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1
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Rodríguez-Espinosa D, Morantes L, García J, Broseta JJ, Cuadrado-Payán E, Colmenero J, Torregrosa JV, Diekmann F, Esforzado N. Long-Term Outcomes of Incidental Liver Malignancies in Simultaneous Liver-Kidney Transplant Recipients. Transplant Proc 2024; 56:330-334. [PMID: 38350821 DOI: 10.1016/j.transproceed.2024.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 01/16/2024] [Indexed: 02/15/2024]
Abstract
BACKGROUND The pretransplant diagnosis of liver malignancies in nodular cirrhotic livers remains a diagnostic challenge despite current advances. Although the prognostic impact of incidental hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCC) in liver transplant recipients is well documented, there are no data on the impact in simultaneous liver kidney transplant (LKT) recipients. METHODS This is a single-center observational, retrospective study of all LKT performed from May 1993 to April 2022. Among these patients, demographic data, immunosuppressive therapy, rejection episodes, and prevalence of incidental HCC or iCC were evaluated. RESULTS One hundred eight LKTs were performed and 6 were excluded. There were 13 patients with incidental carcinomas in the explanted liver: one of them with both an HCC and iCC, one with an iCC, and the remaining with an HCC. One case of iCC died. No other recurrences occurred. There were no cases of incidental HCC nor iCC in patients with a hereditary or metabolic LKT indication. We found no differences in the 5-year patient survival, and death-censored kidney and liver graft survival rates for those LKT with an incidental HCC and those without it (76.9% vs 84.2%, P = .5; 100% vs 91.6%, P = .28; and 100% vs 94.7%, P = 0.39, respectively). Finally, there were no significant associations between explant carcinoma and rejections of the liver (7.7% vs 17.9%, P = .34) or kidney graft (0% vs 16.8%, P = 0.11). CONCLUSION Despite a high prevalence of incidental HCC or iCC, patient, kidney, and liver graft 5-year survival were unaffected by incidental HCC.
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Affiliation(s)
- Diana Rodríguez-Espinosa
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain.
| | - Laura Morantes
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Jenmy García
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - José Jesús Broseta
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Elena Cuadrado-Payán
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | | | - Josep Vicens Torregrosa
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
| | - Nuria Esforzado
- Department of Nephrology and Renal Transplantation, Hospital Clínic of Barcelona, Barcelona, Spain
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2
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Murta MCB, Ferreira GDSA, Watanabe ALC, Trevizoli NC, Figueira AVF, Caja GON, Ferreira CA, Couto CDF. Incidental Finding of Multiple Synchronous Neoplasms in Explanted Liver After Transplantation: A Case Report. Transplant Proc 2022; 54:1380-1383. [PMID: 35760627 DOI: 10.1016/j.transproceed.2022.03.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/13/2022] [Indexed: 11/18/2022]
Abstract
Liver transplantation is the only potentially curative treatment for patients with end-stage liver disease. After the procedure, histopathologic analysis of the liver explant may reveal neoplasms that were not previously diagnosed in preoperative imaging examinations. This incidental finding of primary liver neoplasms in the explant is not an uncommon situation in liver transplant, and hepatocarcinomas and cholangiocarcinomas are the types of tumors most frequently encountered in this scenario. These are the most common primary neoplasms of the liver, and liver transplantation is often a curative treatment for these types of tumors when they are in their earlier stages. In contrast, liver plasmacytoma is a rare type of plasma cell neoplasm, consisting of a single mass of monoclonal plasma cells, which is treated primarily by radiotherapy and is seldom encountered in the setting of liver transplant. We report the case of a patient who underwent liver transplantation for the treatment of cryptogenic cirrhosis, with no preoperative diagnosis of liver tumors. Analysis of the liver explant revealed the presence of three synchronous neoplasms with different histologic origins: a 27-mm hepatocellular carcinoma, a 17-mm intrahepatic cholangiocarcinoma, and a 25-mm solitary hepatic plasmacytoma. The patient received no further adjuvant treatment and remained well and with no signs of disease recurrence over an observation period of 44 months. We found no previous report in the literature of the synchronous presence of these three types of liver neoplasms.
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Affiliation(s)
| | | | | | | | | | | | - Clara Antunes Ferreira
- General Surgery Department, Hospital Metropolitano Dr Célio de Castro, Belo Horizonte, Brazil
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3
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Bhatti ABH, Hassan M, Rana A, Khan NY, Khan ZA, Zia HH. Risk Score Model for Liver Transplant Outcomes after Preoperative Locoregional Therapy for Hepatocellular Carcinoma. J Gastrointest Cancer 2022; 53:84-90. [PMID: 33184772 DOI: 10.1007/s12029-020-00554-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/09/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE The role of preoperative locoregional therapy (LRT) for hepatocellular carcinoma (HCC) before liver transplantation (LT) remains unclear. Moreover, LRT in the setting of living donor liver transplantation (LDLT) merits further exploration. The objective of the current study was to determine risk factors for poor outcomes after LDLT in patients who received locoregional therapy (LRT). METHODS We reviewed patients (n = 46) who underwent LDLT after LRT. Multivariate analysis was performed to determine independent predictors of recurrence-free survival (RFS). Risk scores were developed to define prognostic groups. RESULTS Median tumor size was 3.7 (1.2-12) cm and tumor number was 1 (1-6). Macrovascular invasion was seen in 10/46 (21.7%) patients. There was a significant difference in 5-year RFS with > 3 tumor nodules (P = 0.005), tumors outside University of California San Francisco criteria (P = 0.03), bilobar disease (P = 0.002), AFP > 600 ng/ml (P = 0.006), and poor response to LRT (P = 0.007). On multivariate analysis, bilobar disease (HR = 2.9, P = 0.01), AFP > 600 ng/ml (HR = 2.3 P = 0.008), and poor response to LRT (HR = 2, P = 0.02) were predictors of 5-year RFS. The 5-year RFS in low risk (score = 0), intermediate risk (score = 1-3), and high risk (score = 4-7) groups was 86%, 76%, and 9% (P < 0.0001). There was no recurrence seen in 4/4 (100%) patients with macrovascular invasion in the low-intermediate risk group. The 5-year RFS in the low-intermediate risk group within and outside Milan criteria was 100% and 74% (P = 0.1). CONCLUSIONS LDLT can provide excellent long-term RFS in patients after preoperative LRT in the low and intermediate risk groups.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan.
| | - Muhammad Hassan
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Atif Rana
- Division of Interventional Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Nusrat Yar Khan
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Zahid Amin Khan
- Division of Interventional Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Haseeb Haider Zia
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
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4
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Tsai YF, Liu FC, Chen CY, Lin JR, Yu HP. Effect of Mycophenolate Mofetil Therapy on Recurrence of Hepatocellular Carcinoma after Liver Transplantation: A Population-Based Cohort Study. J Clin Med 2021; 10:jcm10081558. [PMID: 33917215 PMCID: PMC8068064 DOI: 10.3390/jcm10081558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/11/2021] [Accepted: 03/18/2021] [Indexed: 12/23/2022] Open
Abstract
Hepatocellular carcinoma (HCC) recurrence after liver transplantation is associated with immunosuppressants. However, the appropriate immunosuppressant for HCC recipients is still debated. Data for this nationwide population-based cohort study were extracted from the National Health Insurance Research Database of Taiwan. A total of 1250 liver transplant recipients (LTRs) with HCC were included. We analyzed the risk factors for post-transplant HCC recurrences. Cumulative defined daily dose (cDDD) represented the exposure duration and was calculated as the amount of dispensed defined daily dose (DDD) of mycophenolate mofetil (MMF). The dosage effects of MMF on HCC recurrence and liver graft complication rates were investigated. A total of 155 LTRs, having experienced post-transplant HCC recurrence, exhibited low survival probability at 1-, 3-, 5-, and 10-year observations. Our results demonstrated increased HCC recurrence rate after liver transplantation (p = 0.0316) following MMF administration; however, no significant increase was demonstrated following cyclosporine, tacrolimus, or sirolimus administration. Notably, our data demonstrated significantly increased HCC recurrence rate following MMF administration with cDDD > 0.4893 compared with cDDD ≤ 0.4893 or no administration of MMF (p < 0.0001). MMF administration significantly increases the risk of HCC recurrence. Moreover, a MMF-minimizing strategy (cDDD ≤ 0.4893) is recommended for recurrence-free survival.
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Affiliation(s)
- Yung-Fong Tsai
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (Y.-F.T.); (F.-C.L.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Fu-Chao Liu
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (Y.-F.T.); (F.-C.L.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Chun-Yu Chen
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (Y.-F.T.); (F.-C.L.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Jr-Rung Lin
- Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan 333, Taiwan;
- Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Huang-Ping Yu
- Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; (Y.-F.T.); (F.-C.L.); (C.-Y.C.)
