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1
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Granata V, Fusco R, Setola SV, Borzacchiello A, Della Sala F, Rossi I, Ravo L, Albano D, Vanzulli A, Petrillo A, Izzo F. Treatments and cancer: implications for radiologists. Front Immunol 2025; 16:1564909. [PMID: 40308594 PMCID: PMC12040653 DOI: 10.3389/fimmu.2025.1564909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/24/2025] [Indexed: 05/02/2025] Open
Abstract
This review highlights the critical role of radiologists in personalized cancer treatment, focusing on the evaluation of treatment outcomes using imaging tools like Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound. Radiologists assess the effectiveness and complications of therapies such as chemotherapy, immunotherapy, and ablative treatments. Understanding treatment mechanisms and consistent imaging protocols are essential for accurate evaluation, especially in managing complex cases like liver cancer. Collaboration between radiologists and oncologists is key to optimizing patient outcomes through precise imaging assessments.
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Affiliation(s)
- Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale – IRCCS di Napoli, Naples, Italy
| | - Roberta Fusco
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale – IRCCS di Napoli, Naples, Italy
| | - Sergio Venanzio Setola
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale – IRCCS di Napoli, Naples, Italy
| | - Assunta Borzacchiello
- Institute of Polymers, Composites and Biomaterials, National Research Council (IPCB-CNR), Naples, Italy
| | - Francesca Della Sala
- Institute of Polymers, Composites and Biomaterials, National Research Council (IPCB-CNR), Naples, Italy
| | - Ivano Rossi
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale – IRCCS di Napoli, Naples, Italy
| | - Ludovica Ravo
- Division of Radiology, Università degli Studi di Napoli Federico II, Naples, Italy
| | - Domenico Albano
- Diagnostic and Interventional Radiology Unit, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Milano, Italy
| | - Angelo Vanzulli
- Department of Radiology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Antonella Petrillo
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale – IRCCS di Napoli, Naples, Italy
| | - Francesco Izzo
- Division of Epatobiliary Surgical Oncology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, Naples, Italy
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2
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Goodsell KE, Tao AJ, Park JO. Neoadjuvant therapy for hepatocellular carcinoma-priming precision innovations to transform HCC treatment. Front Surg 2025; 12:1531852. [PMID: 40115081 PMCID: PMC11922951 DOI: 10.3389/fsurg.2025.1531852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Accepted: 02/18/2025] [Indexed: 03/23/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is increasing in prevalence globally, and cure remains limited with non-operative treatment. Surgical intervention, through resection or transplantation, offers a potential for cure for select patients. However, many patients present with advanced or unresectable disease, and recurrence rates remain high. Recent advances in systemic therapies, particularly immune checkpoint inhibitors, have demonstrated promise in treating unresectable HCC and as adjuvant therapy. Evidence from adjuvant trials highlights the synergistic potential of combined liver-directed and systemic therapies. These findings have ignited growing interest in neoadjuvant therapy across various scenarios: (1) as a bridging strategy while awaiting transplantation, (2) for downstaging disease to enable transplantation, (3) for converting unresectable disease to a resectable state, or (4) as neoadjuvant treatment in operable cases. Early-stage trials of neoadjuvant therapy in resectable HCC have reported promising outcomes. To realize the potential of neoadjuvant treatment for HCC, thoughtfully designed, adequately powered, multi-center clinical trials are essential.
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Affiliation(s)
- Kristin E Goodsell
- Department of Surgery, University of Washington, Seattle, WA, United States
| | - Alice J Tao
- Department of Surgery, University of Washington, Seattle, WA, United States
| | - James O Park
- Department of Surgery, University of Washington, Seattle, WA, United States
- Department of Surgery, Mount Sinai Hospital, New York, NY, United States
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3
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Mohamed-Chairi MH, Vico-Arias AB, Zambudio-Carroll N, Villegas-Herrera MT, Villar-Del-Moral JM. Comparative analysis of patients transplanted due to hepatocellular carcinoma. Are there survival differences between those who meet the Milan criteria and those who exceed them? REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2025; 90:36-43. [PMID: 40254486 DOI: 10.1016/j.rgmxen.2024.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/05/2024] [Indexed: 04/22/2025]
Abstract
INTRODUCTION AND AIM The Milan criteria have been the subject of discussion in recent years due to their restrictive nature. Expansion of the criteria and the use of locoregional therapies to downstage patients and increase the number of transplant candidates have been proposed. Our study analyzed the results of patients that underwent transplant due to hepatocellular carcinoma, comparing those that met the Milan criteria and those that exceeded them. MATERIALS AND METHODS A retrospective, observational, single-center study was conducted on liver transplantations due to hepatocellular carcinoma, within the time frame of 2010-2021. Demographic and clinical variables, overall survival, and disease-free survival were analyzed. The Student's t test or Mann-Whitney U test were applied for the quantitative variables and the Fisher's exact test for the categorical variables. The survival function was estimated through the Kaplan-Meier method and the log-rank test was applied for comparing the groups. RESULTS Of the 96 transplanted patients, 78 met the Milan criteria and 18 exceeded them. Patients that did not meet the Milan criteria had a higher number of nodules (1.6 vs. 3.5 nodules; p = 0.000), larger main lesions (24.38 vs. 38.55 mm; p = 0.000), a higher bilobar hepatocellular carcinoma rate (21.79% vs. 72.22%, p = 0.000), and higher tumor burden. There were no significant differences regarding overall survival, but there was a lower rate of disease-free survival in the group exceeding the criteria. CONCLUSION Downstaged patients that received locoregional therapies had lower disease-free survival rates than patients that met the Milan criteria, but there were no significant differences regarding overall survival.
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Affiliation(s)
- M H Mohamed-Chairi
- Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain; Instituto de Investigación Biosanitaria IBS, Granada, Spain.
| | - A B Vico-Arias
- Unidad de Cirugía de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - N Zambudio-Carroll
- Unidad de Cirugía de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - M T Villegas-Herrera
- Unidad de Cirugía de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
| | - J M Villar-Del-Moral
- Instituto de Investigación Biosanitaria IBS, Granada, Spain; Unidad de Cirugía de Trasplante Hepático, Servicio de Cirugía General y del Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
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4
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Zhang X, Chen C, Wang Y, Xu J. Recurrence risk prediction models for hepatocellular carcinoma after liver transplantation. J Gastroenterol Hepatol 2024; 39:2272-2280. [PMID: 39113259 DOI: 10.1111/jgh.16693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 12/06/2024]
Abstract
Liver transplantation (LT) is an effective method for curing hepatocellular carcinoma (HCC). However postoperative tumor recurrence can lead to higher mortality rates. To select suitable candidates for LT, the Milan Criteria (MC) were first proposed based on tumor morphological characteristics. For those patients who meet the MC, the MC can effectively reduce the postoperative tumor recurrence rate and improve the prognosis of patients undergoing LT. It has always been internationally recognized as the gold standard for selecting candidates for LT, marking a milestone in the history of LT for HCC. However, its strict conditions exclude some HCC patients who could benefit from LT. Therefore, comprehension consideration criteria, including serum biomarkers, tumor histology, and other factor, have been continuously proposed in addition to tumor morphology. This article summaries the prediction model for HCC recurrence after LT from five aspects: tumor morphology, serum markers, histopathology, cellular inflammatory factors and downstaging treatment before transplantation. The aim is to assist clinicians in accurately assessing HCC status, selecting appropriate liver transplant candidates, maximize graft and patients' survival, and optimizing the utilization of social health resources.
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Affiliation(s)
- Xu Zhang
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Chi Chen
- Department of Statistics, School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Yan Wang
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jun Xu
- Hepatobiliary and Pancreatic Surgery and Liver Transplantation Center, First Hospital of Shanxi Medical University, Taiyuan, China
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5
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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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6
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Derbel H, Galletto Pregliasco A, Mulé S, Calderaro J, Zaarour Y, Saccenti L, Ghosn M, Reizine E, Blain M, Laurent A, Brustia R, Leroy V, Amaddeo G, Luciani A, Tacher V, Kobeiter H. Should Hypervascular Incidentalomas Detected on Per-Interventional Cone Beam Computed Tomography during Intra-Arterial Therapies for Hepatocellular Carcinoma Impact the Treatment Plan in Patients Waiting for Liver Transplantation? Cancers (Basel) 2024; 16:2333. [PMID: 39001395 PMCID: PMC11240509 DOI: 10.3390/cancers16132333] [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] [Received: 04/28/2024] [Revised: 06/22/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
BACKGROUND Current guidelines do not indicate any comprehensive management of hepatic hypervascular incidentalomas (HVIs) discovered in hepatocellular carcinoma (HCC) patients during intra-arterial therapies (IATs). This study aims to evaluate the prognostic value of HVIs detected on per-interventional cone beam computed tomography (CBCT) during IAT for HCC in patients waiting for liver transplantation (LT). MATERIAL AND METHODS In this retrospective single-institutional study, all liver-transplanted HCC patients between January 2014 and December 2018 who received transarterial chemoembolization (TACE) or radioembolization (TARE) before LT were included. The number of ≥10 mm HCCs diagnosed on contrast-enhanced pre-interventional imaging (PII) was compared with that detected on per-interventional CBCT with a nonparametric Wilcoxon test. The correlation between the presence of an HVI and histopathological criteria associated with poor prognosis (HPP) on liver explants was investigated using the chi-square test. Tumor recurrence (TR) and TR-related mortality were investigated using the chi-square test. Recurrence-free survival (RFS), TR-related survival (TRRS), and overall survival (OS) were assessed according to the presence of HVI using Kaplan-Meier analysis. RESULTS Among 63 included patients (average age: 59 ± 7 years, H/F = 50/13), 36 presented HVIs on per-interventional CBCT. The overall nodule detection rate of per-interventional CBCT was superior to that of PII (median at 3 [Q1:2, Q3:5] vs. 2 [Q1:1, Q3:3], respectively, p < 0.001). No significant correlation was shown between the presence of HVI and HPP (p = 0.34), TR (p = 0.095), and TR-related mortality (0.22). Kaplan-Meier analysis did not show a significant impact of the presence of HVI on RFS (p = 0.07), TRRS (0.48), or OS (p = 0.14). CONCLUSIONS These results may indicate that the treatment plan during IAT should not be impacted or modified in response to HVI detection.
