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Chen JL, Chen YS, Hsieh KC, Lee HM, Chen CY, Chen JH, Hung CM, Hsu CT, Huang YL, Ker CG. Clinical Nomogram Model for Pre-Operative Prediction of Microvascular Invasion of Hepatocellular Carcinoma before Hepatectomy. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1410. [PMID: 39336451 PMCID: PMC11433876 DOI: 10.3390/medicina60091410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Revised: 08/09/2024] [Accepted: 08/21/2024] [Indexed: 09/30/2024]
Abstract
Background and Objectives: Microvascular invasion (MVI) significantly impacts recurrence and survival rates after liver resection in hepatocellular carcinoma (HCC). Pre-operative prediction of MVI is crucial in determining the treatment strategy. This study aims to develop a nomogram model to predict the probability of MVI based on clinical features in HCC patients. Materials and Methods: A total of 489 patients with a pathological diagnosis of HCC were enrolled from our hospital. Those registered from 2012-2015 formed the derivation cohort, and those from 2016-2019 formed the validation cohort for pre-operative prediction of MVI. A nomogram model for prediction was created using a regression model, with risk factors derived from clinical and tumor-related features before surgery. Results: Using the nomogram model to predict the odds ratio of MVI before hepatectomy, the AFP, platelet count, GOT/GPT ratio, albumin-alkaline phosphatase ratio, ALBI score, and GNRI were identified as significant variables for predicting MVI. The Youden index scores for each risk variable were 0.287, 0.276, 0.196, 0.185, 0.115, and 0.112, respectively, for the AFP, platelet count, GOT/GPT ratio, AAR, ALBI, and GNRI. The maximum value of the total nomogram scores was 220. An increase in the number of nomogram points indicated a higher probability of MVI occurrence. The accuracy rates ranged from 55.9% to 64.4%, and precision rates ranged from 54.3% to 68.2%. Overall survival rates were 97.6%, 83.4%, and 73.9% for MVI(-) and 80.0%, 71.8%, and 41.2% for MVI(+) (p < 0.001). The prognostic effects of MVI(+) on tumor-free survival and overall survival were poor in both the derivation and validation cohorts. Conclusions: Our nomogram model, which integrates clinical factors, showed reliable calibration for predicting MVI and provides a useful tool enabling surgeons to estimate the probability of MVI before resection. Consequently, surgical strategies and post-operative care programs can be adapted to improve the prognosis of HCC patients where possible.
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Affiliation(s)
- Jen-Lung Chen
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Yaw-Sen Chen
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Kun-Chou Hsieh
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Hui-Ming Lee
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Chung-Yen Chen
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Jian-Han Chen
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
| | - Chao-Ming Hung
- Department of General Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan;
| | - Chao-Tien Hsu
- Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan;
| | - Ya-Ling Huang
- Cancer Registration Center, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan;
| | - Chen-Guo Ker
- Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan; (J.-L.C.); (Y.-S.C.); (K.-C.H.); (H.-M.L.); (C.-Y.C.); (J.-H.C.)
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Gonvers S, Martins-Filho SN, Hirayama A, Calderaro J, Phillips R, Uldry E, Demartines N, Melloul E, Park YN, Paradis V, Thung SN, Alves V, Sempoux C, Labgaa I. Macroscopic Characterization of Hepatocellular Carcinoma: An Underexploited Source of Prognostic Factors. J Hepatocell Carcinoma 2024; 11:707-719. [PMID: 38605975 PMCID: PMC11007400 DOI: 10.2147/jhc.s447848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/29/2024] [Indexed: 04/13/2024] Open
Abstract
The macroscopic appearance of a tumor such as hepatocellular carcinoma (HCC) may be defined as its phenotype which is de facto dictated by its genotype. Therefore, macroscopic characteristics of HCC are unlikely random but rather reflect genomic traits of cancer, presumably acting as a valuable source of information that can be retrieved and exploited to infer prognosis. This review aims to provide a comprehensive overview of the available data on the prognostic value of macroscopic characterization in HCC. A total of 57 studies meeting eligible criteria were identified, including patients undergoing liver resection (LR; 47 studies, 83%) or liver transplant (LT; 9 studies, 16%). The following macroscopic variables were investigated: tumor size (n = 42 studies), number of nodules (n = 28), vascular invasion (n = 24), bile duct invasion (n = 6), growth pattern (n = 15), resection margin (n = 11), tumor location (n = 6), capsule (n = 2) and satellite (n = 1). Although the selected studies provided insightful data with notable prognostic performances, a lack of standardization and substantial gaps were noted in the report and the analysis of gross findings. This topic remains incompletely covered. While the available studies underscored the value of macroscopic variables in HCC prognostication, important lacks were also observed. Macroscopic characterization of HCC is likely an underexploited source of prognostic factors that must be actively explored by future multidisciplinary research.
