patients treated with local ablation. BMC Cancer 2022; 22:221. [PMID: 35227234 PMCID: PMC8887142 DOI: 10.1186/s12885-021-09121-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 12/13/2021] [Indexed: 12/30/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) has high incidence and mortality worldwide. Local ablation using radiofrequency ablation (RFA) or microwave ablation (MWA) is potentially curative for early-stage HCC with outcomes comparable to surgical resection. We explored the influence of demographic, clinical, and laboratory factors on outcomes of HCC patients receiving ablation. Methods This retrospective cohort study included 221 HCC patients receiving local ablation at Mayo Clinic between January 2000 and October 2018, comprising 140 RFA and 81 MWA. Prognostic factors determining overall survival (OS) and disease-free survival (DFS) were identified using multivariate analysis. Results There was no clinically significant difference in OS or DFS between RFA and MWA. In multivariate analysis of OS, pre-ablation lymphocyte-monocyte ratio [Hazard ratio (HR) 0.7, 95% confidence interval (CI) 0.58–0.84, P = 0.0001], MELD score [HR 1.12, 95%CI 1.068–1.17, P < 0.0001], tumor number [HR 1.23, 95%CI 1.041–1.46, P = 0.015] and tumor size [HR 1.18, 95%CI 1.015–1.37, P = 0.031] were clinically-significant prognostic factors. Among HCC patients with chronic hepatitis C (HCV) infection, positive HCV PCR at HCC diagnosis was associated with 1.4-fold higher hazard of death, with 5-year survival of 32.8% vs 53.6% in HCV PCR-negative patients. Regarding DFS, pre-ablation lymphocyte-monocyte ratio [HR 0.77, 95%CI 0.66–0.9, P = 0.001], MELD score [HR 1.06, 95%CI 1.022–1.11, P = 0.002], Log2 AFP [HR 1.11, 95%CI 1.033–1.2, P = 0.005], tumor number [HR 1.29, 95%CI 1.078–1.53, P = 0.005] and tumor size [HR 1.25, 95%CI 1.043–1.51 P = 0.016] were independently prognostic. Conclusions Pre-ablation systemic inflammation represented by lymphocyte-monocyte ratio is significantly associated with OS and DFS in HCC patients treated with local ablation. HCV viremia is associated with poor OS. Tumor biology represented by tumor number and size are strongly prognostic for OS and DFS while AFP is significantly associated with DFS only.
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Affiliation(s)
| | - William Scott Harmsen
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, 205 Third Street SW, Rochester, MN, 55905, USA
| | - Khairy Hammam Morsy
- Department of Tropical Medicine and Gastroenterology, Sohag Faculty of Medicine, Naser City, Sohag, 82524, Egypt
| | - Ghada Moustapha Kamal Galal
- Department of Tropical Medicine and Gastroenterology, Sohag Faculty of Medicine, Naser City, Sohag, 82524, Egypt
| | - Terry M Therneau
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, 205 Third Street SW, Rochester, MN, 55905, USA
| | - Lewis Rowland Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN, 55905, USA.
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9
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Sabrina V, Michael B, Jörg A, Peter B, Wolf B, Susanne B, Thomas B, Frank D, Matthias E, Markus F, Christian LF, Paul F, Andreas G, Eleni G, Martin G, Elke H, Thomas H, Ralf-Thorsten H, Wolf-Peter H, Peter H, Achim K, Gabi K, Jürgen K, David K, Frank L, Hauke L, Thomas L, Philipp L, Andreas M, Alexander M, Oliver M, Silvio N, Huu Phuc N, Johann O, Karl-Jürgen O, Philipp P, Kerstin P, Philippe P, Thorsten P, Mathias P, Ruben P, Jürgen P, Jutta R, Peter R, Johanna R, Ulrike R, Elke R, Barbara S, Peter S, Irene S, Andreas S, Dietrich VS, Daniel S, Marianne S, Alexander S, Andreas S, Nadine S, Christian S, Andrea T, Anne T, Jörg T, Ingo VT, Reina T, Arndt V, Thomas V, Hilke V, Frank W, Oliver W, Heiner W, Henning W, Dane W, Christian W, Marcus-Alexander W, Peter G, Nisar M. S3-Leitlinie: Diagnostik und Therapie des hepatozellulären Karzinoms. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:e56-e130. [PMID: 35042248 DOI: 10.1055/a-1589-7568] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Voesch Sabrina
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Bitzer Michael
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
| | - Albert Jörg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Stuttgart
| | | | - Bechstein Wolf
- Klinik für Allgemein-, Viszeral-, Transplantations- und Thoraxchirurgie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Brunner Thomas
- Klinik für Strahlentherapie, Universitätsklinikum Magdeburg A. ö. R., Magdeburg
| | - Dombrowski Frank
- Institut für Pathologie, Universitätsmedizin Greifswald, Greifswald
| | | | - Follmann Markus
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | | | | | - Geier Andreas
- Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg
| | - Gkika Eleni
- Klinik für Strahlenheilkunde, Department für Radiologische Diagnostik und Therapie, Universitätsklinikum Freiburg, Freiburg
| | | | - Hammes Elke
- Lebertransplantierte Deutschland e. V., Ansbach
| | - Helmberger Thomas
- Institut für Radiologie, Neuroradiologie und minimal-invasive Therapie, München Klinik Bogenhausen, München
| | | | - Hofmann Wolf-Peter
- Gastroenterologie am Bayerischen Platz, medizinisches Versorgungszentrum, Berlin
| | | | | | - Knötgen Gabi
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Körber Jürgen
- Klinik Nahetal, Fachklinik für onkologische Rehabilitation und Anschlussrehabilitation, (AHB), Bad Kreuznach
| | - Krug David
- Klinik für Strahlentherapie, Universitätsklinikum Schleswig-Holstein, Kiel
| | | | - Lang Hauke
- Klinik für Allgemein-, Viszeral und Transplantationschirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz
| | - Langer Thomas
- Office des Leitlinienprogrammes Onkologie, c/o Deutsche Krebsgesellschaft e.V. Berlin
| | - Lenz Philipp
- Universitätsklinikum Münster, Zentrale Einrichtung Palliativmedizin, Münster
| | - Mahnken Andreas
- Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Meining Alexander
- Medizinische Klinik und Poliklinik II des Universitätsklinikums Würzburg, Würzburg
| | - Micke Oliver
- Klinik für Strahlentherapie und Radioonkologie, Franziskus Hospital Bielefeld, Bielefeld
| | - Nadalin Silvio
- Universitätsklinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Oldhafer Karl-Jürgen
- Klinik für Leber-, Gallenwegs- und Pankreaschirurgie, Semmelweis Universität, Asklepios Campus Hamburg, Hamburg
| | - Paprottka Philipp
- Abteilung für interventionelle Radiologie, Klinikum rechts der Isar der Technischen Universität München, München
| | - Paradies Kerstin
- Konferenz onkologischer Kranken- und Kinderkrankenpflege, Hamburg
| | - Pereira Philippe
- Zentrum für Radiologie, Minimal-invasive Therapien und Nuklearmedizin, Klinikum am Gesundbrunnen, SLK-Kliniken Heilbronn GmbH, Heilbronn
| | - Persigehl Thorsten
- Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Köln, Köln
| | | | | | - Pohl Jürgen
- Interventionelles Endoskopiezentrum und Schwerpunkt Gastrointestinale Onkologie, Asklepios Klinik Altona, Hamburg
| | - Riemer Jutta
- Lebertransplantierte Deutschland e. V., Bretzfeld
| | - Reimer Peter
- Institut für diagnostische und interventionelle Radiologie, Städtisches Klinikum Karlsruhe gGmbH, Karlsruhe
| | - Ringwald Johanna
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | - Roeb Elke
- Medizinische Klinik II, Universitätsklinikum Gießen und Marburg GmbH, Gießen
| | - Schellhaas Barbara
- Medizinische Klinik I, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen
| | - Schirmacher Peter
- Pathologisches Institut, Universitätsklinikum Heidelberg, Heidelberg
| | - Schmid Irene
- Zentrum Pädiatrische Hämatologie und Onkologie, Dr. von Haunersches Kinderspital, Klinikum der Universität München, München
| | | | | | - Seehofer Daniel
- Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig
| | - Sinn Marianne
- Medizinische Klinik II, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | | | - Stengel Andreas
- Psychosomatische Medizin und Psychotherapie, Universitätsklinikum Tübingen, Tübingen
| | | | | | - Tannapfel Andrea
- Institut für Pathologie der Ruhr-Universität Bochum am Berufsgenossenschaftlichen Universitätsklinikum Bergmannsheil, Bochum
| | - Taubert Anne
- Kliniksozialdienst, Universitätsklinikum Heidelberg, Bochum
| | - Trojan Jörg
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | | | - Tholen Reina
- Deutscher Verband für Physiotherapie e. V., Köln
| | - Vogel Arndt
- Klinik für Gastroenterologie, Hepatologie, Endokrinologie der Medizinischen Hochschule Hannover, Hannover
| | - Vogl Thomas
- Universitätsklinikum Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt
| | - Vorwerk Hilke
- Klinik für Strahlentherapie, Universitätsklinikum Gießen und Marburg GmbH, Marburg
| | - Wacker Frank
- Institut für Diagnostische und Interventionelle Radiologie der Medizinischen Hochschule Hannover, Hannover
| | - Waidmann Oliver
- Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Wedemeyer Heiner
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie Medizinische Hochschule Hannover, Hannover
| | - Wege Henning
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg
| | - Wildner Dane
- Innere Medizin, Krankenhäuser Nürnberger Land GmbH, Lauf an der Pegnitz
| | | | | | - Galle Peter
- I. Medizinische Klinik und Poliklinik, Universitätsklinikum Mainz, Mainz
| | - Malek Nisar
- Medizinische Klinik I, Universitätsklinikum Tübingen, Tübingen
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10
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Takamatsu FY, Gonzalez AM, Sá GP, Salzedas-Netto AA. Transplantation in Hepatocellular Carcinoma: Observational Multivariate Analysis of Survival and Recurrence Factors in 414 Patients. Transplant Proc 2021; 53:1957-1961. [PMID: 34229903 DOI: 10.1016/j.transproceed.2021.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 04/26/2021] [Accepted: 06/01/2021] [Indexed: 11/15/2022]
Abstract
BACKGROUND We sought to identify the risk factors involved in survival of and tumor recurrence in patients with hepatocellular carcinoma (HCC) undergoing liver transplant (LTx). METHODS We conducted a retrospective observational study and analyzed the medical records of 414 patients with HCC undergoing deceased donor LTx in São Paulo between January 2007 and December 2011. Multifactorial analysis of survival and recurrence was performed using clinical, laboratory, and pathology data. RESULTS The mortality rate was 27.5%; mean survival time was 68.1 months (95% confidence interval, 64.7-71.6); and estimated 1-, 3-, and 5-year survival probabilities were 83.8%, 75.8%, and 71.5%, respectively. Altered donor blood glucose, female sex, vascular invasion, advanced age, high Model for End-Stage Liver Disease, and tumor size were the main risk factors determining survival in LTx recipients. Recurrence was noted in 7.2% of patients during the study period and was more frequent in women (hazard ratio, 2.6). Vascular invasion increased the chance of recurrence by 5.4 times. Each additional 1-year increase in recipient age increased the chance of recurrence by 5.6%, and each 1-mm increase in tumor size increased the chance of recurrence by 3%. CONCLUSIONS Risk factors for reduced survival are donor blood glucose, female recipient, older age, increased Model for End-Stage Liver Disease score, and nodule size. Tumor recurrence risk factors are vascular invasion, female sex, recipient age, and nodule size.