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Correspondence: ; Tel.: +86-886-3-3281200 (ext. 2324)
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5
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Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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6
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de la Fuente S, Citores MJ, Lucena JL, Muñoz P, Cuervas-Mons V. TLR9-1486C/T polymorphism is associated with hepatocellular carcinoma recurrence after liver transplantation. Biomark Med 2019; 13:995-1004. [PMID: 31317790 DOI: 10.2217/bmm-2019-0030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023] Open
Abstract
Aim: To determine whether TLR9 polymorphisms are associated with tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC). Patients & methods: All patients who underwent liver transplantation, and had viable HCC in the explanted liver were included. TLR9-1237C/T and -1486C/T polymorphisms were analyzed by real-time PCR and melting curves analysis. Results: 20 of 159 patients (12.6%) developed post-transplant HCC recurrence. Tumors exceeding Milan criteria, moderately-to-poorly differentiated tumors and microvascular invasion on explants, and pretransplant α-fetoprotein level (all p < 0.01) were associated with an increased risk, while TLR9-1486TT genotype was associated with a decreased risk of HCC recurrence (p = 0.03). Conclusion: TLR9-1486C/T might help to preoperatively identify patients at low risk of post-transplant HCC recurrence.
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Affiliation(s)
- Sara de la Fuente
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
| | - María-Jesús Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Joaquin Rodrigo 2, 28022 Majadahonda, Madrid, Spain
| | - José-Luis Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Surgery, Hospital Universitario Puerta de Hierrdo-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
| | - Pablo Muñoz
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Joaquin Rodrigo 2, 28022 Majadahonda, Madrid, Spain
| | - Valentín Cuervas-Mons
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28022 Majadahonda, Madrid, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo, s/n, 28029 Madrid, Spain
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7
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A Point-based Histologic Scoring System for Hepatocellular Carcinoma Can Stratify Risk of Posttransplant Tumor Recurrence. Am J Surg Pathol 2019; 42:855-865. [PMID: 29649017 DOI: 10.1097/pas.0000000000001053] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Eligibility for liver transplant is most commonly decided by measuring tumor size and number on radiographic imaging. However, this method often underestimates the extent of disease. Evaluation of tumor histology has been shown to improve risk stratification when compared with imaging-based transplant criteria, but the World Health Organization (WHO) guidelines for grading hepatocellular carcinoma (HCC) are imprecise and require subjective interpretation by the pathologist. We performed a retrospective analysis of 190 explanted livers containing HCC and correlated histologic features with posttransplant recurrence to formulate a three-tiered, point-based scoring system that categorizes tumors as having a low, intermediate, or high risk of recurrence. Our Recurrence Risk Assessment Score (RRAS) evaluates tumor architecture and specific cytologic features-nuclear pleomorphism, cytoplasmic amphophilia, and nuclear-to-cytoplasmic ratio-showing superior stratification of HCC recurrence risk compared with imaging criteria and grade assigned by WHO methodology. Stratifying tumors using RRAS criteria, the rate of recurrence after transplant was 0% among low-risk tumors (compared with 3% of well-differentiated tumors), 12% among intermediate-risk tumors (compared with 15% of moderately differentiated tumors), and 54% among high-risk tumors (compared with 29% of poorly differentiated tumors). Receiver operating characteristic analysis shows significantly improved performance of RRAS criteria in predicting HCC recurrence compared with WHO grade (area under curve of 0.841 and 0.671, respectively; P=0.0061). Our results indicate that evaluation of tumor histology offers superior prediction of recurrence risk following liver transplantation compared with radiographic criteria, and that the RRAS system better stratifies recurrence risk compared with HCC grading by WHO methodology.
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8
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Living donor liver transplantation in hepatocellular carcinoma: A single-center experiences. JOURNAL OF SURGERY AND MEDICINE 2019. [DOI: 10.28982/josam.557019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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9
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Citores MJ, Lucena JL, de la Fuente S, Cuervas-Mons V. Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation. World J Hepatol 2019; 11:50-64. [PMID: 30705718 PMCID: PMC6354126 DOI: 10.4254/wjh.v11.i1.50] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.
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Affiliation(s)
- Maria J Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda 28222, Spain.
| | - Jose L Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Sara de la Fuente
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Valentin Cuervas-Mons
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
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10
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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11
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Costentin CE, Amaddeo G, Decaens T, Boudjema K, Bachellier P, Muscari F, Salamé E, Bernard PH, Francoz C, Dharancy S, Vanlemmens C, Radenne S, Dumortier J, Hilleret MN, Chazouillères O, Pageaux GP, Calderaro J, Laurent A, Roudot-Thoraval F, Duvoux C. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models. Liver Int 2017; 37:717-726. [PMID: 28199760 DOI: 10.1111/liv.13388] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Abstract
AIM Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. METHODS Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. RESULTS Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). CONCLUSION Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
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Affiliation(s)
| | | | - Thomas Decaens
- Service d'hépatologie, CHU Grenoble Alpes, Grenoble, France
| | - Karim Boudjema
- Service de Chirurgie digestive, Hôpital Pontchaillou, Rennes, France
| | | | - Fabrice Muscari
- Service de Chirurgie digestive, Hôpital Rangueil, Toulouse, France
| | - Ephrem Salamé
- Service de Chirurgie digestive, CHU de Tours, Chambray-lès-Tours, France
| | | | | | | | | | - Sylvie Radenne
- Service d'hépatologie, Hôpital Lyon Croix Rousse, Lyon, France
| | - Jérôme Dumortier
- Service d'hépatologie, Hospices Civiles de Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | | | | | - Julien Calderaro
- Département de Pathologie, Hôpital Henri Mondor, Créteil, France
| | - Alexis Laurent
- Service de Chirurgie digestive, Hôpital Henri Mondor, Créteil, France
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12
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Donat M, Alonso S, Pereira F, Ferrero E, Carrión L, Acin-Gándara D, Moreno E. Impact of Histological Factors of Hepatocellular Carcinoma on the Outcome of Liver Transplantation. Transplant Proc 2017; 48:1968-77. [PMID: 27569930 DOI: 10.1016/j.transproceed.2016.04.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 04/10/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND The aim of this study was to identify predictors of overall survival (OS), disease-free survival (DFS), and recurrence in a cohort of 151 patients with hepatocellular carcinoma (HCC) and cirrhosis who were treated by liver transplantation (LT). PATIENTS AND METHODS A retrospective database of patients undergoing LT for radiologically diagnosed HCC at "12 de Octubre" Hospital, Madrid during 1986-2006 was analyzed. RESULTS The median follow-up was 67.44 months (SD = 55.7 months). Overall 1-, 3-, 5-, and 10-year survival was 87.5%, 73.7%, 64.1% and 43.4%, respectively. The 5-year OS of patients beyond the Milan criteria was 47.14%, whereas that of patients within the Milan criteria was 70.13% (P = .011). The 5-year OS of patients beyond the Milan criteria and with microvascular invasion (MVI) was 27.27%, whereas that of patients beyond the Milan criteria and without MVI criteria was 57.89% (P = .003). Multivariate analysis of prognostic factors revealed MVI and G3 to be independent and statistically significant factors affecting OS (P < .0001 and P = .045, respectively), DFS (P < .0001 and P = .004, respectively), and recurrence (P = .0002 and P = .028, respectively). Multivariate analysis of prognostic factors also revealed preoperative fine-needle aspiration (FNA) to be an independent negative statistically significant factor affecting recurrence (P = .0022). Multivariate analysis of predictive MVI factors revealed preoperative α-fetoprotein (AFP) levels >200 ng/mL to be an independent positive and statistically significant predictor of MVI (P = .0004). CONCLUSION MVI and G3 are independent negative factors affecting OS, DFS, and recurrence. The presence of MVI or AFP levels >200 ng/mL represent a contraindication for LT, as long as the patient is beyond the Milan criteria.
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Affiliation(s)
- M Donat
- Department of General and Visceral Surgery, Infanta Leonor Hospital, Madrid, Spain
| | - S Alonso
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain.
| | - F Pereira
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - E Ferrero
- Department of General and Visceral Surgery, "12 de Octubre" University Hospital, Madrid, Spain
| | - L Carrión
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - D Acin-Gándara
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - E Moreno
- Department of General and Visceral Surgery, "12 de Octubre" University Hospital, Madrid, Spain
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14
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Buescher N, Seehofer D, Helbig M, Andreou A, Bahra M, Pascher A, Pratschke J, Schoening W. Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era? World J Transplant 2016; 6:599-607. [PMID: 27683639 PMCID: PMC5036130 DOI: 10.5500/wjt.v6.i3.599] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Revised: 05/18/2016] [Accepted: 08/01/2016] [Indexed: 02/05/2023] Open
Abstract
AIM To characterize major determinants of 20-year survival after liver transplantation (LT).
METHODS This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT.
RESULTS Twenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age ≥ 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263).
CONCLUSION LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.