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Affiliation(s)
- Stéphanie Gonvers
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | | | - André Hirayama
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Julien Calderaro
- Department of Pathology, APHP, Henri Mondor University Hospital, Creteil, Val-de-Marne, France
| | - Rebecca Phillips
- Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
| | - Emilie Uldry
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emmanuel Melloul
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
| | - Young Nyun Park
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Valérie Paradis
- Department of Pathology, APHP, Beaujon University Hospital, Clichy, France
| | - Swan N Thung
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Venancio Alves
- Department of Pathology, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Christine Sempoux
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
- Department of Pathology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Ismail Labgaa
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), Lausanne, Switzerland
- Faculty of Biology & Medicine (FBM), University of Lausanne (UNIL), Lausanne, Switzerland
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Franchi E, Dondossola DE, Marini GMF, Iavarone M, Del Prete L, Di Benedetto C, Donato MF, Antonelli B, Lampertico P, Caccamo L. Impact of Pre-Liver Transplant Treatments on the Imaging Accuracy of HCC Staging and Their Influence on Outcomes. Cancers (Basel) 2024; 16:1043. [PMID: 38473400 DOI: 10.3390/cancers16051043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/30/2024] [Accepted: 01/31/2024] [Indexed: 03/14/2024] Open
Abstract
The outcome of liver transplantation (LT) for hepatocarcinoma (HCC) is strongly influenced by HCC staging, which is based on radiological examinations in a pre-LT setting; concordance between pre-LT radiological and definitive pathological staging remains controversial. To address this issue, we retrospectively analyzed our LT series to assess concordance between radiology and pathology and to explore the factors associated with poor concordance and outcomes. We included all LTs with an HCC diagnosis performed between 2013 and 2018. Concordance (Co group) was defined as a comparable tumor burden in preoperative imaging and post-transplant pathology; otherwise, non-concordance was diagnosed (nCo group). Concordance between radiology and pathology was observed in 32/134 patients (Co group, 24%). The number and diameter of the nodules were higher when nCo was diagnosed, as was the number of pre-LT treatments. Although concordance did not affect survival, more than three pre-LT treatments led to a lower disease-free survival. Patients who met the Milan Criteria (Milan-in patients) were more likely to receive ≥three prior treatments, leading to a lower survival in multi-treated Milan-in patients than in other Milan-in patients. In conclusion, the concordance rate between the pre-LT imaging and histopathological results was low in patients with a high number of nodules. Multiple bridging therapies reduce the accuracy of pre-LT imaging in predicting HCC stages and negatively affect outcomes after LT.
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Affiliation(s)
- Eloisa Franchi
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Daniele Eliseo Dondossola
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
| | - Giulia Maria Francesca Marini
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
| | - Massimo Iavarone
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Luca Del Prete
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Clara Di Benedetto
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Maria Francesca Donato
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Barbara Antonelli
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Pietro Lampertico
- Department of Pathophysiology and Transplantation, Università degli Studi, 20122 Milan, Italy
- Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Lucio Caccamo
- General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
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Abdelrahim M, Esmail A, Abudayyeh A, Murakami N, Victor D, Kodali S, Cheah YL, Simon CJ, Noureddin M, Connor A, Saharia A, Moore LW, Heyne K, Kaseb AO, Gaber AO, Ghobrial RM. Transplant Oncology: An Emerging Discipline of Cancer Treatment. Cancers (Basel) 2023; 15:5337. [PMID: 38001597 PMCID: PMC10670243 DOI: 10.3390/cancers15225337] [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: 10/20/2023] [Accepted: 10/30/2023] [Indexed: 11/26/2023] Open
Abstract
Transplant oncology is an emerging concept of cancer treatment with a promising prospective outcome. The applications of oncology, transplant medicine, and surgery are the core of transplant oncology to improve patients' survival and quality of life. The main concept of transplant oncology is to radically cure cancer by removing the diseased organ and replacing it with a healthy one, aiming to improve the survival outcomes and quality of life of cancer patients. Subsequently, it seeks to expand the treatment options and research for hepatobiliary malignancies, which have seen significantly improved survival outcomes after the implementation of liver transplantation (LT). In the case of colorectal cancer (CRC) in the transplant setting, where the liver is the most common site of metastasis of patients who are considered to have unresectable disease, initial studies have shown improved survival for LT treatment compared to palliative therapy interventions. The indications of LT for hepatobiliary malignancies have been slowly expanded over the years beyond Milan criteria in a stepwise manner. However, the outcome improvements and overall patient survival are limited to the specifics of the setting and systematic intervention options. This review aims to illustrate the representative concepts and history of transplant oncology as an emerging discipline for the management of hepatobiliary malignancies, in addition to other emerging concepts, such as the uses of immunotherapy in a peri-transplant setting as well as the use of circulating tumor DNA (ctDNA) for surveillance post-transplantation.
