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Magyar CTJ, Rajendran L, Li Z, Banz V, Vogel A, O'Kane GM, Chan ACY, Sapisochin G. Precision surgery for hepatocellular carcinoma. Lancet Gastroenterol Hepatol 2025; 10:350-368. [PMID: 39993401 DOI: 10.1016/s2468-1253(24)00434-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 12/12/2024] [Accepted: 12/17/2024] [Indexed: 02/26/2025]
Abstract
Hepatocellular carcinoma arises in the setting of cirrhosis in most cases, requiring multidisciplinary input to define resectability. In this regard, more precise surgical management considers patient factors and anatomical states, including resection margins, tumour biology, and perioperative therapy. Together with advances in surgical techniques, this integrated approach has resulted in considerable improvements in patient morbidity and oncological outcomes. Despite this, recurrence rates in hepatocellular carcinoma remain high. As the systemic treatment landscape in hepatocellular carcinoma continues to evolve and locoregional options are increasingly used, we review current and future opportunities to individualise the surgical management of patients with hepatocellular carcinoma.
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Affiliation(s)
- Christian Tibor Josef Magyar
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Luckshi Rajendran
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada; Division of Transplant Surgery, Henry Ford Hospital, Detroit, MI, USA
| | - Zhihao Li
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Vanessa Banz
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Arndt Vogel
- Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Grainne Mary O'Kane
- Medical Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; Department of Medicine Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada; St Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland
| | - Albert Chi-Yan Chan
- Department of Surgery, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Gonzalo Sapisochin
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada; Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.
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2
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Mauro E, Rodríguez‐Perálvarez M, D'Alessio A, Crespo G, Piñero F, De Martin E, Colmenero J, Pinato DJ, Forner A. New Scenarios in Liver Transplantation for Hepatocellular Carcinoma. Liver Int 2025; 45:e16142. [PMID: 39494583 PMCID: PMC11891387 DOI: 10.1111/liv.16142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 10/03/2024] [Accepted: 10/09/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND AND AIMS Despite liver transplantation (LT) is considered the optimal treatment for hepatocellular carcinoma (HCC), particularly in patients with impaired liver function, the shortage of donors has forced the application of very restrictive criteria for selecting ideal candidates for whom LT can offer the best outcome. With the evolving LT landscape due to the advent of direct-acting antivirals (DAAs) and the steady increase in donors, major efforts have been made to expand the transplant eligibility criteria for HCC. In addition, the emergence of immune checkpoint inhibitors (ICIs) for the treatment of HCC, with demonstrated efficacy in earlier stages, has revolutionized the therapeutic approach for these patients, and their integration in the setting of LT is challenging. Management of immunological compromise from ICIs, including the wash-out period before LT and post-LT immunosuppression adjustments, is crucial to balance the risk of graft rejection against HCC recurrence. Additionally, the effects of increased immunosuppression on non-hepatic complications must be understood to prevent them from becoming obstacles to long-term OS. METHODS AND RESULTS In this review, we will evaluate the emerging evidence and its implications for the future of LT in HCC. Addressing these novel challenges and opportunities, while integrating the current clinical evidence with predictive algorithms, would ensure a fair balance between individual patient needs and the overall population benefit in the LT system.
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Affiliation(s)
- Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPSUniversity of BarcelonaBarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | - Manuel Rodríguez‐Perálvarez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
- Department of Hepatology and Liver Transplantation, Hospital Universitario Reina SofíaUniversidad de Córdoba, IMIBIC, CIBERehdCórdobaSpain
| | - Antonio D'Alessio
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
- Division of Oncology, Department of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly
| | - Gonzalo Crespo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPSUniversity of BarcelonaBarcelonaSpain
| | - Federico Piñero
- School of MedicineHospital Universitario Austral, Austral UniversityBuenos AiresArgentina
| | - Eleonora De Martin
- AP‐HP Hôpital Paul‐Brousse, Centre Hépato‐Biliaire, INSERM Unit 1193Université Paris‐Saclay, FHU HepatinovVillejuifFrance
| | - Jordi Colmenero
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
- Liver Transplant Unit, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPSUniversity of BarcelonaBarcelonaSpain
| | - David James Pinato
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
- Division of Oncology, Department of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, ICMDM, Hospital Clinic Barcelona, IDIBAPSUniversity of BarcelonaBarcelonaSpain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
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3
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Schindler P, von Beauvais P, Hoffmann E, Morgül H, Börner N, Masthoff M, Ben Khaled N, Rennebaum F, Lange CM, Trebicka J, Ingrisch M, Köhler M, Ricke J, Pascher A, Seidensticker M, Guba M, Öcal O, Wildgruber M. Combining radiomics and imaging biomarkers with clinical variables for the prediction of HCC recurrence after liver transplantation. Liver Transpl 2025:01445473-990000000-00582. [PMID: 40100771 DOI: 10.1097/lvt.0000000000000603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Accepted: 02/14/2025] [Indexed: 03/20/2025]
Abstract
To develop and validate an integrated model that combines CT-based radiomics and imaging biomarkers with clinical variables to predict recurrence and recurrence-free survival in patients with HCC following liver transplantation (LT), this 2-center retrospective study includes 123 patients with HCC who underwent LT between 2007 and 2021. Radiomic features (RFs) were extracted from baseline CT liver tumor volume. Feature selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method with 10-fold cross-validation in the training cohort (n=48) to build a predictive radiomics signature for HCC recurrence. Combined diagnostic models were built based on the radiomics signature supplemented with imaging features beyond the Milan criteria, the AFP (alpha-fetoprotein) model, and Metroticket 2.0 before LT using multivariate logistic regression. Receiver operating characteristic analyses were performed in both internal (n=22) and external (n=53) validation cohorts, and patients were stratified into either high-risk or low-risk groups for HCC recurrence. Kaplan-Meier analysis was performed to analyze recurrence-free survival. LASSO and multivariate regression analysis revealed 4 independent predictors associated with an increased risk of HCC recurrence: radiomics signature of 5 RF, peritumoral enhancement, satellite nodules, and no bridging therapies. For the prediction of tumor recurrence, the highest AUC of the final integrated models combining clinical variables, non-radiomics imaging features, and radiomics was 0.990 and 0.900 for the internal and external validation sets, respectively, outperforming the Milan and clinical stand-alone models. In all integrated models, the high-risk groups had a shorter recurrence-free survival than the corresponding low-risk group. CT-based radiomics and imaging parameters beyond the Milan criteria representing aggressive behavior, along with the history of bridging therapies, show potential for predicting HCC recurrence after LT.
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Affiliation(s)
| | | | - Emily Hoffmann
- Department of Radiology, University of Muenster, Muenster, Germany
| | - Haluk Morgül
- Department of General, Visceral and Transplant Surgery, University of Muenster, Muenster, Germany
| | - Nikolaus Börner
- Department of General, Visceral and Transplantation Surgery, LMU Munich, Munich, Germany
| | - Max Masthoff
- Department of Radiology, University of Muenster, Muenster, Germany
| | - Najib Ben Khaled
- Department for Internal Medicine II, LMU Munich, Munich, Germany
| | - Florian Rennebaum
- Department for Internal Medicine B, University of Muenster, Muenster, Germany
| | | | - Jonel Trebicka
- Department for Internal Medicine B, University of Muenster, Muenster, Germany
| | | | - Michael Köhler
- Department of Radiology, University of Muenster, Muenster, Germany
| | - Jens Ricke
- Department of Radiology, LMU Munich, Munich, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University of Muenster, Muenster, Germany
| | | | - Markus Guba
- Department of General, Visceral and Transplantation Surgery, LMU Munich, Munich, Germany
| | - Osman Öcal
- Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
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Magyar CTJ, O'Kane GM, Aceituno L, Li Z, Vogel A, Bruix J, Mazzaferro V, Sapisochin G. Liver Transplantation for Hepatocellular Carcinoma: An Expanding Cornerstone of Care in the Era of Immunotherapy. J Clin Oncol 2025; 43:589-604. [PMID: 39680821 DOI: 10.1200/jco.24.00857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 09/20/2024] [Accepted: 10/19/2024] [Indexed: 12/18/2024] Open
Abstract
Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.
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Affiliation(s)
- Christian Tibor Josef Magyar
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Grainne Mary O'Kane
- University of Toronto, Toronto, ON, Canada
- St Vincent's University Hospital and School of Medicine, University College Dublin, Dublin, Ireland
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
| | - Laia Aceituno
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Zhihao Li
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
| | - Arndt Vogel
- Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada
- Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, ON, Canada
- Department of Hepatology, Gastroenterology, Endocrinology & Infectious Diseases, Hannover Medical School, Hannover, Germany
| | - Jordi Bruix
- BCLC Group, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Vincenzo Mazzaferro
- Istituto Nazionale Tumori IRCCS, Hepato Pancreatic Biliary Surgery & Liver Transplantation Unit, Milano, Italy
- Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy
| | - Gonzalo Sapisochin
- HPB Surgical Oncology, University Health Network, Toronto, ON, Canada
- Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada
- University of Toronto, Toronto, ON, Canada
- Department of Medicine, Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
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5
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Magyar CTJ, Li Z, Aceituno L, Claasen MPAW, Ivanics T, Choi WJ, Rajendran L, Sayed BA, Bucur R, Rukavina N, Selzner N, Ghanekar A, Cattral M, Sapisochin G. Temporal evolution of living donor liver transplantation survival-A United Network for Organ Sharing registry study. Am J Transplant 2025; 25:406-416. [PMID: 39163907 DOI: 10.1016/j.ajt.2024.08.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 08/10/2024] [Indexed: 08/22/2024]
Abstract
Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m2 (IQR: 23.2-30.0 kg/m2), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.
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Affiliation(s)
- Christian T J Magyar
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada; Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Zhihao Li
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Laia Aceituno
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Marco P A W Claasen
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada; Department of Surgery, division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands
| | - Tommy Ivanics
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada; Department of Surgery, Henry Ford Hospital, Detroit, Michigan, USA; Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden
| | - Woo Jin Choi
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Luckshi Rajendran
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Blayne A Sayed
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Roxana Bucur
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Nadia Rukavina
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Nazia Selzner
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Anand Ghanekar
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Mark Cattral
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Gonzalo Sapisochin
- HBP & Multi-Organ Transplant Program, University Health Network, Toronto, Canada.
