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1
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Yang Y, He YC, Cai YS, Lv YH, Liu C, Wu H. Living Donor Liver Transplantation Versus Deceased Donor Liver Transplantation for Hepatocellular Carcinoma and HCV Patients: An Initial Umbrella Review. J Clin Med 2025; 14:3047. [PMID: 40364079 PMCID: PMC12072381 DOI: 10.3390/jcm14093047] [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: 02/17/2025] [Revised: 04/12/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Background: Living donor liver transplantation (LDLT) has become a widely accepted alternative to deceased donor liver transplantation (DDLT). Nevertheless, the available meta-analyses shed light on a perplexing issue regarding which transplant is better. Therefore, we performed an umbrella review to summarize and evaluate the evidence from current meta-analyses. Methods: Two independent reviewers conducted a search of PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 1 June 2024. The methodological quality of each included meta-analysis was evaluated using AMSTAR2 (A Measurement Tool to Assess Systematic Reviews). Results: The search identified 10 meta-analyses from 486 individual articles, including cohort studies and observational studies. Regrettably, the quality of these meta-analyses ranged from critically low to moderate. Receipt of LDLT offers a survival advantage to the patients with HCC compared with DDLT but with a higher complication rate. However, high-quality studies are required in the future to validate our assertions owing to the low certainty of the evidence. Conclusions: Despite the complication risks, LDLT remains a cost-effective option without compromising patient and graft survival, especially for HCC patients. Extensive, well-designed studies are essential to validate these conclusions.
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Affiliation(s)
- Ying Yang
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yu-Cheng He
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yun-Shi Cai
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ying-Hao Lv
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chang Liu
- Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, China
| | - Hong Wu
- Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Liver Transplant Center, Transplant Center, West China Hospital, Sichuan University, Chengdu 610041, China
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2
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Sequeira LM, Ozturk NB, Sierra L, Gurakar M, Toruner MD, Zheng M, Simsek C, Gurakar A, Kim AK. Hepatocellular Carcinoma and the Role of Liver Transplantation: An Update and Review. J Clin Transl Hepatol 2025; 13:327-338. [PMID: 40206277 PMCID: PMC11976436 DOI: 10.14218/jcth.2024.00432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/25/2025] [Accepted: 02/08/2025] [Indexed: 04/11/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Multiple treatment modalities are available for the management of HCC, depending on its stage as determined by the Barcelona Clinic Liver Cancer staging system. Because liver transplantation (LT) theoretically removes the cancer and replaces the organ at risk for future malignancy, LT is often considered the most definitive and one of the most efficacious treatment options for HCC. Nevertheless, the success and efficacy of liver transplantation depend on various tumor characteristics. As a result, multiple criteria have been developed to assess the appropriateness of a case of HCC for LT, with the pioneering Milan Criteria established in 1996. Over the past 20 to 30 years, these criteria have been critically evaluated, expanded, and often liberalized to make LT for patients with HCC a more universally applicable option. Furthermore, the development of other treatment modalities has enabled downstaging and bridging strategies for HCC prior to LT. In this narrative and comprehensive review, we provided an update on recent trends in the epidemiology of HCC, selection criteria for LT, implementation of LT across different regions, treatment modalities available as bridges, downstaging strategies, alternatives to LT, and, finally, post-LT surveillance.
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Affiliation(s)
- Lynette M. Sequeira
- Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - N. Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, MI, USA
| | - Leandro Sierra
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Merve Gurakar
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Melanie Zheng
- Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cem Simsek
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Kaslow SR, Torres-Hernandez A, Su F, Liapakis A, Griesemer A, Halazun KJ. Survival benefit of living donor liver transplant for patients with hepatocellular carcinoma. Updates Surg 2024:10.1007/s13304-024-01947-8. [PMID: 39037684 DOI: 10.1007/s13304-024-01947-8] [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: 03/28/2024] [Accepted: 07/12/2024] [Indexed: 07/23/2024]
Abstract
With the increasing incidence of hepatocellular carcinoma (HCC) in both the United States and globally, the role of liver transplantation in management continues to be an area of active conversation as it is often considered the gold standard in the treatment of HCC. The use of living donor liver transplantation (LDLT) and the indications in the setting of malignancy, both generally and in HCC specifically, are frequently debated. In terms of both overall survival and recurrence-free survival, LDLT is at least equivalent to DDLT, especially when performed for disease within Milan criteria. Emerging and compelling evidence suggests that LDLT is superior to DDLT in treating HCC as there is a significant decrease in waitlist mortality. As the oncologic indications for liver transplantation continue to expand and the gap between organ demand and organ availability continues to worsen, high volumes centers should consider using LDLT to shrink the ever-expanding waitlist.
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Affiliation(s)
- Sarah R Kaslow
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
| | - Alejandro Torres-Hernandez
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
- New York University Langone Transplant Institute, New York, NY, USA
| | - Feng Su
- New York University Langone Transplant Institute, New York, NY, USA
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - AnnMarie Liapakis
- New York University Langone Transplant Institute, New York, NY, USA
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - Adam Griesemer
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA
- New York University Langone Transplant Institute, New York, NY, USA
| | - Karim J Halazun
- Department of Surgery, New York University Grossman School of Medicine, New York, NY, USA.
- New York University Langone Transplant Institute, New York, NY, USA.
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4
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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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5
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Boros C, Sutter O, Cauchy F, Ganne-Carrié N, Nahon P, N'kontchou G, Ziol M, Grando V, Demory A, Blaise L, Dondero F, Durand F, Soubrane O, Lesurtel M, Laurent A, Seror O, Nault JC. Upfront multi-bipolar radiofrequency ablation for HCC in transplant-eligible cirrhotic patients with salvage transplantation in case of recurrence. Liver Int 2024; 44:1464-1473. [PMID: 38581233 DOI: 10.1111/liv.15900] [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: 11/03/2023] [Revised: 01/13/2024] [Accepted: 03/04/2024] [Indexed: 04/08/2024]
Abstract
INTRODUCTION We aim to assess the long-term outcomes of percutaneous multi-bipolar radiofrequency (mbpRFA) as the first treatment for hepatocellular carcinoma (HCC) in transplant-eligible cirrhotic patients, followed by salvage transplantation for intrahepatic distant tumour recurrence or liver failure. MATERIALS AND METHODS We included transplant-eligible patients with cirrhosis and a first diagnosis of HCC within Milan criteria treated by upfront mbp RFA. Transplantability was defined by age <70 years, social support, absence of significant comorbidities, no active alcohol use and no recent extrahepatic cancer. Baseline variables were correlated with outcomes using the Kaplan-Meier and Cox models. RESULTS Among 435 patients with HCC, 172 were considered as transplantable with HCCs >2 cm (53%), uninodular (87%) and AFP >100 ng/mL (13%). Median overall survival was 87 months, with 75% of patients alive at 3 years, 61% at 5 years and 43% at 10 years. Age (p = .003) and MELD>10 (p = .01) were associated with the risk of death. Recurrence occurred in 118 patients within Milan criteria in 81% of cases. Local recurrence was observed in 24.5% of cases at 10 years and distant recurrence rates were observed in 69% at 10 years. After local recurrence, 69% of patients were still alive at 10 years. At the first tumour recurrence, 75 patients (65%) were considered transplantable. Forty-one patients underwent transplantation, mainly for distant intrahepatic tumour recurrence. The overall 5-year survival post-transplantation was 72%, with a tumour recurrence of 2.4%. CONCLUSION Upfront multi-bipolar RFA for a first diagnosis of early HCC on cirrhosis coupled with salvage liver transplantation had a favourable intention-to-treat long-term prognosis, allowing for spare grafts.