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Gu L, Jin W, Kan L, Wang X, Shan C, Fan H. A retrospective study to compare the use of tacrolimus and cyclosporine in combination with adriamycin in post-transplant liver cancer patients. Cell Biochem Biophys 2016; 71:565-70. [PMID: 25287673 DOI: 10.1007/s12013-014-0235-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The aim of this study was to compare the clinical effect of tacrolimus (TAC) versus cyclosporine (CycA) in post-transplant hepatic cancer patients undergoing adriamycin hydrochloride (ADM) chemotherapy. Patients with advanced hepatic cancer who underwent liver transplant and subsequent therapy between March 2007 and March 2009 in our hospital were selected for this study. All of these patients were treated with chemotherapeutic agent adriamycin, with respect to immunosuppressant, whereas they received either TAC or CycA, and hence represented two groups, TAC and controls, respectively. The short- and long-term outcomes of two therapies, ADM + TAC and ADM + CsA, were compared. The TAC group patients showed improved remission compared to the control group (40 cases with 46.0 % versus 32 cases with 31.1 % remission, respectively). The 5-year survival in TAC group was significantly prolonged (20.7 %) compared to that of the controls (8.7 %). The short-term outcomes, such as serum levels of calcium, biomarkers of cardiac toxicity/functioning, and regulatory T lymphocytes counts (markers of immune functioning), were found to be significantly more auspicious with TAC treatment than with CycA. Our study showed that use of TAC plus ADM resulted in improved patient survival, tolerance of the graft, and remission compared to CycA combined with ADM. The serum levels of various markers in the short follow-up analysis indicated a better cardiac and immune functioning with TAC than with CycA treatment.
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Affiliation(s)
- Liangfeng Gu
- Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
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16
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Boussouar S, Itti E, Lin SJ, Decaens T, Evangelista E, Chiaradia M, Chalaye J, Baranes L, Calderaro J, Laurent A, Pigneur F, Duvoux C, Azoulay D, Costentin C, Rahmouni A, Luciani A. Functional imaging of hepatocellular carcinoma using diffusion-weighted MRI and (18)F-FDG PET/CT in patients on waiting-list for liver transplantation. Cancer Imaging 2016; 16:4. [PMID: 26883745 PMCID: PMC4756529 DOI: 10.1186/s40644-016-0062-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 02/02/2016] [Indexed: 02/08/2023] Open
Abstract
Background To compare the apparent diffusion coefficient (ADC) on diffusion-weighted imaging (DWI) with the standardized uptake values (SUV) measured by18F-FDG-PET/CT in naïve hepatocellular carcinoma (HCC) nodules, and to determine whether these markers are associated with tumours at high-risk of aggressiveness. Methods From 2007 to 2010, all patients with HCC on the waiting list for liver transplantation and who underwent both FDG-PET/CT and 1.5-T DWI-MRI (b values: 0, 200, 400, and 800 s/mm2) were included in this institutional review board-approved retrospective study. Tumour size, tumour ADC, tumour-to-liver ADC ratio (ADCT/L), maximal tumour SUV and tumour-to-liver SUV ratio (SUVT/L) were measured and compared to serum alpha-fetoprotein (AFP) levels, tumour size and differentiation grade on explanted specimens. Results A total of 37 HCC nodules in 28 patients were available for correlation between MRI and PET/CT, 7 of which (in 7 patients) showed a SUVT/L > 1.15. We did not find any correlation between tumour ADC or ADCT/L and tumour SUV or SUVT/L. To note, SUVT/L was positively correlated with AFP levels (R = 0.95, P ≤ 0.0001), while ADCT/L was not (P = 0.73). Twenty-four patients (with 32 nodules) underwent liver transplantation. In this subgroup, an increased SUVT/L ratio was associated with larger tumours (average size, 32 ± 14 mm; range, 18–60 mm; P < 0.0001) and with poor differentiation on pathology (grades 3 and 4; P = 0.04), while ADCT/L was neither associated with tumour size or differentiation grade. Conclusions ADC and SUV measures in HCC nodules are not correlated. SUVT/L ratio correlates with AFP levels, tumour size and poor differentiation, and should probably be integrated as a co-variable in a predictive outcome model of patients on the waiting-list for liver transplantation.
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Affiliation(s)
- Samia Boussouar
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France.
| | - Emmanuel Itti
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Médecine Nucléaire, Créteil, F-94010, France. .,INSERM Unité U 955, GRC Amyloid Research Institute, Créteil, F-94010, France. .,Service de Médecine Nucléaire, CHU Henri Mondor, 51 Avenue du Marechal de Lattre de Tassigny, 94010, Créteil, Cedex, France.
| | - Shih-Jui Lin
- Biomedical Informatics, Stanford University, Stanford, CA, 94305, USA.
| | - Thomas Decaens
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Hépatologie, Créteil, F-94010, France.
| | - Eva Evangelista
- AP-HP, Hôpitaux Universitaires Henri Mondor, Médecine Nucléaire, Créteil, F-94010, France.
| | - Melanie Chiaradia
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France. .,Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France.
| | - Julia Chalaye
- AP-HP, Hôpitaux Universitaires Henri Mondor, Médecine Nucléaire, Créteil, F-94010, France.
| | - Laurence Baranes
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Médecine Nucléaire, Créteil, F-94010, France.
| | - Julien Calderaro
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Pathologie, Créteil, F-94010, France. .,INSERM Unité U 955, Equipe 18, Créteil, F-94010, France.
| | - Alexis Laurent
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,INSERM Unité U 955, Equipe 18, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Chirurgie hépatique, Créteil, F-94010, France.
| | - Frederic Pigneur
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France.
| | - Christophe Duvoux
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Hépatologie, Créteil, F-94010, France.
| | - Daniel Azoulay
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Chirurgie hépatique, Créteil, F-94010, France.
| | - Charlotte Costentin
- Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,AP-HP, Hôpitaux Universitaires Henri Mondor, Hépatologie, Créteil, F-94010, France.
| | - Alain Rahmouni
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France. .,Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France.
| | - Alain Luciani
- AP-HP, Hôpitaux Universitaires Henri Mondor, Imagerie Médicale, Créteil, F-94010, France. .,Université Paris Est Créteil, Faculte de Médecine, Créteil, F-94010, France. .,INSERM Unité U 955, Equipe 18, Créteil, F-94010, France.
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Schraiber LDS, de Mattos AA, Zanotelli ML, Cantisani GPC, Brandão ABDM, Marroni CA, Kiss G, Ernani L, Marcon PDS. Alpha-fetoprotein Level Predicts Recurrence After Transplantation in Hepatocellular Carcinoma. Medicine (Baltimore) 2016; 95:e2478. [PMID: 26817881 PMCID: PMC4998255 DOI: 10.1097/md.0000000000002478] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of liver transplantation. In an attempt to predict their recurrence after liver transplantation, evaluation of tumor number and size, degree of histologic differentiation, and the presence of vascular invasion already have their importance established. In this context, the role of biologic markers such as alpha-fetoprotein (AFP) is still not clear. This retrospective cross-sectional study analyzed the AFP relationship with recurrence of HCC after orthotopic liver transplantation.The current study retrospectively analyzed data from 206 patients with a histopathologic confirmed HCC between 1997 and 2010.The overall survival rates at 1, 3, 5, and 14 years were 78.6%, 65.4%, 60.5%, and 38.7%, respectively. The frequency of recurrence was 15.5%, and recurrence was significantly associated with a lower survival rate (P < 0.001). No association was observed between survival and AFP level (P = 0.153). A correlation, however, was found between tumor recurrence and AFP level (P = 0.002). Univariate analysis of risk factors for recurrence revealed that an AFP level greater than 200 ng/mL, the number of tumors, the degree of cellular differentiation, and the presence of vascular invasion or satellite nodules were associated with relapse. By multivariate analysis, only an AFP level greater than 200 ng/mL remained as a risk factor.Although an elevated AFP level did not correlate with survival in HCC patients undergoing orthotopic liver transplantation, a high AFP level was associated with a 3.32-folds increase in the probability of HCC recurrence.
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Affiliation(s)
- Luciana Dos Santos Schraiber
- From the Department of Gastroenterology and Hepatology, Universidade Federal de Ciências da Saúde (LSS, AADM, ABMB, CAM, LE, PSM) and Santa Casa de Misericórdia, de Porto Alegre, Brazil (MLZ, GPCC, ABMB, CAM, GK)
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18
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Piras-Straub K, Khairzada K, Gerken G, Saner F, Treckmann J, Paul A, Canbay A, Herzer K. Glutamate dehydrogenase and alkaline phosphatase as very early predictors of hepatocellular carcinoma recurrence after liver transplantation. Digestion 2015; 91:117-27. [PMID: 25662469 DOI: 10.1159/000370212] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 11/26/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although long-term survival rates for patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC) are good, the relatively high rate of tumor recurrence after LT necessitates the identification of biological parameters that supplement morphological predictors of recurrence. METHOD From chart review we identified 175 patients who received liver transplantation due to HCC at our center between January 2000 and December 2013. We documented demographic and clinical data, as well as clinicopathological characteristics of the tumors, with a focus on liver values at the time of LT. RESULTS HCC recurred in 23% of LT patients. Most recurrences (59%) occurred within 12 months after LT; hardly any recurrence was detected later than 3 years after LT. Recurrence was positively correlated with tumor size, tumor stage and alpha-fetoprotein level (AFP), and it was most likely with certain causes of liver disease. Interestingly, tumor recurrence was independently predicted by serum levels of glutamate dehydrogenase (GLDH) and alkaline phosphatase (AP) at the time of LT. CONCLUSIONS Because all HCC recurrence occurs within 36 months after LT, HCC detected more than 3 years after LT may be considered de novo. Liver values, with GLDH and AP being the most preponderant, serve as easy-to-assess biomarkers which contribute to predict the risk of tumor recurrence.
