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Cillo U, Gringeri E, D'Amico FE, Lanari J, Furlanetto A, Vitale A. Hepatocellular carcinoma: Revising the surgical approach in light of the concept of multiparametric therapeutic hierarchy. Dig Liver Dis 2025; 57:809-818. [PMID: 39828438 DOI: 10.1016/j.dld.2024.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 11/20/2024] [Accepted: 12/02/2024] [Indexed: 01/22/2025]
Abstract
The clinical management of hepatocellular carcinoma (HCC) is strongly influenced by several prognostic factors, mainly tumor stage, patient's health, liver function and specific characteristics of each intervention. The interplay between these factors should be carefully evaluated by a multidisciplinary tumor board. To support this, the novel "multiparametric therapeutic hierarchy" (MTH) concept has been recently proposed. This review will present the main features of available surgical treatments for HCC (liver transplantation, liver resection, ablation). Strengths and weaknesses are reported in the light of clinical decision making and of treatment allocation, with a special focus on the collocation of each treatment in the MTH framework and on how MTH may be useful in supporting clinical decision. Sequential treatments and their role to allow further surgical treatments will also be analyzed.
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Affiliation(s)
- Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy.
| | - Enrico Gringeri
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Francesco Enrico D'Amico
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Jacopo Lanari
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Alessandro Furlanetto
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Liu H, Zhang W, Di M, Lee H, Shi L, Wang X, Xingyu Z, Powers CA, Sethi V, Li X, Xiao Y, Crane A, Kaltenmeier C, Alberola RB, Behari J, Duarte-Rojo A, Hughes D, Malik S, Jonassaint N, Geller D, Tohme S, Gunabushanam V, Tevar A, Cruz R, Hughes C, Dharmayan S, Ayloo S, Humar A, Molinari M. Survival benefit associated with liver transplantation for hepatocellular carcinoma based on tumor burden scores at listing. Hepatol Commun 2025; 9:e0619. [PMID: 39774957 PMCID: PMC11717502 DOI: 10.1097/hc9.0000000000000619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/16/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing. METHODS We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT. RESULTS This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001). CONCLUSIONS Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors.
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Affiliation(s)
- Hao Liu
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Wei Zhang
- Department of Mathematics and Statistics, the University of Arkansas at Little Rock, Little Rock, Arkansas, USA
| | - Mengyang Di
- Division of Hematology-Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle, Washington, USA
| | - Hang Lee
- Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Liuhua Shi
- Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA
| | - Xixi Wang
- Department of Mathematics and Statistics, the University of Arkansas at Little Rock, Little Rock, Arkansas, USA
| | - Zhang Xingyu
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Department of Biostatistics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Colin A. Powers
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Vrishketan Sethi
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona, USA
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Andrew Crane
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Christof Kaltenmeier
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Ramon Bataller Alberola
- Liver Unit, Hospital Clinic, Barcelona, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Jaideep Behari
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Andres Duarte-Rojo
- Department of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Dempsey Hughes
- Department of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Shahid Malik
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Naudia Jonassaint
- Division of Gastroenterology, Department of Medicine, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - David Geller
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Samer Tohme
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Vikraman Gunabushanam
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Amit Tevar
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Ruy Cruz
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Christopher Hughes
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Stalin Dharmayan
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Subhashini Ayloo
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
- Department of Surgery, Brown University, Providence, Rhode Island, USA
| | - Abhinav Humar
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
| | - Michele Molinari
- Division of Transplant, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
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Birgin E, Nebelung H, Abdelhadi S, Rink JS, Froelich MF, Hetjens S, Rahbari M, Téoule P, Rasbach E, Reissfelder C, Weitz J, Schoenberg SO, Riediger C, Plodeck V, Rahbari NN. Development and validation of a digital biopsy model to predict microvascular invasion in hepatocellular carcinoma. Front Oncol 2024; 14:1360936. [PMID: 39376989 PMCID: PMC11457731 DOI: 10.3389/fonc.2024.1360936] [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: 12/24/2023] [Accepted: 08/30/2024] [Indexed: 10/09/2024] Open
Abstract
Background Microvascular invasion is a major histopathological risk factor of postoperative recurrence in patients with hepatocellular carcinoma. This study aimed to develop and validate a digital biopsy model using imaging features to predict microvascular invasion before hepatectomy. Methods A total of 217 consecutive patients who underwent hepatectomy for resectable hepatocellular carcinoma were enrolled at two tertiary-care reference centers. An imaging-based digital biopsy model was developed and internally validated using logistic regression analysis with adjustments for age, sex, etiology of disease, size and number of lesions. Results Three imaging features, i.e., non-smoothness of lesion margin (OR = 16.40), ill-defined pseudocapsula (OR = 4.93), and persistence of intratumoral internal artery (OR = 10.50), were independently associated with microvascular invasion and incorporated into a prediction model. A scoring system with 0 - 3 points was established for the prediction model. Internal validation confirmed an excellent calibration of the model. A cutoff of 2 points indicates a high risk of microvascular invasion (area under the curve 0.87). The overall survival and recurrence-free survival stratified by the risk model was significantly shorter in patients with high risk features of microvascular invasion compared to those patients with low risk of microvascular invasion (overall survival: median 35 vs. 75 months, P = 0.027; recurrence-free survival: median 17 vs. 38 months, P < 0.001)). Conclusion A preoperative assessment of microvascular invasion by digital biopsy is reliable, easily applicable, and might facilitate personalized treatment strategies.
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Affiliation(s)
- Emrullah Birgin
- Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
| | - Heiner Nebelung
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Schaima Abdelhadi
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Johann S. Rink
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Matthias F. Froelich
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Svetlana Hetjens
- Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Mohammad Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Patrick Téoule
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Erik Rasbach
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany
| | - Jürgen Weitz
- Department of Visceral-, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Stefan O. Schoenberg
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Carina Riediger
- Department of Visceral-, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Verena Plodeck
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Nuh N. Rahbari
- Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
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Giannini EG, Pasta A, Pieri G, Plaz Torres MC, Marseglia M, Pelizzaro F, Sangiovanni A, Cabibbo G, Ghittoni G, Di Marco M, Foschi FG, Guarino M, Biasini E, Saitta C, Campani C, Svegliati-Baroni G, Gasbarrini A, Brunetto MR, Magalotti D, Azzaroli F, Mega A, Sacco R, Nardone G, Sacerdoti D, Masotto A, Vidili G, Bucci L, Vitale A, Trevisani F. Characteristics and outcome of anti-hepatitis D virus positive patients with hepatocellular carcinoma. Liver Int 2024; 44:1588-1599. [PMID: 38426262 DOI: 10.1111/liv.15855] [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] [Revised: 12/20/2023] [Accepted: 01/07/2024] [Indexed: 03/02/2024]
Abstract
BACKGROUND & AIMS Chronic hepatitis D virus (HDV) often leads to end-stage liver disease and hepatocellular carcinoma (HCC). Comprehensive data pertaining to large populations with HDV and HCC are missing, therefore we sought to assess the characteristics, management, and outcome of these patients, comparing them to patients with hepatitis B virus (HBV) infection. METHODS We analysed the Italian Liver Cancer database focusing on patients with positivity for HBV surface antigen and anti-HDV antibodies (HBV/HDV, n = 107) and patients with HBV infection alone (n = 588). Clinical and oncological characteristics, treatment, and survival were compared in the two groups. RESULTS Patients with HBV/HDV had worse liver function [Model for End-stage Liver Disease score: 11 vs. 9, p < .0001; Child-Turcotte-Pugh score: 7 vs. 5, p < .0001] than patients with HBV. HCC was more frequently diagnosed during surveillance (72.9% vs. 52.4%, p = .0002), and the oncological stage was more frequently Milan-in (67.3% vs. 52.7%, p = .005) in patients with HBV/HDV. Liver transplantation was more frequently performed in HBV/HDV than in HBV patients (36.4% vs. 9.5%), while the opposite was observed for resection (8.4% vs. 20.1%, p < .0001), and in a competing risk analysis, HBV/HDV patients had a higher probability of receiving transplantation, independently of liver function and oncological stage. A trend towards longer survival was observed in patients with HBV/HDV (50.4 vs. 44.4 months, p = .106). CONCLUSIONS In patients with HBV/HDV, HCC is diagnosed more frequently during surveillance, resulting in a less advanced cancer stage in patients with more deranged liver function than HBV alone. Patients with HBV/HDV have a heightened benefit from liver transplantation, positively influencing survival.
