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Varma V, Nekarakanti PK, Agarwal S, Dey R, Gupta S. Role of Locoregional Therapy on Survival After Living Donor Liver Transplantation for Hepatocellular Carcinoma--Experience from a High-volume Center. J Clin Exp Hepatol 2025; 15:102490. [PMID: 39868008 PMCID: PMC11757764 DOI: 10.1016/j.jceh.2024.102490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Background Locoregional therapy (LRT) in patients with hepatocellular carcinoma (HCC) before liver transplantation (LT) has a role in improving the tumor biology and post-LT survival outcome apart from downstaging and bridging. We retrospectively analyzed our database of adult living donor liver transplants (LDLT) for HCC, to compare the survival outcomes in Group-1 (upfront-LT, HCC within Milan/UCSF/AFP<1000 ng/ml) and Group-2 (LT post-LRT, HCC beyond UCSF/irrespective of tumor burden with AFP>1000 ng/ml). We also explored the risk factors for recurrence on follow-up. Methods A study group (n = 506, Group-1-348, Group-2 = 158) of patients with HCC who underwent LDLT between July 2006 and December 2022, excluding incidental HCC (n = 42), patients with other histology (n = 13) and in-hospital mortality (n = 43), were analyzed. Study cohort (n = 341), after propensity score matching, was analyzed for survival outcomes (overall survival, OS and disease-free survival, DFS) and risk factors for recurrence between Group-1 (n = 156) and Group-2 (n = 158). Results Group-2 exhibited a trend towards better mean OS and DFS compared to Group-1 (OS-133 vs. 107-months, P = NS, DFS-118 vs. 102-months, P = NS). Long-term OS (10-year) for those within Milan and UCSF criteria was superior in Group-2, P = NS. Complete pathological response (cPR) after LRT (46.8%), significantly improved OS and DFS compared to those with partial response and stable disease; 152 vs. 94 vs. 49 months, P = 0.001, and 147 vs. 75 vs. 41 months, P = 0.006, respectively. Recipient age, size of tumor, and pre-LT serum alpha-fetoprotein (AFP) were independent predictors of cPR. Independent risk factors for recurrence included pre-LT AFP, tumors beyond UCSF, perineural invasion, and high-grade tumors. Conclusion Locoregional therapy in HCC offers significantly better OS and DFS in those who had a complete pathological response. Risk factors for recurrence post-LT were AFP level, beyond UCSF tumors, and high-grade HCC with PNI on histology.
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Affiliation(s)
- Vibha Varma
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Phani K. Nekarakanti
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Shaleen Agarwal
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Rajesh Dey
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
| | - Subash Gupta
- Max Centre for Liver and Biliary Sciences, Max Super Specialty Hospital, Saket, New Delhi 110017, India
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Desai J, Okeke RI, Desai R, Zhang Z, Engelhardt A, Schnitzler M, Barron J, Varma CR, Randall HB, Lentine KL, Nazzal M. Pre-transplant Loco-Regional Therapy for Hepatocellular Carcinoma and Post-transplant Outcomes: A National Study. Cureus 2024; 16:e67960. [PMID: 39328600 PMCID: PMC11427028 DOI: 10.7759/cureus.67960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2024] [Indexed: 09/28/2024] Open
Abstract
The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.
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Affiliation(s)
- Jay Desai
- Department of Surgery, Saint Louis University Hospital, Saint Louis, USA
| | - Raymond I Okeke
- Department of Surgery, Saint Louis University Hospital, Saint Louis, USA
| | - Roshani Desai
- Gastroenterology, Saint Louis University School of Medicine, Saint Louis, USA
| | - Zidong Zhang
- Surgery, Saint Louis University School of Medicine, Saint Louis, USA
| | | | - Mark Schnitzler
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - John Barron
- Surgery, Saint Louis University School of Medicine, Saint Louis, USA
| | - Chintalapati R Varma
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Henry B Randall
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Krista L Lentine
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
| | - Mustafa Nazzal
- Center for Abdominal Transplantation, Saint Louis University School of Medicine, Saint Louis, USA
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [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: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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Jotz RDF, Horbe AF, Coral GP, Fontana PC, de Morais BG, de Mattos AA. Results of transarterial chemoembolization of hepatocellular carcinoma as a bridging therapy to liver transplantation. Radiol Bras 2023; 56:235-241. [PMID: 38204906 PMCID: PMC10775808 DOI: 10.1590/0100-3984.2023.0040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 06/12/2023] [Accepted: 07/19/2023] [Indexed: 01/12/2024] Open
Abstract
Objective To evaluate the degree of tumor necrosis after transarterial chemoembolization (TACE), used as a bridging therapy in patients awaiting liver transplantation, and its effect on survival. Materials and Methods This was a retrospective cohort study involving 118 patients submitted to TACE prior to liver transplantation, after which the degree of tumor necrosis in the explant and post-transplant survival were evaluated. Results Total necrosis of the neoplastic nodule in the explant was observed in 76 patients (64.4%). Of the patients with total necrosis in the explanted liver, 77.8% had presented a complete response on imaging examinations. Drug-eluting bead TACE (DEB-TACE), despite showing a lower rate of complications than conventional TACE, provided a lower degree of total necrosis, although there was no statistical difference between the two. By the end of the study period, 26 of the patients had died. Survival was longer among the patients with total necrosis than among those with partial or no necrosis (HR = 2.24 [95% CI: 0.91-5.53]; p = 0.078). Conclusion In patients undergoing TACE as a bridging therapy, total tumor necrosis appears to be associated with improved patient survival.
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Affiliation(s)
- Raquel de Freitas Jotz
- Universidade Federal de Ciências da Saúde de Porto
Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | - Alex Finger Horbe
- Irmandade Santa Casa de Misericórdia de Porto Alegre
(ISCMPA), Porto Alegre, RS, Brazil
| | - Gabriela Perdomo Coral
- Universidade Federal de Ciências da Saúde de Porto
Alegre (UFCSPA), Porto Alegre, RS, Brazil
| | | | | | - Angelo Alves de Mattos
- Universidade Federal de Ciências da Saúde de Porto
Alegre (UFCSPA), Porto Alegre, RS, Brazil
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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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7
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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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8
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Caiña Ruiz R, Toledo Martínez E, Anderson EJ, Valbuena Jabares V, Fernández Santiago R, Castillo F, Echeverri J, Achalandabaso M, González Sánchez FJ, Fábrega E, Cuadrado A, Fortea JI, Crespo J, Rodríguez Sanjuán JC. Effect of Bridging Therapy on Survival in Hepatocellular Carcinoma Patients Who Receive Liver Transplants. Transplant Proc 2022. [DOI: 10.1016/j.transproceed.2022.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
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9
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Mohr I, Vogeler M, Pfeiffenberger J, Sprengel SD, Klauss M, Radeleff B, Teufel A, Chang DH, Springfeld C, Longerich T, Merle U, Mehrabi A, Weiss KH, Mieth M. Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma. J Cancer Res Clin Oncol 2022; 148:3163-3174. [PMID: 35076764 PMCID: PMC9508038 DOI: 10.1007/s00432-021-03900-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 12/24/2021] [Indexed: 01/09/2023]
Abstract
Purpose We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. Methods In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. Results The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. Conclusions The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.
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Affiliation(s)
- Isabelle Mohr
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Marie Vogeler
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Jan Pfeiffenberger
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | | | - Miriam Klauss
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, Sana Klinikum Hof, Hof, Germany
| | - Andreas Teufel
- Department of Gastroenterology and Hepatology, Mannheim University Hospital, Mannheim, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - De-Hua Chang
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Thomas Longerich
- Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Uta Merle
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Karl Heinz Weiss
- Internal Medicine, Salem Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany.
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany.
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Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation. Cancers (Basel) 2022; 14:cancers14020396. [PMID: 35053558 PMCID: PMC8773674 DOI: 10.3390/cancers14020396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 01/09/2022] [Accepted: 01/12/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is the fifth most common cancer in men worldwide and the second leading cause of cancer death. Liver transplantation (LT) is one of the treatment options for patients with HCC. Recently, there have been many reports of the usefulness of locoregional therapy, such as transarterial chemoembolization and radiofrequency ablation, for HCC as pretreatment before LT. In Western countries, locoregional therapy is used to bridge until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. With the progress of locoregional therapy, new reports on the effects of bridging and downstaging locoregional therapy as pretransplant treatment are increasing in number. Abstract Recently, there have been many reports of the usefulness of locoregional therapy such as transarterial chemoembolization and radiofrequency ablation for hepatocellular carcinoma (HCC) as pretreatment before liver transplantation (LT). Locoregional therapy is performed with curative intent in Japan, where living donor LT constitutes the majority of LT due to the critical shortage of deceased donors. However, in Western countries, where deceased donor LT is the main procedure, LT is indicated for early-stage HCC regardless of liver functional reserve, and locoregional therapy is used for bridging until transplantation to prevent drop-outs from the waiting list or for downstaging to treat patients with advanced HCC who initially exceed the criteria for LT. There are many reports of the effect of bridging and downstaging locoregional therapy before LT, and its indications and efficacy are becoming clear. Responses to locoregional therapy, such as changes in tumor markers, the avidity of FDG-PET, etc., are considered useful for successful bridging and downstaging. In this review, the effects of bridging and downstaging locoregional therapy as a pretransplant treatment on the results of transplantation are clarified, focusing on recent reports.