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Affiliation(s)
- Haytham Derbel
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Athena Galletto Pregliasco
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
| | - Sébastien Mulé
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Julien Calderaro
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
- Laboratory of Pathology, Henri Mondor University Hospital, 94010 Creteil, France
| | - Youssef Zaarour
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
| | - Laetitia Saccenti
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Mario Ghosn
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Edouard Reizine
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Maxime Blain
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Alexis Laurent
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
- Department of Visceral Surgery, Henri Mondor University Hospital, 94010 Creteil, France
| | - Raffaele Brustia
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
- Department of Visceral Surgery, Henri Mondor University Hospital, 94010 Creteil, France
| | - Vincent Leroy
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
- Department of Hepatology, Henri Mondor University Hospital, 94010 Creteil, France
| | - Giuliana Amaddeo
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
- Department of Hepatology, Henri Mondor University Hospital, 94010 Creteil, France
| | - Alain Luciani
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Vania Tacher
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Institut Mondor de Recherche Biomédicale, Inserm U955, Team n° 18, 94010 Creteil, France
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
| | - Hicham Kobeiter
- Medical Imaging Department, Henri Mondor University Hospital, 51 Avenue du Marechal de Lattre de Tassigny, 94010 Creteil, France (H.K.)
- Faculty of Medicine, University of Paris Est Creteil, 94010 Creteil, France
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7
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Yalcin S, Lacin S, Kaseb AO, Peynircioğlu B, Cantasdemir M, Çil BE, Hurmuz P, Doğrul AB, Bozkurt MF, Abali H, Akhan O, Şimşek H, Sahin B, Aykan FN, Yücel İ, Tellioğlu G, Selçukbiricik F, Philip PA. A Post-International Gastrointestinal Cancers' Conference (IGICC) Position Statements. J Hepatocell Carcinoma 2024; 11:953-974. [PMID: 38832120 PMCID: PMC11144653 DOI: 10.2147/jhc.s449540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/14/2024] [Indexed: 06/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.
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Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Sahin Lacin
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Bora Peynircioğlu
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | | | - Barbaros Erhan Çil
- Department of Radiology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Pervin Hurmuz
- Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ahmet Bülent Doğrul
- Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Murat Fani Bozkurt
- Department of Nuclear Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Hüseyin Abali
- Department of Medical Oncology, Bahrain Oncology Center, Muharraq, Bahrain
| | - Okan Akhan
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Halis Şimşek
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Berksoy Sahin
- Department of Medical Oncology, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Faruk N Aykan
- Department of Medical Oncology, Istinye University Faculty of Medicine Bahçeşehir Liv Hospital, İstanbul, Turkey
| | - İdris Yücel
- Medicana International Hospital Samsun, Department of Medical Oncology, Samsun, Turkey
| | - Gürkan Tellioğlu
- Department of General Surgery, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Fatih Selçukbiricik
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Philip A Philip
- Department of Medicine, Division of Hematology-Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
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8
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Puri P, Malik S. Liver Transplantation: Contraindication and Ineligibility. J Clin Exp Hepatol 2023; 13:1116-1129. [PMID: 37975058 PMCID: PMC10643298 DOI: 10.1016/j.jceh.2023.04.005] [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: 01/24/2023] [Accepted: 04/14/2023] [Indexed: 11/19/2023] Open
Abstract
Liver transplantation (LT) is a life-saving therapeutic modality for patients with various advanced liver diseases. It is crucial to identify that the patient's illness is sufficiently advanced and unlikely to improve with medical management to justify the need for transplantation. At the same time, it is crucial to identify patients with comorbidities and far advanced disease that would result in an unacceptable outcome after LT. Specific care also is required before deciding on LT in the elderly, acute on chronic liver disease, patients with comorbidities, and hepatocellular carcinoma. Transplantation needs to be timed appropriately to avoid unnecessary LT and ensure that the decision is not left too late to avoid losing the patient without a transplant. Also, important is the decision as to when not to transplant. The current review explores some of these issues of contraindications and ineligibility for LT.
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, Fortis Escorts Hospital, New Delhi 110025, India
| | - Sarthak Malik
- Department of Gastroenterology, Manipal Hospital, Dwarka, New Delhi 110075, India
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9
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Pandrowala S, Patkar S, Goel M, Mirza D, Mathur SK. Surgical resection for large hepatocellular carcinoma and those beyond BCLC: systematic review with proposed management algorithm. Langenbecks Arch Surg 2023; 408:144. [PMID: 37041364 DOI: 10.1007/s00423-023-02881-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 04/02/2023] [Indexed: 04/13/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accounts for the sixth most common cancer and ranks third in mortality worldwide with inhomogeneity in terms of resection for advanced-stage disease. METHODS A systematic review of published literature using the PubMed, Medline, and Google Scholar databases from 1995 to 2020 was conducted to identify studies that reported outcomes of resection for solitary HCC > 10 cm, BCLC B/C, and multinodular HCC. Our aim was to assess overall survival for resection, identify poor prognostic factors, and to compare it to trans-arterial chemotherapy (TACE) where data was available. RESULTS Eighty-nine articles were included after a complete database search in the systematic review as per our predefined criteria. Analysis revealed a 5-year overall survival of 33.5% for resection of HCC > 10 cm, 41.7% for BCLC B, 23.3% for BCLC C, and 36.6% for multinodular HCC. Peri-operative mortality ranged from 0 to 6.9%. Studies comparing resection versus TACE for BCLC B/C had a survival of 40% versus 17%, respectively. CONCLUSION Our systematic review justifies hepatic resection wherever feasible for hepatocellular carcinomas > 10 cm, BCLC B, BCLC C, and multinodular tumors. In addition, we identified and proposed an algorithm with five poor prognostic criteria in this group of patients who may benefit from adjuvant TACE.
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Affiliation(s)
- Saneya Pandrowala
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Shraddha Patkar
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India
| | - Mahesh Goel
- Gastrointestinal and Hepato-Pancreato-Biliary Service, Department of Surgical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, India.
| | - Darius Mirza
- Hepato-Pancreato-Biliary and Transplant Surgery, University Hospital Birmingham and Birmingham Children's Hospital, Birmingham, UK
| | - S K Mathur
- Zen Digestive Disease Center, Zen Hospital, Mumbai, India
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10
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Wong JK, Lim HJ, Tam VC, Burak KW, Dawson LA, Chaudhury P, Abraham RJ, Meyers BM, Sapisochin G, Valenti D, Samimi S, Ramjeesingh R, Mujoomdar A, Martins I, Dixon E, Segedi M, Liu DM. Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada. Cancer Treat Rev 2023; 115:102526. [PMID: 36924644 DOI: 10.1016/j.ctrv.2023.102526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 03/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.
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Affiliation(s)
- Jason K Wong
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Howard J Lim
- BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | - Vincent C Tam
- Tom Baker Cancer Centre, University of Calgary, 1331 29 St NW, Calgary, AB T2N 4N2, Canada.
| | - Kelly W Burak
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Laura A Dawson
- Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G 2C1, Canada.
| | | | - Robert J Abraham
- Department of Diagnostic Radiology, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Brandon M Meyers
- Juravinski Cancer Centre, 699 Concession St, Hamilton, ON L8V 5C2, Canada.
| | | | - David Valenti
- McGill University, 845 Rue Sherbrooke O, Montréal, QC H3A 0G4, Canada.
| | - Setareh Samimi
- Hopital Sacre-Coeur de Montreal, University of Montreal, 5400 Boul Gouin O, Montréal, QC H4J 1C5, Canada.
| | - Ravi Ramjeesingh
- Department of Medicine, Dalhousie University, 6299 South St, Halifax, NS B3H 4R2, Canada.
| | - Amol Mujoomdar
- Western University, 1151 Richmond Street, London, ON N6A 5B9, Canada.
| | - Ilidio Martins
- Kaleidoscope Strategic, Inc. 1 King Street W, Suite 4800 - 117, Toronto, ON M5H 1A1, Canada.
| | - Elijah Dixon
- University of Calgary, 2500 University Dr NW, Calgary, AB T2N 1N4, Canada.
| | - Maja Segedi
- Department of Surgery, Vancouver General Hospital, Jim Pattison Pavilion, 899 W 12th Ave, Vancouver, BC V5Z 1M9, Canada.
| | - David M Liu
- School of Biomedical Engineering, University of British Columbia, 2329 West Mall Vancouver, BC V6T 1Z4, Canada.
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11
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Elkomos BE, Abdo M, Mamdouh R, Abdelaal A. Can living donor liver transplantation provide similar outcomes to deceased-donor liver transplantation for hepatocellular carcinoma? A systematic review and meta-analysis. Hepatol Int 2023; 17:18-37. [PMID: 36564609 PMCID: PMC9894961 DOI: 10.1007/s12072-022-10435-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 10/03/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND AIM A potential solution to the deceased organ shortage is to include live organ donations and to identify patients with lower rates of HCC recurrence to fairly allocate liver grafts. Our aims were to detect the long-term outcomes of LDLT versus DDLT for HCC and predictors of recurrence after transplantation. METHODS PubMed, Scopus, Web of Science, Cochrane library were searched for eligible studies from inception to July 2021 and a systematic review and meta-analysis were done. RESULTS 35 studies with a total of 7822 patients were included. The 1-, 3-, 4 year-OS showed trivial improvement for LDLT recipients. However, the two modalities had similar 5-, 6- and 10-year OS. A significant improvement in the ITT-OS was observed for LDLT recipients. Regarding the DFS and recurrence after transplantation, no significant difference was observed between LDLT and DDLT. In addition to that, the pooled hazard ratio of the included studies showed that Milan criteria, level of AFP, presence of vascular invasion, tumor differentiation were significant predictors of recurrence. CONCLUSION The cancer biology (not the graft type) is the most important determinant of recurrence and survival after LT. However, LDLT provided much better survival benefits to HCC patients especially in regions that suffer from low deceased organ availability.