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Affiliation(s)
- Maen Abdelrahim
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Cockrell Center of Advanced Therapeutics Phase I Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Abdullah Esmail
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
| | - Ala Abudayyeh
- Section of Nephrology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Naoka Murakami
- Division of Renal Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - David Victor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Sudha Kodali
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Yee Lee Cheah
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Caroline J. Simon
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Mazen Noureddin
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashton Connor
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Ashish Saharia
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Linda W. Moore
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kirk Heyne
- Section of GI Oncology, Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA; (A.E.)
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Ahmed O. Kaseb
- Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - A. Osama Gaber
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Rafik Mark Ghobrial
- Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, JC Walter Jr. Center for Transplantation, Houston Methodist Hospital, Houston, TX 77030, USA
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Jiang T, He S, Yang H, Dong Y, Yu T, Luo Y, Jiang X. Multiparametric MRI-based radiomics for the prediction of microvascular invasion in hepatocellular carcinoma. Acta Radiol 2023; 64:456-466. [PMID: 35354318 DOI: 10.1177/02841851221080830] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is essential in obtaining a successful surgical treatment, in decreasing recurrence, and in improving survival. PURPOSE To investigate the value of multiparametric magnetic resonance imaging (MRI)-based radiomics in the prediction of peritumoral MVI in HCC. MATERIAL AND METHODS A total of 102 patient with pathologically proven HCC after surgical resection from June 2014 to March 2018 were enrolled in this retrospective study. Histological analysis of resected specimens confirmed positive MVI in 48 patients and negative MVI in 54 patients. Radiomics features were extracted from four MRI sequences and selected with the least absolute shrinkage and selection operator (LASSO) regression and used to analyze the tumoral and peritumoral regions for MVI. Univariate logistic regression was employed to identify the most important clinical factors, which were integrated with the radiomics signature to develop a nomogram. RESULTS In total, 11 radiomics features were selected and used to build the radiomics signature. The serum level of alpha-fetoprotein was identified as the clinical factor with the highest predictive value. The developed nomogram achieved the highest AUC in predicting MVI status. The decision curve analysis confirmed the potential clinical utility of the proposed nomogram. CONCLUSION The multiparametric MRI-based radiomics nomogram is a promising tool for the preoperative diagnosis of peritumoral MVI in HCCs and helps determine the appropriate medical or surgical therapy.