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Affiliation(s)
- Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Giulia Pieri
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Mariarosaria Marseglia
- Division of Internal Medicine, Hepatobiliary Diseases and Immunoallergology, University of Bologna, Bologna, Italy
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padua, Padua, Italy
| | - Angelo Sangiovanni
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale maggiore Policlinico and C.R.C. "A.M. & A. Migliavacca Center for Liver Disease", Milan, Italy
| | - Giuseppe Cabibbo
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | | | | | | | - Maria Guarino
- Department of Clinical Medicine and Surgery, Diseases of the Liver and Biliary System Unit, University of Naples "Federico II", Naples, Italy
| | - Elisabetta Biasini
- Infectious Diseases and Hepatology Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Carlo Saitta
- Department of Clinical and Experimental Medicine, Clinical and Molecular Hepatology Unit, University of Messina, Messina, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, Internal Medicine and Hepatology Unit, University of Florence, Florence, Italy
| | | | - Antonio Gasbarrini
- Liver Unit, CEMAD - Centro Malattie dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Maurizia Rossana Brunetto
- Department of Clinical and Experimental Medicine, Hepatology and Liver Physiopathology Laboratory, University Hospital of Pisa, Pisa, Italy
| | - Donatella Magalotti
- Division of Internal Medicine, Neurovascular and Hepatometabolic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Azzaroli
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Andrea Mega
- Gastroenterology Unit, Bolzano Regional Hospital, Bolzano, Italy
| | - Rodolfo Sacco
- Gastroenterology and Digestive Endoscopy Unit, Foggia University Hospital, Foggia, Italy
| | - Gerardo Nardone
- Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Naples "Federico II", Naples, Italy
| | - David Sacerdoti
- Liver Unit, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Gianpaolo Vidili
- Department of Medical, Surgical and Experimental Sciences, Clinica Medica Unit, University of Sassari, Azienda Ospedaliero-Universitaria di Sassari, Sassari, Italy
| | - Laura Bucci
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna, Bologna, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Franco Trevisani
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Unit of Semeiotics, Liver and Alcohol-related Diseases, University of Bologna, Bologna, Italy
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Du YN, Zhao JW. GDF15: Immunomodulatory Role in Hepatocellular Carcinoma Pathogenesis and Therapeutic Implications. J Hepatocell Carcinoma 2024; 11:1171-1183. [PMID: 38911292 PMCID: PMC11193986 DOI: 10.2147/jhc.s471239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 06/07/2024] [Indexed: 06/25/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally and the sixth most common cancer worldwide. Evidence shows that growth differentiation factor 15 (GDF15) contributes to hepatocarcinogenesis through various mechanisms. This paper reviews the latest insights into the role of GDF15 in the development of HCC, its role in the immune microenvironment of HCC, and its molecular mechanisms in metabolic dysfunction associated steatohepatitis (MASH) and metabolic associated fatty liver disease (MAFLD)-related HCC. Additionally, as a serum biomarker for HCC, diagnostic and prognostic value of GDF15 for HCC is summarized. The article elaborates on the immunological effects of GDF15, elucidating its effects on hepatic stellate cells (HSCs), liver fibrosis, as well as its role in HCC metastasis and tumor angiogenesis, and its interactions with anticancer drugs. Based on the impact of GDF15 on the immune response in HCC, future research should identify its signaling pathways, affected immune cells, and tumor microenvironment interactions. Clinical studies correlating GDF15 levels with patient outcomes can aid personalized treatment. Additionally, exploring GDF15-targeted therapies with immunotherapies could improve anti-tumor responses and patient outcomes.
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Affiliation(s)
- Yi-Ning Du
- Department of Medical Sciences, Li Ka-shing School of Medicine, University of Hong Kong, Hong Kong, People’s Republic of China
| | - Jin-Wei Zhao
- Department of Hepatopancreatobiliary Surgery, Second Hospital of Jilin University, Jilin University, Changchun, Jilin Province, People’s Republic of China
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7
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Bonacini M. Delta virus infection and hepatocellular carcinoma. Liver Int 2024; 44:1106-1107. [PMID: 38634678 DOI: 10.1111/liv.15882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 02/08/2024] [Accepted: 02/12/2024] [Indexed: 04/19/2024]
Affiliation(s)
- Maurizio Bonacini
- Mission Gastroenterology and Hepatology, San Francisco, California, USA
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8
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Liu H, Sethi V, Li X, Xiao Y, Humar A. Liver Transplantation for Hepatocellular Carcinoma: A Narrative Review and A Glimpse into The Future. Semin Liver Dis 2024; 44:79-98. [PMID: 38211621 DOI: 10.1055/a-2242-7543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.
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Affiliation(s)
- Hao Liu
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Vrishketan Sethi
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Xingjie Li
- Division of Transplant Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, Arizona
| | - Yao Xiao
- Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Abhinav Humar
- Department of Surgery, Starzl Transplant Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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9
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Cabibbo G, Daniele B, Borzio M, Casadei-Gardini A, Cillo U, Colli A, Conforti M, Dadduzio V, Dionisi F, Farinati F, Gardini I, Giannini EG, Golfieri R, Guido M, Mega A, Minozzi S, Piscaglia F, Rimassa L, Romanini L, Pecorelli A, Sacco R, Scorsetti M, Viganò L, Vitale A, Trevisani F. Multidisciplinary Treatment of Hepatocellular Carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part I - Surgical treatments. Dig Liver Dis 2024; 56:223-234. [PMID: 38030455 DOI: 10.1016/j.dld.2023.10.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 10/07/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023]
Abstract
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of HCC management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the first part of guidelines, focused on the multidisciplinary tumor board of experts and surgical treatments of HCC.
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Affiliation(s)
- Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; Gastroenterology Unit, Azienda Ospedaliera Universitaria Policlinico "Paolo Giaccone", Palermo, Italy.
| | - Bruno Daniele
- Oncology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Napoli, Italy
| | - Mauro Borzio
- Centro Diagnostico Italiano (CDI), Milano, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Umberto Cillo
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Agostino Colli
- Dipartimento di Medicina Trasfusionale ed Ematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | | | - Vincenzo Dadduzio
- Medical Oncology Unit, "Mons. A.R.Dimiccoli" Hospital, Barletta, ASL BT, Italy
| | - Francesco Dionisi
- Department of Radiation Oncology, IRCCS Regina Elena National Cancer Institute - Rome, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, 35128 Padova, Italy
| | - Ivan Gardini
- EpaC Onlus, Italian Liver Patient Association, Turin, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Rita Golfieri
- Alma Mater Studiorum" Bologna University, Bologna, Italy; Radiology Unit Madre Fortunata Toniolo Private Hospital, coordinator of Radiology centers Medipass Bologna, Bologna, Italy
| | - Maria Guido
- Department of Medicine, University of Padova, Padova- Italy
| | - Andrea Mega
- Department of Gastronterology, Regional Hospital Bolzano, Italy
| | - Silvia Minozzi
- Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milano, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Milan, Italy; Medical Oncology and Hematology Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Laura Romanini
- Radiology Unit, Ospedale di Cremona, ASST Cremona, Cremona, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Rodolfo Sacco
- Gastroenterology and Endoscopy Unit, Department of Surgical and Medical Sciences, University of Foggia, 71100 Foggia, Italy
| | - Marta Scorsetti
- Department of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, Milan, Italy; Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital IRCCS, Via Manzoni 56, 20089, Rozzano, Milan, Italy
| | - Luca Viganò
- Hepatobiliary Unit, Department of Minimally Invasive General & Oncologic Surgery, Humanitas Gavazzeni University Hospital, Viale M. Gavazzeni 21, 24125 Bergamo, Italy; Department of Biomedical Sciences, Humanitas University, Viale Rita Levi Montalcini 4, 20090 Milan, Italy
| | - Alessandro Vitale
- General Surgery 2-Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Padua University Hospital, 35128 Padua, Italy
| | - Franco Trevisani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Unit of Semeiotics, Liver and Alcohol-Related Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
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10
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Soin A, Lesurtel M, Bhangui P, Cocchi L, Bouattour M, Clavien PA. Are patients with hepatocellular carcinoma and portal vein tumour thrombosis candidates for liver transplantation? J Hepatol 2023; 78:1124-1129. [PMID: 37208099 DOI: 10.1016/j.jhep.2023.03.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 03/27/2023] [Indexed: 05/21/2023]
Abstract
In this debate, the authors consider whether patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis are candidates for liver transplantation (LT). The argument for LT in this context is based on the premise that, following successful downstaging treatment, LT confers a much greater clinical benefit in terms of survival outcomes than the available alternative (palliative systemic therapy). A major argument against relates to limitations in the quality of evidence for LT in this setting - in relation to study design, as well as heterogeneity in patient characteristics and downstaging protocols. While acknowledging the superior outcomes offered by LT for patients with portal vein tumour thrombosis, the counterargument is that expected survival in such patients is still below accepted thresholds for LT and, indeed, the levels achieved for other patients who receive transplants beyond the Milan criteria. Based on the available evidence, it seems too early for consensus guidelines to recommend such an approach, however, it is hoped that with higher quality evidence and standardised downstaging protocols, LT may soon be more widely indicated, including for this population with high unmet clinical need.
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Affiliation(s)
- Arvinder Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Mickaël Lesurtel
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Gurgaon, India
| | - Lorenzo Cocchi
- Department of HPB Surgery & Liver Transplantation, APHP Beaujon Hospital, University of Paris Cité, 100, bd General Leclerc, 92110 Clichy, France
| | - Mohamed Bouattour
- Department of Hepatology, APHP Beaujon Hospital, University of Paris Cité, 100, Bd General Leclerc, 92110 Clichy, France
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Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Diagnostics (Basel) 2023; 13:diagnostics13050816. [PMID: 36899960 PMCID: PMC10001363 DOI: 10.3390/diagnostics13050816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/05/2023] [Accepted: 02/06/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND AND OBJECTIVES the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. MATERIALS AND METHODS systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. RESULTS a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.
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12
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Jeon D, Song GW, Lee HC, Shim JH. Treatment patterns for hepatocellular carcinoma in patients with Child-Pugh class B and their impact on survival: A Korean nationwide registry study. Liver Int 2022; 42:2830-2842. [PMID: 36287103 DOI: 10.1111/liv.15464] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/25/2022] [Accepted: 10/20/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND AND AIMS There are no established practice guidelines for treating hepatocellular carcinoma (HCC) in patients with Child-Turcotte-Pugh (CTP) class B liver function. To evaluate the impact of various initial treatment modalities on these patients, we conducted a nationwide registry study in Korea. MATERIALS AND METHODS Treatment patterns and overall survival (OS) of patients with HCC and CTP class B according to initial treatment modalities in each Barcelona Clinic Liver Cancer (BCLC) stage were analysed using data from the Korean Primary Liver Cancer Registry between 2008 and 2016. Initial treatment modalities were categorized as standard, alternative treatment and supportive care only, referring to the 2018 BCLC guidelines, irrespective of liver function. RESULTS Of the 2318 newly diagnosed Korean patients with HCC and CTP class B, 29.7%, 60.3% and 15.6% of patients in BCLC stages A, B and C, respectively, underwent standard treatment. Adjusted OS hazard ratios of alternative treatment referring to standard treatment were 1.55 (95% confidence interval [CI], 1.25-1.94; p < .001) in BCLC-A, 0.82 (95% CI, 0.43-1.56; p = .550) for curative alternative treatment, 1.89 (95% CI, 0.97-3.68; p = .059) for non-curative alternative treatment in BCLC-B, 0.40 (95% CI, 0.28-0.56; p < .001) for curative alternative treatment, 0.84 (95% CI, 0.69-1.02; p = .076) for non-curative alternative treatment for BCLC-C. CONCLUSION Regardless of BCLC stages, chemoembolization was conducted the most among patients with CTP class B. Treatment in line with the BCLC treatment algorithm resulted in favourable OS outcomes, except for those with BCLC stage C, as systemic therapy showed poor OS.