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Affiliation(s)
- Fernanda Yuri Takamatsu
- Department of Surgical Gastroenterology and Liver Transplantation; Post-Graduation in Interdisciplinary Surgical Science, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
| | - Adriano Miziara Gonzalez
- Department of Surgical Gastroenterology and Liver Transplantation; Post-Graduation in Interdisciplinary Surgical Science, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil
| | - Gustavo Piloto Sá
- Post-Graduation in Interdisciplinary Surgical Science, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil
| | - Alcides Augusto Salzedas-Netto
- Department of Surgical Gastroenterology and Liver Transplantation; Post-Graduation in Interdisciplinary Surgical Science, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil
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11
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Survival Analysis after Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Single Center Cohort Study. BIOLOGY 2021; 10:biology10050446. [PMID: 34065172 PMCID: PMC8160725 DOI: 10.3390/biology10050446] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 05/13/2021] [Accepted: 05/19/2021] [Indexed: 12/12/2022]
Abstract
Background: Living-donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) has been used as a curative treatment option for hepatocellular carcinoma (HCC) because of a shortage of deceased donors. This study aimed to investigate survival outcomes after LDLT for HCC. Method: This study included 359 patients undergoing LDLT for HCC. We analyzed overall survival (OS) and recurrence-free survival (RFS) and the prognostic factors related to them. Results: The 5-year OS and RFS rates of patients within the Milan criteria (WM) were better than those of patients beyond the Milan criteria (BM) (87.3% vs. 64.1% and 87.6% vs. 57.8%, respectively, both p < 0.05). Alpha-fetoprotein level (AFP) > 400 ng/mL (hazard ratio (HR), 2.07; 95% CI, 1.28–3.36; p < 0.05) and HCC of BM (HR, 2.61; 95% CI, 1.60–4.26; p < 0.05) at immediate pretransplant were independent risk factors of OS. AFP > 400 ng/mL (HR, 2.16; 95% CI, 1.34–3.49; p < 0.05) and HCC of BM (HR, 3.01; 95% CI, 1.81–5.01; p < 0.05) were also independent risk factors of RFS. In pathologic findings of explanted liver, tumor size, Edmondson–Steiner grade III–IV, and microvascular invasion were independent risk factors of both OS and RFS (p < 0.05). Conclusions: BM and AFP > 400 ng/mL at immediate pretransplant are unfavorable predictors of survival outcomes after LDLT for HCC.
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Maccali C, Chagas AL, Boin I, Quiñonez E, Marciano S, Vilatobá M, Varón A, Anders M, Hoyos Duque S, Lima AS, Menendez J, Padilla-Machaca M, Poniachik J, Zapata R, Maraschio M, Chong Menéndez R, Muñoz L, Arufe D, Figueroa R, Soza A, Fauda M, Perales SR, Vergara Sandoval R, Bermudez C, Beltran O, Arenas Hoyos I, McCormack L, Mattera FJ, Gadano A, Parente García JH, Tani CM, Augusto Carneiro D'Albuquerque L, Carrilho FJ, Silva M, Piñero F. Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort. Liver Int 2021; 41:851-862. [PMID: 33217193 DOI: 10.1111/liv.14736] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/20/2020] [Accepted: 11/16/2020] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIM Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.
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Affiliation(s)
- Claudia Maccali
- São Paulo Clinics Liver Cancer Group - Hospital das Clínicas Complex, Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Aline L Chagas
- São Paulo Clinics Liver Cancer Group - Hospital das Clínicas Complex, Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Ilka Boin
- Unit of Liver Transplantation, State University of Campinas, Campinas, Brazil
| | | | | | - Mario Vilatobá
- Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", México
| | | | | | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe and Gastrohepatology Group, Universidad de Antioquia, Medellín, Colombia
| | - Agnaldo S Lima
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | | | | | | | - Rodrigo Zapata
- Clinica Alemana, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile
| | | | | | | | - Diego Arufe
- Sanatorio Sagrado Corazón, Buenos Aires, Argentina
| | | | - Alejandro Soza
- Department of Gastroenterology, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Martín Fauda
- Hospital Universitario Austral, Buenos Aires, Argentina
| | - Simone R Perales
- Unit of Liver Transplantation, State University of Campinas, Campinas, Brazil
| | | | - Carla Bermudez
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Isabel Arenas Hoyos
- Hospital Pablo Tobón Uribe and Gastrohepatology Group, Universidad de Antioquia, Medellín, Colombia
| | | | | | - Adrián Gadano
- Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Claudia Megumi Tani
- São Paulo Clinics Liver Cancer Group - Hospital das Clínicas Complex, Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Luiz Augusto Carneiro D'Albuquerque
- São Paulo Clinics Liver Cancer Group - Hospital das Clínicas Complex, Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Flair J Carrilho
- São Paulo Clinics Liver Cancer Group - Hospital das Clínicas Complex, Division of Clinical Gastroenterology and Hepatology, Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil
| | - Marcelo Silva
- Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Federico Piñero
- Hospital Universitario Austral, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
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13
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Zhu AX, Finn RS, Kang YK, Yen CJ, Galle PR, Llovet JM, Assenat E, Brandi G, Motomura K, Ohno I, Daniele B, Vogel A, Yamashita T, Hsu CH, Gerken G, Bilbruck J, Hsu Y, Liang K, Widau RC, Wang C, Abada P, Kudo M. Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab. Br J Cancer 2021; 124:1388-1397. [PMID: 33531690 PMCID: PMC8039038 DOI: 10.1038/s41416-021-01260-w] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 12/11/2020] [Accepted: 01/07/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2). METHODS Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed. RESULTS Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6-12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354-0.574; p < 0.0001). CONCLUSIONS AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, REACH (NCT01140347) and REACH-2 (NCT02435433).
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Affiliation(s)
- Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Boston, MA, USA.
- Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
| | - Richard S Finn
- Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
| | - Yoon-Koo Kang
- Asan Medical Center, University of Ulsan, Seoul, South Korea
| | - Chia-Jui Yen
- National Cheng Kung University Hospital, Tainan, Taiwan
| | | | - Josep M Llovet
- Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Institut d'Investigations Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Eric Assenat
- Department of Medical Oncology, CHU de Montpellier, Montpellier, France
| | | | | | - Izumi Ohno
- National Cancer Center Hospital East-Hepatobiliary and Pancreatic Oncology, Kashiwa, Japan
| | - Bruno Daniele
- Azienda Ospedaliera Gaetano Rummo, Benevento, Italy
- Ospedale del Mare, Napoli, Italy
| | - Arndt Vogel
- Medizinische Hochschule Hannover, Hannover, Germany
| | | | - Chih-Hung Hsu
- National Taiwan University Hospital, Taipei, Taiwan, ROC
| | | | | | - Yanzhi Hsu
- Eli Lilly and Company, New York, NY, USA
| | - Kun Liang
- Eli Lilly and Company, Branchburg, NJ, USA
| | | | | | - Paolo Abada
- Eli Lilly and Company, Indianapolis, IN, USA
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Hu H, Qi S, Zeng S, Zhang P, He L, Wen S, Zeng N, Yang J, Zhang W, Zhu W, Xiang N, Fang C. Importance of Microvascular Invasion Risk and Tumor Size on Recurrence and Survival of Hepatocellular Carcinoma After Anatomical Resection and Non-anatomical Resection. Front Oncol 2021; 11:621622. [PMID: 33816254 PMCID: PMC8010691 DOI: 10.3389/fonc.2021.621622] [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: 10/26/2020] [Accepted: 02/15/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose: To establish a valid prediction model to prognose the occurrence of microvascular invasion (MVI), and to compare the efficacy of anatomic resection (AR) or non-anatomic resection (NAR) for hepatocellular carcinoma (HCC). Methods: Two hundred twenty-eight patients with HCC who underwent surgical treatment were enrolled. Their hematological indicators, MRI imaging features, and outcome data were acquired. Result: In the multivariable analysis, alpha-fetoprotein >15 ng/mL, neutrophil to lymphocyte ratio >3.8, corona enhancement, and peritumoral hypointensity on hepatobiliary phase were associated with MVI. According on these factors, the AUROC of the predictive model in the primary and validation cohorts was 0.884 (95% CI: 0.829, 0.938) and 0.899 (95% CI: 0.821, 0.967), respectively. Patients with high risk of MVI or those with low risk of MVI but tumor size >5 cm in the AR group were associated with a lower rate of recurrence and death than patients in the NAR group; however, when patients are in the state of low-risk MVI with tumor size >5 cm, there is no difference in the rate of recurrence and death between AR and NAR. Conclusion: Our predictive model for HCC with MVI is convenient and accurate. Patients with high-risk of MVI or low-risk of MVI but tumor size >5 cm executing AR is of great necessity.
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Affiliation(s)
- Haoyu Hu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Shuo Qi
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Silue Zeng
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Peng Zhang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Linyun He
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Sai Wen
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Ning Zeng
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Jian Yang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Weiqi Zhang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Wen Zhu
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Nan Xiang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
| | - Chihua Fang
- Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China
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15
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Effect of Microvascular Invasion Risk on Early Recurrence of Hepatocellular Carcinoma After Surgery and Radiofrequency Ablation. Ann Surg 2021; 273:564-571. [PMID: 31058694 DOI: 10.1097/sla.0000000000003268] [Citation(s) in RCA: 207] [Impact Index Per Article: 51.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE We compared surgical resection (SR) and radiofrequency ablation (RFA) as first-line treatment in patients with hepatocellular carcinoma (HCC) based on the risk of microvascular invasion (MVI). BACKGROUND The best curative treatment modality between SR and RFA in patients with HCC with MVI remains unclear. METHODS Data from 2 academic cancer center-based cohorts of patients with a single, small (≤3 cm) HCC who underwent SR were used to derive (n = 276) and validate (n = 101) prediction models for MVI using clinical and imaging variables. The MVI prediction model was developed using multivariable logistic regression analysis and externally validated. Early recurrence (<2 years) based on risk stratification between SR (n = 276) and RFA (n = 240) was evaluated via propensity score matching. RESULTS In the multivariable analysis, alpha-fetoprotein (≥15 ng/mL), protein induced by vitamin K absence-II (≥48 mAU/mL), arterial peritumoral enhancement, and hepatobiliary peritumoral hypointensity on magnetic resonance imaging were associated with MVI. Incorporating these factors, the area under the receiver operating characteristic curve of the predictive model was 0.87 (95% confidence interval: 0.82-0.92) and 0.82 (95% confidence interval: 0.74-0.90) in the derivation and validation cohorts, respectively. SR was associated with a lower rate of early recurrence than RFA based on the risk of MVI after propensity score matching (P < 0.05). CONCLUSIONS Our model predicted the risk of MVI in patients with a small (≤ 3 cm) HCC with high accuracy. Patients with MVI who had undergone RFA were more vulnerable to recurrence than those who had undergone SR.