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Affiliation(s)
| | - Mostafa Abdo
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Remon Mamdouh
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
| | - Amr Abdelaal
- General Surgery Department, Ain Shams University Hospital, Cairo, Egypt
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12
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Nak D, Küçük NÖ, Çelebioğlu EC, Bilgiç MS, Hayme S, Kır KM. The Role of 18F-FLT PET/CT in Assessing Early Response to Transarterial Radioembolization and Chemoembolization in Patients with Primary and Metastatic Liver Tumors. Mol Imaging Radionucl Ther 2022; 31:207-215. [PMID: 36268887 DOI: 10.4274/mirt.galenos.2022.85579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objectives Metastases and primary malignancies are common in the liver. Local ablative applications such as transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) provide minimally invasive and safe treatment in unresectable liver tumors. Early detection of response to treatment prevents unnecessary toxicity and cost in non-responder patients and provides an earlier use of other options that may be effective. This study aimed to identify the role of 18F-fluorothymidine (FLT) positron emission tomography/computed tomography (PET/CT) in the assessment of early response to TACE and TARE treatments in patients with unresectable primary and metastatic liver tumors. Methods This single-center study included 63 patients who underwent 18F-FLT PET/CT for response evaluation after TACE and TARE. After excluding 20 patients whose data were missing 43 TARE-receiving patients were analyzed. The compatibility of change in semi-quantitative values obtained from the 18F-FLT PET/CT images with the treatment responses detected in 18F-fluorodeoxyglucose PET/CT, CT, and MR images and survival was evaluated. Results There was no correlation between early metabolic, morphological response, and 18F-FLT uptake pattern, and change in standardized uptake values (SUV) which were ΔSUVmax, ΔSUVmean, ΔSUVpeak., ΔSUVmean, Δ SUVpeak values. There was no significant correlation between 18F-FLT uptake pattern, ΔSUVmax, ΔSUVmean, ΔSUVpeak, and overall survival, progression-free survival (PFS) for the target lobe PFS for the whole-body. The survival distributions for the patients with >30% change in Δ SUVmax and ΔSUVpeak values were statistically significantly longer than the patients with <30% change (p<0.009 and p<0.024, respectively). Conclusion There was significant longer PFS for target liver lobe in patients with more than 30% decrease in 18F-FLT SUVmax and SUVpeak of the liver lesion in primary and metastatic unresectable liver tumors undergoing TARE.
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Affiliation(s)
- Demet Nak
- Recep Tayyip Erdoğan Training and Research Hospital, Clinic of Nuclear Medicine, Rize, Turkey
| | - Nuriye Özlem Küçük
- Ankara University Faculty of Medicine, Department of Nuclear Medicine, Ankara, Turkey
| | - Emre Can Çelebioğlu
- Ankara University Faculty of Medicine, Department of Radiology, Ankara, Turkey
| | - Mehmet Sadık Bilgiç
- Ankara University Faculty of Medicine, Department of Radiology, Ankara, Turkey
| | - Serhat Hayme
- Erzincan Binali Yıldırım University, Department of Biostatistics and Medical Informatics, Erzincan, Turkey
| | - Kemal Metin Kır
- Ankara University Faculty of Medicine, Department of Nuclear Medicine, Ankara, Turkey
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13
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N-acetyl-galactosamine modified metal-organic frameworks to inhibit the growth and pulmonary metastasis of liver cancer stem cells through targeted chemotherapy and starvation therapy. Acta Biomater 2022; 151:588-599. [PMID: 36002126 DOI: 10.1016/j.actbio.2022.08.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/28/2022] [Accepted: 08/15/2022] [Indexed: 11/23/2022]
Abstract
Hepatocellular carcinoma (HCC) is a common high-mortality malignancy which still needs efficient treatments. HCC patients undergoing extrahepatic metastases are mostly with unsatisfactory prognosis. Therefore, specific attention has been paid to extrahepatic HCC metastasis. We integrated Sorafenib (Sor) and glucose oxidase (GOx) into a N-acetyl-galactosamine (GalNAc) modified zeolitic imidazolate framework (ZIF-8), designated as SG@GR-ZIF-8, for targeted bimodal therapies of chemotherapy and starvation therapy against HCC. The hepatic delivery of SG@GR-ZIF was mediated by the specific recognition of GalNAc residues with asialoglycoprotein (ASGPR) on the liver cell surface. Sor is a clinically approved anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. GOx can efficiently induce cell death and disturb malignant progression by suppressing glucose supply of cancer cells, which is highly associated with metabolic rewiring in metastasis. The nano-formulation exhibit significant anti-metastatic HCC activity against C5WN1 cells, a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In a subcutaneous C5WN1-tumor carrying mouse model, SG@GR-ZIF exhibits potent synergistic anti-tumor activity with a tumor inhibition rate of 89% and a prolonged survival status. The growth and pulmonary metastasis of HCC in an orthotopic mouse model of HCC was remarkably suppressed in SG@GR-ZIF treated group. The therapeutic strategy targeting energy supply combined with first-line treatment holds great promise for the future treatment of metastatic HCC. STATEMENT OF SIGNIFICANCE: : SG@GR-ZIF, a N-acetyl-galactosamine modified metal-organic framework carrying Sorafenib and glucose oxidase, was fabricated for treating metastatic hepatocellular carcinoma (HCC). Sorafenib is an anti-proliferation and anti-angiogenesis drug for advanced HCC treatment. Glucose oxidase blocks energy demand in HCC metastasis by depleting glucose. C5WN1 was used for therapeutic evaluations as a liver cancer stem cell-like cell line with tumorigenicity and pulmonary metastasis activity. In subcutaneous C5WN1-tumor bearing mice, SG@GR-ZIF exhibited a tumor inhibition rate of 89% and prolonged survival period. In orthotopic C5WN1-tumor carrying mice, the growth and pulmonary metastasis of hepatocarcinoma was remarkably suppressed by SG@GR-ZIF. Together, this study suggests the great potential of synergistic chemo/starvation therapy mediated by SG@GR-ZIF for treating metastatic HCC.
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14
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Garg T, Shrigiriwar A, Habibollahi P, Cristescu M, Liddell RP, Chapiro J, Inglis P, Camacho JC, Nezami N. Intraarterial Therapies for the Management of Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:cancers14143351. [PMID: 35884412 PMCID: PMC9322128 DOI: 10.3390/cancers14143351] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/11/2022] Open
Abstract
Image-guided locoregional therapies play a crucial role in the management of patients with hepatocellular carcinoma (HCC). Transarterial therapies consist of a group of catheter-based treatments where embolic agents are delivered directly into the tumor via their supplying arteries. Some of the transarterial therapies available include bland embolization (TAE), transarterial chemoembolization (TACE), drug-eluting beads-transarterial chemoembolization (DEB-TACE), selective internal radioembolization therapy (SIRT), and hepatic artery infusion (HAI). This article provides a review of pre-procedural, intra-procedural, and post-procedural aspects of each therapy, along with a review of the literature. Newer embolotherapy options and future directions are also briefly discussed.
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Affiliation(s)
- Tushar Garg
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Apurva Shrigiriwar
- Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA;
| | - Peiman Habibollahi
- Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Mircea Cristescu
- Vascular and Interventional Radiology Division, Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA;
| | - Robert P. Liddell
- Division of Vascular and Interventional Radiology, Russell H Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; (T.G.); (R.P.L.)
| | - Julius Chapiro
- Section of Vascular and Interventional Radiology, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Peter Inglis
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
| | - Juan C. Camacho
- Department of Clinical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA;
- Vascular and Interventional Radiology, Radiology Associates of Florida, Sarasota, FL 34239, USA
| | - Nariman Nezami
- Division of Vascular and Interventional Radiology, Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA;
- Experimental Therapeutics Program, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA
- Correspondence:
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15
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Ramtohul T, Vilgrain V, Soubrane O, Bouattour M, Luciani A, Kobeiter H, Mule S, Tacher V, Laurent A, Amaddeo G, Regnault H, Bulsei J, Nault JC, Nahon P, Durand-Zaleski I, Seror O. Impact of Extended Use of Ablation Techniques in Cirrhotic Patients with Hepatocellular Carcinoma: A Cost-Effectiveness Analysis. Cancers (Basel) 2022; 14:2634. [PMID: 35681618 PMCID: PMC9179352 DOI: 10.3390/cancers14112634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 05/22/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND To evaluate the cost-effectiveness of the extended use of ablation for the treatment of hepatocellular carcinoma (HCC) with cirrhosis in an expert ablation center when compared to the non-extended use of ablation in equivalent tertiary care centers. METHODS Consecutive cirrhotic patients with non-metastatic HCC, no prior treatment, and referred to three tertiary care centers between 2012 and 2016 were retrospectively identified. The Bondy group, including all of the patients treated at Jean Verdier Hospital, where the extended use of ablation is routinely performed, was compared to the standard of care (SOC) group, including all of the patients treated at the Beaujon and Mondor Hospitals, using propensity score matching. A cost-effectiveness analysis was carried out from the perspective of French health insurance using a Markov model on a lifetime horizon. RESULTS 532 patients were matched. The Bondy group led to incremental discounted lifetime effects of 0.8 life-years gained (LYG) (95% confidence interval: 0.4, 1.3) and a decrease in lifetime costs of EUR 7288 (USD 8016) (95% confidence interval: EUR 5730 [USD 6303], EUR 10,620 [USD 11,682]) per patient, compared with the SOC group, resulting in a dominant mean incremental cost-effectiveness ratio (ICER). A compliance with the Barcelona Clinic Liver Classification (BCLC) guidelines for earlier stage contributed to the greater part of the ICER. CONCLUSION The extended use of ablation in cirrhotic patients with HCC was more effective and less expensive than the non-extended use of the ablation strategy.
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Affiliation(s)
- Toulsie Ramtohul
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
- AP-HP, Department of Radiology, Jean Verdier Hospital, 93140 Bondy, France
| | - Valérie Vilgrain
- AP-HP, Department of Radiology, Beaujon Hospital, 92110 Clichy, France;
- INSERM U1149, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3, 75018 Paris, France
| | - Olivier Soubrane
- AP-HP, Department of HPB Surgery and Liver Transplantation, Beaujon Hospital, 92110 Clichy, France;
| | - Mohamed Bouattour
- AP-HP, Department of Digestive Oncology, Beaujon Hospital, 92110 Clichy, France;
| | - Alain Luciani
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Hicham Kobeiter
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Sébastien Mule
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Vania Tacher
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Radiology, Henri Mondor Hospital, 94000 Créteil, France;
| | - Alexis Laurent
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Liver Surgery, Henri Mondor Hospital, 94000 Créteil, France
| | - Giuliana Amaddeo
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Hepatology, Henri Mondor Hospital, 94000 Créteil, France
| | - Hélène Regnault
- INSERM IMRB Unit U 955, Equipe 18, 94010 Créteil, France; (A.L.); (S.M.); (V.T.); (A.L.); (G.A.); (H.R.)
