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Kolar Ramachandra S. Navigating the Complexities of Hepatocellular Carcinoma Management: Optimizing Liver Transplantation Outcomes Through a Multifaceted Approach. J Clin Exp Hepatol 2025; 15:102548. [PMID: 40242278 PMCID: PMC11999416 DOI: 10.1016/j.jceh.2025.102548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2025] [Accepted: 03/12/2025] [Indexed: 04/18/2025] Open
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Liu H, Zhang W, Di M, Lee H, Shi L, Wang X, Xingyu Z, Powers CA, Sethi V, Li X, Xiao Y, Crane A, Kaltenmeier C, Alberola RB, Behari J, Duarte-Rojo A, Hughes D, Malik S, Jonassaint N, Geller D, Tohme S, Gunabushanam V, Tevar A, Cruz R, Hughes C, Dharmayan S, Ayloo S, Humar A, Molinari M. Survival benefit associated with liver transplantation for hepatocellular carcinoma based on tumor burden scores at listing. Hepatol Commun 2025; 9:e0619. [PMID: 39774957 PMCID: PMC11717502 DOI: 10.1097/hc9.0000000000000619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/16/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing. METHODS We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT. RESULTS This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001). CONCLUSIONS Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors.
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Affiliation(s)
- Hao Liu
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Wei Zhang
- Department of Mathematics and Statistics, the University of Arkansas at Little Rock, Little Rock, Arkansas, USA
| | - Mengyang Di
- Division of Hematology-Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Hang Lee
- Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Liuhua Shi
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Xixi Wang
- Department of Mathematics and Statistics, the University of Arkansas at Little Rock, Little Rock, Arkansas, USA
| | - Zhang Xingyu
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Department of Biostatistics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Colin A. Powers
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Vrishketan Sethi
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Crane
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Christof Kaltenmeier
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Ramon Bataller Alberola
- Liver Unit, Hospital Clinic, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Jaideep Behari
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Andres Duarte-Rojo
- Department of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Dempsey Hughes
- Department of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Shahid Malik
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Naudia Jonassaint
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - David Geller
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Samer Tohme
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Vikraman Gunabushanam
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Amit Tevar
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Ruy Cruz
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Christopher Hughes
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Stalin Dharmayan
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Subhashini Ayloo
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Department of Surgery, Brown University, Providence, Rhode Island, USA
| | - Abhinav Humar
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Michele Molinari
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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Mehta N, Kelley RK, Yao FY. Refining the approach to down-staging of HCC prior to liver transplantation: Patient selection, loco-regional treatments, and systemic therapies. Hepatology 2024; 80:238-253. [PMID: 37183865 DOI: 10.1097/hep.0000000000000452] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023]
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
| | - R Katie Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, California, USA
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Yankol Y, Aguirre O, Fernandez LA. Impact of Living Donor Liver Transplantation on the Improvement of Hepatocellular Carcinoma Treatment. SISLI ETFAL HASTANESI TIP BULTENI 2024; 58:1-9. [PMID: 38808046 PMCID: PMC11128703 DOI: 10.14744/semb.2024.87864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Accepted: 01/07/2024] [Indexed: 05/30/2024]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, with increasing incidence. There are different treatment options, but only 30%-40% of HCC cases are diagnosed at an early stage for curative treatment. With the implementation of Milan Criteria for liver transplantation (LT) in HCC cases and its use for organ allocation with successful outcomes, LT has become an optimal treatment. Seeking new criteria for LT and developing updated algorithms for HCC treatment has become a hot topic nowadays. With the experience in living donor liver transplantation (LDLT), especially in Asian countries, LDLT was established and adopted with different criteria for HCC treatment, especially including criteria beyond Milan's size and number of tumors. Living donor grafts are uniquely different than deceased donor grafts as they are not considered a public resource. A living donor graft is rather a private gift intended for a specific recipient. Living donor livers are not limited by organ allocation systems, and this significant advantage of LDLT has opened new frontiers in the treatment of HCC. Improvements in LDLT have had remarkable parallel effects in the successful treatment of HCC as supported by a growing body of literature in the past decade.
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Affiliation(s)
- Yucel Yankol
- Department of Surgery, Chicago Stritch School of Medicine, Loyola University Medical Center, Abdominal Transplant Center, Maywood, IL, United States
| | - Oswaldo Aguirre
- Department of Surgery, Chicago Stritch School of Medicine, Loyola University Medical Center, Abdominal Transplant Center, Maywood, IL, United States
| | - Luis A. Fernandez
- Department of Surgery, Chicago Stritch School of Medicine, Loyola University Medical Center, Abdominal Transplant Center, Maywood, IL, United States
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Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, Kim J, Sinn DH, Joo DJ, Choi Y, Lee JH, Choi HJ, Yoon KT, Yim SY, Park CS, Kim DG, Lee HW, Choi WM, Chon YE, Kang WH, Rhu J, Lee JG, Cho Y, Sung PS, Lee HA, Kim JH, Bae SH, Yang JM, Suh KS, Al Mahtab M, Tan SS, Abbas Z, Shresta A, Alam S, Arora A, Kumar A, Rathi P, Bhavani R, Panackel C, Lee KC, Li J, Yu ML, George J, Tanwandee T, Hsieh SY, Yong CC, Rela M, Lin HC, Omata M, Sarin SK. Asian Pacific Association for the Study of the Liver clinical practice guidelines on liver transplantation. Hepatol Int 2024; 18:299-383. [PMID: 38416312 DOI: 10.1007/s12072-023-10629-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 12/18/2023] [Indexed: 02/29/2024]
Abstract
Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
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Affiliation(s)
- Dong-Sik Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea
| | - Young-In Yoon
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | | | | | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Joong Choi
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University College of Medicine, Yangsan, Republic of Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Cheon-Soo Park
- Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Deok-Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hae Won Lee
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young Eun Chon
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Woo-Hyoung Kang
- Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jinsoo Rhu
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Ilsan, Republic of Korea
| | - Pil Soo Sung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Soek Siam Tan
- Department of Medicine, Hospital Selayang, Batu Caves, Selangor, Malaysia
| | - Zaigham Abbas
- Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - Ananta Shresta
- Department of Hepatology, Alka Hospital, Lalitpur, Nepal
| | - Shahinul Alam
- Crescent Gastroliver and General Hospital, Dhaka, Bangladesh
| | - Anil Arora
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Ashish Kumar
- Department of Gastroenterology and Hepatology, Sir Ganga Ram Hospital New Delhi, New Delhi, India
| | - Pravin Rathi
- TN Medical College and BYL Nair Hospital, Mumbai, India
| | - Ruveena Bhavani
- University of Malaya Medical Centre, Petaling Jaya, Selangor, Malaysia
| | | | - Kuei Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jun Li
- College of Medicine, Zhejiang University, Hangzhou, China
| | - Ming-Lung Yu
- Department of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | | | | | | | | | - H C Lin
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Bunkyo City, Japan
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Liu H, Sethi V, Li X, Xiao Y, Humar A. Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future. Semin Liver Dis 2024; 44:79-98. [PMID: 38211621 DOI: 10.1055/a-2242-7543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.
