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1
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Di Marco L, Romanzi A, Pivetti A, De Maria N, Ravaioli F, Salati M, Villa E, Di Benedetto F, Magistri P, Dominici M, Colecchia A, Di Sandro S, Spallanzani A. Suppressing, stimulating and/or inhibiting: The evolving management of HCC patient after liver transplantation. Crit Rev Oncol Hematol 2025; 207:104607. [PMID: 39725094 DOI: 10.1016/j.critrevonc.2024.104607] [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: 05/23/2024] [Revised: 12/20/2024] [Accepted: 12/22/2024] [Indexed: 12/28/2024] Open
Abstract
Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R_LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R_LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R_LT, and the clinical issues regarding the innovative management of this patient population.
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Affiliation(s)
- Lorenza Di Marco
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy; Department of Biomedical, Metabolic and Neural Sciences, Clinical and Experimental Medicine Program, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Adriana Romanzi
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Alessandra Pivetti
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Nicola De Maria
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Federico Ravaioli
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna 40138, Italy.
| | - Massimiliano Salati
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Erica Villa
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy; National Institute of Gastroenterology IRCCS "Saverio de Bellis", Research Hospital, Castellana Grotte 70013, Italy.
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Massimo Dominici
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
| | - Antonio Colecchia
- Chimomo Department, Gastroenterology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Stefano Di Sandro
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41125, Italy.
| | - Andrea Spallanzani
- Department of Oncology and Hematology, Oncology Unit, University Hospital of Modena and Reggio Emilia, University of Modena and Reggio Emilia, Modena 41124, Italy.
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2
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Mauro E, Sanduzzi-Zamparelli M, Jutras G, Garcia R, Soler Perromat A, Llarch N, Holguin Arce V, Ruiz P, Rimola J, Lopez E, Ferrer-Fàbrega J, García-Criado Á, Colmenero J, Lai JC, Forner A. Challenges in Liver Transplantation for Hepatocellular Carcinoma: A Review of Current Controversies. Cancers (Basel) 2024; 16:3059. [PMID: 39272917 PMCID: PMC11394545 DOI: 10.3390/cancers16173059] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/15/2024] Open
Abstract
Liver transplantation (LT) remains one of the most effective treatments for hepatocellular carcinoma (HCC) and significantly enhances patient survival. However, the application of LT for HCC faces challenges owing to advancements in cancer-specific treatment modalities and the increased burden of patients' comorbidities. This narrative review explores current controversies and advancements in LT for HCC. Key areas of focus include the management of comorbidities and patient education by advanced practice nurses, impacts of frailty on waitlists and post-LT outcomes, selection criteria for LT in the era of new downstaging tools, role of radiology in patient selection, and implications of potential immunotherapy use both before and after LT. Additionally, the importance of immunosuppression management with strategies aimed at minimizing rejection while considering the risk of HCC recurrence and the role of surveillance for HCC recurrence is highlighted. This review also underscores the importance of a multidisciplinary approach for optimizing outcomes in patients with HCC undergoing LT.
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Affiliation(s)
- Ezequiel Mauro
- Liver Oncology Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Marco Sanduzzi-Zamparelli
- Liver Oncology Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Gabrielle Jutras
- Department of Medicine, Division of Hepatology, Centre Hospitalier de l'Université de Montréal, Montreal, QC H2X 3E4, Canada
| | - Raquel Garcia
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08007 Barcelona, Spain
| | - Alexandre Soler Perromat
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, IDIBAPS, 08036 Barcelona, Spain
| | - Neus Llarch
- Liver Oncology Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Victor Holguin Arce
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Pablo Ruiz
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08007 Barcelona, Spain
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, IDIBAPS, 08036 Barcelona, Spain
| | - Eva Lopez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08007 Barcelona, Spain
- Universidad Jaume I, 12006 Castellón de la Plana, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- University of Barcelona, 08007 Barcelona, Spain
| | - Ángeles García-Criado
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, IDIBAPS, 08036 Barcelona, Spain
- University of Barcelona, 08007 Barcelona, Spain
| | - Jordi Colmenero
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08007 Barcelona, Spain
- University of Barcelona, 08007 Barcelona, Spain
| | - Jennifer C Lai
- Departament of Medicine, Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA 94115, USA
| | - Alejandro Forner
- Liver Oncology Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- University of Barcelona, 08007 Barcelona, Spain
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Akabane M, Esquivel CO, Kim WR, Sasaki K. The Future Frontier of Liver Transplantation Exploring Young Donor Allocation Strategies for HCC Recipients. Transplant Direct 2024; 10:e1657. [PMID: 38881743 PMCID: PMC11177833 DOI: 10.1097/txd.0000000000001657] [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: 01/22/2024] [Revised: 02/21/2024] [Accepted: 02/23/2024] [Indexed: 06/18/2024] Open
Abstract
Background The role of donor age in liver transplantation (LT) outcomes for hepatocellular carcinoma (HCC) is controversial. Given the significant risk of HCC recurrence post-LT, optimizing donor/recipient matching is crucial. This study reassesses the impact of young donors on LT outcomes in patients with HCC. Methods A retrospective review of 11 704 LT cases from the United Network for Organ Sharing database (2012-2021) was conducted. The study focused on the effect of donor age on recurrence-free survival, using hazard associated with LT for HCC (HALT-HCC) and Metroticket 2.0 scores to evaluate post-LT survival in patients with HCC. Results Of 4706 cases with young donors, 11.0% had HCC recurrence or death within 2 y, and 18.3% within 5 y. These outcomes were comparable with those of non-young donors. A significant correlation between donor age and post-LT recurrence or mortality (P = 0.04) was observed, which became statistically insignificant after tumor-related adjustments (P = 0.32). The Kaplan-Meier curve showed that recipients with lower HALT-HCC scores (<9) and Metroticket 2.0 scores (<2.2) significantly benefited from young donors, unlike those exceeding these score thresholds. Cox regression analysis showed that donor age significantly influenced outcomes in recipients below certain score thresholds but was less impactful for higher scores. Conclusions Young donors are particularly beneficial for LT recipients with less aggressive HCC, as indicated by their HALT-HCC and Metroticket 2.0 scores. These findings suggest strategically allocating young donors to recipients with less aggressive tumor profiles, which could foster more efficient use of the scarce donor supply and potentially enhance post-LT outcomes.