- AP-HP, Department of Hepatology, Henri Mondor Hospital, 94000 Créteil, France
| | - Julie Bulsei
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
| | - Jean-Charles Nault
- AP-HP, Department of Hepatology, Jean Verdier Hospital, 93140 Bondy, France; (J.-C.N.); (P.N.)
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
| | - Pierre Nahon
- AP-HP, Department of Hepatology, Jean Verdier Hospital, 93140 Bondy, France; (J.-C.N.); (P.N.)
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
- French League Against Cancer, Education and Research in Health Medicine and Human Biology, University Paris 13, Sorbonne Paris Cité, 75005 Paris, France
| | - Isabelle Durand-Zaleski
- AP-HP, Health Economics Research Unit, 75004 Paris, France; (T.R.); (J.B.); (I.D.-Z.)
- ECEVE, UMRS 1123, French National Institute of Health and Medical Research, 75010 Paris, France
- AP-HP, Department of Public Health, Henri Mondor Hospital, 94000 Creteil, France
| | - Olivier Seror
- AP-HP, Department of Radiology, Jean Verdier Hospital, 93140 Bondy, France
- Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale, 75010 Paris, France
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16
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Núñez KG, Sandow T, Patel J, Hibino M, Fort D, Cohen AJ, Thevenot P. Hypoalbuminemia Is a Hepatocellular Carcinoma Independent Risk Factor for Tumor Progression in Low-Risk Bridge to Transplant Candidates. Cancers (Basel) 2022; 14:1684. [PMID: 35406456 PMCID: PMC8996921 DOI: 10.3390/cancers14071684] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/13/2022] [Accepted: 03/24/2022] [Indexed: 02/06/2023] Open
Abstract
Due to active hepatocellular carcinoma (HCC) surveillance, many patients are diagnosed with early-stage disease and are usually amendable to curative treatments. These patients lack poor prognostic factors associated with Milan Criteria and alpha fetoprotein (AFP) biomarker levels. There are currently limited strategies to assess prognosis in the patients who remain at risk of post-treatment HCC progression. In a cohort of liver transplant (LT) candidates with HCC, this study seeks to identify factors prior to liver-directed therapy (LDT) associated with time to progression (TTP). This is a retrospective analysis of prospectively collected data from LT candidates with recently diagnosed HCC and receiving LDT as a bridge to LT at three interventional oncology programs within a single system (n = 373). Demographics, clinical hepatology and serology, and factors related to HCC burden were extracted and analyzed for associations with TTP risk. Albumin level below the cohort median (3.4 g/dL) emerged as an independent risk factor for TTP controlling for AFP > 20 ng/mL as well as Milan, T-stage, and Barcelona Clinic Liver Cancer (BCLC) stage individually. In modality-specific subgroup survival analysis, albumin-based TTP stratification was restricted to patients receiving first cycle microwave ablation (p = 0.007). In n = 162 patients matching all low-risk criteria for Milan, T-stage, BCLC stage, and AFP, the effect of albumin < 3.4 g/dL remained significant for TTP (p = 0.004) with 2-year TTP rates of 68% (<3.4 g/dL) compared to 95% (≥3.4 g/dL). In optimal bridge to LT candidates with small HCC and low AFP biomarker levels, albumin level at treatment baseline provides an HCC-independent positive prognostic factor for risk of HCC progression prior to LT.
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Affiliation(s)
- Kelley G. Núñez
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Tyler Sandow
- Department of Radiology, Ochsner Health, New Orleans, LA 70121, USA;
| | - Jai Patel
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Mina Hibino
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
| | - Daniel Fort
- Center for Outcomes Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA;
| | - Ari J. Cohen
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
- Multi-Organ Transplant Institute, Ochsner Health, New Orleans, LA 70121, USA
- Faculty of Medicine, The University of Queensland, New Orleans, LA 70121, USA
| | - Paul Thevenot
- Institute of Translational Research, Ochsner Clinic Foundation, New Orleans, LA 70121, USA; (K.G.N.); (J.P.); (M.H.); (A.J.C.)
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17
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Biolato M, Galasso T, Marrone G, Miele L, Grieco A. Upper Limits of Downstaging for Hepatocellular Carcinoma in Liver Transplantation. Cancers (Basel) 2021; 13:6337. [PMID: 34944957 PMCID: PMC8699392 DOI: 10.3390/cancers13246337] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/07/2021] [Accepted: 12/13/2021] [Indexed: 11/30/2022] Open
Abstract
In Europe and the United States, approximately 1100 and 1800 liver transplantations, respectively, are performed every year for hepatocellular carcinoma (HCC), compared with an annual incidence of 65,000 and 39,000 new cases, respectively. Because of organ shortages, proper patient selection is crucial, especially for those exceeding the Milan criteria. Downstaging is the reduction of the HCC burden to meet the eligibility criteria for liver transplantation. Many techniques can be used in downstaging, including ablation, chemoembolisation, radioembolisation and systemic treatments, with a reported success rate of 60-70%. In recent years, an increasing number of patient responders to downstaging procedures has been included in the waitlist, generally with a comparable five-year post-transplant survival but with a higher probability of dropout than HCC patients within the Milan criteria. While the Milan criteria are generally accepted as the endpoint of downstaging, the upper limits of tumour burden for downstaging HCC for liver transplantation are controversial. Very challenging situations involve HCC patients with large nodules, macrovascular invasion or even extrahepatic metastasis at baseline who respond to increasingly more effective downstaging procedures and who aspire to be placed on the waitlist for transplantation. This narrative review analyses the most important evidence available on cohorts subjected to "extended" downstaging, including HCC patients over the up-to-seven criteria and over the University of California San Francisco downstaging criteria. We also address surrogate markers of biological aggressiveness, such as alpha-fetoprotein and the response stability to locoregional treatments, which are very useful in selecting responders to downstaging procedures for waitlisting inclusion.
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Affiliation(s)
- Marco Biolato
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Tiziano Galasso
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Luca Miele
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
| | - Antonio Grieco
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy; (M.B.); (G.M.); (L.M.)
- Institute of Internal Medicine, Catholic University of Sacred Hearth, 00168 Rome, Italy;
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18
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Alim A, Karataş C. Prognostic Factors of Liver Transplantation for HCC: Comparative Literature Review. J Gastrointest Cancer 2021; 52:1223-1231. [PMID: 34882291 DOI: 10.1007/s12029-021-00730-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE The aim of the review study is investigation of the prognostic factors of the liver transplantation for hepatocellular carcinoma. METHODS A literature review has been made, especially in countries where dominantly living donor liver transplantation is performed, such as Turkey. Liver transplantation from deceased donor and from living donor has been evaluated about as advantages and disadvantages, and their effects on prognosis have been compared. In addition, hepatocellular carcinoma series of Koç University Liver Transplantation center has been presented. RESULTS Liver transplantation is still the best treatment option with 5-year 50% survival rate for hepatocellular carcinoma even in patient who has locally advanced tumor. The patient's survival is not only an important issue but also the living donor's safety is controversial particularly when expectation of recipient's 5-year survival is below 50% due to donor complication. CONCLUSION Detailed preoperative examination, appropriate patient selection, and timing of surgery are seen the most important issues in liver transplant's patients with hepatocellular carcinoma.
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Affiliation(s)
- Altan Alim
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey.
| | - Cihan Karataş
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey
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19
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Schlögl M, Pak ES, Bansal AD, Schell JO, Ganai S, Kamal AH, Swetz KM, Maguire JM, Perrakis A, Warraich HJ, Jones CA. Top Ten Tips Palliative Care Clinicians Should Know About Prognostication in Critical Illness and Heart, Kidney, and Liver Diseases. J Palliat Med 2021; 24:1561-1567. [PMID: 34283924 DOI: 10.1089/jpm.2021.0330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Specialty palliative care (PC) clinicians are frequently asked to discuss prognosis with patients and their families. When conveying information about prognosis, PC clinicians need also to discuss the likelihood of prolonged hospitalization, cognitive and functional disabilities, and death. As PC moves further and further upstream, it is crucial that PC providers have a broad understanding of curative and palliative treatments for serious diseases and can collaborate in prognostication with specialists. In this article, we present 10 tips for PC clinicians to consider when caring and discussing prognosis for the seriously ill patients along with their caregivers and care teams. This is the second in a three-part series around prognostication in adult and pediatric PC.