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Affiliation(s)
- Dongsub Jeon
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- The Korean Liver Cancer Study Group, Seoul, Republic of Korea
| | - Gi-Won Song
- Department of Surgery, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Han Chu Lee
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- The Korean Liver Cancer Study Group, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- The Korean Liver Cancer Study Group, Seoul, Republic of Korea
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13
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Di Martino M, Vitale A, Ferraro D, Maniscalco M, Pisaniello D, Arenga G, Falaschi F, Terrone A, Iacomino A, Galeota Lanza A, Esposito C, Cillo U, Vennarecci G. Downstaging Therapies for Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation: A Systematic Review and Meta-Analysis on Intention-to-Treat Outcomes. Cancers (Basel) 2022; 14:5102. [PMID: 36291885 PMCID: PMC9600776 DOI: 10.3390/cancers14205102] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/07/2022] [Accepted: 10/12/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Locoregional therapies (LRTs) are commonly used to increase the number of potential candidates for liver transplantation (LT). The aim of this paper is to assess the outcomes of LRTs prior to LT in patients with hepatocellular carcinoma (HCC) beyond the listing criteria. Methods: In accordance with the PRISMA guidelines, we searched the Medline and Web of Science databases for reports published before May 2021. We included papers assessing adult patients with HCC considered for LT and reporting intention-to-treat (ITT) survival outcomes. Two reviewers independently identified and extracted the data and evaluated the papers. Outcomes analysed were drop-out rate; time on the waiting list; and 1, 3 and 5 year survival after LT and based on an ITT analysis. Results: The literature search yielded 3,106 records, of which 11 papers (1874 patients) met the inclusion criteria. Patients with HCC beyond the listing criteria and successfully downstaged presented a higher drop-out rate (OR 2.05, 95% CI 1.45−2.88, p < 0.001) and a longer time from the initial assessment to LT than those with HCC within the listing criteria (MD 1.93, 95% CI 0.91−2.94, p < 0.001). The 1, 3 and 5 year survival post-LT and based on an ITT analysis did not show significant differences between the two groups. Patients with HCC beyond the listing criteria, successfully downstaged and then transplanted, presented longer 3 year (OR 3.77, 95% CI 1.26−11.32, p = 0.02) and 5 year overall survival (OS) (OR 3.08, 95% CI 1.15−8.23, p = 0.02) in comparison with those that were not submitted to LT. Conclusions: Patients with HCC beyond the listing criteria undergoing downstaging presented a higher drop-out rate in comparison with those with HCC within the listing criteria. However, the two groups did not present significant differences in 1, 3 and 5 year survival rates based on an ITT analysis. Patients with HCC beyond the listing, when successfully downstaged and transplanted, presented longer 3 and 5-year OS in comparison with those who were not transplanted.
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Affiliation(s)
- Marcello Di Martino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Vitale
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Daniele Ferraro
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Marilisa Maniscalco
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Donatella Pisaniello
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Giuseppe Arenga
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Federica Falaschi
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alfonso Terrone
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Alessandro Iacomino
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | | | - Ciro Esposito
- Liver Intesive Care Unit, Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
| | - Umberto Cillo
- Department of Surgical, Oncological and Gastroenterological Sciences, Padova University, 35121 Padova, Italy
| | - Giovanni Vennarecci
- Department of Hepatobiliary and Liver Transplantation Surgery, A.O.R.N. Cardarelli, 80128 Napoli, Italy
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Kirimker EO, Kirac AT, Celik SU, Boztug CY, Kaya MB, Balci D, Karayalcin MK. Comparison of Anatomic and Non-Anatomic Liver Resection for Hepatocellular Carcinoma: A Retrospective Cohort Study. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1305. [PMID: 36143982 PMCID: PMC9505104 DOI: 10.3390/medicina58091305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 09/09/2022] [Accepted: 09/12/2022] [Indexed: 11/29/2022]
Abstract
Background and Objectives: The survival benefit of anatomical liver resection for hepatocellular carcinoma has not been elucidated yet. In this study, we aimed to investigate the effects of anatomic and non-anatomic liver resection on surgical outcomes in patients with hepatocellular carcinoma. Materials and Methods: A retrospective analysis of patients undergoing anatomic or non-anatomic resections due to hepatocellular carcinoma between March 2006 and October 2019 was conducted. Demographics, preoperative laboratory assessments, treatment strategies, and postoperative outcomes were analyzed. Results: The total cohort consisted of 94 patients, with a mean age of 63.1 ± 8.9 years, and 74.5% were male. A total of 41 patients underwent anatomic liver resection, and 53 patients underwent non-anatomic resection. The overall survival rates were found to be similar (5-year overall survival was 49.3% for anatomic resection and 44.5% for non-anatomic resection). Estimated median overall survival times were 58.5 months and 57.3 months, respectively (p = 0.777). Recurrence-free 1-, 3-, and 5-year survival rates were found to be 73.6%, 39.1%, and 32.8% in the non-anatomic resection group and 48.8%, 22.7%, and 22.7% in the anatomic resection group, respectively. Grade three or higher complication rates were found to be similar among the groups. Conclusions: This study did not find a difference between two surgical methods, in terms of survival. A tailored selection of the resection method should be made, with the aim of complete removal of tumoral lesions and leaving a suitable functional liver reserve, according to the parenchymal quality and volume of the liver remnant.
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Affiliation(s)
- Elvan Onur Kirimker
- Department of General Surgery, Ankara University School of Medicine, 06230 Ankara, Turkey
| | - Alp Togan Kirac
- Department of General Surgery, Ankara Training and Research Hospital, 06010 Ankara, Turkey
| | - Suleyman Utku Celik
- Department of General Surgery, Gulhane Training and Research Hospital, 06000 Ankara, Turkey
| | - Can Yahya Boztug
- Department of General Surgery, Division of Surgical Oncology, Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, 06200 Ankara, Turkey
| | - Muharrem Berat Kaya
- Department of General Surgery, Ankara University School of Medicine, 06230 Ankara, Turkey
| | - Deniz Balci
- Department of General Surgery, Bahcesehir University School of Medicine, 34353 Istanbul, Turkey
| | - Mehmet Kaan Karayalcin
- Department of General Surgery, Ankara University School of Medicine, 06230 Ankara, Turkey
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15
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Iwasa M, Eguchi A, Tamai Y, Shigefuku R, Nakagawa R, Hasegawa H, Kondo J, Morikawa M, Miyoshi E, Nakagawa H. Elevation of enterococcus-specific antibodies associated with bacterial translocation is predictive of survival rate in chronic liver disease. Front Med (Lausanne) 2022; 9:982128. [PMID: 36035413 PMCID: PMC9403143 DOI: 10.3389/fmed.2022.982128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/26/2022] [Indexed: 11/13/2022] Open
Abstract
Introduction/purposeThe gut-liver axis contributes to disease progression, a rise in infection rate, organ failure and a poor overall outcome in chronic liver diseases (CLD). Monitoring of the gut-liver axis is critical in understanding disease status, but biomarkers have not been elucidated. The aim of this study is to determine the level of serum antibodies against Enterococcus (E.) faecalis in evaluating patients with CLD, including those treated with rifaximin (a minimally absorbed antibiotic), and in patients with alcohol-associated liver disease (ALD).Materials and methodsWe enrolled 109 CLD patients (cohort 1), 30 hepatic encephalopathy patients treated with rifaximin (cohort 2), 53 inpatients with ALD undergoing alcohol cessation (cohort 3) and 33 healthy subjects. To assess the consequences of E. faecalis translocation, we developed an assay for the detection of a serum antibody against E. faecalis capsular polysaccharide (E.CPS).ResultsSerum E.CPS antibody titer was elevated only in those patients with advanced CLD and ALD. The E.CPS antibody titer was an independent prognostic factor (p < 0.05), while Mac-2 binding protein and albumin-bilirubin score were not independent predictors of survival. The improvement of predictive model in integrated factors was significant [continuous net reclassification index (value 0.699, p < 0.05) and integrated discrimination improvement (value 0.164, p = 0.051)]. Furthermore, rifaximin treatment led to a decrease of serum E.CPS antibody titer resulting in a significantly longer overall rate of survival.ConclusionThe E.CPS antibody titer appears to be a strong predictor of survival in CLD patients. Serum E.CPS levels decrease in CLD patients receiving rifaximin, and may be associated with an overall improvement in rate of survival.
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Affiliation(s)
- Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Akiko Eguchi
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
- *Correspondence: Akiko Eguchi,
| | - Yasuyuki Tamai
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Ryuta Shigefuku
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | | | - Hiroshi Hasegawa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
| | - Jumpei Kondo
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
| | | | - Eiji Miyoshi
- Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hayato Nakagawa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan
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16
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Torimura T, Iwamoto H. Treatment and the prognosis of hepatocellular carcinoma in Asia. Liver Int 2022; 42:2042-2054. [PMID: 34894051 DOI: 10.1111/liv.15130] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 12/07/2021] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma is the most common type of malignant tumour in Asia. Treatment is decided according to the staging system with information on tumour burden and liver function. The Barcelona Clinic Liver Cancer staging system is the most commonly used staging system for the selection of appropriate treatments worldwide, and although it is highly evidenced-base, it has very strict guidelines for treatment. In Asian countries, many efforts have been made to expand the indications of each treatment and combination therapies as well as alternative therapies for better outcomes. The guidelines in Asia are less evidence-based than those in Western countries. More aggressive treatments for hepatocellular carcinoma are generally employed in the guidelines of Asian countries. Surgical resection is frequently employed for selected hepatocellular carcinoma patients with the Barcelona Clinic Liver Cancer stages B and C, and combination therapies are sometimes selected, which are contrary to the recommendations of American and European association for the study of the liver guidelines. Recently, a paradigm shift in treatments for advanced hepatocellular carcinoma has occurred with molecular targeted agents, antibodies and immune checkpoint inhibitors in Asia. Atezolizumab+bevacizumab therapy has become the first-line systemic treatment ineligible for radical treatment or transarterial chemoembolization in Asian countries. The overall survival of patients with hepatocellular carcinoma varies substantially across Asia. Taiwan and Japan have the best clinical outcomes for patients with hepatocellular carcinoma worldwide. Intensive surveillance programmes and the development of radical and non-radical treatments are indispensable for the improvement of prognosis in patients with hepatocellular carcinoma.