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6
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Sha M, Wang J, Cao J, Zou ZH, Qu XY, Xi ZF, Shen C, Tong Y, Zhang JJ, Jeong S, Xia Q. Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation. Clin Mol Hepatol 2025; 31:S285-S300. [PMID: 39159949 PMCID: PMC11925443 DOI: 10.3350/cmh.2024.0323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 08/11/2024] [Accepted: 08/12/2024] [Indexed: 08/21/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
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Affiliation(s)
- Meng Sha
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jun Wang
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Cao
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-Hui Zou
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Military Medical University, Shanghai, China
| | - Xiao-ye Qu
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zhi-feng Xi
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chuan Shen
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Tong
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jian-jun Zhang
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Seogsong Jeong
- Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Korea
| | - Qiang Xia
- Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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7
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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8
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Piñero F, Lai Q, Costentin C, Degroote H, Schnitzbauer A, Geissler EK, Duvoux C. Validation of the R3-AFP model for risk prediction of HCC recurrence after liver transplantation in the SiLVER randomized clinical trial. Liver Transpl 2025; 31:45-57. [PMID: 39297745 DOI: 10.1097/lvt.0000000000000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 08/27/2024] [Indexed: 10/23/2024]
Abstract
Explant-based models for assessing HCC recurrence after liver transplantation serve as the gold standard, guiding post-liver transplantation screening and immunosuppression adjustment. Incorporating alpha-fetoprotein (AFP) levels into these models, such as the novel R3-AFP score, has notably enhanced risk stratification. However, validation of these models in high-evidence data is mandatory. Therefore, the aim of the present research was to validate the R3-AFP score in a randomized clinical trial. We analyzed the intention-to-treat population from the 2-arm SiLVER trial (NCT00355862), comparing calcineurin-based ([calcineurin inhibitors]-Group A) versus mammalian target of rapamycin inhibitors-based (sirolimus-Group B) immunosuppression for post-liver transplantation HCC recurrence. Competing risk analysis estimated sub-hazard ratios, with testing of discriminant function and calibration. Overall, 508 patients from the intention-to-treat analysis were included (Group A, n = 256; Group B, n = 252). The R3-AFP score distribution was as follows: 42.6% low-risk (n = 216), 35.7% intermediate-risk (n = 181), 19.5% high-risk (n = 99), and 2.2% very-high-risk (n = 11) groups. The R3-AFP score effectively stratified HCC recurrence risk, with increasing risk for each stratum. Calibration of the R3-AFP model significantly outperformed other explant-based models (Milan, Up-to-7, and RETREAT), whereas discrimination power (0.75 [95% CI: 0.69; 0.81]) surpassed these models, except for the RETREAT model ( p = 0.49). Subgroup analysis showed lower discrimination power in the mammalian target of rapamycin group versus the calcineurin inhibitors group ( p = 0.048). In conclusion, the R3-AFP score accurately predicted HCC recurrence using high-quality evidence-based data, exhibiting reduced performance under mammalian target of rapamycin immunosuppression. This highlights the need for further research to evaluate surveillance schedules and adjuvant regimens.
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Affiliation(s)
- Federico Piñero
- Hepatology Section, Liver Transplant Unit, Hepatology, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Quirino Lai
- Department of Surgery, General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Charlotte Costentin
- Gastroenterology, Hepatology and GI Oncology Department, Grenoble Alpes University, Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, Digidune, Grenoble Alpes University Hospital, La Tronche, France
| | - Helena Degroote
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Andreas Schnitzbauer
- Department of Surgery, HPB and Transplant Surgery, University Hospital Frankfurt, Frankfurt, Germany
| | - Edward K Geissler
- Department of Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Christophe Duvoux
- Department of Hepatology, Medical Liver Transplant Unit, Hospital Henri Mondor AP-HP, University of Paris-Est Créteil (UPEC), Créteil, France
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9
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Zhang X, Chen C, Wang Y, Xu J. Recurrence risk prediction models for hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol 2024; 39:2272-2280. [PMID: 39113259 DOI: 10.1111/jgh.16693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 12/06/2024]
Abstract
Liver transplantation (LT) is an effective method for curing hepatocellular carcinoma (HCC). However postoperative tumor recurrence can lead to higher mortality rates. To select suitable candidates for LT, the Milan Criteria (MC) were first proposed based on tumor morphological characteristics. For those patients who meet the MC, the MC can effectively reduce the postoperative tumor recurrence rate and improve the prognosis of patients undergoing LT. It has always been internationally recognized as the gold standard for selecting candidates for LT, marking a milestone in the history of LT for HCC. However, its strict conditions exclude some HCC patients who could benefit from LT. Therefore, comprehension consideration criteria, including serum biomarkers, tumor histology, and other factor, have been continuously proposed in addition to tumor morphology. This article summaries the prediction model for HCC recurrence after LT from five aspects: tumor morphology, serum markers, histopathology, cellular inflammatory factors and downstaging treatment before transplantation. The aim is to assist clinicians in accurately assessing HCC status, selecting appropriate liver transplant candidates, maximize graft and patients' survival, and optimizing the utilization of social health resources.
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Affiliation(s)
- Xu Zhang
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Chi Chen
- Department of Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Yan Wang
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Xu
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
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10
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Shih HW, Lai Y, Hung HC, Lee JC, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC, Cheng CH. Liver Resection Criteria for Patients with Hepatocellular Carcinoma and Multiple Tumors Based on Total Tumor Volume. Dig Dis Sci 2024; 69:3069-3078. [PMID: 38824258 PMCID: PMC11341635 DOI: 10.1007/s10620-024-08500-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/11/2024] [Indexed: 06/03/2024]
Abstract
BACKGROUND In many Asian hepatocellular carcinoma (HCC) guidelines, resection is an option for multiple HCCs. It is difficult to compare small but multiple tumors vs. fewer large tumors in terms of the traditional tumor burden definition. We aimed to evaluate the role of liver resection for multiple HCCs and determine factors associated with survival benefits. METHODS We reviewed 160 patients with multiple HCCs who underwent liver resection between July 2003 and December 2018. The risk factors for tumor recurrence were assessed using Cox proportional hazards modeling, and survival was analyzed using the Kaplan-Meier method. RESULTS In all 160 patients, 133 (83.1%) exceeded the Milan criteria. Total tumor volume (TTV) > 275 cm3 and serum alpha-fetoprotein (AFP) level > 20 ng/mL were associated with disease-free survival. Patients beyond the Milan criteria were grouped into three risk categories: no risk (TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL, n = 39), one risk (either TTV > 275 cm3 or AFP > 20 ng/mL, n = 76), and two risks (TTV > 275 cm3 and AFP > 20 ng/mL, n = 18). No-risk group had comparable disease-free survival (p = 0.269) and overall survival (p = 0.215) to patients who met the Milan criteria. CONCLUSION Patients with TTV ≤ 275 cm3 and AFP ≤ 20 ng/mL can have good outcomes even exceed the Milan criteria.
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Affiliation(s)
- Hao-Wen Shih
- Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yin Lai
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hao-Chien Hung
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Jin-Chiao Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu-Chao Wang
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Kun-Ming Chan
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Division of Liver and Transplantation Surgery, Department of General Surgery, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan, Taiwan.
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11
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Chan KM, Lee WC. Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis. Biomed J 2024; 48:100757. [PMID: 38942384 PMCID: PMC12001119 DOI: 10.1016/j.bj.2024.100757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/22/2024] [Accepted: 06/25/2024] [Indexed: 06/30/2024] Open
Abstract
Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Wei-Chen Lee
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
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12
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Piñero F, Mauro E, Casciato P, Forner A. From evidence to clinical practice: Bridging the gap of new liver cancer therapies in Latin America. Ann Hepatol 2024; 29:101185. [PMID: 38042481 DOI: 10.1016/j.aohep.2023.101185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Accepted: 10/26/2023] [Indexed: 12/04/2023]
Abstract
The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.
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Affiliation(s)
- Federico Piñero
- Hospital Universitario Austral, Austral University, School of Medicine, Buenos Aires, Argentina.
| | - Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain
| | | | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) group. IDIBAPS. Barcelona. Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit. Liver Oncology Unit. ICMDM. Hospital Clinic Barcelona. Barcelona, Spain; University of Barcelona, Barcelona, Spain.
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13
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Lindemann J, Doyle MBM. Expanding the Boundaries for Liver Transplantation for Hepatocellular Carcinoma. Surg Clin North Am 2024; 104:129-143. [PMID: 37953032 DOI: 10.1016/j.suc.2023.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which was the third most common cause of cancer death worldwide in 2020. Transplantation remains the preferred treatment for cure in otherwise unresectable HCC. There are several areas of active research that have led to expansion of eligibility criteria for transplantation including local-regional therapy for downstaging patients presenting outside of the Milan criteria and identification of tumor biomarkers aiding in the early diagnosis, determining prognosis and likelihood of recurrence after transplantation for HCC. New neoadjuvant therapies and post-transplant immunosuppression regimens may also result in expansion of transplant eligibility criteria for HCC.
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Affiliation(s)
- Jessica Lindemann
- Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, Saint Louis, MO, USA
| | - Maria Bernadette Majella Doyle
- Section of Abdominal Transplantation, Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, Saint Louis, MO 63110, USA.
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14
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He X, Xu S, Tang L, Ling S, Wei X, Xu X. Insights into the history and tendency of liver transplantation for liver cancer: a bibliometric-based visual analysis. Int J Surg 2024; 110:406-418. [PMID: 37800536 PMCID: PMC10793788 DOI: 10.1097/js9.0000000000000806] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 09/18/2023] [Indexed: 10/07/2023]
Abstract
Research on liver transplantation (LT) for liver cancer has gained increasing attention. This paper has comprehensively described the current status, hotspots and trends in this field. A total of 2991 relevant articles from 1 January 1963 to 28 February 2023 were obtained from the Web of Science Core Collection. VOSviewer and CiteSpace software were utilized as bibliometric tools to analyze and visualize knowledge mapping. Between 1963 and 2023, the number of papers in the area of LT for liver cancer increased continuously. A total of 70 countries/regions, 2303 institutions and 14 840 researchers have published research articles, with the United States and China being the two most productive countries. Our bibliometric-based visual analysis revealed the expansion of LT indications for liver cancer and the prevention/treatment of cancer recurrence as ongoing research hotspots over the past decades. Meanwhile, emerging studies also focus on downstaging/bridging treatments before LT and the long-term survival of LT recipient, in particular the precise application of immunosuppressants.
