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Sequeira LM, Ozturk NB, Sierra L, Gurakar M, Toruner MD, Zheng M, Simsek C, Gurakar A, Kim AK. Hepatocellular Carcinoma and the Role of Liver Transplantation: An Update and Review. J Clin Transl Hepatol 2025; 13:327-338. [PMID: 40206277 PMCID: PMC11976436 DOI: 10.14218/jcth.2024.00432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/25/2025] [Accepted: 02/08/2025] [Indexed: 04/11/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Multiple treatment modalities are available for the management of HCC, depending on its stage as determined by the Barcelona Clinic Liver Cancer staging system. Because liver transplantation (LT) theoretically removes the cancer and replaces the organ at risk for future malignancy, LT is often considered the most definitive and one of the most efficacious treatment options for HCC. Nevertheless, the success and efficacy of liver transplantation depend on various tumor characteristics. As a result, multiple criteria have been developed to assess the appropriateness of a case of HCC for LT, with the pioneering Milan Criteria established in 1996. Over the past 20 to 30 years, these criteria have been critically evaluated, expanded, and often liberalized to make LT for patients with HCC a more universally applicable option. Furthermore, the development of other treatment modalities has enabled downstaging and bridging strategies for HCC prior to LT. In this narrative and comprehensive review, we provided an update on recent trends in the epidemiology of HCC, selection criteria for LT, implementation of LT across different regions, treatment modalities available as bridges, downstaging strategies, alternatives to LT, and, finally, post-LT surveillance.
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Affiliation(s)
- Lynette M. Sequeira
- Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - N. Begum Ozturk
- Department of Internal Medicine, Beaumont Hospital, Royal Oak, MI, USA
| | - Leandro Sierra
- Department of Internal Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Merve Gurakar
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | | | - Melanie Zheng
- Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Cem Simsek
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Ahmet Gurakar
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amy K. Kim
- Division of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Allkushi E, Wehrle CJ, Kim J, Khalil M, Kwon DCH, Fujiki M, Pinna AD, Miller C, Schlegel A, Aucejo F, Hashimoto K, Pita A. Expanding Indications in Transplant Oncology. Cancers (Basel) 2025; 17:773. [PMID: 40075625 PMCID: PMC11898796 DOI: 10.3390/cancers17050773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/16/2025] [Accepted: 02/20/2025] [Indexed: 03/14/2025] Open
Abstract
Liver transplantation is aptly described as the only curative treatment for cirrhosis and cirrhosis with co-morbid hepatocellular carcinoma (HCC). Its utility in the management of various other primary and secondary liver cancers is gaining traction rapidly, with more thorough assessments on broader populations continuing to emerge. Most prominently, this includes colorectal cancer liver metastasis (CRLM), cholangiocarcinoma (CCA), neuroendocrine tumors (NETs), and more. Furthermore, despite being a well described treatment for HCC for many years, growing evidence supports a change in oncological strategy for HCC, with broadened selection criteria and more advanced systemic and locoregional therapies available. Our review aims to describe the evidence supporting the expansion of indications and selection criteria for liver transplantation in various oncologic indications of primary and secondary liver tumors.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Alejandro Pita
- Transplantation Center, Department of Liver Transplantation, Cleveland Clinic, Cleveland, OH 44195, USA (C.J.W.); (J.K.); (M.K.); (D.C.H.K.); (M.F.); (A.D.P.); (A.S.); (K.H.)
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3
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Chan KM, Lai Y, Hung HC, Lee JC, Cheng CH, Wang YC, Wu TH, Lee CF, Wu TJ, Chou HS, Lee WC. Disadvantage of Viable Portal Vein Tumor Thrombosis in Liver Transplantation for Advanced Hepatocellular Carcinoma. Cancers (Basel) 2025; 17:188. [PMID: 39857970 PMCID: PMC11764340 DOI: 10.3390/cancers17020188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Liver transplantation (LT) is a promising treatment option for patients with hepatocellular carcinoma (HCC) comorbid with cirrhosis. However, HCC with portal vein tumor thrombosis (PVTT) remains an absolute contraindication for LT. This study aimed to analyze the outcomes of LT in patients with HCC plus portal vein thrombosis and further evaluate the impact of PVTT on the long-term outcomes of patients. METHODS Among the 501 patients who underwent LT for HCC between January 2000 and March 2023, 29 (5.8%) patients with HCC who had portal vein thrombosis were further analyzed. Of these 29 patients with portal vein thrombosis, 12 (41.4%) were preoperatively diagnosed with PVTT and underwent LT after receiving downstaging therapy. The remaining 17 (58.6%) patients were PVTT-free prior to LT. RESULTS Overall, the recurrence-free survival rates at 1, 3, and 5 years were 96.3%, 74.2%, and 74.2%, respectively, while the 1-, 3-, and 5-year overall survival rates were 82.4%, 74.2%, and 70.1%, respectively. However, patients with viable PVTT had significantly worse outcomes than those without viable PVTT (p = 0.030). The 5-year recurrence-free and overall survival rates for patients with viable PVTT were 57.5% and 57.0%, respectively. CONCLUSIONS LT may still be a promising option for patients with HCC and PVTT after appropriate downstaging. However, caution should be adopted, as remnant viable PVTT might lead to unsatisfactory outcomes after transplantation.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery, Chang Gung Transplantation Institute, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan 33302, Taiwan; (Y.L.); (H.-C.H.); (J.-C.L.); (C.-H.C.); (Y.-C.W.); (T.-H.W.); (C.-F.L.); (T.-J.W.); (H.-S.C.); (W.-C.L.)
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Zhang X, Chen C, Wang Y, Xu J. Recurrence risk prediction models for hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol 2024; 39:2272-2280. [PMID: 39113259 DOI: 10.1111/jgh.16693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 12/06/2024]
Abstract
Liver transplantation (LT) is an effective method for curing hepatocellular carcinoma (HCC). However postoperative tumor recurrence can lead to higher mortality rates. To select suitable candidates for LT, the Milan Criteria (MC) were first proposed based on tumor morphological characteristics. For those patients who meet the MC, the MC can effectively reduce the postoperative tumor recurrence rate and improve the prognosis of patients undergoing LT. It has always been internationally recognized as the gold standard for selecting candidates for LT, marking a milestone in the history of LT for HCC. However, its strict conditions exclude some HCC patients who could benefit from LT. Therefore, comprehension consideration criteria, including serum biomarkers, tumor histology, and other factor, have been continuously proposed in addition to tumor morphology. This article summaries the prediction model for HCC recurrence after LT from five aspects: tumor morphology, serum markers, histopathology, cellular inflammatory factors and downstaging treatment before transplantation. The aim is to assist clinicians in accurately assessing HCC status, selecting appropriate liver transplant candidates, maximize graft and patients' survival, and optimizing the utilization of social health resources.
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Affiliation(s)
- Xu Zhang
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Chi Chen
- Department of Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Yan Wang
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Xu
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
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Tajima T, Hata K, Tanaka K, Iyama N, Kusakabe J, Kageyama S, Ogawa E, Okamoto T, Haga H, Uemoto S, Hatano E. Chronological alterations in de novo malignancies after living-donor liver transplantation: A cohort study of 1781 recipients using annual comparisons of standardized incidence ratios. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2024; 31:455-467. [PMID: 38845404 PMCID: PMC11503454 DOI: 10.1002/jhbp.12002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/26/2024]
Abstract
BACKGROUND De novo malignancies (DNMs) are a major adverse event after solid organ transplantation; however, their characteristics and recent trends after living-donor liver transplantation (LDLT) remain unclear. METHODS We retrospectively reviewed 1781 primary LDLT recipients (1990-2020) and annually calculated standardized incidence ratios (SIRs) of DNMs compared to the age-adjusted Japanese general population. RESULTS After 21 845 person-years follow-up, 153 DNM lesions (8.6%) were identified in 131 patients (7.4%). The incidence was 0.007 person-years. DNMs included 81 post-transplant lymphoproliferative disorders (PTLDs), 14 colorectal, 12 lung, and 12 gastric cancers, and so on. Comorbid DNMs significantly worsened recipient survival than those without (p < .001). The 5- and 10-year recipient survival after DNM diagnosis were 65% and 58%, respectively. Notably, SIR1993-1995: 8.12 (95% CI: 3.71-15.4, p < .001) and SIR1996-1998: 3.11 (1.34-6.12, p = .01) were significantly high, but had decreased time-dependently to SIR2005-2007: 1.31 (0.68-2.29, p = .42) and SIR2008-2010: 1.34 (0.75-2.20, p = .33), indicating no longer significant difference in DNMs development. Currently, however, SIR2014-2016: 2.27 (1.54-3.22, p < .001) and SIR2017-2019: 2.07 (1.40-2.96, p < .001) have become significantly higher again, reflecting recent aging of recipients (>50 years) and resultant increases in non-PTLD DNMs. Furthermore, characteristically in LDLT, the fewer the donor-recipient HLA-mismatches, the less the post-transplant DNMs development. CONCLUSION DNM development after LDLT was significantly higher than in the general population due to higher PTLD incidence (1993-1998), but once became equivalent (2005-2013), then significantly increased again (2014-2019) due to recent recipient aging and resultant increase in solid cancers.