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Affiliation(s)
- Mathias Schlögl
- Centre on Aging and Mobility, University Hospital Zurich and City Hospital Waid Zurich, Zurich, Switzerland.,University Clinic for Acute Geriatric Care, City Hospital Waid Zurich, Zurich, Switzerland
| | - Esther S Pak
- Advanced Heart Failure/Transplantation, Philadelphia VA Medical Center, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Amar D Bansal
- Section of Palliative Care and Medical Ethics, Department of General Medicine, Pittsburgh, Pennsylvania, USA.,Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, UPMC Health System, Pittsburgh, Pennsylvania, USA
| | - Jane O Schell
- Section of Palliative Care and Medical Ethics, Department of General Medicine, Pittsburgh, Pennsylvania, USA.,Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, UPMC Health System, Pittsburgh, Pennsylvania, USA
| | - Sabha Ganai
- Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Fargo, North Dakota, USA
| | - Arif H Kamal
- Duke Cancer Institute, Duke University, Durham, North Carolina, USA.,Duke Fuqua School of Business, Duke University, Durham, North Carolina, USA
| | - Keith M Swetz
- Center for Palliative and Supportive Care, Division of Gerontology, Geriatrics, and Palliative Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.,Department of Medicine, Division of Gerontology, Geriatrics and Palliative Care, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Jennifer M Maguire
- Division of Pulmonary and Critical Care Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Aristotelis Perrakis
- Department of General, Visceral, Vascular and Transplant Surgery, University Hospital Magdeburg, Magdeburg, Germany
| | - Haider J Warraich
- Department of Medicine, Brigham and Women's Hospital and Veterans Affairs Boston Healthcare System, Harvard Medical School, Boston, Massachusetts, USA
| | - Christopher A Jones
- Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
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20
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Kierans AS, Najjar M, Dutruel SP, Gavlin A, Chen C, Lee MJ, Askin G, Halazun KJ. Evaluation of the LI-RADS treatment response algorithm in hepatocellular carcinoma after trans-arterial chemoembolization. Clin Imaging 2021; 80:117-122. [PMID: 34303189 DOI: 10.1016/j.clinimag.2021.06.009] [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: 04/13/2021] [Revised: 05/26/2021] [Accepted: 06/08/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE To evaluate the diagnostic performance of LI-RADS treatment response algorithm (LR-TRA) and modified RECIST (mRECIST) for the detection of viable hepatocellular carcinoma (HCC) on MRI after trans-arterial chemoembolization (TACE). MATERIALS AND METHODS This retrospective study includes cirrhotic patients that underwent trans-arterial chemoembolization prior to liver transplantation from 2013 to 2017 with a pre- and post-treatment MRI available. Three blinded readers assigned a LR-TRA and mRECIST category to each lesion. Lesions on MRI and explant pathology were matched and characterized as complete (100% necrosis) or incomplete necrosis (≤99% necrosis). Diagnostic performance of LR-TRA and mRECIST were calculated with a generalized estimating equation. RESULTS A total of 52 patients with 71 lesions were included, 47 with incomplete and 24 with complete necrosis. In consensus, 45 lesions were categorized as LR-TR Nonviable, of which 62.2% (28/45) had incomplete and 37.8% (17/45) had complete necrosis. Six lesions were categorized as LR-TR Equivocal, of which 33.3% (2/6) had incomplete and 66.7% (4/6) had complete necrosis. Twenty lesions were categorized as LR-TR Viable of which 85.0% (17/20) had incomplete and 15.0% (3/20) had complete necrosis. The sensitivity of LR-TR Viable for detecting incompletely necrotic tumor when LR-TR Equivocal was considered as viable, in consensus was 40.4%; specificity 70.8%; accuracy 50.7%. The sensitivity of mRECIST for detecting incompletely necrotic tumor was 37.0%; specificity 79.2%; accuracy 51.4%. There was no significant difference in diagnostic performance between mRECIST and LR-TRA (p = 0.14-0.33). Agreement for LR-TRA category was moderate (k = 0.53 [95% CI: 0.45, 0.67]). CONCLUSION LI-RADS treatment response algorithm demonstrates high specificity and low to moderate sensitivity for the detection of viable HCC after TACE in a North American cirrhotic cohort, without significant difference in diagnostic performance between LR-TRA and mRECIST.
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Affiliation(s)
- Andrea S Kierans
- Weill Cornell Medical College, Department of Radiology, United States of America.
| | - Marc Najjar
- Columbia University Medical Center, Center for Liver Disease and Transplantation, Department of Surgery, United States of America
| | - Silvina P Dutruel
- Weill Cornell Medical College, Department of Radiology, United States of America
| | - Alexander Gavlin
- Weill Cornell Medical College, Department of Radiology, United States of America
| | - Christine Chen
- Weill Cornell Medical College, Department of Radiology, United States of America
| | - Michael J Lee
- Columbia University Medical Center, Department of Pathology, United States of America
| | - Gulce Askin
- Weill Cornell Medical College, Department of Population Health Sciences, United States of America
| | - Karim J Halazun
- Weill Cornell Medical College, Division of Liver Transplantation and Hepatobiliary Surgery, United States of America
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21
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da Fonseca L, Carrilho FJ. Expanding TACTICS trial into a different setting in hepatocellular carcinoma. Ann Hepatol 2021; 19:230-231. [PMID: 32139261 DOI: 10.1016/j.aohep.2020.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 02/04/2023]
Abstract
Systemic treatment for hepatocellular carcinoma (HCC) is recommended for patients with advanced stage and for those who progressed on locoregional modalities. The first agent approved for advanced HCC was sorafenib, and it remains one of the cornerstones of systemic treatment. In the past years, immunotherapy has shown promising results and has been incorporated into the treatment armamentarium. The rates of recurrence and progression after locoregional therapies are significant, what highlights the need to explore systemic agents for preventing or delaying these negative outcomes. Recently, sorafenib was shown to benefit patients with unresectable HCC under transarterial chemoembolization (TACE) by delaying tumor progression and prolonging time to vascular invasion and extrahepatic spread. Although this result was reported in patients with intermediate stage, it provides background to test the strategy of combining systemic treatment plus TACE as a bridge therapy to HCC patients awaiting liver transplantation, for which the risk of dropout due to tumor progression impairs the possibility of cure.
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Affiliation(s)
- Leonardo da Fonseca
- Sao Paulo Clínicas Liver Cancer Group - Hospital das Clínicas Complex, Instituto do Cancer do Estado de São Paulo, University of São Paulo School of Medicine, Brazil.
| | - Flair José Carrilho
- Sao Paulo Clínicas Liver Cancer Group - Hospital das Clínicas Complex, Instituto do Cancer do Estado de São Paulo, University of São Paulo School of Medicine, Brazil
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22
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Benson AB, D'Angelica MI, Abbott DE, Anaya DA, Anders R, Are C, Bachini M, Borad M, Brown D, Burgoyne A, Chahal P, Chang DT, Cloyd J, Covey AM, Glazer ES, Goyal L, Hawkins WG, Iyer R, Jacob R, Kelley RK, Kim R, Levine M, Palta M, Park JO, Raman S, Reddy S, Sahai V, Schefter T, Singh G, Stein S, Vauthey JN, Venook AP, Yopp A, McMillian NR, Hochstetler C, Darlow SD. Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2021; 19:541-565. [PMID: 34030131 DOI: 10.6004/jnccn.2021.0022] [Citation(s) in RCA: 545] [Impact Index Per Article: 136.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
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Affiliation(s)
- Al B Benson
- 1Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | | | | | | | - Robert Anders
- 5The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | | | - Prabhleen Chahal
- 11Case Comprehensive Cancer Center, University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | | | - Jordan Cloyd
- 13The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | - Evan S Glazer
- 14St. Jude Children's Research HospitalThe University of Tennessee Health Science Center
| | | | - William G Hawkins
- 16Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | - R Kate Kelley
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Robin Kim
- 20Huntsman Cancer Institute at the University of Utah
| | - Matthew Levine
- 21Abramson Cancer Center at the University of Pennsylvania
| | | | - James O Park
- 23Fred Hutchinson Cancer Research CenterSeattle Cancer Care Alliance
| | | | | | | | | | | | | | | | - Alan P Venook
- 19UCSF Helen Diller Family Comprehensive Cancer Center
| | - Adam Yopp
- 31UT Southwestern Simmons Comprehensive Cancer Center; and
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23
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Frankul L, Frenette C. Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy. J Clin Transl Hepatol 2021; 9:220-226. [PMID: 34007804 PMCID: PMC8111105 DOI: 10.14218/jcth.2020.00037] [Citation(s) in RCA: 6] [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: 04/30/2020] [Revised: 10/04/2020] [Accepted: 03/04/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.
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Affiliation(s)
| | - Catherine Frenette
- Correspondence to: Catherine Frenette, Scripps Center for Organ Transplant, Scripps Clinic/Green Hospital, 10666 N. Torrey Pines Rd N200, La Jolla, CA 92037, USA. ORCID: https://orcid.org/0000-0002-2245-8173 Tel: +1-858-554-4310, Fax: +1-858-554-3009, E-mail:
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24
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Impact of liver-directed therapy and non-therapy on the waiting time list of patient candidates for liver transplantation: retrospective survival analysis. Clin Exp Hepatol 2021; 6:304-312. [PMID: 33511277 PMCID: PMC7816629 DOI: 10.5114/ceh.2020.102175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/23/2020] [Indexed: 11/22/2022] Open
Abstract
Aim of the study To determine whether liver-directed therapies (LDT) and no therapy affect waiting list times for liver transplant candidates from a single center. Material and methods This retrospective study included patients > 12 years of age diagnosed with hepatocellular carcinoma between January 2014 and June 2019 and followed until the date of transplant, date of delisting, loss to follow-up, or date of death. Waiting list time and associated factors were analyzed using Kaplan-Meier and Cox proportional-hazards methods. Results A total of 181 patients met the selection criteria. The mean age was 60 years with standard deviation (SD) of 7.8 years. Sixty-six percent underwent transplant, and 64% were classified within the Milan criteria. Men had a lower median waiting list time than women (191 days vs. 236 days, p = 0.0093). The overall median survival time or time to transplant for 50% of the population was 218 days (95% CI: 195-235). Men displayed a 3.1-fold (95% CI: 1.5-6.2) higher probability of transplantation than women (p = 0.002). Patients who received no therapy had a 5-fold higher probability of undergoing transplantation than patients under arterial LDT (HR [95% CI]: 5 [1.2, 20], p = 0.02). Patients under combined LDT displayed a 70% reduced probability of transplantation compared to patients who received arterial LDTs (p = 0.0009). Conclusions LDT was associated with a prolonged stay on the transplant list, likely due to the presence of an aggressive liver tumor. However, LDTs allow the patient to remain active on the liver transplant list, increasing their chances of undergoing transplantation.
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25
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Role of Locoregional Therapies in Patients With Hepatocellular Cancer Awaiting Liver Transplantation. Am J Gastroenterol 2021; 116:57-67. [PMID: 33110015 DOI: 10.14309/ajg.0000000000000999] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/14/2020] [Indexed: 02/08/2023]
Abstract
Hepatocellular cancer (HCC) is the fifth most common cancer in the world and the third most common cause of cancer-related deaths. The United Network for Organ Sharing has its own staging criteria for organ allocation, which is a modification of tumor-node-metastasis staging of American Joint Committee on Cancer. For the purpose of clarity, United Network for Organ Sharing staging will be described as uT1, uT2 (Milan criteria), and uT3 (eligible for downstaging) in this review. For those with unresectable HCC or those with advanced liver disease and HCC but within the Milan criteria, liver transplantation is the treatment of choice. Because of prolonged waiting period on the liver transplant list in many parts of the world for deceased donor liver transplantation, there is a serious risk of dropout from the liver transplant list because of tumor progression. For those patients, locoregional therapies might need to be considered, and moreover, there is circumstantial evidence to suggest that tumor progression after locoregional therapies might be a surrogate marker of unfavorable tumor biology. There is no consensus on the role or type of locoregional therapies in the management of patients with uT1 and uT2 eligible for liver transplant and of those with lesions larger than uT2 but eligible for downstaging protocol (uT3 lesions). In this review, we examine the role of locoregional therapies in these patients stratified by staging and propose treatment options based on the current evidence of tumor progression rates while awaiting liver transplantation and tumor recurrence rates after liver transplantation.