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Affiliation(s)
- Xinyu He
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Shengjun Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Linsong Tang
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
| | - Sunbin Ling
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xuyong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine
| | - Xiao Xu
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province
- Zhejiang University School of Medicine
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China
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15
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Lindemann J, Yu J, Doyle MBM. Downstaging Hepatocellular Carcinoma before Transplantation: Role of Immunotherapy Versus Locoregional Approaches. Surg Oncol Clin N Am 2024; 33:143-158. [PMID: 37945140 DOI: 10.1016/j.soc.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer-related death in the United States. With advances in locoregional therapy for unresectable HCC during the last 2 decades and the recent expansion of transplant criteria for HCC, as well as ongoing organ shortages, patients are spending more time on the waitlist, which has resulted in an increased usage of locoregional therapies. The plethora of molecularly targeted therapies and immune checkpoint inhibitors under investigation represent the new horizon of treatment of HCC not only in advanced stages but also potentially at every stage of diagnosis and management.
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Affiliation(s)
- Jessica Lindemann
- Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA
| | - Jennifer Yu
- Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA
| | - Maria Bernadette Majella Doyle
- Department of Surgery, Division of Abdominal Organ Transplantation, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA.
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16
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Hoang TPT, Schindler P, Börner N, Masthoff M, Gerwing M, von Beauvais P, De Toni EN, Lange CM, Trebicka J, Morgül H, Seidensticker M, Ricke J, Pascher A, Guba M, Ingrisch M, Wildgruber M, Öcal O. Imaging-Derived Biomarkers Integrated with Clinical and Laboratory Values Predict Recurrence of Hepatocellular Carcinoma After Liver Transplantation. J Hepatocell Carcinoma 2023; 10:2277-2289. [PMID: 38143909 PMCID: PMC10740736 DOI: 10.2147/jhc.s431503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Accepted: 11/22/2023] [Indexed: 12/26/2023] Open
Abstract
Purpose To investigate the prognostic value of computed tomography (CT) derived imaging biomarkers in hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) and develop a predictive nomogram model. Patients and Methods This retrospective study included 178 patients with histopathologically confirmed HCC who underwent liver transplantation between 2007 and 2021 at the two academic liver centers. We evaluated dedicated imaging features from baseline multiphase contrast-enhanced CT supplemented by several clinical findings and laboratory parameters. Time-to-recurrence was estimated by Kaplan-Meier analysis. Univariable Cox proportional hazard regression and multivariable Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent prognostic factors for recurrence. A nomogram model was then built based on the independent factors selected through LASSO regression, to predict the probabilities of HCC recurrence at one, three, and five years. Results The rate of HCC recurrence after LT was 17.4% (31 of 178). The LASSO analysis revealed six independent predictors associated with an elevated risk of tumor recurrence. These predictors included the presence of peritumoral enhancement, the presence of over three tumor lesions, the largest tumor diameter greater than 3 cm, serum alpha-fetoprotein (AFP) levels exceeding 400 ng/mL, and the presence of a tumor capsule. Conversely, a history of bridging therapies was found to be correlated with a reduced risk of HCC recurrence. In addition, Kaplan-Meier curves showed patients with irregular margin, satellite nodules, or small lesions displayed shorter time-to-recurrence. Our nomogram demonstrated good performance, yielding a C-index of 0.835 and AUC values of 0.86, 0.88, and 0.85 for the predictions of 1-year, 3-year, and 5-year TTR, respectively. Conclusion Imaging parameters derived from baseline contrast-enhanced CT showing malignant behavior and aggressive growth patterns, along with serum AFP and history of bridging therapies, show potential as biomarkers for predicting HCC recurrence after transplantation.
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Affiliation(s)
| | - Philipp Schindler
- Clinic for Radiology, University Hospital Muenster, Muenster, Germany
| | - Nikolaus Börner
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Max Masthoff
- Clinic for Radiology, University Hospital Muenster, Muenster, Germany
| | - Mirjam Gerwing
- Clinic for Radiology, University Hospital Muenster, Muenster, Germany
| | | | - Enrico N De Toni
- Department for Internal Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Christian M Lange
- Department for Internal Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Jonel Trebicka
- Department for Internal Medicine B, Universitätsklinikum Münster, Münster, Germany
| | - Haluk Morgül
- Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Jens Ricke
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, Universitätsklinikum Münster, Münster, Germany
| | - Markus Guba
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Munich, Germany
| | - Michael Ingrisch
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Moritz Wildgruber
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
| | - Osman Öcal
- Department of Radiology, University Hospital, LMU Munich, Munich, Germany
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17
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Huang C, Xiao X, Zhou L, Chen F, Wang J, Hu X, Gao C. Chinese expert consensus statement on the clinical application of AFP/AFP-L3%/DCP using GALAD and GALAD-like algorithm in HCC. J Clin Lab Anal 2023; 37:e24990. [PMID: 38063322 PMCID: PMC10756949 DOI: 10.1002/jcla.24990] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 10/16/2023] [Accepted: 11/01/2023] [Indexed: 12/31/2023] Open
Abstract
BACKGROUND Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up. RESULTS Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer. CONCLUSIONS The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.
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Affiliation(s)
- Chenjun Huang
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Xiao Xiao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Lin Zhou
- Department of Laboratory MedicineShanghai Changzheng HospitalShanghaiChina
| | - Fuxiang Chen
- Department of Laboratory Medicine, Shanghai Ninth People's HospitalShanghai JiaoTong University School of MedicineShanghaiChina
| | - Jianyi Wang
- Department of Liver Diseases, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
| | - Xiaobo Hu
- Shanghai Clinical Laboratory CenterShanghaiChina
| | - Chunfang Gao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina
- Shanghai Eastern Hepatobiliary Surgery HospitalShanghaiChina
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18
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Oh RK, Hwang S, Song GW, Ahn CS, Moon DB, Ha TY, Jung DH, Park GC, Yoon YI, Kang WH. Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation. Ann Surg Treat Res 2023; 105:133-140. [PMID: 37693289 PMCID: PMC10485355 DOI: 10.4174/astr.2023.105.3.133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/11/2023] [Accepted: 08/01/2023] [Indexed: 09/12/2023] Open
Abstract
Purpose Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. Methods This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). Results Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). Conclusion Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.
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Affiliation(s)
- Rak Kyun Oh
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Park GC, Hwang S, You YK, Choi Y, Kim JM, Joo DJ, Ryu JH, Choi D, Kim BW, Kim DS, Nah YW, Kang KJ, Cho JY, Yu HC, Kim DG. Quantitative Prediction of Posttransplant Hepatocellular Carcinoma Prognosis Using ADV Score: Validation with Korea-Nationwide Transplantation Registry Database. J Gastrointest Surg 2023; 27:1353-1366. [PMID: 37039979 DOI: 10.1007/s11605-023-05670-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 03/18/2023] [Indexed: 04/12/2023]
Abstract
OBJECTIVE The aim of this study is to validate the prognostic impact of ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting prognosis of hepatocellular carcinoma (HCC) following liver transplantation (LT). BACKGROUND ADV score has been reported as a prognostic surrogate biomarker of HCC following LT and hepatectomy. METHODS The study patients were 1599 LT recipients selected from the Korean Organ Transplantation Registry database. RESULTS Deceased-donor and living-donor LTs were performed in 143 and 1456 cases, respectively. Weak correlation was present among AFP, DCP, and TV. The viable HCC group showed ADV score-dependent disease-free survival (DFS) and overall patient survival (OS) rates from 1log to 10log (p<0.001). Prognosis of complete pathological response group was comparable to that of ADV score <1log (p≥0.099). ADV score cutoff of 5log (ADV-5log) for DFS and OS was obtained through receiver operating characteristic curve analysis with area under the curve ≥0.705. Both ADV-5log and Milan criteria were independent risk factors for DFS and OS, and their prognostic impacts were comparable to each other. Combination of these two factors resulted in further prognostic stratification, showing hazard ratios for DFS and OS as 2.98 and 2.26 respectively for one risk factor and 7.92 and 8.19 respectively for two risk factors (p<0.001). ABO-incompatible recipients with ADV score ≥8log or two risk factors showed higher recurrence rates. CONCLUSIONS This validation study revealed that ADV score is a reliable surrogate biomarker for posttransplant HCC prognosis, which can be used for selecting LT candidates and guiding risk-based posttransplant follow-up surveillance.
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Affiliation(s)
- Gil-Chun Park
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea.
| | - Young Kyoung You
- Department of Surgery, College of Medicine, The Catholic University of Korea, Banpodae-ro 222, Seocho-gu, Seoul, 06591, Korea.
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Jin Joo
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Je Ho Ryu
- Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Pusan, Korea
| | - Donglak Choi
- Department of Surgery, Catholic University of Daegu, Daegu, Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Dong-Sik Kim
- Division of HBP Surgery and Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - Yang Won Nah
- Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Koo Jeong Kang
- Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Korea
| | - Jai Young Cho
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Hee Chul Yu
- Department of Surgery, Jeonbuk National University Medical School, Jeonju, Korea
| | - Deok Gie Kim
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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20
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Huang X, Tian H, Huang L, Chen Q, Yang Y, Zeng R, Xu J, Chen S, Zhou X, Liu G, Li H, Zhang Y, Zhang J, Zheng J, Cai H, Zhou H. Well-Ordered Au Nanoarray for Sensitive and Reproducible Detection of Hepatocellular Carcinoma-Associated miRNA via CHA-Assisted SERS/Fluorescence Dual-Mode Sensing. Anal Chem 2023; 95:5955-5966. [PMID: 36916246 DOI: 10.1021/acs.analchem.2c05640] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
Abstract
Ultra-sensitive detection of cancer-related biomarkers in serum is of great significance for early diagnosis, treatment, prognosis, and staging of cancer. In this work, we proposed a surface-enhanced Raman scattering and fluorescence (SERS/FL) dual-mode biosensor for hepatocellular carcinoma (HCC)-related miRNA (miR-224) detection using the composition of well-arranged Au nanoarrays (Au NAs) substrate coupled with the target-catalyzed hairpin assembly (CHA) strategy. The hot spots densely and uniformly distributed on the Au array offers considerably enhanced and reproducible SERS signals, along with their wide and open surface to facilitate miR-224 adsorption. By this sensing strategy, the target miR-224 can be detected in a wide linear range (1 fM to 1 nM) with a limit of detection of 0.34 fM in the SERS mode and 0.39 fM in the FL mode. Meanwhile, this biosensor with exceptional specificity and anti-interference ability can discriminate target miR-224 from other interference miRNAs. Practical analysis of human blood samples also demonstrated considerable reliability and repeatability of our developed strategy. Furthermore, this biosensor can distinguish HCC cancer subjects from normal ones and monitor HCC patients before and after hepatectomy as well as guide the distinct Barcelona clinic liver cancer (BCLC) stages. Overall, benefiting from a well-arranged Au nanoarray, CHA amplification strategy, and SERS/metal enhanced fluorescence effect, this established biosensor opens new avenues for the early prediction, warning, monitoring, and staging of HCC.