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Affiliation(s)
- Tetsuya Tajima
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Koichiro Hata
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of SurgeryKyoto City HospitalKyotoJapan
| | - Kosuke Tanaka
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Naomi Iyama
- Organ Transplant UnitKyoto University HospitalKyotoJapan
| | - Jiro Kusakabe
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Shoichi Kageyama
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Eri Ogawa
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Tatsuya Okamoto
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Hironori Haga
- Department of Diagnostic PathologyKyoto University HospitalKyotoJapan
| | - Shinji Uemoto
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Shiga University of Medical ScienceOtsuJapan
| | - Etsuro Hatano
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
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Chan KM, Lee WC. Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis. Biomed J 2024; 48:100757. [PMID: 38942384 PMCID: PMC12001119 DOI: 10.1016/j.bj.2024.100757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/22/2024] [Accepted: 06/25/2024] [Indexed: 06/30/2024] Open
Abstract
Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Wei-Chen Lee
- Department of General Surgery and Chang Gung Transplantation Institute, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
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7
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Yang S, Rong G, Tan H, Liu X, Si S, Zhou R, Wang H, Zhu J, Li X, He Q, Han D. "No-Touch" Left Approach for Recipient Hepatectomy: A Promising Strategy to Minimize Hepatocellular Carcinoma Recurrence in Liver Transplantation. Transplant Direct 2024; 10:e1646. [PMID: 38769986 PMCID: PMC11104727 DOI: 10.1097/txd.0000000000001646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Revised: 03/07/2024] [Accepted: 03/11/2024] [Indexed: 05/22/2024] Open
Abstract
Background Managing hepatocellular carcinoma (HCC) presents significant clinical challenges, often necessitating orthotopic liver transplantation (OLT). To mitigate the risk of iatrogenic metastasis during OLT and reduce posttransplantation recurrence (PTR), we introduced the "no-touch" left (NTL) approach for recipient hepatectomy in OLT. Methods In this retrospective cohort study, our aim was to compare the safety and PTR rates in patients undergoing OLT via either the NTL technique or the conventional approach for recipient hepatectomy. We included 106 patients who met the Hangzhou criteria and exhibited a high tumor burden in the right lobe, with 50 patients assigned to the NTL group and 56 to the conventional group. The primary endpoint was the 1-y PTR rate, whereas secondary endpoints encompassed the safety of the NTL approach, PTR rates at 2 and 5 y, and overall survival. Results Baseline demographics and clinical characteristics showed no significant differences between the groups. The NTL approach exhibited major surgical outcomes similar to those of the conventional approach. The cumulative PTR rates at 1, 2, and 5 y were 14.0% in the NTL group, compared with 24.5%, 35.8%, and 35.8% in the conventional group (P = 0.013). Cumulative overall survival rates at 1, 2, and 5 y were 94.0%, 91.9%, and 89.7% in the NTL group and 88.7%, 75.5%, and 72.5% in the conventional group (P = 0.03). Conclusions This innovative surgical technique enhances safety and significantly reduces the risk of PTR, leading to improved long-term survival. Further prospective studies with larger cohorts and longer follow-up periods are needed to validate our findings and establish the NTL approach as a standard practice in OLT.
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Affiliation(s)
- Shiwei Yang
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Guanghua Rong
- Department of Cancer Biotherapy, the Fifth Medical Center of the PLA General Hospital, Beijing, China
| | - Haidong Tan
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Xiaolei Liu
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Shuang Si
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Ruiquan Zhou
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Haotong Wang
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
| | - Jiqiao Zhu
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Beijing, China
| | - Xianliang Li
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Beijing, China
| | - Qiang He
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Beijing, China
| | - Dongdong Han
- Department of Hepatobiliary Surgery, Liver Transplant Center, China-Japan Friendship Hospital, Beijing, China
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Lai Q, Ito T, Iesari S, Ikegami T, Nicolini D, Larghi Laureiro Z, Rossi M, Vivarelli M, Yoshizumi T, Hatano E, Lerut J. Role of protein induced by vitamin-K absence-II in transplanted patients with HCC not producing alpha-fetoprotein. Liver Transpl 2024; 30:472-483. [PMID: 37729520 DOI: 10.1097/lvt.0000000000000259] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 08/30/2023] [Indexed: 09/22/2023]
Abstract
Elevated Protein Induced by Vitamin-K Absence-II (PIVKA-II) has been shown to be an adverse prognostic factor in HCC patients undergoing liver transplantation (LT). No definitive data are available about the impact of PIVKA-II concerning post-LT recurrence in patients not secreting (≤ 20 ng/mL) alpha-fetoprotein (AFP). An observational retrospective study of the East-West HCC-LT consortium is reported. Between 2000 and 2019, 639 HCC patients were enrolled in 5 collaborative European and Japanese centers. To minimize the initial selection bias, an inverse probability therapy weighting method was adopted to analyze the data. In the post-inverse probability therapy weighting population, PIVKA-II (HR = 2.00; 95% CI: 1.52-2.64; p < 0.001) and AFP (HR=1.82; 95% CI: 1.48-2.24; p < 0.001) were the most relevant independent risk factors for post-LT recurrence. A sub-analysis focusing only on patients who are AFP non-secreting confirmed the negative role of PIVKA-II (HR=2.06, 95% CI: 1.26-3.35; p =0.004). When categorizing the entire population into 4 groups according to the AFP levels (≤ or > 20 ng/mL) and PIVKA (≤ or > 300 mUA/mL) at the time of LT, the lowest recurrence rates were observed in the low AFP-PIVKA-II group (5-year recurrence rate = 8.0%). Conversely, the high AFP-PIVKA-II group had the worst outcome (5-year recurrence rate = 35.1%). PIVKA-II secretion is a relevant risk factor for post-LT HCC recurrence. The role of this marker is independent of the AFP status. Combining both tumor markers, especially in the setting of LT, should be of great relevance for adding information about predicting the post-LT risk of tumor recurrence and selecting these patients for transplantation.
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Affiliation(s)
- Quirino Lai
- Department of General and Specialistic Surgery, General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Takashi Ito
- Department of Surgery, Kyoto University, Kyoto, Japan
| | - Samuele Iesari
- Department of Surgery, Universitè catholique de Louvain, Brussels, Belgium
| | - Toru Ikegami
- Department of Surgery and Science, Kyushu University, Fukuoka, Japan
| | - Daniele Nicolini
- Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Zoe Larghi Laureiro
- Department of General and Specialistic Surgery, General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Massimo Rossi
- Department of General and Specialistic Surgery, General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Marco Vivarelli
- Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy
| | | | | | - Jan Lerut
- Institute for Experimental and Clinical Research IREC-Université catholique de Louvain, Brussels, Belgium
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Pahari H, Raj A, Sawant A, Ahire DS, Rathod R, Rathi C, Sankalecha T, Palnitkar S, Raut V. Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040? World J Transplant 2024; 14:88833. [PMID: 38576752 PMCID: PMC10989470 DOI: 10.5500/wjt.v14.i1.88833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 12/21/2023] [Accepted: 01/22/2024] [Indexed: 03/15/2024] Open
Abstract
BACKGROUND Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.
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Affiliation(s)
- Hirak Pahari
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Amruth Raj
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Ambreen Sawant
- Department of Liver Transplant Anaesthesia, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Dipak S Ahire
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Navi Mumbai 410210, India
| | - Raosaheb Rathod
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
| | - Chetan Rathi
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Aurangabad 431003, India
| | - Tushar Sankalecha
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Nashik 422009, India
| | - Sachin Palnitkar
- Department of Gastroenterology and Hepatology, Medicover Hospitals, Pune 411026, India
| | - Vikram Raut
- Department of Liver Transplant and HPB Surgery, Medicover Hospitals, Navi Mumbai 410210, Maharashtra, India
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Villalba-López F, Sáenz-Mateos LF, Sánchez-Lorencio MI, De La Orden-García V, Alconchel-Gago F, Cascales-Campos PA, García-Bernardo C, Noguera-Velasco JA, Baroja-Mazo A, Ramírez-Romero P. Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma. Sci Rep 2023; 13:5621. [PMID: 37024609 PMCID: PMC10079651 DOI: 10.1038/s41598-023-32879-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 04/04/2023] [Indexed: 04/08/2023] Open
Abstract
The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.
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Affiliation(s)
| | | | | | | | - Felipe Alconchel-Gago
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
| | | | | | | | | | - Pablo Ramírez-Romero
- Liver Transplant Unit, University Hospital Virgen de la Arrixaca, 30120, Murcia, Spain
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Kim SJ, Kim JM. Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review. Clin Mol Hepatol 2022; 28:739-753. [PMID: 35468711 PMCID: PMC9597239 DOI: 10.3350/cmh.2022.0060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/05/2022] [Accepted: 04/15/2022] [Indexed: 01/05/2023] Open
Abstract
Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.
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Affiliation(s)
- Sang Jin Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
- Division of Hepatobiliopancreas and Transplant Surgery, Korea University Ansan Hospital, Republic of Korea, Ansan, Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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12
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Prognostic significance of cachexia index in patients with advanced hepatocellular carcinoma treated with systemic chemotherapy. Sci Rep 2022; 12:7647. [PMID: 35538112 PMCID: PMC9090914 DOI: 10.1038/s41598-022-11736-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 04/26/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer cachexia affects quality of life, response to chemotherapy, and survival in many advanced cancer patients. The aim of this study was to evaluate the prognostic value of pretreatment cachexia index (CXI) in patients with advanced hepatocellular carcinoma (HCC) treated with systematic chemotherapy. Patients with advanced HCC treated with lenvatinib therapy between October 2018 and October 2020 were retrospectively studied. The CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil-to-lymphocyte ratio). The association with treatment response and early adverse events within the first two months of lenvatinib therapy was investigated. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method with log-rank test. Multivariable Cox regression was used to identify the predictors of survival. A total of 116 patients (median age: 60, male: 84.5% ) with calculated CXI. They divided into two groups: high CXI (≥ 53, n = 82) and low CXI (< 53, n = 34). Patients with low CXI had a significantly lower disease control rate (61.8% vs. 89.0%, p = 0.001) and a shorter median OS (8.0 [95% CI 6.2–9.8] vs. 12.3 [95% CI 10.1–14.4] months, p = 0.002) than those with high CXI. In multivariable analysis, low CXI was independently associated with shorter OS (HR: 2.07, 95% CI: 1.17–3.65, p = 0.01) and PFS (HR: 1.84, 95% CI: 1.09–3.09, p = 0.02). Of note, during the first two months of lenvatinib therapy, anorexia (41.2% vs. 22.0%, p = 0.04) developed more frequently among patients with low CXI than those with high CXI. The CXI may be a clinically useful index for predicting poor treatment response and prognosis in patients with advanced HCC undergoing lenvatinib treatment.
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13
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Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study. Ann Hepatol 2021; 22:100294. [PMID: 33276136 DOI: 10.1016/j.aohep.2020.100294] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/20/2020] [Accepted: 10/21/2020] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called "Brazilian Milan Criteria" (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. MATERIALS AND METHODS We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. RESULTS Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. CONCLUSIONS In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.
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Magro B, Pinelli D, De Giorgio M, Lucà MG, Ghirardi A, Carrobio A, Baronio G, Del Prete L, Nounamo F, Gianatti A, Colledan M, Fagiuoli S. Pre-Transplant Alpha-Fetoprotein > 25.5 and Its Dynamic on Waitlist Are Predictors of HCC Recurrence after Liver Transplantation for Patients Meeting Milan Criteria. Cancers (Basel) 2021; 13:5976. [PMID: 34885087 PMCID: PMC8656660 DOI: 10.3390/cancers13235976] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIM Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. METHODS We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. RESULTS The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9-16). The median time on the waitlist was 92 (41-170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6-6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). CONCLUSIONS In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.