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Affiliation(s)
- Hao Liu
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Vrishketan Sethi
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Abhinav Humar
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Yilma M, Mehta N. Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma. Surg Oncol Clin N Am 2024; 33:133-142. [PMID: 37945139 DOI: 10.1016/j.soc.2023.06.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Liver transplantation continues to be the optimal treatment for hepatocellular carcinoma (HCC). Given the limited organ supply, patient selection for liver transplant must carefully balance tumor progression with risk of recurrence posttransplant. There are several pretransplant selection criteria that incorporate biomarkers as well as imaging modality to risk-stratify patients as we continue to look for the optimal transplant cutoff for patients with HCC, which should be transplant-center specific, and account for organ availability and dynamic response to locoregional therapy.
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Affiliation(s)
- Mignote Yilma
- Department of Surgery, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA; National Clinician Scholars Program, University of California San Francisco, 513 Parnassus Avenue, S-321, San Francisco, CA 94143, USA. https://twitter.com/mignoteyilmaMD
| | - Neil Mehta
- Department of Medicine, University of California San Francisco, Connie Frank Transplant Center, 400 Parnassus Avenue 7th Floor, San Francisco, CA 94143, USA.
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Yoon JH, Choi SK. Management of early-stage hepatocellular carcinoma: challenges and strategies for optimal outcomes. JOURNAL OF LIVER CANCER 2023; 23:300-315. [PMID: 37734717 PMCID: PMC10565545 DOI: 10.17998/jlc.2023.08.27] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 08/24/2023] [Accepted: 08/27/2023] [Indexed: 09/23/2023]
Abstract
Although hepatocellular carcinoma (HCC) is associated with a poor prognosis, management of early-stage HCC is often successful with highly efficacious treatment modalities such as liver transplantation, surgical resection, and radiofrequency ablation. However, unfavorable clinical outcomes have been observed under certain circumstances, even after efficient treatment. Factors that predict unsuitable results after treatment include tumor markers, inflammatory markers, imaging findings reflecting tumor biology, specific outcome indicators for each treatment modality, liver functional reserve, and the technical feasibility of the treatment modalities. Various strategies may overcome these challenges, including the application of reinforced treatment indication criteria with predictive markers reflecting tumor biology, compensation for technical issues with up-to-date technologies, modification of treatment modalities, downstaging with locoregional therapies (such as transarterial chemotherapy or radiotherapy), and recently introduced combination immunotherapies. In this review, we discuss the challenges to achieving optimal outcomes in the management of early-stage HCC and suggest strategies to overcome these obstacles.
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Affiliation(s)
- Jae Hyun Yoon
- Department of Gastroenterology and hepatology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
| | - Sung Kyu Choi
- Department of Gastroenterology and hepatology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Korea
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Pandrowala S, Patkar S, Goel M, Mirza D, Mathur SK. Surgical resection for large hepatocellular carcinoma and those beyond BCLC: systematic review with proposed management algorithm. Langenbecks Arch Surg 2023; 408:144. [PMID: 37041364 DOI: 10.1007/s00423-023-02881-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 04/02/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for the sixth most common cancer and ranks third in mortality worldwide with inhomogeneity in terms of resection for advanced-stage disease. METHODS A systematic review of published literature using the PubMed, Medline, and Google Scholar databases from 1995 to 2020 was conducted to identify studies that reported outcomes of resection for solitary HCC > 10 cm, BCLC B/C, and multinodular HCC. Our aim was to assess overall survival for resection, identify poor prognostic factors, and to compare it to trans-arterial chemotherapy (TACE) where data was available. RESULTS Eighty-nine articles were included after a complete database search in the systematic review as per our predefined criteria. Analysis revealed a 5-year overall survival of 33.5% for resection of HCC > 10 cm, 41.7% for BCLC B, 23.3% for BCLC C, and 36.6% for multinodular HCC. Peri-operative mortality ranged from 0 to 6.9%. Studies comparing resection versus TACE for BCLC B/C had a survival of 40% versus 17%, respectively. CONCLUSION Our systematic review justifies hepatic resection wherever feasible for hepatocellular carcinomas > 10 cm, BCLC B, BCLC C, and multinodular tumors. In addition, we identified and proposed an algorithm with five poor prognostic criteria in this group of patients who may benefit from adjuvant TACE.
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Affiliation(s)
- Saneya Pandrowala
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Mahesh Goel
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India.
| | - Darius Mirza
- Hepato-Pancreato-Biliary and Transplant Surgery, University Hospital Birmingham and Birmingham Children's Hospital, Birmingham, UK
| | - S K Mathur
- Zen Digestive Disease Center, Zen Hospital, Mumbai, India
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Bauschke A, Altendorf-Hofmann A, Brückner L, Drescher R, Freesmeyer M, Settmacher U. Impact of metabolic indices of 18F-fluorodeoxyglucose positron emission tomography/computed tomography on post transplantation recurrence of hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:1401-1410. [PMID: 35451699 PMCID: PMC10020288 DOI: 10.1007/s00432-022-04009-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 04/02/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors. METHODS This retrospective study analyzes 103 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates. RESULTS Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, "up-to-seven" out tumors, grade 3 tumors, α- fetoprotein level >400 ng/ml and lesions > 5cm in diameter. Factors with statistically significant influence on the 10- year overall survival in the univariate analysis were Milan, up-to-seven" criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, "up-to-seven" criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significant. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates. CONCLUSIONS Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma. If we focus on preoperative findings, such as tumor size, tumor number and AFP value adding the information given by TLR of 18F-FDG PET/CT allows to estimate the risk of tumor recurrence more accurate than the established classifications Milan and UTS. Therefore, it may add valuable information to other preoperative findings, such as tumor size, tumor number and AFP level.