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Affiliation(s)
- Tao Jiang
- Department of Biomedical Engineering, 159407China Medical University, Shenyang, PR China
| | - Shuai He
- Department of Radiology, 74665Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, PR China
| | - Huazhe Yang
- Department of Biophysics, School of Fundamental Sciences, 159407China Medical University, Shenyang, PR China
| | - Yue Dong
- Department of Radiology, 74665Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, PR China
| | - Tao Yu
- Department of Radiology, 74665Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, PR China
| | - Yahong Luo
- Department of Radiology, 74665Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, PR China
| | - Xiran Jiang
- Department of Biomedical Engineering, 159407China Medical University, Shenyang, PR China
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Park HJ, Kim KW, Lee SS. Artificial intelligence in radiology and its application in liver disease. ARTIFICIAL INTELLIGENCE, MACHINE LEARNING, AND DEEP LEARNING IN PRECISION MEDICINE IN LIVER DISEASES 2023:53-79. [DOI: 10.1016/b978-0-323-99136-0.00002-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Degroote H, Geerts A, Verhelst X, Van Vlierberghe H. Different Models to Predict the Risk of Recurrent Hepatocellular Carcinoma in the Setting of Liver Transplantation. Cancers (Basel) 2022; 14:cancers14122973. [PMID: 35740638 PMCID: PMC9221160 DOI: 10.3390/cancers14122973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Liver transplantation is considered the first-choice curative therapy for hepatocellular carcinoma in the early phase of the disease, when surgical resection is not possible. Even when implementing restrictive criteria to select patients for liver transplantation, there is a risk of recurrence in the transplanted liver, influencing the long-term outcome and prognosis. As it is challenging to predict the individual risk of recurrence, there is a need for validated and predictive scoring systems to use to stratify patients before and/or after liver transplantation. Most of the proposed scorings include biological markers for tumour behavior, in addition to the number and size of tumoral nodules. In this review, we discuss different published models to assess the risk of recurrent hepatocellular carcinoma after transplantation. Our aim is to refine clinical decisions about prioritization and listing for liver transplantation, to better inform patients and provide an appropriate surveillance strategy to influence their prognosis. Abstract Liver transplantation is the preferred therapeutic option for non-resectable hepatocellular carcinoma in early-stage disease. Taking into account the limited number of donor organs, liver transplantation is restricted to candidates with long-term outcomes comparable to benign indications on the waiting list. Introducing the morphometric Milan criteria as the gold standard for transplant eligibility reduced the recurrence rate. Even with strict patient selection, there is a risk of recurrence of between 8 and 20% in the transplanted liver, and this is of even greater importance when using more expanded criteria and downstaging protocols. Currently, it remains challenging to predict the risk of recurrence and the related prognosis for individual patients. In this review, the recurrence-risk-assessment scores proposed in the literature are discussed. Currently there is no consensus on the optimal model or the implications of risk stratification in clinical practice. The most recent scorings include additional biological markers for tumour behavior, such as alfa-foetoprotein, and the response to locoregional therapies, in addition to the number and diameter of tumoral nodules. The refinement of the prediction of recurrence is important to better inform patients, guide decisions about prioritization and listing and implement individualized surveillance strategies. In the future, this might also provide indications for tailored immunosuppressive therapy or inclusion in trials for adjuvant treatment.
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Costentin C, Piñero F, Degroote H, Notarpaolo A, Boin IF, Boudjema K, Baccaro C, Podestá LG, Bachellier P, Ettorre GM, Poniachik J, Muscari F, Dibenedetto F, Duque SH, Salame E, Cillo U, Marciano S, Vanlemmens C, Fagiuoli S, Burra P, Van Vlierberghe H, Cherqui D, Lai Q, Silva M, Rubinstein F, Duvoux C. R3-AFP score is a new composite tool to refine prediction of hepatocellular carcinoma recurrence after liver transplantation. JHEP Rep 2022; 4:100445. [PMID: 35360522 PMCID: PMC8961219 DOI: 10.1016/j.jhepr.2022.100445] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND & AIMS Patients with hepatocellular carcinoma (HCC) are selected for liver transplantation (LT) based on pre-LT imaging ± alpha-foetoprotein (AFP) level, but discrepancies between pre-LT tumour assessment and explant are frequent. Our aim was to design an explant-based recurrence risk reassessment score to refine prediction of recurrence after LT and provide a framework to guide post-LT management. METHODS Adult patients who underwent transplantation between 2000 and 2018 for HCC in 47 centres were included. A prediction model for recurrence was developed using competing-risk regression analysis in a European training cohort (TC; n = 1,359) and tested in a Latin American validation cohort (VC; n=1,085). RESULTS In the TC, 76.4% of patients with HCC met the Milan criteria, and 89.9% had an AFP score of ≤2 points. The recurrence risk reassessment (R3)-AFP model was designed based on variables independently associated with recurrence in the TC (with associated weights): ≥4 nodules (sub-distribution of hazard ratio [SHR] = 1.88, 1 point), size of largest nodule (3-6 cm: SHR = 1.83, 1 point; >6 cm: SHR = 5.82, 5 points), presence of microvascular invasion (MVI; SHR = 2.69, 2 points), nuclear grade >II (SHR = 1.20, 1 point), and last pre-LT AFP value (101-1,000 ng/ml: SHR = 1.57, 1 point; >1,000 ng/ml: SHR = 2.83, 2 points). Wolber's c-index was 0.76 (95% CI 0.72-0.80), significantly superior to an R3 model without AFP (0.75; 95% CI 0.72-0.79; p = 0.01). Four 5-year recurrence risk categories were identified: very low (score = 0; 5.5%), low (1-2 points; 15.1%), high (3-6 points; 39.1%), and very high (>6 points; 73.9%). The R3-AFP score performed well in the VC (Wolber's c-index of 0.78; 95% CI 0.73-0.83). CONCLUSIONS The R3 score including the last pre-LT AFP value (R3-AFP score) provides a user-friendly, standardised framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials for HCC not limited to the Milan criteria. CLINICAL TRIALS REGISTRATION NCT03775863. LAY SUMMARY Considering discrepancies between pre-LT tumour assessment and explant are frequent, reassessing the risk of recurrence after LT is critical to further refine the management of patients with HCC. In a large and international cohort of patients who underwent transplantation for HCC, we designed and validated the R3-AFP model based on variables independently associated with recurrence post-LT (number of nodules, size of largest nodule, presence of MVI, nuclear grade, and last pre-LT AFP value). The R3-AFP model including last available pre-LT AFP value outperformed the original R3 model only based on explant features. The final R3-AFP scoring system provides a robust framework to design post-LT surveillance strategies, protocols, or adjuvant therapy trials, irrespective of criteria used to select patients with HCC for LT.