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Butcher DA, Brandis KJ, Wang H, Spannenburg L, Bridle KR, Crawford DH, Liang X. Long-term survival and postoperative complications of pre-liver transplantation transarterial chemoembolisation in hepatocellular carcinoma: A systematic review and meta-analysis. Eur J Surg Oncol 2021; 48:621-631. [PMID: 34774394 DOI: 10.1016/j.ejso.2021.09.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/20/2021] [Accepted: 09/21/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVES The aim of this meta-analysis was to conduct a contemporary systematic review of high quality non-randomised controlled trials to determine the effect of pre-liver transplantation (LT) transarterial chemoembolisation (TACE) on long-term survival and complications of hepatocellular carcinoma (HCC) patients. BACKGROUND TACE is used as a neoadjuvant therapy to mitigate waitlist drop-out for patients with HCC awaiting LT. Previous studies have conflicting conclusions on the effect of TACE on long-term survival and complications of HCC patients undergoing LT. METHODS CINAHL, Cochrane Controlled Register of Trials, Embase, PubMed, and Web of Science were systematically searched. Baseline characteristics included number of patients outside Milan criteria, tumour diameter, MELD score, and time on the waiting list. Primary outcomes included 3- and 5-year overall and disease-free survival. Secondary outcomes included tumour recurrence, 30-day postoperative mortality, and hepatic artery and biliary complications. RESULTS Twenty-one high-quality NRCTs representing 8242 patients were included. Tumour diameter was significantly larger in TACE patients (3.49 cm vs 3.15 cm, P = 0.02) and time on the waiting list was significantly longer in TACE patients (4.87 months vs 3.46 months, P = 0.05), while MELD score was significantly higher in non-TACE patients (10.81 vs 12.35, P = 0.005). All primary and secondary outcomes displayed non-significant differences. CONCLUSION Patients treated with TACE had similar survival and postoperative outcomes to non-TACE patients, however, they had worse prognostic features compared to non-TACE patients. These findings strongly support the current US and European clinical practice guidelines that neoadjuvant TACE can be used for patients with longer expected waiting list times (specifically >6 months). Randomised controlled trials would be needed to increase the quality of evidence.
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Affiliation(s)
- Daniel A Butcher
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Kelli J Brandis
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Haolu Wang
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia; The Prince Charles Hospital, Chermside, QLD, Australia
| | - Liam Spannenburg
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Kim R Bridle
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia
| | - Darrell Hg Crawford
- Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia
| | - Xiaowen Liang
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, 4102, Australia; Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia; Gallipoli Medical Research Institute, Greenslopes Private Hospital, Brisbane, QLD, Australia.
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12
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Piñero F, Tanno M, Aballay Soteras G, Tisi Baña M, Dirchwolf M, Fassio E, Ruf A, Mengarelli S, Borzi S, Fernández N, Ridruejo E, Descalzi V, Anders M, Mazzolini G, Reggiardo V, Marciano S, Perazzo F, Spina JC, McCormack L, Maraschio M, Lagues C, Gadano A, Villamil F, Silva M, Cairo F, Ameigeiras B. Argentinian clinical practice guideline for surveillance, diagnosis, staging and treatment of hepatocellular carcinoma. Ann Hepatol 2020; 19:546-569. [PMID: 32593747 DOI: 10.1016/j.aohep.2020.06.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 06/05/2020] [Accepted: 06/10/2020] [Indexed: 02/08/2023]
Abstract
The A.A.E.E.H has developed this guideline for the best care of patients with hepatocellular carcinoma (HCC) from Argentina. It was done from May 2018 to March 2020. Specific clinical research questions were systematically searched. The quality of evidence and level of recommendations were organized according to GRADE. HCC surveillance is strongly recommended with abdominal ultrasound (US) every six months in the population at risk for HCC (cirrhosis, hepatitis B or hepatitis C); it is suggested to add alpha-feto protein (AFP) levels in case of inexeperienced sonographers. Imaging diagnosis in patients at risk for HCC has high specificity and tumor biopsy is not mandatory. The Barcelona Clinic Liver Cancer algorithm is strongly recommended for HCC staging and treatment-decision processes. Liver resection is strongly recommended for patients without portal hypertension and preserved liver function. Composite models are suggested for liver transplant selection criteria. Therapies for HCC with robust clinical evidence include transarterial chemoembolization (TACE) and first to second line systemic treatment options (sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). Immunotherapy with nivolumab and pembrolizumab has failed to show statistical benefit but the novel combination of atezolizumab plus bevacizumab has recently shown survival benefit over sorafenib in frontline.
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Affiliation(s)
- Federico Piñero
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina.
| | - Mario Tanno
- Hospital Centenario de Rosario, Santa Fe, Argentina
| | | | - Matías Tisi Baña
- Internal Medicine and Epidemiology Department, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Andrés Ruf
- Hospital Privado de Rosario, Santa Fe, Argentina
| | | | - Silvia Borzi
- Instituto Rossi, La Plata, Buenos Aires, Argentina
| | | | - Ezequiel Ridruejo
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina; Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Ciudad de Buenos Aires, Argentina
| | | | | | - Guillermo Mazzolini
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | | | | | | | | | - Cecilia Lagues
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
| | | | | | - Marcelo Silva
- Hepatology and Liver Unit, Hospital Universitario Austral, School of Medicine, Austral University, B1629HJ Buenos Aires, Argentina
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13
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Vogeler M, Mohr I, Pfeiffenberger J, Sprengel SD, Klauss M, Teufel A, Chang DH, Springfeld C, Longerich T, Merle U, Mehrabi A, Weiss KH, Mieth M. Applicability of scoring systems predicting outcome of transarterial chemoembolization for hepatocellular carcinoma. J Cancer Res Clin Oncol 2020; 146:1033-1050. [PMID: 32107625 PMCID: PMC7085483 DOI: 10.1007/s00432-020-03135-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 01/20/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary. METHODS Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child-Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation. RESULTS In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child-Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002). CONCLUSIONS Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child-Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy.
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Affiliation(s)
- Marie Vogeler
- Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Isabelle Mohr
- Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Jan Pfeiffenberger
- Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | | | - Miriam Klauss
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Andreas Teufel
- Division of Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - De-Hua Chang
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Thomas Longerich
- Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Uta Merle
- Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Karl Heinz Weiss
- Internal Medicine IV, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany.
- Liver Cancer Center Heidelberg (LCCH), Heidelberg University Hospital, Heidelberg, Germany.
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14
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Cools KS, Moon AM, Burke LM, McGinty KA, Strassle PD, Gerber DA. Validation of the Liver Imaging Reporting and Data System Treatment Response Criteria After Thermal Ablation for Hepatocellular Carcinoma. Liver Transpl 2020; 26:203-214. [PMID: 31677319 PMCID: PMC6980979 DOI: 10.1002/lt.25673] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2018] [Accepted: 10/26/2019] [Indexed: 12/17/2022]
Abstract
Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.