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Affiliation(s)
- Astrid Bauschke
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany.
| | - Annelore Altendorf-Hofmann
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Lukas Brückner
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
| | - Robert Drescher
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Martin Freesmeyer
- Department of Nuclear Medizine, University Hospital Jena, Am Klinikum1, 07740, Jena, Germany
| | - Utz Settmacher
- Department of General, Visceral and Vascular Surgery, University Hospital Jena, Am Klinikum 1, Erlanger Allee 101, 07740, Jena, Germany
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2023; 23:1-120. [PMID: 37384024 PMCID: PMC10202234 DOI: 10.17998/jlc.2022.11.07] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 11/07/2022] [Indexed: 06/30/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Affiliation(s)
- Korean Liver Cancer Association (KLCA) and National Cancer Center (NCC) Korea
- Corresponding author: KLCA-NCC Korea Practice Guideline Revision Committee (KPGRC) (Committee Chair: Joong-Won Park) Center for Liver and Pancreatobiliary Cancer, Division of Gastroenterology, Department of Internal Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea Tel. +82-31-920-1605, Fax: +82-31-920-1520, E-mail:
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2022 KLCA-NCC Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2022; 23:1126-1240. [PMID: 36447411 PMCID: PMC9747269 DOI: 10.3348/kjr.2022.0822] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma. Clin Mol Hepatol 2022; 28:583-705. [PMID: 36263666 PMCID: PMC9597235 DOI: 10.3350/cmh.2022.0294] [Citation(s) in RCA: 174] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 09/23/2022] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
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Tabrizian P, Holzner ML, Mehta N, Halazun K, Agopian VG, Yao F, Busuttil RW, Roberts J, Emond JC, Samstein B, Brown RS, Najjar M, Chapman WC, Doyle MM, Florman SS, Schwartz ME, Llovet JM. Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma. JAMA Surg 2022; 157:779-788. [PMID: 35857294 PMCID: PMC9301590 DOI: 10.1001/jamasurg.2022.2800] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging. Objective To establish the 10-year outcomes of patients with HCC after LT in a large, multicenter US study based on individual data; provide robust data on the long-term role of downstaging; and evaluate the association of treatment modalities with postrecurrence survival. Design, Setting, and Participants In this cohort study, a retrospective, multicenter analysis of prospectively collected data was conducted for 2645 adults who had undergone LT for HCC at 5 US academic centers between January 2001 and December 2015. The analysis was performed from May 2019 through June 2021. Outcomes of 341 patients whose disease was downstaged to within MC were compared with those in 2122 patients whose disease was always within MC and 182 patients whose disease was not downstaged. The associations of tumor and treatment factors on postrecurrence survival were analyzed using Cox proportional hazards regression and multivariable logistic regression models. Main Outcomes and Measures The primary outcome was overall survival for the whole cohort and according to downstaging status. Secondary outcomes were time to recurrence, recurrence-free survival, and recurrence after specific post-LT therapies. Results Of the 2645 patients studied, the median age was 59.9 years (IQR, 54.7-64.7 years). The majority of the patients were men (2028 [76.7%] vs 617 [23.3%] women). The 10-year post-LT survival and recurrence rates were, respectively, 52.1% and 20.6% among those whose disease was downstaged; 61.5% and 13.3% in those always within MC; and 43.3% and 41.1% in those whose disease was not downstaged. Independent variables associated with downstaging failure were tumor size greater than 7 cm at diagnosis (OR, 2.62; 95% CI, 1.20-5.75; P = .02), more than 3 tumors at diagnosis (OR, 2.34; 95% CI, 1.22-4.50; P = .01), and α-fetoprotein response of at least 20 ng/mL with less than 50% improvement from maximum α-fetoprotein before LT (OR, 1.99; 95% CI, 1.14-3.46; P = .02). Surgically treated patients with recurrent HCC differed in clinicopathologic characteristics and had improved 5-year postrecurrence survival rates (31.6% vs 7.3%; P < .001). Conclusions and Relevance In a large, multicenter cohort of patients with HCC successfully downstaged to within MC, 10-year post-LT outcomes were excellent, validating national downstaging policies and showing a clear utility benefit for LT prioritization decision making. Surgical management of HCC recurrence after LT was associated with improved survival in well-selected patients and should be pursued, if feasible.
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Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Matthew L. Holzner
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Neil Mehta
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco
| | - Karim Halazun
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Vatche G. Agopian
- Division of Liver and Pancreas Transplantation, David Geffen School of Medicine, University of California, Los Angeles
| | - Francis Yao
- Division of Gastroenterology/Hepatology, Department of Medicine, University of California, San Francisco
| | - Ronald W. Busuttil
- Division of Liver and Pancreas Transplantation, David Geffen School of Medicine, University of California, Los Angeles
| | - John Roberts
- Division of Transplant Surgery, University of California, San Francisco
| | - Jean C. Emond
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, New York
| | - Benjamin Samstein
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Robert S. Brown
- Center for Liver Disease and Transplantation, Weill Cornell Medicine, New York, New York
| | - Marc Najjar
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, New York
| | - William C. Chapman
- Section of Transplant Surgery, Division of General Surgery, Washington University School of Medicine in St Louis, Missouri
| | - Majella Mb. Doyle
- Section of Transplant Surgery, Division of General Surgery, Washington University School of Medicine in St Louis, Missouri
| | - Sander S. Florman
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Myron E. Schwartz
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Josep M. Llovet
- Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- Translational Research in Hepatic Oncology, Liver Unit, August Pi i Sunyer Biomedica Research Institute, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana d’Estudis Avançats, Barcelona, Catalonia, Spain
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Kang S, Kim JD, Choi DL, Choi B. Predicting the Recurrence of Hepatocellular Carcinoma after Primary Living Donor Liver Transplantation Using Metabolic Parameters Obtained from 18F-FDG PET/CT. J Clin Med 2022; 11:jcm11020354. [PMID: 35054048 PMCID: PMC8778128 DOI: 10.3390/jcm11020354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/07/2022] [Accepted: 01/10/2022] [Indexed: 11/26/2022] Open
Abstract
This study evaluated the prognostic value of metabolic parameters based on the standardized uptake value (SUV) normalized by total body weight (bwSUV) and by lean body mass (SUL) measured on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for predicting tumor recurrence after primary living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) without transplantation locoregional therapy. This retrospective study enrolled 49 patients with HCC. The maximum tumor bwSUV (T-bwSUVmax) and SUL (T-SULmax) were measured on PET. The maximum bwSUV (L-bwSUVmax), mean bwSUV (L-bwSUVmean), maximum SUL (L-SULmax), and mean SUL (L-SULmean) were measured in the liver. All metabolic parameters were evaluated using survival analyses and compared to clinicopathological factors. Tumor recurrence occurred in 16/49 patients. Kaplan–Meier analysis revealed that all metabolic parameters were significant (p < 0.05). Univariate analysis revealed that prothrombin-induced by vitamin K absence or antagonist-II; T-stage; tumor number; tumor size; microvascular invasion; the Milan criteria, University of California, San Francisco (UCSF), and up-to-seven criteria; T-bwSUVmax/L-bwSUVmean; T-SULmax; T-SULmax/L-SULmax; and T-SULmax/L-SULmean were significant predictors. Multivariate analysis revealed that the T-SULmax/L-SULmean (hazard ratio = 115.6; p = 0.001; cut-off, 1.81) and UCSF criteria (hazard ratio = 172.1; p = 0.010) were independent predictors of tumor recurrence. SUL-based metabolic parameters, especially T-SULmax/L-SULmean, were significant, independent predictors of HCC recurrence post-LDLT.