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Affiliation(s)
- Xueqin Huang
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Hemi Tian
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Lei Huang
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Qiuxia Chen
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Yingqi Yang
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Runmin Zeng
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Jun Xu
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Shanze Chen
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Xia Zhou
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Guangqiang Liu
- School of Physics and Physical Engineering, Shandong Provincial Key Laboratory of Laser Polarization and Information Technology, Qufu Normal University, Qufu 273100, China
| | - Haoyu Li
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, Key Laboratory of Material Physics Ministry of Education, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, China
| | - Yuan Zhang
- Henan Key Laboratory of Diamond Optoelectronic Materials and Devices, Key Laboratory of Material Physics Ministry of Education, School of Physics and Microelectronics, Zhengzhou University, Zhengzhou 450052, China
| | - Jianglin Zhang
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
| | - Junxia Zheng
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
| | - Huaihong Cai
- College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China
| | - Haibo Zhou
- The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.,College of Pharmacy, Jinan University, Guangzhou 510632, China
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21
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Chen IH, Hsu CC, Yong CC, Cheng YF, Wang CC, Lin CC, Chen CL. AFP Response to Locoregional Therapy Can Stratify the Risk of Tumor Recurrence in HCC Patients after Living Donor Liver Transplantation. Cancers (Basel) 2023; 15:cancers15051551. [PMID: 36900345 PMCID: PMC10001078 DOI: 10.3390/cancers15051551] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 02/17/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023] Open
Abstract
(1) Background: Alpha-fetoprotein (AFP) has been incorporated into the selection criteria of liver transplantation and been used to predict the outcome of hepatocellular carcinoma (HCC) recurrence. Locoregional therapy (LRT) is recommended for bridging or downstaging in HCC patients listed for liver transplantation. The aim of this study was to evaluate the effect of the AFP response to LRT on the outcomes of hepatocellular carcinoma patients after living donor liver transplantation (LDLT). (2) Methods: This retrospective study included 370 HCC LDLT recipients with pretransplant LRT from 2000 to 2016. The patients were divided into four groups according to AFP response to LRT. (3) Results: The nonresponse group had the worst 5-year cumulative recurrence rates whereas the complete-response group (patients with abnormal AFP before LRT and with normal AFP after LRT) had the best 5-year cumulative recurrence rate among the four groups. The 5-year cumulative recurrence rate of the partial-response group (AFP response was over 15% lower) was comparable to the control group. (4) Conclusions: AFP response to LRT can be used to stratify the risk of HCC recurrence after LDLT. If a partial AFP response of over 15% declineis achieved, a comparable result to the control can be expected.
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Affiliation(s)
- I-Hsuan Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Chien-Chin Hsu
- Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Yu-Fan Cheng
- Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
- Correspondence: ; Tel.: +886-77317123 (ext. 8093); Fax: +886-77354309
| | - Chao-Long Chen
- Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan
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22
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Kurihara T, Harada N, Morinaga A, Tomiyama T, Toshida K, Kosai Y, Tomino T, Toshima T, Nagao Y, Morita K, Itoh S, Yoshizumi T. Predictive Factors for the Resectable Type of Hepatocellular Carcinoma Recurrence After Living Donor Liver Transplant. Transplant Proc 2023; 55:191-196. [PMID: 36564321 DOI: 10.1016/j.transproceed.2022.09.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 09/19/2022] [Accepted: 09/20/2022] [Indexed: 12/24/2022]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after living donor liver transplant (LDLT) is an essential factor defining prognosis, and surgical resection is the only curative treatment. However, the factors that define whether surgical resection is possible remain unclear. Here, we compared resectable and unresectable HCC recurrence cases after LDLT and examined factors that determine whether surgical resection is possible. Resectable (n = 17) and unresectable (n = 14) groups among 264 patients who underwent LDLT for HCC from January 1999 to March 2020 were compared and examined for recurrence type, prognosis, and clinicopathologic factors. Overall survival after LDLT (median, 8.5 vs 1.7 years, P < .01) was significantly longer in the resectable group. In univariate analysis, female recipient rate, lymphocyte to monocyte ratio (LMR) ≥2.75, and tumor size ≤5.0 cm were significantly higher in the resectable group. Younger donors, lower Model for End-Stage Liver Disease scores, lower graft volume, and lower graft volume to standard liver volume ratio were evident in the resectable group. In multivariate analysis, female recipient rate (P = .0034) and LMR ≥2.75 (P = .0203) were independent predictive factors for resectable HCC recurrence after LDLT. Female recipient and LMR ≥2.75 before transplant could predict the surgically resectable type of HCC recurrence after LDLT.
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Affiliation(s)
- Takeshi Kurihara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noboru Harada
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Akinari Morinaga
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomiyama
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Katsuya Toshida
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yukiko Kosai
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takahiro Tomino
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshihiro Nagao
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazutoyo Morita
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Itoh
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
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23
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Yan H, Xiang Z, Zhao C, Zou S, Huang M. Long-term Outcomes of Patients with Hepatocellular Carcinoma Who Underwent Microwave Ablation after Downstaging with Transarterial Chemoembolization to Barcelona Clinic Liver Cancer Stage A. J Vasc Interv Radiol 2022; 34:768-776. [PMID: 36581194 DOI: 10.1016/j.jvir.2022.12.466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 10/23/2022] [Accepted: 12/19/2022] [Indexed: 12/28/2022] Open
Abstract
PURPOSE To compare the clinical results of microwave ablation (MWA) between patients downstaged to Barcelona Clinic Liver Cancer (BCLC) Stage A with transarterial chemoembolization (TACE) and those initially classified as BCLC Stage A. MATERIALS AND METHODS From January 2012 to May 2017, 1,087 patients were reviewed retrospectively using propensity score matching (1:1): 86 patients underwent MWA as a curative treatment after downstaging to BCLC Stage A by TACE (downstaging group) and 86 patients initially classified as BCLC Stage A underwent MWA (control group). The overall survival (OS) and disease-free survival (DFS) between the 2 groups were compared. RESULTS The 1-, 3-, and 5-year OS rates were 95.3%, 79.1%, and 58.1%, respectively, in the downstaging group and 93.0%, 81.4%, and 61.6%, respectively, in the control group (hazard ratio [HR], 0.75; 95% CI, 0.50-1.13; P = .162). The 1-, 3-, and 5-year DFS rates were 80.2%, 50.0%, and 24.4%, respectively, in the downstaging group and 77.9%, 52.3%, and 27.9%, respectively, in the control group (HR, 1.08; 95% CI, 0.76-1.53; P = .678). No significant differences were found in OS and DFS. CONCLUSIONS The long-term prognosis in patients with HCC who underwent MWA after downstaging to BCLC Stage A using TACE was similar to that in patients with initial BCLC Stage A.
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Affiliation(s)
- Huzheng Yan
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Minimally Invasive & Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhanwang Xiang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Chenghao Zhao
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sibin Zou
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Mingsheng Huang
- Department of Interventional Radiology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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24
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Di Martino M, Vitale A, Ferraro D, Maniscalco M, Pisaniello D, Arenga G, Falaschi F, Terrone A, Iacomino A, Galeota Lanza A, Esposito C, Cillo U, Vennarecci G. Downstaging Therapies for Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation: A Systematic Review and Meta-Analysis on Intention-to-Treat Outcomes. Cancers (Basel) 2022; 14:5102. [PMID: 36291885 PMCID: PMC9600776 DOI: 10.3390/cancers14205102] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45−2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91−2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26−11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15−8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted.
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Affiliation(s)
- Marcello Di Martino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Daniele Ferraro
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Marilisa Maniscalco
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Donatella Pisaniello
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Giuseppe Arenga
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Federica Falaschi
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alfonso Terrone
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Iacomino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | | | - Ciro Esposito
- Liver Intesive Care Unit, Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Giovanni Vennarecci
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
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25
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Ince V, Sahin TT, Akbulut S, Yilmaz S. Liver transplantation for hepatocellular carcinoma: Historical evolution of transplantation criteria. World J Clin Cases 2022; 10:10413-10427. [PMID: 36312504 PMCID: PMC9602233 DOI: 10.12998/wjcc.v10.i29.10413] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 07/27/2022] [Accepted: 08/25/2022] [Indexed: 02/05/2023] Open
Abstract
Liver transplantation (LT) for hepatocellular carcinoma is still a hot topic, and the main factor that is associated with the success of treatment is to determine the patients who will benefit from LT. Milan criteria have been defined 25 years ago and still is being used for patient selection for LT. However, in living donor LT, the Milan criteria is being extended. Current criteria for patient selection do not only consider morphologic characteristics such as tumor size and number of tumor nodules but also biologic markers that show tumor aggressiveness is also being considered. In the present review article, we have summarized all the criteria and scoring systems regarding LT for hepatocellular carcinoma. All criteria have 5-year overall survival rates that were comparable to the Milan Criteria and ranged between 60%-85%. On the other hand, it was seen that the recurrence rates had increased as the Milan criteria were exceeded; the 5-year recurrence rates ranged between 4.9% to 39.9%. Treatment of hepatocellular carcinoma needs a multidisciplinary approach. Ideal selection criteria are yet to be discovered. The same is true for treatment modalities. The goal will be achieved by a harmonic interplay between basic science researchers and clinicians.
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Affiliation(s)
- Volkan Ince
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Tevfik Tolga Sahin
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Sami Akbulut
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
- Biostatistics and Medical Informatics, Inonu University Faculty of Medicine, Malatya 44280, Turkey
| | - Sezai Yilmaz
- Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya 44280, Turkey
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26
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Hepatocellular Carcinoma, Alpha Fetoprotein, and Liver Allocation for Transplantation: Past, Present and Future. Curr Oncol 2022; 29:7537-7551. [PMID: 36290870 PMCID: PMC9600271 DOI: 10.3390/curroncol29100593] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/01/2022] [Accepted: 10/02/2022] [Indexed: 11/05/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading indications for liver transplantation and has been the treatment of choice due to the oncologic benefit for patients with advanced chronic liver disease (AdvCLD) and small tumors for the last 25 years. For HCC patients undergoing liver transplantation, alpha fetoprotein (AFP) has increasingly been applied as an independent predictor for overall survival, disease free recurrence, and waitlist drop out. In addition to static AFP, newer studies evaluating the AFP dynamic response to downstaging therapy show enhanced prognostication compared to static AFP alone. While AFP has been utilized to select HCC patients for transplant, despite years of allocation policy changes, the US allocation system continues to take a uniform approach to HCC patients, without discriminating between those with favorable or unfavorable tumor biology. We aim to review the history of liver allocation for HCC in the US, the utility of AFP in liver transplantation, the implications of weaving AFP as a biomarker into policy. Based on this review, we encourage the US transplant community to revisit its HCC organ allocation model, to incorporate more precise oncologic principles for patient selection, and to adopt AFP dynamics to better stratify waitlist dropout risk.