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Affiliation(s)
- Katherine S. Cools
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Andrew M. Moon
- Division of Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Lauren M.B. Burke
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Katrina A. McGinty
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Paula D. Strassle
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Department of Epidemiology, University of North Carolina School of Public Health
| | - David A. Gerber
- Department of Surgery, University of North Carolina School of Medicine, Chapel Hill, NC,Lineberger Cancer Center, University of North Carolina, Chapel Hill, NC
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15
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Lee GC, Gamblin TC, Qadan M. Percutaneous Transcatheter Particle Therapies. CANCER REGIONAL THERAPY 2020:265-279. [DOI: 10.1007/978-3-030-28891-4_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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16
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Korean J Radiol 2019; 20:1042-1113. [PMID: 31270974 PMCID: PMC6609431 DOI: 10.3348/kjr.2019.0140] [Citation(s) in RCA: 191] [Impact Index Per Article: 31.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Accepted: 02/24/2019] [Indexed: 01/10/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology, and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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17
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Santopaolo F, Lenci I, Milana M, Manzia TM, Baiocchi L. Liver transplantation for hepatocellular carcinoma: Where do we stand? World J Gastroenterol 2019; 25:2591-2602. [PMID: 31210712 PMCID: PMC6558441 DOI: 10.3748/wjg.v25.i21.2591] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
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Affiliation(s)
- Francesco Santopaolo
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Ilaria Lenci
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Martina Milana
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Tommaso Maria Manzia
- Transplant Surgery Unit, Department of Surgery, Policlinico Universitario Tor Vergata, Rome 00133, Italy
| | - Leonardo Baiocchi
- Hepatology Unit, Department of Medicine, Policlinico Universitario Tor Vergata, Rome 00133, Italy
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18
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Schmitz S, Lurje G, Ulmer F, Andert A, Bruners P, Schulze-Hagen M, Neumann U, Schoening W. Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation. Hepatobiliary Pancreat Dis Int 2019; 18:228-236. [PMID: 30718181 DOI: 10.1016/j.hbpd.2019.01.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 01/15/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Liver transplantation remains the main curative treatment option for hepatocellular carcinoma (HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points (exceptional MELD, exMELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional (neoadjuvant) treatment (LRT) is used. For patients unlikely to timely receive an organ via primary allocation, "extended critera donor (ECD) organs" are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. METHODS Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42 (84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients (82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. RESULTS One- and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached (P = 0.487). LRT had no impact on overall survival (P = 0.629). Median waiting time was shorter if no LRT was performed (4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival (P = 0.663). CONCLUSIONS Patients with an expected waiting time to transplantation of >6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.
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Affiliation(s)
- Sophia Schmitz
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Georg Lurje
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Florian Ulmer
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Anne Andert
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
| | - Philipp Bruners
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Maximilian Schulze-Hagen
- Department of Diagnostic and Interventional Radiology, University Hospital of RWTH Aachen, Aachen, Germany
| | - Ulf Neumann
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Maastricht University Medical Center (MUMC), Maastricht, Netherlands
| | - Wenzel Schoening
- Department of General-, Visceral- and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany; Department of Surgery, Charité - University Medicine at Berlin, Germany.
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19
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2018 Korean Liver Cancer Association-National Cancer Center Korea Practice Guidelines for the Management of Hepatocellular Carcinoma. Gut Liver 2019; 13:227-299. [PMID: 31060120 PMCID: PMC6529163 DOI: 10.5009/gnl19024] [Citation(s) in RCA: 241] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infection is high in middle-aged and elderly patients. These practice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radiation oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions.
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20
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Brautigan DL, Gielata M, Heo J, Kubicka E, Wilkins LR. Selective toxicity of caffeic acid in hepatocellular carcinoma cells. Biochem Biophys Res Commun 2018; 505:612-617. [DOI: 10.1016/j.bbrc.2018.09.155] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 09/24/2018] [Indexed: 01/14/2023]
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21
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Werner JD, Frangakis C, Ruck JM, Hong K, Philosophe B, Cameron AM, Saberi B, Gurakar A, Georgiades C. Neoadjuvant Transarterial Chemoembolization Improves Survival After Liver Transplant in Patients With Hepatocellular Carcinoma. EXP CLIN TRANSPLANT 2018; 17:638-643. [PMID: 30251938 DOI: 10.6002/ect.2018.0017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Our aims were to determine whether transarterial chemoembolization before liver transplant for hepatocellular carcinoma improves posttransplant survival and whether patients downstaged by transarterial chemoembolization within Milan criteria have a posttransplant survival benefit. MATERIALS AND METHODS In this retrospective analysis of prospectively collected data, survival rates of 87 patients treated with and 68 patients not treated with transarterial chemoembolization before liver transplant were compared using 2-sample t tests and multivariate Cox regression. We also compared posttransplant survival of patients within Milan criteria versus those downstaged after transarterial chemoembolization. We controlled for disease severity by assessing, among other variables, tumor diameter before and at transplant and alpha-fetoprotein levels before transplant and transarterial chemoembolization. RESULTS Overall 1-, 3-, and 5-year survival rates were 84%, 71%, and 63%, respectively. These rates were 91%, 78%, and 73% for patients who received and 76%, 63%, and 54% for patients who did not receive transarterial chemoembolization. Hazard ratios were 0.56 for having versus not having transarterial chemoembolization (P = .04), 1.06 for total tumor diameter on explantation (P = .01), 1.5 for largest tumor > 3 cm (P = .15), and 2.9 for pretransplant alpha-fetoprotein > 659 ng/mL (P = .006). A higher end-stage liver disease score correlated with poorer overall survival (hazard ratio = 1.53; P < .001). Laboratory values, lipiodol uptake, imaging response, and downstaging into Milan criteria were not correlated with survival. CONCLUSIONS Patients with hepatocellular carcinoma who were treated with neoadjuvant transarterial chemoembolization had better survival rates posttransplant than those not treated with transarterial chemoembolization. A high pretransplant alpha-fetoprotein level was negatively correlated with survival. Patients downstaged to Milan criteria after transarterial chemoembolization fared equally well versus those who met Milan criteria initially. Pretreatment with transarterial chemoembolization was positively correlated with survival posttransplant, with patients having a 44% reduction in posttransplant mortality.
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Affiliation(s)
- John D Werner
- From the Division of Vascular and Interventional Radiology, Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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22
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A Model for Adaptive Decision Making of "Ablate-and-Wait" Versus Transplantation in Patients With Hepatocellular Carcinoma. J Clin Gastroenterol 2018; 52:655-661. [PMID: 29356782 DOI: 10.1097/mcg.0000000000000981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND/AIMS In patients with early-stage hepatocellular carcinoma (HCC), selection of candidates for liver transplantation (LT) requires refinement based on tumor biology to maximize the outcome. We aimed to prognosticate LT candidates with HCC using a risk prediction model for post-LT recurrence. PATIENTS AND METHODS A total of 197 consecutive patients were included who underwent LT for hepatitis B-related HCC within the Milan criteria. A risk prediction model was developed for post-LT recurrence using the Cox model and was internally validated. RESULTS Among those undergoing LT as their first HCC treatment (n=70, initial LT group), poor prognosis was associated with maximal tumor size and multinodularity. The remaining 127 patients (deferred LT group) received radiofrequency ablation (n=69) and/or transarterial chemoembolization (n=98) before LT. Multinodularity, maximal tumor size, posttransarterial chemoembolization progressive disease, baseline alpha-fetoprotein, and alpha-fetoprotein difference (between baseline and pre-LT) were incorporated into a risk prediction model for the deferred LT group, which was thereby stratified into low-risk (score<5), intermediate-risk, and high-risk (score≥8) subgroups. Recurrence-free survival was significantly different among the deferred LT prognostic subgroups (P<0.001). CONCLUSIONS This risk prediction model may help refinement of "ablate-and-wait" strategy for LT candidates by avoiding LT in those with either high risk score at baseline or increasing score under repeated locoregional therapies.
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23
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Dorcaratto D, Udupa V, Hogan NM, Brophy DP, McCann JW, Maguire D, Geoghegan J, Cantwell CP, Hoti E. Does neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization improve survival in patients undergoing liver transplant for hepatocellular carcinoma? Diagn Interv Radiol 2018; 23:441-447. [PMID: 29063856 DOI: 10.5152/dir.2017.17106] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE We aimed to compare the overall (OS) and disease-free survival (DFS) of patients undergoing orthotopic liver transplant (OLT) for hepatocellular carcinoma who did and did not have neoadjuvant doxorubicin drug-eluting bead transarterial chemoembolization (DEB-TACE). METHODS This is a retrospective study of 94 patients with HCC transplanted between 2000 and 2014 in a single tertiary center. Pre- and postoperative features, DFS and OS were compared between patients who received pre-OLT DEB-TACE (n=34, DEB-TACE group) and those who did not (n=60, non-TACE group). Radiologic and histologic response to neoadjuvant treatment as well as its complications were also studied. RESULTS There were no significant differences in post-transplantation DFS and OS rates between groups (5-year DFS: 70% in DEB-TACE group vs. 63% in non-TACE group, P = 0.454; 5-year OS: 70% in DEB-TACE group vs. 65% in non-TACE group, P = 0.532). The DEB-TACE group had longer OLT waiting time compared with the non-TACE group (110 vs. 72 days; P = 0.01). On univariate and multivariate analyses, alpha-fetoprotein (AFP) levels >500 ng/mL prior to OLT were associated with decreased OS and DFS regardless of neoadjuvant approach (hazard ratio of 6, P = 0.001 and 5.5, P = 0.002, respectively). CONCLUSION Patients who underwent neoadjuvant DEB-TACE and OLT for hepatocellular carcinoma had no statistically different OS or DFS at 3 and 5 years from patients undergoing OLT alone.