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Affiliation(s)
- Carina Boros
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Olivier Sutter
- Interventional Radiology Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - François Cauchy
- Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, University of Geneva, Geneva, Switzerland
| | - Nathalie Ganne-Carrié
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Pierre Nahon
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Gisele N'kontchou
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Marianne Ziol
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
- Pathology Department, and Centre de ressources biologiques (BB-0033-00027) Hôpitaux Universitaires Paris-Seine-Saint-Denis, Avicenne Hospital, APHP, Université Paris Norr, Bobigny, France
| | - Véronique Grando
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Alix Demory
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Lorraine Blaise
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
| | - Fédérica Dondero
- Department of HPB Surgery and Liver Transplantation, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - François Durand
- Liver Unit, Beaujon Hospital, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - Olivier Soubrane
- Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France
| | - Mickael Lesurtel
- Department of HPB Surgery and Liver Transplantation, APHP, Beaujon Hospital-University of Paris Cité, Paris, France
| | - Alexis Laurent
- Department of Digestive Surgery, Assistance Publique - Hôpitaux de Paris, Henri Mondor and Albert Chenevier Teaching Hospital, Université Paris Est Créteil, Créteil, France
| | - Oliver Seror
- Interventional Radiology Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
| | - Jean Charles Nault
- Liver Unit, Avicenne Hospital, APHP, Paris Nord University, Bobigny, France
- Cordeliers Research Center, Sorbonne Université, Inserm, Université de Paris, Team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, Paris, France
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Di Sandro S, Centonze L, Catellani B, Odorizzi R, Caracciolo D, Guidetti C, Magistri P, Esposito G, Guerrini GP, Di Benedetto F. Current role and perspectives of living donor liver transplantation for hepatocellular carcinoma: systematic review of the past 20 years. Updates Surg 2024:10.1007/s13304-024-01862-y. [PMID: 38704462 DOI: 10.1007/s13304-024-01862-y] [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: 01/11/2024] [Accepted: 04/19/2024] [Indexed: 05/06/2024]
Abstract
Hepatocellular carcinoma (HCC) poses a significant global health challenge, and liver transplantation (LT) remains the best curative option. Living donor liver transplantation (LDLT) emerged as a potential solution to organ scarcity, reducing waitlist times. This comprehensive review explores LDLT practices, focusing on patient selection criteria and oncologic outcomes. A systematic review following PRISMA guidelines included 50 studies (2004-2023) with 8062 patients. Data encompassed baseline characteristics, HCC features, and oncologic outcomes. Further analysis categorized results by geography and publication year. Heterogeneity in patient demographics, tumor burden, and transplant characteristics was observed. Recent LDLT series demonstrated a shift towards refined selection criteria, increased neoadjuvant treatment, and improved oncologic outcomes. Geographic disparities revealed unique challenges in Eastern and Western practices. LDLT proves effective for HCC, addressing donor shortages. Evolving practices highlight the importance of refining inclusion criteria and optimizing tumor management. While geographic differences exist, LDLT, when judiciously applied, offers promising outcomes.
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Affiliation(s)
- Stefano Di Sandro
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.
| | - Leonardo Centonze
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Barbara Catellani
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Roberta Odorizzi
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Daniela Caracciolo
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Cristiano Guidetti
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Paolo Magistri
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Giuseppe Esposito
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy
| | - Gian Piero Guerrini
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
| | - Fabrizio Di Benedetto
- Hepatopancreatobiliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy
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7
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Rohland O, Freye L, Schwenk L, Ali-Deeb A, Ardelt M, Bauschke A, Settmacher U, Rauchfuß F, Dondorf F. Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy. Cancers (Basel) 2024; 16:920. [PMID: 38473282 PMCID: PMC10930899 DOI: 10.3390/cancers16050920] [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: 01/19/2024] [Revised: 02/21/2024] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open
Abstract
PURPOSE This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.
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Affiliation(s)
- Oliver Rohland
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Lea Freye
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
| | - Laura Schwenk
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Aladdin Ali-Deeb
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Michael Ardelt
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Falk Rauchfuß
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
| | - Felix Dondorf
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747 Jena, Germany
- Cancer Center Central Germany (CCCG), 04103 Leipzig, Germany
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8
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Liu H, Sethi V, Li X, Xiao Y, Humar A. Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future. Semin Liver Dis 2024; 44:79-98. [PMID: 38211621 DOI: 10.1055/a-2242-7543] [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] [Indexed: 01/13/2024]
Abstract
Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.
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Affiliation(s)
- Hao Liu
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Vrishketan Sethi
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Abhinav Humar
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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9
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Waked I, Alsammany S, Tirmazy SH, Rasul K, Bani-Issa J, Abdel-Razek W, Omar A, Shafik A, Eid S, Abdelaal A, Hosni A, Esmat G. Multidisciplinary consensus recommendations for management of hepatocellular carcinoma in Middle East and North Africa region. Liver Int 2023; 43:2062-2077. [PMID: 37553777 DOI: 10.1111/liv.15685] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 06/30/2023] [Accepted: 07/20/2023] [Indexed: 08/10/2023]
Abstract
Hepatocellular carcinoma (HCC) is a growing health concern projected to cross over a million cases worldwide by 2025. HCC presents a significant burden of disease in Middle East and North African (MENA) countries due to a high prevalence of risk factors such as hepatitis C and B infections and rising incidence of non-alcoholic steatohepatitis and non-alcoholic fatty liver disease. In August 2022, an advisory meeting consisting of experts from 5 MENA countries was convened in an attempt to provide consensus recommendations on HCC screening, early diagnosis, current treatment modalities and unmet medical needs in the region. Data were collected from a pre-meeting survey questionnaire and responses analysed and presented during the advisory meeting. This review summarizes the evidence discussed at the meeting and provides expert recommendations on the management of HCC. The 2022 update of Barcelona clinic liver cancer (BCLC) staging and treatment strategy and its implementation in the MENA region was extensively discussed. A key consensus of the expert panel was that multidisciplinary care is crucial to effective patient management that results in better clinical outcomes and overall survival of the patient. The panel recommended the use of predictive and early response biomarkers to guide clinicians in arriving at more effective therapeutic decisions. The experts also emphasized the role of robust screening/surveillance systems, population-based registries, effective referral pathways and standardization of guidelines to ensure the successful management of HCC in the region.
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Affiliation(s)
- Imam Waked
- Department of Medicine, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Sherif Alsammany
- Department of Medical Oncology, King Abdullah Medical City, Mecca, KSA
| | | | - Kakil Rasul
- Department of Medical Oncology, GI Unit, National Centre for Cancer Care and Research, Doha, Qatar
| | - Jafar Bani-Issa
- Department of Interventional Radiology, King Hussein Cancer Center, Amman, Jordan
| | - Wael Abdel-Razek
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin El-Kom, Egypt
| | - Ashraf Omar
- Department of Endemic Medicine and Hepato-Gastroentrology, Cairo University, Cairo, Egypt
| | - Amr Shafik
- Department of Clinical Oncology, Ain Shams University, Cairo, Egypt
| | - Salem Eid
- Department of Medical Oncology, National Cancer Institute, Cairo University, Cairo, Egypt
| | - Amr Abdelaal
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Ain Shams University, Cairo, Egypt
| | - Ahmed Hosni
- Department of Diagnostic and Interventional Radiology, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- Department of Endemic Medicine and Hepato-Gastroentrology, Cairo University, Cairo, Egypt
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10
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Parente A, Cho HD, Kim KH, Schlegel A. Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review. Int J Mol Sci 2023; 24:6224. [PMID: 37047199 PMCID: PMC10093934 DOI: 10.3390/ijms24076224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 03/21/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
The aim of this work was to assess the association between graft-to-recipient weight ratio (GRWR) in adult-to-adult living donor liver transplantation (LDLT) and hepatocellular carcinoma (HCC) recurrence. A search of the MEDLINE and EMBASE databases was performed until December 2022 for studies comparing different GRWRs in the prognosis of HCC recipients in LDLT. Data were pooled to evaluate 1- and 3-year survival rates. We identified three studies, including a total of 782 patients (168 GRWR < 0.8 vs. 614 GRWR ≥ 0.8%). The pooled overall survival was 85% and 77% at one year and 90% and 83% at three years for GRWR < 0.8 and GRWR ≥ 0.8, respectively. The largest series found that, in patients within Milan criteria, the GRWR was not associated with lower oncological outcomes. However, patients with HCC outside the Milan criteria with a GRWR < 0.8% had lower survival and higher tumor recurrence rates. The GRWR < 0.8% appears to be associated with lower survival rates in HCC recipients, particularly for candidates with tumors outside established HCC criteria. Although the data are scarce, the results of this study suggest that considering the individual GRWR not only as risk factor for small-for-size-syndrome but also as contributor to HCC recurrence in patients undergoing LDLT would be beneficial. Novel perfusion technologies and pharmacological interventions may contribute to improving outcomes.