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16
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Min JH, Lee MW, Park HS, Lee DH, Park HJ, Lim S, Choi SY, Lee J, Lee JE, Ha SY, Cha DI, Carriere KC, Ahn JH. Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma. Radiology 2020; 297:573-581. [PMID: 32990512 DOI: 10.1148/radiol.2020201940] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment is critical for selecting a proper treatment strategy. Purpose To evaluate the interobserver agreement and the diagnostic performance of the MRI assessment of MVI in HCC according to the level of radiologist experience. Materials and Methods This retrospective study included 100 patients with surgically confirmed HCCs smaller than 5 cm who underwent gadoxetic acid-enhanced MRI between 2013 and 2016. Eight postfellowship radiologists (four with 7-13 years of experience [more experienced] and four with 3-6 years of experience [less experienced]) evaluated four imaging features (nonsmooth tumor margin, irregular rim-like enhancement in the arterial phase, peritumoral arterial phase hyperenhancement, peritumoral hepatobiliary phase hypointensity) and assigned the possibility of MVI. Interobserver agreement was determined by using Fleiss κ statistics according to reviewer experience and tumor size (≤3 cm vs >3 cm). With reference standards of histopathologic specimens, the diagnostic performance in the identification of MVI was assessed by using receiver operating characteristic curve analysis. Results In 100 patients (mean age, 58 years ± 10 [standard deviation]; 70 men) with 100 HCCs (mean size, 2.8 cm ± 0.9), 39 (39%) HCCs had MVI. The overall interobserver agreement was fair to moderate for the imaging features and their combinations (κ = 0.38-0.47) and MVI probability (κ = 0.41; 95% confidence interval: 0.33, 0.45). More experienced reviewers demonstrated higher agreement in MVI probability than less experienced reviewers (κ = 0.55 vs 0.36, respectively; P = .002). Diagnostic performance of each reviewer was modest for MVI prediction (area under the receiver operating characteristic curve [AUC] range, 0.60-0.74). The AUCs for the diagnosis of MVI were lower for HCCs larger than 3 cm (range, 0.55-0.69) than for those less than or equal to 3 cm (range, 0.59-0.75). Conclusion Considerable interobserver variability exists in the assessment of microvascular invasion in hepatocellular carcinoma using MRI, even for more experienced radiologists. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Tang in this issue.
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Affiliation(s)
- Ji Hye Min
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Min Woo Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Hee Sun Park
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Dong Ho Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Hyun Jeong Park
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Sanghyeok Lim
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Seo-Youn Choi
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Jisun Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Ji Eun Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Sang Yun Ha
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Dong Ik Cha
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Keumhee Chough Carriere
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Joong Hyun Ahn
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
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17
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Czauderna C, Schmidtmann I, Koch S, Pilz L, Heinrich S, Otto G, Mittler J, Lang H, Kloeckner R, Düber C, Sprinzl MF, Worns MA, Galle PR, Marquardt JU, Weinmann A. High pre-treatment static and dynamic alpha-fetoprotein values predict reduced overall survival in hepatocellular carcinoma. United European Gastroenterol J 2020; 9:2050640620972611. [PMID: 33226301 PMCID: PMC8259127 DOI: 10.1177/2050640620972611] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 10/13/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma is one of the most lethal cancers worldwide. Novel prognostic and/or predictive biomarkers are urgently needed to improve patient management. Alpha-fetoprotein is a well-established and widely used biomarker for hepatocellular carcinoma. However, diagnostic accuracy of static alpha-fetoprotein values is limited and the clinical potential is a matter of ongoing scientific discussion. OBJECTIVE We here evaluated the prognostic impact of pre-treatment static and dynamic alpha-fetoprotein variables on overall survival of hepatocellular carcinoma patients in a Western cohort. METHODS Patients with confirmed hepatocellular carcinoma (n = 809) treated at the Johannes Gutenberg-University Mainz between 1998 and 2014 and two available pre-treatment alpha-fetoprotein-values (AFP-slope) were retrospectively analysed. Clinico-pathological baseline parameters, pre-treatment static values and AFP-slope were assessed. Prognostic impact was determined by Kaplan-Meier analyses and Cox regression models. RESULTS High static and dynamic alpha-fetoprotein variables prior to therapy were associated with reduced survival rates of hepatocellular carcinoma patients. Several known clinical parameters such as Child-Pugh B (p < 0.01) and C stage (p < 0.001), portal vein thrombosis (p < 0.001) and extrahepatic spread (p < 0.001) were confirmed as independent predictors for overall survival. Addition of static and/or dynamic alpha-fetoprotein variable resulted in higher time-dependent area under the curves. Notably, in patients with more favourable prognosis, AFP-slope prior to therapy was a slightly stronger predictor for overall survival compared with static alpha-fetoprotein values. CONCLUSION Static and dynamic alpha-fetoprotein variables prior to therapy are predictive for overall survival of hepatocellular carcinoma patients. Addition of AFP-slope to established prognostic parameters might improve prognostic classification for a subgroup of hepatocellular carcinoma patients with preserved liver function and without portal vein tumour thrombosis.
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Affiliation(s)
- Carolin Czauderna
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
- Department of Medicine IUniversity Medical Centre SchleswigHolstein—Campus LübeckLübeckGermany
| | - Irene Schmidtmann
- Institute of Medical BiostatisticsEpidemiology and Informatics (IMBEI)Johannes Gutenberg UniversityMainzGermany
- Department of General, Visceral and Transplant SurgeryJohannes Gutenberg UniversityMainzGermany
| | - Sandra Koch
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Lukas Pilz
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Sophia Heinrich
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Gerd Otto
- Department of General, Visceral and Transplant SurgeryJohannes Gutenberg UniversityMainzGermany
| | - Jens Mittler
- Department of General, Visceral and Transplant SurgeryJohannes Gutenberg UniversityMainzGermany
| | - Hauke Lang
- Department of General, Visceral and Transplant SurgeryJohannes Gutenberg UniversityMainzGermany
| | - Roman Kloeckner
- Department of Diagnostic and Interventional RadiologyJohannes Gutenberg UniversityMainzGermany
| | - Christoph Düber
- Department of Diagnostic and Interventional RadiologyJohannes Gutenberg UniversityMainzGermany
| | - Martin F. Sprinzl
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Marcus A. Worns
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Peter R. Galle
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
| | - Jens U. Marquardt
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
- Department of Medicine IUniversity Medical Centre SchleswigHolstein—Campus LübeckLübeckGermany
| | - Arndt Weinmann
- Department of Internal Medicine IJohannes Gutenberg UniversityMainzGermany
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18
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Long-term outcomes of living donor liver transplantation after locoregional treatment for hepatocellular carcinoma: an experience from a single institute. Surg Today 2020; 51:350-357. [PMID: 32767130 DOI: 10.1007/s00595-020-02095-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 07/15/2020] [Indexed: 12/17/2022]
Abstract
PURPOSE The precise role of downstaging or bridge therapy for cirrhotic patients with hepatocellular carcinoma (HCC) beyond or within the Milan criteria (MC) before living donor liver transplantation (LDLT) remains undefined. METHODS We conducted a single-center, retrospective cohort study of 40 cirrhotic patients with HCC who underwent LDLT from 2000 to 2018. Dynamic computed tomography images at the initial presentation and immediately before LDLT as well as the final histopathological findings were reviewed to determine whether they met or exceeded MC. RESULTS Overall, 29 patients underwent various pre-transplant HCC treatments, including ablation and embolization (bridge therapy, n = 20; downstaging, n = 9). Of the 9 patients who were initially beyond the MC, 4 (44.4%) were successfully downstaged to within the MC. Five patients beyond the MC immediately before LDLT demonstrated a significantly worse 5-year overall survival rate than patients within the MC (16.7% vs. 82.2%, P = 0.004), regardless of the radiological HCC stage at presentation or the final pathological tumor status. All 3 recurrent patients had HCC beyond the MC immediately before transplant and died of their disease at 13, 24, and 50 months after transplantation. CONCLUSIONS Successful downstaging for HCC cases beyond the MC provides similar outcomes to those within the MC at presentation, regardless of the histopathological findings.
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19
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Hong YM, Cho M, Yoon KT, Ryu JH, Yang KH, Hwang TH. Preoperative blood neutrophil count predicts survival in hepatocellular carcinoma patients with living donor liver transplantation. KOREAN JOURNAL OF TRANSPLANTATION 2020; 34:92-99. [PMID: 35769348 PMCID: PMC9194438 DOI: 10.4285/kjt.2020.34.2.92] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 03/31/2020] [Accepted: 04/12/2020] [Indexed: 11/12/2022] Open
Abstract
Background The Milan criteria (MC) used to select patients for liver transplantation among patients with hepatocellular carcinoma (HCC) do not include tumor biology. Furthermore, systemic inflammatory markers have been identified to predict tumor biology. The present study investigated prognostic value of systemic inflammatory markers, including neutrophil count, in predicting the prognosis of patients with HCC undergoing living donor liver transplantation (LDLT). Methods We retrospectively analyzed data regarding peripheral blood inflammatory markers, as well as patient and tumor characteristics of patients with HCC who underwent LDLT. Univariate and multivariate analyses were performed to analyze variables associated with survival. Results A total of 103 patients with HCC who underwent LDLT were included. The 3- and 5-year recurrence-free survival (RFS) in patients with a high neutrophil count (>2,640/µL) were significantly lower than those in patients with a low neutrophil count (≤2,640/µL; 70.0% and 64.7% vs. 88.3% and 84.6%, respectively; P=0.02). Patients with a high neutrophil count also had lower 5-year overall survival (OS; 63.9% vs. 79.3%, P=0.03). In multivariate analysis, radiologic MC (hazard ratio [HR], 5.04; P=0.02) and neutrophil count (HR, 4.47; P=0.04) were independent factors predicting RFS. Among patients exceeding the MC, those with a high neutrophil count had significantly lower 5-year RFS than those with low neutrophil count (10% vs. 83%; P<0.01). Conclusions We demonstrated that high preoperative neutrophil count is associated with poor RFS and OS in patients with HCC undergoing LDLT.