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26
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Alqahtani SA, Sanai FM, Alolayan A, Abaalkhail F, Alsuhaibani H, Hassanain M, Alhazzani W, Alsuhaibani A, Algarni A, Forner A, Finn RS, Al-hamoudi WK. Saudi Association for the Study of Liver diseases and Transplantation practice guidelines on the diagnosis and management of hepatocellular carcinoma. Saudi J Gastroenterol 2020; 26:S1-S40. [PMID: 33078723 PMCID: PMC7768980 DOI: 10.4103/sjg.sjg_477_20] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 09/10/2020] [Indexed: 01/27/2023] Open
Affiliation(s)
- Saleh A. Alqahtani
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, United States
| | - Faisal M. Sanai
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Medicine, Gastroenterology Unit, King Abdulaziz Medical City, Jeddah, Saudi Arabia
| | - Ashwaq Alolayan
- Adult Medical Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Faisal Abaalkhail
- Department of Medicine, Gastroenterology Section, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- College of Medicine, Al Faisal University, Riyadh, Saudi Arabia
| | - Hamad Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mazen Hassanain
- Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States
| | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Abdullah Alsuhaibani
- Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdullah Algarni
- Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic Barcelona, IDIBAPS, CIBEREHD, University of Barcelona, Barcelona, Spain
| | - Richard S Finn
- Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California,United States
| | - Waleed K. Al-hamoudi
- Liver Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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27
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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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Server S, Sabet S, Bilgin R, Inan N, Yuzer Y, Tokat Y. Intravoxel Incoherent Motion Parameters for Assessing the Efficiency of Locoregional Bridging Treatments before Liver Transplantation. Transplant Proc 2019; 51:2391-2396. [PMID: 31474296 DOI: 10.1016/j.transproceed.2019.01.161] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 01/28/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To evaluate the diagnostic accuracy of Intravoxel Incoherent Motion (IVIM) parameters for assessment of tumor response after locoregional treatment (LRT) of hepatocellular carcinoma (HCC). METHODS Fifteen patients with HCC who had undergone LRTs (11 transarterial radioembolization, 4 transarterial chemoembolization) were included. In addition to routine upper abdominal magnetic resonance imaging sequences, IVIM with 16 different b values and conventional diffusion weighted imaging with 3 different b factors were obtained immediately before and 8 weeks after LRTs. Magnetic resonance imaging response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) and HCCs were categorized into 2 subgroups, responders and nonresponders. Quantitatively, the number of diffusion-changes were calculated with apparent diffusion coefficient (ADC) and IVIM parameters, including mean D (true diffusion coefficient), pseudo-diffusion coefficient associated with blood flow, and f (perfusion fraction) values. Subsequently, the pre- and post-treatment parameters were compared using the Mann-Whitney U test. RESULTS Considering all HCCs, a significant decrease was observed according to mRECIST criteria (-38.43 ± 16.49). The ADC and D values after LRTs were significantly higher than those of the preceding ones. The f values after LRTs were significantly lower than those of pre-treatment. In the responders group, ADC and D values were significantly increased and f values were significantly decreased after LRTs. No difference of statistical significance was achieved in the nonresponders group. CONCLUSIONS ADC values and IVIM parameters appear to reflect the response of LRTs as effectively as those of mRECIST. This promises new horizons in the management of pretransplant patients, especially in renal insufficiency clinical settings, owing to the elimination of contrast media administration.
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Affiliation(s)
- Sadık Server
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey.
| | - Soheil Sabet
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Refik Bilgin
- Department of Nuclear Medicine, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Nagihan Inan
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Yıldıray Yuzer
- Department of Liver Transplantation, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Yaman Tokat
- Department of Liver Transplantation, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
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Liver Grafts with Major Extended Donor Criteria May Expand the Organ Pool for Patients with Hepatocellular Carcinoma. J Clin Med 2019; 8:jcm8101692. [PMID: 31618968 PMCID: PMC6832253 DOI: 10.3390/jcm8101692] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 10/05/2019] [Indexed: 02/06/2023] Open
Abstract
The major extended donor criteria (maEDC; steatosis >40%, age >65 years, and cold ischemia time >14 h) influence graft and patient outcomes after liver transplantation. Despite organ shortages, maEDC organs are often considered unsuitable for transplantation. We investigated the outcomes of maEDC organ liver transplantation in patients with hepatocellular carcinoma (HCC). Two hundred and sixty-four HCC liver transplant patients were eligible for analysis. Risk factor analysis was performed for early allograft dysfunction; primary nonfunction; 30-day and 90-day graft failure; and 30-day, 90-day, and 1-year patient mortality. One-year graft survival was higher in recipients of no-maEDC grafts. One-year patient survival did not differ between the recipients of no-maEDC and maEDC organs. The univariate and multivariate analyses revealed no association between maEDC grafts and one-year patient mortality. Graft survival differed between the recipients of no-maEDC and maEDC organs after correcting for a laboratory model of end-stage liver disease (labMELD) score with a cut-off value of 20, but patient survival did not. Patient survival did not differ between recipients who did and did not meet the Milan criteria and who received grafts with and without maEDC. Instead of being discarded, maEDC grafts may expand the organ pool for patients with HCC without impairing patient survival or recurrence-free survival.
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Wilson GC, Geller DA. Evolving Surgical Options for Hepatocellular Carcinoma. Surg Oncol Clin N Am 2019; 28:645-661. [DOI: 10.1016/j.soc.2019.06.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Bale R, Schullian P, Eberle G, Putzer D, Zoller H, Schneeberger S, Manzl C, Moser P, Oberhuber G. Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers. Hepatology 2019; 70:840-850. [PMID: 30520063 PMCID: PMC6766867 DOI: 10.1002/hep.30406] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 11/25/2018] [Indexed: 12/23/2022]
Abstract
This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic RFA (SRFA). The median interval between the first SRFA and transplantation was 6.8 months (range, 0-71). The rate of residual vital tissue (RVT) could be assessed in 188 of 195 lesions in 96 of 97 patients by histological examination of the explanted livers using hematoxylin and eosin (H&E) and Tdt-mediated UTP nick-end labeling (TUNEL) stains. Histopathological results were compared with the findings of the last computed tomography (CT) imaging before liver transplantation (LT). Median number and size of treated tumors were 1 (range, 1-8) and 2.5 cm (range, 1-8). Complete radiological response was achieved in 186 of 188 nodules (98.9%) and 94 of 96 patients (97.9%) and complete pathological response in the explanted liver specimen in 183 of 188 nodules (97.3%) and 91 of 96 patients (94.8%), respectively. In lesions ≥3 cm, complete tumor cell death was achieved in 50 of 52 nodules (96.2%). Residual tumor did not correlate with tumor size (P = 0.5). Conclusion: Multiprobe SRFA with intraprocedural image fusion represents an efficient, minimally invasive therapy for HCC, even with tumor sizes larger than 3 cm, and without the need of a combination with additional treatments. The results seem to justify the additional efforts related to the stereotactic approach.
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Affiliation(s)
- Reto Bale
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Peter Schullian
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Gernot Eberle
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Daniel Putzer
- Department of Radiology, Section of Interventional Oncology ‐ Microinvasive TherapyMedical University InnsbruckInnsbruckAustria
| | - Heinz Zoller
- Departments of Medicine II Gastroenterology and HepatologyMedical University InnsbruckInnsbruckAustria
| | | | - Claudia Manzl
- PathologyMedical University InnsbruckInnsbruckAustria
| | - Patrizia Moser
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
| | - Georg Oberhuber
- INNPATH, Institute of Pathology, Tirol Kliniken InnsbruckInnsbruckAustria
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Gutin L, Yao F, Dodge JL, Grab J, Mehta N. Comparison of Liver Transplant Wait-List Outcomes Among Patients With Hepatocellular Carcinoma With Public vs Private Medical Insurance. JAMA Netw Open 2019; 2:e1910326. [PMID: 31469395 PMCID: PMC6724163 DOI: 10.1001/jamanetworkopen.2019.10326] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
IMPORTANCE There are well-documented racial/ethnic and socioeconomic disparities in access to health care among patients with hepatocellular carcinoma (HCC); however, there are little data on the association of insurance type with liver transplant (LT) wait-list outcomes for patients with HCC. OBJECTIVE To examine LT wait-list outcomes for patients with HCC and public insurance compared with patients with private insurance. DESIGN, SETTING, AND PARTICIPANTS This single-center cohort study included 705 adult patients with HCC who had Model for End-Stage Liver Disease exceptions and were included on a waiting list for LT from January 1, 2010, to December 31, 2016. Patients with Kaiser Permanente medical insurance, other private medical insurance, or public medical insurance were included. Data analysis was conducted from May 2018 to October 2018. MAIN OUTCOMES AND MEASURES The main outcome was cumulative incidence of LT waiting list dropout within 2 years of waiting list enrollment (baseline). Secondary outcomes included competing-risks analysis to identify risk factors associated with wait-list outcomes. RESULTS Among 705 patients (median [interquartile range] age, 61 [57-65] years; 537 [76.2%] men) with HCC on an LT waiting list, 349 patients (49.5%) had Kaiser Permanente insurance, 157 patients (22.3%) had other private insurance, and 199 patients (28.2%) had public insurance. Median (interquartile range) follow-up was 13.2 (7.8-18.7) months. Tumor characteristics were similar among insurance types. The cumulative incidence of dropout owing to tumor progression or death within 2 years of baseline was 21.8% (95% CI, 17.2%-26.7%) among the Kaiser Permanente insurance group, 25.5% (95% CI, 18.6%-33.0%) among the other private insurance group, and 35.5% (95% CI, 28.3%-42.7%) among the public insurance group (P < .001). The cumulative incidence of LT within 2 years of baseline was 67.3% (95% CI, 61.2%-72.6%) among the Kaiser Permanente insurance group, 64.1% (95% CI, 55.2%-71.7%) among the other private insurance group, and 48.5% (95% CI, 40.4%-56.1%) among the public insurance group (P < .001). In competing-risks multivariable analysis compared with patients with Kaiser Permanente insurance, patients with public insurance were associated with increased risk of dropout (hazard ratio [HR], 1.69 [95% CI, 1.17-2.43]; P = .005), but patients with other private insurance were not (HR, 1.40 [95% CI, 0.94-2.08]; P = .10). Waiting list dropout was also significantly associated with an α-fetoprotein level 100 ng/mL or higher (HR, 2.8 [95% CI, 1.98-3.88]; P < .001), Model for End-Stage Liver Disease score at baseline (HR per point, 1.06 [95% CI, 1.03-1.09]; P < .001), and 3 or more lesions at baseline (HR vs 1 lesion of 2- to 3-cm diameter, 2.07 [95% CI, 1.27-3.37]; P = .004). CONCLUSIONS AND RELEVANCE In this large cohort of patients with HCC on an LT waiting list, patients with public insurance were associated with worse wait-list outcomes compared with patients with Kaiser Permanente insurance or other private insurance, despite similar tumor-related characteristics at baseline. Improved health care coordination and delivery may be options to reduce these disparities.