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Affiliation(s)
- Katja Piras-Straub
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
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EXP CLIN TRANSPLANTExp Clin Transplant 2015; 13. [DOI: 10.6002/ect.2014.0266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Li HL, Ji WB, Zhao R, Duan WD, Chen YW, Wang XQ, Yu Q, Luo Y, Dong JH. Poor prognosis for hepatocellular carcinoma with transarterial chemoembolization pre-transplantation: retrospective analysis. World J Gastroenterol 2015; 21:3599-3606. [PMID: 25834326 PMCID: PMC4375583 DOI: 10.3748/wjg.v21.i12.3599] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2014] [Revised: 09/30/2014] [Accepted: 10/21/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate whether transarterial chemoembolization (TACE) before liver transplantation (LT) improves long-term survival in hepatocellular carcinoma (HCC) patients. METHODS A retrospective study was conducted among 204 patients with HCC who received LT from January 2002 to December 2010 in PLA General Hospital. Among them, 88 patients received TACE before LT. Prognostic factors of serum α-fetoprotein (AFP), intraoperative blood loss, intraoperative blood transfusion, disease-free survival time, survival time with tumor, number of tumor nodules, tumor size, tumor number, presence of blood vessels and bile duct invasion, lymph node metastasis, degree of tumor differentiation, and preoperative liver function were determined in accordance with the Child-Turcotte-Pugh (Child) classification and model for end-stage liver disease. We also determined time of TACE before transplant surgery and tumor recurrence and metastasis according to different organs. Cumulative survival rate and disease-free survival rate curves were prepared using the Kaplan-Meier method, and the log-rank and χ(2) tests were used for comparisons. RESULTS In patients with and without TACE before LT, the 1, 3 and 5-year cumulative survival rate was 70.5% ± 4.9% vs 91.4% ± 2.6%, 53.3% ± 6.0% vs 83.1% ± 3.9%, and 46.2% ± 7.0% vs 80.8% ± 4.5%, respectively. The median survival time of patients with and without TACE was 51.857 ± 5.042 mo vs 80.930 ± 3.308 mo (χ(2) = 22.547, P < 0.001, P < 0.05). The 1, 3 and 5-year disease-free survival rates for patients with and without TACE before LT were 62.3% ± 5.2% vs 98.9% ± 3.0%, 48.7% ± 6.7% vs 82.1% ± 4.1%, and 48.7% ± 6.7% vs 82.1% ± 4.1%, respectively. The median survival time of patients with and without TACE before LT was 50.386 ± 4.901 mo vs 80.281 ± 3.216 mo (χ(2) = 22.063, P < 0.001, P < 0.05). TACE before LT can easily lead to pulmonary or distant metastasis of the primary tumor. Although there was no significant difference between the two groups, the chance of metastasis of the primary tumor in the group with TACE was significantly higher than that of the group without TACE. CONCLUSION TACE pre-LT for HCC patients increased the chances of pulmonary or distant metastasis of the primary tumor, thus reducing the long-term survival rate.
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Abstract
Hepatocellular carcinoma (HCC) is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT) representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.
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Affiliation(s)
- Ahmad A. Madkhali
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada
| | - Zahir T. Fadel
- Section of Hepatopancreatobilairy and Transplant, Transplant, McGill University, Montreal, Canada,Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Murad M. Aljiffry
- Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mazen M. Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Department of Oncology, McGill University, Montreal, Canada,Address for correspondence: Dr. Mazen Hassanain, Assistant Professor of Surgery and Consultant HPB and Transplant Surgery, Department of Surgery, College of Medicine, Scientific Director Liver Disease Research Centre, King Saud University, P.O.Box 25179, Riyadh, 11466, Saudi Arabia. E-mail:
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Hu Z, Li Z, Xiang J, Zhou J, Yan S, Wu J, Zhou L, Zheng S. Intent-to-treat analysis of liver transplant for hepatocellular carcinoma in the MELD era: impact of hepatitis C and advanced status. Dig Dis Sci 2014; 59:3062-3072. [PMID: 25008426 DOI: 10.1007/s10620-014-3266-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Accepted: 06/23/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND/AIM Liver transplantation is a well-recognized treatment for non-resectable hepatocellular carcinoma (HCC); however, the overall survival and waiting list removal rates for hepatitis C virus (HCV)-related HCC have not been assessed. METHODS The present study included 11,146 patients with HCC and 64,788 patients without HCC, listed for liver transplantation on the Scientific Registry of Transplant Recipients database between 2003 and 2010. RESULTS In a multivariate analysis, HCV infection was an independent predictor of being transplanted or remaining on the waiting list in HCC candidates (HR 0.65, 95% CI 0.60-0.71, p < 0.001). However, patients in the advanced status (model for end-stage liver disease score over 20, tumor stage exceed tumor-node-metastasis stage II, or alpha fetoprotein lover 400 ng/ml) but without HCV had better post-transplant survival than patients in the advanced status and with HCV (64 vs. 47% at 5 years, p < 0.001), and comparable survival to patients with HCV but not in the advanced status (62%, p = 0.461). CONCLUSIONS HCC candidates with HCV infection are more likely to be transplanted, remain on the waiting list for longer, and have worse post-transplant survival. Patients in the advanced status but without HCV also could share a similar post-transplant survival to those not in the advanced status but with HCV.
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Affiliation(s)
- Zhenhua Hu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Key Laboratory of Combined Multi-organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation, No. 79 Qingchun Road, Hangzhou, 310003, Zhejiang Province, China,
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Lee JY, Kim YH, Yi NJ, Kim HS, Lee HS, Lee BK, Kim H, Choi YR, Hong G, Lee KW, Suh KS. Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation. Clin Mol Hepatol 2014; 20:192-203. [PMID: 25032186 PMCID: PMC4099335 DOI: 10.3350/cmh.2014.20.2.192] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 06/07/2014] [Accepted: 06/10/2014] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD). RESULTS The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive (18)fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.
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Affiliation(s)
- Ju-Yeun Lee
- Department of Pharmacy, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea. ; College of Pharmacy, Hanyang University, Gyeonggi-do, Korea
| | - Yul Hee Kim
- Ewha Graduate School of Clinical Health Sciences, Ewha Women's University, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyang Sook Kim
- Department of Pharmacy, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Suk Lee
- Department of Pharmacy, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Byung Koo Lee
- Ewha Graduate School of Clinical Health Sciences, Ewha Women's University, Seoul, Korea
| | - Hyeyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Young Rok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Geun Hong
- Department of Surgery, Ewha Women's University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Foltys D, Zimmermann T, Kaths M, Strempel M, Heise M, Hoppe-Lotichius M, Weiler N, Scheuermann U, Ruckes C, Hansen T, Pitton M, Otto G. Hepatocellular carcinoma in Child's A cirrhosis: a retrospective analysis of matched pairs following liver transplantation vs. liver resection according to the intention-to-treat principle. Clin Transplant 2013; 28:37-46. [DOI: 10.1111/ctr.12273] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2013] [Indexed: 01/19/2023]
Affiliation(s)
- Daniel Foltys
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Tim Zimmermann
- Department of Internal Medicine I; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Moritz Kaths
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Mari Strempel
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Michael Heise
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Maria Hoppe-Lotichius
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Nina Weiler
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Uwe Scheuermann
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Christian Ruckes
- Institute of Medical Biostatistics, Epidemiology and Informatics; University Medical Center; Johannes Gutenberg University; Mainz Germany
| | - Torsten Hansen
- Department of Pathology; University Medical Center; Johannes Gutenberg University; Mainz Germany
| | - Michael Pitton
- Department of Radiology; University Medical Center; Johannes Gutenberg-University; Mainz Germany
| | - Gerd Otto
- Department of Transplantation and Hepatobiliary Surgery; University Medical Center; Johannes Gutenberg-University; Mainz Germany
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25
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Jiang L, Yan LN, Wen TF, Li B, Yang JY. Comparison of hepatitis B prophylactic outcomes in living donor liver transplantation recipients who meet the Milan or UCSF criteria. Hepatobiliary Pancreat Dis Int 2013; 12:494-9. [PMID: 24103279 DOI: 10.1016/s1499-3872(13)60078-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The tumor burden before liver transplantation indicates that hepatitis B virus (HBV) may hide in the extrahepatic and micrometastatic sites which serve as a source of HBV replication. Currently, many liver transplant centers, especially in Western countries, use the Milan or UCSF criteria to select patients with hepatocellular carcinoma for liver transplantation. This study was undertaken to compare the HBV prophylactic outcomes in two groups of living donor liver transplantation (LDLT) recipients. Patients in group A met the Milan criteria and those in group B exceeded the Milan criteria but were within the UCSF criteria. METHODS A database of adult-to-adult right-lobe LDLT performed at our institution for HBV-related hepatocellular carcinoma within the Milan or UCSF criteria between June 2002 and May 2012 was used to compare the HBV prophylactic outcomes between patients within the Milan criteria (group A, 41 patients) and those exceeding the Milan criteria but within the UCSF criteria (group B, 19 patients). RESULTS The 1-, 3-, and 5-year survival rates were similar between groups A and B (87.8%, 85.1% and 74.0% vs 73.3%, 61.1% and 61.1%, respectively, P=0.067). HBV recurred in 1 patient in 3.1 months after LDLT in group A and in 2 patients in group B (1 in 11.9 months and 1 in 24.1 months after LDLT). The 1-, 3-, and 5-year HBV recurrence rates were 2.6%, 2.6% and 2.6% in group A, and 7.3%, 17.9% and 17.9% in group B, respectively (P=0.118). CONCLUSION LDLT recipients who exceed the Milan criteria but remain within the UCSF criteria may have post-transplant HBV prophylactic outcomes similar to those who meet the Milan criteria.