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Affiliation(s)
- Dimitri Dorcaratto
- Hepatobiliary and Liver Transplant Surgical Unit, St. Vincent's University Hospital, Elm Park, Dublin, Ireland.
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Nazzal M, Gadani S, Said A, Rice M, Okoye O, Taha A, Lentine KL. Liver targeted therapies for hepatocellular carcinoma prior to transplant: contemporary management strategies. GLOBAL SURGERY (LONDON) 2018; 4. [PMID: 29782618 DOI: 10.15761/gos.1000171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Hepatocellular carcinoma (HCC) is an aggressive neoplastic disease that has been rapidly increasing in incidence. It usually occurs in the background of liver disease, and cirrhosis. Definitive therapy requires surgical resection. However, in majority of cases surgical resection is not tolerated, especially in the presence of portal hypertension and cirrhosis. Orthotopic liver transplant (OLT) in well selected candidates has been accepted as a viable option. Due to a relative scarcity of donors compared to the number of listed recipients, long waiting times are anticipated. To prevent patients with HCC from dropping out from the transplant list due to progression of their disease, most centers utilize loco-regional therapies. These loco-regional therapies(LRT) include minimally invasive treatments like percutaneous thermal ablation, trans-arterial chemoembolization, trans-arterial radio-embolization or a combination thereof. The type of therapy or combination used is determined by the size and location of the HCC and Barcelona Clinic Liver Cancer (BCLC) classification. The data regarding the efficacy of LRT in reducing post-transplant recurrence or disease-free survival is limited. This article reviews the available therapies, their strengths, limitations, and current use in the management of patients with hepatocellular carcinoma awaiting transplant.
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Affiliation(s)
- Mustafa Nazzal
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Sameer Gadani
- Interventional Radiology, Department of Radiology, St. Louis University Hospital, USA
| | - Abdullah Said
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Mandy Rice
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Obi Okoye
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Ahmad Taha
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA
| | - Krista L Lentine
- Division of Abdominal Transplant Surgery, Department of General Surgery, St. Louis University Hospital, USA.,Division of Nephrology, Department of Medicine, St Louis University Hospital, USA
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25
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Tan CHN, Yu Y, Tan YRN, Lim BLK, Iyer SG, Madhavan K, Kow AWC. Bridging therapies to liver transplantation for hepatocellular carcinoma: A bridge to nowhere? Ann Hepatobiliary Pancreat Surg 2018. [PMID: 29536053 PMCID: PMC5845608 DOI: 10.14701/ahbps.2018.22.1.27] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Backgrounds/Aims Liver Transplantation (LT) is a recognized treatment for Hepatocellular Carcinoma (HCC). The role of Bridging Therapies (BT) remains controversial. Methods From January 2001 to October 2012, 192 patients were referred to the National University Hospital, Singapore for consideration of LT for HCC. Sixty-five patients (33.8%) were found suitable for transplant and were placed on the waitlist. Analysis was performed in these patients. Results The most common etiology of HCC was Hepatitis B (n=28, 43.1%). Thirty-six patients (55.4%) received BT. Seventeen patients (47.2%) received TACE only, while 10 patients (27.8%) received radiofrequency ablation (RFA) only. The remaining patients received a combination of transarterial chemoembolization (TACE) and RFA. Baseline tumor and patient characteristics were comparable between the two groups. The overall dropout rate was 44.4% and 31.0% in the BT and non-BT groups, respectively (p=0.269). The dropout rate due to disease progression beyond criteria was 6.9% (n=2) in the non-bridged group and 22.2% (n=8) in the bridged group (p=0.089). Thirty-nine patients (60%) underwent LT, of which all patients who underwent Living Donor LT did not receive BT (n=4, 21.1%, p=0.030). The median time to LT was 180 days (range, 20–558 days) in the non-BT group and 291 days (range, 17–844 days) in the BT group (p=0.214). There was no difference in survival or recurrence between the BT and non-BT groups (p=0.862). Conclusions BT does not influence the dropout rate or survival after LT but it should be considered in patients who are on the waitlist for more than 6 months.
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Affiliation(s)
- Chun Han Nigel Tan
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Yue Yu
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Yan Rui Nicholas Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Boon Leng Kieron Lim
- Department of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Shridhar Ganpathi Iyer
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Krishnakumar Madhavan
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Alfred Wei Chieh Kow
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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26
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Rubinstein MM, Kaubisch A, Kinkhabwala M, Reinus J, Liu Q, Chuy JW. Bridging therapy effectiveness in the treatment of hepatocellular carcinoma prior to orthotopic liver transplantation. J Gastrointest Oncol 2017; 8:1051-1055. [PMID: 29299366 DOI: 10.21037/jgo.2017.08.11] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Background Orthotopic liver transplantation (OLT) is the most effective treatment for hepatocellular carcinoma (HCC) in patients with underlying cirrhosis and portal hypertension. Availability of OLT is limited by donor-organ shortages, which increase patient waiting time until OLT. A variety of bridging therapies (BT) have been used to halt tumor progression in patients on the OLT waiting list. Despite complete radiologic responses following BT, viable tumor is often present in explants. Methods Treatment outcomes were evaluated in 50 patients who had a total of 125 BT for treatment of 93 nodules. Success of BT was assessed by radiologic response compared to histopathological examination of explanted livers. Results Pre-transplant treatments included: transcatheter arterial chemoembolization (TACE), alcohol ablation (ETOH), radiofrequency ablation (RFA), microwave ablation (MWA), selective internal radiation therapy (SIRT) and stereotactic body radiation therapy (SBRT). Fifty-nine (64%) nodules had a complete radiographic response to therapy; however, only 28 nodules (30%) had complete tumor necrosis (CTN) on explant examination. Ten nodules with CTN were treated with TACE alone. Seven of the 28 nodules with CTN were treated with TACE and RFA. Three of seven nodules treated with TACE and SIRT had CTN. Patients underwent a mean of 2.5 BTs. Six of 50 patients (12%) had no residual HCC in their explants. Five of those six patients (83%) had complete response (CR) on pre-transplant imaging. Conclusions Although favorable radiologic responses are seen following BT, viable HCC is seen in the majority of liver explants and radiographic imaging cannot always accurately predict pathological response. This underscores the need for aggressive treatment of patients who otherwise may not be eligible for OLT.
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Affiliation(s)
| | | | - Milan Kinkhabwala
- Montefiore-Einstein Center for Transplantation, Bronx, New York, USA
| | - John Reinus
- Montefiore-Einstein Center for Transplantation, Bronx, New York, USA
| | - Qiang Liu
- Montefiore Medical Center, Bronx, New York, USA
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Coletta M, Nicolini D, Benedetti Cacciaguerra A, Mazzocato S, Rossi R, Vivarelli M. Bridging patients with hepatocellular cancer waiting for liver transplant: all the patients are the same? Transl Gastroenterol Hepatol 2017; 2:78. [PMID: 29034351 PMCID: PMC5639014 DOI: 10.21037/tgh.2017.09.01] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Accepted: 08/28/2017] [Indexed: 12/13/2022] Open
Abstract
Liver transplant (LT) is considered the best curative treatment for patients with cirrhosis and hepatocellular carcinoma (HCC) within Milan criteria. The possibility to perform LT in HCC patients is limited by the liver grafts supply; indeed, the shortage of donors often leads to a long time on waiting list and then to dropout because of tumor progression. Bridging therapies are neo-adjuvant treatments given to patients on LT waitlist, with the aim to prevent tumor progression and to reduce dropout rate. Many bridging modalities have been proposed. The choice of each treatment is based on the characteristics of the patient, liver function, comorbidities and on the number, dimensions and localization of HCC. This review article describes several types of bridging therapies, focusing on the indications for different kind of patients.