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Affiliation(s)
- Liat Gutin
- Department of Medicine, University of California, San Francisco
| | - Francis Yao
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Joshua Grab
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco
| | - Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco
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Mehta N, Dodge JL, Hirose R, Roberts JP, Yao FY. Predictors of low risk for dropout from the liver transplant waiting list for hepatocellular carcinoma in long wait time regions: Implications for organ allocation. Am J Transplant 2019; 19:2210-2218. [PMID: 30861298 PMCID: PMC7072024 DOI: 10.1111/ajt.15353] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 02/24/2019] [Accepted: 02/28/2019] [Indexed: 01/25/2023]
Abstract
All patients with hepatocellular carcinoma meeting United Network for Organ Sharing T2 criteria currently receive the same listing priority for liver transplant (LT). A previous study from our center identified a subgroup with a very low risk of waitlist dropout who may not derive immediate LT benefit. To evaluate this issue at a national level, we analyzed within the United Network for Organ Sharing database 2052 patients with T2 hepatocellular carcinoma receiving priority listing from 2011 to 2014 in long wait time regions 1, 5, and 9. Probabilities of waitlist dropout were 18.3% at 1 year and 27% at 2 years. In multivariate analysis, factors associated with a lower risk of waitlist dropout included Model for End-Stage Liver Disease-Na < 15, Child's class A, single 2- to 3-cm lesion, and α-fetoprotein ≤20 ng/mL. The subgroup of 245 (11.9%) patients meeting these 4 criteria at LT listing had a 1-year probability of dropout of 5.5% vs 20% for all others (P < .001). On explant, the low dropout risk group was more likely to have complete tumor necrosis (35.5% vs 24.9%, P = .01) and less likely to exceed Milan criteria (9.9% vs 17.7%, P = .03). We identified a subgroup with a low risk of waitlist dropout who should not receive the same LT listing priority.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California
| | - Jennifer L. Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - John P. Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
| | - Francis Y. Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, California
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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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Subramanian V, Chapman W. Living Donor Liver Transplant for Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1594-1595. [PMID: 30937661 DOI: 10.1245/s10434-019-07250-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Vijay Subramanian
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA
| | - William Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO, USA.
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Titano J, Voutsinas N, Kim E. The Role of Radioembolization in Bridging and Downstaging Hepatocellular Carcinoma to Curative Therapy. Semin Nucl Med 2019; 49:189-196. [PMID: 30954184 DOI: 10.1053/j.semnuclmed.2019.01.003] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Radioembolization with yttrium-90 microspheres has a growing role in the interventional oncological management of patient's with hepatocellular carcinoma. Patients with Barcelona Clinic Liver Cancer early or intermediate hepatocellular carcinoma may be offered radioembolization in order to control tumor burden while awaiting a transplant organ-referred to as "bridging" a patient to transplantation-or to reduce tumor burden such that patients will subsequently meet criteria for curative therapies-known as "downstaging" a patient to eligible tumor characteristics. More specific applications of radioembolization have been developed over the past two decades. Radioembolization may be employed to perform a radiation "lobectomy" in order to induce regression of the treated segments and hypertrophy of the untreated liver lobe such that the future liver remnant is sizeable enough to sustain life following resection. Similarly, the concept of radiation "segmentectomy"-involving the more selective administration of yttrium-90 microspheres with the intention of treating tumor and leading to the regression of the treated segment over time-has been proposed as a potential curative application of radioembolization. These radioembolization applications combine to augment the treatment options available to hepatocellular carcinoma patients both within and beyond transplantation criteria.
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Affiliation(s)
- Joseph Titano
- Icahn School of Medicine at Mount Sinai, Department of Radiology, New York, NY
| | - Nicholas Voutsinas
- Icahn School of Medicine at Mount Sinai, Department of Radiology, New York, NY
| | - Edward Kim
- Icahn School of Medicine at Mount Sinai, Department of Radiology, New York, NY.
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Abstract
For patients with unresectable or medically inoperable hepatocellular carcinoma, there are many local and regional therapies available, including stereotactic body radiotherapy, radiofrequency ablation, and transcatheter embolic approaches. This article will describe these treatment options and review the current comparative literature, suggesting that stereotactic body radiotherapy provides similar or better tumor control and a favorable side effect profile.
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Affiliation(s)
- Yao Yu
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA
| | - Mary Feng
- Department of Radiation Oncology, University of California San Francisco, San Francisco, CA.
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Hass HG, Vogel U, Scheurlen M, Jobst J. Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays. Gut Liver 2018; 12:306-315. [PMID: 29271183 PMCID: PMC5945262 DOI: 10.5009/gnl17277] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 08/09/2017] [Accepted: 08/14/2017] [Indexed: 12/17/2022] Open
Abstract
Background/Aims The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed. Methods To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (AffymetrixU133A) were used. Overexpressed genes were checked for their potential use as new markers for discrimination and their expression values were validated by reverse transcription polymerase chain reaction and immunohistochemistry analyses. Results 695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p＜0.05, fold change >2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and nonmalignant liver tissues was established. A panel of 12 genes (e.g., HSP90β, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers. Conclusions A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.
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Affiliation(s)
- Holger G Hass
- Department of Internal Medicine, Oncology and Rehabilitation, Paracelsus Hospital, Scheidegg, Germany
| | - Ulrich Vogel
- Department of Pathology, University of Tübingen, Tübingen, Germany
| | - Michael Scheurlen
- Department of Gastroenterology, Oncology, Rheumatology, University of Würzburg, Würzburg, Germany
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Mehta N, Dodge JL, Hirose R, Roberts JP, Yao FY. Increasing Liver Transplantation Wait-List Dropout for Hepatocellular Carcinoma With Widening Geographical Disparities: Implications for Organ Allocation. Liver Transpl 2018; 24:1346-1356. [PMID: 30067889 PMCID: PMC6445639 DOI: 10.1002/lt.25317] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Revised: 06/25/2018] [Accepted: 07/24/2018] [Indexed: 12/22/2022]
Abstract
Given the increasing incidence of hepatocellular carcinoma (HCC) and regional variation in liver transplantation (LT) rates for HCC, we investigated temporal and geographic disparities in LT and wait-list dropout. LT candidates receiving Model for End-Stage Liver Disease (MELD) exception from 2005 to 2014 were identified from the United Network for Organ Sharing database (n = 14,320). Temporal differences were compared across 2 eras (2005-2009 and 2010-2014). Regional groups were defined based on median wait time as long-wait region (LWR; regions 1, 5, and 9), mid-wait region (MWR; regions 2, 4, 6, 7, and 8), and short-wait region (SWR; regions 3, 10, and 11). Fine and Gray competing risk regression estimated risk of wait-list dropout as hazard ratios (HRs). The cumulative probability of LT within 3 years was 70% in the LWR versus 81% in the MWR and 91% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, median time to LT increased by 6.0 months (5.6 to 11.6 months) in the LWR compared with 3.8 months (2.6 to 6.4 months) in the MWR and 1.3 months (1.0 to 2.3 months) in the SWR. The cumulative probability of dropout within 3 years was 24% in the LWR versus 16% in the MWR and 8% in the SWR (P < 0.001). From 2005-2009 to 2010-2014, the LWR also had the greatest increase in probability of dropout. Risk of dropout was increased in the LWR (HR, 3.5; P < 0.001) and the MWR (HR, 2.2; P < 0.001) compared with the SWR, and year of MELD exception 2010-2014 (HR, 1.9; P < 0.001) compared with 2005-2009. From 2005-2009 to 2010-2014, intention-to-treat 3-year survival decreased from 69% to 63% in the LWR (P < 0.001), 72% to 69% in the MWR (P = 0.008), and remained at 74% in the SWR (P = 0.48). In conclusion, we observed a significant increase in wait-list dropout in HCC patients in recent years that disproportionately impacted LWR patients. Widening geographical disparities call for changes in allocation policy as well as enhanced efforts at increasing organ donation and utilization.
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Affiliation(s)
- Neil Mehta
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Jennifer L. Dodge
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Ryutaro Hirose
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - John P. Roberts
- Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
| | - Francis Y. Yao
- Divisions of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA,Transplant Surgery, Department of Surgery, University of California, San Francisco, San Francisco, CA
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Lee HA, Cho EY, Kim TH, Lee Y, Suh SJ, Jung YK, Kim JH, An H, Seo YS, Kim DS, Yim HJ, Yeon JE, Byun KS, Um SH. Risk Factors for Dropout From the Liver Transplant Waiting List of Hepatocellular Carcinoma Patients Under Locoregional Treatment. Transplant Proc 2018; 50:3521-3526. [PMID: 30577230 DOI: 10.1016/j.transproceed.2018.08.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Accepted: 08/29/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.