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Affiliation(s)
- Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
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26
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Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown RS, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond JC, Stiles JB, Lukose T, Chang MS, Klintmalm G. Multicenter review of liver transplant for hepatitis B-related liver disease: disparities in gender and ethnicity. Clin Transplant 2013; 27:829-37. [PMID: 24033475 DOI: 10.1111/ctr.12224] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2013] [Indexed: 12/15/2022]
Abstract
Orthotopic liver transplantation (OLT) is the preferred treatment for selected patients with hepatitis B virus (HBV)-related liver disease. This study aimed to (i) define long-term outcomes following OLT for HBV; (ii) to quantify the incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii) to determine outcomes for specific patient subgroups. We performed a retrospective chart review of 738 patients undergoing OLT between 1985 and 2010 at seven US transplant centers and divided the patients into 3 eras, 1985-1994, 1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer (p < 0.001), and retransplantation (p = 0.01) were significantly associated with worse survival on multivariate analysis. Survival at three yr was poor for all ethnicities in Era 1, but significantly improved for all except black Americans by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of combination antiviral and immunoglobulin therapy, women and black Americans may not have realized an equal benefit. The rate of rHBV is significant even 10 yr post-transplant with survival affected.
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Affiliation(s)
- Jeffrey Campsen
- Baylor University Medical Center at Dallas, Dallas, TX, USA; University of Utah Health Sciences Center, Salt Lake City, UT, USA
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27
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Schoening WN, Buescher N, Rademacher S, Andreou A, Kuehn S, Neuhaus R, Guckelberger O, Puhl G, Seehofer D, Neuhaus P. Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases. Am J Transplant 2013; 13:2384-94. [PMID: 23915357 DOI: 10.1111/ajt.12384] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 05/13/2013] [Accepted: 06/12/2013] [Indexed: 02/06/2023]
Abstract
With excellent short-term survival in liver transplantation (LT), we now focus on long-term outcome and report the first European single-center 20-year survival data. Three hundred thirty-seven LT were performed in 313 patients (09/88-12/92). Impact on long-term outcome was studied and a comparison to life expectancy of matched normal population was performed. A detailed analysis of 20-years follow-up concerning overweight (HBMI), hypertension (HTN), diabetes (HGL), hyperlipidemia (HLIP) and moderately or severely impaired renal function (MIRF, SIRF) is presented. Patient and graft survival at 1, 10, 20 years were 88.4%, 72.7%, 52.5% and 83.7%, 64.7% and 46.6%, respectively. Excluding 1-year mortality, survival in the elderly LT recipients was similar to normal population. Primary indication (p < 0.001), age (p < 0.001), gender (p = 0.017), impaired renal function at 6 months (p < 0.001) and retransplantation (p = 0.034) had significant impact on patient survival. Recurrent disease (21.3%), infection (20.6%) and de novo malignancy (19.9%) were the most common causes of death. Prevalence of HTN (57.3-85.2%, p < 0.001), MIRF (41.8-55.2%, p = 0.01) and HBMI (33.2-45%, p = 0.014) increased throughout follow-up, while prevalence of HLIP (78.0-47.6%, p < 0.001) declined. LT has conquered many barriers to achieve these outstanding long-term results. However, much work is needed to combat recurrent disease and side effects of immunosuppression (IS).
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28
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Campsen J, Zimmerman M, Trotter J, Hong J, Freise C, Brown R, Cameron A, Ghobrial M, Kam I, Busuttil R, Saab S, Holt C, Emond J, Stiles J, Lukose T, Chang M, Klintmalm G. Liver transplantation for hepatitis B liver disease and concomitant hepatocellular carcinoma in the United States With hepatitis B immunoglobulin and nucleoside/nucleotide analogues. Liver Transpl 2013; 19:1020-9. [PMID: 23852663 DOI: 10.1002/lt.23703] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2012] [Accepted: 06/03/2013] [Indexed: 12/24/2022]
Abstract
Reinfection with hepatitis B virus (HBV) after liver transplantation (LT) may favor the recurrence of hepatocellular carcinoma (HCC), and combination therapy with hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogues may reduce HBV recurrence after LT. To test associations between HBV, HCC, and survival, we performed a retrospective chart review of patients undergoing LT for HBV between January 1985 and December 2010 at 7 US transplant centers. After we divided the patients into 3 eras based on evolving strategies in antiviral therapy (1985-1994, 1995-2004, and 2005-2010), we reviewed 16 variables to determine whether there were associations between survival and HCC recurrence. Seven hundred thirty-eight patients underwent transplantation for HBV, and 354 (48.0%) had concomitant HCC, which recurred in 58 patients (16.4%). Three-year survival was much better in era 3 versus era 1 (87% versus 40%, P = 0.001), and the incidence of HCC recurrence was lower (12% versus 29%, P = 0.009). The lungs were the most frequent first site of HCC recurrence, and they were followed by the liver. A multivariate analysis showed that HBV reinfection, HCC recurrence, and HBIG use were associated with worse survival (P < 0.001, P < 0.001, and P = 0.002, respectively); HCC recurrence and stage 3 HCC, among other factors, were associated with HBV reinfection (P < 0.001 and P = 0.004); and stage 3 HCC, vascular invasion of the explanted tumor, and post-LT chemotherapy were associated with HCC recurrence (P = 0.008, P < 0.001, and P < 0.001, respectively). Patients with HBV reinfection were 3.6 times more likely than patients without HBV to have HCC recurrence. These data suggest further study of attempts at LT for patients with HBV and HCC beyond the Milan criteria if their HBV is aggressively and successfully treated.
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Affiliation(s)
- Jeffrey Campsen
- Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
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29
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Young RS, Aldiwani M, Hakeem AR, Nair A, Guthrie A, Wyatt J, Treanor D, Morris-Stiff G, Jones RL, Prasad KR. Pre-liver transplant biopsy in hepatocellular carcinoma: a potential criterion for exclusion from transplantation? HPB (Oxford) 2013; 15:418-27. [PMID: 23458127 PMCID: PMC3664045 DOI: 10.1111/hpb.12008] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Accepted: 10/17/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND In cirrhotic patients with hepatocellular carcinoma (HCC), poor differentiation in pre-liver transplantation (LT) biopsy of the largest tumour is used as a criterion for exclusion from LT in some centres. The potential role of pre-LT biopsy at one centre was explored. METHODS A prospective database of patients undergoing orthotopic LT for radiologically diagnosed HCC at St James's University Hospital, Leeds during 2006-2011 was analysed. RESULTS A total of 60 predominantly male (85.0%) patients with viral hepatitis were identified. There were discrepancies between radiological and histopathological findings with respect to the number of tumours identified (in 27 patients, 45.0%) and their size (in 63 tumours, 64.3%). In four (6.7%) patients, the largest lesion, which would theoretically have been targeted for biopsy, was not the largest in the explant. Nine (31.0%) patients with multifocal HCC had tumours of differing grades. In two (6.9%) patients, the largest tumour was well differentiated, but smaller tumours in the explant were poorly differentiated. In one patient, the largest lesion was benign and smaller invasive tumours were confirmed histologically. CONCLUSIONS The need to optimize selection for LT in HCC remains. In the present series, the largest tumour was not always representative of overall tumour burden or biological aggression and its potential use to exclude patients from LT is questionable.