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Affiliation(s)
- Sungmin Kang
- Department of Nuclear Medicine, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea;
| | - Joo Dong Kim
- Division of Hepatobiliary Pancreas Surgery and Abdominal Organ Transplantation, Department of Surgery, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea; (J.D.K.); (D.L.C.)
| | - Dong Lak Choi
- Division of Hepatobiliary Pancreas Surgery and Abdominal Organ Transplantation, Department of Surgery, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea; (J.D.K.); (D.L.C.)
| | - Byungwook Choi
- Department of Nuclear Medicine, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, 33, Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea;
- Correspondence: ; Tel.: +82-53-650-4789
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Bhatti ABH, Naqvi W, Khan NY, Zia HH, Dar FS, Khan ZA, Rana A. Living donor liver transplantation for advanced hepatocellular carcinoma including macrovascular invasion. J Cancer Res Clin Oncol 2022; 148:245-253. [PMID: 34117916 PMCID: PMC8752562 DOI: 10.1007/s00432-021-03665-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 05/13/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The indications for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) continue to evolve. The aim of this study was to report outcomes in patients who underwent living donor liver transplantation (LDLT) for HCC outside traditional criteria including macrovascular invasion (MVI). METHODS We reviewed outcomes in patients who met the University of California San Francisco (UCSF) criteria (n = 159) and our center-specific criteria (UCSF+) (largest tumor diameter ≤ 10 cm, any tumor number, AFP ≤ 1000 ng/ml) (n = 58). We also assessed outcomes in patients with MVI (n = 27). RESULTS The median follow was 28 (10.6-42.7) months. The 5 year overall survival and risk of recurrence (RR) in the UCSF and UCSF + group was 71% vs 69% (P = 0.7) and 13% vs 36% (P = 0.1) respectively. When patients with AFP > 600 ng/ml were excluded from the UCSF + group, RR was 27% (P = 0.3). Among patients with MVI who had downstaging (DS), 4/5(80%) in low-risk group (good response and AFP ≤ 100 ng/ml) and 2/10 (20%) in the high-risk group (poor response or AFP > 100 ng/ml) were alive at the last follow-up. When DS was not feasible, 3/3 (100%) in the low-risk group (AFP ≤ 100 ng/ml + Vp1-2 MVI) and 1/9 (9.1%) in the high-risk group (AFP > 100 or Vp3 MVI) were alive. The 5 year OS in the low-risk MVI group was 85% (P = 0.003). CONCLUSION With inclusion of AFP, response to downstaging and degree of MVI, acceptable survival can be achieved with LDLT for HCC outside traditional criteria.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan.
- Department of Surgery, Shifa Tameer-e-Millat University Islamabad, Islamabad, Pakistan.
| | - Wajih Naqvi
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Nusrat Yar Khan
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Faisal Saud Dar
- Division of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Shifa International Hospital Islamabad, Sector H-8/4, Pitras Bukhari Road, Islamabad, 44000, Pakistan
| | - Zahid Amin Khan
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
| | - Atif Rana
- Division of Radiology, Shifa International Hospital Islamabad, Islamabad, Pakistan
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Biolato M, Galasso T, Marrone G, Miele L, Grieco A. Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation. Cancers (Basel) 2021; 13:6337. [PMID: 34944957 PMCID: PMC8699392 DOI: 10.3390/cancers13246337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022] Open
Abstract
In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60-70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to "extended" downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
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Affiliation(s)
- Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Tiziano Galasso
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Luca Miele
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
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Liang HR, Hsieh CE, Lin KH, Ko CJ, Hung YJ, Hsu YL, Chen YL. Living donor liver transplantation for hepatocellular carcinoma beyond the Milan criteria: outcome of expanded criteria in tumor size. BMC Surg 2021; 21:401. [PMID: 34798847 PMCID: PMC8603535 DOI: 10.1186/s12893-021-01403-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 11/09/2021] [Indexed: 11/23/2022] Open
Abstract
Background The Milan criteria are the universal standard of liver transplantation for hepatocellular carcinoma (HCC). Numerous expanded criteria have shown outcomes as good as the Milan criteria. In Taiwan, living donor liver transplant (LDLT) accounts for the majority of transplantations due to organ shortages. Methods We retrospectively enrolled 155 patients who underwent LDLT for HCC from July 2005 to June 2017 and were followed up for at least 2 years. Patients beyond the Milan criteria (n = 78) were grouped as recurrent or nonrecurrent, and we established new expanded criteria based on these data. Results Patients beyond the Milan criteria with recurrence (n = 31) had a significantly larger maximal tumor diameter (4.13 ± 1.96 cm versus 6.10 ± 3.41 cm, p = 0.006) and total tumor diameter (7.19 ± 4.13 cm versus 10.21 ± 5.01 cm, p = 0.005). Therefore, we established expanded criteria involving maximal tumor diameter ≤ 6 cm and total tumor diameter < 10 cm. The 5-year survival rate of patients who met these criteria (n = 134) was 77.3%, and the 5-year recurrence rate was 20.5%; both showed no significant differences from those of the Milan criteria. Under the expanded criteria, the pool of eligible recipients was 35% larger than that of the Milan criteria. Conclusion Currently, patients with HCC who undergo LDLT can achieve good outcomes even when they are beyond the Milan criteria. Under the new expanded criteria, patients can achieve outcomes as good as those with the Milan criteria and more patients can benefit.