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Affiliation(s)
- Miho Akabane
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - Carlos O Esquivel
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
| | - W Ray Kim
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Stanford, CA
| | - Kazunari Sasaki
- Division of Abdominal Transplant, Department of Surgery, Stanford University Medical Center, Stanford, CA
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Marrone G, Leone MS, Biolato M, Liguori A, Bianco G, Spoletini G, Gasbarrini A, Miele L, Pompili M. Therapeutic Approach to Post-Transplant Recurrence of Hepatocellular Carcinoma: Certainties and Open Issues. Cancers (Basel) 2023; 15:5593. [PMID: 38067299 PMCID: PMC10705300 DOI: 10.3390/cancers15235593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/03/2023] [Accepted: 11/18/2023] [Indexed: 01/12/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a growing indication for liver transplantation (LT). Careful candidate selection is a prerequisite to keep post-LT recurrence rates within acceptable percentages. In the pre-LT period, various types of locoregional treatments and/or systemic therapies can be used for bridging or downstaging purposes. In this context, one of the factors limiting the possibility of treatment is the degree of functional liver impairment. In the LT subject, no widely accepted indications are available to guide treatment of disease recurrence and heterogeneity exists between transplant centers. Improved liver function post LT makes multiple therapeutic strategies theoretically feasible, but patient management is complicated by the need to adjust immunosuppressive therapy and to assess potential toxicities and drug-drug interactions. Finally, there is controversy and uncertainty about the use of recently introduced immunotherapeutic drugs, mainly due to the risk of organ rejection. In this paper, we will review the most recent available literature on the management of post-transplant HCC recurrence, discussing evidence and controversies.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Maurizio Pompili
- Medical and Surgical Sciences Department, Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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Li J, Yang F, Li J, Huang ZY, Cheng Q, Zhang EL. Postoperative adjuvant therapy for hepatocellular carcinoma with microvascular invasion. World J Gastrointest Surg 2023; 15:19-31. [PMID: 36741072 PMCID: PMC9896490 DOI: 10.4240/wjgs.v15.i1.19] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/29/2022] [Accepted: 12/21/2022] [Indexed: 01/17/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal tumors in the world. Liver resection (LR) and liver transplantation (LT) are widely considered as radical treatments for early HCC. However, the recurrence rates after curative treatment are still high and overall survival is unsatisfactory. Microvascular invasion (MVI) is considered to be one of the important prognostic factors affecting postoperative recurrence and long-term survival. Unfortunately, whether HCC patients with MVI should receive postoperative adjuvant therapy remains unknown. In this review, we summarize the therapeutic effects of transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, tyrosine protein kinase inhibitor-based targeted therapy, and immune checkpoint inhibitors in patients with MVI after LR or LT, aiming to provide a reference for the best adjuvant treatment strategy for HCC patients with MVI after LT or LR.
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Affiliation(s)
- Jiang Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, College of Medicine, Shihezi University, Shihezi 832000, Xinjiang Uygur Autonomous Regions, China
| | - Fan Yang
- Department of General Surgery, Affiliated Hospital of Hubei Minzu University, Enshi 445000, Hubei Province, China
| | - Jian Li
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Qi Cheng
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Sposito C, Citterio D, Virdis M, Battiston C, Droz Dit Busset M, Flores M, Mazzaferro V. Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma. World J Gastroenterol 2022; 28:4929-4942. [PMID: 36160651 PMCID: PMC9494935 DOI: 10.3748/wjg.v28.i34.4929] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 03/05/2022] [Accepted: 07/26/2022] [Indexed: 02/06/2023] Open
Abstract
Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2–3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1–2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.
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Affiliation(s)
- Carlo Sposito
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Matteo Virdis
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Carlo Battiston
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Michele Droz Dit Busset
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Maria Flores
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20100, Italy
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7
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Parente A, Flores Carvalho M, Eden J, Dutkowski P, Schlegel A. Mitochondria and Cancer Recurrence after Liver Transplantation-What Is the Benefit of Machine Perfusion? Int J Mol Sci 2022; 23:9747. [PMID: 36077144 PMCID: PMC9456431 DOI: 10.3390/ijms23179747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/23/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
Tumor recurrence after liver transplantation has been linked to multiple factors, including the recipient's tumor burden, donor factors, and ischemia-reperfusion injury (IRI). The increasing number of livers accepted from extended criteria donors has forced the transplant community to push the development of dynamic perfusion strategies. The reason behind this progress is the urgent need to reduce the clinical consequences of IRI. Two concepts appear most beneficial and include either the avoidance of ischemia, e.g., the replacement of cold storage by machine perfusion, or secondly, an endischemic organ improvement through perfusion in the recipient center prior to implantation. While several concepts, including normothermic perfusion, were found to reduce recipient transaminase levels and early allograft dysfunction, hypothermic oxygenated perfusion also reduced IRI-associated post-transplant complications and costs. With the impact on mitochondrial injury and subsequent less IRI-inflammation, this endischemic perfusion was also found to reduce the recurrence of hepatocellular carcinoma after liver transplantation. Firstly, this article highlights the contributing factors to tumor recurrence, including the surgical and medical tissue trauma and underlying mechanisms of IRI-associated inflammation. Secondly, it focuses on the role of mitochondria and associated interventions to reduce cancer recurrence. Finally, the role of machine perfusion technology as a delivery tool and as an individual treatment is discussed together with the currently available clinical studies.
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Affiliation(s)
- Alessandro Parente
- The Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham B15 2GW, UK
| | - Mauricio Flores Carvalho
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
| | - Janina Eden
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
| | - Andrea Schlegel
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
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8
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Utilization of elderly donors in liver transplantation for patients with hepatocellular carcinoma: A national retrospective cohort study of China. Int J Surg 2022; 105:106839. [PMID: 35987333 DOI: 10.1016/j.ijsu.2022.106839] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 08/07/2022] [Accepted: 08/11/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Profound organ shortages worldwide have led to the increased utilization of marginal organs from older individuals. However, the effectiveness of liver transplantation (LT) with organs from elderly donors for patients with hepatocellular carcinoma (HCC) remains controversial. The objective of the current study was to assess the overall survival (OS) and disease-free survival (DFS) of patients with HCC following LT using grafts from deceased donors over 60 years old. MATERIAL AND METHODS Patients with HCC who underwent LT between 2015 and 2018 were identified in the China Liver Transplant Registry database. The overall survival and disease-free survival of older liver donors (OLDs) were compared with those of younger liver donors (YLDs) after propensity score matching. RESULTS From January 2015 to December 2018, a total of 4971 HCC patients were enrolled in the study according to the screening criteria. The absolute and relative utilization of liver grafts from elderly patients over 60 years for HCC patients increased every year, from 65 (9.3%) in 2015 to 268 (14.5%) in 2018. Disease-free survival (DFS) was significantly lower in HCC patients with elderly donors (both P < 0.05) after propensity score matching. The OLD group had worse DFS than YLD group if patients had tumors beyond the Milan criteria (P < 0.05). CONCLUSIONS The use of older donors for LT has been growing quickly in the last few years in China. Grafts from older donors can be safely used in HCC recipients with similar OS and comparable perioperative complications. However, further investigation into whether older donor has an impact on recurrence is warranted, especially among those with tumors beyond the Milan criteria.
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9
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Zucchetta P, Lacognata C, Girardi F, Spimpolo A, Crimì F, Cabrelle G, Zanon C, Boccagni P, Evangelista L, Cecchin D, Cillo U. [18F]FDG PET/MRI in the follow-up of hepatocellular carcinoma after liver transplantation. Nucl Med Commun 2022; 43:359-367. [PMID: 35019883 PMCID: PMC9897275 DOI: 10.1097/mnm.0000000000001518] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 11/24/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND There is limited evidence regarding the application of [18F] fluorodeoxyglucose (FDG)-PET/MRI in patients with a suspected clinical recurrence, who underwent liver transplantation for hepatocellular carcinoma (HCC). Therefore, we compared the accuracy of PET/MR and standard-of-care (SOC) imaging in these patients. METHODS We retrospectively reviewed 26 patients, whose liver were transplanted for HCC and were suspected of disease relapse based on biochemical analysis or SOC follow-up imaging, and carried out PET/MRI with diffusion-weighted imaging sequences on them. All patients underwent SOC imaging within the 2 months prior to the PET/MRI examination and had follow-up data for at least 12 months after. Reference standards were histopathology, clinical and imaging follow-up data. RESULTS Sensitivity, specificity, positive predictive value, negative predictive value and accuracy for PET/MRI were 100, 94, 91, 100 and 96%, whereas for SOC imaging were 80, 69, 61, 85 and 73%. The accuracy of PET/MRI was higher with respect to SOC imaging, although not significantly. CONCLUSIONS PET/MRI is useful for oncological surveillance of patients who have undergone liver transplantation for HCC, particularly in cases of allergy to contrast media, renal failure or persistently elevated alpha-fetoprotein levels, and with no identification of metastatic/relapsing foci at standard-of-care imaging.