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Affiliation(s)
- Martina Coletta
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Daniele Nicolini
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Andrea Benedetti Cacciaguerra
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Susanna Mazzocato
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Roberta Rossi
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
| | - Marco Vivarelli
- Hepato-biliary and Abdominal Transplantation Surgery, Department of Gastroenterology and Transplantation, Polytechnic University of Marche, A.O.U. "Ospedali Riuniti", Ancona, Italy
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28
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Györi GP, Felsenreich DM, Silberhumer GR, Soliman T, Berlakovich GA. Multimodality locoregional treatment strategies for bridging HCC patients before liver transplantation. Eur Surg 2017; 49:236-243. [PMID: 29104589 PMCID: PMC5653748 DOI: 10.1007/s10353-017-0487-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 07/24/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND It is current practice that patients with hepatocellular carcinoma (HCC) listed for liver transplantation should receive locoregional treatment if the suspected waiting time for transplantation is longer than 6 months, even in the absence of prospective randomized data. Aim of this study was the comparison of single versus multimodality locoregional treatment strategies on outcomes after liver transplantation. METHODS This is a retrospective analysis of 150 HCC patients listed for liver transplantation at our center between 2004 and 2011. Outcomes were analyzed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) in relation to intention-to-treat and overall survival after liver transplantation. RESULTS Overall, 92 patients (63%) were transplanted in this cohort. The intention-to-treat 1‑, 3‑, 5‑year waiting list survival was 80, 59, and 50% respectively. In RFA-(radiofrequency ablative) and TACE-(transarterial chemoembolisation)-based regimens, rates of transplanted patients were comparable (69 vs. 58%, p = ns). No difference was seen in overall survival after liver transplantation when comparing TACE- and RFA-based regimens. Patients receiving multimodality locoregional therapy had lower overall survival after transplantation (p = 0.05). CONCLUSION TACE- and RFA-based regimens showed equal outcomes in terms of transplantation rate, tumor response, and post-transplant survival. Patients in need of more than one treatment modality might identify a cohort with poorer post-transplant survival. POINTS OF NOVELTY Direct comparison of TACE and RFA in a multimodality setting, analysis according to mRECIST.
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Affiliation(s)
- Georg P. Györi
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - D. Moritz Felsenreich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gerd R. Silberhumer
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Thomas Soliman
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
| | - Gabriela A. Berlakovich
- Department of Surgery, Division of Transplantation, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria
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29
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Si T, Chen Y, Ma D, Gong X, Guan R, Shen B, Peng C. Transarterial chemoembolization prior to liver transplantation for patients with hepatocellular carcinoma: A meta-analysis. J Gastroenterol Hepatol 2017; 32:1286-1294. [PMID: 28085213 DOI: 10.1111/jgh.13727] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Revised: 12/28/2016] [Accepted: 01/08/2017] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIM A debate exists over whether using preoperative transarterial chemoembolization for patients with hepatocellular carcinoma before liver transplantation. Numerous studies have been investigating on this, but there is still no unanimous conclusion about the effect of preoperative transarterial chemoembolization. We conducted the meta-analysis of all available studies to systematically evaluate the influence of preoperative transarterial chemoembolization on liver transplant. METHODS A systematic search was performed by two authors (Si TF. and Guan RY.) through PubMed, Embase, Cochrane, and Science Citation Index Expanded, combined with Manual Retrieval and Cited Reference Search. The searching cut-off date was 2016/07/31, and all the data obtained were statistically analyzed using Review Manager version 5.1 software (Copenhagen, The Nordic Cochrane Center, The Cochrane Collaboration, 2011) recommended by Cochrane Collaboration. RESULTS The study showed that there was no difference between the experimental group and the control group on perioperative mortality (RR = 1.10, 95% confidence interval (CI) = [0.49-2.48], P = 0.82) or biliary complications (RR = 0.96, 95%CI = [0.66-1.39], P = 0.83). Preoperative transarterial chemoembolization had no obvious effect on improving overall survival (HR = 1.05, 95%CI = [0.65-1.72], P = 0. 83) but would result in a higher rate of vascular complications (RR = 2.01, 95%CI = [1.23-3.27], P = 0.005) and a reduction of disease free survival (HR = 1.66, 95%CI = [1.02-2.70], P = 0.04). Subgroup analysis also revealed that patients from transarterial chemoembolization group in Asia had a much lower overall survival rate (HR = 2.65, 95%CI = [1.49-4.71], P = 0.0009) compared with the control group. CONCLUSIONS Considering the possible adverse impacts on liver transplantation and the variation in sensitivity to transarterial chemoembolization, clinicians should be more cautious when considering transarterial chemoembolization as the bridging therapy for patients in the waiting list.
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Affiliation(s)
- Tengfei Si
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yongjun Chen
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Di Ma
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Xiaoyong Gong
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Ruoyu Guan
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Boyong Shen
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chenghong Peng
- Department of Hepatobiliary Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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30
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Treatment Options in Patients Awaiting Liver Transplantation with Hepatocellular Carcinoma and Cholangiocarcinoma. Clin Liver Dis 2017; 21:231-251. [PMID: 28364811 DOI: 10.1016/j.cld.2016.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver transplantation (LT) provides a good chance of cure for selected patients with hepatocellular carcinoma (HCC) and perihilar cholangiocarcinoma (pCCA). Patients with HCC on a waiting list for LT are at risk for tumor progression and dropout. Treatment of HCC with locoregional therapies may lessen dropout due to tumor progression. Strict selection and adherence to the LT criteria for patients with pCCA before and after neoadjuvant chemotherapy are critical for optimal outcome with LT. This article reviews the existing data for the various treatment strategies used for patients with HCC and pCCA awaiting LT.
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31
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Oligane HC, Xing M, Kim HS. Effect of Bridging Local-Regional Therapy on Recurrence of Hepatocellular Carcinoma and Survival after Orthotopic Liver Transplantation. Radiology 2017; 282:869-879. [DOI: 10.1148/radiol.2016160288] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Hayley C. Oligane
- From the Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pa (H.C.O., H.S.K.); Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 330 Cedar St, TE 2-224, New Haven, CT 06510 (M.X., H.S.K.); and Yale Cancer Center, New Haven, Conn (H.S.K.)
| | - Minzhi Xing
- From the Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pa (H.C.O., H.S.K.); Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 330 Cedar St, TE 2-224, New Haven, CT 06510 (M.X., H.S.K.); and Yale Cancer Center, New Haven, Conn (H.S.K.)
| | - Hyun S. Kim
- From the Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, Pa (H.C.O., H.S.K.); Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 330 Cedar St, TE 2-224, New Haven, CT 06510 (M.X., H.S.K.); and Yale Cancer Center, New Haven, Conn (H.S.K.)
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32
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Notarpaolo A, Layese R, Magistri P, Gambato M, Colledan M, Magini G, Miglioresi L, Vitale A, Vennarecci G, Ambrosio CD, Burra P, Di Benedetto F, Fagiuoli S, Colasanti M, Maria Ettorre G, Andreoli A, Cillo U, Laurent A, Katsahian S, Audureau E, Roudot-Thoraval F, Duvoux C. Validation of the AFP model as a predictor of HCC recurrence in patients with viral hepatitis-related cirrhosis who had received a liver transplant for HCC. J Hepatol 2017; 66:552-559. [PMID: 27899297 DOI: 10.1016/j.jhep.2016.10.038] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2015] [Revised: 09/16/2016] [Accepted: 10/31/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The AFP model was shown to be superior to the Milan criteria for predicting hepatocellular carcinoma (HCC) recurrence after liver transplantation in a French population. Our aim was to test the AFP model in a non-French, post-hepatitic cirrhosis-based population of HCC candidates. METHODS 574 patients transplanted for HCC in four Italian centers were studied. AFP score was assessed at the last evaluation before liver transplantation (LT). Probabilities of recurrence and survival were estimated by the log-rank test or competing risk analysis and compared according to the AFP model. RESULTS 24.7% patients were beyond Milan criteria. HCC complicated hepatitis C virus (HCV) and hepatitis B virus (HBV) cirrhosis in 58.7% and 24% of the cases, respectively. Five-year probabilities of recurrence differed according to AFP score ⩽2 vs. >2 in the whole population (13.2±1.8% vs. 49.8±8.7%, p<0.001, HR=4.98), in patients within Milan criteria (12.8±2.0% vs. 32.4±12.1%, p=0.009, HR=3.51), beyond Milan criteria (14.9±4.2% vs. 58.9±11.5%, p<0.001, HR=4.26), HCV patients (14.9±2.5% vs. 67.6±14.7%, p<0.001, HR=6.56) and HBV patients (11.6±3.4% vs. 34.3±12.5%, p=0.012, HR=3.49). By net reclassification improvement analysis AFP score significantly improved prediction of non-recurrence compared to Milan criteria. Overall five-year survival rates according to AFP score ⩽2 or >2 were 71.7±2.2% vs. 42.2±8.3% (p<0.001, HR=2.14). CONCLUSIONS The AFP model identifies HCC candidates at low risk of recurrence, otherwise excluded by Milan criteria in a population with a predominance of post-hepatitic-related HCC. The AFP score can be proposed for selection of HCC candidates in programs with a high proportion of viral/HCV-related cirrhosis. LAY SUMMARY Selection criteria for liver transplantation of patients affected with hepatocellular carcinoma (HCC) are based on the Milan criteria, which have been shown to be too restrictive, precluding access to liver transplantation for some patients who might be cured by this operation. Recently, a French group of researchers developed a new selection model called the AFP model, or AFP score, allowing some patients with HCC not meeting Milan criteria to be transplanted with excellent results. In the present work, the AFP score was tested in a population of non-French patients transplanted for HCC occurring mainly on post-hepatitic (HCV or HBV) cirrhosis. The results confirm that in this specific population, as in the original French population of patients, the AFP model better selects patients with HCC eligible for transplantation, compared to Milan criteria. We conclude that the AFP score, which has been officially adopted by the French organization for Organ Sharing for HCC patients, can also be implemented in countries with an important burden of HCC occurring on post-hepatitic cirrhosis.