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Affiliation(s)
- Bianca Magro
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Domenico Pinelli
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Massimo De Giorgio
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Maria Grazia Lucà
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
| | - Arianna Ghirardi
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Alessandra Carrobio
- FROM Research Foundation, Papa Giovanni XXIII Hospital, 24122 Bergamo, Italy; (A.G.); (A.C.)
| | - Giuseppe Baronio
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Luca Del Prete
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Franck Nounamo
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Andrea Gianatti
- Pathology Unit, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy;
| | - Michele Colledan
- Unit of Hepato-Biliary Surgery and Liver Transplantation, ASST Papa Giovanni XXIII, 24122 Bergamo, Italy; (D.P.); (G.B.); (L.D.P.); (F.N.); (M.C.)
| | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Liver Transplantation, Department of Medicine-Papa Giovanni, XXIII Hospital, 24122 Bergamo, Italy; (M.D.G.); (M.G.L.); (S.F.)
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15
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Lee SG, Jeng LB, Saliba F, Singh Soin A, Lee WC, De Simone P, Nevens F, Suh KS, Fischer L, Jin Joo D, Fung J, Joh JW, Kaido T, Grant D, Meier M, Rauer B, Sips C, Kaneko S, Levy G. Efficacy and Safety of Everolimus With Reduced Tacrolimus in Liver Transplant Recipients: 24-month Results From the Pooled Analysis of 2 Randomized Controlled Trials. Transplantation 2021; 105:1564-1575. [PMID: 33741847 PMCID: PMC8221719 DOI: 10.1097/tp.0000000000003394] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 06/17/2020] [Indexed: 01/10/2023]
Abstract
BACKGROUND AND METHODS Data from 2 randomized liver transplant trials (N = 772; H2304 [deceased donor, n = 488], H2307 [living donor, n = 284]) were pooled to further evaluate the efficacy and safety of everolimus with reduced tacrolimus (EVR + rTAC) versus standard tacrolimus (sTAC) regimen at month 24. RESULTS EVR + rTAC was comparable to sTAC for composite efficacy failure of treated biopsy-proven acute rejection, graft loss, or death (9.8% versus 10.8%; difference, -1.0%; 95% confidence interval, -5.4 to 3.4; P = 0.641) at month 24. EVR + rTAC was superior to sTAC for the mean change in estimated glomerular filtration rate (eGFR) from randomization to month 24 (-8.37 versus -13.40 mL/min/1.73 m2; P = 0.001). A subanalysis of renal function by chronic kidney disease (CKD) stage at randomization showed significantly lower decline in eGFR from randomization to month 24 for patients with CKD stage 1/2 (eGFR ≥ 60 mL/min/1.73 m2) in EVR + rTAC group versus sTAC (-12.82 versus -17.67 mL/min/1.73 m2, P = 0.009). In patients transplanted for hepatocellular carcinoma (HCC) beyond Milan criteria, HCC recurrence was numerically lower although not statistically significant with EVR + rTAC versus sTAC group (5.9% [1 of 17] versus 23.1% [6 of 26], P = 0.215), while comparable in patients within Milan criteria (2.9% [3 of 102] versus 2.1% [2 of 96], P = 1.000), irrespective of pretransplant alpha-fetoprotein levels. CONCLUSIONS EVR + rTAC versus sTAC showed comparable efficacy and safety with significantly better renal function, particularly in patients with normal/mildly decreased renal function (CKD stage 1/2) at randomization and a trend toward lower HCC recurrence in patients transplanted with HCC beyond Milan at month 24. Further long-term data would be required to confirm these results.
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Affiliation(s)
- Sung-Gyu Lee
- Asan Medical Center, Ulsan University College of Medicine, Seoul, Republic of Korea
| | | | - Faouzi Saliba
- AP-HPHôpital Paul Brousse, Villejuif; Université Paris-Saclay, INSERM Unit 935, and 1193, France
| | | | - Wei-Chen Lee
- Chang Gung Memorial Hospital, Tao-Yuan, Lin-Ko, Taiwan
| | | | - Frederik Nevens
- University Hospital Gasthuisberg, KU Leuven, Leuven, Belgium
| | - Kyung-Suk Suh
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Lutz Fischer
- University Medical Center Eppendorf, Hamburg, Germany
| | - Dong Jin Joo
- Yonsei University College of Medicine, Seoul, Republic of Korea
| | - John Fung
- Cleveland Clinic Foundation, Cleveland, OH
| | - Jae-Won Joh
- Samsung Medical Center, Seoul, Republic of Korea
| | | | | | | | | | | | | | - Gary Levy
- University of Toronto, Toronto, Canada
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16
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Ma KW, Chan ACY, Chok KSH, She WH, Cheung TT, Dai WC, Fung JYY, Lo CM. Liver transplantation: would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion? Hepatobiliary Surg Nutr 2021; 10:308-314. [PMID: 34159158 PMCID: PMC8188125 DOI: 10.21037/hbsn.2020.03.09] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Accepted: 10/15/2019] [Indexed: 01/11/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with portal vein tumour thrombus (PVTT) signifies advanced disease, whether LT confers any survival superiority over resection remains uncertain. METHODS A propensity score matched (PSM) analysis of liver transplantation (LT) and liver resection (LR) for HCC with PVTT was performed. RESULTS A consecutive series of 88 patients who received either LT (10 DDLTs and 3 LDLTs) or LR (n=75) respectively were recruited. Before PSM, the LT group has a higher MELD score (17.3 vs. 7.8, P<0.001), lower serum AFP levels (96 vs. 2,164 ng/mL, P=0.017) and smaller tumour size (4 vs. 10 cm, P<0.001). The 5-year overall survival for LT and LR were 55.4% and 15.9% respectively (P=0.007). After matching for serum AFP levels and tumour size, 1-, 3- and 5-year overall survival for LT were 81 ng/mL, 3.9 cm, 80%, 70% and 70% and the corresponding rates for LR were 1,417 ng/mL, 5.3 cm, 51.8%, 19,6% and 9.8% (P value =0.12, 0.27 and 0.009 respectively). CONCLUSIONS LT is associated with significantly better oncological outcomes in HCC patients with PVTT involving the lobar or segmental level. A modest expansion of selection criteria to include small HCC with segmental PVTT should be considered.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | | | - Wong Hoi She
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Tan To Cheung
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Wing Chiu Dai
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | | | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
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17
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Amado V, González-Rubio S, Zamora J, Alejandre R, Espejo-Cruz ML, Linares C, Sánchez-Frías M, García-Jurado G, Montero JL, Ciria R, Rodríguez-Perálvarez M, Ferrín G, De la Mata M. Clearance of Circulating Tumor Cells in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection or Liver Transplantation. Cancers (Basel) 2021; 13:2476. [PMID: 34069569 PMCID: PMC8160727 DOI: 10.3390/cancers13102476] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 05/14/2021] [Accepted: 05/17/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND In patients with hepatocellular carcinoma (HCC), a complete clearance of circulating tumor cells (CTCs) early after liver transplantation (LT) or surgical resection (LR) could prevent tumor recurrence. METHODS prospective pilot study including patients with HCC who underwent LR or LT from September 2017 to May 2020. Enumeration of CTCs was performed in peripheral blood samples (7 mL) using the Isoflux® system (Fluxion Biosciences) immediately before surgery, at post-operative day 5 and at day 30. A clinically relevant number of CTCs was defined as >30 CTCs/sample. RESULTS 41 HCC patients were included (mean age 58.7 ± 6.3; 82.9% male). LR was performed in 10 patients (24.4%) and 31 patients (75.6%) underwent LT. The main etiology of liver disease was chronic hepatitis C (31.7%). Patients undergoing LR and LT were similar in terms of preoperative CTC count (p = 0.99), but clearance of CTCs within the first month was more pronounced in the LT group. Clusters of CTCs at baseline were associated with incomplete clearance of CTCs at day 30 (54.2% vs. 11.8%, p = 0.005), which in turn impacted negatively on survival (p = 0.038). CONCLUSION Incomplete clearance of CTCs after surgery could be a surrogate marker of HCC aggressiveness.
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Affiliation(s)
- Víctor Amado
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
| | - Sandra González-Rubio
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
| | - Javier Zamora
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
| | - Rafael Alejandre
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
| | - María Lola Espejo-Cruz
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
| | - Clara Linares
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
| | | | - Gema García-Jurado
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
| | - José Luis Montero
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
| | - Rubén Ciria
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Department of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Manuel Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
| | - Gustavo Ferrín
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
| | - Manuel De la Mata
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain; (V.A.); (J.Z.); (R.A.); (J.L.M.); (M.D.l.M.)
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, 14004 Córdoba, Spain; (S.G.-R.); (M.L.E.-C.); (C.L.); (G.G.-J.); (R.C.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades hepáticas y digestivas (CIBERehd), 28029 Madrid, Spain
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Kwong A, Mehta N. Expanding the Limits of Liver Transplantation for Hepatocellular Carcinoma: Is There a Limit? Clin Liver Dis 2021; 25:19-33. [PMID: 33978578 DOI: 10.1016/j.cld.2020.08.002] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation is a treatment option for hepatocellular carcinoma within Milan criteria. With careful selection practices, patients with larger tumors can do well with successful downstaging followed by liver transplantation and should not be excluded based on tumor size or number alone. When considering expanded criteria for hepatocellular carcinoma, however, survival outcomes after liver transplantation should be comparable with patients without hepatocellular carcinoma. Surrogate measures of tumor biology, such as α-fetoprotein, other biomarkers, and dynamic tumor behavior including response to locoregional therapy can aid in risk stratification of patients before liver transplantation.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University, 420 Broadway Street, 3rd Floor, Redwood City, CA 94063, USA
| | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, 513 Parnassus Avenue, S-357, San Francisco, CA 94143, USA.