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Affiliation(s)
- Pietro Zucchetta
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | | | - Francesca Girardi
- Medicina Nucleare, Dipartimento di Diagnostica per Immagini, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste
| | | | | | | | | | - Patrizia Boccagni
- Department of Surgery, Hepatobiliary Surgery and Liver Transplant Center, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
| | - Laura Evangelista
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | - Diego Cecchin
- Department of Medicine – DIMED, Nuclear Medicine Unit, University of Padua
| | - Umberto Cillo
- Department of Surgery, Hepatobiliary Surgery and Liver Transplant Center, Oncology and Gastroenterology (DISCOG), University of Padua, Padua, Italy
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10
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Cusumano C, De Carlis L, Centonze L, Lesourd R, Levi Sandri GB, Lauterio A, De Carlis R, Ferla F, Di Sandro S, Camus C, Jézéquel C, Bardou-Jacquet E, Rayar M. Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two-centre analysis using competing risk analysis. Transpl Int 2021; 34:1948-1958. [PMID: 34145653 DOI: 10.1111/tri.13950] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 04/15/2021] [Accepted: 04/22/2021] [Indexed: 12/30/2022]
Abstract
The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65 years and < or ≥80 years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow-up of 86 months were analysed. The 1-, 3- and 5-year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P < 0.01), number of lesions (sHR: 1.05 [1.04; 1.06], P < 0.001), maximum size of the lesions (sHR: 1.37 [1.27; 1.48], P < 0.01), presence of a hepatocholangiocarcinoma (sHR: 6.47 [2.91; 14.38], P < 0.01) and microvascular invasion (sHR: 3.48 [2.42; 5.02], P < 0.01) were significantly associated with HCC recurrence. After propensity score matching, neither donor age ≥65 (P = 0.29) nor donor age ≥80 (P = 0.84) years increased the risk of HCC recurrence. In conclusion, donor age was not found to be a risk factor for HCC recurrence. Patients listed for HCC can receive a graft from an elderly donor without compromising the outcome.
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Affiliation(s)
- Caterina Cusumano
- Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Leonardo Centonze
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Romain Lesourd
- Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France
- Faculté de médecine, Université Rennes1, Rennes, France
| | | | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Riccardo De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Fabio Ferla
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Stefano Di Sandro
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Christophe Camus
- Service de Maladies Infectieuses et Réanimation Médicale, CHU Rennes, Rennes, France
- CIC 1414, INSERM, Rennes, France
| | | | - Edouard Bardou-Jacquet
- Faculté de médecine, Université Rennes1, Rennes, France
- Service des Maladies du foie, CHU Rennes, Rennes, France
| | - Michel Rayar
- Service de Chirurgie Hépatobiliaire et Digestive, CHU Rennes, Rennes, France
- Faculté de médecine, Université Rennes1, Rennes, France
- CIC 1414, INSERM, Rennes, France
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11
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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12
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Surveillance for HCC After Liver Transplantation: Increased Monitoring May Yield Aggressive Treatment Options and Improved Postrecurrence Survival. Transplantation 2021; 104:2105-2112. [PMID: 31972705 DOI: 10.1097/tp.0000000000003117] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Currently, no surveillance guidelines for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) exist. In this retrospective, multicenter study, we have investigated the role of surveillance imaging on postrecurrence outcomes. METHODS Patients with recurrent HCC after LT from 2002 to 2016 were reviewed from 3 transplant centers (University of California San Francisco, Mayo Clinic Florida, and University of Toronto). For this study, we proposed the term cumulative exposure to surveillance (CETS) as a way to define the cumulative sum of all the protected intervals that each surveillance test provides. In our analysis, CETS has been treated as a continuous variable in months. RESULTS Two hundred twenty-three patients from 3 centers had recurrent HCC post-LT. The median follow-up was 31.3 months, and median time to recurrence was 13.3 months. Increasing CETS was associated with improved postrecurrence survival (hazard ratio, 0.94; P < 0.01) as was treatment of recurrence with resection or ablation (hazard ratio, 0.31; P < 0.001). An receiver operating characteristic curve (area under the curve, 0.64) for CETS covariate showed that 252 days of coverage (or 3 surveillance scans) within the first 24 months provided the highest probability for aggressive postrecurrence treatment. CONCLUSIONS In this review of 223 patients with post-LT HCC recurrence, we found that increasing CETS does lead to improved postrecurrence survival as well as a higher probability for aggressive recurrence treatment. We found that 252 days of monitoring (ie, 3 surveillance scans) in the first 24 months was associated with the ability to offer potentially curative treatment.
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Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managing recurrence for patients undergoing LT for HCC. AREAS COVERED In this review, we will provide an overview of methods of patient risk stratification in the post-transplant period, the data around surveillance for HCC recurrence, and the evidence for and against post-LT adjuvant treatment strategies. Finally, we will provide data regarding treatment options for patients with HCC recurrence after LT. Using an extensive search of original papers and society guidelines, this paper provides a comprehensive review of the data for assessing risk and managing recurrence for patients undergoing LT for HCC. EXPERT OPINION The development of multiple post-transplant prognostic scoring systems have allowed for improved assessment of recurrence risk and stratification of patients. However, the ability to translate this information into surveillance and therapeutic strategies that improve patient outcomes still have to be fully demonstrated. Post-LT immunosuppression strategies have been implemented in order to attempt to reduce this risk. Evidence-based strategies for managing recurrent HCC are evolving. We expect that with further understanding of individual patient characteristics will allow for optimal therapeutic selection.
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Affiliation(s)
- Daniel Hoffman
- Department of Surgery, University of California , San Francisco, CA, USA
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California , San Francisco, CA, USA
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14
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A National Survey of Hepatocellular Carcinoma Surveillance Practices Following Liver Transplantation. Transplant Direct 2020; 7:e638. [PMID: 33324743 PMCID: PMC7725259 DOI: 10.1097/txd.0000000000001086] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/24/2020] [Accepted: 09/25/2020] [Indexed: 12/13/2022] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) is an important predictor of survival after liver transplantation (LT). Recent studies show that early diagnosis, aggressive treatment, and surveillance may improve outcomes after HCC recurrence. We sought to determine the current practices and policies regarding surveillance for HCC recurrence after LT. Methods We conducted a web-based national survey of adult liver transplant centers in the United States to capture center-specific details of HCC surveillance post-LT. Responses were analyzed to generate numerical and graphical summaries. Results Of 101 eligible adult liver transplant centers, 48 (48%) centers across the United States responded to the survey. Among the participating centers, 79% stratified transplant recipients for HCC recurrence risk, while 19% did not have any risk stratification protocol. Explant microvascular invasion (mVI) was the most common factor used in risk stratification. Use of pretransplant serum biomarkers such as alpha-fetoprotein (AFP) was variable, with only 48% of the participating centers reporting specific "cutoff" values. While a majority of centers (88%) reported having a routine imaging protocol for HCC recurrence surveillance, there was considerable heterogeneity in terms of frequency and duration of such surveillance. Of the centers that did risk stratify patients to identify those at higher risk of HCC recurrence, about 50% did not change their surveillance protocol. Conclusions Our study affirms significant variability in center practices, and our results reflect the need for high-quality studies to guide risk stratification and surveillance for HCC recurrence.