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Affiliation(s)
- Young Mi Hong
- Department of Internal Medicine, Pusan National University School of Medicine, Liver center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Mong Cho
- Department of Internal Medicine, Pusan National University School of Medicine, Liver center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University School of Medicine, Liver center, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University School of Medicine, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Kwang Ho Yang
- Department of Surgery, Pusan National University School of Medicine, Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Tae Ho Hwang
- Department of Pharmacology, Pusan National University School of Medicine, Yangsan, Korea
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20
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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: 96] [Impact Index Per Article: 19.2] [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.
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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
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21
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Polat KY, Acar S, Gencdal G, Yazar S, Kargi A, Donmez R, Aslan S, Kavlak ME, Arikan C, Akyildiz M. Hepatocellular Carcinoma and Liver Transplantation: A Single-Center Experience. Transplant Proc 2020; 52:259-264. [PMID: 31911056 DOI: 10.1016/j.transproceed.2019.10.029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2019] [Accepted: 10/06/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Liver transplantation (LT) is the best treatment in selected patients with hepatocellular carcinoma (HCC). Morphologic criteria alone are not sufficient to predict survival. In this study, we investigated the clinical, biochemical, and pathologic factors affecting survival in patients who underwent LT due to HCC. METHODS Between October 2011 and January 2018, 165 of 749 LT for HCC cases performed at the Memorial Atasehir Hospital were evaluated retrospectively. Survival, demographic characteristics and etiology, preoperative alpha-fetoprotein (AFP) level, Model for End-Stage Liver Disease (MELD) score, prognostic staging, and morphologic and histologic properties were evaluated. RESULTS One hundred and thirty-nine cases of 165 were living donor liver transplantation (LDLT). The mean age was 57.7 ± 7.3 years, the mean follow-up period was 27.8 ± 20 months, and 41 patients (24%) died before follow-up. Recurrence of HCC was detected in 23 (14%) cases. Overall survival was 85%, 71%, and 64% for 1, 3, and 5 years, respectively. In terms of 1-, 3-, and 5-year survival within vs beyond Milan criteria was 90%, 80%, and 76% vs 75%, 66%, and 44%, respectively. In the University of California San Francisco criteria, it was 86%, 76%, and 70% vs 76%, 60%, and 30% compared with 1-, 3-, and 5-year survival. While histopathological poor differentiation and AFP elevation affected the course negatively. Good differentiation did not have a significant effect on survival. It was determined that poor differentiation, lymphovascular invasion, and an increased number of nodules significantly affected survival in both within and beyond cases. CONCLUSION A transplant decision is controversial in patients with HCC with other than previously defined morphologic criteria. In these cases, AFP level and histologic differentiation determine survival. The results were not satisfactory in both high and/or poorly differentiated cases.
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Affiliation(s)
- Kamil Yalcin Polat
- Department of General Surgery and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Sencan Acar
- Department of Gastroenterology and Organ Transplantation Center, Sakarya University School of Medicine, Sakarya, Turkey
| | - Genco Gencdal
- Department of Gastroenterology and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Serafettin Yazar
- Department of General Surgery and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Ahmet Kargi
- Department of General Surgery and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Ramazan Donmez
- Department of General Surgery and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Serdar Aslan
- Department of General Surgery and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Mustafa Emre Kavlak
- Department of Anesthesiology and Intensive Care Unit and Organ Transplantation Center, Memorial Atasehir Hospital, Istanbul, Turkey
| | - Cigdem Arikan
- Department of Pediatric Gastroenterology and Organ Transplantation Center, Koc University School of Medicine, Istanbul, Turkey
| | - Murat Akyildiz
- Department of Gastroenterology and Organ Transplantation Center, Koc University School of Medicine, Istanbul, Turkey
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22
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Welling TH, Eddinger K, Carrier K, Zhu D, Kleaveland T, Moore DE, Schaubel DE, Abt PL. Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence Following Transplantation. Liver Transpl 2018; 24:1233-1242. [PMID: 29729113 PMCID: PMC6153067 DOI: 10.1002/lt.25194] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Accepted: 04/23/2018] [Indexed: 12/12/2022]
Abstract
Orthotopic liver transplantation (OLT) and resection are effective treatments for hepatocellular carcinoma (HCC). However, optimizing OLT and limiting HCC recurrence remains a vexing problem. New HCC Model for End-Stage Liver Disease and allocation algorithms provide greater observation of HCC patients, many while receiving local-regional treatments. Potential benefits of local-regional treatment for limiting HCC recurrence after OLT remain incompletely understood. Therefore, we aimed to define HCC-specific prognostic factors affecting recurrence in a contemporary, multicenter cohort of HCC patients undergoing OLT and specifically whether local-regional therapies limited recurrence. We identified 441 patients undergoing OLT for HCC at 3 major transplant centers from 2008 to 2013. Cox regression was used to analyze covariate-adjusted recurrence and mortality rates after OLT. "Bridging" or "downstaging" therapy was used in 238 (54%) patients with transarterial chemoembolization (TACE) being used in 170 (71%) of treated patients. The survival rate after OLT was 88% and 78% at 1 and 3 years, respectively, with HCC recurrence (28% of deaths) significantly increasing the mortality rate (hazard ratio [HR], 19.87; P < 0.001). Tumor size, not tumor number, either at presentation or on explant independently predicted HCC recurrence (HR, 1.36 and 1.73, respectively; P < 0.05) with a threshold effect noted at 4.0-cm size. Local-regional therapy (TACE) reduced HCC recurrence by 64% when adjusting for presenting tumor size (HR, 0.36; P < 0.05). Explant tumor size and microvascular invasion predicted mortality (HR, 1.19 and 1.51, respectively; P < 0.05) and pathologic response to therapy (TACE or radiofrequency ablation) significantly decreased explant tumor size (0.56-1.62 cm diameter reduction; P < 0.05). In conclusion, HCC tumor size at presentation or explant is the most important predictor for HCC recurrence after OLT. Local-regional therapy to achieve a pathologic response (decreasing tumor size) can limit HCC recurrences after OLT. Liver Transplantation 00 000-000 2018 AASLD.
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Affiliation(s)
| | - Kevin Eddinger
- Department of Surgery, Hospital of the University of Pennsylvania
| | | | - Danting Zhu
- School of Public Health, University of Michigan, Ann Arbor, MI
| | | | | | | | - Peter L. Abt
- Department of Surgery, Hospital of the University of Pennsylvania
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23
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Huang AC, Mehta N, Dodge JL, Yao FY, Terrault NA. Direct-acting antivirals do not increase the risk of hepatocellular carcinoma recurrence after local-regional therapy or liver transplant waitlist dropout. Hepatology 2018; 68:449-461. [PMID: 29476694 PMCID: PMC6097892 DOI: 10.1002/hep.29855] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/03/2018] [Accepted: 02/02/2018] [Indexed: 02/06/2023]
Abstract
UNLABELLED Whether direct-acting antivirals (DAAs) increase the risk of hepatocellular carcinoma (HCC) recurrence after tumor-directed therapy is controversial. We sought to determine the impact of DAA therapy on HCC recurrence after local-regional therapy (LRT) and waitlist dropout among liver transplant (LT) candidates with HCC. We performed a retrospective cohort study of 149 LT candidates with hepatitis C virus (HCV) and HCC at a single center from 2014 through 2016. Cumulative incidence of HCC recurrence post-LRT and waitlist dropout was estimated by the DAA group. Factors associated with each outcome were evaluated using competing risks regression. A propensity score stabilized inverse probability weighting approach was used to account for differences in baseline characteristics between groups. The no DAA group (n = 87) had more severe cirrhosis and lower rates of complete radiologic tumor response after LRT than those treated with DAA (n = 62) but had similar alpha-fetoprotein and tumor burden at listing. Cumulative incidence of HCC recurrence within 1 year of complete response after LRT was 47.0% in the DAA group and 49.8% in the no DAA group (P = 0.93). In adjusted competing risk analysis using weighted propensity score modeling, risk of HCC recurrence was similar in the DAA group compared to those without DAA (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.58-1.42; P = 0.67). Patients treated with DAAs had lower risk of waitlist dropout due to tumor progression or death compared to the no DAA group in adjusted weighted analysis (HR, 0.30; 95% CI 0.13-0.69; P = 0.005). CONCLUSION In LT candidates with HCV and HCC with initial complete response to LRT, DAA use is not associated with increased risk of HCC recurrence but rather is associated with reduced risk of waitlist dropout due to tumor progression or death. (Hepatology 2018).
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Affiliation(s)
- Annsa C. Huang
- Department of Medicine, Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Neil Mehta
- Department of Medicine, Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Department of Medicine, Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA,Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Norah A. Terrault
- Department of Medicine, Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA,Department of Surgery, University of California San Francisco, San Francisco, CA
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Kim AY, Sinn DH, Jeong WK, Kim YK, Kang TW, Ha SY, Park CK, Choi GS, Kim JM, Kwon CHD, Joh JW, Kim MJ, Sohn I, Jung SH, Paik SW, Lee WJ. Hepatobiliary MRI as novel selection criteria in liver transplantation for hepatocellular carcinoma. J Hepatol 2018; 68:1144-1152. [PMID: 29410377 DOI: 10.1016/j.jhep.2018.01.024] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Revised: 12/18/2017] [Accepted: 01/24/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Hepatobiliary magnetic resonance imaging (MRI) provides additional information beyond the size and number of tumours, and may have prognostic implications. We examined whether pretransplant radiological features on MRI could be used to stratify the risk of tumour recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC). METHODS A total of 100 patients who had received a liver transplant and who had undergone preoperative gadoxetic acid-enhanced MRI, including the hepatobiliary phase (HBP), were reviewed for tumour size, number, and morphological type (e.g. nodular, nodular with perinodular extension, or confluent multinodular), satellite nodules, non-smooth tumour margins, peritumoural enhancement in arterial phase, peritumoural hypointensity on HBP, and apparent diffusion coefficients. The primary endpoint was time to recurrence. RESULTS In a multivariable adjusted model, the presence of satellite nodules [hazard ratio (HR) 3.07; 95% confidence interval (CI) 1.14-8.24] and peritumoural hypointensity on HBP (HR 4.53; 95% CI 1.52-13.4) were identified as independent factors associated with tumour recurrence. Having either of these radiological findings was associated with a higher tumour recurrence rate (72.5% vs. 15.4% at three years, p <0.001). When patients were stratified according to the Milan criteria, the presence of these two high-risk radiological findings was associated with a higher tumour recurrence rate in both patients transplanted within the Milan criteria (66.7% vs. 11.6% at three years, p <0.001, n = 68) and those who were transplanted outside the Milan criteria (75.5% vs. 28.6% at three years, p <0.001, n = 32). CONCLUSIONS Radiological features on preoperative hepatobiliary MRI can stratify the risk of tumour recurrence in patients who were transplanted either within or outside the Milan criteria. Therefore, hepatobiliary MRI can be a useful way to select potential candidates for LT. LAY SUMMARY High-risk radiological findings on preoperative hepatobiliary magnetic resonance imaging (either one of the following features: satellite nodule and peritumoural hypointensity on hepatobiliary phase) were associated with a higher tumour recurrence rate in patients transplanted either within or outside the Milan criteria.