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Affiliation(s)
- Alessandro Parente
- HPB and Transplant Unit, Department of Surgical Science, University of Rome Tor Vergata, 00133 Rome, Italy
- Division of Hepatobiliary and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Hwui-Dong Cho
- Division of Hepatobiliary and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Ki-Hun Kim
- Division of Hepatobiliary and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea
| | - Andrea Schlegel
- Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, 20122 Milan, Italy
- Department of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, 8091 Zurich, Switzerland
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11
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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Elkomos BE, Abdo M, Mamdouh R, Abdelaal A. Can living donor liver transplantation provide similar outcomes to deceased-donor liver transplantation for hepatocellular carcinoma? A systematic review and meta-analysis. Hepatol Int 2023; 17:18-37. [PMID: 36564609 PMCID: PMC9894961 DOI: 10.1007/s12072-022-10435-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 10/03/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM A potential solution to the deceased organ shortage is to include live organ donations and to identify patients with lower rates of HCC recurrence to fairly allocate liver grafts. Our aims were to detect the long-term outcomes of LDLT versus DDLT for HCC and predictors of recurrence after transplantation. METHODS PubMed, Scopus, Web of Science, Cochrane library were searched for eligible studies from inception to July 2021 and a systematic review and meta-analysis were done. RESULTS 35 studies with a total of 7822 patients were included. The 1-, 3-, 4 year-OS showed trivial improvement for LDLT recipients. However, the two modalities had similar 5-, 6- and 10-year OS. A significant improvement in the ITT-OS was observed for LDLT recipients. Regarding the DFS and recurrence after transplantation, no significant difference was observed between LDLT and DDLT. In addition to that, the pooled hazard ratio of the included studies showed that Milan criteria, level of AFP, presence of vascular invasion, tumor differentiation were significant predictors of recurrence. CONCLUSION The cancer biology (not the graft type) is the most important determinant of recurrence and survival after LT. However, LDLT provided much better survival benefits to HCC patients especially in regions that suffer from low deceased organ availability.
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Affiliation(s)
| | - Mostafa Abdo
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Remon Mamdouh
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Amr Abdelaal
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
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13
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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14
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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15
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Muhammad H, Gurakar M, Ting PS, Alsughayer AM, Luu H, Zaffar D, Alqahtani S, Bonder A, Gurakar A, Saberi B. Long-Term Outcomes of Living Donor Versus Deceased Donor Liver Transplant for Hepatocellular Carcinoma in the United States. EXP CLIN TRANSPLANT 2022; 20:279-284. [PMID: 35352634 DOI: 10.6002/ect.2021.0479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Although living donor liver transplant has become a vital treatment option in hepatocellular carcinoma, controversy remains on whether recurrence and survival rates are different versus deceased donor recipients. Here, we compared clinical characteristics and outcomes between recipients of living and deceased donor liver transplants for hepatocellular carcinoma in the United States. MATERIALS AND METHODS Our comparisons used data from the United Network of Organ Sharing/Organ Procurement and Transplantation Network. RESULTS There were 385 living donor and 25 274 deceased donor liver transplant recipients with diagnosis of hepatocellular carcinoma. Transplant list wait times of ≥6 months were more common in deceased donor(55.9%) versus living donor recipients (45.2%; P < .001). Both recipient groups were comparable with regard to alpha-fetoprotein level <200 ng/mL (P = .18). Only a small percentage in both groups had ≥3 total tumors (P = .73); both groups had similar low transplants outside of Milan criteria (P = .45). Overall, 1-, 5-, and 10-year overall survival rates for deceased versus living donor recipients were similar (91.2% vs 92%, 74% vs 76.4%, 58.9% vs 56.5%; P = .69). On multivariate analysis, Black/African American race/ethnicity was associated with worse outcomes than White race/ethnicity as reference (P < .001), whereas Hispanic and Asian race/ethnicity were more protected. Hepatitis C virus as liver disease etiology was associated with worse outcomes than other etiologies. Tumor characteristics, ≥3 lesions, tumor size, and higher alpha-fetoprotein levels were associated with worse outcomes. Living donor transplant was not associated with higher hazard of death. Among living donor recipients only, largest tumor size was associated with higher risk of death (P = .005). CONCLUSIONS Survival was similarin between the living donor versus deceased donor recipients with hepatocellular carcinoma. With changes in Model for End-Stage Liver Disease exception policies for hepatocellular carcinoma in the United States, living donor transplant for hepatocellular carcinoma could expand the donor pool.
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Affiliation(s)
- Haris Muhammad
- From the Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Zhang N, Wang Z, Lv J, Zhang S, Liu Y, Liu T, Li W, Gong L, Zhang X, El-Omar EM, Lu W. Characterization of Gut Microbiota and Exploration of Potential Predictive Model for Hepatocellular Carcinoma Microvascular Invasion. Front Med (Lausanne) 2022; 9:836369. [PMID: 35372388 PMCID: PMC8971959 DOI: 10.3389/fmed.2022.836369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
Background The association between gut microbiota and microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains unclarified. Hence, the microbiome analysis of patients with HCC might predict MVI development as an accurate, non-invasive, and convenient assessment. The aim of this study was to investigate the characteristics of gut microbiota in patients with HCC-MVI and establish a microbial prediction model of HCC-MVI based on a microbiome study. Methods Fecal samples were collected from 59 patients with HCC (24 of the total with MVI disease and 16 healthy controls) and were further analyzed by 16S rRNA amplicon sequencing followed by a comprehensive bioinformatic analysis. The diagnostic performance of microbiome characteristics in predicting MVI was assessed by receiver operating characteristic (ROC) curves. The correlation between gut microbiota and tumor microenvironment (TME) in the HCC-MVI group was further analyzed by using immunohistochemistry and immunofluorescence assay. Results A significant differentiation trend of microbiota composition and structure was observed between the HCC-MVI group and those without vascular invasion (HCC-NVI). Compared with HCC-NVI group and healthy controls, gut bacteria Klebsiella, Proteobacteria, Prevotellaceae, and Enterobacteriaceae were significantly enriched, whereas Firmicutes, Ruminococcus, and Monoglobaceae were significantly decreased in patients with HCC-MVI. Klebsiella was considered to be the key microbiome signature for patients with HCC-MVI. The area under the curve (AUC) of the established HCC-MVI microbial prediction model was 94.81% (95% CI: 87.63–100%). The percentage of M2-type tumor-associated macrophages (TAMs) was increased in the HCC-MVI group compared with the HCC-NVI group (p < 0.001). M2-type TAMs in TME were negatively correlated with Shannon and Simpson index of HCC-MVI gut microbiota (all p < 0.01). In addition, predicted KEGG pathways showed that the functional differences in the metabolic pathways of microbiota varied among the groups. Conclusion The results indicated that differences existed in the fecal microbiome of patients with HCC-MVI and healthy controls. The prediction model of HCC-MVI established with certain gut bacterial signatures may have the potential to predict HCC-MVI outcome, and the characteristics of the fecal microbiome in patients with HCC may be associated with TME, though future larger-cohort studies are required to validate this supposition.