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Affiliation(s)
- Hsin-Rou Liang
- Department of General Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Chia-En Hsieh
- Department of Nursing, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Kuo-Hua Lin
- Department of General Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Chih-Jan Ko
- Department of General Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Yu-Ju Hung
- Department of General Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Ya-Lan Hsu
- Department of Nursing, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.)
| | - Yao-Li Chen
- Department of General Surgery, Changhua Christian Hospital, No. 135 Nanxiao St., Changhua, 500, Taiwan (R.O.C.).
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YANKOL Y, HOŞ G, KANMAZ T, MECİT N, ÇAKALOĞLU Y, KALAYOĞLU M, ACARLI KS. Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center. Turk J Med Sci 2021; 51:2383-2395. [PMID: 33754656 PMCID: PMC8742484 DOI: 10.3906/sag-2101-51] [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] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 03/20/2021] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND/AIM With the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center. MATERIAL AND METHODS Between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed. RESULTS In 191 patients, one-, three- and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three- and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). CONCLUSION LDLT allows us to push the limits forward and the question “Are the criteria always right?” is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.
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Affiliation(s)
- Yücel YANKOL
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
- Organ Transplant Center, Memorial Şişli Hospital, İstanbulTurkey
| | - Gültekin HOŞ
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
- Department of Surgery, Şişli Etfal Training and Research Hospital, İstanbulTurkey
| | - Turan KANMAZ
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
- Organ Transplant Center, School of Medicine, Koç University, İstanbulTurkey
| | - Nesimi MECİT
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
- Organ Transplant Center, School of Medicine, Koç University, İstanbulTurkey
| | - Yılmaz ÇAKALOĞLU
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
| | - Münci KALAYOĞLU
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
- Organ Transplant Center, School of Medicine, Koç University, İstanbulTurkey
| | - Koray S. ACARLI
- Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WIUnited States
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Lerut J, Foguenne M, Lai Q. Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score. Updates Surg 2021; 73:1599-1614. [PMID: 34003479 PMCID: PMC8500859 DOI: 10.1007/s13304-021-01078-4] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022]
Abstract
The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.
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Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrates 55, 1200 Brussels, Belgium
| | - Maxime Foguenne
- University Hospitals Saint-Luc Université Catholique de Louvain (UCL), Brussels, Belgium
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
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Abstract
Gastrointestinal malignancies encompass a variety of primary tumor sites, each with different staging criteria and treatment approaches. In this review we discuss technical aspects of 18F-FDG-PET/CT scanning to optimize information from both the PET and computed tomography components. Specific applications for 18F-FDG-PET/CT are summarized for initial staging and follow-up of the major disease sites, including esophagus, stomach, hepatobiliary system, pancreas, colon, rectum, and anus.
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Affiliation(s)
- Brandon A Howard
- Division of Nuclear Medicine and Radiotheranostics, Department of Radiology, Duke University Medical Center, DUMC Box 3949, 2301 Erwin Road, Durham, NC 27710, USA.
| | - Terence Z Wong
- Division of Nuclear Medicine and Radiotheranostics, Department of Radiology, Duke University Medical Center, DUMC Box 3949, 2301 Erwin Road, Durham, NC 27710, USA
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22
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Kwong A, Mehta N. Expanding the Limits of Liver Transplantation for Hepatocellular Carcinoma: Is There a Limit? Clin Liver Dis 2021; 25:19-33. [PMID: 33978578 DOI: 10.1016/j.cld.2020.08.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation is a treatment option for hepatocellular carcinoma within Milan criteria. With careful selection practices, patients with larger tumors can do well with successful downstaging followed by liver transplantation and should not be excluded based on tumor size or number alone. When considering expanded criteria for hepatocellular carcinoma, however, survival outcomes after liver transplantation should be comparable with patients without hepatocellular carcinoma. Surrogate measures of tumor biology, such as α-fetoprotein, other biomarkers, and dynamic tumor behavior including response to locoregional therapy can aid in risk stratification of patients before liver transplantation.
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Affiliation(s)
- Allison Kwong
- Division of Gastroenterology and Hepatology, Stanford University, 420 Broadway Street, 3rd Floor, Redwood City, CA 94063, USA
| | - Neil Mehta
- Division of Gastroenterology, University of California, San Francisco, 513 Parnassus Avenue, S-357, San Francisco, CA 94143, USA.
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23
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Downstaging to Liver Transplant: Success Involves Choosing the Right Patient. Clin Liver Dis 2020; 24:665-679. [PMID: 33012452 DOI: 10.1016/j.cld.2020.07.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Hepatocellular carcinoma is a rising indication for liver transplantation in the United States. Downstaging, defined as the reduction of tumor burden using local-regional therapy into Milan criteria, opens an avenue to access cure through transplant for patients who traditionally would not qualify. Approaching the selection of downstaging candidates through an assessment of hepatic function, staying within a modest expansion of tumor burden, and incorporation of serologic/imaging markers for tumor biology provide the best chance for successful downstaging. Following well-defined downstaging protocols with built-in failure criteria ensures excellent post-transplant outcomes.