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Key Words
- AFP, alpha-foetoprotein
- Explants pathology
- HBV, hepatitis B virus
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- LT, liver transplantation
- Liver cancer
- Liver transplantation
- MVI, microvascular invasion
- Prediction
- R3, recurrence risk reassessment
- RETREAT, Risk Estimation of Tumour Recurrence After Transplant
- Recurrence
- SHR, sub-distribution of hazard ratio
- TC, test cohort
- TTR, time to recurrence
- VC, validation cohort
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Affiliation(s)
- Charlotte Costentin
- Grenoble Alpes University, Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, Grenoble, France
- Gastroenterology, Hepatology and GI Oncology Department, Digidune, Grenoble Alpes University Hospital, La Tronche, France
| | - Federico Piñero
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Helena Degroote
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | | | | | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Pontchaillou Hospital Rennes 1 University, Rennes, France
| | | | - Luis G. Podestá
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | | | | | - Jaime Poniachik
- Hospital Clínico de la Universidad de Chile, Santiago, Chile
| | - Fabrice Muscari
- Digestive Surgery and Transplant Unit, Hôpital Rangueil, Toulouse, France
| | - Fabrizio Dibenedetto
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, Department of General Surgery, University of Modena and Reggio Emilia, Modena, Italy
| | - Sergio Hoyos Duque
- Hospital Pablo Tobón Uribe y Grupo de Gastrohepatología de la Universidad de Antioquía, Medellín, Colombia
| | | | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplant Unit, Padova University Hospital, Padua, Italy
| | | | | | - Stefano Fagiuoli
- Gastroenterology, Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padua, Italy
| | - Hans Van Vlierberghe
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Daniel Cherqui
- Hospital Paul Brousse, University of Paris, Paris, France
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
| | - Marcelo Silva
- Hospital Universitario Austral, School of Medicine, Austral University, Buenos Aires, Argentina
- Latin American Liver Research Educational and Awareness Network (LALREAN), Buenos Aires, Argentina
| | - Fernando Rubinstein
- Instituto de Efectividad Clínica y Sanitaria (IECS), Buenos Aires, Argentina
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9
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Alim A, Karataş C. Prognostic Factors of Liver Transplantation for HCC: Comparative Literature Review. J Gastrointest Cancer 2021; 52:1223-1231. [PMID: 34882291 DOI: 10.1007/s12029-021-00730-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/06/2021] [Indexed: 12/16/2022]
Abstract
PURPOSE The aim of the review study is investigation of the prognostic factors of the liver transplantation for hepatocellular carcinoma. METHODS A literature review has been made, especially in countries where dominantly living donor liver transplantation is performed, such as Turkey. Liver transplantation from deceased donor and from living donor has been evaluated about as advantages and disadvantages, and their effects on prognosis have been compared. In addition, hepatocellular carcinoma series of Koç University Liver Transplantation center has been presented. RESULTS Liver transplantation is still the best treatment option with 5-year 50% survival rate for hepatocellular carcinoma even in patient who has locally advanced tumor. The patient's survival is not only an important issue but also the living donor's safety is controversial particularly when expectation of recipient's 5-year survival is below 50% due to donor complication. CONCLUSION Detailed preoperative examination, appropriate patient selection, and timing of surgery are seen the most important issues in liver transplant's patients with hepatocellular carcinoma.