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Affiliation(s)
- Ningning Zhang
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Zeyu Wang
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Jiayu Lv
- Department of Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Shuwen Zhang
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Yang Liu
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Tian Liu
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Wang Li
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
| | - Lan Gong
- Department of Medicine, University of New South Wales, Sydney, NSW, Australia
- St George & Sutherland Clinical School, Microbiome Research Centre, University of New South Wales, Sydney, NSW, Australia
| | - Xiaodong Zhang
- Key Laboratory of Cancer Prevention and Therapy, Department of Gastrointestinal Cancer Biology, Liver Cancer Center, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
- Xiaodong Zhang
| | - Emad M. El-Omar
- Department of Medicine, University of New South Wales, Sydney, NSW, Australia
- St George & Sutherland Clinical School, Microbiome Research Centre, University of New South Wales, Sydney, NSW, Australia
- Emad M. El-Omar
| | - Wei Lu
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Tianjin, China
- *Correspondence: Wei Lu
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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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18
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Lai Q, Sapisochin G, Gorgen A, Vitale A, Halazun KJ, Iesari S, Schaefer B, Bhangui P, Mennini G, Wong TC, Uemoto S, Lin CC, Mittler J, Ikegami T, Yang Z, Frigo AC, Zheng SS, Soejima Y, Hoppe-Lotichius M, Chen CL, Kaido T, Lo CM, Rossi M, Soin AS, Finkenstedt A, Emond JC, Cillo U, Lerut JP. Evaluation of the Intention-to-Treat Benefit of Living Donation in Patients With Hepatocellular Carcinoma Awaiting a Liver Transplant. JAMA Surg 2021; 156:e213112. [PMID: 34259797 PMCID: PMC8281041 DOI: 10.1001/jamasurg.2021.3112] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 04/25/2021] [Indexed: 01/10/2023]
Abstract
IMPORTANCE Living-donor liver transplant (LDLT) offers advantages over deceased-donor liver transplant (DDLT) of improved intention-to-treat outcomes and management of the shortage of deceased-donor allografts. However, conflicting data still exist on the outcomes of LDLT in patients with hepatocellular carcinoma (HCC). OBJECTIVE To investigate the potential survival benefit of an LDLT in patients with HCC from the time of waiting list inscription. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study with an intention-to-treat design analyzed the data of patients aged 18 years or older who had an HCC diagnosis and were on a waiting list for a first transplant. Patients from 12 collaborative centers in Europe, Asia, and the US who were on a transplant waiting list between January 1, 2000, and December 31, 2017, composed the international cohort. The Toronto cohort comprised patients from 1 transplant center in Toronto, Ontario, Canada who were on a waiting list between January 1, 2000, and December 31, 2015. The international cohort centers performed either an LDLT or a DDLT, whereas the Toronto cohort center was selected for its capability to perform both LDLT and DDLT. The benefit of LDLT was tested in the 2 cohorts before and after undergoing an inverse probability of treatment weighting (IPTW) analysis. Data were analyzed from February 1 to May 31, 2020. MAIN OUTCOMES AND MEASURES Intention-to-treat death was defined as a patient death that occurred for any reason and was calculated from the time of waiting list inscription for liver transplant to the last follow-up date (December 31, 2019). Four multivariable Cox proportional hazards regression models for intention-to-treat death were created. RESULTS A total of 3052 patients were analyzed in the international cohort, of whom 2447 were men (80.2%) and the median (IQR) age at first referral was 58 (53-63) years. The Toronto cohort comprised 906 patients, of whom 743 were men (82.0%) and the median (IQR) age at first referral was 59 (53-63) years. In all the settings, LDLT was an independent protective factor, reducing the risk of overall death by 49% in the pre-IPTW analysis for the international cohort (HR, 0.51; 95% CI, 0.36-0.71; P < .001), 33% in the post-IPTW analysis for the international cohort (HR, 0.67; 95% CI, 0.53-0.85; P = .001), 43% in the pre-IPTW analysis for the Toronto cohort (HR, 0.57; 95% CI, 0.45-0.73; P < .001), and 48% in the post-IPTW analysis for the Toronto cohort (HR, 0.52; 95% CI, 0.42 to 0.65; P < .001). The discriminatory ability of the mathematical models further improved in all of the cases in which LDLT was incorporated. CONCLUSIONS AND RELEVANCE This study suggests that having a potential live donor could decrease the intention-to-treat risk of death in patients with HCC who are on a waiting list for a liver transplant. This benefit is associated with the elimination of the dropout risk and has been reported in centers in which both LDLT and DDLT options are equally available.
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Affiliation(s)
- Quirino Lai
- Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium
- General Surgery and Organ Transplantation Unit, Department of General 3 Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Gonzalo Sapisochin
- Abdominal Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Andre Gorgen
- Abdominal Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Alessandro Vitale
- Liver Transplantation and Hepatobiliary Surgery, Padua University Hospital, University of Padua, Padua, Italy
| | - Karim J. Halazun
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medicine, New York, New York
| | - Samuele Iesari
- Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Benedikt Schaefer
- Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Guragram, Delhi, India
| | - Gianluca Mennini
- General Surgery and Organ Transplantation Unit, Department of General 3 Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Tiffany C.L. Wong
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jens Mittler
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsmedizin Mainz, Mainz, Germany
| | - Toru Ikegami
- Department of Surgery and Science, Kyushu University, Fukuoka, Japan
| | - Zhe Yang
- Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital, Shulan Health Zhejiang University Hospital, Hangzhou, China
| | | | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital, Shulan Health Zhejiang University Hospital, Hangzhou, China
| | - Yuji Soejima
- Department of Surgery and Science, Kyushu University, Fukuoka, Japan
| | - Maria Hoppe-Lotichius
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsmedizin Mainz, Mainz, Germany
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Massimo Rossi
- General Surgery and Organ Transplantation Unit, Department of General 3 Surgery and Organ Transplantation, Sapienza University of Rome, Rome, Italy
| | - Arvinder Singh Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Guragram, Delhi, India
| | - Armin Finkenstedt
- Department of Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Jean C. Emond
- Center for Liver Disease and Transplantation, Columbia University Medical Center, New York Presbyterian Hospital, New York
- Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, Weill Cornell Medicine, New York, New York
| | - Umberto Cillo
- Liver Transplantation and Hepatobiliary Surgery, Padua University Hospital, University of Padua, Padua, Italy
| | - Jan Paul Lerut
- Institut de Recherche Clinique, Université Catholique de Louvain, Brussels, Belgium
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Barbetta A, Aljehani M, Kim M, Tien C, Ahearn A, Schilperoort H, Sher L, Emamaullee J. Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation. Am J Transplant 2021; 21:2399-2412. [PMID: 33300241 PMCID: PMC9048132 DOI: 10.1111/ajt.16440] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/01/2020] [Accepted: 12/01/2020] [Indexed: 01/25/2023]
Abstract
Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81-0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R2 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.
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Affiliation(s)
- Arianna Barbetta
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Mayada Aljehani
- Lawrence J Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, CA
| | - Michelle Kim
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Christine Tien
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Aaron Ahearn
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | | | - Linda Sher
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Juliet Emamaullee
- Department of Surgery, University of Southern California, Los Angeles, CA
- Keck School of Medicine, University of Southern California, Los Angeles, CA
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20
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Doğan SM, Kutlutürk K. Living Donor Versus Deceased Donor Liver Transplantation for HCC. J Gastrointest Cancer 2021; 51:1104-1106. [PMID: 32833221 DOI: 10.1007/s12029-020-00481-1] [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] [Indexed: 12/31/2022]
Abstract
INTRODUCTION Liver transplantation is the definitive treatment modality of the patients having an end-stage liver disease with hepatocellular carcinoma. DISCUSSION The number of living donor liver transplantations has been increased because of the deceased donor organ shortage, especially in Asian countries. CONCLUSION Reports of different clinics about the postoperative course and tumor recurrence rates comparing living donor versus deceased donor liver transplantations, besides patient selection criteria, are reviewed along with our clinic's experiences.
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Affiliation(s)
- Sait Murat Doğan
- Department of Surgery and Liver Transplantation Institute, İnönü University Faculty of Medicine, Elazığ yolu 10.km, 44280, Malatya, Turkey.
| | - Koray Kutlutürk
- Department of Surgery and Liver Transplantation Institute, İnönü University Faculty of Medicine, Elazığ yolu 10.km, 44280, Malatya, Turkey
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21
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Kwong A, Mehta N. Expanding the Limits of Liver Transplantation for Hepatocellular Carcinoma: Is There a Limit? Clin Liver Dis 2021; 25:19-33. [PMID: 33978578 DOI: 10.1016/j.cld.2020.08.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation is a treatment option for hepatocellular carcinoma within Milan criteria. With careful selection practices, patients with larger tumors can do well with successful downstaging followed by liver transplantation and should not be excluded based on tumor size or number alone. When considering expanded criteria for hepatocellular carcinoma, however, survival outcomes after liver transplantation should be comparable with patients without hepatocellular carcinoma. Surrogate measures of tumor biology, such as α-fetoprotein, other biomarkers, and dynamic tumor behavior including response to locoregional therapy can aid in risk stratification of patients before liver transplantation.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University, 420 Broadway Street, 3rd Floor, Redwood City, CA 94063, USA
| | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, 513 Parnassus Avenue, S-357, San Francisco, CA 94143, USA.