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Affiliation(s)
- Takuji Torimura
- Division of Gastroenterology Department of Medicine, Kurume University School of Medicine, Research Center for Innovative Cancer Therapy Kurume University, Kurume City, Japan
| | - Hideki Iwamoto
- Division of Gastroenterology Department of Medicine, Kurume University School of Medicine, Research Center for Innovative Cancer Therapy Kurume University, Kurume City, Japan
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17
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Polanco PM, Ju MR, Chansard M, Mathew Augustine M, Meier J, Mortensen E, Zeh HJ, Yopp AC. Trends and Disparities in Treatment Utilization for Early-Stage Hepatocellular Carcinoma in the Veteran Population. Ann Surg Oncol 2022; 29:5488-5497. [DOI: 10.1245/s10434-022-11897-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 04/28/2022] [Indexed: 12/24/2022]
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18
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Renzulli M, Brandi N, Pecorelli A, Pastore LV, Granito A, Martinese G, Tovoli F, Simonetti M, Dajti E, Colecchia A, Golfieri R. Segmental Distribution of Hepatocellular Carcinoma in Cirrhotic Livers. Diagnostics (Basel) 2022; 12:diagnostics12040834. [PMID: 35453882 PMCID: PMC9032124 DOI: 10.3390/diagnostics12040834] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 03/25/2022] [Accepted: 03/27/2022] [Indexed: 02/07/2023] Open
Abstract
Background: To evaluate the segmental distribution of hepatocellular carcinoma (HCC) according to Couinaud’s anatomical division in cirrhotic patients. Methods: Between 2020 and 2021, a total of 322 HCC nodules were diagnosed in 217 cirrhotic patients who underwent computed tomography (CT) or magnetic resonance imaging (MRI) for the evaluation of suspicious nodules (>1 cm) detected during ultrasound surveillance. For each patient, the segmental position of the HCC nodule was recorded according to Couinaud’s description. The clinical data and nodule characteristics were collected. Results: A total of 234 (72.7%) HCC nodules were situated in the right lobe whereas 79 (24.5%) were detected in the left lobe (p < 0.0001) and only 9 nodules were in the caudate lobe (2.8%). HCC was most common in segment 8 (n = 88, 27.4%) and least common in segment 1 (n = 9, 2.8%). No significant differences were found in the frequencies of segmental or lobar involvement considering patient demographic and clinical characteristics, nodule dimension, or disease appearance. Conclusions: The intrahepatic distribution of HCC differs among Couinaud’s segments, with segment 8 being the most common location and segment 1 being the least common. The segmental distribution of tumour location was similar to the normal liver volume distribution, supporting a possible correlation between HCC location and the volume of hepatic segments and/or the volumetric distribution of the portal blood flow.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
- Correspondence: (M.R.); (N.B.)
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
- Correspondence: (M.R.); (N.B.)
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
| | - Luigi Vincenzo Pastore
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
| | - Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.G.); (F.T.)
| | - Giuseppe Martinese
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
| | - Francesco Tovoli
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (A.G.); (F.T.)
| | - Mario Simonetti
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
| | - Elton Dajti
- Department of Medical and Surgical Sciences (DIMEC), IRCCS, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy;
| | - Antonio Colecchia
- Unit of Gastroenterology, Borgo Trento University Hospital of Verona, 25122 Verona, Italy;
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (A.P.); (L.V.P.); (G.M.); (M.S.); (R.G.)
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Zanus G, Tagliente G, Rossi S, Bonis A, Zambon M, Scopelliti M, Brizzolari M, Grossi U, Romano M, Finotti M. Pulsed Microwave Liver Ablation: An Additional Tool to Treat Hepatocellular Carcinoma. Cancers (Basel) 2022; 14:748. [PMID: 35159014 PMCID: PMC8833939 DOI: 10.3390/cancers14030748] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/26/2022] [Accepted: 01/29/2022] [Indexed: 12/15/2022] Open
Abstract
This study aimed to analyze the outcomes of HCC patients treated with a novel technique-pulsed microwave ablation (MWA)-in terms of safety, local tumor progression (LTP), intrahepatic recurrence (IHR), and overall survival (OS). A total of 126 pulsed microwave procedures have been performed in our center. We included patients with mono- or multifocal HCC (BCLC 0 to D). The LTP at 12 months was 9.9%, with an IHR rate of 27.8% at one year. Survival was 92.0% at 12 months with 29.4% experiencing post-operative complications (28.6% Clavien-Dindo 1-2, 0.8% Clavien-Dindo 3-4). Stratifying patients by BCLC, we achieved BCLC 0, A, B, C, and D survival rates of 100%, 93.2%, 93.3%, 50%, and 100%, respectively, at one year, which was generally superior to or in line with the expected survival rates among patients who are started on standard treatment. The pulsed MWA technique is safe and effective. The technique can be proposed not only in patients with BCLC A staging but also in the highly selected cases of BCLC B, C, and D, confirming the importance of the concept of stage migration. This procedure, especially if performed with a minimally invasive technique (laparoscopic or percutaneous), is repeatable with a short postoperative hospital stay.
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Affiliation(s)
- Giacomo Zanus
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Giovanni Tagliente
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Serena Rossi
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Alessandro Bonis
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Mattia Zambon
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Michele Scopelliti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Marco Brizzolari
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Ugo Grossi
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Maurizio Romano
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
| | - Michele Finotti
- 4th Surgery Unit, Regional Hospital Treviso, University of Padua, DISCOG, 31100 Padua, Italy; (G.Z.); (G.T.); (S.R.); (A.B.); (M.Z.); (M.S.); (M.B.); (U.G.); (M.R.)
- Baylor Scott & White Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX 75204, USA
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20
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Trevisani F, Giannini EG. The ITA.LI.CA Consortium: How multicentre collaboration helped shape the management of patients with hepatocellular carcinoma on the basis of real-world evidence. Ann Hepatol 2022; 27 Suppl 1:100564. [PMID: 34688886 DOI: 10.1016/j.aohep.2021.100564] [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: 08/18/2021] [Accepted: 08/19/2021] [Indexed: 02/04/2023]
Abstract
The growing diffusion of digitalisation and informatics has promoted the creation and analysis of large databases able to provide solid information. Analyses of "big data" generated by real-world practice are particularly useful for knowing incidence and mortality, disparities, temporal trends of diseases, identifying risk factors, predicting future scenarios, obtaining inputs for cost-effectiveness and treatment benefit modelling, designing new studies, and monitoring rare diseases. Although randomised controlled trials (RCTs) represent the gold-standard for generating evidence about new diagnostic, preventive or therapeutic procedures, their results should be integrated with real-world data to personalise patient management. Indeed, a substantial proportion of patients observed in field-practice have characteristics that prevent the access to RCTs or, when included, form sub-groups too small to provide robust post-hoc analyses. Furthermore, as RCTs are resource-consuming and designed to maximize the probability of success, they are generally performed in expert centres of high-income areas, excluding economically-deprived regions which could complementarily contribute to the medical progress as huge sources of real-world data. These considerations fuelled the creation in 1998 of the Italian Liver Cancer (ITA.LI.CA) consortium, with the aim to merge data of patients with hepatocellular carcinoma (HCC) managed in several centres. This cooperation permitted to analyse a multicentre, large cohort of HCC patients. Since then, the ITA.LI.CA group has progressively expanded to currently include 24 centres, and its database counts more than 9,000 patients. This article describes the history of the ITA.LI.CA consortium and presents its scientific production whose results greatly contributed to the incessant improvement of HCC management.
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Affiliation(s)
- Franco Trevisani
- Medical Semeiotics Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
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21
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Khatib SA, Wang XW. Causes and functional intricacies of inter- and intratumor heterogeneity of primary liver cancers. Adv Cancer Res 2022; 156:75-102. [DOI: 10.1016/bs.acr.2022.01.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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22
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Sun Z, Shi Z, Xin Y, Zhao S, Jiang H, Wang D, Zhang L, Wang Z, Dai Y, Jiang H. Artificial Intelligent Multi-Modal Point-of-Care System for Predicting Response of Transarterial Chemoembolization in Hepatocellular Carcinoma. Front Bioeng Biotechnol 2021; 9:761548. [PMID: 34869272 PMCID: PMC8634755 DOI: 10.3389/fbioe.2021.761548] [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: 08/20/2021] [Accepted: 10/22/2021] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) ranks the second most lethal tumor globally and is the fourth leading cause of cancer-related death worldwide. Unfortunately, HCC is commonly at intermediate tumor stage or advanced tumor stage, in which only some palliative treatment can be used to offer a limited overall survival. Due to the high heterogeneity of the genetic, molecular, and histological levels, HCC makes the prediction of preoperative transarterial chemoembolization (TACE) efficacy and the development of personalized regimens challenging. In this study, a new multi-modal point-of-care system is employed to predict the response of TACE in HCC by a concept of integrating multi-modal large-scale data of clinical index and computed tomography (CT) images. This multi-modal point-of-care predicting system opens new possibilities for predicting the response of TACE treatment and can help clinicians select the optimal patients with HCC who can benefit from the interventional therapy.