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19
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Chagas AL, Mattos AAD, Carrilho FJ, Bittencourt PL, Vezozzo DCP, Horvat N, Rocha MDS, Alves VAF, Coral GP, Alvares-DA-Silva MR, Barros FMDR, Menezes MR, Monsignore LM, Coelho FF, Silva RFD, Silva RDCMA, Boin IDFSF, D Albuquerque LAC, Garcia JHP, Felga GEG, Moreira AM, Braghiroli MIFM, Hoff PMG, Mello VBD, Dottori MF, Branco TP, Schiavon LDL, Costa TDFA. BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF HEPATOCELLULAR CARCINOMA. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:1-20. [PMID: 32294682 DOI: 10.1590/s0004-2803.202000000-20] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Accepted: 12/19/2019] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2015 its first recommendations about the management of HCC. Since then, new data have emerged in the literature, prompting the governing board of SBH to sponsor a single-topic meeting in August 2018 in São Paulo. All the invited experts were asked to make a systematic review of the literature reviewing the management of HCC in subjects with cirrhosis. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of updated recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present manuscript is the final version of the reviewed manuscript containing the recommendations of SBH.
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Affiliation(s)
- Aline Lopes Chagas
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Natally Horvat
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Manoel de Souza Rocha
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
| | - Venâncio Avancini Ferreira Alves
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto Alegre e Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
| | | | | | - Marcos Roberto Menezes
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
- Hospital Sírio-Libanês, São Paulo, SP, Brasil
| | - Lucas Moretti Monsignore
- Universidade de São Paulo, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, São Paulo, SP, Brasil
| | | | - Renato Ferreira da Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | - Rita de Cássia Martins Alves Silva
- Faculdade de Medicina de São José do Rio Preto (FAMERP) e Hospital de Base de São José do Rio Preto (FUNFARME), São José do Rio Preto, SP, Brasil
| | | | | | | | | | - Airton Mota Moreira
- Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brasil
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | - Paulo Marcelo Gehm Hoff
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
| | | | | | - Tiago Pugliese Branco
- Universidade de São Paulo, Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil
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20
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Lai Q, Vitale A, Halazun K, Iesari S, Viveiros A, Bhangui P, Mennini G, Wong T, Uemoto S, Lin CC, Mittler J, Ikegami T, Zhe Y, Zheng SS, Soejima Y, Hoppe-Lotichius M, Chen CL, Kaido T, Lo CM, Rossi M, Soin AS, Finkenstedt A, Emond JC, Cillo U, Lerut J. Identification of an Upper Limit of Tumor Burden for Downstaging in Candidates with Hepatocellular Cancer Waiting for Liver Transplantation: A West-East Collaborative Effort. Cancers (Basel) 2020; 12:452. [PMID: 32075133 PMCID: PMC7072306 DOI: 10.3390/cancers12020452] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 02/02/2020] [Accepted: 02/12/2020] [Indexed: 02/07/2023] Open
Abstract
Abstract: Since the introduction of Milan Criteria, all scoring models describing the prognosis of hepatocellular cancer (HCC) after liver transplantation (LT) have been exclusively based on characteristics available at surgery, therefore neglecting the intention-to-treat principles. This study aimed at developing an intention-to-treat model through a competing-risk analysis. Using data available at first referral, an upper limit of tumor burden for downstaging was identified beyond which successful LT becomes an unrealistic goal. Twelve centers in Europe, United States, and Asia (Brussels, Sapienza Rome, Padua, Columbia University New York, Innsbruck, Medanta-The Medicity Dehli, Hong Kong, Kyoto, Kaohsiung Taiwan, Mainz, Fukuoka, Shulan Hospital Hangzhou) created a Derivation (n = 2318) and a Validation Set (n = 773) of HCC patients listed for LT between January2000-March 2017. In the Derivation Set, the competing-risk analysis identified two independent covariables predicting post-transplant HCC-related death: combined HCC number and diameter (SHR = 1.15; p < 0.001) and alpha-fetoprotein (AFP) (SHR = 1.80; p < 0.001). WE-DS Model showed good diagnostic performances at internal and external validation. The identified upper limit of tumor burden for downstaging was AFP ≤ 20 ng/mL and up-to-twelve as sum of HCC number and diameter; AFP = 21-200 and up-to-ten; AFP = 201-500 and up-to-seven; AFP = 501-1000 and up-to-five. The WE-DS Model proposed here, based on morphologic and biologic data obtained at first referral in a large international cohort of HCC patients listed for LT, allowed identifying an upper limit of tumor burden for downstaging beyond which successful LT, following downstaging, results in a futile transplantation.
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Affiliation(s)
- Quirino Lai
- Institut de Recherche Expérimentale et Clinique Université catholique de Louvain, Brussels 1200, Belgium;
- Hepatobiliary and Organ Transplantation Unit, Sapienza University, Rome 00161, Italy; (G.M.); (M.R.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplant Unit, University of Padua, Padua 35121, Italy; (A.V.); (U.C.)
| | - Karim Halazun
- Columbia University and New York-Presbyterian/Weill Cornell Medical Center, New York, NY 10065, USA; (K.H.); (J.C.E.)
| | - Samuele Iesari
- Institut de Recherche Expérimentale et Clinique Université catholique de Louvain, Brussels 1200, Belgium;
| | - André Viveiros
- Department of Medicine I, Medical University of Innsbruck, Innsbruck 6020, Austria; (A.V.); (A.F.)
| | - Prashant Bhangui
- Medicine Medanta-The Medicity, Guragram, Dehli 122006, India; (P.B.); (A.S.S.)
| | - Gianluca Mennini
- Hepatobiliary and Organ Transplantation Unit, Sapienza University, Rome 00161, Italy; (G.M.); (M.R.)
| | - Tiffany Wong
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (T.W.); (C.M.L.)
| | - Shinji Uemoto
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto 615-8530, Japan; (S.U.); (T.K.)
| | - Chih-Che Lin
- Chang Gung Memorial Hospital, Kaohsiung 33305, Taiwan; (C.-C.L.); (C.-L.C.)
| | - Jens Mittler
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsmedizin Mainz, Mainz 76726, Germany; (J.M.); (M.H.-L.)
| | - Toru Ikegami
- Department of Surgery and Science, Kyushu University, Fukuoka 819-0395, Japan; (T.I.); (Y.S.)
| | - Yang Zhe
- Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital, Shulan Health Zhejiang University Hospital, Hangzhou 310014, China; (Y.Z.); (S.-S.Z.)
| | - Shu-Sen Zheng
- Department of Hepatobiliary and Pancreatic Surgery Shulan Hospital, Shulan Health Zhejiang University Hospital, Hangzhou 310014, China; (Y.Z.); (S.-S.Z.)
| | - Yuji Soejima
- Department of Surgery and Science, Kyushu University, Fukuoka 819-0395, Japan; (T.I.); (Y.S.)
| | - Maria Hoppe-Lotichius
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie Universitätsmedizin Mainz, Mainz 76726, Germany; (J.M.); (M.H.-L.)
| | - Chao-Long Chen
- Chang Gung Memorial Hospital, Kaohsiung 33305, Taiwan; (C.-C.L.); (C.-L.C.)
| | - Toshimi Kaido
- Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto 615-8530, Japan; (S.U.); (T.K.)
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China; (T.W.); (C.M.L.)
| | - Massimo Rossi
- Hepatobiliary and Organ Transplantation Unit, Sapienza University, Rome 00161, Italy; (G.M.); (M.R.)
| | - Arvinder Singh Soin
- Medicine Medanta-The Medicity, Guragram, Dehli 122006, India; (P.B.); (A.S.S.)
| | - Armin Finkenstedt
- Department of Medicine I, Medical University of Innsbruck, Innsbruck 6020, Austria; (A.V.); (A.F.)
| | - Jean C. Emond
- Columbia University and New York-Presbyterian/Weill Cornell Medical Center, New York, NY 10065, USA; (K.H.); (J.C.E.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, University of Padua, Padua 35121, Italy; (A.V.); (U.C.)
| | - Jan Lerut
- Institut de Recherche Expérimentale et Clinique Université catholique de Louvain, Brussels 1200, Belgium;
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21
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Chan KM, Cheng CH, Wu TH, Lee CF, Wu TJ, Chou HS, Lee WC. Salvage living donor liver transplantation for posthepatectomy recurrence: a higher incidence of recurrence but promising strategy for long-term survival. Cancer Manag Res 2019; 11:7295-7305. [PMID: 31447587 PMCID: PMC6684549 DOI: 10.2147/cmar.s215732] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 07/12/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The scarcity of deceased donor organ donation has led to increasing utilization of living donor liver transplantation (LDLT), which is an optimal treatment for cirrhosis associated with hepatocellular carcinoma (HCC). The study thus aims to analyze prognostic factors and beneficial effects of LDLT for patients with HCC. METHODS All patients who underwent LDLT for HCC were included in this study. A multivariate analysis of patients' clinicopathologic parameters was performed to determine prognostic factors. Subsequently, the type of LDLT was further analyzed and compared based on the result of multivariate analysis. RESULTS Overall, 36 (11.9%) of 303 patients were identified as having HCC recurrence after LDLT. Salvage LDLT (sLDLT) defined by liver transplantation for those patients with recurrent HCC after primary liver resection (LR) was identified as the major prognostic factor of HCC recurrence following the transplantation (HR=2.49 [1.12-5.54], p=0.025). The HCC recurrence incidence and recurrence-free survival after LDLT were significantly inferior in the salvage group than the other group. The pre-transplantation factors were further evaluated and resulted in only maximum tumour size ≥5 cm at primary LR(HR=10.79 [2.10-55.43], p=0.004) affecting post-transplantation HCC recurrence in those patients who had been performed sLDLT. However, patients receiving salvage LDLT had 5- and 10-year overall survival of 86.7% and 52.9%, respectively, measured from the time of initial HCC diagnosis. CONCLUSION Overall, LDLT achieves a satisfactory result with low incidence of HCC recurrence based on certain transplantation criteria. Despite the higher incidence of HCC recurrence after sLDLT, it remains a promising strategy to improve long-term outcomes.