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15
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Al-Ameri AAM, Wei X, Wen X, Wei Q, Guo H, Zheng S, Xu X. Systematic review: risk prediction models for recurrence of hepatocellular carcinoma after liver transplantation. Transpl Int 2020; 33:697-712. [PMID: 31985857 DOI: 10.1111/tri.13585] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/10/2019] [Accepted: 01/21/2020] [Indexed: 12/17/2022]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a significant clinical problem associated with poor surgical outcomes. This study aims to summarize the current evidence on risk prediction models of HCC recurrence after LT. PubMed and EMBASE were searched to May 25, 2019, for relevant articles. Studies originally designed to develop or validate a risk prediction model for HCC recurrence after LT were included. Two independent authors summarized the study characteristics and evaluated the risk of bias and applicability concerns in the included studies. From 26 included studies, 18 original risk prediction models were determined, but only five models were externally validated. The average number of predictors involved in the construction of risk models was three. The most frequently employed predictors were alpha-fetoprotein, tumor size, vascular invasion, tumor number, tumor differentiation, and neutrophil-lymphocyte ratio. Most studies showed good discriminatory performance (AUC >0.75). The overall quality of the included studies was generally low. Most of the original models lacked the highly recommended external and prospective validation in diverse populations. The AFP model was the well-validated preoperative risk model that can stratify patients into high- and low-risk groups.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xue Wen
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Haijun Guo
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
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16
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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: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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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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17
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Diniz PHC, Silva SDDC, Faria LC, Vidigal PVT, Ferrari TCDA. Clinical and laboratory parameters as predictors of long-term outcome according to the etiology of underlying chronic liver disease in patients who underwent liver transplantation for hepatocellular carcinoma treatment. Clinics (Sao Paulo) 2020; 75:e1529. [PMID: 32520221 PMCID: PMC7247738 DOI: 10.6061/clinics/2020/e1529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 02/14/2020] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVES This study aimed to analyze clinical and laboratory parameters and their association with long-term outcomes in patients who underwent liver transplantation for hepatocellular carcinoma treatment, according to the etiology of the underlying chronic liver disease, in order to identify predictors of response to this therapeutic modality. METHODS Demographic, clinical, and laboratory data from a cohort of 134 patients who underwent orthotopic liver transplantation for hepatocellular carcinoma treatment at a referral center in Brazil were retrospectively selected and compared according to the etiologic group of the underlying chronic liver disease. Events, defined as tumor recurrence or death from any cause, and event-free survival were also analyzed, and multivariate analysis was performed. RESULTS The etiologies comprised hepatitis C and B virus infection, alcohol abuse, and cryptogenic disorder. Although liver transplantation was performed outside the Milan criteria in 33.3% of the subjects, according to pathologic examination of the explanted liver, the Model for End-Stage Liver Disease score was low (<22) in most patients (70.6%) and recurrence was identified in only 10 (7.9%) patients. Events occurred in 37 patients (28.5%), and the median event-free survival was 75 months (range, 24-116 months). No difference among etiologic groups was found in the parameters analyzed, which were not independently associated with outcome. CONCLUSION Clinical and laboratory characteristics according to etiologic groups were not different, which might have led to comparable long-term outcomes among these patient groups and failure to identify predictors that could aid in better selection of subjects for liver transplantation in the management of this cancer.
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Affiliation(s)
- Paulo Henrique Costa Diniz
- Servico de Oncologia, Hospital das Clinicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BR
- *Corresponding author. E-mail:
| | | | - Luciana Costa Faria
- Departamento de Clinica Medica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BR
| | - Paula Vieira Teixeira Vidigal
- Departamento de Anatomia Patologica e Medicina Legal, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BR
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18
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Al-Ameri AAM, Wei X, Lin L, Shao Z, Guo H, Xie H, Zhou L, Zheng S, Xu X. Preoperative risk stratification for early recurrence of HBV-related hepatocellular carcinoma after deceased donor liver transplantation: a five-eight model development and validation. BMC Cancer 2019; 19:1136. [PMID: 31752756 PMCID: PMC6873730 DOI: 10.1186/s12885-019-6343-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
Background Early recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is associated with poor surgical outcomes. This study aims to construct a preoperative model to predict individual risk of post-LT HCC recurrence. Methods Data of 748 adult patients who underwent deceased donor LT for HCC between January 2015, and February 2019 were collected retrospectively from the China Liver Transplant Registry database and randomly divided into training (n = 486) and validation(n = 262) cohorts. A multivariate analysis was performed and the five-eight model was developed. Results A total of 748 patients were included in the study; of them, 96% had hepatitis B virus (HBV) and 84% had cirrhosis. Pre-LT serum alpha-fetoprotein (AFP), tumor number and largest tumor diameter were incorporated to construct the 5–8 model which can stratify patients accurately according to their risk of recurrence into three prognostic subgroups; low-(0–5 points), medium-(6–8 points) and high-risk (> 8 points) with 2-year post-LT recurrence rate of (5,20 and 51%,p < 0.001) respectively. The 5–8 model was better than Milan, Hangzhou, and AFP-model for prediction of HCC early recurrence. These findings were confirmed by the results of the validation cohort. Conclusions The 5–8 model is a simple validated and accurate tool for preoperative stratification of early recurrence of HCC after LT.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Lidan Lin
- China Liver Transplant Registry, Hangzhou, China
| | - Zhou Shao
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Haijun Guo
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Haiyang Xie
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Lin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China.,China Liver Transplant Registry, Hangzhou, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine; Institution of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China. .,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, Zhejiang Province, China. .,China Liver Transplant Registry, Hangzhou, China.
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19
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A Point-based Histologic Scoring System for Hepatocellular Carcinoma Can Stratify Risk of Posttransplant Tumor Recurrence. Am J Surg Pathol 2019; 42:855-865. [PMID: 29649017 DOI: 10.1097/pas.0000000000001053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eligibility for liver transplant is most commonly decided by measuring tumor size and number on radiographic imaging. However, this method often underestimates the extent of disease. Evaluation of tumor histology has been shown to improve risk stratification when compared with imaging-based transplant criteria, but the World Health Organization (WHO) guidelines for grading hepatocellular carcinoma (HCC) are imprecise and require subjective interpretation by the pathologist. We performed a retrospective analysis of 190 explanted livers containing HCC and correlated histologic features with posttransplant recurrence to formulate a three-tiered, point-based scoring system that categorizes tumors as having a low, intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score (RRAS) evaluates tumor architecture and specific cytologic features-nuclear pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing superior stratification of HCC recurrence risk compared with imaging criteria and grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the rate of recurrence after transplant was 0% among low-risk tumors (compared with 3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared with 15% of moderately differentiated tumors), and 54% among high-risk tumors (compared with 29% of poorly differentiated tumors). Receiver operating characteristic analysis shows significantly improved performance of RRAS criteria in predicting HCC recurrence compared with WHO grade (area under curve of 0.841 and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor histology offers superior prediction of recurrence risk following liver transplantation compared with radiographic criteria, and that the RRAS system better stratifies recurrence risk compared with HCC grading by WHO methodology.
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20
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Filgueira NA. Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation. World J Hepatol 2019; 11:261-272. [PMID: 30967904 PMCID: PMC6447422 DOI: 10.4254/wjh.v11.i3.261] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/06/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the best treatment option for cirrhotic patients with early-stage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases, despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein (AFP) levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated. Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.