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Affiliation(s)
- Andrea Notarpaolo
- Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Liver Transplant Unit- Department of Hepatology, Henri Mondor Hospital-APHP, University of Paris-Est, Creteil, France
| | - Richard Layese
- Department of Public Health & Biostatistics, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Paolo Magistri
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Department of General Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Michele Colledan
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Giulia Magini
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | | | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplant Unit, Padova University Hospital, Padova, Italy
| | - Giovanni Vennarecci
- Multiorgan Transplantation Program-General Surgery and Transplantation Unit, Ospedale San Camillo di Roma, Roma, Italy
| | | | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy
| | - Fabrizio Di Benedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Department of General Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Fagiuoli
- Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Marco Colasanti
- Multiorgan Transplantation Program-General Surgery and Transplantation Unit, Ospedale San Camillo di Roma, Roma, Italy
| | - Giuseppe Maria Ettorre
- Multiorgan Transplantation Program-General Surgery and Transplantation Unit, Ospedale San Camillo di Roma, Roma, Italy
| | | | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Padova University Hospital, Padova, Italy
| | - Alexis Laurent
- Liver Transplant Unit- Department of Hepatology, Henri Mondor Hospital-APHP, University of Paris-Est, Creteil, France
| | - Sandrine Katsahian
- Department of Public Health & Biostatistics, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Etienne Audureau
- Department of Public Health & Biostatistics, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Françoise Roudot-Thoraval
- Department of Public Health & Biostatistics, Henri Mondor Hospital, University of Paris-Est, Créteil, France
| | - Christophe Duvoux
- Liver Transplant Unit- Department of Hepatology, Henri Mondor Hospital-APHP, University of Paris-Est, Creteil, France.
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Jianyong L, Jinjing Z, Lunan Y, Jingqiang Z, Wentao W, Yong Z, Bo L, Tianfu W, Jiaying Y. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma. Sci Rep 2017; 7:41624. [PMID: 28155861 PMCID: PMC5290748 DOI: 10.1038/srep41624] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 12/22/2016] [Indexed: 02/06/2023] Open
Abstract
Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.
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Affiliation(s)
- Lei Jianyong
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China.,Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zhong Jinjing
- Department of Pathology, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yan Lunan
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zhu Jingqiang
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Wang Wentao
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Zeng Yong
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Li Bo
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Wen Tianfu
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
| | - Yang Jiaying
- Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, China
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Bridging locoregional therapy: Longitudinal trends and outcomes in patients with hepatocellular carcinoma. Transplant Rev (Orlando) 2017; 31:136-143. [PMID: 28214240 DOI: 10.1016/j.trre.2017.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 01/28/2017] [Indexed: 12/19/2022]
Abstract
The purpose of this article is to analyze longitudinal trends in locoregional therapy (LRT) use and review locoregional therapy's role in the management of hepatocellular carcinoma prior to orthotropic liver transplantation Porrett et al. (2006) . LRT has a role in both bridge to transplantation and downstaging of patients not initially meeting Milan or UCSF Criteria. Due to the lack of randomized controlled trials, no specific bridging LRT modality is recommended over another for treating patients on the waiting list, however each modality has unique and patient-specific advantages. Pre-transplant LRT use in the United States has increased dramatically over the last two decades with more than 50% of the currently listed patients receiving LRT Freeman et al. (2008) . Despite these national trends, significant differences in LRT utilization, referral patterns, recurrence rates and survival have been observed among UNOS regions, socioeconomic levels and races. The use of LRT as a biologic selection tool based on response to treatment has shown promising results in its ability to predict successful post-transplant outcomes.
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35
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Huang X, Lu S. Impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma: a meta-analysis. Scand J Gastroenterol 2017; 52:143-149. [PMID: 27623157 DOI: 10.1080/00365521.2016.1236396] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED Abstracts Objective: To evaluate the impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation for hepatocellular carcinoma (HCC). METHODS We searched medical literature databases to identify appropriate studies assessing the impact of preoperative locoregional therapy on recurrence and patient survival following liver transplantation from January 1962 to April 2014. Study inclusion criteria were the existence of a control group, a sufficiently long follow-up period and reporting of survival outcomes. We then performed a meta-analysis of these studies. RESULTS Our search identified 12 studies from among a possible 1105. A total of 1504 patients were included in our analysis. There was no significant heterogeneity among the studies. In the meta-analysis, preoperative locoregional therapy was not statistically significant in affecting five-year survival rates following liver transplantation (hazard ratio [HR] = 1.06; 95% confidence interval [CI] = 0.82-1.38). For patients meeting the Milan criteria, preoperative locoregional therapy did not affect survival rates following liver transplantation (HR =1.04, 95% CI =0.74-1.45). The recurrence-free survival rate also had no association with preoperative locoregional therapy (HR =1.02, 95% CI =0.70-1.50). CONCLUSION Our meta-analysis suggests that preoperative locoregional therapy has no impact on survival following liver transplantation for HCC.
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Affiliation(s)
- Xinli Huang
- a Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health , Nanjing , China
| | - Sen Lu
- a Center of Liver Transplantation, The First Affiliated Hospital of Nanjing Medical University, The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health , Nanjing , China
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36
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Xing M, Sakaria S, Dhanasekaran R, Parekh S, Spivey J, Knechtle SJ, Zhang D, Kim HS. Bridging Locoregional Therapy Prolongs Survival in Patients Listed for Liver Transplant with Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2016; 40:410-420. [PMID: 27900445 DOI: 10.1007/s00270-016-1505-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Accepted: 11/09/2016] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIMS To evaluate the long-term survival benefit of bridging locoregional therapy (LRT) prior to orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria. METHODS Our transplant center registry was studied for all HCC patients within the Milan criteria who were listed for OLT from 1998 to 2013. Baseline clinical characteristics and median overall survival (OS) were calculated and stratified by LRT, OLT status, and wait times. Survival analysis was conducted using Kaplan-Meier estimation and log-rank test. RESULTS Of 265 listed, 205 underwent OLT (mean follow-up 7.6 years). Of 205, 111 received bridging LRT (A), and 94 did not (B). Both were similar in demographics and tumor characteristics (p > 0.05). Median OS from HCC for A/B were 86.4 vs. 68.9 months (p = 0.01). Median OS from OLT for A/B were 74.6 vs. 63.6 months (p = 0.03). On multivariate analysis, independent predictors for survival from HCC were bridging LRT (p = 0.002) and high wait time (p = 0.008); independent predictors for survival from OLT were bridging LRT (p = 0.005) and high wait time (p = 0.005). Of 60 who were listed but did not undergo transplant, 44 received LRT (C) and 16 received best supportive care (D). Median OS from HCC for C/D were 37.1 vs. 24.8 months (p = 0.03). CONCLUSIONS Bridging LRT and high wait times were independent positive prognostic factors for survival from HCC diagnosis and OLT.
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Affiliation(s)
- Minzhi Xing
- Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, P.O. Box 208042, New Haven, CT, 06510, USA
| | - Sonali Sakaria
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Renumathy Dhanasekaran
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Samir Parekh
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - James Spivey
- Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Stuart J Knechtle
- Division of Transplant Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC, USA
| | - Di Zhang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
| | - Hyun S Kim
- Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, 333 Cedar Street, P.O. Box 208042, New Haven, CT, 06510, USA. .,Yale Cancer Center, New Haven, CT, USA.