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Affiliation(s)
- Ah Yeong Kim
- Department of Radiology and Center for Imaging Sciences, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Internal Medicine, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Sciences, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Young Kon Kim
- Department of Radiology and Center for Imaging Sciences, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Tae Wook Kang
- Department of Radiology and Center for Imaging Sciences, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Yun Ha
- Department of Pathology, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Chul Keun Park
- Department of Pathology, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyu Seong Choi
- Department of Surgery, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong Man Kim
- Department of Surgery, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae-Won Joh
- Department of Surgery, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Min-Ji Kim
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Insuk Sohn
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sin-Ho Jung
- Department of Biostatics and Bioinformatics, Duke University, USA
| | - Seung Woon Paik
- Department of Internal Medicine, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Sciences, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Satapathy SK, Das K, Kocak M, Helmick RA, Eason JD, Nair SP, Vanatta JM. No apparent benefit of preemptive sorafenib therapy in liver transplant recipients with advanced hepatocellular carcinoma on explant. Clin Transplant 2018; 32:e13246. [PMID: 29577449 DOI: 10.1111/ctr.13246] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. AIM Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. METHODS We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. RESULTS During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. CONCLUSION Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.
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Affiliation(s)
- Sanjaya K Satapathy
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Kanak Das
- Division of Gastroenterology, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Mehmet Kocak
- Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Ryan A Helmick
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - James D Eason
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Satheesh P Nair
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
| | - Jason M Vanatta
- Transplantation, Methodist University Hospital Transplant Institute/University of Tennessee Health Sciences Center, Memphis, TN, USA
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Lee S, Kim SH, Lee JE, Sinn DH, Park CK. Preoperative gadoxetic acid-enhanced MRI for predicting microvascular invasion in patients with single hepatocellular carcinoma. J Hepatol 2017; 67:526-534. [PMID: 28483680 DOI: 10.1016/j.jhep.2017.04.024] [Citation(s) in RCA: 328] [Impact Index Per Article: 41.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 03/22/2017] [Accepted: 04/19/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS This study aimed to identify preoperative magnetic resonance (MR) imaging biomarkers for predicting microvascular invasion (MVI), to determine their diagnostic performance and to evaluate whether they are associated with early recurrence after surgery for single hepatocellular carcinoma (HCC). METHODS The study included 197 patients with surgically resected HCC (≤5cm) who underwent preoperative gadoxetic acid-enhanced MR imaging. Significant MR imaging findings for predicting MVI were identified by univariate and multivariate analyses. Early recurrence rates (<2years) were analyzed with respect to significant imaging findings for predicting MVI. RESULTS Three MR imaging features were independently associated with MVI: arterial peritumoral enhancement (odds ratio [OR]=5.184; 95% confidence interval [CI]: 2.228, 12.063; p<0.001), non-smooth tumor margin (OR=3.555; 95% CI: 1.627, 7.769; p=0.001), and peritumoral hypointensity on hepatobiliary phase (HBP) (OR=4.705; 95% CI: 1.671, 13.246; p=0.003). When two of three findings were combined, the specificity was 92.5% (124/134). When all three findings were satisfied, the specificity was 99.3% (133/134). Early recurrence rates were significantly higher in patients with single HCC, with two or three significant MR imaging findings, compared to those with none (27.9% vs. 12.6%, respectively, p=0.030). CONCLUSIONS A combination of two or more of the following; arterial peritumoral enhancement, non-smooth tumor margin, and peritumoral hypointensity on HBP, can be used as a preoperative imaging biomarker for predicting MVI, with specificity >90%, and is associated with early recurrence after surgery of single HCC. Lay summary: A combination of two or more of the following; arterial peritumoral enhancement, non-smooth tumor margin, and peritumoral hypointensity on hepatobiliary phase, can be used as a preoperative imaging biomarker for predicting microvascular invasion, with specificity >90%, and is associated with early recurrence after curative resection of single HCC.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-Ro, Gangnam-gu, Seoul, Republic of Korea
| | - Seong Hyun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-Ro, Gangnam-gu, Seoul, Republic of Korea.
| | - Ji Eun Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Ilwon-Ro, Gangnam-gu, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 81 Ilwon-Ro, Gangnam-gu, Seoul, Republic of Korea
| | - Cheol Keun Park
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, 81 Ilwon-Ro, Gangnam-gu, Seoul, Republic of Korea
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Lewin SM, Mehta N, Kelley RK, Roberts JP, Yao FY, Brandman D. Liver transplantation recipients with nonalcoholic steatohepatitis have lower risk hepatocellular carcinoma. Liver Transpl 2017; 23:1015-1022. [PMID: 28340509 DOI: 10.1002/lt.24764] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 02/06/2017] [Accepted: 03/02/2017] [Indexed: 12/15/2022]
Abstract
Liver transplantation (LT) is a well-established treatment for hepatocellular carcinoma (HCC) in carefully selected patients. Risk factors for tumors with poor prognostic features on explant have not been well described in a national cohort. We performed a retrospective cohort study of adult LT recipients with HCC transplanted from April 8, 2012 (when explant pathology in United Network for Organ Sharing [UNOS] became available) until September 30, 2014. We evaluated the association between listing diagnosis and other demographic factors with tumor features on explant using logistic regression. High-risk tumor features included the following: > 3 tumors, largest tumor > 5 cm, presence of vascular invasion, presence of metastases, and poor differentiation of tumor. In total, 3733 LT recipients with HCC who had complete explant data in UNOS were included. The median age was 60 years; 78% were male; and 68% were white. Of the primary non-HCC listing diagnoses, 2608 (70%) had hepatitis C virus (HCV); 271 (7%) had nonalcoholic steatohepatitis (NASH); 246 (7%) had alcoholic cirrhosis; and 189 (5%) had hepatitis B virus. Also, 1140 (31%) had evidence of ≥ 1 high-risk explant feature(s). The presence of ≥ 1 high-risk explant feature(s) was associated with HCC recurrence after transplant (odds ratio [OR], 5.00; P < 0.001). Compared with HCV-associated HCC transplant recipients, individuals with NASH had lower likelihood of high-risk explant features (OR, 0.71; P = 0.02) after adjusting for covariables. Women were more likely to have high-risk explant features (OR, 1.23; P = 0.04). Diabetes mellitus (DM) was not associated with high-risk explant features. In conclusion, LT recipients with NASH-associated HCC had fewer high-risk tumor features on explant compared with HCV-associated HCC, despite having higher rates of DM and other potential risk factors for the development of HCC. Women had a higher likelihood of high-risk tumor features. Further study is warranted whether these differences are due to disease-specific or sex-specific influences on tumor biology or due to selection criteria for transplant. Liver Transplantation 23 1015-1022 2017 AASLD.
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Affiliation(s)
- Sara M Lewin
- Department of Medicine, Divisions of Gastroenterology, University of California, San Francisco, San Francisco, CA
| | - Neil Mehta
- Department of Medicine, Divisions of Gastroenterology, University of California, San Francisco, San Francisco, CA
| | - R Kate Kelley
- Hematology/Oncology, University of California, San Francisco, San Francisco, CA
| | - John P Roberts
- Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y Yao
- Department of Medicine, Divisions of Gastroenterology, University of California, San Francisco, San Francisco, CA
| | - Danielle Brandman
- Department of Medicine, Divisions of Gastroenterology, University of California, San Francisco, San Francisco, CA
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shen JY, Li C, Wen TF, Yan LN, Li B, Wang WT, Yang JY, Xu MQ, wen J. Transplantation versus hepatectomy for HCC beyond the Milan criteria: A propensity score analysis. Int J Surg 2017; 44:33-42. [DOI: 10.1016/j.ijsu.2017.05.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Revised: 05/01/2017] [Accepted: 05/15/2017] [Indexed: 01/27/2023]
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Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation. Transplantation 2017; 101:341-349. [PMID: 28121741 PMCID: PMC5265688 DOI: 10.1097/tp.0000000000001524] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background A recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North America (n = 211) had increased risk factors for posttransplant renal insufficiency at study start, relative to patients from Europe and rest of world (eg, worse renal function, more diabetes, older age). Methods A post hoc analysis was performed to assess whether these regional disparities affected study outcomes in North American patients. Results In this subpopulation, estimated glomerular filtration rates at randomization were higher in TAC-C over EVR + rTAC (76.4 vs 69.3 mL/min per 1.73 m2). Mean changes in estimated glomerular filtration rate values (mL/min per 1.73 m2) favored EVR + rTAC over TAC-C at months 12 (+3.7 vs −4.5; P = 0.032), 24 (+2.7 vs −6.6; P = 0.042), and 36 (+4.3 vs −8.1; P = 0.059). The composite efficacy endpoint of treated biopsy-proven acute rejection, graft loss, or death was 10.9%, 14.1%, and 14.1% for EVR + rTAC and 13.1%, 17.2%, and 19.3% for TAC-C at months 12, 24, and 36, respectively. Conclusions Although the North American cohort had more comorbidities, results were consistent with the overall population for efficacy and renal function. In order to reduce nephrotoxicity in liver transplantation, several strategies are being explored including early everolimus-facilitated tacrolimus dose reduction, which in a recent multicenter study led to better kidney function versus standard TAC without compromising efficacy. In this North American cohort sub-analysis, results are similar despite higher baseline comorbidities.