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Affiliation(s)
- Norma Arteiro Filgueira
- Department of Internal Medicine, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
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Ling Q, Liu J, Zhuo J, Zhuang R, Huang H, He X, Xu X, Zheng S. Development of models to predict early post-transplant recurrence of hepatocellular carcinoma that also integrate the quality and characteristics of the liver graft: A national registry study in China. Surgery 2018; 164:S0039-6060(18)30079-5. [PMID: 29709370 DOI: 10.1016/j.surg.2018.01.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 01/11/2018] [Accepted: 01/29/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Donor characteristics and graft quality were recently reported to play an important role in the recurrence of hepatocellular carcinoma after liver transplantation. Our aim was to establish a prognostic model by using both donor and recipient variables. METHODS Data of 1,010 adult patients (training/validation: 2/1) undergoing primary liver transplantation for hepatocellular carcinoma were extracted from the China Liver Transplant Registry database and analyzed retrospectively. A multivariate competing risk regression model was developed and used to generate a nomogram predicting the likelihood of post-transplant hepatocellular carcinoma recurrence. RESULTS Of 673 patients in the training cohort, 70 (10.4%) had hepatocellular carcinoma recurrence with a median recurrence time of 6 months (interquartile range: 4-25 months). Cold ischemia time was the only independent donor prognostic factor for predicting hepatocellular carcinoma recurrence (hazard ratio = 2.234, P = .007). The optimal cutoff value was 12 hours when patients were grouped according to cold ischemia time at 2-hour intervals. Integrating cold ischemia time into the Milan criteria (liver transplantation candidate selection criteria) improved the accuracy for predicting hepatocellular carcinoma recurrence in both training and validation sets (P < .05). A nomogram composed of cold ischemia time, tumor burden, differentiation, and α-fetoprotein level proved to be accurate and reliable in predicting the likelihood of 1-year hepatocellular carcinoma recurrence after liver transplantation. Additionally, donor anti-hepatitis B core antibody positivity, prolonged cold ischemia time, and anhepatic time were linked to the intrahepatic recurrence, whereas older donor age, prolonged donor warm ischemia time, cold ischemia time, and ABO incompatibility were relevant to the extrahepatic recurrence. CONCLUSION The graft quality integrated models exhibited considerable predictive accuracy in early hepatocellular carcinoma recurrence risk assessment. The identification of donor risks can further help understand the mechanism of different patterns of recurrence.
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Affiliation(s)
- Qi Ling
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China
| | - Jimin Liu
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Jianyong Zhuo
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Runzhou Zhuang
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Haitao Huang
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | | | - Xiao Xu
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China; China Liver Transplant Registry, Hangzhou, China
| | - Shusen Zheng
- Department of Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, China; China Liver Transplant Registry, Hangzhou, China.
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22
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Wait Time of Less Than 6 and Greater Than 18 Months Predicts Hepatocellular Carcinoma Recurrence After Liver Transplantation: Proposing a Wait Time "Sweet Spot". Transplantation 2017; 101:2071-2078. [PMID: 28353492 DOI: 10.1097/tp.0000000000001752] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes. METHODS This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012. RESULTS Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis. CONCLUSIONS This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.
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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: 29] [Impact Index Per Article: 3.6] [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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Tao R, Wang ZF, Qiu W, He YF, Yan WQ, Sun WY, Li HJ. Role of S100A3 in human hepatocellular carcinoma and the anticancer effect of sodium cantharidinate. Exp Ther Med 2017; 13:2812-2818. [PMID: 28588665 PMCID: PMC5450779 DOI: 10.3892/etm.2017.4294] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2016] [Accepted: 11/15/2016] [Indexed: 12/11/2022] Open
Abstract
The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), which has an annual mortality rate of ~800,000. Although surgical procedures for HCC, such as hepatic resection and liver transplantation, have progressed and the outcomes of patients have improved, HCC is still characterized by frequent recurrence, even after liver transplantation. In the present study the expression of the protein coding gene, S100 calcium binding protein A3 (S100A3), was observed in 62 HCC tissues and tumor-surrounding tissues. The present study indicated that S100A3 activation was involved in tumorigenesis and tumor aggressiveness. The protein and mRNA expression levels of S100A3 in the human HCC cell line (HepG2) were investigated using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, respectively. The function of sodium cantharidinate in inducing HCC cell apoptosis was also investigated. Sodium cantharidinate inhibited the protein and gene expression of S100A3 in HepG2 cells in vitro. These data suggested that S100A3 has an important role in human HCC. The present study indicates that the functional properties of sodium cantharidinate are promising for the development of a novel drug that may control the expression of S100A3 and improve the treatment of human HCC in the near future.
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Affiliation(s)
- Ran Tao
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
- Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Zhong-Feng Wang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wei Qiu
- Department of Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
| | - Yu-Fang He
- Institute of Phytochemistry, Jilin Academy of Chinese Medicine Sciences, Changchun, Jilin 130012, P.R. China
| | - Wei-Qun Yan
- Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Wen-Yi Sun
- Department of Clinical Pharmacy and Pharmaceutical Management, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
| | - Hai-Jun Li
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
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26
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Zhang JA, Kwee SA, Wong LL. Late recurrence of hepatocellular carcinoma after liver transplantation. ACTA ACUST UNITED AC 2017; 3:58-66. [PMID: 28966983 DOI: 10.20517/2394-5079.2017.05] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIMS Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and liver transplant (LT) prolongs survival. However, 15-20% will experience recurrent HCC, most occurring within 2 years of LT. HCC patients with late recurrences (>5 years after LT) may have distinctive clinical/biological characteristics. METHODS A retrospective review was conducted of 88 patients who underwent LT for HCC between 1993-2015, analyzing demographics, clinical factors, explant pathology, and outcome. RESULTS Median follow-up was 6.4 years. HCC recurred in 15 (17.0%) patients with mean time to recurrence of 3.96 +/- 3.99 years. Five patients recurred >5 years post-LT. All late recurrences involved males in their 50s, recurring at 8.5 years on average. Recurrences occurred in chest wall (2), liver (2), lung (2), bone (1) and pelvis (1), with multifocal involvement in 2 patients. Four patients died within 18 months of late recurrence. The fifth patient is alive after ablation of liver recurrence and treatment with sorafenib and everolimus. CONCLUSIONS One-third of post-LT patients with recurrent HCC experienced late recurrence. Although the sample size makes it difficult to identify significant risk factors, this study highlights the importance of long-term follow up and need for biomarkers to identify patients at risk for late recurrences.
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Affiliation(s)
- Julia A Zhang
- Department of Surgery, University of Hawaii School of Medicine, Honolulu, HI 96813, United States
| | - Sandi A Kwee
- The Queens Medical Center, Honolulu, HI 96813, United States
| | - Linda L Wong
- Department of Surgery, University of Hawaii School of Medicine, Honolulu, HI 96813, United States
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 323] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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Postoperative Care of the Liver Transplant Recipient. ANESTHESIA AND PERIOPERATIVE CARE FOR ORGAN TRANSPLANTATION 2017. [PMCID: PMC7120127 DOI: 10.1007/978-1-4939-6377-5_29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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29
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Thomas SM, Moke D, Lopez R, Hanna R, Kabbany MN, Alkhouri N. Liver Transplantation for Hepatocellular Carcinoma in Young Adults: A United Network for Organ Sharing Study. J Adolesc Young Adult Oncol 2016; 6:286-293. [PMID: 27996360 DOI: 10.1089/jayao.2016.0048] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Orthotopic liver transplantation (OLT) is curative for hepatocellular carcinoma (HCC). HCC is typically a disease of older adults (OAs); therefore, characteristics and outcomes of OLT for young adults (YAs) (ages 18-40) are not described. The objective of this study was to assess the characteristics and outcomes of YAs with HCC receiving OLT and compare these to OAs (ages >40 years). METHODS YAs with HCC who had OLT from the United Network for Organ Sharing (UNOS) database were included in this study. As a comparison group, OAs with HCC were matched 4:1 to the YA group. Descriptive statistics of demographics, comorbidities, and outcomes were generated. Kaplan-Meier product limit estimates were used to assess patient and graft survival. Conditional logistic regression and Cox proportional hazards frailty models were used to compare the groups. RESULTS A total of 464 YAs received OLT for HCC. The most common underlying liver diseases were hepatitis C virus (21.3%), hepatitis B virus (HBV, 15.5%), and autoimmune/cholestatic disease (12.3%). An increased number of YAs received OLT for HCC after implementation of model for end-stage liver disease scoring. One thousand two hundred eighty OAs served as the comparison group. Post-transplant 5-year survival was 73.1% in YAs with a retransplantation rate of 7.8%. In OAs, survival and retransplantation rates were lower (68.6% p = 0.093; 4.3% p = 0.001). CONCLUSION Four hundred sixty-four YAs with HCC received OLT in the UNOS database. Compared to the older population, survival and retransplantation rates were higher. HBV, which is vaccine preventable, is a frequent contributor to HCC in YAs.