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27
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Shan Y, Yu X, Yang Y, Sun J, Wu S, Mao S, Lu C. Nomogram for the Preoperative Prediction of the Macrotrabecular-Massive Subtype of Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:717-728. [PMID: 35974953 PMCID: PMC9375985 DOI: 10.2147/jhc.s373960] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 07/25/2022] [Indexed: 12/12/2022] Open
Abstract
Background The macrotrabecular-massive subtype of hepatocellular carcinoma (MTM-HCC) is an aggressive histological type and results in poor prognosis. We developed a nomogram model based on laboratory results to predict the presence of MTM-HCC. Methods A total of 357 HCC patients who underwent radical surgery between January 2015 and December 2020 at Ningbo Medical Center Lihuili Hospital were grouped according to histological type. After propensity score matching (PSM), 267 patients were divided into MTM-HCC (n = 76) and non-MTM-HCC (n = 191) groups. A LASSO regression analysis model was used to select predictive factors. Finally, a nomogram for predicting the presence of MTM-HCC was established. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Results The 1-, 3-, and 5-year disease-free survival (DFS) and overall survival (OS) rates for MTM-HCC were 60.0%, 36.0%, 32.4% and 92.1%, 68.7%, 52.2%, respectively. Survival analysis indicated that the probabilities of achieving DFS and OS were significantly worse in the MTM-HCC group than in the non-MTM-HCC group (P < 0.05). The nomogram model that included AST levels, PT and AFP levels achieved a better C-index of 0.723 (95% CI: 0.659-0.787). DCA revealed that the nomogram model could lead to net benefits and exhibited a wider range of threshold probabilities in the prediction of MTM-HCC. Conclusion The nomogram model included AST, PT and AFP could achieve an optimal performance in the preoperative prediction of MTM-HCC.
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Affiliation(s)
- Yuying Shan
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Xi Yu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Yong Yang
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Jiannan Sun
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Shengdong Wu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Shuqi Mao
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
| | - Caide Lu
- Department of Hepatopancreatobiliary Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo, Zhejiang, 315041, People's Republic of China
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28
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Bae JS, Lee DH, Lee SM, Suh KS, Lee KW, Yi NJ, Lee KB, Kim H, Han JK. Performance of LI-RADS Version 2018 on CT for Determining Eligibility for Liver Transplant According to Milan Criteria in Patients at High Risk for Hepatocellular Carcinoma. AJR Am J Roentgenol 2022; 219:86-96. [PMID: 35138137 DOI: 10.2214/ajr.21.27186] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND. LI-RADS has been investigated primarily in terms of detection of hepatocellular carcinoma (HCC), with less attention given to its performance, particularly on CT, in determining eligibility for liver transplant (LT). OBJECTIVE. The purpose of our study was to assess the performance of LI-RADS version 2018 (v2018) on CT for the diagnosis of HCC and determination of LT eligibility according to the Milan criteria (MC). METHODS. This retrospective study included 136 patients (110 men, 26 women; mean age, 53.9 ± 8.1 [SD] years) at high-risk for HCC who underwent liver protocol CT within 3 months before LT between January 2010 and December 2018. Two radiologists independently reviewed CT examinations using LI-RADS v2018; Organ Procurement and Transplantation Network (OPTN) classes were constructed from the LI-RADS interpretations. Histopathologic analysis of liver explants served as the reference standard for determining the presence of HCC and LT eligibility based on MC. Diagnostic performance was evaluated. Overall survival (OS) was assessed based on medical record review. RESULTS. Based on histopathologic evaluation of liver explants in the 136 patients, 27 patients had no malignancy, 77 were eligible for LT due to HCC within MC, and 32 were unsuitable for LT (i.e., HCC beyond MC in 16 patients, HCC with macrovascular invasion in 12, non-HCC malignancy in four). LR-5 exhibited per-lesion sensitivity and PPV for HCC of 55.9% and 92.8%, respectively, for reader 1 and 39.8% and 86.5% for reader 2. When considering LR-5 observations to represent HCC in assessing MC, LI-RADS had accuracy for determining LT eligibility of 92.7% for reader 1 and 85.3% for reader 2; OPTN criteria had accuracy for determining LT eligibility of 89.0% for reader 1 and 84.4% for reader 2. Five-year OS for patients within MC versus 5-year OS for patients unsuitable for LT was 92.2 months versus 56.0 months for LI-RADS, 92.6 months versus 47.6 months for OPTN criteria, and 93.3 months versus 55.1 months for histopathologic assessment of liver explants. CONCLUSION. LI-RADS v2018, as evaluated on CT in high-risk patients, shows high PPV for HCC detection and high accuracy for determining LT eligibility based on MC. LT eligibility based on preoperative LI-RADS evaluation is associated with post-LT survival. CLINICAL IMPACT. These findings support the use of LI-RADS on CT in assessing eligibility in patients who are candidates for LT.
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Affiliation(s)
- Jae Seok Bae
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Min Lee
- Department of Radiology, Hallym University Sacred Heart Hospital, Anyang-si, Republic of Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kyoung Bun Lee
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Joon Koo Han
- Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
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The efficacy of transarterial chemoembolization in downstaging unresectable hepatocellular carcinoma to curative therapy: a predicted regression model. Invest New Drugs 2022; 40:1146-1152. [PMID: 35723760 DOI: 10.1007/s10637-022-01261-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 05/23/2022] [Indexed: 10/18/2022]
Abstract
Patients with hepatocellular carcinoma (HCC) outside Milan criteria (MC) may be candidates for curative therapy after successful downstaging. We aimed to identify the predictors of successful downstaging of unresectable HCC in patient by transarterial chemoembolization (TACE) outside MC. We performed a retrospective study on patients with unresectable HCC outside MC who received downstaging with TACE. Clinical and laboratory variables were recorded. We identified 101 patients with unresectable HCC who underwent initial TACE, who formed the derivation set of this study. Thirty patients who treated by TACE with the same selection criteria served as an external validation set. We performed univariate and multivariate logistic regression analyses to identify variables associated with successful downstaging. Then we did the predictive model to predict the efficiency of TACE. Of the 101 patients in the study, 26 patients (25.7%) were successfully downstaging and 75 patients (74.3%) failed downstaging. Multivariate analysis of factors to predict successful downstaging of HCC outside MC the number of tumor (P = 0.01), portal vein tumor thrombosis (PVTT)(p < 0.01), the size of tumor (P = 0.02), hepatitis B surface antigen (HBsAg) (P = 0.01), α-fetoprotein (AFP) (P = 0.02) as significant predictors of successful downstaging. Then we constructed the predictive model. The area under the ROC curve (AUROC) of the predictive equation was 0.90 (95% confidence interval, 0.83-0.95). We found in our study that the number and size of tumors, PVTT, HBsAg, and AFP are good predictors of successful downstaging of unresectable HCC in patients by TACE outside the MC.
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Degroote H, Geerts A, Verhelst X, Van Vlierberghe H. Different Models to Predict the Risk of Recurrent Hepatocellular Carcinoma in the Setting of Liver Transplantation. Cancers (Basel) 2022; 14:cancers14122973. [PMID: 35740638 PMCID: PMC9221160 DOI: 10.3390/cancers14122973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Liver transplantation is considered the first-choice curative therapy for hepatocellular carcinoma in the early phase of the disease, when surgical resection is not possible. Even when implementing restrictive criteria to select patients for liver transplantation, there is a risk of recurrence in the transplanted liver, influencing the long-term outcome and prognosis. As it is challenging to predict the individual risk of recurrence, there is a need for validated and predictive scoring systems to use to stratify patients before and/or after liver transplantation. Most of the proposed scorings include biological markers for tumour behavior, in addition to the number and size of tumoral nodules. In this review, we discuss different published models to assess the risk of recurrent hepatocellular carcinoma after transplantation. Our aim is to refine clinical decisions about prioritization and listing for liver transplantation, to better inform patients and provide an appropriate surveillance strategy to influence their prognosis. Abstract Liver transplantation is the preferred therapeutic option for non-resectable hepatocellular carcinoma in early-stage disease. Taking into account the limited number of donor organs, liver transplantation is restricted to candidates with long-term outcomes comparable to benign indications on the waiting list. Introducing the morphometric Milan criteria as the gold standard for transplant eligibility reduced the recurrence rate. Even with strict patient selection, there is a risk of recurrence of between 8 and 20% in the transplanted liver, and this is of even greater importance when using more expanded criteria and downstaging protocols. Currently, it remains challenging to predict the risk of recurrence and the related prognosis for individual patients. In this review, the recurrence-risk-assessment scores proposed in the literature are discussed. Currently there is no consensus on the optimal model or the implications of risk stratification in clinical practice. The most recent scorings include additional biological markers for tumour behavior, such as alfa-foetoprotein, and the response to locoregional therapies, in addition to the number and diameter of tumoral nodules. The refinement of the prediction of recurrence is important to better inform patients, guide decisions about prioritization and listing and implement individualized surveillance strategies. In the future, this might also provide indications for tailored immunosuppressive therapy or inclusion in trials for adjuvant treatment.