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Hepatocellular carcinoma biology predicts survival outcome after liver transplantation in the USA. Indian J Gastroenterol 2017; 36:117-125. [PMID: 28194604 DOI: 10.1007/s12664-017-0732-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 01/20/2017] [Indexed: 02/04/2023]
Abstract
PURPOSE The aim of this study is to evaluate the clinicopathologic prognostic factors of cancer-specific survival (CSS) in hepatocellular carcinoma (HCC) patients who underwent liver transplantation (LT) stratified by tumor size. METHODS From the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2004-2012), we retrieved data of 570 patients who underwent LT for a solitary primary HCC lesion ≤5 cm. A two multivariable Cox models were constructed to identify prognostic factors of CSS in a two different tumor sizes (2 cm cutoff). RESULTS Out of 570 HCC patients (median age 57 years), 16% had microvascular invasion (MVI) and 12% had a poorly differentiated tumor. Male sex (odds ratio [OR] 2.6), tumor size >2 cm (OR 1.78), elevated AFP (OR 2.31), and poor tumor differentiation (OR 2.59) are significant predictors of MVI. With a median follow up of 41.5 months (range 1-107 months), the 5-year CSS rate was 90% in the absence of MVI compared to 75% in the presence of MVI (p<0.001). Multivariate models revealed that age ≥60 years (hazard ratio [HR] 2.08), MVI (HR 2.26), and poor tumor differentiation (HR 2.42), were significant risk factors of a dismal CSS with HCC size >2 cm, but not with HCC ≤2 cm. CONCLUSIONS Primary HCC tumor size ≤2 cm had an excellent prognosis after LT and was not affect by the presence of MVI or poor tumor differentiation.
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Preoperative Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Prediction of Microvascular Invasion in Small Hepatocellular Carcinoma. J Comput Assist Tomogr 2017; 40:524-30. [PMID: 26966955 DOI: 10.1097/rct.0000000000000405] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES This study aimed to assess the value of preoperative fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) for predicting microvascular invasion (MVI) in small hepatocellular carcinoma (HCC). METHODS We retrospectively examined 60 patients who received F-FDG PET-CT prior to hepatic resection for small HCC (≤30 mm) with subsequent MVI confirmation by histopathology. The associations between PET-positive status and tumor factors were assessed. Furthermore, independent predictors for MVI and diagnostic utility of each MVI predictor were assessed. RESULTS Multivariate analysis revealed the presence of MVI as an independent predictor of PET-positive status (P = 0.023). Maximum standardized uptake value (SUVmax) of 3.2 or greater (P = 0.017) and lens culinaris agglutinin a-reactive α-fetoprotein (AFP-L3) 19% or greater (P = 0.010) were independent predictors of MVI. Areas under the receiver operating characteristic curves for SUVmax of 3.2 or greater, AFP-L3 19% or greater, and both factors combined for predicting MVI were 0.712 (0.493-0.932), 0.755 (0.563-0.947), and 0.856 (0.721-0.991), respectively. The sensitivity and specificity for predicting MVI were 77.8% and 74.5% for SUVmax of 3.2 or greater, 66.7% and 84.3% for AFP-L3 19% or greater, and 88.9% and 82.4% for the combination. CONCLUSIONS F-FDG PET-CT and AFP-L3 may be useful for predicting MVI in small HCC, and the combination of the 2 factors provided reliable assessment for selection of suitable hepatic resection and liver transplantation candidates.
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Charrière B, Maulat C, Suc B, Muscari F. Contribution of alpha-fetoprotein in liver transplantation for hepatocellular carcinoma. World J Hepatol 2016; 8:881-890. [PMID: 27478538 PMCID: PMC4958698 DOI: 10.4254/wjh.v8.i21.881] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Revised: 05/30/2016] [Accepted: 06/29/2016] [Indexed: 02/06/2023] Open
Abstract
Alpha-fetoprotein (AFP) is the main tumor biomarker available for the management of hepatocellular carcinoma (HCC). Although it is neither a good screening test nor an accurate diagnostic tool for HCC, it seems to be a possible prognostic marker. However, its contribution in liver transplantation for HCC has not been fully determined, although its use to predict recurrence after liver transplantation has been underlined by international societies. In an era of organ shortages, it could also have a key role in the selection of patients eligible for liver transplantation. Yet unanswered questions remain. First, the cut-off value of serum AFP above which liver transplantation should not be performed is still a subject of debate. We show that a concentration of 1000 ng/mL could be an exclusion criterion, whereas values of < 15 ng/mL indicate patients with an excellent prognosis whatever the size and number of tumors. Monitoring the dynamics of AFP could also prove useful. However, evidence is lacking regarding the values that should be used. Today, the real input of AFP seems to be its integration into new criteria to select patients eligible for a liver transplantation. These recent tools have associated AFP values with morphological criteria, thus refining pre-existing criteria, such as Milan, University of California, San Francisco, or “up-to-seven”. We provide a review of the different criteria submitted within the past years. Finally, AFP can be used to monitor recurrence after transplantation, although there is little evidence to support this claim. Future challenges will be to draft new international guidelines to implement the use of AFP as a selection tool, and to determine a clear cut-off value above which liver transplantation should not be performed.
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Three-year Outcomes in De Novo Liver Transplant Patients Receiving Everolimus With Reduced Tacrolimus: Follow-Up Results From a Randomized, Multicenter Study. Transplantation 2016; 99:1455-62. [PMID: 26151607 DOI: 10.1097/tp.0000000000000555] [Citation(s) in RCA: 93] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Data are lacking regarding the long-term effect of preemptive conversion to everolimus from calcineurin inhibitors early after liver transplantation to avoid renal deterioration. METHODS In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30 to (i) everolimus + reduced exposure tacrolimus (EVR + Reduced TAC), (ii) everolimus + tacrolimus elimination (TAC Elimination), or (iii) standard exposure tacrolimus (TAC Control). RESULTS Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR) during TAC withdrawal. Of 370 patients who completed the 24-month core study on-treatment, 282 (76.2%) entered an additional 12-month extension phase. The composite efficacy failure endpoint (tBPAR, graft loss or death) occurred in 11.5% of EVR+Reduced TAC patients versus 14.6% TAC Controls from randomization to month 36 (difference, -3.2%; 95% confidence interval, -10.5% to 4.2%; P = 0.334). Treated BPAR occurred in 4.8% versus 9.2% of patients (P = 0.076). From randomization to month 36, mean (SD) estimated glomerular filtration rate decreased by 7.0 (31.3) mL/min per 1.73 m in the EVR+Reduced TAC group, and 15.5 (22.7) mL/min per 1.73 m in the TAC Control group (P = 0.005). Rates of adverse events, serious adverse events, and discontinuation due to adverse events were similar in both groups during the extension. CONCLUSIONS A clinically relevant renal benefit after introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation was maintained to 3 years in patients who continued everolimus therapy to the end of the core study, with comparable efficacy and no late safety concerns.
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Yao FY, Fidelman N, Sibille C, Najimi M, Sokal EM. Reassessing the boundaries of liver transplantation for hepatocellular carcinoma: Where do we stand with tumor down-staging? Hepatology 2016; 63:1014-25. [PMID: 26560491 DOI: 10.1002/hep.28139] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2015] [Accepted: 08/21/2015] [Indexed: 01/06/2023]
Abstract
UNLABELLED Down-staging of hepatocellular carcinoma prior to liver transplantation (LT) has generated a lot of interest in recent years and has been identified in two recent national conferences on hepatocellular carcinoma as one of the priorities for research. Down-staging is defined as reduction in the tumor burden using local regional therapy specifically to meet acceptable criteria for LT. The rationale behind down-staging of tumors initially exceeding conventional criteria for LT is to select a subgroup of tumors with favorable biology and prognosis for LT as assessed by their response to local regional therapy. The expectation is to achieve comparable posttransplant survival between patients who achieve successful tumor down-staging before LT and those whose tumors meet LT criteria at the outset without needing down-staging. The application of tumor down-staging requires a highly structured approach using a treatment protocol that includes five essential components: eligibility criteria, down-staging endpoints, selection of the type of local regional therapy, minimal observation period from successful tumor down-staging to LT, and criteria for treatment failure and exclusion from LT. This review article summarizes published data on down-staging and addresses key questions related to each of the components of the down-staging protocol as well as treatment efficacy. CONCLUSION Based on a review of published data and recommendations from recent national and international conferences on hepatocellular carcinoma and LT, a standardized down-staging protocol is proposed to further evaluate the feasibility and efficacy of applying tumor down-staging on a broader scale.
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Affiliation(s)
- Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA
| | - Nicholas Fidelman
- Division of Interventional Radiology, Department of Radiology, University of California, San Francisco, CA
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Kumar S. Metastatic Recurrent Hepatocellular Carcinoma Post Liver Transplant With Marked Pretransplant Elevation of Alpha Fetoprotein and No Evidence of Primary Neoplasm. EXP CLIN TRANSPLANT 2016; 16:99-102. [PMID: 26789285 DOI: 10.6002/ect.2015.0093] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Determinants of hepatocellular carcinoma recurrence posttransplant include hepatic tumor burden, presence of vascular invasion, and serum alpha-fetoprotein level. However, the significance of marked alpha-fetoprotein elevation in cirrhosis, in the absence of a hepatic mass lesion on imaging studies, is unclear and no longer qualifies for a Model for End-Stage Liver disease exception for transplant listing in the United States. We report a case of posttransplant metastatic recurrent hepatocellular carcinoma in a patient with marked elevation of alpha-fetoprotein pretransplant without imaging evidence of primary hepatic tumor before or after transplant or histopathologic evidence of neoplasm in the explant. This report underscores the significance of marked alpha-fetoprotein elevation in the setting of cirrhosis, even in the absence of a liver lesion, as it may identify a subset of patients with microvascular invasion and microscopic tumor cell dissemination placing them at high risk of posttransplant recurrence. Longer follow-up may be considered in these patients pretransplant to optimize outcomes by lowering posttransplant recurrence risk.
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Affiliation(s)
- Shiva Kumar
- From the Center for Liver Disease and Transplantation, Aurora St. Luke's Medical Center, Milwaukee, Wisconsin, USA, and the Digestive Disease Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
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Schraiber LDS, de Mattos AA, Zanotelli ML, Cantisani GPC, Brandão ABDM, Marroni CA, Kiss G, Ernani L, Marcon PDS. Alpha-fetoprotein Level Predicts Recurrence After Transplantation in Hepatocellular Carcinoma. Medicine (Baltimore) 2016; 95:e2478. [PMID: 26817881 PMCID: PMC4998255 DOI: 10.1097/md.0000000000002478] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplantation. In an attempt to predict their recurrence after liver transplantation, evaluation of tumor number and size, degree of histologic differentiation, and the presence of vascular invasion already have their importance established. In this context, the role of biologic markers such as alpha-fetoprotein (AFP) is still not clear. This retrospective cross-sectional study analyzed the AFP relationship with recurrence of HCC after orthotopic liver transplantation.The current study retrospectively analyzed data from 206 patients with a histopathologic confirmed HCC between 1997 and 2010.The overall survival rates at 1, 3, 5, and 14 years were 78.6%, 65.4%, 60.5%, and 38.7%, respectively. The frequency of recurrence was 15.5%, and recurrence was significantly associated with a lower survival rate (P < 0.001). No association was observed between survival and AFP level (P = 0.153). A correlation, however, was found between tumor recurrence and AFP level (P = 0.002). Univariate analysis of risk factors for recurrence revealed that an AFP level greater than 200 ng/mL, the number of tumors, the degree of cellular differentiation, and the presence of vascular invasion or satellite nodules were associated with relapse. By multivariate analysis, only an AFP level greater than 200 ng/mL remained as a risk factor.Although an elevated AFP level did not correlate with survival in HCC patients undergoing orthotopic liver transplantation, a high AFP level was associated with a 3.32-folds increase in the probability of HCC recurrence.