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Affiliation(s)
- H A Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - E Y Cho
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - T H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S J Suh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Y K Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - J H Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - H An
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Y S Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - D-S Kim
- Department of Surgery, Korea University College of Medicine, Seoul, Korea
| | - H J Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
| | - J E Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - K S Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - S H Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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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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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: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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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Abstract
Liver-directed therapy is a critical component of treatment strategies for hepatocellular carcinoma. These therapies included percutaneous image-guided ablation, transarterial chemoembolization, and transarterial radioembolization, and are administered by interventional radiologists. Depending on the stage of disease, a particular treatment modality, or a combination thereof, is expected to be most efficacious in achieving the goals of treatment for a particular patient. This article seeks to review the various liver-directed treatment modalities for treatment of hepatocellular carcinoma, with attention to their efficacy and patient selection criteria.
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Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018; 67:358-380. [PMID: 28130846 DOI: 10.1002/hep.29086] [Citation(s) in RCA: 2979] [Impact Index Per Article: 425.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Accepted: 01/10/2017] [Indexed: 12/07/2022]
Affiliation(s)
- Julie K Heimbach
- Division of Transplant Surgery, William J. von Liebig Transplant Center, Mayo Clinic, Rochester, MN
| | - Laura M Kulik
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL
| | - Richard S Finn
- Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica Geffen School of Medicine at UCLA, Los Angeles, California
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California, San Diego
| | | | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Andrew X Zhu
- Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA
| | - M Hassan Murad
- Mayo Clinic Evidence-based Practice Center, Mayo Clinic, Rochester, MN
| | - Jorge A Marrero
- Digestive and Liver Diseases Division, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Kulik L, Heimbach JK, Zaiem F, Almasri J, Prokop LJ, Wang Z, Murad MH, Mohammed K. Therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta-analysis. Hepatology 2018; 67:381-400. [PMID: 28859222 DOI: 10.1002/hep.29485] [Citation(s) in RCA: 218] [Impact Index Per Article: 31.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 04/03/2017] [Accepted: 06/02/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Patients with hepatocellular carcinoma (HCC) who are listed for liver transplantation (LT) are often treated while on the waiting list with locoregional therapy (LRT), which is aimed at either preventing progression of HCC or reducing the measurable disease burden of HCC in order to receive increased allocation priority. We aimed to synthesize evidence regarding the effectiveness of LRT in the management of patients with HCC who were on the LT waitlist. We conducted a comprehensive search of multiple databases from 1996 to April 25, 2016, for studies that enrolled adults with cirrhosis awaiting LT and treated with bridging or down-staging therapies before LT. Therapies included transcatheter arterial chemoembolization, transarterial radioembolization, ablation, and radiotherapy. We included both comparative and noncomparative studies. There were no randomized controlled trials identified. For adults with T1 HCC and waiting for LT, there were only two nonrandomized comparative studies, both with a high risk of bias, which reported the outcome of interest. In one series, the rate of dropout from all causes at 6 months in T1 HCC patients who underwent LRT was 5.3%, while in the other series of T1 HCC patients who did not receive LRT, the dropout rate at median follow-up of 2.4 years and the progression rate to T2 HCC were 30% and 88%, respectively. For adults with T2 HCC awaiting LT, transplant with any bridging therapy showed a nonsignificant reduction in the risk of waitlist dropout due to progression (relative risk [RR], 0.32; 95% confidence interval [CI], 0.06-1.85; I2 = 0%) and of waitlist dropout from all causes (RR, 0.38; 95% CI, 0.060-2.370; I2 = 85.7%) compared to no therapy based on three comparative studies. The quality of evidence is very low due to high risk of bias, imprecision, and inconsistency. There were five comparative studies which reported on posttransplant survival rates and 10 comparative studies which reported on posttransplant recurrence, and there was no significant difference seen in either of these endpoints. For adults initially with stage T3 HCC who received LRT, there were three studies reporting on transplant with any down-staging therapy versus no downstaging, and this showed a significant increase in 1-year (two studies, RR, 1.11; 95% CI, 1.01-1.23) and 5-year (1 study, RR, 1.17; 95% CI, 1.03-1.32) post-LT survival rates for patients who received LRT. The quality of evidence is very low due to serious risk of bias and imprecision. CONCLUSION In patients with HCC listed for LT, the use of LRT is associated with a nonsignificant trend toward improved waitlist and posttransplant outcomes, though there is a high risk of selection bias in the available evidence. (Hepatology 2018;67:381-400).
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Affiliation(s)
- Laura Kulik
- Division of Gastroenterology and Hepatology, Northwestern School of Medicine, Chicago, IL
| | | | - Feras Zaiem
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Jehad Almasri
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Larry J Prokop
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Zhen Wang
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - M Hassan Murad
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Center, Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
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Habibollahi P, Shamchi SP, Tondon R, Ecker BL, Gade TP, Hunt S, Soulen MC, Furth EE, Levine MH, Nadolski G. Combination of Neoadjuvant Transcatheter Arterial Chemoembolization and Orthotopic Liver Transplantation for the Treatment of Cirrhotomimetic Hepatocellular Carcinoma. J Vasc Interv Radiol 2017; 29:237-243. [PMID: 29221923 DOI: 10.1016/j.jvir.2017.09.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 08/30/2017] [Accepted: 09/12/2017] [Indexed: 12/22/2022] Open
Abstract
PURPOSE To examine differences in outcome and response of cirrhotomimetic (CMM) hepatocellular carcinoma (HCC) to a combination of bridging transcatheter arterial chemoembolization and orthotopic liver transplantation (OLT) compared with non-CMM HCC. MATERIALS AND METHODS All patients with pathologically proven CMM HCC who underwent bridging transcatheter arterial chemoembolization before OLT between 2007 and 2013 (n = 23) were retrospectively compared with a control group of patients with pathologically proven non-CMM HCC (n = 46). RESULTS There were 29 tumors in the CMM HCC group and 64 tumors in the non-CMM group identified and treated. Objective response rate on MR imaging at 1 and 3 months after transcatheter arterial chemoembolization for CMM HCC tumors (including patients with complete and partial response) was 93.1% and 86.4% compared with 85.2% and 93.2% for non-CMM tumors without statistically significant difference (P = .54 and P = .09, respectively). Pathologic study of liver explants showed complete tumor necrosis in 62.3% of non-CMM tumors (38/61) compared with 10.3% of CMM tumors (3/29) (P < .0001). Overall 2-year survival after transcatheter arterial chemoembolization and OLT was significantly lower for patients with CMM HCC compared with patients non-CMM HCC (65.2% vs 87%, P = .03). Patients with CMM HCC with extranodular tumor extension involving > 50% of liver parenchyma had worse survival with mean 2-year survival of 402 days ± 102 vs 656 days ± 39 for the remaining patients with CMM HCC (P = .02). CONCLUSIONS Despite similar early imaging response rates, CMM HCC tumors had markedly lower rates of complete pathologic necrosis on liver explants and were associated with reduced survival after OLT compared with conventional HCCs.
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Affiliation(s)
- Peiman Habibollahi
- Penn Image Guided Interventions Laboratory, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104; Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Sara P Shamchi
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Rashmi Tondon
- Department of Pathology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Brett L Ecker
- Division of Transplant Surgery, Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Terence P Gade
- Penn Image Guided Interventions Laboratory, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Stephen Hunt
- Penn Image Guided Interventions Laboratory, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Michael C Soulen
- Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Emma E Furth
- Department of Pathology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Matthew H Levine
- Division of Transplant Surgery, Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104
| | - Gregory Nadolski
- Penn Image Guided Interventions Laboratory, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104; Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA, 19104.
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Mehta N, Dodge JL, Roberts JP, Hirose R, Yao FY. Misdiagnosis of hepatocellular carcinoma in patients receiving no local-regional therapy prior to liver transplant: An analysis of the Organ Procurement and Transplantation Network explant pathology form. Clin Transplant 2017; 31. [PMID: 28881064 DOI: 10.1111/ctr.13107] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2017] [Indexed: 12/13/2022]
Abstract
Patients with T1 hepatocellular carcinoma (HCC) are not eligible for Model for End Stage Liver Disease (MELD) exception for liver transplant (LT) in part due to a high rate of misdiagnosis (no HCC on explant). The likelihood of misdiagnosis for T2 HCC and factors associated with misdiagnosis are unknown. We analyzed the Organ Procurement and Transplantation Network database including 5664 adults who underwent LT from 2012 to 2015 with MELD exception for T2 HCC, and searched for no evidence of HCC in the explant pathology file. We focused on those (n = 324) receiving no local-regional therapy (LRT) to evaluate the probability of no HCC found in explant. Median waiting time was short at 1.7 months, and 35 (11%) had no HCC on explant. On multivariable logistic regression, factors associated with no HCC on explant were age <50 (OR: 17.3, P < .001), non-HCV (OR: 5.4, P = .001), and alpha-fetoprotein <10 (OR: 2.9, P = .04). Tumor size and number were not different between groups. The proportion of misdiagnosis did not change significantly after implementation of Liver Imaging Reporting and Data System (LI-RADS) for HCC diagnosis. CONCLUSION The rate of misdiagnosis was 11% among T2 HCC patients who underwent LT without receiving LRT prior to LT and did not change significantly after implementation of LI-RADS. More efforts are needed to eliminate unnecessary LT for patients without HCC.
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Affiliation(s)
- Neil Mehta
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Jennifer L Dodge
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, USA
| | - John P Roberts
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, USA
| | - Ryutaro Hirose
- Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, USA
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA.,Division of Transplant Surgery, Department of Surgery, University of California, San Francisco, CA, USA
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48
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Wait Time of Less Than 6 and Greater Than 18 Months Predicts Hepatocellular Carcinoma Recurrence After Liver Transplantation: Proposing a Wait Time "Sweet Spot". Transplantation 2017; 101:2071-2078. [PMID: 28353492 DOI: 10.1097/tp.0000000000001752] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes. METHODS This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012. RESULTS Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis. CONCLUSIONS This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.
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49
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Wedd JP. Model for end-stage liver disease exceptions: A common problem. Liver Transpl 2017; 23:1251-1252. [PMID: 28837747 DOI: 10.1002/lt.24857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 08/22/2017] [Indexed: 01/13/2023]
Affiliation(s)
- Joel P Wedd
- Department of Internal Medicine Division of Digestive Diseases, Section of Hepatology Emory Transplant Center Emory University, Atlanta, GA
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50
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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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