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Ryan RJ, Taner T, Heimbach JK. When the Sun Sets, Who Doth Not Look for Night? Liver Transpl 2022; 28:747-748. [PMID: 35106929 DOI: 10.1002/lt.26423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 01/28/2022] [Indexed: 01/13/2023]
Affiliation(s)
- Randi J Ryan
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN
| | - Timucin Taner
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN
| | - Julie K Heimbach
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN
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Wong PC, She WH, Ma KW, Sin SL, Wong TCL, Dai WC, Cheung TT, Chan ACY, Lo CM. Impact of Time to Recurrence on Survival Outcome of Salvage Liver Transplantation. J Gastrointest Surg 2022; 26:813-821. [PMID: 34622351 DOI: 10.1007/s11605-021-05146-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Accepted: 08/25/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND Salvage liver transplantation (SLT) is the ideal treatment for patients with recurrent hepatocellular carcinoma (HCC) and liver cirrhosis. The optimal timing for offering SLT was controversial. This study aimed at investigating the impact of time to recurrence and other prognostic factors on survival outcome after SLT. METHODS Between May 2000 and April 2019, patients who had undergone hepatectomy or ablation for HCC and later received SLT in Queen Mary Hospital were included. Clinico-pathological data during primary treatment and SLT were retrospectively reviewed. Kaplan-Meier analysis and log-rank test were used to determine overall and disease-free survival after SLT. Prognostic factors affecting overall and disease-free survival were determined by multivariate analysis using Cox regression analysis. P-value of less than 0.05 was considered statistically significant. RESULTS Fifty-three patients were identified within the specified period including 22 patients in early recurrence group (ER group, time to recurrence within 1 year) and 31 patients in late recurrence group (LR group, time to recurrence more than 1 year). The 1-, 5-, and 10-year overall survival after primary treatment was 100%, 76.6%, and 61.1% in the ER group and 100%, 90%, and 76.4% in the LR group (p = 0.59). There were no statistical differences in overall survival (p = 0.84) and disease-free survival (p = 0.85) after SLT between ER and LR group. Pre-transplant alpha-fetoprotein > = 400 ng/mL (p = 0.007) and macrovascular invasion in explant (p = 0.002) were independent risk factors for shorter overall survival after primary treatment. CONCLUSION Time to recurrence after primary treatment of HCC did not affect survival outcome after SLT. With careful patient selection, SLT could be offered to patient with early or late tumor recurrence.
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Affiliation(s)
- Pak Chiu Wong
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Wong Hoi She
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong.
| | - Ka Wing Ma
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Sui Ling Sin
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Tiffany Cho Lam Wong
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Wing Chiu Dai
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Tan To Cheung
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Albert Chi Yan Chan
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
| | - Chung Mau Lo
- Division of Liver Transplantation, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong
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Papaconstantinou D, Hewitt DB, Brown ZJ, Schizas D, Tsilimigras DI, Pawlik TM. Patient stratification in hepatocellular carcinoma: impact on choice of therapy. Expert Rev Anticancer Ther 2022; 22:297-306. [PMID: 35157530 DOI: 10.1080/14737140.2022.2041415] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION HCC comprises around 60 to 80% of all primary liver cancers and exhibits wide geographical variability. Appropriate treatment allocation needs to include both patient and tumor characteristics. AREAS COVERED Current HCC classification systems to guide therapy are either liver function-centric and evaluate physiologic liver function to guide therapy or prognostic stratification classification systems broadly based on tumor morphologic parameters, patient performance status, and liver reserve assessment. This review focuses on different classification systems for HCC, their strengths, and weaknesses as well as the use of artificial intelligence in improving prognostication in HCC. EXPERT OPINION Future HCC classification systems will need to incorporate clinic-pathologic data from a multitude of sources and emerging therapies to develop patient-specific treatment plans targeting a patient's unique tumor profile.
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Affiliation(s)
- Dimitrios Papaconstantinou
- Third Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - D Brock Hewitt
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Zachary J Brown
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Dimitrios Schizas
- First Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Medical School, Greece
| | - Diamantis I Tsilimigras
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
| | - Timothy M Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio
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Guo L, Wan L, Hu Y, Huang H, He B, Wen Z. Serum N-glycan profiling as a diagnostic biomarker for the identification of hepatitis B virus-associated hepatocellular carcinoma. J Gastrointest Oncol 2022; 13:344-354. [PMID: 35284106 PMCID: PMC8899740 DOI: 10.21037/jgo-22-93] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/11/2022] [Indexed: 03/09/2025] Open
Abstract
BACKGROUND Changes in N-glycosylation of proteins are thought to play a key role in cancer. This study aims to investigate the changes in the serum N-glycan profiles of patients with hepatitis B virus (HBV)-related liver disease, and to evaluate the role of N-glycan markers in the noninvasive diagnosis of hepatocellular carcinoma (HCC). METHODS Serum samples were available for 21 patients with HCC, 20 patients with liver cirrhosis (LC), 20 patients with chronic hepatitis B (CHB), and 20 healthy subjects. Serum N-glycans were released and analyzed using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Serum AFP was determined by electrochemiluminescence (ECL) (AFP reference value range: <10 ng/mL). RESULTS There were characteristic changes in the serum N-glycan profiles of patients with HBV-related liver disease, including NA2FB, NA3, and NA3Fb. NA2FB was the most abundant in LC patients, while NA3Fb abundance was the highest in HCC patients. For HCC screening in patients, especially in patients with LC, the sensitive of Log peak 9 (94.4%) and Log (peak 9/peak 7) (88.9%) were better than alpha-fetoprotein (AFP) (33.3-61.1%), and their specificity was similar to that of AFP. The receiver operating characteristic (ROC) curve showed that the accuracy of Log peak 9 (AUC: 0.81±0.07) and Log (peak 9/peak 7) (AUC: 0.87±0.06) was better than that of AFP (AUC: 0.72±0.09), while the accuracy of AFP combined with the above 2 indexes was better than that of a single index. Moreover, Log (peak 9/peak 7) combined with AFP (AUC: 0.89±0.06) had the best accuracy in the diagnosis of HCC. CONCLUSIONS Our research indicates that N-glycan may serve a new, valuable, and noninvasive alternative method for diagnosing HCC, and it may be a supplement to AFP in the diagnosis of HCC in patients with HBV-related liver disease.
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Hu X, Chen R, Wei Q, Xu X. The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We? Int J Biol Sci 2022; 18:536-551. [PMID: 35002508 PMCID: PMC8741863 DOI: 10.7150/ijbs.64537] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/15/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has been acknowledged as a leading cause of death among cirrhosis patients. Difficulties in early diagnosis and heterogeneity are obstacles to effective treatment, especially for advanced HCC. Liver transplantation (LT) is considered the best therapy for HCC. Although many biomarkers are being proposed, alpha-fetoprotein (AFP), which was identified over 60 years ago, remains the most utilized. Recently, much hope has been placed in the immunogenicity of AFP to develop novel therapies, such as AFP vaccines and AFP-specific adoptive T-cell transfer (ACT). This review summarizes the performance of AFP as a biomarker for HCC diagnosis and prognosis, as well as its correlation with molecular classes. In addition, the role of AFP in LT is also described. Finally, we highlight the mechanism and application prospects of two immune therapies (AFP vaccine and ACT) for HCC. In general, our review points out the prevalence of AFP in HCC, accompanied by some controversies and novel directions for future research.
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Affiliation(s)
- Xin Hu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.,Zhejiang University Cancer Center, Hangzhou, 310058, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Ronggao Chen
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.,Zhejiang University Cancer Center, Hangzhou, 310058, China.,Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China.,Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China
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Lozanovski VJ, Ramouz A, Aminizadeh E, Al-Saegh SAH, Khajeh E, Probst H, Picardi S, Rupp C, Chang DH, Probst P, Mehrabi A. Prognostic role of selection criteria for liver transplantation in patients with hepatocellular carcinoma: a network meta-analysis. BJS Open 2022; 6:zrab130. [PMID: 35211739 PMCID: PMC8874238 DOI: 10.1093/bjsopen/zrab130] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Revised: 10/27/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Patients with hepatocellular carcinoma (HCC) are selected for transplantation if they have a low tumour burden and low risk of recurrence. The morphometric Milan criteria have been the cornerstone for patient selection, but dynamic morphological and biological tumour characteristics surfaced as an encouraging tool to refine the selection of patients with HCC and to support the expansion of the Milan criteria. The outcomes of the most prevalent models that select patients with HCC for liver transplantation were analysed in this study, which aimed to identify the selection model that offered the best recurrence-free and overall survival after transplantation. METHODS Studies that compared Milan, University of California San Francisco (UCSF), up-to-seven (UPTS), alpha-fetoprotein (AFP), and MetroTicket 2.0 (MT2) models were included. One-year, 3-year, and 5-year recurrence-free and overall survival rates of patients selected for transplantation using different models were analysed. RESULTS A total of 60 850 adult patients with HCC selected for liver transplantation using Milan, UCSF, UPTS, AFP, or MT2 criteria were included. Patients selected for transplantation using the MT2 model had the highest 1-, 3-, and 5-year recurrence-free survival. In addition, patients selected for transplantation using MT2 criteria had the best 1- and 3-year overall survival, whereas patients selected for transplantation using the Milan criteria had the best 5-year overall survival rates. CONCLUSION The MT2 model offered the best post-transplant outcomes in patients with HCC, highlighting the importance of considering tumour morphology and biology when selecting patients with HCC for liver transplantation.
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Affiliation(s)
- Vladimir J Lozanovski
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
| | - Ali Ramouz
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Ehsan Aminizadeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Sadeq Ali-Hasan Al-Saegh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Elias Khajeh
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Heike Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Susanne Picardi
- Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Rupp
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
- Department of Internal Medicine IV, University Hospital Heidelberg, Heidelberg, Germany
| | - De-Hua Chang
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
- Department of Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Pascal Probst
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- The Study Center of the German Surgical Society (SDGC), University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), University Hospital Heidelberg, Heidelberg, Germany
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Orci LA, Combescure C, Fink M, Oldani G, Compagnon P, Andres A, Berney T, Toso C. Predicting recurrence of hepatocellular carcinoma after liver transplantation using a novel model that incorporates tumor and donor-related factors. Transpl Int 2021; 34:2875-2886. [PMID: 34784081 DOI: 10.1111/tri.14161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 01/11/2023]
Abstract
Evidence suggests that liver graft quality impacts on posttransplant recurrence of hepatocellular carcinoma (HCC). As of today, selection criteria only use variables related to tumor characteristics. Within the Scientific Registry of Transplant Recipients, we identified patients with HCC who underwent liver transplantation between 2004 and 2016 (development cohort, n = 10 887). Based on tumor recurrence rates, we fitted a competing-risk regression incorporating tumor- and donor-related factors, and we developed a prognostic score. Results were validated both internally and externally in the Australia and New Zealand Liver Transplant Registry. Total tumor diameter (subhazard ratio [sub-HR] 1.52 [1.28-1.81]), alpha-feto protein (sub-HR 1.27 [1.23-1.32], recipient male gender (sub-HR 1.43 [1.18-1.74]), elevated donor body mass index (sub-HR 1.26 [1.01-1.58]), and shared graft allocation policy (sub-HR 1.20 [1.01-1.43]) were independently associated with tumor recurrence. We next developed the Darlica score (sub-HR 2.72 [2.41-3.08] P < 0.001) that allows identifying risky combinations between a given donor and a given recipient. Results were validated internally (n = 3 629) and externally in the Australia and New Zealand Liver Transplant Registry (n = 370). The current score is based on variables that are readily available at the time of graft offer. It allows identifying hazardous donor-recipient combinations in terms of risk of tumor recurrence and overall survival.