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Affiliation(s)
- Kun-Ming Chan
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chih-Hsien Cheng
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tsung-Han Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chen-Fang Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ting-Jung Wu
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hong-Shiue Chou
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Wei-Chen Lee
- Department of General Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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22
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Kow AWC. Transplantation versus liver resection in patients with hepatocellular carcinoma. Transl Gastroenterol Hepatol 2019; 4:33. [PMID: 31231700 DOI: 10.21037/tgh.2019.05.06] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 05/08/2019] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common solid cancers in the world. Its treatment strategies have evolved significantly over the past few decades but the best treatment outcomes remain in the surgical arena. Especially for early HCCs, the options are abundant. However, surgical resection and liver transplantation provide the best long-term survival. In addition, there are evidence the ablative therapy such as radiofrequency ablation, could provide equivalent outcome as compared to resection. However, HCC is a unique malignancy as the majority of patients develop this cancer in the background of cirrhotic livers. As such, the treatment consideration should not only look at the oncological perspective but also the functional status of the liver parenchyma, i.e., the state of cirrhosis and presence of portal hypertension. Even with the most widely adopted staging systems for HCC such as the Barcelona Clinic Liver Cancer (BCLC) staging system and many other staging systems, none of them are ideal in including the various considerations for patients with HCCs. In this article, the key issues between choosing surgical resection and liver transplantation are discussed. A comprehensive review of the current surgical options are outlined in order to explore the pros and cons of each option.
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Affiliation(s)
- Alfred Wei Chieh Kow
- Division of Hepatopancreaticobiliary Surgery and Liver Transplantation, Department of Surgery, National University Health System Singapore, Singapore.,Department of Surgery, National University of Singapore, Singapore
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23
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Amado V, Rodríguez-Perálvarez M, Ferrín G, De la Mata M. Selecting patients with hepatocellular carcinoma for liver transplantation: incorporating tumor biology criteria. J Hepatocell Carcinoma 2018; 6:1-10. [PMID: 30613572 PMCID: PMC6306074 DOI: 10.2147/jhc.s174549] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) is the optimal therapeutic option for patients with liver cirrhosis and hepatocellular carcinoma (HCC). Due to universal donor shortage, only the patients with limited tumor burden (under the so-called Milan criteria) are considered as potential candidates for LT in most institutions. It is expected that in the near future, more liver grafts will be available for patients with HCC due to the implementation of new direct antivirals against hepatitis C, leaving a prone scenario to consider expanding Milan criteria. A moderate expansion of Milan criteria could be implemented without increasing the risk of tumor recurrence if patients with favorable biological behavior are carefully selected. Incorporating information regarding tumor biology in the decision-making algorithm would result in a more rational use of LT in patients with HCC. In the present review, surrogate markers of tumor biology are critically evaluated as potential tools to be combined with existing radiological criteria. In addition, the current state of liquid biopsy is discussed, as this cutting-edge technology may reshape the management of HCC in the upcoming years.
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Affiliation(s)
- Víctor Amado
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Manuel Rodríguez-Perálvarez
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Gustavo Ferrín
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
| | - Manuel De la Mata
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, IMIBIC, CIBERehd, Córdoba, Spain,
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24
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Ma KW, Chok KSH, Fung JYY, Lo CM. Liver Transplantation for Hepatitis B Virus-related Hepatocellular Carcinoma in Hong Kong. J Clin Transl Hepatol 2018; 6:283-288. [PMID: 30271740 PMCID: PMC6160307 DOI: 10.14218/jcth.2017.00058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 01/09/2018] [Accepted: 01/31/2018] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related deaths worldwide. Curative resection is frequently limited in Hong Kong by hepatitis B virus-related cirrhosis, and liver transplantation is the treatment of choice. Liver transplantation has been shown to produce superior oncological benefits, when compared to hepatectomy for HCC. New developments in the context of patient selection criteria, modification of organ allocation, bridging therapy, salvage liver transplantation and pharmaceutical breakthrough have improved the survival of HCC patients. In this article, we will share our experience in transplanting hepatitis B virus-related HCC patients in Hong Kong and discuss the recent progress in several areas of liver transplantation.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Kenneth Siu Ho Chok
- Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - James Yan Yue Fung
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Chung Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, China
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
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25
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Sternby Eilard M, Holmberg E, Naredi P, Söderdahl G, Rizell M. Addition of alfa fetoprotein to traditional criteria for hepatocellular carcinoma improves selection accuracy in liver transplantation. Scand J Gastroenterol 2018; 53:976-983. [PMID: 30169974 DOI: 10.1080/00365521.2018.1488180] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Liver transplantation in hepatocellular cancer (HCC) is curative only for a selection of patients. Commonly used criteria are mostly based on tumor size and number. However, patients within criteria do have tumor recurrences after transplantation and patients outside criteria are excluded even though some could benefit from transplantation. The tumor marker alpha fetoprotein (AFP) is associated with poor outcome and has already been reported to improve selection. We investigated the hypothesis that AFP level combined with traditional selection criteria could ameliorate the selection accuracy for liver transplantation in HCC. MATERIALS AND METHODS A retrospective national cohort study in 336 patients who had liver transplantation for HCC in Sweden 1996-2014. RESULTS AFP cut-off levels of 20, 100, 1000 and >1000 ng/mL stratified both survival and tumor recurrence, with estimated 5-year survival rates of 74, 61, 49 and 31%, respectively. A simple score, combining three risk levels according to Milan and UCSF fulfillment with three levels of AFP, increased predictive accuracy. A high score identified 35 at-risk patients with estimated post-transplant 5-year survival rate of only 29% compared to 50% for 76 patients excluded by UCSF. More patients were within the combined score cut-off compared to within UCSF, but 5-year survival was similar, 67% versus 66%. CONCLUSION AFP combined with traditional selection criteria ameliorates the selection accuracy for liver transplantation in HCC.
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Affiliation(s)
- Malin Sternby Eilard
- a Department of Surgery , Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Sweden.,b Transplantation Centre , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - Erik Holmberg
- c Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy , University of Gothenburg , Sweden.,d Regional Cancer Centre West , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - Peter Naredi
- a Department of Surgery , Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Sweden.,e Department of Surgery , Sahlgrenska University Hospital , Gothenburg , Sweden
| | - Gunnar Söderdahl
- f Department of Transplantation, CLINTEC , Karolinska Institute and Karolinska University Hospital , Stockholm , Sweden
| | - Magnus Rizell
- a Department of Surgery , Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Sweden.,b Transplantation Centre , Sahlgrenska University Hospital , Gothenburg , Sweden
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26
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Lai Q, Iesari S, Levi Sandri GB, Lerut J. Des-gamma-carboxy prothrombin in hepatocellular cancer patients waiting for liver transplant: a systematic review and meta-analysis. Int J Biol Markers 2017; 32:e370-e374. [PMID: 28561879 DOI: 10.5301/ijbm.5000276] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/27/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND The use of des-gamma-carboxy prothrombin (DCP) as a predictor of the risk of recurrence of hepatocellular cancer (HCC) after liver transplant (LT) has recently gained interest, especially in view of the recent extension of the eligibility criteria of these patients for LT. The aim of the present study is to look into this important matter based on a systematic review and meta-analysis. METHODS A systematic literature review about the role of DCP in the specific setting of LT for HCC has been conducted. RESULTS Three selected studies, which showed a high rate of homogeneity (I2 = 0.0%), confirmed that the tumor marker DCP is a useful predictive factor, indicating a 5-fold increased risk for HCC recurrence after LT (p<0.001). CONCLUSIONS The meta-analysis enabled us to underline the importance of DCP in the refinement of the eligibility criteria of HCC patients for LT. This information, based on Japanese studies performed in the setting of living-donor LT only, needs further validation in the Western world both in the setting of post-mortem and living-donor LT.
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Affiliation(s)
- Quirino Lai
- Starzl Abdominal Transplant Unit, University Hospitals Saint Luc, Université Catholique Louvain, Brussels - Belgium
- Transplant Unit, Department of Surgery, La Sapienza University, Rome - Italy
| | - Samuele Iesari
- Starzl Abdominal Transplant Unit, University Hospitals Saint Luc, Université Catholique Louvain, Brussels - Belgium
| | | | - Jan Lerut
- Starzl Abdominal Transplant Unit, University Hospitals Saint Luc, Université Catholique Louvain, Brussels - Belgium
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27
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Takada Y, Kaido T, Shirabe K, Nagano H, Egawa H, Sugawara Y, Taketomi A, Takahara T, Wakabayashi G, Nakanishi C, Kawagishi N, Kenjo A, Gotoh M, Toyoki Y, Hakamada K, Ohtsuka M, Akamatsu N, Kokudo N, Takeda K, Endo I, Takamura H, Okajima H, Wada H, Kubo S, Kuramitsu K, Ku Y, Ishiyama K, Ohdan H, Ito E, Maehara Y, Honda M, Inomata Y, Furukawa H, Uemoto S, Yamaue H, Miyazaki M, Takada T. Significance of preoperative fluorodeoxyglucose-positron emission tomography in prediction of tumor recurrence after liver transplantation for hepatocellular carcinoma patients: a Japanese multicenter study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2017; 24:49-57. [PMID: 27806426 DOI: 10.1002/jhbp.412] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Accepted: 10/31/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5 months (range 1-125 months). RESULTS Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level ≥115 ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level <115 ng/ml and PET-negative status (n = 22) had a significantly lower 5-year recurrence rate than the other patients (n = 27, 19% vs. 53%, P = 0.019). CONCLUSIONS These results suggest that preoperative FDG-PET status offers additional information on HCC recurrence risk after LT. Over-MC patients with PET-negative status and lower AFP level may achieve successful outcome comparable to that of within-MC patients.