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Affiliation(s)
- Richard S Young
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Mohammed Aldiwani
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Abdul R Hakeem
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Amit Nair
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Ashley Guthrie
- Department of Radiology, St James's University HospitalLeeds, UK
| | - Judy Wyatt
- Department of Histology, St James's University HospitalLeeds, UK
| | - Darren Treanor
- Department of Histology, St James's University HospitalLeeds, UK
| | - Gareth Morris-Stiff
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK
| | - Rebecca L Jones
- Department of Hepatology, St James's University HospitalLeeds, UK
| | - K Rajendra Prasad
- Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University HospitalLeeds, UK,Correspondence K. Rajendra Prasad, Department of Transplant and Hepaticopancreaticobiliary Surgery, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK. Tel: + 44 113 206 5921. Fax: + 44 113 244 8182. E-mail:
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30
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Kim PTW, Onaca N, Chinnakotla S, Davis GL, Jennings LW, McKenna GJ, Ruiz RM, Levy MF, Goldstein R, Klintmalm GB. Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation. Clin Transplant 2013; 27:311-8. [DOI: 10.1111/ctr.12089] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2012] [Indexed: 01/06/2023]
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Abstract
Liver transplantation (LT) may be the best curative treatment that offers a chance of cure for the tumor and the underlying cirrhosis by complete extirpation of both. In Asia, where the supply of cadaveric grafts remains scarce and the incidence of HCC combined with chronic hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver disease is high, adult living donor liver transplantation (LDLT) has been settled upon as a practical alternative to deceased-donor liver transplantation (DDLT). Even in Western countries, where adequate access to DDLT is feasible for HCC patients satisfying the Milan criteria, the necessity for LDLT is well established in particular for more advanced HCC patients who are disadvantaged by current allocation algorithms for grafts from deceased donors due to organ shortage, increasing waiting lists, and the expectation that many patients listed for LT will die while awaiting a suitable organ. In the field of LDLT in Asia, numerous technical innovations were achieved to secure donor safety, as well as to ensure patient survival. The experience with LDLT for HCC has been progressively increasing in many Asian countries to date. Although there are questions regarding the higher recurrence of HCC after LDLT than after DDLT, the application of the Milan and UCSF criteria to LDLT in high-volume multicenter cohorts from Japan and Korea has resulted in patient survival outcomes very similar to those following DDLT. Recently, inclusion of biologic tumor markers such as alpha fetoprotein (AFP), protein induced by vitamin K antagonist II (PIVKA II), and positive positron emission tomography (PET) in addition to parameters of tumor morphology might be the key to establishing the best criteria for LDLT for HCC. As pretransplant treatments, most LDLT centers in Asia cannot adopt the strategy of bridging therapy under scarcity of cadaveric organ donation but have to use those multi-modality treatments as a salvage intending for primary curative treatment or a downstaging therapy before LDLT. After LDLT, basically there is no difference in the management strategy for HCC recurrence between DDLD and LDLT.
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Cauchy F, Fuks D, Belghiti J. HCC: current surgical treatment concepts. Langenbecks Arch Surg 2012; 397:681-95. [DOI: 10.1007/s00423-012-0911-2] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Accepted: 01/17/2012] [Indexed: 12/28/2022]
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Foltys D, Zimmermann T, Heise M, Kaths M, Lautem A, Wisser G, Weiler N, Hoppe-Lotichius M, Hansen T, Otto G. Liver transplantation for hepatocellular carcinoma--is there a risk of recurrence caused by intraoperative blood salvage autotransfusion? ACTA ACUST UNITED AC 2011; 47:182-7. [PMID: 21986299 DOI: 10.1159/000330746] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2011] [Accepted: 06/28/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND/AIMS The use of intraoperative blood salvage autotransfusion (IBSA) during surgical approaches may contribute to tumour cell dissemination. Therefore, IBSA should be avoided in cases of malignancy. However, the risks of IBSA might be acceptable in liver transplantation (LT) for selected small hepatocellular carcinoma (HCC). METHODS In total, 136 recipients of LT with histologically proven HCC in the explanted liver were included in this analysis. With regard to tumour recurrence, 40 patients receiving IBSA despite HCC (IBSA group) were compared to 96 patients without IBSA (non-IBSA group). RESULTS Milan criteria as assessed in the explanted liver were fulfilled in 24 of 40 IBSA patients and 58 of 96 non-IBSA patients (p = 0.85). Five of 40 patients in the IBSA group and 18 of 96 patients in the non-IBSA group experienced tumour recurrence (p = 0.29). In spite the theoretical risk of tumour cell dissemination, the recurrence rate was not increased in the IBSA group. CONCLUSION Our results indicate that IBSA does not modify the risk of HCC recurrence. Therefore, in highly selected HCC patients undergoing LT, the use of IBSA appears to be justified.
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Affiliation(s)
- D Foltys
- Department of Transplantation and Hepatobiliary Surgery, University Medical Centre, Johannes Gutenberg University, Mainz, Germany.
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Duvoux C, Kiuchi T, Pestalozzi B, Busuttil R, Miksad R. What is the role of adjuvant therapy after liver transplantation for hepatocellular carcinoma? Liver Transpl 2011; 17 Suppl 2:S147-58. [PMID: 21714065 PMCID: PMC3417809 DOI: 10.1002/lt.22367] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Christophe Duvoux
- Liver Transplant Unit, Henri Mondor Hospital AP-HP, Paris–Est Créteil University, Créteil, France
| | - Tetsuya Kiuchi
- Division of Transplantation Surgery, Department of Surgery, Nagoya University Hospital, Nagoya University of Medicine, Nagoya, Japan
| | - Bernhard Pestalozzi
- Clinic and Polyclinic for Oncology, University Hospital, Zurich, Switzerland
| | - Ronald Busuttil
- Division of Liver and Pancreas Transplantation, Department of Surgery, University of California Los Angeles, Los Angeles, CA
| | - Rebecca Miksad
- Division of Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA
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35
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Alvite Canosa M, Pita Fernández S, Quintela Fandiño J, Aguirrezabalaga J, Otero A, Suárez F, Corbal G, Fernández C, Gutiérrez MG. [Surgical treatment of liver cancer: experience of the A Coruña UHC (Spain)]. Cir Esp 2011; 89:223-9. [PMID: 21353668 DOI: 10.1016/j.ciresp.2010.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2010] [Revised: 10/21/2010] [Accepted: 12/02/2010] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Liver cancer (LC) is one of the most frequent tumours, in which the potentially curative treatment is surgery: partial surgical resection or liver transplant. OBJECTIVES To determine the morbidity and mortality, survival, and their associated factors in patients with LC, according to the type of surgical treatment: partial surgical resection or liver transplant. MATERIAL AND METHODS A retrospective, observational follow-up study of LC patients diagnosed and treated from June 1994 to December 2007. A descriptive analysis of the variables was performed, as well as a Kaplan- Meier survival analysis and Cox regression. RESULTS The incidence of tumour recurrence in the 150 transplant patients was 13.3%, with a survival at 1, 3, and 5 years of 89.3%, 73.1% and 61.4%, respectively. The multivariate analysis showed that only the histological grade/differentiation was an independent risk factor. In the 33 patients with partial surgical resection, the incidence of tumour was 51.5%, with a survival at 1, 3, and 5 years of 90.9%, 60.2%, and 38.6%, respectively. A significantly higher mortality was observed in patients with higher tumour and TNM staging. CONCLUSIONS The survival throughout follow-up was higher in liver transplant, and tumour recurrence was more frequent in patients with partial surgical resection. The survival results in transplanted patients are consistent with the Spanish and European Liver Transplant Register and with the United Network for Organ Sharing register.
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Affiliation(s)
- Marlén Alvite Canosa
- Unidad de Cirugía Hepatobiliopancreática y Trasplante Hepático, Complejo Hospitalario Universitario de A Coruña, A Coruña, España.
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Liver transplantation for advanced hepatocellular carcinoma using poor tumor differentiation on biopsy as an exclusion criterion. Ann Surg 2011; 253:166-72. [PMID: 21294289 DOI: 10.1097/sla.0b013e31820508f1] [Citation(s) in RCA: 227] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors. OBJECTIVE We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy. METHODS Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008. RESULTS Imaging understaged 30% of the M group and over staged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031). CONCLUSIONS Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.
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37
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Alvite-Canosa M, Pita-Fernández S, Quintela-Fandiño J, Aguirrezabalaga J, Corbal G, Fernández C, Suárez F, Otero A, Gómez-Gutiérrez M. Prognostic and developmental factors in patients receiving liver transplant due to hepatocellular carcinoma: one center's experience in the north of Spain. Transplant Proc 2010; 42:4578-81. [PMID: 21168741 DOI: 10.1016/j.transproceed.2010.09.161] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2010] [Accepted: 09/30/2010] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most frequent types of tumor. The aim of this study was to determine the survival of patients who had received liver transplants as a result of the disease. METHODS This observational follow-up study included 150 patients who received liver transplantations from June 1994 to December 2007. The study considered epidemiological and staging variables, tumor descriptions, and follow-up variables. We employed Kaplan-Meier methodology together with a Cox multivariate regression analysis. RESULTS The incidence of tumor relapse was 13.3%, with survival rates at 1, 3, and 5 years of 89.3%, 73.1%, and 61.4%, respectively. Variables that showed an independent effect to predict mortality were the degree of histological differentiation and of macrovascular invasion. Patients with poorly differentiated HCC had a 4.03 fold (95% confidence interval [CI]: 1.61-10.06) greater possibility of dying. Macrovascular involvement increased the risk of death (relative risk = 2.23), an effect that was at the limit of significance (95% CI 0.99-5.04). CONCLUSIONS The survival rate was consistent with the literature. Poor tumor differentiation and macrovascular involvement were independent predictors of mortality.