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Affiliation(s)
- Zhongqi Sun
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhongxing Shi
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanjie Xin
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Sheng Zhao
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Hao Jiang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Dandan Wang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Linhan Zhang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ziao Wang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Yanmei Dai
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Huijie Jiang
- Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
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23
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:cancers13194882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Hepatocellular carcinoma (HCC) is an increasingly important indication for liver transplantation (LT) worldwide. However, LT in the setting of liver cancer is burdened by the risk of tumor recurrence. The prognosis of patients with post-LT HCC recurrence is still very poor and several areas of uncertainty remain in the management of these patients. In this paper, we provide a comprehensive evaluation of available evidence regarding the management of HCC recurrence after LT, starting from the pre- and post-transplant stratification criteria and encompassing post-LT surveillance, preventive strategies and treatment. Much work has been done in the last several years but further effort is still needed in order to improve the outcome of these patients. Abstract Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10–15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
- Correspondence:
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24
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Miao K, Zhang L. Application of Immune Checkpoint Inhibitors in Solid Organ Transplantation Recipients: A Systematic Review. Interdiscip Sci 2021; 13:801-814. [PMID: 34152556 DOI: 10.1007/s12539-021-00437-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 01/26/2023]
Abstract
BACKGROUND Solid organ transplantation (SOT) is a treatment method for end-stage organ diseases and improve their life quality, while using long-term immunosuppressant drugs (ISD) is needed to suppress the function of the immune system. Immune checkpoint inhibitors (ICIs) are a class of anti-tumor drugs that kill tumors by activating the autoimmune system. The primary objective of our systematic review is to investigate the risk factors for organ rejection and the efficacy of ICIs in solid organ transplantation recipients (SOTRs). METHODS We searched four databases to find relevant articles up to January 2021. A total of 61 articles involving 106 SOTRs met the screening criteria and were included in our systematic review. The collected data were statistical described, and the risk factors were analyzed by logistic regression. RESULTS Forty-four patients (41.5%) developed host-versus-graft response (HVGR) after ICIs. mTOR inhibitors (pre-ICIs) (p = 0.069, OR = 0.377, 95% CI 0.132-1.078) and calcineurin inhibitors (post-ICIs) (p = 0.056, OR = 0.375, 95%CI 0.137-1.025) may help reduce the incidence of HVGR. Hormones (pre-ICIs) (p = 0.026, OR = 3.150, 95%CI 1.150-8.628) and anti-metabolites (pre-ICIs) (p = 0.022, OR = 3.214, 95%CI 1.185-8.720) may adversely affect the efficacy of ICIs. Only 35.6% of patients both responded well to ICIs treatment and did not develop HVGR. CONCLUSIONS Our systematic review summarizes the use of ICIs in SOTRs and evaluates the efficacy of ICIs and the risk factors that induce HVGR. Through risk factor analysis, we found that mTOR inhibitors and calcineurin inhibitors may help to reduce the occurrence of HVGR; hormones and anti-metabolic drugs may have adverse effects on the efficacy of ICIs. In addition, there is a contradictory relationship between the occurrence of HVGR and the efficacy of ICIs.
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Affiliation(s)
- Kang Miao
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 53 Dongdan North Avenue, Dongcheng District, Beijing, China
| | - Li Zhang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 53 Dongdan North Avenue, Dongcheng District, Beijing, China.
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25
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Lai Q, Vitale A. BCLC staging system and liver transplantation: From a stage to a therapeutic hierarchy. Hepatobiliary Pancreat Dis Int 2021; 20:4-5. [PMID: 33358081 DOI: 10.1016/j.hbpd.2020.12.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 12/09/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Quirino Lai
- Hepato-biliary and Organ Transplant Unit, Department of Surgery, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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26
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The Perioperatively Altered Neutrophil-to-Lymphocyte Ratio Associates with Impaired DNA Damage Response in Liver Transplantation Recipients with Hepatocellular Carcinoma. Diagnostics (Basel) 2021; 11:diagnostics11020209. [PMID: 33573309 PMCID: PMC7912615 DOI: 10.3390/diagnostics11020209] [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: 01/06/2021] [Accepted: 01/25/2021] [Indexed: 01/10/2023] Open
Abstract
Increasing evidence has suggested that elevated systemic inflammation with a high neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis after liver transplantation (LT). The ongoing molecular events involved in poor survival remain unclear. This retrospective study evaluated LT recipients whose data was collected at Kaohsiung Chang Gung Memorial Hospital between 2005 and 2014. Clinical records of 347 patients with hepatocellular carcinoma from seven days before LT to 30 days after LT illustrated that longitudinal values of lymphocytes, RBC, and hemoglobin were persistently low in patients with peritransplant high NLR (PTH-NLR, pre-LT ≥ 4 and post-LT ≥ 5), which indicated a significantly worse survival rate in association with increased RDW-CV and pancytopenia when compared to other patients (p = 0.008). We further found that PTH-NLR patients had decreased DNA damage response (DDR) genes and detoxifying enzymes of ADH and ALDH families, and increased mitochondrial stress response genes in their liver tissues. Reduced lineage markers of liver progenitor cells were also observed in PTH-NLR patients signifying the presence of unresolved impairments after LT. Our results demonstrate the association between hematopoietic deficiencies and lack of protection against DDR with PTH-NLR in LDLT recipients with HCC and may imply abnormal hematological and organismal defects in those patients.
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27
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Organ allocation in the age of the algorithm: avoiding futile transplantation - utility in allocation. Curr Opin Organ Transplant 2020; 25:305-309. [PMID: 32304427 DOI: 10.1097/mot.0000000000000752] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW This review describes and questions the evolution of allocation systems from local team decisions in the 20th century to patient-oriented allocation using complex algorithm predicting transplant benefit. RECENT FINDINGS The opening years of the 2000s have seen the implementation of prioritization scores aiming at increasing transparency and reducing waitlist mortality. The 2010s have underlined the necessity of drawing the upper limits of how sick a patient can be while still ensuring acceptable survival. More complex algorithms evaluating transplant benefit have been implemented in allocation systems to take this issue into account. SUMMARY Allocation algorithms are becoming more and more complex, integrating numerous parameters from both donor and recipient to achieve optimal matching. The limitations of implementing these complex algorithms are represented by the evermoving waiting list demography, geographic disparities between recipients and donors, team policy adaptation to rule changes, and implicit biases within the transplant community. Survival as the only metric by which to define benefit may be seen as restrictive; quality of life may be a fruitful measure for better defining benefit in organ transplantation in the future.
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28
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Finotti M, Vitale A, Volk M, Cillo U. A 2020 update on liver transplant for hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2020; 14:885-900. [PMID: 32662680 DOI: 10.1080/17474124.2020.1791704] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma is the most frequent liver tumor and is associated with chronic liver disease in 90% of cases. In selected cases, liver transplantation represents an effective therapy with excellent overall survival. AREA COVERED Since the introduction of Milan criteria in 1996, numerous alternative selection systems to LT for HCC patients have been proposed. Debate remains about how best to select HCC patients for transplant and how to prioritize them on the waiting list. EXPERT OPINION The selection of the best scoring system to propose in the context of LT for HCC is far to be identified. In this review, we analyze and categorize the various selection systems, assessing their roles in the different decisional phases.
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Affiliation(s)
- Michele Finotti
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
| | - Michael Volk
- Division of Gastroenterology and Hepatology, Loma Linda University Health , Loma Linda, California, USA
| | - Umberto Cillo
- Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplantation Unit, Padova University Hospital , Padova, Italy
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29
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Lee E, Johnston CJC, Oniscu GC. The trials and tribulations of liver allocation. Transpl Int 2020; 33:1343-1352. [PMID: 32722866 DOI: 10.1111/tri.13710] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 05/18/2020] [Accepted: 07/23/2020] [Indexed: 12/12/2022]
Abstract
Allocation policies are necessary to ensure a fair distribution of a scarce resource. The goal of any liver transplant allocation policy is to achieve the best possible outcomes for the waiting list population, irrespective of the indication for transplant, whilst maximizing organ utilization. Organ allocation for liver transplantation has evolved from simple centre-based approaches driven by local issues, to complex, evidence-based algorithm prioritizing according to need. Despite the rapid evolution of allocation policies, there remain a number of challenges and new approaches are required to ensure transparency and equity on the decision-making process and the best possible outcomes for patients on the waiting list. New ways of modelling, together with novel outcome criteria, will be required to enable a dynamic adaptability of the allocation policies to the ever changing demographics of the donor population and the changing landscape of indications for transplantation.
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Affiliation(s)
- Eunice Lee
- Department of Surgery, Austin Hospital, University of Melbourne, Melbourne, Vic., Australia
| | | | - Gabriel C Oniscu
- Edinburgh Transplant Centre, Edinburgh, UK.,University of Edinburgh, Edinburgh, UK
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30
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Thermal Ablation versus SBRT in liver tumours: pros and cons. Med Oncol 2020; 37:52. [PMID: 32350765 DOI: 10.1007/s12032-020-01377-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 04/16/2020] [Indexed: 02/06/2023]
Abstract
Non-surgical locally ablative treatments for primary liver cancer and liver metastases represent an effective therapeutic choice when surgery cannot be performed or is not indicated. Thermal ablative employing electric currents or electromagnetic fields have historically played an important role in this setting. Radiotherapy, in the last decades, due to a series of important technological development, has become an attractive option for the treatment of liver tumours, especially with the introduction of Stereotactic Body Radiotherapy. Published literature so far evidenced both for radiotherapy and thermal ablative techniques a benefit in terms of local control and other oncological outcomes; however, no direct prospective comparison between the two techniques have been published so far. The aim of this review is to summarize the technical and clinical implications of these treatment modalities and to identify criteria to allocate patients to one or another option in consideration of the expected efficacy. The main features and critical aspects of both thermoablative techniques and external beam radiation will also be covered in the present paper.