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Affiliation(s)
- Yasutsugu Takada
- Department of HBP and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Toshimi Kaido
- Division of HBP Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Ken Shirabe
- Department of Hepatobiliary and Pancreatic Surgery, Gunma University, Gunma, Japan
| | - Hiroaki Nagano
- Department of Gastroenterological Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Hiroto Egawa
- Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Yasuhiko Sugawara
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Takeshi Takahara
- Department of Surgery, Iwate Medical University School of Medicine, Iwate, Japan
| | - Go Wakabayashi
- Center for Advanced Treatment of Hepatobiliary and Pancreatic Diseases, Surgical Services, Ageo Central General Hospital, Saitama, Japan
| | - Chikashi Nakanishi
- Department of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Miyagi, Japan
| | - Naoki Kawagishi
- Department of Transplantation, Reconstruction and Endoscopic Surgery, Tohoku University Hospital, Miyagi, Japan
| | - Akira Kenjo
- Department of Regenerative Surgery, Fukushima Medical University, Fukushima, Japan
| | - Mitsukazu Gotoh
- Department of Regenerative Surgery, Fukushima Medical University, Fukushima, Japan
| | - Yoshikazu Toyoki
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | - Kenichi Hakamada
- Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | - Masayuki Ohtsuka
- Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Artificial Organ and Transplantation Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan
| | - Kazuhisa Takeda
- National Hospital Organization Yokohama Medical Center, Kanagawa, Japan
| | - Itaru Endo
- Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Kanagawa, Japan
| | - Hiroyuki Takamura
- Department of Gastroenterological Surgery, Kanazawa University, Ishikawa, Japan
| | - Hideaki Okajima
- Division of HBP Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroshi Wada
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kaoru Kuramitsu
- Hepato-Biliary-Pancreatic Surgery, Kobe University Hospital, Hyogo, Japan
| | - Yonson Ku
- Hepato-Biliary-Pancreatic Surgery, Kobe University Hospital, Hyogo, Japan
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Eitaro Ito
- Department of HBP and Breast Surgery, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Yoshihiko Maehara
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masaki Honda
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan
| | - Hiroyuki Furukawa
- Division of Gastroenterologic Surgery, Department of Surgery, Asahikawa Medical University, Hokkaido, Japan
| | - Shinji Uemoto
- Division of HBP Surgery and Transplantation, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroki Yamaue
- Second Department of Surgery, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Masaru Miyazaki
- International University of Health and Welfare, Mita Hospital, Tokyo, Japan
| | - Tadahiro Takada
- Japanese Society of Hepato-biliary-Pancreatic Surgery, Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
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Ma KW, Cheung TT. When to consider liver transplantation in hepatocellular carcinoma patients? Hepat Oncol 2017; 4:15-24. [PMID: 30191050 PMCID: PMC6095144 DOI: 10.2217/hep-2016-0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Accepted: 04/06/2017] [Indexed: 12/12/2022] Open
Abstract
Orthotopic liver transplantation (LT) has been regarded as the best cure among the three curative treatment modalities. However, when to consider LT in hepatocellular carcinoma (HCC) patients remains a complicated clinical question. In this article, we will look into the recent updates in the context of LT for HCC, including the timing of orthotopic LT (primary or salvage LT), patient selection criteria, newer prognostic markers and scoring systems, down-staging and bridging therapy, salvage LT and treatment option of post-LT HCC recurrence. Evolution of immunosuppressive therapy and future development of the LT for HCC will also be discussed.
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Affiliation(s)
- Ka Wing Ma
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
| | - Tan To Cheung
- Department of Surgery, Queen Mary Hospital, the University of Hong Kong, Hong Kong
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Development and Applicability of the A-P 200 Criteria for Liver Transplantation for Hepatocellular Carcinoma. Transplant Proc 2016; 48:3317-3322. [PMID: 27931576 DOI: 10.1016/j.transproceed.2016.08.050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 07/28/2016] [Accepted: 08/22/2016] [Indexed: 02/07/2023]
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Affiliation(s)
- Adam S Bodzin
- Department of Surgery, Section of Abdominal Organ Transplantation, University of Chicago, California, USA
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Lai Q, Inostroza M, Rico Juri JM, Goffette P, Lerut J. Delta-slope of alpha-fetoprotein improves the ability to select liver transplant patients with hepatocellular cancer. HPB (Oxford) 2015; 17:1085-1095. [PMID: 26373980 PMCID: PMC4644360 DOI: 10.1111/hpb.12486] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 07/03/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The aim of the present study was to investigate the role of different alpha-foetoprotein (AFP) determinations in order to propose a new model aimed at predicting intention-to-treat (ITT) death and post- liver transplantation (LT) recurrence in a cohort of patients with hepatocellular cancer (HCC) enlisted for LT. BACKGROUND Recent studies have increasingly focused on the role of AFP as a useful tool for patient selection in the setting of LT for HCC. However, no definitive AFP model has been definitively validated. METHODS A retrospective analysis was performed on 124 consecutive patients enlisted for LT in a UCL Brussels LT centre during the period January 2004 to March 2012. The median follow-up was 3.3 years (ranges: 1.7-6.3). RESULTS The area under the receiver-operating characteristic (AUROC) analysis showed the ability of the AFP delta-slope as a useful prognosticator of tumour-related drop-out and post-LT recurrence. In multivariate analyses, the delta-slope was an independent predictor of ITT death [hazard ratio (HR) = 1.014, P < 0.017] and post-LT tumour recurrence (HR = 1.020, P = 0.027). The 5-year ITT survival and disease-free survival rates were 66.0% versus 36.7% and 92.3% versus 53.8%, for patients meeting and exceeding the delta-slope cut-off value of 15 ng/ml/month, respectively. CONCLUSIONS Integration of the AFP delta-slope with conventional criteria may further improve patient selection and post-LT outcomes; prospective studies are needed to validate the present proposed model.
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Affiliation(s)
- Quirino Lai
- Starzl Unit of Abdominal Transplantation, University Hospitals St. Luc, Université Catholique Louvain UCLBrussels, Belgium
- Department of General Surgery and Organ Transplantation, Umberto I Hospital, University SapienzaRome, Italy
| | - Milton Inostroza
- Hospital Las Higueras Talcahuano, Universidad De ConcepcionConception, Chile
| | - Juan M Rico Juri
- Department of Hepatobiliary Surgery, Hospital IbanacoCali, Colombia
| | - Pierre Goffette
- Department of Imaging-Interventional Radiology, University Hospitals St. Luc, Université Catholique Louvain UCLBrussels, Belgium
| | - Jan Lerut
- Starzl Unit of Abdominal Transplantation, University Hospitals St. Luc, Université Catholique Louvain UCLBrussels, Belgium
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Kariyama K, Wakuta A, Nishimura M, Kishida M, Oonishi A, Ohyama A, Nouso K, Kudo M. Percutaneous Radiofrequency Ablation for Intermediate-Stage Hepatocellular Carcinoma. Oncology 2015; 89 Suppl 2:19-26. [DOI: 10.1159/000440627] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
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Hori T, Kirino I, Uemoto S. Right posterior segment graft in living donor liver transplantation. Hepatol Res 2015; 45:1076-1082. [PMID: 25559984 DOI: 10.1111/hepr.12469] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Revised: 12/15/2014] [Accepted: 12/23/2014] [Indexed: 12/28/2022]
Abstract
AIM Living donor liver transplantation (LDLT) is widely performed for end-stage liver disease. Liver volume is important for donor safety and recipient survival. In adult-to-adult LDLT, left lobe graft is frequently insufficient for the recipient, while right lobe graft carries a higher donor risk. The right posterior segment graft (RPSG) was introduced to increase donor selection options. However, only a few institutions have reported LDLT with an RPSG. METHODS In total, 587 adult recipients underwent LDLT at Kyoto University Hospital from 2001 to 2011. Here, we retrospectively report 14 LDLT with RPSG. All donors underwent volumetric analyses and detailed investigation of the hepatic vein (HV), portal vein (PV), hepatic artery (HA) and biliary duct (BD). Anatomical anomalies were detected in four donors' BD. The mean Model for End-Stage Liver Disease score was 22.6 ± 12.4 points. ABO blood groups were characterized as incompatible in three cases. The mean graft-to-recipient weight ratio was 0.897 ± 0.203. RESULTS Donors' postoperative courses were uneventful. To adjust diameters and lengths between grafts and recipients, dual anastomoses for PV reconstruction and graft interpositions for PV and HA reconstruction were required in one case each. HA thrombosis occurred in two cases and PV thrombosis in one. Biliary complications occurred in two cases. Though there was no significant difference in survival following RPSG versus other grafts, critical complications were observed in recipients. CONCLUSION The RPSG is a useful option in LDLT. However, careful consideration is required for RPSG harvest and LDLT performance, both before and during surgery.
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Affiliation(s)
- Tomohide Hori
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Izumi Kirino
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University, Kyoto, Japan
| | - Shinji Uemoto
- Division of Hepatobiliary Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University, Kyoto, Japan
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Dutkowski P, Linecker M, DeOliveira ML, Müllhaupt B, Clavien PA. Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology 2015; 148:307-23. [PMID: 25224524 DOI: 10.1053/j.gastro.2014.08.045] [Citation(s) in RCA: 199] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 08/29/2014] [Accepted: 08/29/2014] [Indexed: 02/07/2023]
Abstract
Liver transplantation (LT) is a highly successful treatment for many patients with nonmalignant and malignant liver diseases. However, there is a worldwide shortage of available organs; many patients deteriorate or die while on waiting lists. We review the important clinical challenges to LT and the best use of the scarce organs. We focus on changes in indications for LT and discuss scoring systems to best match donors with recipients and optimize outcomes, particularly for the sickest patients. We also cover controversial guidelines for the use of LT in patients with hepatocellular carcinoma and cholangiocarcinoma. Strategies to increase the number of functional donor organs involve techniques to perfuse the organs before implantation. Partial LT (living donor and split liver transplantation) techniques might help to overcome organ shortages, and we discuss small-for-size syndrome. Many new developments could increase the success of this procedure, which is already one of the major achievements in medicine during the second part of the 20th century.
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Affiliation(s)
- Philipp Dutkowski
- Swiss HPB and Transplantation Center, Departments of Surgery and Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Michael Linecker
- Swiss HPB and Transplantation Center, Departments of Surgery and Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Michelle L DeOliveira
- Swiss HPB and Transplantation Center, Departments of Surgery and Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Beat Müllhaupt
- Swiss HPB and Transplantation Center, Departments of Surgery and Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Pierre-Alain Clavien
- Swiss HPB and Transplantation Center, Departments of Surgery and Medicine, University Hospital Zurich, Zurich, Switzerland.
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Takada Y, Tohyama T, Watanabe J. Biological markers of hepatocellular carcinoma for use as selection criteria in liver transplantation. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2014; 22:279-86. [PMID: 25408520 DOI: 10.1002/jhbp.195] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The Milan criteria (MC) have been widely accepted as an effective way of selecting patients with early-stage hepatocellular carcinoma (HCC) for curative liver transplantation (LT). However, since a substantial subset of HCC patients exists that is beyond the MC but with the potential for good outcomes after LT, several institutions have recently proposed new extended criteria. To explore optimal criteria that can reasonably predict the risk of recurrence, it is considered that new markers of biological behavior are needed in addition to morphological tumor size and number. Several promising candidates for such biological markers have been reported, including serum tumor markers such as alpha-fetoprotein and des-gamma-carboxy prothrombin, inflammatory markers such as C-reactive protein and neutrophil-to-lymphocyte ratio, response to pre-transplant treatments for bridging therapy or down-staging, and fluorine-18-fluorodeoxyglucose positron emission tomography. However, the role of these biological markers in patient selection criteria for LT has yet to be clarified. This review article aims to summarize the results of recent reported studies and to display perspectives for the establishment of optimal criteria that incorporate such biological markers.