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Affiliation(s)
- Luciana Dos Santos Schraiber
- From the Department of Gastroenterology and Hepatology, Universidade Federal de Ciências da Saúde (LSS, AADM, ABMB, CAM, LE, PSM) and Santa Casa de Misericórdia, de Porto Alegre, Brazil (MLZ, GPCC, ABMB, CAM, GK)
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38
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Ahn SY, Lee JM, Joo I, Lee ES, Lee SJ, Cheon GJ, Han JK, Choi BI. Prediction of microvascular invasion of hepatocellular carcinoma using gadoxetic acid-enhanced MR and (18)F-FDG PET/CT. ACTA ACUST UNITED AC 2015; 40:843-51. [PMID: 25253426 DOI: 10.1007/s00261-014-0256-0] [Citation(s) in RCA: 95] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE To identify the gadoxetic acid-enhanced MR and the (18)F-fludeoxyglucose (FDG) PET/CT findings associated with microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in patients who are undergoing liver transplantation (LT). METHODS Fifty-one patients with 78 HCCs underwent LT. Preoperative MRI and (18)F-FDG PET/CT findings were retrospectively analyzed and the association of the imaging findings with MVI was assessed. RESULTS Univariate analysis revealed that hypointensity seen on T1WI (OR = 4.329, p = 0.011), peritumoral enhancement (OR = 7.000, p = 0.008), inhomogeneity on arterial phase (OR = 4.321, p = 0.011), delayed phase (OR = 4.519, p = 0.009) or hepatobiliary phase (OR = 3.564, p = 0.032), and the large tumor size (>5 cm) (OR = 12.091, p = 0.001) showed statistically significant associations with MVI. The ratio of tumor maximum standardized uptake value (SUV) to normal liver mean SUV (TSUVmax/LSUVmean) (2.05 ± 1.43 vs. 1.08 ± 0.37) revealed significantly higher value in the MVI-positive group. Multivariate analysis revealed that peritumoral enhancement and a TSUVmax/LSUVmean of 1.2 or greater had a statistically significant association with MVI, with odds ratios of 10.648 (p = 0.016) and 14.218 (p = 0.001), respectively. CONCLUSIONS Preoperative imaging findings such as peritumoral enhancement seen on gadoxetic acid-enhanced MR and a TSUVmax/LSUVmean of 1.2 or more on (18)F-FDG PET/CT, may suggest the presence of MVI in HCC patients.
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Affiliation(s)
- Su Yeon Ahn
- Department of Radiology, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
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39
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Osório FMF, Vidigal PVT, Ferrari TCA, Lima AS, Lauar GM, Couto CA. Histologic Grade and Mitotic Index as Predictors of Microvascular Invasion in Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2015. [PMID: 26221994 DOI: 10.6002/ect.2015.0045] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Microvascular invasion is a well-known risk factor for hepatocellular carcinoma recurrence and mortality after hepatic resection and liver transplant. We sought to determine the clinico-pathological predictive factors associated with microvascular invasion. MATERIALS AND METHODS We studied all patients who had undergone liver transplant because of hepatocellular carcinoma between July 2001 and December 2010 at our institution. Laboratory tests, clinical, and demographic data were obtained. Histopathological hematoxylin and eosin specimens were performed by a single liver pathologist. RESULTS During the study, 107 patients had LT because of HCC and they were selected for this investigation: 76 were men (71%) and 31 women (29%) (mean age, 56.8 ± 8.7 y). It was not possible to retrieve histologic samples from 5 patients; therefore, the final studied analysis was 102 individuals. Tumor recurrence rate was 12.9%. One-, three- and five-year overall survivals were 75.0%, 71.4%, and 67.5%. Mitotic index, histologic grade, tumor architecture, alpha-fetoprotein, and tumor fibrosis were associated with microvascular invasion on univariate analysis. Significant independent predictors of microvascular invasion on logistic regression analysis were histologic grade and mitotic index (P < .001; odds ratio, 3.16; 95% confidence interval, 1.525-4.156, and P = .046; odds ratio, 2.56; 95% confidence interval, 1.061-6.451). CONCLUSIONS Mitotic index and histologic grade are significant predictors of microvascular invasion. No other risk factor was identified in the logistic regression. As both pathological characteristics may be assessed by liver biopsy, these results highlight the importance of discussing pretransplant liver biopsy to access prognosis and define treatment modalities in the setting of liver transplant.
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Affiliation(s)
- Fernanda Maria Farage Osório
- Department of Internal Medicine, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte; and the Alfa Gastroenterology Institute, University Hospital, Federal University of Minas Gerais, Belo Horizonte
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Tanaka T, Kurosaki M, Lilly LB, Izumi N, Sherman M. Identifying candidates with favorable prognosis following liver transplantation for hepatocellular carcinoma: Data mining analysis. J Surg Oncol 2015; 112:72-9. [PMID: 26032085 DOI: 10.1002/jso.23944] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 04/17/2015] [Accepted: 05/13/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES The optimal cutoff of each value in configuring selection criteria for pre-transplant assessment of hepatocellular carcinoma (HCC) remains uncertain. METHODS To build a predictive model for recurrent HCC, we performed data mining analysis on patients who underwent LT for HCC at University Health Network (n = 246). The model was externally validated using a cohort from the Scientific Registry of Transplant Recipients (SRTR) database (n = 9,769). RESULTS Among 246 patients, 14.6% (n = 36) experienced recurrent HCC within 2.5 years post-LT. The risk prediction model for recurrent HCC identified two subgroups with low-risk (total tumor diameter [TTD] <4 cm and serum alpha-fetoprotein [AFP] <73 ng/ml, n = 135) and with high-risk (TTD >4 cm and/or AFP >73 ng/ml, n = 111). The reproducibility of the model was validated through the SRTR database; overall patient survival rate was significantly better in low-risk group than high-risk group (P < 0.0001). Using Cox regression model, this yardstick, not Milan criteria, was revealed to efficiently predict post-transplant survival independent of underlying characteristics (P < 0.0001). CONCLUSIONS Grouping LT candidates with pre-LT HCC by the cutoffs of TTD 4 cm and AFP 73 ng/ml which were unearthed by data mining analysis efficiently classify patients according by the post-transplant prognosis.
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Affiliation(s)
- Tomohiro Tanaka
- Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.,Division of Gastroenterology, University Health Netowrk, University of Toronto, Toronto, Ontario, Canada
| | - Masayuki Kurosaki
- Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
| | - Leslie B Lilly
- Multiorgan Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.,Division of Gastroenterology, University Health Netowrk, University of Toronto, Toronto, Ontario, Canada
| | - Namiki Izumi
- Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino-shi, Tokyo, Japan
| | - Morris Sherman
- Division of Gastroenterology, University Health Netowrk, University of Toronto, Toronto, Ontario, Canada
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41
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2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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Lee S, Kim BK, Kim SU, Park JY, Kim DY, Ahn SH, Han KH. Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib. J Hepatocell Carcinoma 2015; 2:39-47. [PMID: 27508193 PMCID: PMC4918283 DOI: 10.2147/jhc.s79353] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC). We investigated whether the α-fetoprotein (AFP) response is associated with survival in patients with advanced HCC treated with sorafenib. METHODS We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6-8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. RESULTS The median overall survival (OS) and progression-free survival (PFS) were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR) was identified in 5 patients (4.0%), stable disease (SD) in 65 patients (51.6%), and progressive disease (PD) in 57 patients (44.4%), respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response), together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05), and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response), together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05). SD or PR was more frequently found in AFP responders than in non-responders (72.1% vs 47.0%, respectively; P=0.007). In a sub-group with SD, OS (median 12.7 vs 5.8 months, respectively) and PFS (median 9.1 vs 3.7 months, respectively) were significantly longer in AFP responders than in non-responders (all P<0.05). CONCLUSION Early AFP response may be useful for predicting survival in patients with advanced HCC treated with sorafenib.
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Affiliation(s)
- Sangheun Lee
- Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
- Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea
- Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea
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Dubash SR, Idowu OA, Sharma R. The emerging role of positron emission tomography in hepatocellular carcinoma. Hepat Oncol 2015; 2:191-200. [PMID: 30190998 DOI: 10.2217/hep.15.6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. HCC a heterogeneous disease occurring on the background of cirrhosis. The presence of cirrhosis limits the sensitivity of conventional imaging modalities in differentiating HCC from surrounding cirrhotic parenchyma. Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is widely used for assessing a variety of malignancies, however, has poor sensitivity in the evaluation of HCC. This has led to the investigation of other radiotracers such as 11C-acetate and 11C-choline, with improved sensitivity in terms of detection and therapeutic response. In this review, we discuss the emerging field of PET imaging for the detection, staging and assessment of treatment response in HCC. In particular we discuss the role of 18F-FDG-PET in imaging hepatocellular cancer, the limitations of this PET tracer and emerging novel PET tracers being investigated that exploit key metabolic processes including fatty acid and lipid synthesis, choline kinase activity and gene expression.
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Affiliation(s)
- Suraiya R Dubash
- Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.,Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK
| | - Oluwagbemiga A Idowu
- Department of Medical Oncology, Hammersmith Hospital, London, UK.,Department of Medical Oncology, Hammersmith Hospital, London, UK
| | - Rohini Sharma
- Division of Translational & Experimental Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.,Medical Oncology & Clinical Pharmacology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0HS, UK.,Division of Translational & Experimental Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, UK.,Medical Oncology & Clinical Pharmacology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0HS, UK
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Sadykov N, Soyama A, Hidaka M, Kinoshita A, Takatsuki M, Adachi T, Kitasato A, Fujita F, Kuroki T, Eguchi S. Peritoneal recurrence of initially controlled hepatocellular carcinoma after living donor liver transplantation. Case Rep Gastroenterol 2015; 9:29-35. [PMID: 25802495 PMCID: PMC4342861 DOI: 10.1159/000375117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
It is well known that the presence of end-stage liver disease increases the risk of developing hepatocellular carcinoma (HCC). Liver transplantation (LT) for patients within the Milan criteria has become a standard treatment for HCC in most developed centers worldwide. However, a major cause of death in cirrhotic patients with HCC after transplantation is tumor recurrence, including peritoneal recurrences, which develops rarely but presents a significant problem with regard to their management. Our experience includes two cases with HCC within the Milan criteria of peritoneal recurrences after living donor LT. Both patients had interventions for HCC in their medical history before LT, and we propose that these might have been a possible cause of the HCC peritoneal recurrence.