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31
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Tan Y, Xie XY, Li XJ, Liu DH, Zhou LY, Zhang XE, Lin Y, Wang W, Wu SS, Liu J, Huang GL. Comparison of hepatic epithelioid angiomyolipoma and non-hepatitis B, non-hepatitis C hepatocellular carcinoma on contrast-enhanced ultrasound. Diagn Interv Imaging 2020; 101:733-738. [PMID: 32331793 DOI: 10.1016/j.diii.2020.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/22/2020] [Accepted: 03/09/2020] [Indexed: 01/10/2023]
Abstract
PURPOSE The purpose of this study was to retrospectively compare the imaging features of hepatic epithelioid angiomyolipoma (HEAML) to those of hepatocellular carcinoma negative for hepatitis B surface antigen and hepatitis C antibody (NBNC-HCC) on contrast-enhanced ultrasound (CEUS) with sulphur hexafluoride microbubbles. MATERIAL AND METHODS Twenty-two patients (4 men, 18 women) with a mean age of 42.6±10.2 (SD) years (range: 22-63 years) with histopathologically confirmed HEMAL were included in the study. Forty-four patients (30 men, 14 women) with a mean age of 57.3±15.9 years (range: 19-85 years) with histopathologically confirmed NBNC-HCC were randomly selected from our institution's database as a control group. The CEUS characteristics of the two groups were compared. RESULTS On conventional ultrasound, significant differences in tumor diameter were found between HEAML (4.0±2.0 [SD] cm; range: 1.3-8.9cm) and NBNC-HCC (8.4±4.4 [SD] cm; range: 1.6-18cm) (P<0.001) as well as in degrees of enhancement during the portal (P=0.001) and late phases (P=0.003), contrast distribution (P<0.001) and absence of pseudocaspule (P<0.001). On CEUS, hyperenhancement during the arterial phase was observed in 21/22 (95.5%) HEAMLs and in 43/44 (97.7%) NBNC-HCCs (P>0.999). Homogeneous enhancement was more frequent in HEAMLs (20/22; 90.9%) than in NBNC-HCCs (13/44; 29.6%) (P<0.001). Pseudocapsule was observed in 0/22 HEAMLs (0.0%) and in 36/44 NBNC-HCCs (81.8%) (P=0.017). A prolonged enhancement was observed in 5/22 HEAMLs (22.7%) and in 0/44 NBNC-HCCs (0.0%) (P<0.001) during the late phase. CONCLUSION CEUS with sulphur hexafluoride microbubbles is helpful in discriminating between HEAML and NBNC-HCC. Homogeneous enhancement and lack of pseudocapsule are suggestive features for the diagnosis of HEAML.
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Affiliation(s)
- Y Tan
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - X-Y Xie
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - X-J Li
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - D-H Liu
- Department of Medical Ultrasonics, the First Affiliated Hospital of Sun Yat-Sen University, 510080 Guangzhou, China
| | - L-Y Zhou
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - X-E Zhang
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - Y Lin
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - W Wang
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - S-S Wu
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China
| | - J Liu
- Department of Medical Ultrasonics, the First Affiliated Hospital of Sun Yat-Sen University, 510080 Guangzhou, China
| | - G-L Huang
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, 510080 Guangzhou, China.
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Wang H, Guo Q, Nampoukime KPB, Yang P, Ma K. Long non-coding RNA LINC00467 drives hepatocellular carcinoma progression via inhibiting NR4A3. J Cell Mol Med 2020; 24:3822-3836. [PMID: 32125766 PMCID: PMC7171408 DOI: 10.1111/jcmm.14942] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/28/2019] [Accepted: 11/26/2019] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a main cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) play important roles in diverse cancers. Our previous microarray-based lncRNA profiling showed that LINC00467 was highly expressed in HCC. Here, we further explored the expression, role and functional mechanism of lncRNA LINC00467 in HCC. Our findings revealed that LINC00467 was up-regulated in HCC tissues and HCC cell lines. Increased expression of LINC00467 was positively associated with tumour size and vascular invasion. In vitro functional experiments revealed that LINC00467 accelerated HCC cell proliferation, cell cycle progression and migration and reduced HCC cell apoptosis. In vivo functional assays revealed that LINC00467 drove HCC xenograft growth and HCC cell proliferation and repressed HCC cell apoptosis in vivo. Moreover, LINC00467 inhibited NR4A3 post-transcriptionally via interacting with NR4A3 mRNA to form double-stranded RNA, which was further degraded by Dicer. The expression of NR4A3 was inversely associated with LINC00467 in HCC tissues. Functional rescue assays found that restore of NR4A3 expression blocked the oncogenic roles of LINC00467 in HCC. Taken together, our results demonstrated that lncRNA LINC00467 was a novel highly expressed and oncogenic lncRNA in HCC via inhibiting NR4A3. Targeting LINC00467 or enhancing NR4A3 may be potential therapeutic strategies against HCC.
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Affiliation(s)
- Haihao Wang
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Qiannan Guo
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Kan-Paatib Barnabo Nampoukime
- Division of Cardiothoracic and Vascular Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Peiwen Yang
- Reproductive Medicine Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Ke Ma
- Division of Infectious Disease, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
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Kumar A, Acharya SK, Singh SP, Arora A, Dhiman RK, Aggarwal R, Anand AC, Bhangui P, Chawla YK, Datta Gupta S, Dixit VK, Duseja A, Kalra N, Kar P, Kulkarni SS, Kumar R, Kumar M, Madhavan R, Mohan Prasad V, Mukund A, Nagral A, Panda D, Paul SB, Rao PN, Rela M, Sahu MK, Saraswat VA, Shah SR, Shalimar, Sharma P, Taneja S, Wadhawan M. 2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations. J Clin Exp Hepatol 2020; 10:43-80. [PMID: 32025166 PMCID: PMC6995891 DOI: 10.1016/j.jceh.2019.09.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/15/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.
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Key Words
- AFP, alpha-fetoprotein
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- DAA, direct-acting antiviral
- DALY, disability-adjusted life-year
- DNA, deoxyribonucleic acid
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- Gd-BOPTA, gadolinium benzyloxypropionictetraacetate
- Gd-EOB-DTPA, gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HIV, human immunodeficiency virus
- IARC, International Agency for Research on Cancer
- IFN, interferon
- INASL, Indian National Association for Study of the Liver
- MiRNA, micro-RNA
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- PIVKA, protein induced by vitamin K absence
- RFA
- RNA, ribonucleic acid
- SVR, sustained virological response
- TACE
- TACE, trans-arterial chemoembolization
- TARE, transarterial radioembolization
- TNF, tumor necrosis factor
- WHO, World Health Organization
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Anil C. Anand
- Department of Gastroenterology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Suyash S. Kulkarni
- Division of Interventional Radiology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, 400 012, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Ram Madhavan
- Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Peeliyadu Road, Ponekkara, Edappally, Kochi, Kerala, 682 041, India
| | - V.G. Mohan Prasad
- Department of Gastroenterology, VGM Gastro Centre, 2100, Trichy Road, Rajalakshmi Mills Stop, Singanallur, Coimbatore, Tamil Nadu, 641 005, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Dipanjan Panda
- Department of Oncology, Institutes of Cancer, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600 100, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Super Specialty Hospital, Delhi, 110 005, India
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Viganò L, Costa G, Di Tommaso L. Liver resection for multifocal hepatocellular carcinoma: is it an option? Hepatobiliary Surg Nutr 2019; 8:530-533. [PMID: 31673548 DOI: 10.21037/hbsn.2019.05.12] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Luca Viganò
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
| | - Guido Costa
- Division of Hepatobiliary & General Surgery, Department of Surgery, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Pathology Unit, Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy.,Department of Biomedical Sciences, Humanitas University, Rozzano, Milan, Italy
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Extremes of Liver Transplantation for Hepatocellular Carcinoma. J Clin Med 2019; 8:jcm8060787. [PMID: 31163668 PMCID: PMC6616997 DOI: 10.3390/jcm8060787] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 05/28/2019] [Accepted: 05/30/2019] [Indexed: 12/12/2022] Open
Abstract
The aim of this retrospective observational study was to evaluate outcomes of patients with extremely advanced hepatocellular carcinoma (HCC) after liver transplantation. A total of 285 HCC patients after liver transplantation were screened for eligibility based on either intrahepatic dissemination (≥10 tumors) or macrovascular invasion. Tumor recurrence was the primary end-point. The study cohort comprised 26 patients. Median recurrence-free survival was 23.2 months with hepatitis B virus (HBV) infection (p = 0.038), higher AFP model score (p = 0.001), prolonged graft ischemia (p = 0.004), and younger donor age (p = 0.016) being significant risk factors. Median recurrence-free survival of HBV-negative and HBV-positive patients was 29.8 and 9.3 months, respectively (p = 0.053). In patients with macrovascular invasion, recurrence-free survival at 3 years was 46.3% with no specific predictors. Tumor size (p = 0.044), higher AFP model score (p = 0.019), prolonged graft ischemia (p = 0.016), and younger donor age (p = 0.041) were significant risk factors in patients with intrahepatic dissemination. Superior 3-year outcomes were observed in patients with intrahepatic dissemination and tumor size <3.5 cm (83.3%, p = 0.027) and HBV-negative patients with ischemia <9.7 h (85.7%, p = 0.028). In conclusion, patients with extremely advanced HCCs are remarkably heterogeneous with respect to their profile of tumor recurrence risk. This heterogeneity is largely driven by factors other than standard predictors of post-transplant HCC recurrence.
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Moreno Gonzales M, Sanchez W, Taner T. Liver transplantation: When to say yes or no? Based on a case report. TRANSPLANTATION REPORTS 2019. [DOI: 10.1016/j.tpr.2019.100027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Watanabe M, Yokomori H, Takahashi Y, Okada T, Shibuya A, Koizumi W. Assessing the characteristics and feasibility of preventing early mortality in patients with hepatocellular carcinoma. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 30:541-548. [PMID: 31144660 DOI: 10.5152/tjg.2019.18654] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND/AIMS To determine strategies to prevent early death (ED) and improve the prognosis of patients with advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS Patients who were diagnosed with HCC from January 2012 to June 2017 were considered for the study. Those who survived for ≤6 months from the date of diagnosis were classified into the ED group (n=21) and those who survived for ≥12 months from the date of diagnosis were classified into the non-ED group (n=88). RESULTS There were significant differences between the ED and non-ED groups in the following conditions: when the patient age was ≥80 years (38.1% vs. 14.8% patients); maximum nodule size was >3 cm (90.5% vs. 27.3%); Child-Pugh class C liver disease was seen (66.7% vs. 26.1%); tumor-node-metastasis (TNM) Stage III-IV tumor was present (85.7% vs. 21.6%); BCLC stage C/D of liver cancer was seen (81.0% vs. 21.6%); JIS score was ≥4 (52.4% vs. 3.4%); serum creatinine level was ≥1.0 mg/dL (52.4% vs. 22.7%); and there was absence of aggressive treatments such as hepatic resection, radiofrequency ablation, transarterial chemoembolization, and chemotherapy (66.7% vs. 4.5%). Logistic regression analysis identified maximum nodule size of >3 cm (p=0.005, OR=58.7, 95% CI=3.43-1003.9), JIS score of ≥4 (p=0.021, OR=12.0, 95% CI=1.44-100.1), and absence of aggressive treatments (p=0.006, OR=24.7, 95% CI=2.47-247.2) as predictive factors for ED. The presence of aggressive treatments significantly improved the 12-month survival rate of advanced HCC patients with BCLC stage C/D (presence vs. absence: 78.3% vs. 7.4%), a maximum nodule size of >3 cm (76.7% vs. 7.7%), and a JIS score of ≥4 (60.0% vs. 0%). CONCLUSION Although delayed detection of HCC strongly increased the onset ED, the aggressiveness of HCC treatment is not readily downgraded, and the most aggressive treatment possible should be considered to prevent ED in patients with advanced HCC.