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Alqahtani SA, Sanai FM, Alolayan A, Abaalkhail F, Alsuhaibani H, Hassanain M, Alhazzani W, Alsuhaibani A, Algarni A, Forner A, Finn RS, Al-hamoudi WK. Saudi Association for the Study of Liver diseases and Transplantation practice guidelines on the diagnosis and management of hepatocellular carcinoma. Saudi J Gastroenterol 2020; 26:S1-S40. [PMID: 33078723 PMCID: PMC7768980 DOI: 10.4103/sjg.sjg_477_20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 01/27/2023] Open
Affiliation(s)
- Saleh A. Alqahtani
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, United States
| | - Faisal M. Sanai
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, Gastroenterology Unit, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Ashwaq Alolayan
- Adult Medical Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Hamad Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mazen Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
| | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Abdullah Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Algarni
- Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Richard S Finn
- Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California,United States
| | - Waleed K. Al-hamoudi
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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23
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Tang W, Qiu JG, Cai Y, Cheng L, Du CY. Increased Surgical Complications but Improved Overall Survival with Adult Living Donor Compared to Deceased Donor Liver Transplantation: A Systematic Review and Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1320830. [PMID: 32908865 PMCID: PMC7468609 DOI: 10.1155/2020/1320830] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 07/19/2020] [Accepted: 08/07/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Living donor liver transplantation (LDLT) provides an alternative to deceased donor liver transplantation (DDLT) for patients with end-stage liver disease in the circumstance of scarcity of deceased grafts. However, the outcomes of LDLT remain controversial. METHOD A systematic review and meta-analysis were performed to compare the outcomes of LDLT with DDLT. Twelve outcomes were assessed. RESULTS Thirty-nine studies involving 38563 patients were included. LDLT was comparable in red blood cell transfusion, perioperative mortality, length of hospital stay, retransplantation rate, hepatitis C virus recurrence rate, and hepatocellular carcinoma recurrence rate with DDLT. Cold ischemia time was shorter and duration of recipient operation was longer in LDLT. Postoperative intra-abdominal bleeding rate occurred less frequently in LDLT recipients (odds ratio (OR) = 0.64, 95%confidence interval (CI) = 0.46 - 0.88, P = 0.006), but this did not decrease the perioperative mortality. LDLT was associated with significantly higher biliary (OR = 2.23, 95%CI = 1.59 - 3.13, P < 0.00001) and vascular (OR = 2.00, 95%CI = 1.31 - 3.07, P = 0.001) complication rates and better overall survival (OS) (1 year: OR = 1.32, 95%CI = 1.01 - 1.72, P = 0.04; 3 years: OR = 1.39, 95%CI = 1.14 - 1.69, P = 0.0010; and 5 years: OR = 1.33, 95%CI = 1.04 - 1.70, P = 0.02). According to subgroup analysis, biliary complication rate and OS improved dramatically as experience increased, while vascular complication rate could not be improved because it was mainly caused by the difference of the donor type itself. CONCLUSIONS LDLT remains a valuable option for patients in need of liver transplantation for it provides an excellent alternative to DDLT without compromising recipient outcomes. Further refinement in biliary and vascular reconstruction techniques and the accumulation of liver transplantation centers' experience are the key factors in expanding the application of LDLT.
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Affiliation(s)
- Wei Tang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Jian-Guo Qiu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Yang Cai
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Luo Cheng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Cheng-You Du
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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24
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Allaire M, Goumard C, Lim C, Le Cleach A, Wagner M, Scatton O. New frontiers in liver resection for hepatocellular carcinoma. JHEP Rep 2020; 2:100134. [PMID: 32695968 PMCID: PMC7360891 DOI: 10.1016/j.jhepr.2020.100134] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 04/23/2020] [Accepted: 05/15/2020] [Indexed: 02/08/2023] Open
Abstract
Liver resection is one of the main curative options for early hepatocellular carcinoma (HCC) in patients with cirrhosis and is the treatment of choice in non-cirrhotic patients. However, careful patient selection is required to balance the risk of postoperative liver failure and the potential benefit on long-term outcomes. In the last decades, improved surgical techniques and perioperative management, as well as better patient selection, have enabled the indications for liver resection to be expanded. In this review, we aim to describe the main indications for liver resection in the management of HCC, its role compared to percutaneous ablation and liver transplantation in the therapeutic algorithm, as well as the recent advances in liver surgery that could be used to improve the prognosis of patients with HCC.
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Key Words
- ALPPS, associating liver partition and portal vein ligation for staged hepatectomy
- BCLC, Barcelona Clinic liver cancer
- CSPH, clinically significant portal hypertension
- DFS, disease-free survival
- GSA, galactosyl serum albumin
- HCC
- HCC, hepatocellular carcinoma
- HVGP, hepatic venous pression gradient
- ICG, indocyanine green
- ICG-R15, hepatic clearance of ICG 15 minutes after its intravenous administration
- IL-6, interleukin 6
- LR, liver resection
- LSM, liver stiffness measurement
- Laparoscopy
- Liver resection
- MELD, model for end-stage liver disease
- NAFLD, non-alcoholic fatty liver disease
- OS, overall survival
- PVL, portal vein ligation
- PVTT, tumour-related portal vein thrombosis
- RFA, radiofrequency ablation
- SSM, spleen stiffness measurement
- Surgery
- TACE, transarterial chemoembolisation
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Affiliation(s)
- Manon Allaire
- Sorbonne Université, Service d'Hépatologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
- Inserm U1149, Centre de Recherche sur l'Inflammation, France Faculté de Médecine Xavier Bichat, Université Paris Diderot, Paris, France
| | - Claire Goumard
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Chetana Lim
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Aline Le Cleach
- Sorbonne Université, Service d'Hépatologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Mathilde Wagner
- Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale (LIB), Service de Radiologie, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
| | - Olivier Scatton
- Sorbonne Université, CRSA, Service de chirurgie digestive, hépato-biliaire et transplantation hépatique, Hôpitaux Universitaires Pitié Salpêtrière - Charles Foix, AP-HP, Paris, France
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25
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Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, Durand F, Ijzermans J, Polak W, Zheng S, Roberts JP, Sapisochin G, Hibi T, Kwan NM, Ghobrial M, Soin A. Liver Transplantation for Hepatocellular Carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1136-1142. [PMID: 32217938 DOI: 10.1097/tp.0000000000003174] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) offers excellent long-term outcome for certain patients with hepatocellular carcinoma (HCC), with a push to not simply rely on tumor size and number. Selection criteria should also consider tumor biology (including alpha-fetoprotein), probability of waitlist and post-LT survival (ie, transplant benefit), organ availability, and waitlist composition. These criteria may be expanded for live donor LT (LDLT) compared to deceased donor LT though this should not adversely affect the double equipoise in LDLT, namely ensuring both acceptable recipient outcomes and donor safety. HCC patients with compensated liver disease and minimal tumor burden have low urgency for LT, especially after local-regional therapy with complete response, and do not appear to derive the same benefit from LT as other waitlist candidates. These guidelines were developed to assist in selecting appropriate HCC patients for both deceased donor LT and LDLT.
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Affiliation(s)
- Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Francis Y Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Vincenzo Mazzaferro
- Department of Surgery, GI Surgery and Liver Transplantation, Istituto Nazionale Tumori, Milan, Italy
| | - Christian Toso
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Francois Durand
- Service d'Hépatologie & Réanimation Hépatodigestive, Université Paris VII Hôpital Beaujon, Paris, France
| | - Jan Ijzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wojciech Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - John P Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Taizo Hibi
- Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nancy Man Kwan
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Mark Ghobrial
- J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Avi Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
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26
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Abstract
PURPOSE OF REVIEW As experience grows, living donor liver transplantation (LDLT) has become an effective treatment option to overcome the deceased donor organ shortage. RECENT FINDINGS Donor safety is the highest priority in LDLT. Strict donor selection according to structured protocols and center experience are the main factors that determine donor safety. However, with increased experience, many centers have explored increasing organ availability within living donation by means of ABO incompatible LDLT, dual graft LDLT, and anonymous living donation. Also, this growing experience in LDLT has allowed the transplant community to cautiously explore the role of liver transplantation for hepatocellular carcinoma outside of Milan criteria and patients with unresectable colorectal liver metastases. SUMMARY LDLT has become established as a viable strategy to ameliorate the organ shortage experienced by centers around the world. Improved understanding of this technique has allowed the improved utilization of live donor graft resources, without compromising donor safety. Moreover, LDLT may offer some advantages over deceased donor liver transplantation and a unique opportunity to assess the broader applicability of liver transplantation.