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Affiliation(s)
- Yasutsugu Takada
- Department of HPB and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, 791-0295, Japan.
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Chan SC, Fan ST. Selection of patients of hepatocellular carcinoma beyond the Milan criteria for liver transplantation. Hepatobiliary Surg Nutr 2014; 2:84-8. [PMID: 24570921 DOI: 10.3978/j.issn.2304-3881.2012.12.04] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Accepted: 12/13/2012] [Indexed: 12/11/2022]
Abstract
The Milan criteria have been proven to be reliable and easily applicable in selection of patients with small unresectable hepatocellular carcinomas for liver transplantation. It has been repeatedly shown that patients who met these criteria had a 5-year survival of over 70% after transplantation. Such a result is remarkably good for an otherwise incurable malignancy. The main disadvantage of this set of criteria is that it is rather restrictive. Following it religiously denies transplantation to many patients who have tumor stage slightly more advanced. There have been many attempts to extend the criteria to include tumors with larger sizes (as in the UCSF criteria) or with a larger number (as in the Kyoto criteria). Alpha-fetoprotein and PIVKA-II, two biological markers in more aggressive tumors, have also been employed in the selection of patients, and biopsies have been used by the University of Toronto to determine tumor aggressiveness before deciding on transplantation. Patients with tumors beyond the Milan criteria yet not of a high grade have been accepted for transplantation and their survival is comparable to that of transplant recipients who were within the Milan criteria. Preoperative dual-tracer ((11)C-acetate and FDG) positron emission tomography has been used to determine tumor grade, and transarterial chemoembolization has been used to downstage tumors, rendering them meeting the Milan criteria. Patients with downstaged tumors have excellent survival after transplantation. Partial response to chemical treatment is a reflection of less aggressive tumor behavior. Careful selection of patients beyond the Milan criteria with the aid of serum tumor marker assay, positron emission tomography or tumor biopsy allows transplanting more patients without compromising survival. The use of liver grafts either from the deceased or from living donors could thus be justified.
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Affiliation(s)
- See Ching Chan
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China; ; Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Sheung Tat Fan
- State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China; ; Department of Surgery, The University of Hong Kong, Hong Kong, China
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Hangzhou criteria for liver transplantation in hepatocellular carcinoma: a single-center experience. Eur J Gastroenterol Hepatol 2014; 26:200-4. [PMID: 23995766 DOI: 10.1097/meg.0b013e3283652b66] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM The inclusion criteria for liver transplantation (LT) in hepatocellular carcinoma (HCC) are being expanded, and the Hangzhou criteria are the most accepted criteria in China. The aim of our study was to evaluate the Hangzhou criteria for LT in HCC with respect to the Milan criteria. METHODS We retrospectively collected data of 298 cases of LT in HCC in our center from August 2000 to December 2010, and then divided these patients into three groups according to the tumor characteristics: the Milan criteria group (n=97), the Hangzhou criteria group (n=172), and the out of Hangzhou criteria group (n=126). We compared the baseline characteristics and outcome of these three groups of patients. RESULTS Baseline patient characteristics showed no significant difference among the three groups, except for younger age in the out of Hangzhou group (P<0.05). Overall the 1-, 3-, and 5-year survival rates were 91.8, 88.7, and 86.6%, respectively, for the Milan criteria group; 86.6, 76.7, and 73.8% for the Hangzhou criteria group; and 76.2, 57.1, and 56.3% for the out of Hangzhou criteria group (P<0.05). The 1-, 3-, and 5-year tumor-free survival rates were 88.7, 86.6, and 86.6%, respectively, for the Milan criteria group; 83.7, 73.8, and 73.3% for the Hangzhou criteria group (P=0.014); and 63.5, 48.4, and 48.4% for the out of Hangzhou group, which was significantly lower than the rates in the other two groups (P=0.000). CONCLUSION Although the Hangzhou criteria lead to lower overall survival and tumor-free survival rates compared with the Milan criteria, the Hangzhou criteria indicate more HCC patients for LT and are associated with a considerable long-term outcome. The Hangzhou criteria should be accepted as the inclusion criteria for LT in HCC.
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Chen CL, Kabiling CS, Concejero AM. Why does living donor liver transplantation flourish in Asia? Nat Rev Gastroenterol Hepatol 2013; 10:746-51. [PMID: 24100300 DOI: 10.1038/nrgastro.2013.194] [Citation(s) in RCA: 178] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The success of liver transplantation worldwide has brought increased demand for the liver graft. Western and Asian countries have coped differently with the problems of the shortages in organ donation. In the West, efforts have focused on promoting deceased donor organ donation, whereas in Asia the focus has been on living donor liver transplantation (LDLT), as this procedure is more acceptable in most Asian cultures. LDLT, which was initially devised for paediatric liver transplant patients, has evolved from using a left lobe graft to a right lobe graft for an adult recipient. To widen the donor pool, dual grafts for a single recipient have been used in LDLT, and donors with hepatitis B core antibody positivity have been accepted, as well as ABO incompatible donors and recipients. The great advances in the field of LDLT have been dictated by the needs and the norms of Asian society. In this Perspectives article, we outline the reasons why LDLT flourishes in Asia.
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Affiliation(s)
- Chao-Long Chen
- Liver Transplant Program and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan 833
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Ishii T, Hatano E, Yasuchika K, Taura K, Seo S, Uemoto S. High risk of lung metastasis after resection of hepatocellular carcinoma more than 7 cm in diameter. Surg Today 2013; 44:1900-5. [PMID: 24264061 DOI: 10.1007/s00595-013-0792-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 10/21/2013] [Indexed: 12/16/2022]
Abstract
PURPOSE The relationship between the tumor size and organs of recurrence was analyzed to identify a high-risk group for the extrahepatic recurrence of hepatocellular carcinoma (HCC) after resection. METHODS A total of 544 patients with HCC underwent primary surgical resection for HCC between 2001 and 2010. Of these, 293 patients had a solitary tumor but no macroscopic vascular invasion. The prognostic factors for the overall survival and relapse-free survival were analyzed among these 293 patients. The recurrent organs and frequency of recurrence were also examined. RESULTS The analysis of the 293 patients showed that both the overall and relapse-free survival rates of the patients with a large tumor (>7 cm in diameter) were significantly worse than those of the patients with a tumor <7 cm. The incidence of lung metastasis was remarkably high in the group of patients with tumors more than 7 cm (24.0 %), in comparison to those with tumors <7 cm. A multivariate analysis revealed that the tumor size was the only independent risk factor for lung metastasis. CONCLUSIONS The patients with large HCC tumors more than 7 cm in diameter were at high-risk for a poor prognosis due to a high percentage of lung metastasis, even if there was no macroscopic vascular invasion.
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Affiliation(s)
- Takamichi Ishii
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan,
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41
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Chan SC, Sharr WW, Cheung TT, Chan ACY, Tsang SHY, Chok KSH, Leung KC, Lo CM. Retrohepatic vena cava deroofing in living donor liver transplantation for caudate hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2013; 12:552-555. [PMID: 24103288 DOI: 10.1016/s1499-3872(13)60087-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The removal of tumor together with the native liver in living donor liver transplantation for hepatocellular carcinoma is challenged by a very close resection margin if the tumor abuts the inferior vena cava. This is in contrast to typical deceased donor liver transplantation where the entire retrohepatic inferior vena cava is included in total hepatectomy. Here we report a case of deroofing the retrohepatic vena cava in living donor liver transplantation for caudate hepatocellular carcinoma. In order to ensure clear resection margins, the anterior portion of the inferior vena cava was included. The right liver graft was inset into a Dacron vascular graft on the back table and the composite graft was then implanted to the recipient inferior vena cava. Using this technique, we observed the no-touch technique in tumor removal, hence minimizing the chance of positive resection margin as well as the chance of shedding of tumor cells during manipulation in operation.
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Affiliation(s)
- See Ching Chan
- Department of Surgery; State Key Laboratory for Liver Research, The University of Hong Kong, 102 Pokfulam Road, Hong Kong, China.
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Abstract
Hepatitis B is endemic in many regions of Asia, including China, Korea and India. This results in a heavy burden of hepatocellular carcinoma (HCC) because hepatitis B virus is a major risk factor in the development of the disease. In addition, the incidence of hepatitis-C-related HCC is on the rise in the United States. HCC patients with poor liver function reserve are not suitable candidates for resection, and liver transplantation (LT) has emerged as the treatment of choice for small unresectable HCCs. To treat more HCC patients with LT, the standard patient selection criteria have been expanded at a number of centers. Careful and well-considered selection of patients is the key to success in LT for HCC. Although tumor size and tumor number are used to predict whether transplantation is likely to be successful, the weighting that should be attached these two parameters has not been determined. In addition to the size and number of lesions, the morphology of HCC is also predictive of its behavior. Well-circumscribed lesions, in general, are less aggressive than those with poorly defined borders. On the waiting list for LT, HCC patients compete with liver failure patients. It is essential that the criteria used for selecting HCC patients for LT should be easily applicable and fair to other transplant candidates. In the face of the scarcity of deceased-donor livers and the inevitable risks for living liver donors, a predictably low rate of recurrence of HCC after LT is mandatory.
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Affiliation(s)
- See Ching Chan
- *See Ching Chan, MBBS, MS, PhD, MD, Department of Surgery, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, SAR (China), Tel. +852 2255 3025, E-mail
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Ferreira MVC, Chaib E, Nascimento MUD, Nersessian RSF, Setuguti DT, D'Albuquerque LAC. Liver transplantation and expanded Milan criteria: does it really work? ARQUIVOS DE GASTROENTEROLOGIA 2013; 49:189-94. [PMID: 23011240 DOI: 10.1590/s0004-28032012000300004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2012] [Accepted: 07/18/2012] [Indexed: 12/12/2022]
Abstract
CONTEXT Orthotopic liver transplantation is an excellent treatment approach for hepatocellular carcinoma in well-selected candidates. Nowadays some institutions tend to Expand the Milan Criteria including tumor with more than 5 cm and also associate with multiple tumors none larger than 3 cm in order to benefit more patients with the orthotopic liver transplantation. METHODS The data collected were based on the online database PubMED. The key words applied on the search were "expanded Milan criteria" limited to the period from 2000 to 2009. We excluded 19 papers due to: irrelevance of the subject, lack of information and incompatibility of the language (English only). We compiled patient survival and tumor recurrence free rate from 1 to 5-years in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation according to expanded the Milan criteria from different centers. RESULTS Review compiled data from 23 articles. Fourteen different criteria were found and they are also described in detail, however the University of California - San Francisco was the most studied one among them. CONCLUSION Expanded the Milan criteria is a useful attempt for widening the preexistent protocol for patients with hepatocellular carcinoma in waiting-list for orthotopic liver transplantation. However there is no significant difference in patient survival rate and tumor recurrence free rate from those patients that followed the Milan criteria.