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Xing M, Kim HS. Independent prognostic factors for posttransplant survival in hepatocellular carcinoma patients undergoing liver transplantation. Cancer Med 2016; 6:26-35. [PMID: 27860456 PMCID: PMC5269691 DOI: 10.1002/cam4.936] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 08/18/2016] [Accepted: 09/12/2016] [Indexed: 12/21/2022] Open
Abstract
The aim of this study was to investigate longitudinal trends in locoregional therapy (LRT) use in hepatocellular carcinoma (HCC) patients listed for transplant, and evaluate independent prognostic factors for overall survival (OS) in HCC patients undergoing orthotopic liver transplantation (OLT). The United Network for Organ Sharing (UNOS) database was used to identify HCC patients listed for liver transplantation from 1988 to 2014, and longitudinal rates of bridging LRT were calculated. OLT recipients listed from 2002 to 2013 and transplanted up to 2014, with ≥1 year of follow‐up were further analyzed. OS was compared between patients receiving bridging LRT versus none, high versus low wait times (HWT vs. LWT), and by geographic region. Bridging LRT use in the US has increased dramatically over 25 years, with more than 50% of listed patients receiving at least 1 LRT in 2014. Of 17,291 HCC patients listed for LT from 2002 to 2013, 14,511 received OLT, mean age 57.4 years, 76.8% male; 3889 received bridging LRT. Comparison groups were similar for gender, race, body mass index (BMI), HCC etiology, and biological MELD scores (P > 0.05). Significant differences in mean OS in regions with HWT/high LRT (122.4 months), HWT/low LRT (104.5 months), LWT/high LRT (104.2 months), and LWT/low LRT (102.3 months) were observed, P = 0.0006. Recipient age, donor age, bridging LRT, and longer wait times were independent prognostic factors of survival from OLT. Increasing longitudinal trends in bridging LRT for HCC patients were observed. Younger age, younger donor age, high wait times, and bridging LRT were significant independent prognostic factors for prolonged survival from transplant.
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Affiliation(s)
- Minzhi Xing
- Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Hyun S Kim
- Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut.,Yale Cancer Center, New Haven, Connecticut
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Strassburg CP. HCC-Associated Liver Transplantation - Where Are the Limits and What Are the New Regulations? Visc Med 2016; 32:263-271. [PMID: 27722163 DOI: 10.1159/000446385] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) represents an increasing health burden worldwide and a challenging disease both in terms of diagnosis and treatment. METHODS The literature available on PubMed for the period of 1990-2016 was reviewed with reference to liver allocation, HCC, liver transplantation (LT), and prediction, and the allocation rules of the German Transplant Act were reviewed. RESULTS Due to etiological and geographical diversity, HCC is not a homogeneous disease. In the vast majority of patients, HCC develops as a complication of chronic liver disease and cirrhosis. While most patients present with advanced HCC for which palliative strategies are the only available option, LT is the best treatment approach as it not only eliminates the diseased liver and the underlying hepatocarcinogenic mechanisms but also the cancer. The decision for LT is not an easy one to make, because outcome prediction, staging, bridging therapy, and recurrence prevention are difficult and are estimated against the background of the scarce resource of donor organs which are also competitively sought after by patients suffering from non-neoplastic terminal liver diseases, raising the issue of equality of chances in a rationed therapeutic modality. Currently, the Milan criteria are the best evaluated decision tool for LT, but many issues such as down-staging, favorable biological behavior during treatment, expansion of the morphological classification, molecular predictors, and individualized approaches are not yet satisfactorily addressed. CONCLUSION In order to provide a fair and effective approach to LT in HCC, the employed allocation rules require continuous development and scientific evaluation. Recently, the allocation rules for standard exception priority according to the German Transplant Act have been revised to improve patient selection for LT in HCC.
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Finkenstedt A, Vikoler A, Portenkirchner M, Mülleder K, Maglione M, Margreiter C, Moser P, Vogel W, Bale R, Freund M, Luger A, Tilg H, Petersen J, Schneeberger S, Graziadei I, Zoller H, Glodny B. Excellent post-transplant survival in patients with intermediate stage hepatocellular carcinoma responding to neoadjuvant therapy. Liver Int 2016; 36:688-95. [PMID: 26386273 DOI: 10.1111/liv.12966] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Current treatment guidelines preclude liver transplantation for patients with BCLC B (intermediate stage) HCC, and expanding transplantation criteria for selected patients beyond early stage HCC remains controversial. The aim of this study was to determine stage-dependent HCC recurrence and overall survival rates in transplant recipients and the impact of response to neoadjuvant treatment on outcome. METHODS The CT/MRI scans of patients who underwent liver transplantation for HCC at our transplant centre during a time period of 12 years were reviewed by two radiologists to assess tumour stage and response to neoadjuvant treatment according to mRECIST. RESULTS Of 174 HCC patients, 48 (28%) were BCLC intermediate stage. Neoadjuvant treatment was performed in 94% of patients. When patients were stratified according to tumour stage, no significant difference in overall survival was observed between very early or early and intermediate stage. When stratified according to treatment response, patients with complete response had a 5-year overall survival of 87%, which was significantly higher than in patients with progressive disease (62%, P = 0.02). HCC recurrence in intermediate stage patients without disease progression after neoadjuvant treatment was equal to that in patients with very early or early stage HCC. Tumour grading, histological and radiological evidence of vascular invasion, but not tumour stage were identified as independent risk factors for HCC recurrence. CONCLUSIONS Liver transplantation may be an option for selected patients with BCLC intermediate stage HCC and complete response after neoadjuvant treatment because of excellent long-term survival and low recurrence rates.
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Affiliation(s)
- Armin Finkenstedt
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Anja Vikoler
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | | | - Kerstin Mülleder
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Manuel Maglione
- Department of Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Christian Margreiter
- Department of Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Patrizia Moser
- Department of Pathology, Medical University Innsbruck, Innsbruck, Austria
| | - Wolfgang Vogel
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Reto Bale
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Martin Freund
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Anna Luger
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Herbert Tilg
- Department of Medicine I, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Johannes Petersen
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
| | - Stefan Schneeberger
- Department of Transplant Surgery, Medical University Innsbruck, Innsbruck, Austria
| | - Ivo Graziadei
- Department of Internal Medicine, Academic Teaching Hospital Hall in Tirol, Hall, Austria
| | - Heinz Zoller
- Department of Medicine II, Gastroenterology and Hepatology, Medical University of Innsbruck, Innsbruck, Austria
| | - Bernhard Glodny
- Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria
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She WH, Cheung TT. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation. Transl Gastroenterol Hepatol 2016; 1:34. [PMID: 28138601 DOI: 10.21037/tgh.2016.03.04] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 01/04/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common primary malignancy worldwide especially in the patients with the background of chronic liver disease. Liver transplantation (LT) is the only curative treatment effective for both malignancy as well as the cirrhosis and portal hypertension. Unfortunately, living donor is not always possible and the deceased graft is scarce. Neoadjuvant therapies, therefore, have been developed as a downstaging treatment to try to downstage the tumor within the transplant criteria, or as a bridging therapy to control the tumor growth in patients while waiting in the transplant list. This paper reviewed the common modalities used as bridging and downstaging therapies for patients suffering from HCC before undergoing LT.
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Affiliation(s)
- Wong Hoi She
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Tan To Cheung
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
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Forner A, Reig M, Varela M, Burrel M, Feliu J, Briceño J, Sastre J, Martí-Bonmati L, Llovet JM, Bilbao JI, Sangro B, Pardo F, Ayuso C, Bru C, Tabernero J, Bruix J. [Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH]. Med Clin (Barc) 2016; 146:511.e1-511.e22. [PMID: 26971984 DOI: 10.1016/j.medcli.2016.01.028] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2015] [Revised: 01/22/2016] [Accepted: 01/28/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.
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Affiliation(s)
- Alejandro Forner
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Reig
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España
| | - María Varela
- Sección de Hepatología, Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias (HUCA), Universidad de Oviedo, Oviedo, España
| | - Marta Burrel
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Jaime Feliu
- Servicio de Oncología Médica, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Sociedad Española de Oncología Médica, Madrid, España
| | - Javier Briceño
- Unidad de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Reina Sofía, Córdoba, España
| | - Javier Sastre
- Servicio de Oncología Médica, Hospital Clínico San Carlos, Madrid, España
| | - Luis Martí-Bonmati
- Departamento de Radiología, Hospital Universitario y Politécnico La Fe, Valencia, España
| | - Josep María Llovet
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, Estados Unidos
| | - José Ignacio Bilbao
- Unidad de Radiología Vascular e Intervencionista, Departamento de Radiodiagnóstico, Clínica Universidad de Navarra, Pamplona, España
| | - Bruno Sangro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España; Unidad de Hepatología, Departamento de Medicina Interna, Clínica Universidad de Navarra, Pamplona, España
| | - Fernando Pardo
- Servicio de Cirugía Hepatobliopancreática y Trasplante, Clínica Universidad de Navarra, Pamplona, España
| | - Carmen Ayuso
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Concepció Bru
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Radiodiagnóstico, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España
| | - Josep Tabernero
- Servicio de Oncología Médica, Hospital Universitario Vall d'Hebrón, Barcelona, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Bruix
- Unidad de Oncología Hepática (Barcelona Clinic Liver Cancer), Servicio de Hepatología, Hospital Clínic, Barcelona, IDIBAPS, Universidad de Barcelona, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), España.