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27
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McMillan RR, Agopian VG. The Management of Hepatocellular Carcinoma. THE CRITICALLY ILL CIRRHOTIC PATIENT 2020:237-271. [DOI: 10.1007/978-3-030-24490-3_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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28
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How far can we go with hepatocellular carcinoma in living donor liver transplantation? Curr Opin Organ Transplant 2019; 24:644-650. [DOI: 10.1097/mot.0000000000000692] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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29
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Chan KM, Cheng CH, Wu TH, Lee CF, Wu TJ, Chou HS, Lee WC. Salvage living donor liver transplantation for posthepatectomy recurrence: a higher incidence of recurrence but promising strategy for long-term survival. Cancer Manag Res 2019; 11:7295-7305. [PMID: 31447587 PMCID: PMC6684549 DOI: 10.2147/cmar.s215732] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 07/12/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The scarcity of deceased donor organ donation has led to increasing utilization of living donor liver transplantation (LDLT), which is an optimal treatment for cirrhosis associated with hepatocellular carcinoma (HCC). The study thus aims to analyze prognostic factors and beneficial effects of LDLT for patients with HCC. METHODS All patients who underwent LDLT for HCC were included in this study. A multivariate analysis of patients' clinicopathologic parameters was performed to determine prognostic factors. Subsequently, the type of LDLT was further analyzed and compared based on the result of multivariate analysis. RESULTS Overall, 36 (11.9%) of 303 patients were identified as having HCC recurrence after LDLT. Salvage LDLT (sLDLT) defined by liver transplantation for those patients with recurrent HCC after primary liver resection (LR) was identified as the major prognostic factor of HCC recurrence following the transplantation (HR=2.49 [1.12-5.54], p=0.025). The HCC recurrence incidence and recurrence-free survival after LDLT were significantly inferior in the salvage group than the other group. The pre-transplantation factors were further evaluated and resulted in only maximum tumour size ≥5 cm at primary LR(HR=10.79 [2.10-55.43], p=0.004) affecting post-transplantation HCC recurrence in those patients who had been performed sLDLT. However, patients receiving salvage LDLT had 5- and 10-year overall survival of 86.7% and 52.9%, respectively, measured from the time of initial HCC diagnosis. CONCLUSION Overall, LDLT achieves a satisfactory result with low incidence of HCC recurrence based on certain transplantation criteria. Despite the higher incidence of HCC recurrence after sLDLT, it remains a promising strategy to improve long-term outcomes.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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30
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Recent advances in liver transplantation for cancer: The future of transplant oncology. JHEP Rep 2019; 1:377-391. [PMID: 32039389 PMCID: PMC7005652 DOI: 10.1016/j.jhepr.2019.07.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is widely indicated as a curative treatment for selected patients with hepatocellular carcinoma. However, with recent therapeutic advances, as well as efforts to increase the donor pool, liver transplantation has been carefully expanded to patients with other primary or secondary malignancies in the liver. Cholangiocarcinoma, colorectal and neuroendocrine liver metastases, and hepatic epithelioid haemangioendothelioma are amongst the most relevant new indications. In this review we discuss the fundamental concepts of this ambitious undertaking, as well as the newest indications for liver transplantation, with a special focus on future perspectives within the recently established concept of transplant oncology.
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31
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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32
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Subramanian V, Chapman W. Living Donor Liver Transplant for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1594-1595. [PMID: 30937661 DOI: 10.1245/s10434-019-07206-0] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Indexed: 09/07/2023]
Affiliation(s)
- Vijay Subramanian
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA
| | - William Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA.
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33
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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34
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Segmental Distribution of Hepatocellular Carcinoma Correlates with Microvascular Invasion in Liver Explants Undergoing Transplantation. J Cancer Epidemiol 2019; 2019:8534372. [PMID: 31186641 PMCID: PMC6521314 DOI: 10.1155/2019/8534372] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/12/2019] [Accepted: 04/15/2019] [Indexed: 12/13/2022] Open
Abstract
Introduction Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI. Methods A single center, retrospective chart review, including 98 HCC patients, aged 18 years and older who had liver transplantation in our institute between 2012 and 2017. We reviewed the radiological images of the HCC tumors, the pathological findings of the explanted livers, and the follow-up imaging after transplantation. Results 98 patients with the diagnosis of HCC underwent liver transplantation between 2012 and 2017. The mean age of the cohort was 63 ± 8.2. Males represented 75% and Caucasian race represented 75% of the cohort. The most common etiology of cirrhosis was chronic hepatitis C virus infection followed by alcohol abuse and nonalcoholic steatohepatitis (NASH) with percentages of 50%, 23%, and 10%, respectively. Microvascular invasion was found in 16% of the patients while PVT and the recurrence of HCC were found in 17% and 6 % of the cohort, respectively. MVI was found in 10 single HCC and 6 multifocal HCC. Right lobe HCC had more MVI when compared to the left and multilobar HCC, with percentages of 11%, 2%, and 3%, respectively. Localization of HCC in segment 8 was associated with the highest percentage of MVI when compared to all other segments. The risk of MVI in segment 8 HCC was 3.5 times higher than the risk from the other segments (p=0.002) while no vascular invasion was found in segments 1, 3, and 5. The risk of vascular invasion in untreated HCC is 3 times the risk in treated HCC (P=0.03). Conclusion Our data indicate that the risk of microvascular invasion is highest in tumors localized to segment 8. The size and number of HCC tumors were not associated with an increased risk of microvascular invasion.
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Vatansever S, Farajov R, Yılmaz HC, Zeytunlu M, Paköz ZB, Kılıç M. Hepatitis B and hepatocellular carcinoma recurrence after living donor liver transplantation: The role of the Milan criteria. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:75-80. [PMID: 30644364 DOI: 10.5152/tjg.2018.18794] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND/AIMS The aim of this study was to evaluate the effect of the Milan criteria on the hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrence in patients who underwent living donor liver transplantation due to HBV-induced cirrhosis and HCC. MATERIALS AND METHODS We evaluated a total of 142 patients, 88 who underwent transplantation due to HBV-induced cirrhosis and 54 due to HCC, between 2009 and 2014. In the posttranplant period, after the HBsAg seroconversion, 400 IU of hepatitis B immunoglobulin were applied intramuscularly every 2 weeks, and daily nucleos(t)ide analogs were continued as prophylaxis. The HBV recurrence was defined as the presence of HBsAg in serum. Patients were screened for alpha-fetoprotein levels and imaging for evaluation of HCC recurrence. RESULTS The average follow-up period was 26 (2-65) months. Fifty-four patients had HCC. The HCC recurrence was observed in 12 patients during the follow-up period. The HBV recurrence was observed in four patients. Three of the patients who developed HBV recurrence had liver transplantation due to HCC. Tumor recurrence was observed 1.4-12 months following the HBV recurrence. The HCC recurrence within the Milan criteria and beyond the Milan criteria was 0% vs. 28.4 % in the first year and 3.4% vs. 47.5% in the third year. The cumulative incidence of the HBV recurrence was 2.8% and 3.7% for the first year and 3.7% for the third year. The HBV recurrence was more frequently detected in patients with HCC (p=0.048), especially with HCC beyond the Milan criteria (p=0.044). CONCLUSION The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who underwent liver transplantation due to HCC with exceeding Milan criteria.