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Affiliation(s)
- Masaaki Watanabe
- Department of Gastroenterology, Kitasato University Medical Center, Kitamoto, Saitama, Japan
| | - Hiroaki Yokomori
- Department of General Internal Medicine, Kitasato University Medical Center, Kitamoto, Saitama, Japan
| | - Yoshihito Takahashi
- Department of Surgery, Kitasato University Medical Center, Kitamoto, Saitama, Japan
| | - Takemichi Okada
- Department of Radiology, Kitasato University Medical Center, Kitamoto, Saitama, Japan
| | - Akitaka Shibuya
- Department of Risk Management and Health Care Administration, Kitasato University School of Medicine, Kitamoto, Saitama, Japan
| | - Wasaburo Koizumi
- Department of Gastroenterology, Kitasato University School of Medicine, Kitamoto, Saitama, Japan
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Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma. Transplant Proc 2019; 51:1147-1152. [PMID: 31101189 DOI: 10.1016/j.transproceed.2019.01.093] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 01/21/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Scarce data are available comparing outcomes of hepatic resection vs orthotopic liver transplantation (OLT) for localized hepatocellular carcinoma (HCC) patients both meeting and exceeding the Milan criteria. This study compared the clinical and oncological outcomes of patients undergoing hepatic resection vs transplantation localized HCC. METHOD Between January 2005 and February 2017, clinical and oncological outcomes of patients who underwent liver resection (n = 38) vs OLT (n = 28) for localized HCC were compared using a prospectively maintained database. RESULTS A total of 66 patients (with a median age of 62) who met the study criteria were analyzed. Comparable postoperative complications (13.2% vs 28.6%, P = .45) and perioperative mortality rates (7.9% vs 10.7%, P = .2) were noted for the resection vs OLT groups. While Child-Pugh Class A patients were more prevalent in the resection group (78.9% vs 7.1%, P = .0001), the rate of patients who met the Milan criteria was higher in the OLT group (89.3% vs 34.25, P = .0001). Recurrence rates were 36.8% in the resection group and 3.6% in the OLT group at the end of the median follow-up period (32 vs 39 months, respectively). The HCC-related mortality rate was significantly higher in the resection group (39.5% vs 10.7%, P = .034). However, a subgroup analysis of patients who met the Milan criteria revealed similar rates of recurrence and HCC-related mortality (15.4% vs 8%, P = .63). Based on logistic regression analysis, number of tumors (P = .034, odds ratio: 2.1) and "resection"-type surgery (P = .008, odds ratio: 20.2) were independently associated with recurrence. CONCLUSION Compared to liver transplantation, hepatic resection for localized hepatocellular carcinoma is associated with a higher rate of recurrence and disease-related mortality.
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39
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Vitale A, Donato MF. From individual to population-based benefit of split liver transplantation. Dig Liver Dis 2019; 51:181-182. [PMID: 30553748 DOI: 10.1016/j.dld.2018.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Accepted: 11/04/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
| | - Maria Francesca Donato
- Transplant Hepatology Unit, Division of Gastroenterology and Hepatology, IRCCS Cà Granda Maggiore Hospital Policlinico and RC "A. M. and A. Migliavacca" Center for the Study of Liver Disease, University of Milan, Milan, Italy
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Lai Q, Vitale A. Transplantation for hepatocellular cancer: pushing to the limits? Transl Gastroenterol Hepatol 2018; 3:61. [PMID: 30363754 DOI: 10.21037/tgh.2018.09.07] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 09/04/2018] [Indexed: 12/12/2022] Open
Abstract
Milan criteria (MC) represents the cornerstone in the selection of patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT). MC represent the precursor of the scores based on the idea of "utility": in other terms, the scoring systems typically used in the field of LT oncology present the exclusive aim of selecting the cases with the best post-LT outcomes. However, some other scores have been proposed specifically investigating the risk of death or tumour progression during the waiting list. In this case, the selection process is connected with the idea of "priority": patients at higher risk for drop-out (DO) should be selected, prioritising them or, conversely, deciding to de-list them due to the high risk of post-LT futile transplant. Lastly, models based on the concept of "benefit", namely the balancing between priority and utility, have been recently created. The present review aims to examine these three different types of scoring systems, trying to underline their pro and cons in the allocation process of HCC patients.
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Affiliation(s)
- Quirino Lai
- General Surgery and Organ Transplantation Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy
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Garancini M, Nespoli S, Romano F, Uggeri F, Degrate L, Okolicsanyi S, Gianotti L. Traitement chirurgical du carcinome hépatocellulaire dans le cadre et en dehors des indications de Barcelone dans un centre de moyen volume. JOURNAL DE CHIRURGIE VISCÉRALE 2018; 155:278-285. [DOI: 10.1016/j.jchirv.2017.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
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42
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Ke R, Lv L, Li J, Zhang X, Yang F, Zhang K, Jiang Y. Prognostic value of heterogeneous ribonucleoprotein A1 expression and inflammatory indicators for patients with surgically resected hepatocellular carcinoma: Perspectives from a high occurrence area of hepatocellular carcinoma in China. Oncol Lett 2018; 16:3746-3756. [PMID: 30127985 PMCID: PMC6096241 DOI: 10.3892/ol.2018.9079] [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] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Accepted: 05/16/2018] [Indexed: 12/15/2022] Open
Abstract
Heterogeneous ribonucleoproteinA1 (hnRNPA1) is a documented tumor biomarker known to be aberrantly expressed in a number of types of human cancer. However, to the best of our knowledge, its prognostic value for surgically resected HCC (RHCC) in the high incidence areas of China has not been described; the association between hnRNPA1 expression, pre-operative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) is also not understood. In the present study, hnRNPA1 expression was retrospectively measured in two independent cohorts of patients with hepatocellular carcinoma (HCC) who underwent surgery to remove the primary cancer at one center in Fujian, an area with a high incidence of HCC in China. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting and immunohistochemistry (IHC) were used to quantify hnRNPA1 expression in RHCC tissues. The survival curves were plotted using the Kaplan-Meier method, and the prognostic significance of hnRNPA1, NLR and PLR was analyzed using the log-rank test. The relevant prognostic factors were identified by multivariate Cox regression analysis. RT-qPCR and western blotting revealed that hnRNPA1 was upregulated in HCC tissues (P<0.001), and particularly overexpressed in tumor tissues of patients with recurrent HCC (P<0.001) (cohort 1; 54 patients). Differential hnRNPA1 expression was measured in 426HCC tissues with IHC; 259 exhibited high hnRNPA1 expression and 167 exhibited low expression. High hnRNPA1 expression was significantly associated with Tumor-Node-Metastasis stage (P=0.024), tumor size (P=0.027), vascular invasion (P<0.001), Edmonson grade (P<0.001), pre-operative serum α-fetoprotein (AFP) (P<0.001), NLR (P<0.001) and PLR (P<0.001). In addition, multivariate Cox regression analysis confirmed that high hnRNPA1 expression was associated with relapse-free survival (RFS; HR, 0.685; 95% CI, 0.506-0.928; P=0.015) and overall survival (OS; HR, 0.629; 95% CI, 0.454-0.871; P=0.005). Multivariate analysis confirmed that higher pre-operative serum AFP had an unfavorable impact on RFS (HR, 1.350; 95% CI, 1.006-1.811; P=0.045) and OS (HR=1.564; 95% CI, 1.151-2.126; P=0.004), while higher pre-operative NLR had an unfavorable impact on OS (HR, 1.758; 95% CI, 1.161-2.661; P=0.008) (cohort 2;426 patients). The expression of hnRNPA1 was also positively correlated with NLR (Spearman's correlation; r=0.122, P=0.012) and PLR (Spearman's correlation; r=0.140, P=0.004). In conclusion, high hnRNPA1 expression was revealed as prognostic for poor survival in patients with RHCC, and detection of hnRNPA1 protein in tumor tissues demonstrated potential in estimating survival for patients with RHCC in areas with high incidence rates. Furthermore, the combination of high hnRNPA1 expression and pre-operative serum AFP levels (>400 µg) proved to be a good diagnostic and prognostic biomarker for this specific population of patients. Finally, a correlation may also exist between hnRNPA1 expression and other markers of systemic inflammation.