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Affiliation(s)
- Marina Vilela Chagas Ferreira
- Liver Transplantation Unit Laboratory of Medical investigation, Department Gastroenterology, School of Medicine, University of São Paulo, São Paulo, Brazil
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Lerut J, Julliard O, Ciccarelli O, Lannoy V, Gofette P. Hepatocellular cancer and liver transplantation: a Western experience. Recent Results Cancer Res 2013; 190:127-144. [PMID: 22941018 DOI: 10.1007/978-3-642-16037-0_9] [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] [Indexed: 06/01/2023]
Abstract
Orthotopic liver transplantation is the preferred treatment option in patients with hepatocellular carcinoma developing in chronic liver disease. Unfortunately, based on classical transplantation criteria (Milan criteria), only a minority of patients with hepatocellular carcinoma are candidate to orthotopic liver transplantation. Major improvements in treatment strategy and surgical technique including the use of neoadjuvant locoregional therapies and progresses of post-transplant immunosuppressive treatment have contributed to safely expand transplantation criteria preserving acceptable surgical morbidity-mortality and good oncologic outcome. Further extension of transplantation criteria may have advantages including an increase in the number of transplant candidates and improvement of the prognosis of the disease and also disadvantages including an increase of surgical morbidity and deterioration of global oncologic outcome of orthotopic liver transplantation in hepatocellular carcinoma. In the future, identification of imaging or molecular prognostic markers could help to better define transplantation criteria.
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Affiliation(s)
- Jan Lerut
- Department of Imaging - Interventional Radiology, Université catholique de Louvain-UCL, Brussels, Belgium.
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Nojiri K, Sugimoto K, Shiraki K, Tameda M, Inagaki Y, Ogura S, Kasai C, Kusagawa S, Yoneda M, Yamamoto N, Takei Y, Nobori T, Ito M. Sorafenib and TRAIL have synergistic effect on hepatocellular carcinoma. Int J Oncol 2012; 42:101-8. [PMID: 23123700 DOI: 10.3892/ijo.2012.1676] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Accepted: 08/21/2012] [Indexed: 02/06/2023] Open
Abstract
A multi-kinase inhibitor, sorafenib, was recently approved and is currently recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, HCC treatment outcomes are still poor and necessitate improvement. Therefore, we investigated the influence of sorafenib in combination with each of cytotoxic chemotherapy agents, hypoxia or tumor necrosis factor (TNF)-related apoptosis‑inducing ligand (TRAIL), on cytotoxicity to determine which is the better adjuvant. Additive cytotoxicity of sorafenib to chemotherapy agents, hypoxia and TRAIL, to HCC cells was assessed using cell viability assay. Intracellular levels of anti-apoptotic proteins were determined using western blot analysis. Activation of Wnt/β-catenin signaling was assessed using a luciferase reporter gene assay. Sorafenib significantly and synergistically enhanced the cytotoxicity of TRAIL to HCC cells and 4',6-diamidino-2-phenylindole (DAPI) staining showed increased apoptosis among cells treated with sorafenib and TRAIL. This augmentation in cytotoxicity was derived from sorafenib-mediated downregulation of anti-apoptotic proteins. However, sorafenib did not enhance the cytotoxicity of chemotherapy agents (cisplatin, 5-FU or doxorubicin) or hypoxic treatment to HCC. Moreover, hypoxic treatment induced Wnt/β-catenin signaling activation. Our data showed that in combination TRAIL and sorafenib had a synergistic cytokilling effect on HCC cells and that this effect derived from sorafenib-mediated downregulation of anti-apoptotic proteins.
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Affiliation(s)
- Keiichiro Nojiri
- First Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan
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Ciccarelli O, Lai Q, Goffette P, Finet P, De Reyck C, Roggen F, Sempoux C, Doffagne E, Reding R, Lerut J. Liver transplantation for hepatocellular cancer: UCL experience in 137 adult cirrhotic patients. Alpha-foetoprotein level and locoregional treatment as refined selection criteria. Transpl Int 2012; 25:867-875. [PMID: 22716073 DOI: 10.1111/j.1432-2277.2012.01512.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver transplantation (LT) is a validated treatment for selected cirrhotics with hepatocellular cancer (HCC). A retrospective single center study including 137 recipients having proven HCC was done to refine inclusion criteria for LT as well as to look at impact of locoregional treatment (LRT) on outcome. At pre-LT imaging, 42 (30.6%) patients were Milan criteria (MC)-OUT; 28 (20.4%) were University of California San Francisco criteria (UCSFC)-OUT. Pre-LT LRT was performed in 109 (79.6%) patients. Multivariate analysis identified four factors to be independently predictive of recurrence: tumour number >3, AFP level ≥400 ng/ml, microvascular invasion and rejection needing anti-lymphocytic antibodies. When considering pre-transplant variables only, AFP level ≥400 ng/ml (HR = 5.13; P < 0.0001) was the unique risk factor for recurrence; conversely, application of LRT was protective (HR = 0.42; P = 0.04). MC-IN patients having LRT (n = 79) had the best 5-year tumour-free survival (TFS) (91.6%). MC-IN patients without LRT (n = 16) and MC-OUT patients with LRT (n = 30) had similar good TFS (72.7% vs.77.5%); finally MC-OUT patients without LRT (n = 12) had the worst results (45.0%; vs. 1st group: P < 0.0001). Immediate pre-LT AFP and aggressive pre-transplant LRT strategy, especially in MC-OUT patients, are both important elements to further expand inclusion criteria without compromising long-term results of HCC liver recipients.
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Affiliation(s)
- Olga Ciccarelli
- Starzl Unit Abdominal Transplantation, University Hospitals St Luc, Université catholique de Louvain, Brussels, Belgium.
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Puneet P, Perera MTPR, Mirza DF. Current opinion on the role of resection and liver transplantation for hepatocellular cancer. Indian J Gastroenterol 2012; 31:89-99. [PMID: 22711364 DOI: 10.1007/s12664-012-0200-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Accepted: 05/25/2012] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide with rising incidence in developed countries. The best treatment options with curative intent for patients with HCC are liver resection or transplantation, although the role of hepatic ablative therapies has also been recognized. Surgical resection has emerged as the primary treatment in carefully selected patients of HCC. With the advances in surgical and radiological techniques, the perioperative mortality has been reduced to less than 5 % depending on the extent of resection and hepatic reserve. The role of liver transplantation (LT) as the mainstay of treatment for the majority of patients with HCC has evolved in the last few decades. Historically, the Milan criteria have been considered the gold standard for selecting patients; more expanded selection criteria to include those with more advanced tumors have been implemented in recent years. Living donor liver transplantation (LDLT) has emerged as a way to expand the donor pool and has influenced the role of transplantation for HCC, especially in communities with little access to cadaveric transplantation. Salvage transplantation is an alternative option as it allows a window for the biologically less favorable lesions to declare tumor behavior. Salvage transplantation also decreases the burden on transplant resources. Sirolimus, a novel immunosuppressant drug with anti-tumor effect, may have a role in limiting the severity of recurrent disease after transplantation for HCC, and play an important role in the future management of transplant recipients. This article examines the literature on current status of management of HCC.
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Affiliation(s)
- P Puneet
- The Liver Unit, Queen Elizabeth Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, UK
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Using sorafenib for recurrent hepatocellular carcinoma after liver transplantation--interactions between calcineurin inhibitor: two case reports. Transplant Proc 2012; 43:2800-5. [PMID: 21911167 DOI: 10.1016/j.transproceed.2011.06.063] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2011] [Accepted: 06/16/2011] [Indexed: 01/05/2023]
Abstract
No effective therapeutic approaches have been available for early recurrences following liver transplantation for hepatocellular carcinoma (HCC). The prognosis for such patients has been poor. We encountered two patients with recurrent HCC following liver transplantation, and in the prescribed sorafenib after the failure of various therapeutic approaches. In vitro experiments have shown sorafenib to be metabolized by the drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and glucuronosyltransferase (UGT1A9). The metabolic pathway is predicted to overlap that of calcineurin inhibitors (CNIs). In the two cases in which we used sorafenib, tacrolimus (FK506) was used in case 1 and cyclosporine, in case 2. We therefore have also reported the blood levels of the CNI at the time of sorafenib use. Patients with recurrent HCC following liver transplantation were less tolerant of sorafenib than advanced HCC patients who had not undergone transplantation. Poor tolerance was believed to be due to pharmacological interactions of sorafenib and CNIs. Likewise in our patients, determining blood levels of sorafenib, including the area under the blood concentration-time curve of at least the CNI, in each case allowed us to determine the optimal sorafenib dose for each patient. In the future, when administering sorafenib to treat recurrent liver cancers following liver transplantation, the dose of sorafenib should be started at 200 mg/d and gradually increased while measuring CNI blood levels.
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Wang Y, Speeg KV, Washburn WK, Halff G. Sirolimus plus sorafenib in treating HCC recurrence after liver transplantation: A case report. World J Gastroenterol 2010; 16:5518-22. [PMID: 21086573 PMCID: PMC2988248 DOI: 10.3748/wjg.v16.i43.5518] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A case of hepatocellular carcinoma (HCC) with pulmonary recurrence after liver transplantation for HCC is presented in this report. The patient showed disease progression on sorafenib therapy demonstrated by computed tomography scans as well as serial serum α-fetoprotein (AFP) elevation. After his immunosuppression therapy was successfully transitioned to sirolimus and a continuation of sorafenib, he achieved partial remission based on RECIST criteria and normalization of AFP. Mammalian target of rapamycin inhibitors including sirolimus alone or in conjunction with sorafenib may be useful in the treatment of post transplant HCC.
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