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Affiliation(s)
- Stefanie M Thomas
- 1 Children's Center for Cancer and Blood Disease , Children's Hospital Los Angeles, Los Angeles, California
- 2 Division of Hematology, Oncology and Blood and Marrow Transplantation, Department of Pediatrics, Keck School of Medicine, University of Southern California , Los Angeles, California
| | - Diana Moke
- 1 Children's Center for Cancer and Blood Disease , Children's Hospital Los Angeles, Los Angeles, California
| | - Rocio Lopez
- 3 Department of Quantitative Health Sciences, Cleveland Clinic , Cleveland, Ohio
| | - Rabi Hanna
- 4 Department of Pediatric Hematology, Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children's , Cleveland, Ohio
| | - Mohammad Nasser Kabbany
- 5 Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic , Cleveland, Ohio
| | - Naim Alkhouri
- 5 Department of Pediatric Gastroenterology and Hepatology, Cleveland Clinic , Cleveland, Ohio
- 6 Digestive Disease Institute , Cleveland Clinic, Cleveland, Ohio
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30
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Does Donation After Cardiac Death Utilization Adversely Affect Hepatocellular Cancer Survival? Transplantation 2016; 100:1916-24. [DOI: 10.1097/tp.0000000000001150] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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31
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Sharma P, Parikh ND, Yu J, Barman P, Derstine BA, Sonnenday CJ, Wang SC, Su GL. Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients. Liver Transpl 2016; 22:1092-8. [PMID: 27064263 PMCID: PMC4961525 DOI: 10.1002/lt.24458] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Revised: 03/18/2016] [Accepted: 03/21/2016] [Indexed: 01/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Data on adult LT recipients who received Model for End-Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty-two (27%) patients died during the median follow-up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P < 0.001), BMD (HR = 0.90/Hounsfield units [HU]; P = 0.03), pre-LT locoregional therapy (HR = 0.14; P < 0.001), and donor age (HR = 1.05; P < 0.001) were the independent predictors of post-LT mortality. DMG area did not affect post-LT survival. In conclusion, in addition to number of HCC lesions and pre-LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092-1098 2016 AASLD.
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Affiliation(s)
- Pratima Sharma
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI,Gastroenterology, Veteran Affairs Ann Arbor Healthcare System, Ann Arbor, MI
| | | | | | - Brian A Derstine
- Morphomics Analysis Group, University of Michigan, Ann Arbor, MI
| | | | - Stewart C Wang
- Department of Surgery, University of Michigan, Ann Arbor, MI,Morphomics Analysis Group, University of Michigan, Ann Arbor, MI
| | - Grace L Su
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI,Morphomics Analysis Group, University of Michigan, Ann Arbor, MI,Gastroenterology, Veteran Affairs Ann Arbor Healthcare System, Ann Arbor, MI
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Gu XQ, Zheng WP, Teng DH, Sun JS, Zheng H. Impact of non-oncological factors on tumor recurrence after liver transplantation in hepatocellular carcinoma patients. World J Gastroenterol 2016; 22:2749-2759. [PMID: 26973413 PMCID: PMC4777997 DOI: 10.3748/wjg.v22.i9.2749] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2015] [Revised: 12/13/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary neoplasm of the liver and is one of the leading causes of cancer-related death worldwide. Liver transplantation (LT) has become one of the best curative therapeutic options for patients with HCC, although tumor recurrence after LT is a major and unaddressed cause of mortality. Furthermore, the factors that are associated with recurrence are not fully understood, and most previous studies have focused on the biological properties of HCC, such as the number and size of the HCC nodules, the degree of differentiation, the presence of hepatic vascular invasion, elevated serum levels of alpha-fetoprotein, and the tumor stage outside of the Milan criteria. Thus, little attention has been given to factors that are not directly related to HCC (i.e., "non-oncological factors"), which have emerged as predictors of tumor recurrence. This review was performed to assess the effects of non-oncological factors on tumor recurrence after LT. The identification of these factors may provide new research directions and clinical strategies for the prophylaxis and surveillance of tumor recurrence after LT, which can help reduce recurrence and improve patient survival.
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Follow-up Imaging After Liver Transplantation Should Take Into Consideration Primary Hepatocellular Carcinoma Characteristics. Transplantation 2015; 99:1613-8. [DOI: 10.1097/tp.0000000000000659] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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34
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Extravascular complications following abdominal organ transplantation. Clin Radiol 2015; 70:898-908. [DOI: 10.1016/j.crad.2015.04.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Revised: 03/03/2015] [Accepted: 04/09/2015] [Indexed: 12/15/2022]
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Orci LA, Berney T, Majno PE, Lacotte S, Oldani G, Morel P, Mentha G, Toso C. Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation. Br J Surg 2015; 102:1250-7. [PMID: 26098966 DOI: 10.1002/bjs.9868] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Revised: 04/05/2015] [Accepted: 05/07/2015] [Indexed: 01/27/2023]
Abstract
BACKGROUND To date, studies assessing the risk of post-transplant hepatocellular carcinoma (HCC) recurrence have focused on tumour characteristics. This study investigated the impact of donor characteristics and graft quality on post-transplant HCC recurrence. METHODS Using the Scientific Registry of Transplant Recipients patients with HCC who received a liver transplant between 2004 and 2011 were included, and post-transplant HCC recurrence was assessed. A multivariable competing risk regression model was fitted, adjusting for confounders such as recipient sex, age, tumour volume, α-fetoprotein, time on the waiting list and transplant centre. RESULTS A total of 9724 liver transplant recipients were included. Patients receiving a graft procured from a donor older than 60 years (adjusted hazard ratio (HR) 1.38, 95 per cent c.i. 1.10 to 1.73; P = 0.006), a donor with a history of diabetes (adjusted HR 1.43, 1.11 to 1.83; P = 0.006) and a donor with a body mass index of 35 kg/m(2) or more (adjusted HR 1.36, 1.04 to 1.77; P = 0.023) had an increased rate of post-transplant HCC recurrence. In 3007 patients with documented steatosis, severe graft steatosis (more than 60 per cent) was also linked to an increased risk of recurrence (adjusted HR 1.65, 1.03 to 2.64; P = 0.037). Recipients of organs from donation after cardiac death donors with prolonged warm ischaemia had higher recurrence rates (adjusted HR 4.26, 1.20 to 15.1; P = 0.025). CONCLUSION Donor-related factors such as donor age, body mass index, diabetes and steatosis are associated with an increased rate of HCC recurrence after liver transplantation.