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Fahrner R, Dondorf F, Ardelt M, Dittmar Y, Settmacher U, Rauchfuß F. Liver transplantation for hepatocellular carcinoma - factors influencing outcome and disease-free survival. World J Gastroenterol 2015; 21:12071-12082. [PMID: 26576092 PMCID: PMC4641125 DOI: 10.3748/wjg.v21.i42.12071] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 08/04/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide. Liver transplantation can be a curative treatment in selected patients. However, there are several factors that influence disease-free survival after transplantation. This review addresses the pre-, intra- and postoperative factors that influence the risk of tumor recurrence after liver transplantation.
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Sciarra A, Ronot M, Di Tommaso L, Raschioni C, Castera L, Belghiti J, Bedossa P, Vilgrain V, Roncalli M, Paradis V. TRIP: a pathological score for transarterial chemoembolization resistance individualized prediction in hepatocellular carcinoma. Liver Int 2015; 35:2466-73. [PMID: 25865109 DOI: 10.1111/liv.12844] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2015] [Accepted: 04/02/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Although potentially very useful in optimizing patient selection and follow-up, the individual response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is generally unpredictable. The aim of this study was to identify tissue predictors of tumour resistance to TACE for use in clinical practice on pretreatment biopsies. METHODS We investigated the association of residual tumour in post-TACE-resected HCC with pathological and immunophenotypical features, mainly related to hypoxia and angiogenesis. Comparison of tumour phenotype between post-TACE HCC and both paired pre-TACE biopsies and control TACE-untreated HCC was performed. Cases showing >50% residual tumour (RT) were defined as TACE-resistant. RESULTS A consecutive series of 108 HCC from 41 patients was studied. Overall, 45/108 (44%) HCC were classified as TACE-resistant. Among these, 32 (71%) and 40 (89%) showed diffuse CD34 vascular staining and negative VEGF staining respectively (p<0.05). The association of these two parameters in a weighted score (TRIP) was able to predict TACE resistance with 81% accuracy, 89% sensitivity and 59% specificity. The effectiveness of TRIP was validated in an independent series of 28 HCC biopsies from patients subsequently treated with TACE and for whom radiological follow-up was available. CONCLUSIONS This study demonstrates the potential value of pretreatment tumour biopsy as predictors of TACE resistance in HCC.
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Affiliation(s)
- Amedeo Sciarra
- Pathology Department, Humanitas clinical and Research Center and University of Milan School of Medicine, Milan, Italy
| | - Maxime Ronot
- Radiology Department, Beaujon Hospital, Clichy, 92110, France
| | - Luca Di Tommaso
- Pathology Department, Humanitas clinical and Research Center and University of Milan School of Medicine, Milan, Italy
| | - Carlotta Raschioni
- Pathology Department, Humanitas clinical and Research Center and University of Milan School of Medicine, Milan, Italy
| | - Laurent Castera
- Hepatology Department, Beaujon Hospital, Clichy, 92110, France
| | - Jacques Belghiti
- Liver Surgery and Transplantation Department, Beaujon Hospital, Clichy, 92110, France
| | - Pierre Bedossa
- Pathology Department, Beaujon Hospital, Clichy, 92110, France
| | | | - Massimo Roncalli
- Pathology Department, Humanitas clinical and Research Center and University of Milan School of Medicine, Milan, Italy
| | - Valérie Paradis
- Pathology Department, Beaujon Hospital, Clichy, 92110, France
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46
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Han K, Kim JH. Transarterial chemoembolization in hepatocellular carcinoma treatment: Barcelona clinic liver cancer staging system. World J Gastroenterol 2015; 21:10327-10335. [PMID: 26420959 PMCID: PMC4579879 DOI: 10.3748/wjg.v21.i36.10327] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 06/11/2015] [Accepted: 08/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the fifth most common cancer that predominantly occurs in liver cirrhosis patients, requires staging systems to design treatments. The barcelona clinic liver cancer staging system (BCLC) is the most commonly used HCC management guideline. For BCLC stage B (intermediate HCC), transarterial chemoembolization (TACE) is the standard treatment. Many studies support the use of TACE in early and advanced HCC patients. For BCLC stage 0 (very early HCC), TACE could be an alternative for patients unsuitable for radiofrequency ablation (RFA) or hepatic resection. In patients with BCLC stage A, TACE plus RFA provides better local tumor control than RFA alone. TACE can serve as bridge therapy for patients awaiting liver transplantation. For patients with BCLC B, TACE provides survival benefits compared with supportive care options. However, because of the substantial heterogeneity in the patient population with this stage, a better patient stratification system is needed to select the best candidates for TACE. Sorafenib represents the first line treatment in patients with BCLC C stage HCC. Sorafenib plus TACE has shown a demonstrable effect in delaying tumor progression. Additionally, TACE plus radiotherapy has yielded better survival in patients with HCC and portal venous thrombosis. Considering these observations together, TACE clearly has a critical role in the treatment of HCC as a stand-alone or combination therapy in each stage of HCC. Diverse treatment modalities should be used for patients with HCC and a better patient stratification system should be developed to select the best candidates for TACE.
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Yeh MM, Yeung RS, Apisarnthanarax S, Bhattacharya R, Cuevas C, Harris WP, Hon TLK, Padia SA, Park JO, Riggle KM, Daoud SS. Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience. World J Hepatol 2015; 7:1460-83. [PMID: 26085907 PMCID: PMC4462686 DOI: 10.4254/wjh.v7.i11.1460] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 04/03/2015] [Accepted: 04/27/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics.
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Affiliation(s)
- Matthew M Yeh
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Raymond S Yeung
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Smith Apisarnthanarax
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Renuka Bhattacharya
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Carlos Cuevas
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - William P Harris
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Tony Lim Kiat Hon
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Siddharth A Padia
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - James O Park
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Kevin M Riggle
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
| | - Sayed S Daoud
- Matthew M Yeh, Raymond S Yeung, Department of Pathology, University of Washington School of Medicine, Seattle, WA 99210, United States
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48
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2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma. Gut Liver 2015; 9:267-317. [PMID: 25918260 PMCID: PMC4413964 DOI: 10.5009/gnl14460] [Citation(s) in RCA: 101] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 03/09/2015] [Indexed: 12/23/2022] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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49
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2014 Korean Liver Cancer Study Group-National Cancer Center Korea practice guideline for the management of hepatocellular carcinoma. Korean J Radiol 2015; 16:465-522. [PMID: 25995680 PMCID: PMC4435981 DOI: 10.3348/kjr.2015.16.3.465] [Citation(s) in RCA: 143] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC.
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50
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Guerrero-Misas M, Rodríguez-Perálvarez M, De la Mata M. Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation. World J Hepatol 2015; 7:649-661. [PMID: 25866602 PMCID: PMC4388993 DOI: 10.4254/wjh.v7.i4.649] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2014] [Revised: 12/15/2014] [Accepted: 01/15/2015] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the only therapeutic option which allows to treat both, the hepatocellular carcinoma and the underlying liver disease. Indeed, liver transplantation is considered the standard of care for a subset of patients with cirrhosis and hepatocellular carcinoma. However, tumour recurrence rates are as high as 20%, and once the recurrence is established the therapeutic options are scarce and with little impact on prognosis. Strategies to minimize tumour recurrence and thus to improve outcome may be classified into 3 groups: (1) An adequate selection of candidates for liver transplantation by using the Milan criteria; (2) An optimized management within waiting list including prioritization of patients at high risk of tumour progression, and the implementation of bridging therapies, particularly when the expected length within the waiting list is longer than 6 mo; and (3) Tailored immunosuppression comprising reduced exposure to calcineurin inhibitors, particularly early after liver transplantation, and the addition of mammalian target of rapamycin inhibitors. In the present manuscript the available scientific evidence supporting these strategies is comprehensively reviewed, and future directions are provided for novel research approaches, which may contribute to the final target: to cure more patients with hepatocellular carcinoma and with an improved long term outcome.
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Affiliation(s)
- Marta Guerrero-Misas
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel Rodríguez-Perálvarez
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Marta Guerrero-Misas, Manuel Rodríguez-Perálvarez, Manuel De la Mata, Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Maimónides Institute of Biomedical Research of Córdoba, CIBERehd, 14004 Córdoba, Spain
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