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24
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Bhatti ABH, Qureshi AI, Tahir R, Dar FS, Khan NY, Zia HH, Riyaz S, Rana A. When to call it off: defining transplant candidacy limits in liver donor liver transplantation for hepatocellular carcinoma. BMC Cancer 2020; 20:754. [PMID: 32787864 PMCID: PMC7425141 DOI: 10.1186/s12885-020-07238-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/29/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Living donor liver transplantation (LDLT) is an acceptable treatment option for hepatocellular carcinoma (HCC). Traditional transplant criteria aim at best utilization of donor organs with low risk of post transplant recurrence. In LDLT, long term recurrence free survival (RFS) of 50% is considered acceptable. The objective of the current study was to determine preoperative factors associated with high recurrence rates in LDLT. METHODS Between April 2012 and December 2019, 898 LDLTs were performed at our center. Out of these, 242 were confirmed to have HCC on explant histopathology. We looked at preoperative factors associated with ≤ 50%RFS at 4 years. For survival analysis, Kaplan Meier curves were used and Cox regression analysis was used to identify independent predictors of recurrence. RESULTS Median AFP was 14.4(0.7-11,326.7) ng/ml. Median tumor size was 2.8(range = 0.1-11) cm and tumor number was 2(range = 1-15). On multivariate analysis, AFP > 600 ng/ml [HR:6, CI: 1.9-18.4, P = 0.002] and microvascular invasion (MVI) [HR:5.8, CI: 2.5-13.4, P < 0.001] were independent predictors of 4 year RFS ≤ 50%. When AFP was > 600 ng/ml, MVI was seen in 88.9% tumors with poor grade and 75% of tumors outside University of California San Francisco criteria. Estimated 4 year RFS was 78% for the entire cohort. When AFP was < 600 ng/ml, 4 year RFS for well-moderate and poor grade tumors was 88 and 73%. With AFP > 600 ng/ml, RFS was 53% and 0 with well-moderate and poor grade tumors respectively (P < 0.001). CONCLUSION Patients with AFP < 600 ng/ml have acceptable outcomes after LDLT. In patients with AFP > 600 ng/ml, a preoperative biopsy to rule out poor differentiation should be considered for patient selection.
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Affiliation(s)
- Abu Bakar Hafeez Bhatti
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan.
| | - Ammal Imran Qureshi
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Rizmi Tahir
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Faisal Saud Dar
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Nusrat Yar Khan
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Haseeb Haider Zia
- Division of Hepato-Pancreatico-Biliary Surgery and Liver Transplantation, Shifa International Hospital, Islamabad, Pakistan
| | - Shahzad Riyaz
- Division of Transplant Hepatology, Shifa International Hospital, Islamabad, Pakistan
| | - Atif Rana
- Division of Radiology, Shifa International Hospital, Islamabad, Pakistan
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25
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Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, Durand F, Ijzermans J, Polak W, Zheng S, Roberts JP, Sapisochin G, Hibi T, Kwan NM, Ghobrial M, Soin A. Liver Transplantation for Hepatocellular Carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1136-1142. [PMID: 32217938 DOI: 10.1097/tp.0000000000003174] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) offers excellent long-term outcome for certain patients with hepatocellular carcinoma (HCC), with a push to not simply rely on tumor size and number. Selection criteria should also consider tumor biology (including alpha-fetoprotein), probability of waitlist and post-LT survival (ie, transplant benefit), organ availability, and waitlist composition. These criteria may be expanded for live donor LT (LDLT) compared to deceased donor LT though this should not adversely affect the double equipoise in LDLT, namely ensuring both acceptable recipient outcomes and donor safety. HCC patients with compensated liver disease and minimal tumor burden have low urgency for LT, especially after local-regional therapy with complete response, and do not appear to derive the same benefit from LT as other waitlist candidates. These guidelines were developed to assist in selecting appropriate HCC patients for both deceased donor LT and LDLT.
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Affiliation(s)
- Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Francis Y Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Vincenzo Mazzaferro
- Department of Surgery, GI Surgery and Liver Transplantation, Istituto Nazionale Tumori, Milan, Italy
| | - Christian Toso
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Francois Durand
- Service d'Hépatologie & Réanimation Hépatodigestive, Université Paris VII Hôpital Beaujon, Paris, France
| | - Jan Ijzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wojciech Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - John P Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Taizo Hibi
- Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nancy Man Kwan
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Mark Ghobrial
- J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Avi Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
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26
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Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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27
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Mehta N. Hepatocellular Carcinoma-How to Determine Therapeutic Options. Hepatol Commun 2020; 4:342-354. [PMID: 32140653 PMCID: PMC7049673 DOI: 10.1002/hep4.1481] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 12/31/2019] [Indexed: 02/06/2023] Open
Abstract
Deciding on specific treatment strategies involves not only tumor stage, performance status, and severity of underlying liver disease, but additional factors such as biomarkers, organ availability, and radiographic tumor response to treatment. In this review, we present hepatocellular carcinoma (HCC) cases to highlight how to determine therapeutic options for HCC in specific scenarios, including resection versus liver transplant, choice of initial local regional treatment, tumor downstaging, and systemic therapies for advanced HCC.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology Department of Medicine University of California San Francisco San Francisco CA
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28
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29
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How far can we go with hepatocellular carcinoma in living donor liver transplantation? Curr Opin Organ Transplant 2019; 24:644-650. [DOI: 10.1097/mot.0000000000000692] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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30
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Ling LLL, Hsu CC, Yong CC, Elsarawy AM, Chan YC, Wang CC, Li WF, Lin TL, Kuo FY, Cheng YF, Lin LM, Chen CL, Lin CC. FDG-PET predicted unfavorable tumor histology in living donor liver transplant recipients; a retrospective cohort study. Int J Surg 2019; 69:124-131. [DOI: 10.1016/j.ijsu.2019.07.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 07/26/2019] [Accepted: 07/26/2019] [Indexed: 02/07/2023]
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31
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Mullath A, Krishna M. Hepatocellular carcinoma - time to take the ticket. World J Gastrointest Surg 2019; 11:287-295. [PMID: 31367276 PMCID: PMC6658361 DOI: 10.4240/wjgs.v11.i6.287] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 06/13/2019] [Accepted: 06/20/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading malignancies worldwide. Early detection of hepatocellular carcinoma and its management in the form of liver transplantation offers an attractive treatment option. The Milan criteria, proposed by Mazzaferro et al, have been the standard for selecting patients with hepatocellular carcinoma for transplantation. Recently, several studies have shown that even patients selected outside the Milan criteria can undergo transplantation with a relatively good outcome. This article examines the currently existing criteria other than the Milan criteria and also evaluates use of alpha-fetoprotein and positron emission tomography scans to predict the chance of recurrence.
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Affiliation(s)
- Anju Mullath
- Department of Gastroenterology, Lakeshore Hospital and Research Centre, Kochi 682040, Kerala, India
| | - Murali Krishna
- Department of Surgery, Military Hospital, Palampur 176061, Himachal Pradesh, India
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32
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Subramanian V, Chapman W. Living Donor Liver Transplant for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1594-1595. [PMID: 30937661 DOI: 10.1245/s10434-019-07250-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Vijay Subramanian
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA
| | - William Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA.