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Affiliation(s)
- M Alvite-Canosa
- Liver Transplant Unit, Complejo Hospitalario Universitario A Coruña, Xubias, A Coruña, Spain.
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Abstract
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, being the fifth most frequent cancer worldwide. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Following the diagnosis, this disease requires multidisciplinary management. Orthotopic liver transplantation is theoretically the best treatment for early, unresectable HCC. However, the major practical obstacle is the extreme shortage of organs, which makes this a practical option only in selected patients. In this report we describe new advancements in diagnosis, classification, and treatment that have emerged in the field of HCC in recent years.
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39
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Abstract
Hepatocellular carcinoma (HCC) accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related death. Partial hepatectomy remains the best treatment option for select patients with HCC without cirrhosis. Liver transplantation is well established as the gold standard for patients with HCC and cirrhosis in the absence of extrahepatic spread and macrovascular invasion. Local regional therapy is indicated in select patients who are not surgical candidates, and its role as adjuvant therapy remains to be clarified by prospective studies.
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Affiliation(s)
- Peter Abrams
- Department of Surgery, Thomas East Starzl Transplantation Institute, Montefiore Hospital, University of Pittsburgh School of Medicine, N755.8, 3459 Fifth Avenue, Pittsburgh, PA 15215, USA
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40
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Koschny R, Schmidt J, Ganten TM. Beyond Milan criteria--chances and risks of expanding transplantation criteria for HCC patients with liver cirrhosis. Clin Transplant 2010; 23 Suppl 21:49-60. [PMID: 19930317 DOI: 10.1111/j.1399-0012.2009.01110.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Orthotopic liver transplantation (OLT) is, apart from resection, one important curative treatment for hepatocellular carcinoma (HCC) in liver cirrhosis, and especially attractive because it eliminates both the tumor and the underlying liver disease. The application of restrictive inclusion criteria for OLT in HCC patients resulted in favorable long-term recurrence-free survival. These criteria, however, exclude a subgroup of patients which, despite advanced tumor size, demonstrate an acceptable outcome. As a consequence, expansion of the strict Milan criteria has been discussed. However, this will also deteriorate the average outcome of OLT in HCC patients. Considering that we run short of donor organs, more sophisticated prediction models for survival after OLT for HCC patients are needed to identify patients who benefit best from OLT. Neoadjuvant treatment that is frequently applied as a bridging technique for patients on the waiting list for OLT could provide useful information on tumor behavior to better predict the risk of post-OLT tumor recurrence. This might also allow expansion of the Milan criteria to patients with good response to downstaging methods without negatively affecting post-OLT survival. Furthermore, alternative scoring systems have been suggested to identify HCC patients that might still benefit from resection instead of OLT, and molecular tools are being explored to provide predictive information on HCC biology. This review discusses the advantages and risks of extended inclusion criteria for OLT and the currently available data on alternative prediction models and bridging methods in HCC patients.
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Affiliation(s)
- Ronald Koschny
- Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany
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41
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Yamashiki N, Sugawara Y, Tamura S, Tateishi R, Yoshida H, Kaneko J, Matsui Y, Togashi J, Akahane M, Makuuchi M, Omata M, Kokudo N. Postoperative surveillance with monthly serum tumor markers after living-donor liver transplantation for hepatocellular carcinoma. Hepatol Res 2010; 40:278-86. [PMID: 20070400 DOI: 10.1111/j.1872-034x.2009.00591.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
AIM Recurrence of hepatocellular carcinoma (HCC) after liver transplantation decreases patient survival. The usefulness of post-transplant surveillance with tumor markers, however, is not clear. We evaluated our cumulative experience with recurrent HCC detected during post-transplant surveillance. METHODS We analyzed 100 patients with HCC detected in the explanted liver. Monthly to bimonthly measurement of tumor markers and yearly computed tomography were scheduled postoperatively. RESULTS Preoperatively, 82 met the Milan criteria. The histological findings indicated that 61 fulfilled the Milan criteria. In nine patients, HCC recurred 10 months (2-29) after liver transplantation in the graft (n = 1), lung (n = 2), bone (n = 3) and multiple organs (n = 3). In all nine recipients, HCC was first suspected based on an increase in tumor marker levels. Recurrent HCC was confirmed by computed tomography (n = 7) or magnetic resonance imaging (n = 2) within 4 months (0-6) after first identifying an increase in the tumor marker levels. Six cases were treated surgically, two of which achieved prolonged survival of 16 and 38 months. CONCLUSION Frequent measurement of alpha-fetoprotein and des-gamma carboxy prothrombin was useful for detecting recurrent HCC and may be useful long-term follow-up markers for post-transplant surveillance.
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Affiliation(s)
- Noriyo Yamashiki
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
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42
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Raphe R, Felício H, Rocha M, Duca W, Arroyo P, D'Santi Neto D, da Silva R, da Silva R. Histopathologic Characteristics of Incidental Hepatocellular Carcinoma After Liver Transplantation. Transplant Proc 2010; 42:505-6. [DOI: 10.1016/j.transproceed.2010.01.034] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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43
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Chinnakotla S, Davis GL, Vasani S, Kim P, Tomiyama K, Sanchez E, Onaca N, Goldstein R, Levy M, Klintmalm GB. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl 2009; 15:1834-42. [PMID: 19938137 DOI: 10.1002/lt.21953] [Citation(s) in RCA: 124] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Tumor recurrence after liver transplantation for hepatocellular carcinoma is associated with a poor prognosis. Because immunosuppression is a well-known risk factor for tumor growth, it is surprising that its possible role in the outcome of liver transplantation has been poorly evaluated. We performed a case-control review of prospectively collected data and compared 2 groups of patients according to the type of immunosuppression after liver transplantation for hepatocellular carcinoma at a single center. One hundred six patients received tacrolimus and mycophenolate mofetil, and 121 received sirolimus. Patients in the sirolimus group had significantly higher recurrence-free survival rates than patients in the tacrolimus group (P = 0.0003). The sirolimus group also had significantly higher patient survival rates than the tacrolimus group at 1 year (94% versus 79%), 3 years (85% versus 66%), and 5 years (80% versus 59%; P = 0.001). Sirolimus was well tolerated, and the patients in this study did not have the increase in surgical complications noted by other investigators. Leukopenia was the most common side effect, but it typically resolved with dose reduction. Dyslipidemia and mouth ulcers were common but were easily controlled. In summary, the data suggest a beneficial effect of sirolimus immunosuppression on recurrence-free survival, which translates into patient survival benefits.
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Affiliation(s)
- Srinath Chinnakotla
- Department of Transplant Surgery, Baylor Regional Transplant Institute, Baylor University Medical Center, Dallas, TX 75246, USA.
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44
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Morris-Stiff G, Gomez D, de Liguori Carino N, Prasad K. Surgical management of hepatocellular carcinoma: Is the jury still out? Surg Oncol 2009; 18:298-321. [DOI: 10.1016/j.suronc.2008.08.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 08/19/2008] [Indexed: 02/07/2023]
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45
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Liver transplantation, liver resection, and transarterial chemoembolization for hepatocellular carcinoma in cirrhosis: which is the best oncological approach? Dig Dis Sci 2009; 54:2264-73. [PMID: 19057997 DOI: 10.1007/s10620-008-0604-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2008] [Accepted: 10/24/2008] [Indexed: 01/17/2023]
Abstract
The aim of the study was to evaluate our institutional experience with monotherapies for hepatocellular carcinoma (HCC) in the setting of cirrhosis. A retrospective cohort study was carried out at the tertiary care academic referral center and involved 185 consecutive HCC patients with cirrhosis and no previous treatment who underwent resection (n = 61), transarterial chemoembolization (TACE) (n = 64), or liver transplantation (LT) (n = 60). Long-term survival and survival according to the Milan criteria were the main outcomes measured. Median survival after resection, TACE, and LT was 11, 14, and 23 months, respectively. Five-year cumulative survival after resection, TACE, and LT was 23, 10, and 59%, respectively (P = 0.001). Five-year cumulative disease-free survival after resection and LT was 15% and 77%, respectively (P = 0.002). The presence of complications in the resection group (P = 0.004), MELD score (P = 0.0003), and maximum tumor diameter (P = 0.05) in the TACE group, and tumor grade (P = 0.01) and complications (P = 0.004) in the LT group were found to be independent predictors of survival. Five-year survival for patients within the Milan criteria after resection, TACE, and LT was 26, 37, and 66%, respectively. Five-year survival for patients outside the Milan criteria for patients undergoing LT was 53%. The results suggest that LT represents the best oncological treatment option for patients with HCC in the setting of cirrhosis, even for those beyond the Milan criteria. Considering the scarcity of available organs, liver resection remains the best alternative option. TACE remains a potential therapy in patients within the Milan criteria, where it may be more beneficial than resection.