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Affiliation(s)
- Lorenzo A Orci
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | | | - Michael Fink
- Department of Surgery, Austin Health, Medicine Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia
| | - Graziano Oldani
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Philippe Compagnon
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Axel Andres
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Thierry Berney
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
| | - Christian Toso
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.,Faculty of Medicine, Hepato-pancreato-biliary Centre, Geneva University Hospitals, Geneva, Switzerland
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Hwang S, Song GW, Ahn CS, Kim KH, Moon DB, Ha TY, Jung DH, Park GC, Yoon YI, Lee SG. Quantitative Prognostic Prediction Using ADV Score for Hepatocellular Carcinoma Following Living Donor Liver Transplantation. J Gastrointest Surg 2021; 25:2503-2515. [PMID: 33532981 DOI: 10.1007/s11605-021-04939-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 01/18/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND We assessed the prognostic impact of the ADV score (α-fetoprotein [AFP]-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score) for predicting hepatocellular carcinoma (HCC) recurrence and patient survival after living donor liver transplantation (LDLT). METHODS This study included 843 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. These cases were divided into treatment-naïve (TN, n = 256]) and pretransplant-treated (PT, n = 587 [69.6%]) groups. RESULTS There were weak or nearly no correlations among AFP, DCP, and TV. There existed high correlations between the pretransplant and explant findings regarding tumor number, size, and ADV score. Right lobe grafts were implanted in 760 (90.2%) patients. HCC recurrence and all-cause patient death occurred in 182 (15.9%) and 126 (15.0%) respectively during the follow-up period for 75.6 ± 35.5 months. The 5-year tumor recurrence (TR) and overall patient survival (OS) rates were 21.5% and 86.2%, respectively. The PT group showed higher TR (p < 0.001) and lower OS rates (p < 0.001). TR and OS were closely correlated with both pretransplant and explant ADV scores in the TN and PT groups. The ADV score enabled further prognostic stratification of the patients within and beyond the Milan, UCSF, and Asan Medical Center criteria. Compared with the 7 pre-existing selection criteria, ADV score with a cutoff of 5log showed the highest prognostic contrast regarding TR and OS. CONCLUSIONS Our prognostic prediction model using ADV scores is an integrated quantitative surrogate biomarker for posttransplant prognosis in HCC patients and can provide reliable information that assists the decision-making for LDLT.
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Affiliation(s)
- Shin Hwang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea.
| | - Gi-Won Song
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Chul-Soo Ahn
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Deok-Bog Moon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Tae-Yong Ha
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Dong-Hwan Jung
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Gil-Chun Park
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
| | - Sung-Gyu Lee
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Olympic-ro 43-gil 88, Songpa-gu, Seoul, 05505, Korea
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 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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Núñez KG, Sandow T, Fort D, Patel J, Hibino M, Carmody I, Cohen AJ, Thevenot P. Baseline Alpha-Fetoprotein, Alpha-Fetoprotein-L3, and Des-Gamma-Carboxy Prothrombin Biomarker Status in Bridge to Liver Transplant Outcomes for Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:4765. [PMID: 34638251 PMCID: PMC8507524 DOI: 10.3390/cancers13194765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/08/2021] [Accepted: 09/20/2021] [Indexed: 11/16/2022] Open
Abstract
The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP > 20 ng/mL, AFP-L3 > 15%, and DCP > 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with < 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.
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Affiliation(s)
- Kelley G. Núñez
- Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Tyler Sandow
- Department of Radiology, Ochsner Health, New Orleans, LA 70121, USA;
| | - Daniel Fort
- Center for Outcomes and Health Services Research, Ochsner Health, New Orleans, LA 70121, USA;
| | - Jai Patel
- Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Mina Hibino
- Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Ian Carmody
- Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA 70121, USA;
| | - Ari J. Cohen
- Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
- Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA 70121, USA;
- Faculty of Medicine, The University of Queensland, New Orleans, LA 70121, USA
| | - Paul Thevenot
- Institute of Translational Research, Ochsner Health, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
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Liver Transplantation in Patients with Hepatocellular Carcinoma beyond the Milan Criteria: A Comprehensive Review. J Clin Med 2021; 10:jcm10173932. [PMID: 34501381 PMCID: PMC8432180 DOI: 10.3390/jcm10173932] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Revised: 08/22/2021] [Accepted: 08/29/2021] [Indexed: 02/07/2023] Open
Abstract
The Milan criteria (MC) were developed more than 20 years ago and are still considered the benchmark for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). However, the strict application of MC might exclude some patients who may receive a clinical benefit of LT. Several expanded criteria have been proposed. Some of these consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. This essential review aims to present the current data on the pretransplant selection criteria for LT in patients with HCC exceeding the MC at presentation based on morphological and histological characteristics of the tumor and to critically discuss those that have been validated in clinical practice. Moreover, the role of HCC biological markers and the tumor response to downstaging procedures as new tools for selecting patients with a tumor burden outside of the MC for LT is evaluated.
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Lang SA, Bednarsch J, Czigany Z, Joechle K, Kroh A, Amygdalos I, Strnad P, Bruns T, Heise D, Ulmer F, Neumann UP. Liver transplantation in malignant disease. World J Clin Oncol 2021; 12:623-645. [PMID: 34513597 PMCID: PMC8394155 DOI: 10.5306/wjco.v12.i8.623] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 06/15/2021] [Accepted: 07/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.
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Affiliation(s)
- Sven Arke Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Zoltan Czigany
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Katharina Joechle
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Andreas Kroh
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Iakovos Amygdalos
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Pavel Strnad
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Tony Bruns
- Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Florian Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
| | - Ulf Peter Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen 52074, Germany
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Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study. Eur J Surg Oncol 2021; 48:121-132. [PMID: 34456082 DOI: 10.1016/j.ejso.2021.08.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 07/25/2021] [Accepted: 08/09/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%-40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown. METHODS Data of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups. RESULTS 489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162-1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922-1.786, P = 0.139). CONCLUSION HCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.
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Recurrent Hepatocellular Carcinoma After Liver Transplantation: Validation of a Pathologic Risk Score on Explanted Livers to Predict Recurrence. Transplant Proc 2021; 53:1975-1979. [PMID: 34272052 DOI: 10.1016/j.transproceed.2021.05.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 04/25/2021] [Accepted: 05/04/2021] [Indexed: 01/23/2023]
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) after liver transplantation is a major cause of morbidity and mortality. To date, there is no widely accepted pathologic assessment tool to predict HCC recurrence. In 2007, we developed a pathologic risk score that stratified patients into low, intermediate, or high risk for recurrence based on explant pathology. The aim of this study was to externally validate this risk score. METHODS We retrospectively evaluated 124 patients over a 10-year period who underwent liver transplantation for HCC. Using explanted pathology reports, each patient was stratified according to the pathologic risk score and followed over time for HCC recurrence. RESULTS Recurrence occurred in 15 patients (12%) after a mean follow-up of 25 months. Using the pathologic risk score, 10 (8%), 21 (17%), and 93 (75%) patients were stratified into high, intermediate, and low risk of recurrence, respectively. Among these risk groups, recurrence occurred in 50%, 28.5%, and 4.3% (P < .01) of patients, respectively. Using the optimal cutoff value ≤3.5, our risk score had a sensitivity of 80% and specificity of 79% with an area under the receiver operator characteristic curve of 0.8. Those with lower risk scores had higher recurrence-free survival (P < .0001). CONCLUSIONS Our pathologic risk score accurately risks stratified patients for HCC recurrence after liver transplant. It can be used to tailor surveillance strategies for those deemed to be at elevated risk for recurrence.
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Simple parameters predicting extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma. Sci Rep 2021; 11:12984. [PMID: 34155324 PMCID: PMC8217564 DOI: 10.1038/s41598-021-92503-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 06/10/2021] [Indexed: 02/06/2023] Open
Abstract
Extrahepatic recurrence (EHR) after curative hepatectomy for hepatocellular carcinoma (HCC) is associated with a poor prognosis. We investigated the features of EHR and identified its predictive factors. This retrospective study included 398 treatment-naive patients who underwent curative hepatectomy for HCC at two tertiary hospitals. Multivariate Cox-regression analysis was performed to identify the variables associated with EHR. EHR was diagnosed in 94 patients (23.6%) over a median follow-up period of 5.92 years, most commonly in the lungs (42.6%). The 5-/10-year cumulative rates of HCC recurrence and EHR were 63.0%/75.6% and 18.1%/35.0%, respectively. The median time to EHR was 2.06 years. Intrahepatic HCC recurrence was not observed in 38.3% of patients on EHR diagnosis. On multivariate analysis, pathologic modified Union for International Cancer Control stage (III, IVa), surgical margin involvement, tumor necrosis, sum of tumor size > 7 cm, and macrovascular invasion were predictive factors of EHR. Four risk levels and their respective EHR rates were defined as follows: very low risk, 1-/5-year, 3.1%/11.6%; low risk, 1-/5-year, 12.0%/27.7%; intermediate risk, 1-/5-year, 36.3%/60.9%; and high risk, 1-year, 100.0%. Our predictive model clarifies the clinical course of EHR and could improve the follow-up strategy to improve outcomes.