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33
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Abstract
Despite advancements in early diagnosis and medico-surgical treatment, hepatocellular carcinoma (HCC) is still a major cancer that causes substantial mortality in Asian countries. Liver transplantation (LT) has been accepted worldwide as the most effective treatment modality for patients with HCC; however, with the high incidence of HCC and low organ donation rate, Asia has developed distinctive features of indications and strategies for the application of LT. Unlike Western countries, living donor liver transplantation (LDLT) accounts for most LT cases for HCC in Asian countries, and most major transplantation centers perform LDLT for HCC patients with extended criteria. This article reviewed the current practice and outcome of LDLT for HCC from an Asian perspective and summarized the strategies that the high-volume LT centers in Asia use to obtain satisfactory oncologic results.
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34
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Lee SM, Kim HS, Lee S, Lee JW. Emerging role of 18F-fluorodeoxyglucose positron emission tomography for guiding management of hepatocellular carcinoma. World J Gastroenterol 2019; 25:1289-1306. [PMID: 30918424 PMCID: PMC6429342 DOI: 10.3748/wjg.v25.i11.1289] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 02/25/2019] [Accepted: 03/02/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of major causes of cancer mortality worldwide. For decades, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been widely used for staging, predicting prognosis, and detecting cancer recurrence in various types of malignant diseases. Due to low sensitivity of FDG PET for detecting intrahepatic HCC lesions, the clinical value of FDG PET in HCC patients has been limited. However, recent studies with diverse analytic methods have shown that FDG PET has promising role in aiding management of HCC patients. In this review, we will discuss the clinical role of FDG PET for staging, predicting prognosis, and evaluating treatment response in HCC. Further, we will focus on recent clinical studies regarding implication of volumetric FDG PET parameters, the significance of FDG uptake in HCC for selecting treatment and predicting treatment response, and the use of radiomics of FDG PET in HCC.
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Affiliation(s)
- Sang Mi Lee
- Department of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Chungcheongnam-do 31151, South Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Chungcheongnam-do 31151, South Korea
| | - Sangheun Lee
- Division of Hepatology, Department of Internal medicine, Catholic Kwandong University College of Medicine, International St. Mary’s Hospital, Incheon 22711, South Korea
- Institute for Health and Life Science, Catholic Kwandong University College of Medicine, International St. Mary’s Hospital, Incheon 22711, South Korea
| | - Jeong Won Lee
- Department of Nuclear Medicine, Catholic Kwandong University College of Medicine, International St. Mary’s Hospital, Incheon 22711, South Korea
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35
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Kornberg A, Friess H. 18F-fludeoxyglucose positron emission tomography for diagnosis of HCC: implications for therapeutic strategy in curative and non-curative approaches. Therap Adv Gastroenterol 2019; 12:1756284819836205. [PMID: 30915167 PMCID: PMC6429646 DOI: 10.1177/1756284819836205] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 02/15/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a global health issue with increasing incidence and high mortality rate. Depending on the tumor load and extent of underlying liver cirrhosis, aggressive surgical treatment by hepatectomy or liver transplantation (LT) may lead to cure, whereas different modalities of liver-directed locoregional or systemic tumor treatments are currently available for a noncurative approach. Apart from tumor burden and grade of liver dysfunction, assessment of prognostic relevant biological tumor aggressiveness is vitally important for establishing a promising multimodal therapeutic strategy and improving the individual treatment-related risk/benefit ratio. In recent years, an increasing body of clinical evidence has been presented that 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), which is a standard nuclear imaging device in oncology, may serve as a powerful surrogate for tumor invasiveness and prognosis in HCC patients and, thereby, impact individual decision making on most appropriate therapy concept. This review describes the currently available data on the prognostic value of 18F-FDG PET in patients with early and advanced HCC stages and the resulting implications for treatment strategy.
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Affiliation(s)
| | - Helmut Friess
- Department of Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany
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36
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Mehta N, Dodge JL, Roberts JP, Hirose R, Yao FY. Alpha-Fetoprotein Decrease from > 1,000 to < 500 ng/mL in Patients with Hepatocellular Carcinoma Leads to Improved Posttransplant Outcomes. Hepatology 2019; 69:1193-1205. [PMID: 30548884 PMCID: PMC7087461 DOI: 10.1002/hep.30413] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 09/23/2018] [Indexed: 12/13/2022]
Abstract
High alpha-fetoprotein (AFP) > 1,000 ng/mL is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). A new national policy has been implemented for AFP > 1,000 ng/mL requiring a decrease to < 500 ng/mL before LT, but there is a paucity of data on the optimal AFP threshold before LT. We aimed to evaluate the effects of a reduction in AFP from > 1,000 ng/mL to different AFP thresholds before LT on survival and HCC recurrence after LT using the United Network for Organ Sharing database. We identified 407 patients who underwent transplant between January 2005 and September 2015 and who had AFP > 1,000 ng/mL at least once before LT. The last AFP measurement before LT was > 1,000 ng/mL in 72.0%, decreased from > 1,000 to 101-499 ng/mL in 9.6%, and decreased to ≤ 100 ng/mL in 14.3%. Local-regional therapy was not performed in 45.4% of patients with AFP > 1,000 ng/mL at LT versus 12.8% of those with AFP of 101-499 ng/mL and 10.3% of those with AFP ≤ 100 ng/mL at LT (P < 0.001). Kaplan-Meier 5-year post-LT survival for those with AFP > 1,000 ng/mL at LT was 48.8% versus 67.0% for those with a decrease in AFP to 101-499 ng/mL (P < 0.001) and 88.4% for those with AFP ≤ 100 ng/mL at LT (P < 0.001). HCC recurrence probability at 5 years was 35.0% for patients with AFP > 1,000 ng/mL versus 13.3% for patients with AFP of 101-499 ng/mL and 7.2% for patients with AFP ≤ 100 ng/mL at LT (P < 0.001). In multivariable analysis, a decrease in the AFP to 101-499 ng/mL was associated with a > 2-fold reduction in posttransplant mortality (P = 0.01) and a nearly 3-fold reduction in HCC recurrence (P = 0.02) compared with AFP > 1,000 ng/mL at LT. Conclusion: Our results demonstrated significantly improved post-LT outcomes when restricting LT to patients with a reduction in AFP from > 1,000 to < 500 ng/mL, validating the recently implemented national policy.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA,Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
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37
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Mehta N, Yao FY. What Are the Optimal Liver Transplantation Criteria for Hepatocellular Carcinoma? Clin Liver Dis (Hoboken) 2019; 13:20-25. [PMID: 31168361 PMCID: PMC6465780 DOI: 10.1002/cld.793] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Accepted: 12/08/2018] [Indexed: 02/04/2023] Open
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of MedicineUniversity of CaliforniaSan FranciscoSan FranciscoCA
| | - Francis Y. Yao
- Division of Gastroenterology, Department of MedicineUniversity of CaliforniaSan FranciscoSan FranciscoCA
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38
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Yaprak O, Acar S, Ertugrul G, Dayangac M. Role of pre-transplant 18F-FDG PET/CT in predicting hepatocellular carcinoma recurrence after liver transplantation. World J Gastrointest Oncol 2018; 10:336-343. [PMID: 30364796 PMCID: PMC6198297 DOI: 10.4251/wjgo.v10.i10.336] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 05/27/2018] [Accepted: 06/14/2018] [Indexed: 02/05/2023] Open
Abstract
The last two decades have seen a paradigm shift in the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation. Microvascular invasion and differentiation have been the most significant factors affecting post-transplant recurrence; however, because of inherent disadvantages of pre-transplant biopsy, histological criteria never gained popularity. Recently, the selection criteria evolved from morphological to biological criteria, such as biomarkers and response to loco-regional therapy. With the introduction of multimodality imaging, combination of computed tomography with nuclear medicine imaging, particularly, 18F-fluorodeoxyglucose positron emission tomography fulfilled an unmet need and rapidly became a critical component of HCC management. This review article will focus on the use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the pre-transplant evaluation of HCC patients with special discussion on its ability to predict HCC recurrence after liver transplantation.