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Affiliation(s)
- Sezgin Vatansever
- Department of Gastroenterology, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir, TurkeyDepartment of Gastroenterology, İzmir Katip Çelebi University Atatürk Training and Research Hospital, İzmir, Turkey
| | - Rasim Farajov
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
| | | | - Murat Zeytunlu
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
| | - Zehra Betül Paköz
- Department of Gastroenterology, Tepecik Training and Research Hospital, İzmir, Turkey
| | - Murat Kılıç
- Department of Liver Transplantation, Kent Hospital, İzmir, Turkey
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Subramanian V, Chapman W. Living Donor Liver Transplant for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1594-1595. [PMID: 30937661 DOI: 10.1245/s10434-019-07250-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Vijay Subramanian
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA
| | - William Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA.
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Goldaracena N, Gorgen A, Doyle A, Hansen BE, Tomiyama K, Zhang W, Ghanekar A, Lilly L, Cattral M, Galvin Z, Selzner M, Bhat M, Selzner N, McGilvray I, Greig PD, Grant DR, Sapisochin G. Live donor liver transplantation for patients with hepatocellular carcinoma offers increased survival vs. deceased donation. J Hepatol 2019; 70:666-673. [PMID: 30630009 DOI: 10.1016/j.jhep.2018.12.029] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND & AIMS There are conflicting reports on the outcomes after live donor liver transplantation in patients with hepatocellular carcinoma (HCC). We aimed to compare the survival of patients with HCC, with a potential live donor (pLDLT) at listing vs. no potential donor (pDDLT), on an intention-to-treat basis. METHODS All patients with HCC listed for liver transplantation between 2000-2015 were included. The pLDLT group was comprised of recipients with a potential live donor identified at listing. Patients without a live donor were included in the pDDLT group. Survival was assessed by the Kaplan-Meier method. Multivariable Cox regression was applied to identify potential predictors of mortality. RESULTS A total of 219 patients were included in the pLDLT group and 632 patients in the pDDLT group. In the pLDLT group, 57 patients (26%) were beyond the UCSF criteria whereas 119 patients (19%) in the pDDLT group were beyond (p = 0.02). Time on the waiting list was shorter for the pLDLT than the pDDLT group (4.8 [2.9-8.5] months vs. 6.2 [3.0-12.0] months, respectively, p = 0.02). The dropout rate was 32/219 (14.6%) in the pLDLT and 174/632 (27.5%) in the pDDLT group, p <0.001. The 1-, 3- and 5-year intention-to-treat survival rates were 86%, 72% and 68% in the pLDLT vs. 82%, 63% and 57% in the pDDLT group, p = 0.02. Having a potential live donor was a protective factor for death (hazard ratio [HR] 0.67; 95% CI 0.53-0.86). Waiting times of 9-12 months (HR 1.53; 95% CI 1.02-2.31) and ≥12 months (HR 1.69; 95% CI 1.23-2.32) were predictors of death. CONCLUSION Having a potential live donor at listing was associated with a significant decrease in the risk of death in patients with HCC in this intention-to-treat analysis. This benefit is related to a lower dropout rate and a shorter waiting period. LAY SUMMARY Liver transplantation (LT) offers the best chance of survival for patients with hepatocellular carcinoma and can be performed using grafts from deceased donors or live donors. In this work, we aimed to assess the differences in survival after live donor LT when compared to deceased donor LT. We studied 219 patients listed for live donor LT and 632 patients listed for deceased donor LT. Patients who had a potential live donor at the time of listing had a higher survival rate. Therefore, being listed for a live donor LT was a protective factor against death.
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Affiliation(s)
- Nicolas Goldaracena
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Andre Gorgen
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Adam Doyle
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Department of Medicine, University Health Network, University of Toronto, Canada
| | - Bettina E Hansen
- Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Canada
| | - Koji Tomiyama
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Wei Zhang
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Anand Ghanekar
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Les Lilly
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Department of Medicine, University Health Network, University of Toronto, Canada
| | - Mark Cattral
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Zita Galvin
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Department of Medicine, University Health Network, University of Toronto, Canada
| | - Markus Selzner
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Mamatha Bhat
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Department of Medicine, University Health Network, University of Toronto, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Department of Medicine, University Health Network, University of Toronto, Canada
| | - Ian McGilvray
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Paul D Greig
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - David R Grant
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada; Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Canada.
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Shimamura T, Akamatsu N, Fujiyoshi M, Kawaguchi A, Morita S, Kawasaki S, Uemoto S, Kokudo N, Hasegawa K, Ohdan H, Egawa H, Furukawa H, Todo S. Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study. Transpl Int 2019; 32:356-368. [PMID: 30556935 DOI: 10.1111/tri.13391] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 11/26/2018] [Accepted: 12/11/2018] [Indexed: 12/14/2022]
Abstract
Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living-donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5-year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha-fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5-5-500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa-fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5-year recurrence rate of 7.3% (5.2-9.3) and a 19% increase in the number of eligible patients. In addition, the 5-5-500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria - the 5-5-500 rule - might provide rational expansion for LDLT candidates with HCC.
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Affiliation(s)
- Tsuyoshi Shimamura
- Division of Organ Transplantation, Hokkaido University Hospital, Sapporo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Masato Fujiyoshi
- Department of Gastroenterological Surgery 1, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | - Atushi Kawaguchi
- Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga, Japan
| | - Satoshi Morita
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hiroyuki Furukawa
- Division of Gastroenterological Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Satoru Todo
- Research Institute of St. Mary's Hospital, Kurume, Japan
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Zhu B, Wang J, Li H, Chen X, Zeng Y. Living or deceased organ donors in liver transplantation for hepatocellular carcinoma: a systematic review and meta-analysis. HPB (Oxford) 2019; 21:133-147. [PMID: 30503300 DOI: 10.1016/j.hpb.2018.11.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 10/18/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The outcomes of living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT) for HCC patients were not well defined and it was necessary to reassess. METHODS A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, Google Scholar and WanFang database for eligible studies. Perioperative and survival outcomes of HCC patients underwent LDLT were pooled and compared to those underwent DDLT. RESULTS Twenty-nine studies with 5376 HCC patients were included. For HCC patients underwent LDLT and DDLT, there were comparable rates of overall survival (OS) (1-year, RR = 1.04, 95%CI = 1.00-1.09, P = 0.03; 3-year, RR = 1.03, 95%CI = 0.96-1.11, P = 0.39; 5-year, RR = 1.04, 95%CI = 0.95-1.13, P = 0.43), disease free survival (DFS) (1-year, RR = 1.00, 95%CI = 0.95-1.05, P = 0.99; 3-year, RR = 1.00, 95%CI = 0.94-1.08, P = 0.89; 5-year, RR = 1.01, 95%CI = 0.93-1.09, P = 0.85), recurrence (1-year, RR = 1.41, 95%CI = 0.72-2.77, P = 0.32; 3-year, RR = 0.89, 95%CI = 0.57-1.39, P = 0.60; and 5-year, RR = 0.85, 95%CI = 0.56-1.31, P = 0.47), perioperative mortality within 3 months (RR = 0.89, 95%CI = 0.50-1.59, p = 0.70) and postoperative complication (RR = 0.99, 95%CI = 0.70-1.39, P = 0.94). LDLT was associated with better 5-year intention-to-treat patient survival (ITT-OS) than DDLT (RR = 1.11, 95% CI = 1.01-1.22, P = 0.04). CONCLUSION This meta-analysis suggested that LDLT was not inferior to DDLT in consideration of comparable perioperative and survival outcomes. However, in terms of 5-year ITT-OS, LDLT was a possibly better choice for HCC patients.