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Affiliation(s)
- L A Orci
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - T Berney
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - P E Majno
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - S Lacotte
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland
| | - G Oldani
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - P Morel
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - G Mentha
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - C Toso
- Division of Abdominal and Transplantation Surgery, Department of Surgery, University of Geneva, Geneva, Switzerland.,Hepato-Pancreato-Biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
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36
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Vagefi PA, Dodge JL, Yao FY, Roberts JP. Potential role of the donor in hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl 2015; 21:187-94. [PMID: 25371243 PMCID: PMC4308564 DOI: 10.1002/lt.24042] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 10/08/2014] [Accepted: 10/14/2014] [Indexed: 12/12/2022]
Abstract
A subset of liver transplantation (LT) recipients who undergo transplantation for hepatocellular carcinoma (HCC) will develop postoperative recurrence. There has yet to be a thorough investigation of donor factors influencing recurrence. Data regarding adult, primary LT recipients with HCC (n = 5002) who underwent transplantation between January 1, 2006 and September 30, 2010 were extracted from the United Network for Organ Sharing database, and the cumulative incidence of post-LT recurrence by donor factors was subsequently estimated. Among the HCC LT recipients, 324 (6.5%) developed recurrence. An analysis of donor characteristics demonstrated a higher cumulative incidence of recurrence within 4 years of transplantation among recipients with donors ≥ 60 years old (11.8% versus 7.3% with donors < 60 years old, P < 0.001) and with donors from a nonlocal share distribution (10.6% versus 7.4% with donors with a local share distribution, P = 0.004). The latter 2 findings held true in a multivariate analysis: the risk of HCC recurrence increased by 70% for recipients of livers from donors ≥ 60 years old [subhazard ratio (SHR) = 1.70, 95% confidence interval (CI) = 1.31-2.20, P < 0.001] and by 42% for recipients of nonlocal share distribution livers (SHR = 1.42, 95% CI = 1.09-1.84, P = 0.009) after adjustments for clinical characteristics. In conclusion, the consideration of certain donor factors may reduce the cumulative incidence of posttransplant HCC recurrence and thus improve long-term survival after LT.
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Affiliation(s)
- Parsia A Vagefi
- Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA
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37
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Garcia-Saenz-de-Sicilia M, Olivera-Martinez MA, Grant WJ, Mercer DF, Baojjang C, Langnas A, McCashland T. Impact of anti-thymocyte globulin during immunosuppression induction in patients with hepatitis C after liver transplantation. Dig Dis Sci 2014; 59:2804-12. [PMID: 24865255 DOI: 10.1007/s10620-014-3215-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Accepted: 05/12/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Induction immunosuppression with anti-thymocyte globulin (ATG) provides potential benefits after liver transplantation (LT). However, its use in patients with LT and hepatitis C (HCV) is controversial. AIM To evaluate the 1- and 2-year patient survival and HCV recurrence rate in patients receiving ATG during the induction phase of immunosuppression (IPI) after LT. METHODS A total of 49 patients undergoing their first LT for HCV were randomized to receive ATG during IPI. Patient survival and HCV recurrence were determined at 1 and 2 years. The frequency of acute cellular rejection (ACR), infections, and neoplasms was also evaluated. RESULTS Twenty-six patients were randomized to receive ATG (Arm-1) and 23 to standard induction therapy (Arm-2). Those given ATG had lower HCV recurrence (26.9 vs 73.9 %, p = 0.001). The 1- and 2-year patient survival rates were similar for both arms (p = 0.33). Infections occurred in 46.1 % subjects in Arm-1 and 34.7 % in Arm-2 (p = 0.562). There was a greater proportion of fungal infections in Arm-1 (19.2 vs 0 %, p = 0.032). CONCLUSIONS ATG during the IPI was associated with lower frequency of recurrence of HCV in patients undergoing LT. This, however, did not affect the 1- and 2-year survival and the frequency of ACR, infections, or neoplasms.
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Affiliation(s)
- Mauricio Garcia-Saenz-de-Sicilia
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W Markham St #567, Little Rock, AR, 72205, USA,
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38
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Lee C, Kim A, Santos I, Cen Y, Alexopoulos S, Navarro S, Wallman M, Dhanireddy K, Grant E. Cardiophrenic lymph nodes in liver transplant candidates with hepatocellular carcinoma: imaging characteristics and post-transplant outcomes. Clin Transplant 2014; 28:1402-9. [PMID: 25284352 DOI: 10.1111/ctr.12471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/22/2014] [Indexed: 11/30/2022]
Abstract
BACKGROUND No guidelines exist for the management of cardiophrenic lymph nodes in patients with hepatocellular carcinoma (HCC) being evaluated for liver transplantation. METHODS One hundred and seventy-eight patients with HCC listed for liver transplant received both pre-transplant computed tomography (CT) and follow-up CT scans. Enlarged cardiophrenic lymph nodes on CT were characterized and followed on subsequent scans; lymph node outcomes were assigned to "reduced" and "not reduced" categories. Tumor and patient characteristics were also recorded. RESULTS Seventy-one of one hundred and seventy-eight patients (39.9%) had at least one cardiophrenic lymph node larger than 8 mm in diameter on pre-transplant CT. One hundred and sixty-six total lymph nodes were characterized. Six lymph nodes (3.6%) in two patients increased in size on follow-up imaging; all six cardiophrenic lymph nodes were presumed to represent metastases. There was a statistically significant reduction in lymph node size in patients who were transplanted vs. those who were not transplanted. Furthermore, a statistically significant association was found between increasing Model for End-Stage Liver Disease score and lymph node size reduction. There were no significant differences in post-transplant survival between patients with different lymph node outcomes. CONCLUSION In the absence of metastatic disease in other sites, these lymph nodes are probably reactive; further workup is likely not necessary.
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Affiliation(s)
- Christopher Lee
- Department of Radiology, Keck School of Medicine of USC, Los Angeles, CA, USA
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Schlansky B, Chen Y, Scott DL, Austin D, Naugler WE. Waiting time predicts survival after liver transplantation for hepatocellular carcinoma: a cohort study using the United Network for Organ Sharing registry. Liver Transpl 2014; 20:1045-56. [PMID: 24838471 DOI: 10.1002/lt.23917] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Accepted: 05/12/2014] [Indexed: 12/13/2022]
Abstract
Recipients of liver transplantation (LT) for hepatocellular carcinoma (HCC) have an 8% to 20% risk of HCC recurrence. Single-center studies suggest that a period of waiting after HCC therapy may facilitate the selection of patients at low risk for post-LT HCC recurrence and mortality. We evaluated whether a longer waiting time after Model for End-Stage Liver Disease (MELD) prioritization for HCC predicts longer post-LT survival. From the United Network for Organ Sharing registry, we selected 2 groups registered for LT between March 2005 and March 2009: (1) HCC patients receiving MELD prioritization and (2) non-HCC patients. Patients were stratified by their MELD status at LT (a marker of time on the wait list after HCC MELD prioritization) and were followed from LT until death or censoring through October 2012. By comparing post-LT survival to intention-to-treat (ITT) survival from registration, we assessed predictors of post-LT survival and estimated the benefit of LT. The median MELD scores at LT were 22 (HCC) and 24 (non-HCC). A higher MELD score at LT was independently associated with lower post-LT mortality in the HCC group [hazard ratio (HR) = 0.84, 95% confidence interval (CI) = 0.73-0.98] and higher post-LT mortality in the non-HCC group (HR = 1.20, 95% CI = 1.15-1.25). Compared with the HCC group, the non-HCC group had lower post-LT mortality [relative risk (RR) = 0.85, log-rank P < 0.01] but higher ITT mortality (RR = 1.25, log-rank P < 0.01) because of a 33 percentage point lower probability of undergoing LT. In conclusion, a longer waiting time before LT for HCC predicted longer post-LT survival in a national transplant registry. Delaying LT for HCC may reduce disparities in ITT survival and access to LT among different indications and thereby improve system utility and organ allocation equity for the overall pool of LT candidates.