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Affiliation(s)
- Ruisheng Ke
- Department of Hepatobiliary Surgery, The Fuzhou Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China
| | - Lizhi Lv
- Department of Hepatobiliary Surgery, The Fuzhou Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.,Department of Hepatobiliary Surgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China
| | - Jiayan Li
- Department of Surgery, Fuzhou Hospital of Traditional Chinese Medicine, Fuzhou, Fujian 350025, P.R. China
| | - Xiaojin Zhang
- Department of Hepatobiliary Surgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China
| | - Fang Yang
- Department of Hepatobiliary Surgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China
| | - Kun Zhang
- Department of Hepatobiliary Surgery, The Fuzhou Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.,Department of Hepatobiliary Surgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China
| | - Yi Jiang
- Department of Hepatobiliary Surgery, The Fuzhou Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.,Department of Hepatobiliary Surgery, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. China
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43
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Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, Schirmacher P, Vilgrain V. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol 2018; 69:182-236. [PMID: 29628281 DOI: 10.1016/j.jhep.2018.03.019] [Citation(s) in RCA: 5774] [Impact Index Per Article: 824.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023]
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44
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Commander SJ, Shaw B, Washburn L, Yoeli D, Rana A, Goss JA. A long-term experience with expansion of Milan criteria for liver transplant recipients. Clin Transplant 2018; 32:e13254. [DOI: 10.1111/ctr.13254] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2018] [Indexed: 12/16/2022]
Affiliation(s)
- Sarah Jane Commander
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Brian Shaw
- Division of Abdominal Transplantation; University of California-San Francisco; San Francisco CA USA
| | - Laura Washburn
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Dor Yoeli
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - Abbas Rana
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
| | - John A. Goss
- Division of Abdominal Transplantation; Michael E. DeBakey Department of Surgery; Baylor College of Medicine; Houston TX USA
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45
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Individualized laparoscopic B-ultrasound-guided microwave ablation for multifocal primary liver cancer. Wideochir Inne Tech Maloinwazyjne 2018; 13:9-16. [PMID: 29643953 PMCID: PMC5890848 DOI: 10.5114/wiitm.2018.72730] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Accepted: 10/11/2017] [Indexed: 11/17/2022] Open
Abstract
Introduction Liver cancer is one of the most common malignancies of the digestive system. Minimally invasive ablation procedures have become one of the major means for treating unresectable multifocal liver cancer and have been extensively applied in primary and metastatic liver cancer treatment. Laparoscopic B-ultrasound-guided microwave ablation is an example of the progress made in this field. Aim To analyze and summarize the results of and experience with laparoscopic B-ultrasound-guided microwave ablation for multifocal primary liver cancer; moreover, the ablation effects were compared between tumors of different sizes. Material and methods Laparoscope-guided needle ablation was conducted on 84 lesions from 32 patients with primary liver cancer based on tumor size, quantity, and location. Moreover, the perioperative data, ablation effects according to tumor size, and long-term follow-up results were analyzed. Results Among the 84 nodules treated via microwave ablation, tumors measuring ≤ 3 cm demonstrated complete ablation upon imaging analysis conducted 1 month after surgery. Moreover, 5 of the tumors measuring > 3 cm demonstrated incomplete ablation. In these cases, a second procedure was performed, until imaging studies confirmed that complete ablation was achieved. Conclusions Laparoscopic microwave ablation allows for precise puncture positioning, an effective ablation range, and safe and feasible surgery, which is especially suitable for liver tumors located in sites difficult to access.
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46
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Lai Q, Vitale A. Reply. Hepatology 2018; 67:1639-1640. [PMID: 29451324 DOI: 10.1002/hep.29757] [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: 12/17/2017] [Accepted: 12/19/2017] [Indexed: 12/07/2022]
Affiliation(s)
- Quirino Lai
- Hepato-bilio-pancreatic and Liver Transplant Unit, Department of Surgery, Sapienza University of Rome, Rome, Italy
| | - Alessandro Vitale
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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47
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Garancini M, Nespoli S, Romano F, Uggeri F, Degrate L, Okolicsanyi S, Gianotti L. Surgical management of hepatocellular carcinoma within and beyond BCLC indications in a middle volume center. J Visc Surg 2018; 155:275-282. [PMID: 29606603 DOI: 10.1016/j.jviscsurg.2017.12.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
AIM OF THE STUDY Current criteria for hepatic resection in patients with hepatocellular carcinoma (HCC) according to Barcellona Clinic Liver Cancer (BCLC) classification is debated. Actually, patients with multinodular or large HCC>5cm are excluded from surgical treatment following the algorithm, but several studies from referral centers showed that such patients may benefit from surgical resection in the clinical practice. The aim of this study was to compare short- and long-term outcomes after liver resection for HCC in stage 0/A or B in a middle volume center. PATIENTS AND METHODS Patients were grouped according to BCLC classification. Postoperative mortality, morbidity, overall and disease-free survival, univariate analysis of prognostic factors on survival was analyzed. RESULTS Among 66 surgical procedures in 64 patients included in the study, 41 were BCLC stage 0/A (62.1%) and 25 BCLC stage B (37.9%). The overall 30- and the 90-days mortality rates were 1.5% and 3%. Patients in BCLC stage B had higher transfusion rate (P=0.04) but similar morbidity and mortality compared to patients in BCLC stage 0/A. After a median follow-up of 35 months (range: 14-147), the overall survival at 1, 3 and 5 years resulted 95%, 61.1%, 46.2% for stage 0-A and 83.3%, 50%, 41.2% for stage B (P=0.73). Univariate analysis identified poorly differentiated tumors (P=0.02) and positive margin (P=0.02) as negative prognostic factors on survival. CONCLUSIONS Surgical treatment of HCC in BCLC stage B offers similar results than the ones in BCLC stage 0/A and consequently should not be considered contraindicated for such patients.
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Affiliation(s)
- M Garancini
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy.
| | - S Nespoli
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
| | - F Romano
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
| | - F Uggeri
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
| | - L Degrate
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
| | - S Okolicsanyi
- Department of Gastroenterology, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
| | - L Gianotti
- Department of Surgery, San Gerardo Hospital, School of Medicine and Surgery, University of Milano- Bicocca, via Pergolesi 33, 20900 Monza, MI, Italy
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48
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Lei J, Zhong J, Hao J, Liu Z, Zhang P, Wu L, Yan L, Zhu J, Zeng Y, Li B, Wen T, Wang W. Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence. Oncotarget 2018; 7:42598-42607. [PMID: 26981887 PMCID: PMC5173159 DOI: 10.18632/oncotarget.3799] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2015] [Accepted: 03/20/2015] [Indexed: 02/05/2023] Open
Abstract
Background and Aims Liver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence. Results Most of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211–2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017–1.543; P = 0.046) in HCC patients who underwent radical hepatic resection. Patients and Methods We retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis. Conclusions HCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.
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Affiliation(s)
- Jianyong Lei
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China.,Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.,State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Jinjing Zhong
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Jingcheng Hao
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Zhengni Liu
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Peng Zhang
- Third General Surgery, The First Hospital of Handan, Handan, Hebei, China
| | - Lixue Wu
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Lunan Yan
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Jinqiang Zhu
- Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yong Zeng
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bo Li
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Tianfu Wen
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Wentao Wang
- Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
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49
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Ponziani FR, Spinelli I, Rinninella E, Cerrito L, Saviano A, Avolio AW, Basso M, Miele L, Riccardi L, Zocco MA, Annicchiarico BE, Garcovich M, Biolato M, Marrone G, De Gaetano AM, Iezzi R, Giuliante F, Vecchio FM, Agnes S, Addolorato G, Siciliano M, Rapaccini GL, Grieco A, Gasbarrini A, Pompili M. Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma. World J Hepatol 2017; 9:1322-1331. [PMID: 29359015 PMCID: PMC5756721 DOI: 10.4254/wjh.v9.i36.1322] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2017] [Revised: 09/28/2017] [Accepted: 11/12/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the factors predicting the achievement of disease control (DC).
METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded.
RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6-17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).
CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients’ survival confers them as useful predictive tools for treatment management and clinical decisions.
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Affiliation(s)
- Francesca Romana Ponziani
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Irene Spinelli
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Emanuele Rinninella
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Lucia Cerrito
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Saviano
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Michele Basso
- Department of Oncology, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Luca Miele
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Laura Riccardi
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Maria Assunta Zocco
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Matteo Garcovich
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Marco Biolato
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Giuseppe Marrone
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Anna Maria De Gaetano
- Department of Bioimaging and Radiological Sciences, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Roberto Iezzi
- Department of Bioimaging and Radiological Sciences, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Felice Giuliante
- Department of Hepatobiliary Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
| | | | - Salvatore Agnes
- Department of Liver Transplant Surgery, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Giovanni Addolorato
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Massimo Siciliano
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Gian Lodovico Rapaccini
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Grieco
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
| | - Maurizio Pompili
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Rome 00168, Italy
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50
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Glantzounis GK, Paliouras A, Stylianidi MC, Milionis H, Tzimas P, Roukos D, Pentheroudakis G, Felekouras E. The role of liver resection in the management of intermediate and advanced stage hepatocellular carcinoma. A systematic review. Eur J Surg Oncol 2017; 44:195-208. [PMID: 29258719 DOI: 10.1016/j.ejso.2017.11.022] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 11/15/2017] [Accepted: 11/23/2017] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The ideal management for patients with intermediate and advanced stage hepatocellular carcinoma (HCC) is controversial. The main purpose of this systematic review is to examine the role of liver resection in patients with intermediate stage HCC (multinodular HCCs) and in advanced stage HCC [mainly patients with portal vein tumor thrombosis (PVTT)]. METHODS A systematic search of the literature was performed in Pud Med and the Cochrane Library from 01.01.2000 to 30.06.2016. RESULTS Twenty-three articles with 2412 patients with multinodular HCCs were selected. Also, 29 studies with 3659 patients with HCCs with macrovascular invasion were selected. In patients with multinodular HCCs the median post-operative morbidity was 25% and the 90-day mortality was 2.7%. The median survival was 37 months and the 5-year survival 35%. The 5-year survival was much better for patients with a number of HCCs ≤3 vs. HCCs >3 (49% vs. 23%). In patients with macrovascular invasion, who underwent hepatic resection, the median post-operative morbidity was 33% and the in-hospital mortality 2.7%. The median survival was 15 months. The 3 and 5year survival was 33% and 20% respectively. Moreover a significant difference in survival was noted according to PVTT stage: 5- year survival for distal PVTT, PVTT of the main intrahepatic PV branch and PVTT extending to the main PV was 45%, 19% and 14.5% respectively. CONCLUSIONS Liver resection in patients with multinodular HCCs and HCCs with PVTT offers satisfactory long-term survival and should be considered in selected patients.
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Affiliation(s)
- G K Glantzounis
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece.
| | - A Paliouras
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - M-C Stylianidi
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - H Milionis
- Department of Internal Medicine, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - P Tzimas
- Department of Anesthesia and Postoperative Intensive Care, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - D Roukos
- Department of Surgery, University Hospital of Ioannina and School of Medicine, University of Ioannina, 45 500, Ioannina, Greece
| | - G Pentheroudakis
- Department of Medical Oncology, University Hospital of Ioannina and School of Medicine, University of Ioannina, Ioannina, Greece
| | - E Felekouras
- 1st Department of Surgery, Laikon General Hospital, National and Kapodistrian University of Athens, Athens, Greece
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