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Affiliation(s)
- Onur Yaprak
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
| | - Sencan Acar
- Atasehir Memorial Hospital, Center for Organ Transplantation, Istanbul 34758, Turkey
| | - Gokhan Ertugrul
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
| | - Murat Dayangac
- Medipol University Hospital, Center for Organ Transplantation, Istanbul 34214, Turkey
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39
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Mehta N, Yao FY. Living donor liver transplantation for hepatocellular carcinoma: To expand (beyond Milan) or downstage (to Milan)? Liver Transpl 2018; 24:327-329. [PMID: 29351366 DOI: 10.1002/lt.25017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 01/16/2018] [Indexed: 12/20/2022]
Affiliation(s)
- Neil Mehta
- Division of Gastroenterology Department of Medicine, University of California, San Francisco San Francisco, CA
| | - Francis Y Yao
- Division of Gastroenterology Department of Medicine, University of California, San Francisco San Francisco, CA
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40
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Kornberg A, Schernhammer M, Friess H. 18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:224-234. [PMID: 28936404 PMCID: PMC5606969 DOI: 10.14218/jcth.2017.00014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 05/18/2017] [Accepted: 06/05/2017] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.
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Affiliation(s)
- Arno Kornberg
- *Correspondence to: Arno Kornberg, Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, D-81675 Munich, Germany. Tel: +89-41405087, Fax: +89-41404884, E-mail:
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Moon H, Choi JE, Lee IJ, Kim TH, Kim SH, Ko YH, Kim HB, Nam BH, Park JW. All-treatment array of hepatocellular carcinoma from initial diagnosis to death: observation of cumulative treatments. J Cancer Res Clin Oncol 2017; 143:2327-2339. [PMID: 28744575 PMCID: PMC5640756 DOI: 10.1007/s00432-017-2480-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Accepted: 07/15/2017] [Indexed: 12/14/2022]
Abstract
PURPOSE In clinical practice, most patients with hepatocellular carcinoma require subsequent treatments for remaining, progressing, or recurring tumors. We investigated all-treatment array and outcomes in an HCC cohort from initial diagnosis to death. METHODS We enrolled 1687 consecutive patients with HCC who underwent initial diagnosis and treatment at the National Cancer Center, Korea, from January 2004 to December 2009. RESULTS In total, 1357 patients (80.4%) showed RPRTs during median 20.4-month follow-up. Initial transplantation resulted in the least rate (32.3%) of RPRTs. Median treatment frequency was 3.0 times (range 1-20) and 382 patients (27.3%) received treatments ≥6 times. The median treatment frequency was different based on four factors (p < 0.05): age, tumor stage, tumor type and initial treatment modality. Patients with Barcelona Clinic Liver Cancer stage 0 received less frequent treatments. As the stage progressed from 0 to B, the median treatment frequency increased. Radiofrequency ablation as initial treatment was associated with the longest median treatment interval at 19.0 weeks, followed by resection at 14.1 weeks. The median treatment interval was significantly shorter as the stage progressed (p < 0.01). TACE was most frequently performed for RPRTs; the median number of subsequent TACE was 3 (range 1-19). Subsequent treatment array was very heterogeneous, and no certain pattern was found. CONCLUSIONS Our findings suggest that the survival outcome of patients with HCC is based on the results of cumulative multiple treatments rather than an initial treatment. It is time to consider prospective studies evaluating sequential treatment array of HCC.
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Affiliation(s)
- Hae Moon
- Department of Internal Medicine, National Cancer Center, Goyang, Republic of Korea
| | - Ji Eun Choi
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - In Joon Lee
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Tae Hyun Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Seong Hoon Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Young Hwan Ko
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Hyun Boem Kim
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Byung-Ho Nam
- Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea
| | - Joong-Won Park
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea. .,Department of Cancer Control and Policy, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Republic of Korea.
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Cascales-Campos PA, Romero PR, Schneider MA, Lopez-Lopez V, Navarro JL, Frutos L, Pons Miñano JA, Paricio PP. Positron emission tomography/computed tomography in patients with hepatocellular carcinoma undergoing liver transplantation. Useful, necessary or irrelevant? Eur J Radiol 2017. [DOI: 10.1016/j.ejrad.2017.03.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Lee HW, Suh KS. Advancements of liver transplantation for hepatocellular carcinoma in Korea. Jpn J Clin Oncol 2016; 47:93-100. [DOI: 10.1093/jjco/hyw168] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 09/21/2016] [Accepted: 11/14/2016] [Indexed: 02/06/2023] Open
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