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Affiliation(s)
- Barry Schlansky
- Division of Gastroenterology and Hepatology, Department of Medicine, Oregon Health and Science University, Portland, OR
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40
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Preoperative tumour biopsy does not affect the oncologic course of patients with transplantable HCC. J Hepatol 2014; 61:589-93. [PMID: 24818985 DOI: 10.1016/j.jhep.2014.04.046] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Revised: 04/17/2014] [Accepted: 04/21/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Preoperative fine-needle aspiration biopsy (PFNAB) allows obtaining reliable hepatocellular carcinoma (HCC) diagnosis before liver transplantation (LT) in doubtful situations, but may result in higher recurrence rates following LT. This study aimed to evaluate whether PFNAB actually jeopardized the outcome of patients with transplantable HCC. METHODS From 2002 to 2012, among 309 HCC patients listed for LT, 80 (26%) underwent PFNAB (PFNAB+). Their characteristics, modalities of recurrence, and survivals were retrospectively compared to those of the 229 (74%) patients without PFNAB (PFNAB-). RESULTS The two groups (PFNAB+ vs. PFNAB-) were similar in terms of demography, rates of lesions within the Milan criteria (81% vs. 79%, p=0.676), and duration on the waiting list (7.0 vs. 6.9 months, p=0.891). Dropout following tumour progression was similar between both groups (6% vs. 11%, p=0.424). Among the 278 (90%) transplanted patients, pathological analysis revealed that 11 (4%) patients had non-HCC lesions including 10 in PFNAB- patients. Median follow-up was 34 months (12-135) and recurrence after LT was observed in 25 (9%) patients with no difference between both groups (9.3% vs. 8.9%, p=0.904). Parietal recurrence was observed in one PFNAB+ patient and in 2 PFNAB- patients after radiofrequency ablation (p=0.797). On an intention to treat basis, 1-, 3-, and 5-year overall survivals (89%, 69%, and 60% vs. 85%, 67%, and 61%, p=0.601) were not significantly different between PFNAB+ and PFNAB- patients. CONCLUSIONS This study supports that preoperative tumour biopsy does not negatively influence the oncologic course of HCC patients eligible for LT. Hence, there is no argument to restrict biopsy in doubtful situations.
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41
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Ramanathan R, Sharma A, Lee DD, Behnke M, Bornstein K, Stravitz RT, Sydnor M, Fulcher A, Cotterell A, Posner MP, Fisher RA. Multimodality therapy and liver transplantation for hepatocellular carcinoma: a 14-year prospective analysis of outcomes. Transplantation 2014; 98:100-6. [PMID: 24503764 PMCID: PMC4088318 DOI: 10.1097/01.tp.0000441090.39840.b0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma is a major cause of death among patients with cirrhosis. A standardized approach of multimodality therapy with intent-to-treat by transplantation for all patients with hepatocellular carcinoma was instituted at our transplant center in 1997. Data were prospectively collected to evaluate the impact of multimodality therapy on posttransplant patient survival, tumor recurrence, and patient survival without transplantation. METHODS All patients with hepatocellular carcinoma were eligible for multimodality therapy. Multimodality therapy consisted of hepatic resection, radiofrequency ablation, transarterial chemoembolization, transarterial chemoinfusion, yttrium-90 microsphere radioembolization, and sorafenib. RESULTS Approximately 715 patients underwent multimodality therapy; 231 patients were included in the intent-to-treat with transplantation arm, and 484 patients were treated with multimodality therapy or palliative therapy because of contraindications for transplantation. A 60.2% transplantation rate was achieved in the intent-to-treat with transplantation arm. Posttransplant survivals at 1 and 5 years were 97.1% and 72.5%, respectively. Tumor recurrence rates at 1, 3, and 5 years were 2.4%, 6.2%, and 11.6%, respectively. Patients with contraindications to transplant had increased 1- and 5-year survival from diagnosis with multimodality therapy compared with those not treated (73.1% and 46.5% versus 15.5% and 4.4%, P<0.0001). CONCLUSIONS Using multimodality therapy before liver transplantation for hepatocellular carcinoma achieved low recurrence rates and posttransplant survival equivalent to patients with primary liver disease without hepatocellular carcinoma. Multimodality therapy may help identify patients with less active tumor biology and result in improved disease-free survival and organ utilization.
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Affiliation(s)
- Rajesh Ramanathan
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Amit Sharma
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - David D Lee
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Martha Behnke
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Karen Bornstein
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - R Todd Stravitz
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Malcolm Sydnor
- Department of Radiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Ann Fulcher
- Department of Radiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Adrian Cotterell
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Marc P Posner
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
| | - Robert A Fisher
- Hume-Lee Transplant Center, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298
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42
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Roma J, Balbi E, Pacheco-Moreira L, Zyngier I, Araujo A, Agoglia L, Steinbruck K, Velaverde LG, Martinho JM. Impact of model for end-stage liver disease score on long-term survival following liver transplantation for hepatocellular carcinoma. Transplant Proc 2013; 44:2423-7. [PMID: 23026611 DOI: 10.1016/j.transproceed.2012.07.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Survival rates after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) have significantly increased after Milan criteria and Model for End-Stage Liver Disease (MELD) score implementation. However, few studies have reported this survival in countries with organ donor shortages over a period of 10 years and long waiting lists. METHODS This retrospective analysis of clinical data from 93 consecutive HCC patients who underwent OLT from June 2001 to September 2011 excluded 22 who underwent living donor liver transplantation (LDLT). Seventy-one deceased donor liver transplantations (DDLT) were evaluated before and after the MELD era. Kaplan-Meier analysis was used to plot survival rates. The follow-up was 2 months to 10 years. RESULTS The overall survival and recurrence rates at 10 years were 67% and 12.2%, respectively. After MELD, patient survival at 5 years decreased from 70% to 64% and the recurrence rate decreased from 15.3% to 12.5%. The most frequent recurrence sites were lung and liver. CONCLUSION In our center MELD score implementation had a small impact on long-term survival post OLT for HCC.
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Affiliation(s)
- J Roma
- Liver Transplantation Unit, Bonsucesso General Hospital, Rio de Janeiro, Brazil.
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Rostaing L, Saliba F, Calmus Y, Dharancy S, Boillot O. Review article: use of induction therapy in liver transplantation. Transplant Rev (Orlando) 2012; 26:246-60. [PMID: 22863028 DOI: 10.1016/j.trre.2012.06.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2012] [Accepted: 06/12/2012] [Indexed: 02/07/2023]
Abstract
Induction therapy is used relatively infrequently in liver transplantation, but developments in induction regimens and strategies for their use are prompting a re-examination of its benefits. Rabbit antithymocyte globulin (rATG) induces protracted, dose-dependent lymphocytopenia with preferential reconstitution of regulatory T-lymphocytes. Non-depleting interleukin-2 receptor antagonists (IL-2RA) act selectively on activated T-lymphocytes with a shorter duration of effect. IL-2RA induction with delayed and reduced calcineurin inhibitor (CNI) exposure appears to preserve efficacy, while more aggressive CNI minimisation has been attempted successfully using rATG. Steroid-free tacrolimus monotherapy with rATG or IL-2RA induction is effective if adequate tacrolimus exposure is maintained. Early concerns that addition of induction to a conventional maintenance regimen could lead to accelerated progression of hepatitis C disease, or to an increased risk of hepatocellular cancer recurrence, now appear unfounded using modern regimens. Similarly, with routine use of systemic prophylaxis, recent prospective and retrospective data have not shown a higher rate of infections overall, or cytomegalovirus infection specifically, using rATG or IL-2RA induction. Historical evidence that lymphocyte-depleting agents increased the risk of non-Hodgkin lymphoma has not been confirmed for rATG. Wider use of induction in liver transplantation is now merited, using individualized strategies to support reduced CNI exposure or steroid-free immunosuppression.
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Affiliation(s)
- Lionel Rostaing
- Nephrology, Dialysis and Organ Transplantation Service, CHU Rangueil, Toulouse, France.
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