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46
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Onaca N, Klintmalm GB. Liver transplantation for hepatocellular carcinoma: the Baylor experience. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2009; 17:559-66. [PMID: 19727543 DOI: 10.1007/s00534-009-0163-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2009] [Accepted: 07/13/2009] [Indexed: 01/08/2023]
Abstract
BACKGROUND Liver transplantation (LTX) is indicated in selected patients with hepatocellular carcinoma (HCC) and cirrhosis. METHODS We compared the outcome of LTX for patients with and without HCC in 5-year time periods between 1987 and 2007 to reflect the implementation of the Milan tumor selection criteria in 1997 and of the model for end-stage liver disease (MELD) score-based liver allocation in 2002. RESULTS Of 2350 patients who underwent primary LTX, 330 had HCC. Five-year patient survival for HCC patients was 28.6% in 1987-1992 and 42.3% in 1992-1997, which was 41.4-31.4% lower than that in non-HCC patients (P < 0.0001). After 1997, 5-year survival was 76% for HCC patients, similar to the survival for non-HCC patients (P = 0.8784). Five-year tumor recurrence dropped from 52.9% (1987-1992) and 48.2% (1992-1997) to 11.4% (1997-2002) and 8.4% (2002-2007) (P < 0.0001). Multivariate analysis for tumor recurrence showed the following significant factors: tumor size >6 cm [hazard ratio (HR) 3.67], >or=5 nodules (HR 3.441), vascular invasion (HR 3.18), transplant in 1987-1992 (HR 6.772), and transplant in 1992-1997 (HR 3.059). MELD-based liver allocation reduced median waiting time for LTX for HCC versus non-HCC (35 vs. 111 days; P = 0.005) without compromise in patient outcome. CONCLUSIONS The results of LTX for HCC continue to improve and are equal to results in patients without HCC.
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Affiliation(s)
- Nicholas Onaca
- Baylor Regional Transplant Institute, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246, USA
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47
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Pelletier SJ, Fu S, Thyagarajan V, Romero-Marrero C, Batheja MJ, Punch JD, Magee JC, Lok AS, Fontana RJ, Marrero JA. An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data. Liver Transpl 2009; 15:859-68. [PMID: 19642139 DOI: 10.1002/lt.21778] [Citation(s) in RCA: 115] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Single-center studies have shown acceptable long-term outcomes following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) when tumors are within the Milan criteria. However, the overall survival and waiting list removal rates have not been described at a national level with pooled registry data. To evaluate this, a retrospective cohort of patients listed for OLT with a diagnosis of HCC between January 1998 and March 2006 was identified from Organ Procurement Transplant Network data. Analysis was performed from the time of listing. Adjusted Cox models were used to assess the relative effect of potential confounders on removal from the waiting list as well as survival from the time of wait listing. A total of 4482 patients with HCC were placed on the liver waiting list during the study period. Of these, 65% underwent transplantation, and 18% were removed from the list because of tumor progression or death. The overall 1- and 5-year intent-to-treat survival for all patients listed was 81% and 51%, respectively. The 1- and 5-year survival was 89% and 61% for those listed with tumors meeting the Milan criteria versus 70% and 32% for those exceeding the Milan criteria (P < 0.0001). On multivariate analysis, advanced liver failure manifested by Child-Pugh class B or C increased the risk of death, while age < 55 years, meeting the Milan criteria, and obtaining a liver transplant were associated with better survival. The current criteria for liver transplantation of candidates with HCC lead to acceptable 5-year survival while limiting the dropout rate. Liver Transpl 15:859-868, 2009. (c) 2009 AASLD.
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Affiliation(s)
- Shawn J Pelletier
- Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI, USA.
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Rampone B, Schiavone B, Martino A, Viviano C, Confuorto G. Current management strategy of hepatocellular carcinoma. World J Gastroenterol 2009; 15:3210-6. [PMID: 19598295 PMCID: PMC2710775 DOI: 10.3748/wjg.15.3210] [Citation(s) in RCA: 105] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons. Surgery, including liver transplantation, is the most important therapeutic approach for patients with this disease. HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative. This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.
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49
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Onaca N, Davis GL, Jennings LW, Goldstein RM, Klintmalm GB. Improved results of transplantation for hepatocellular carcinoma: a report from the International Registry of Hepatic Tumors in Liver Transplantation. Liver Transpl 2009; 15:574-80. [PMID: 19479800 DOI: 10.1002/lt.21738] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Improved outcome after liver transplantation (LTX) for hepatocellular carcinoma (HCC) made LTX a legitimate treatment of the disease. We analyzed trends of LTX for HCC with tumors known before transplantation in 902 patients in a large international registry across 3 periods: 1983-1990, 1991-1996, and 1997-2005. Patient survival improved gradually across eras, with 5-year survival rates of 25.3%, 44.4%, and 67.8%, respectively (P < 0.0001), and the 5-year tumor recurrence rate declined from 59% to 41.3% and 15%, respectively (P < 0.0001). The number of HCC nodules and tumor size decreased over time, and there were fewer moderately or poorly differentiated tumors. Tumors > 5 cm decreased from 54.5% to 31.7% and 11.7%, respectively (P < 0.0001), and LTX with >or=4 nodules decreased from 38.9% to 23.5% and 15.1%, respectively (P = 0.0044). Poorly differentiated tumors decreased from 37.2% to 31.8% and 20.3%, respectively (P = 0.0005). Tumor microvascular invasion remained at 21.2% to 23.8% despite changes in patient selection over time (P = 0.7124). Stepwise Cox regression analysis (n = 502) showed significant risk for tumor recurrence and patient survival for transplants before 1997 [hazard ratio (HR), 1.82 and 1.88, respectively], tumor size > 6 cm (HR, 2.09 and 1.76), microvascular invasion (HR, 1.75 and 1.69, respectively), and alpha-fetoprotein > 200 (HR, 2.45 and 2.32, respectively). In conclusion, outcome after LTX for HCC has improved continuously over the past 20 years. Improved perioperative care and better patient selection may partially explain the improved outcome after LTX for HCC.
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Affiliation(s)
- Nicholas Onaca
- Baylor Regional Transplant Institute, Dallas/Fort Worth, TX 75246, USA
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50
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Castillo E, Pelletier S, Kumer S, Abouljoud M, Divine G, Moonka D. Incidental hepatocellular carcinoma after liver transplantation: population characteristics and outcomes. Transplant Proc 2009; 41:219-21. [PMID: 19249518 DOI: 10.1016/j.transproceed.2008.10.053] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2008] [Revised: 09/14/2008] [Accepted: 10/20/2008] [Indexed: 11/29/2022]
Abstract
We combined data from two liver transplant centers to determine the tumor characteristics and outcomes of 51 patients transplanted with incidental hepatocellular carcinoma (iHCC) compared with 143 patients transplanted for previously known HCC (pkHCC). There were no differences in age, gender, or frequency of hepatitis C infection. Patients with iHCC were more likely to be African-American (22% vs 10%; P = .016), more likely to be screened by ultrasound (38% vs 9%; P < .001), had a lower alpha-fetoprotein (83.9 +/- 258.1 vs 572.4 +/- 2376.4 ng/mL; P = .005), and had a higher model for end-stage liver disease (MELD) score (14.3 +/- 4.1 vs 11.8 +/- 4.7; P < .001). The liver explants of patients with iHCC had smaller total tumor burden than patients with pkHCC (3.1 +/- 3.5 vs 4.1 +/- 2.6 cm; P < .001), but a similar percentage of single lesions (66% vs 65%) and tumors that met Milan criteria (76% vs 65%). Patients with iHCC had 1-, 3-, and 5-year survivals of 78%, 67%, and 58%, and 1-, 3-, and 5-year recurrence-free survivals of 90%, 87%, and 87% compared with the 1-, 3-, and 5-year survivals of 90%, 82%, and 70%, and the 1-, 3-, and 5-year tumor-free survivals of 91%, 84%, and 78% in patients with pkHCC. We concluded that patients with iHCC were more likely to be African-American, to be screened by ultrasound, to have a lower alpha-fetoprotein, and a higher MELD score. Ultrasound is not a sensitive modality for screening patients for HCC. Patients with iHCC do not have an advantage in survival over those with pkHCC.
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Affiliation(s)
- E Castillo
- Division of Gastroenterology, Henry Ford Health System, Detroit, Michigan 48322, USA
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