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Affiliation(s)
- Nariman Sadykov
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan ; Department of HPB Surgery, Syzganov's National Scientific Center of Surgery, Almaty, Kazakhstan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Ayaka Kinoshita
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Mitsuhisa Takatsuki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Amane Kitasato
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Fumihiko Fujita
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tamotsu Kuroki
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Senkerikova R, Frankova S, Sperl J, Oliverius M, Kieslichova E, Filipova H, Kautznerova D, Honsova E, Trunecka P, Spicak J. Incidental hepatocellular carcinoma: risk factors and long-term outcome after liver transplantation. Transplant Proc 2015; 46:1426-9. [PMID: 24935308 DOI: 10.1016/j.transproceed.2014.03.010] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2013] [Revised: 03/11/2014] [Accepted: 03/27/2014] [Indexed: 12/26/2022]
Abstract
BACKGROUND Orthotopic liver transplantation (OLT) currently represents the treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively known HCC (pkHCC) is diagnosed via imaging methods before OLT or before HCC is found postoperatively in the liver explant, denoted as incidental HCC (iHCC). The aim of this study was a comprehensive analysis of the post-transplantation survival of patients with iHCC and the identification of risk factors of iHCC occurrence in cirrhotic liver. METHODS We retrospectively reviewed 33 adult cirrhotic patients with incidentally found HCC, comparing them with 606 tumor-free adult cirrhotic patients with end-stage liver disease (group Ci) who underwent OLT in our center from January 1995 to August 2012. Within the same period, a total of 84 patients underwent transplantation for pkHCC. We compared post-transplantation survivals of iHCC, Ci, and pkHCC patients. In the group of cirrhotic patients (Ci + iHCC), we searched for risk factors of iHCC occurrence. RESULTS There was no difference in sex, Model for End-Stage Liver Disease score, and time spent on the waiting list in either group. In the multivariate analysis we identified age >57 years (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.75-8.14; P < .001), hepatitis C virus or alcoholic liver disease (OR, 3.89; 95% CI, 1.42-10.7; P < .001), and alpha-fetoprotein level >6.4 μg/L (OR, 6.65; 95% CI, 2.82-15.7; P = .002) to be independent predictors of iHCC occurrence. Both the 1-, 3-, and 5-year overall survival (OS) and the 1-, 3- and 5-year recurrence-free survival (RFS) differed in iHCC patients compared with the Ci group (iHCC: OS 79%, 72%, and 68%, respectively; RFS 79%, 72%, and 63%, respectively; vs Ci: OS = RFS: 93%, 94%, and 87%, respectively; P < .001). CONCLUSIONS The survival of iHCC patients is worse than in tumor-free cirrhotic patients, but similar to pkHCC patients. The independent risk factors for iHCC occurrence in cirrhotic liver are age, hepatitis C virus, or alcoholic liver disease etiology of liver cirrhosis and alpha-fetoprotein level.
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Affiliation(s)
- R Senkerikova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - S Frankova
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
| | - J Sperl
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - M Oliverius
- Department of Transplant Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - E Kieslichova
- Department of Anesthesiology and Resuscitation, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - H Filipova
- Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - D Kautznerova
- Department of Radiodiagnostic and Interventional Radiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - E Honsova
- Department of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - P Trunecka
- Transplantacenter, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - J Spicak
- Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
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47
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De novo hepatocellular carcinoma of liver allograft: a neglected issue. Cancer Lett 2014; 357:47-54. [PMID: 25444925 DOI: 10.1016/j.canlet.2014.11.032] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 11/13/2014] [Accepted: 11/14/2014] [Indexed: 12/19/2022]
Abstract
De novo hepatocellular carcinoma (HCC) is a rare neoplasm, ensuing after liver transplantation. Its definitive identification requires sophisticated molecular analyses. Hence, some cases, particularly those ensuing in patients who have been transplanted with HCC, are probably misclassified as recurrences of the primary tumor. Nevertheless, a tumor recurrence cannot be excluded in patients transplanted without apparent malignancy, because of an occult HCC. The main risk factor for de novo HCC is the recurrence of hepatitis/cirrhosis in the allograft. All the described de novo HCCs occurred at least 2 years after OLT, whereas most recurrent HCCs develop within 2 years from surgery. The treatment of this tumor can follow the recommendations of guidelines for primary HCC and, unlike recurrent HCC, re-transplant can be considered a therapeutic option for these patients. Prevention of this tumor relies on the prevention/cure of recurrent liver disease in the allograft and on judicious post-transplant immunosuppression. The present review analyzes this topic by addressing seven key questions. An algorithm based on clinical factors - regarding primary and secondary tumors - to trigger the suspicion of de novo origin of a post-transplant HCC is proposed.
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Menon KV, Hakeem AR, Heaton ND. Review article: liver transplantation for hepatocellular carcinoma - a critical appraisal of the current worldwide listing criteria. Aliment Pharmacol Ther 2014; 40:893-902. [PMID: 25155143 DOI: 10.1111/apt.12922] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 01/16/2014] [Accepted: 07/27/2014] [Indexed: 12/08/2022]
Abstract
BACKGROUND Liver transplantation (LT) plays an important role in the management of patients with hepatocellular carcinoma (HCC). Although early results following LT for HCC were poor, since the introduction of the Milan criteria in 1996 morphological criteria have since been well established. Thereafter, various expansions of the Milan criteria were introduced worldwide. Listing criteria for LT for HCC in the United Kingdom (UK) initially conformed to the Milan criteria but were re-defined in 2009 by expansion of the Milan criteria. AIMS To look at the evidence in literature on listing criteria and management of HCC worldwide in comparison with the UK. Secondly, we aim to review worldwide vs. UK literature on prioritisation models, loco-regional therapy protocols and role of alpha-fetoprotein (AFP) in LT for HCC. METHODS An electronic literature search with Medline was carried out to identify articles related to LT for HCC. RESULTS Although various expansions of the Milan criteria have been described, they remain the gold standard against which other criteria are measured. The UK criteria are an expansion of the Milan criteria that go beyond Milan and University of California, San Francisco (UCSF) criteria. The current UK listing criteria for LT for HCC when compared to the worldwide criteria have a worse survival benefit (projected 5-year survival between 35-50%) when plotted on the metroticket calculator. CONCLUSIONS In keeping with most transplant centres worldwide, the UK have adopted expansions to Milan to allow more patients to benefit from LT. However, currently, as it stands the UK criteria when plotted in the modification of the Metroticket model project worse survival that would seem unjustified.
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Affiliation(s)
- K V Menon
- Institute of Liver Studies, Kings College Hospital, London, UK
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Abstract
During the last 5 decades, liver transplantation has witnessed rapid development in terms of both technical and pharmacologic advances. Since their discovery, calcineurin inhibitors (CNIs) have remained the standard of care for immunosuppression therapy in liver transplantation, improving both patient and graft survival. However, adverse events, particularly posttransplant nephrotoxicity, associated with long-term CNI use have necessitated the development of alternate treatment approaches. These include combination therapy with a CNI and the inosine monophosphate dehydrogenase inhibitor mycophenolic acid and use of mammalian target of rapamycin (mTOR) inhibitors. Everolimus, a 40-O-(2-hydroxyethyl) derivative of mTOR inhibitor sirolimus, has a distinct pharmacokinetic profile. Several studies have assessed the role of everolimus in liver transplant recipients in combination with CNI reduction or as a CNI withdrawal strategy. The efficacy of everolimus-based immunosuppressive therapy has been demonstrated in both de novo and maintenance liver transplant recipients. A pivotal study in 719 de novo liver transplant recipients formed the basis of the recent approval of everolimus in combination with steroids and reduced-dose tacrolimus in liver transplantation. In this study, everolimus introduced at 30 days posttransplantation in combination with reduced-dose tacrolimus (exposure reduced by 39%) showed comparable efficacy (composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, or death) and achieved superior renal function as early as month 1 and maintained it over 2 years versus standard exposure tacrolimus. This review provides an overview of the efficacy and safety of everolimus-based regimens in liver transplantation in the de novo and maintenance settings, as well as in special populations such as patients with hepatocellular carcinoma recurrence, hepatitis C virus-positive patients, and pediatric transplant recipients. We also provide an overview of ongoing studies and discuss potential expansion of the role for everolimus in these settings.
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Affiliation(s)
| | - Jörg-Matthias Pollok
- Department of General, Visceral, Thoracic, and Vascular Surgery, University of Bonn, Bonn, Germany
| | | | - Guido Junge
- Integrated Hospital Care, Novartis Pharma AG, Basel, Switzerland
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Teng F, Wang GH, Tao YF, Guo WY, Wang ZX, Ding GS, Shi XM, Fu ZR. Criteria-specific long-term survival prediction model for hepatocellular carcinoma patients after liver transplantation. World J Gastroenterol 2014; 20:10900-10907. [PMID: 25152592 PMCID: PMC4138469 DOI: 10.3748/wjg.v20.i31.10900] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 03/06/2014] [Accepted: 05/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish a model to predict long-term survival of hepatocellular carcinoma (HCC) patients after liver transplantation (MHCAT).
METHODS: Two hundred and twenty-three patients with HCC were followed for at least six years to identify independent risk factors for long-term survival after liver transplantation (LT). The criteria for HCC liver transplantation included the Milan, University of California San Francisco, Hangzhou and Shanghai Fudan criteria. The Cox regression model was used to build MHCAT specifying these criteria. A survival analysis was carried out for patients with high or low risk.
RESULTS: The one-, three- and five-year cumulative survival of HCC patients after LT was 78.9%, 53.2% and 46.4%, respectively. Of the HCC patients, the proportion meeting the Hangzhou and Fudan criteria was significantly higher than the proportion meeting the Milan criteria (64.6% vs 39.5%, 52.0% vs 39.5%, P < 0.05). Moreover, the proportion meeting the Hangzhou criteria was also significantly higher than the proportion meeting other criteria (P < 0.01). Pre-operative alfa-fetoprotein level, intraoperative blood loss and retransplantation were common significant predictors of long-term survival in HCC patients with reference to the Milan, University of California San Francisco and Fudan criteria, whereas in MHCAT based on the Hangzhou criteria, total bilirubin, intraoperative blood loss and retransplantation were independent predictors. The c-statistic for MHCAT was 0.773-0.824, with no statistical difference among these four criteria. According to the MHCAT scoring system, patients with low risk showed a higher five-year survival than those with high risk (P < 0.001).
CONCLUSION: MHCAT can effectively predict long-term survival for HCC patients, but needs to be verified by multi-center retrospective or randomized controlled trials.
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