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Wu J, Zhou X, Li P, Lin X, Wang J, Hu Z, Zhang P, Chen D, Cai H, Niessner R, Haisch C, Sun P, Zheng Y, Jiang Z, Zhou H. Ultrasensitive and Simultaneous SERS Detection of Multiplex MicroRNA Using Fractal Gold Nanotags for Early Diagnosis and Prognosis of Hepatocellular Carcinoma. Anal Chem 2021; 93:8799-8809. [PMID: 34076420 DOI: 10.1021/acs.analchem.1c00478] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Sensitive and simultaneous detection of multiple cancer-related biomarkers in serum is essential for diagnosis, therapy, prognosis, and staging of cancer. Herein, we proposed a magnetically assisted sandwich-type surface-enhanced Raman scattering (SERS)-based biosensor for ultrasensitive and multiplex detection of three hepatocellular carcinoma-related microRNA (miRNA) biomarkers. The biosensor consists of an SERS tag (probe DNA-conjugated DNA-engineered fractal gold nanoparticles, F-AuNPs) and a magnetic capture substrate (capture DNA-conjugated Ag-coated magnetic nanoparticles, AgMNPs). The proposed strategy achieved simultaneous and sensitive detection of three miRNAs (miRNA-122, miRNA-223, and miRNA-21), and the limits of detection of the three miRNAs in human serum are 349 aM for miRNA-122, 374 aM for miRNA-223, and 311 aM for miRNA-21. High selectivity and accuracy of the SERS biosensor were proved by practical analysis in human serum. Moreover, the biosensor exhibited good practicability in multiplex detection of three miRNAs in 92 clinical sera from AFP-negative patients, patients before and after hepatectomy, recurred and relapse-free patients after hepatectomy, and hepatocellular carcinoma patients at distinct Barcelona clinic liver cancer stages. The experiment results demonstrate that our SERS-based assay is a promising candidate in clinical application and exhibited potential for the prediction, diagnosis, monitoring, and staging of cancers.
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Affiliation(s)
- Jiamin Wu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Xia Zhou
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Ping Li
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Xiaoling Lin
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Jinhua Wang
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Ziwei Hu
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Pengcheng Zhang
- College of Chemistry and Chemical Engineering, Zhoukou Normal University, Zhoukou, Henan 466000, China
| | - Dong Chen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Huaihong Cai
- College of Chemistry and Materials Science, Jinan University, Guangzhou, Guangdong 510632, China
| | - Reinhard Niessner
- Institute of Hydrochemistry and Chair for Analytical Chemistry, Technical University of Munich, Marchioninistr. 17, Munich D-81377, Germany
| | - Christoph Haisch
- Institute of Hydrochemistry and Chair for Analytical Chemistry, Technical University of Munich, Marchioninistr. 17, Munich D-81377, Germany
| | - Pinghua Sun
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, China
| | - Zhengjin Jiang
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
| | - Haibo Zhou
- College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, China
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Ho SY, Hsu CY, Liu PH, Lee RC, Ko CC, Huang YH, Su CW, Hou MC, Huo TI. Albumin-Bilirubin (ALBI) Grade-Based Nomogram for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization. Dig Dis Sci 2021; 66:1730-1738. [PMID: 32548811 DOI: 10.1007/s10620-020-06384-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 06/01/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIM The prognosis of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is highly heterogeneous because of variable characteristics of tumor burden and liver dysfunction. We aimed to propose and validate an albumin-bilirubin (ALBI) grade-based prognostic nomogram for HCC patients undergoing TACE. METHODS A total of 1051 patients with HCC undergoing TACE were randomly assigned to derivation (n = 525) and validation (n = 526) set in this retrospective study based on prospective data. The multivariate Cox proportional hazards model in derivation set was used to generate the nomogram. The predictive accuracy of the nomogram was evaluated by discrimination and calibration tests. RESULTS In multivariate analysis, presence of ascites, ALBI grade 2-3, serum ɑ-fetoprotein level ≥ 400 ng/mL, total tumor volume ≥ 396 cm3, presence of vascular invasion, and poor performance status were independently associated with decreased survival of patients in the derivation set. Each patient had an individualized score from 0 to 41 by adding up the points from these six prognostic predictors. The nomogram generated from the derivation set had a concordance index of 0.72 (95% confidence interval [CI] 0.63-0.82). Discrimination test in the validation set provided a good concordance index 0.72 (95% CI 0.62-0.81), and the calibration plots consistently matched the ideal 45-degree reference line for 3- and 5-year survival prediction. CONCLUSIONS The ALBI grade-based prognostic model can well discriminate the survival in HCC patients undergoing TACE. The proposed easy-to-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient in the precision medicine era.
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Affiliation(s)
- Shu-Yein Ho
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chia-Yang Hsu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Po-Hong Liu
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Rheun-Chuan Lee
- Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chih-Chieh Ko
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Chien-Wei Su
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Ming-Chih Hou
- Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan
| | - Teh-Ia Huo
- Department of Medical Research, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Taipei, 11217, Taiwan. .,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan. .,Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
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Na BG, Kim YK, Hwang S, Lee KJ, Park GC, Ahn CS, Kim KH, Moon DB, Ha TY, Song GW, Jung DH, Yang H, Yoon YI, Tak E, Park YH, Lee SG. Absence of association between pretransplant serum soluble programmed death protein-1 level and prognosis following living donor liver transplantation in patients with hepatocellular carcinoma. Medicine (Baltimore) 2021; 100:e25640. [PMID: 33907121 PMCID: PMC8084037 DOI: 10.1097/md.0000000000025640] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 11/26/2022] Open
Abstract
ABSTRACT Programmed death protein 1 (PD-1) pathway is one of the most critical mechanisms in tumor biology of hepatocellular carcinoma (HCC). The study aimed to assess the prognostic influence of pretransplant serum soluble PD-1 (sPD-1) in patients undergoing liver transplantation for treatment of HCC.Data from 229 patients with HCC who underwent living donor liver transplantation between January 2010 and December 2015 were retrospectively evaluated. Stored serum samples were used to measure sPD-1 concentrations.Overall survival (OS) and disease-free survival (DFS) rates were 94.3% and 74.5% at 1 year; 78.2% and 59.2% at 3 years; and 75.4% and 55.5% at 5 years, respectively. Prognostic analysis using pretransplant serum sPD-1 with a cut-off of 93.6 μg/mL (median value of the study cohort) did not have significant prognostic influence on OS (P = .69) and DFS (P = .26). Prognostic analysis using sPD-1 with a cut-off of 300 μg/mL showed similar OS (P = .46) and marginally lower DFS (P = .070). Combination of Milan criteria and sPD-1 with a cutoff of 300 μg/mL showed similar outcomes of OS and DFS in patients within and beyond Milan criteria. Multivariate analysis revealed that only Milan criteria was an independent prognostic for OS and DFS, but pretransplant sPD1 with a cut-off of 300 μg/mL did not become a prognostic factor.The results of this study demonstrate that pretransplant serum sPD-1 did not show significant influences on post-transplant outcomes in patients with HCC. Further large-scale, multicenter studies are necessary to clarify the role of serum sPD-1 in liver transplantation recipients.
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Affiliation(s)
- Byeong-Gon Na
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Yun Kyu Kim
- Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Shin Hwang
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Kyung Jin Lee
- Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Gil-Chun Park
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Chul-Soo Ahn
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Ki-Hun Kim
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Deok-Bog Moon
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Tae-Yong Ha
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Gi-Won Song
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Dong-Hwan Jung
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Hunji Yang
- Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Young-In Yoon
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
| | - Eunyoung Tak
- Asan Institute of Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul
| | - Yo-Han Park
- Department of Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation
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Alim A, Erdogan Y, Dayangac M, Yuzer Y, Tokat Y, Oezcelik A. Living Donor Liver Transplantation: The Optimal Curative Treatment for Hepatocellular Carcinoma Even Beyond Milan Criteria. Cancer Control 2021; 28:10732748211011960. [PMID: 33926242 PMCID: PMC8204628 DOI: 10.1177/10732748211011960] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Introduction: Liver transplantation offers the most reasonable expectation for curative treatment for hepatocellular carcinoma. Living-donor liver transplantation represents a treatment option, even in patients with extended Milan criteria. This study aimed to evaluate the outcomes of hepatocellular carcinoma patients, particularly those extended Milan criteria. Materials and Patients: All HCC patients who received liver transplant for HCC were included in this retrospective study. Clinical characteristics including perioperative data and survival data (graft and patient) were extracted from records. Univariate and multivariate analyses was performed to identify significant prognostic factors for survival, postoperative complications and recurrence. Results: Two-hundred and two patients were included. The median age was 54.8 years (IQR 53-61). Fifty-one patients (25.3%) underwent deceased donors liver transplantation and 151 patients (74.7%) underwent living donor liver transplantation. Perioperative mortality rate was 5.9% (12 patients). Recurrent disease occurred in 43 patients (21.2%). The overall 1-year and 5-year survival rates were 90.7% and 75.6%, respectively. Significant differences between patients beyond Milan criteria compared to those within Milan criteria were not found. Alpha-fetoprotein level >300 ng/mL, vascular invasion, and bilobar tumor lesions were independent negative prognostic factors for survival. Conclusion: Liver transplantation is the preferred treatment for hepatocellular carcinoma and it has demonstrated an excellent potential to cure even in patients with beyond Milan criteria. This study shows that the Milan criteria alone are not sufficient to predict survival after transplantation. The independent parameters for survival prediction are Alpha-Fetoprotein-value and status of vascular invasion.
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Affiliation(s)
- Altan Alim
- Department of General and Transplantation Surgery, University Hospital of the Istanbul Bilim University, Florence Nightingale Sisli Hospital, Istanbul, Turkey
| | - Yalcin Erdogan
- Department of General and Transplantation Surgery, University Hospital of the Istanbul Bilim University, Florence Nightingale Sisli Hospital, Istanbul, Turkey
| | - Murat Dayangac
- Department of General and Transplantation Surgery, University Hospital of the Istanbul Bilim University, Florence Nightingale Sisli Hospital, Istanbul, Turkey
| | - Yildiray Yuzer
- Department of General and Transplantation Surgery, University Hospital of the Istanbul Bilim University, Florence Nightingale Sisli Hospital, Istanbul, Turkey
| | - Yaman Tokat
- Department of General and Transplantation Surgery, University Hospital of the Istanbul Bilim University, Florence Nightingale Sisli Hospital, Istanbul, Turkey
| | - Arzu Oezcelik
- Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Germany
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Frankul L, Frenette C. Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy. J Clin Transl Hepatol 2021; 9:220-226. [PMID: 34007804 PMCID: PMC8111105 DOI: 10.14218/jcth.2020.00037] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 10/04/2020] [Accepted: 03/04/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
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Affiliation(s)
| | - Catherine Frenette
- Correspondence to: Catherine Frenette, Scripps Center for Organ Transplant, Scripps Clinic/Green Hospital, 10666 N. Torrey Pines Rd N200, La Jolla, CA 92037, USA. ORCID: https://orcid.org/0000-0002-2245-8173 Tel: +1-858-554-4310, Fax: +1-858-554-3009, E-mail:
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