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Affiliation(s)
- Bo Zhu
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jinju Wang
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hui Li
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xing Chen
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yong Zeng
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University, Chengdu, 610041, China; Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
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Wong TCL, Ng KKC. ASO Author Reflections: Liver Transplantation for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1463-1464. [PMID: 30684160 DOI: 10.1245/s10434-019-07199-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Indexed: 11/18/2022]
Affiliation(s)
- Tiffany C L Wong
- Department of Surgery, The University of Hong Kong, Pok Fu Lam, Hong Kong.,Department of Surgery, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Kelvin K C Ng
- Department of Surgery, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
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Gavriilidis P, Tobias A, Sutcliffe RP, Roberts KJ. Survival following right lobe split graft, living- and deceased-donor liver transplantation in adult patients: a systematic review and network meta-analysis. Transpl Int 2018; 31:1071-1082. [DOI: 10.1111/tri.13317] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 06/18/2018] [Accepted: 07/11/2018] [Indexed: 01/16/2023]
Affiliation(s)
- Paschalis Gavriilidis
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery; Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust; Birmingham UK
| | - Aurelio Tobias
- Biostatistician in Tommy's National Centre for Miscarriage Research; Institute of Metabolism and Systems Research; University of Birmingham; Birmingham UK
| | - Robert P. Sutcliffe
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery; Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust; Birmingham UK
| | - Keith J. Roberts
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery; Queen Elizabeth University Hospitals Birmingham NHS Foundation Trust; Birmingham UK
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Burt AD, Alves V, Bedossa P, Clouston A, Guido M, Hübscher S, Kakar S, Ng I, Park YN, Reeves H, Wyatt J, Yeh MM, Ellis DW. Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 2018; 73:369-385. [DOI: 10.1111/his.13520] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Alastair D Burt
- Faculty of Health and Medical Sciences; University of Adelaide; Adelaide Australia
| | - Venâncio Alves
- Department of Pathology; University of São Paulo School of Medicine; São Paulo Brazil
| | - Pierre Bedossa
- Pathology Department; AP-HP; Beaujon Hospital; Clichy France
- Centre de Recherche Bichat-Beaujon; University Paris-Diderot; Paris France
| | - Andrew Clouston
- Envoi Specialist Pathologists; Brisbane Queensland Australia
| | - Maria Guido
- Surgical Pathology and Cytopathology Unit; Department of Medicine-DIMED; University of Padova; Padova Italy
| | - Stefan Hübscher
- Department of Cellular Pathology; Institute of Immunology and Immunotherapy; University of Birmingham; Queen Elizabeth Hospital; Birmingham UK
| | | | - Irene Ng
- Department of Pathology; State Key Laboratory for Liver Research; The University of Hong Kong; Hong Kong Hong Kong
| | - Young N Park
- Department of Pathology Yonsei; Univesity College of Medicine Seodaemun-gu; Seoul Korea
| | - Helen Reeves
- Northern Institute for Cancer Research, Newcastle University; Newcastle upon Tyne UK
| | - Judith Wyatt
- Department of Histopathology; St James University Hospital; Leeds UK
| | - Matthew M Yeh
- Department of Pathology; University of Washington School of Medicine; Seattle WA USA
| | - David W Ellis
- Clinpath Laboratories; Kent Town South Australia Australia
- ICCR Steering Group Representative; Adelaide Australia
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Abstract
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach.
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Affiliation(s)
- Daniel Zamora-Valdes
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
| | - Timucin Taner
- 1 Divisions of Transplantation Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN, USA
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Prenner S, Kulik L. Hepatocellular Carcinoma. ZAKIM AND BOYER'S HEPATOLOGY 2018:668-692.e9. [DOI: 10.1016/b978-0-323-37591-7.00046-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.
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Pinheiro RS, Waisberg DR, Nacif LS, Rocha-Santos V, Arantes RM, Ducatti L, Martino RB, Lai Q, Andraus W, D’Albuquerque LAC. Living donor liver transplantation for hepatocellular cancer: an (almost) exclusive Eastern procedure? Transl Gastroenterol Hepatol 2017; 2:68. [PMID: 28905009 PMCID: PMC5590014 DOI: 10.21037/tgh.2017.08.02] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Accepted: 07/21/2017] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer and it is linked with chronic liver disease. Liver transplantation (LT) is the best curative treatment modality, since it can cure simultaneously the underlying liver disease and HCC. Milan criteria (MC) are the benchmark for selecting patients with HCC for LT, achieving up to 91% 1-year survival post transplantation. However, when considering intention-to-treat (ITT) rates are substantially lower, mainly due dropout. Additionally, Milan criteria (MC) are too restrictive and more inclusive criteria have been reported with good outcomes. Mainly, in Eastern countries, deceased donors are scarce, therefore Asian centers have developed living-donor liver transplantation (LDLT) to a state-of-art status. There are many eastern centers reporting huge numbers of LDLT with outstanding results. Regarding HCC patients, they have reported many criteria including more advanced tumors achieving reasonable outcomes. Western countries have well-established deceased-donor liver transplantation (DDLT) programs. However, organ shortage and restrictive criteria for listing patients with HCC endorses LDLT as a good option to offer curative treatment to more HCC patients. However, there are some controversial reports claiming higher rates of HCC recurrence after LDLT than DDLT. An extensive review included 30 studies with cohorts of HCC patients who underwent LDLT in both East and West countries. We reported also the results of our Institution, in Brazil, where it was performed the first LDLT. This review also addresses the eligibility criteria for transplanting patients with HCC developed in Western and Eastern countries.
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Affiliation(s)
- Rafael S. Pinheiro
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Daniel R. Waisberg
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Lucas S. Nacif
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Vinicius Rocha-Santos
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Rubens M. Arantes
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Liliana Ducatti
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Rodrigo B. Martino
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Quirino Lai
- Transplant Unit, Department of Surgery, University of L’Aquila, San Salvatore Hospital, L’Aquila, Italy
| | - Wellington Andraus
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Luiz A. C. D’Albuquerque
- Digestive Organs Transplant Unit, Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
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Abstract
Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients. Compared to cadaveric liver transplantation, live donor LT (LDLT) is challenged by ethical, medical and surgical considerations, many of which are still unresolved. The aim of this guideline is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT.
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Fernandez-Sevilla E, Allard MA, Selten J, Golse N, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Adam R. Recurrence of hepatocellular carcinoma after liver transplantation: Is there a place for resection? Liver Transpl 2017; 23:440-447. [PMID: 28187493 DOI: 10.1002/lt.24742] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Revised: 01/12/2017] [Accepted: 01/26/2017] [Indexed: 02/06/2023]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is widely considered as a terminal condition. Therefore, the role of surgery is uncertain in this case. The purpose of this study was to identify the prognostic factors of survival after post-LT HCC recurrence and to evaluate the impact of surgery in this setting. All patients transplanted for HCC between 1991 and 2013 in a single institution and who further developed a post-LT recurrence were included in this study. Univariate and multivariate analyses were performed to identify factors affecting postrecurrence survival. Of the 493 patients transplanted for HCC, a total of 70 (14.2%) consecutive patients developed a recurrence after a median disease-free interval of 17 months. Median survival (MS) from the time of recurrence was 19 months, with a 3-year postrecurrence survival of 26%. Most recurrences were extrahepatic (lung, lymph node, and bone; n = 51; 72.9%), whereas only intrahepatic recurrences were observed in 2 (2.8%) patients. Both intrahepatic and extrahepatic locations were found in 17 (24.3%) patients. A total of 22 (31.4%) patients underwent macroscopically complete resection of the recurrence (intrahepatic [n = 2] and extrahepatic [n = 20]). The MS for resected patients after transplantation was 35 months compared with 15 months for nonresected patients (P < 0.001). In multivariate analysis, the independent unfavorable factors of postrecurrence survival were alpha-fetoprotein level > 100 ng/mL at relapse (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.1; P = 0.03), intrahepatic location (HR, 1.8; 95% CI, 1.0-3.2; P = 0.05), and multifocal recurrence (HR, 1.8; 95% CI, 1.1-3.1; P = 0.04). The management including surgery (HR, 0.4; 95% CI, 0.2-0.7; P = 0.004) was identified as an independent favorable factor. In conclusion, recurrence of HCC after LT is associated with a poor prognosis. However, resection is associated with improved survival and should therefore be considered when feasible. Liver Transplantation 23 440-447 2017 AASLD.
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Affiliation(s)
| | - Marc-Antoine Allard
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 935, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Jasmijn Selten
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France
| | - Nicolas Golse
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Eric Vibert
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Antonio Sa Cunha
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France
| | - Daniel Cherqui
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - Denis Castaing
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 785, Institut National de la Santé et de la Recherche, Villejuif, France
| | - René Adam
- Centre Hépatobiliaire, Hôpital Paul Brousse, Villejuif, France.,Université Paris-Sud, Villejuif, France.,Unité 935, Institut National de la Santé et de la Recherche, Villejuif, France
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