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Affiliation(s)
- Altan Alim
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey.
| | - Cihan Karataş
- Liver Transplantation Center, Koç Universitiy Hospital, Davutpaşa Cd. No:4, 34010, Topkapi Zeytinburnu/Istanbul, Turkey
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10
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Radulova-Mauersberger O, Weitz J, Riediger C. Vascular surgery in liver resection. Langenbecks Arch Surg 2021; 406:2217-2248. [PMID: 34519878 PMCID: PMC8578135 DOI: 10.1007/s00423-021-02310-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 08/18/2021] [Indexed: 01/04/2023]
Abstract
Vascular surgery in liver resection is a standard part of liver transplantation, but is also used in oncological liver surgery. Malignant liver tumors with vascular involvement have a poor prognosis without resection. Surgery is currently the only treatment to provide long-term survival in advanced hepatic malignancy. Even though extended liver resections are increasingly performed, vascular involvement with need of vascular reconstruction is still considered a contraindication for surgery in many institutions. However, vascular resection and reconstruction in liver surgery-despite being complex procedures-are safely performed in specialized centers. The improvements of the postoperative results with reduced postoperative morbidity and mortality are a result of rising surgical and anesthesiological experience and advancements in multimodal treatment concepts with preconditioning measures regarding liver function and systemic treatment options. This review focuses on vascular surgery in oncological liver resections. Even though many surgical techniques were developed and are also used during liver transplantation, this special procedure is not particularly covered within this review article. We provide a summary of vascular reconstruction techniques in oncological liver surgery according to the literature and present also our own experience. We aim to outline the current advances and standards in extended surgical procedures for liver tumors with vascular involvement established in specialized centers, since curative resection improves long-term survival and shifts palliative concepts to curative therapy.
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Affiliation(s)
- Olga Radulova-Mauersberger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
- German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Carina Riediger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
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11
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Lerut J, Foguenne M, Lai Q. Hepatocellular cancer selection systems and liver transplantation: from the tower of babel to an ideal comprehensive score. Updates Surg 2021; 73:1599-1614. [PMID: 34003479 PMCID: PMC8500859 DOI: 10.1007/s13304-021-01078-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022]
Abstract
The Milan criteria (MC) remain the cornerstone for the selection of patients with hepatocellular cancer (HCC) to be listed for liver transplantation (LT). Recently, several expanded criteria have been proposed to increase the transplantability of HCC patients without compromising their (oncologic) outcome. This paper aims to systematically review the different reported HCC-LT selection systems looking thereby at their ability to increase the number of transplantable patients and the overall survival and oncological outcome. A systematic review of the literature covering the period 1993 (date of the first reported HCC-LT selection system)-2021 identified 59 different inclusion criteria of HCC for LT. Among the 59 studies reporting HCC-LT selection systems, 15 (28.3%) were exclusively based on morphological aspects of the tumor; 29 (54.7%) included biologic, seven (13.2%) radiological, and two (3.8%) only included pathological tumor features. Overall, 31% more patients could be transplanted when adhering to the new HCC-LT selection systems. Despite the increased number of LT, 5-year patient and disease-free survival rates were similar between MC-IN and MC-OUT/new HCC-LT-IN criteria. A careful extension of the inclusion criteria should allow many more patients to access a potentially curative LT without compromising their outcome. The development of a widely accepted "comprehensive" HCC-LT Score able to offer a fair chance of justified transplantation to more patients should become a priority within the liver transplant community. Further studies are needed to develop internationally accepted, expanded selection criteria for liver transplantation of HCC patients.
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Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université Catholique de Louvain (UCL), Avenue Hippocrates 55, 1200 Brussels, Belgium
| | - Maxime Foguenne
- University Hospitals Saint-Luc Université Catholique de Louvain (UCL), Brussels, Belgium
| | - Quirino Lai
- General Surgery and Organ Transplantation Unit, Sapienza University of Rome, Rome, Italy
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12
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Lee JC, Hung HC, Wang YC, Cheng CH, Wu TH, Lee CF, Wu TJ, Chou HS, Chan KM, Lee WC. Risk Score Model for Microvascular Invasion in Hepatocellular Carcinoma: The Role of Tumor Burden and Alpha-Fetoprotein. Cancers (Basel) 2021; 13:4403. [PMID: 34503212 PMCID: PMC8430980 DOI: 10.3390/cancers13174403] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 08/26/2021] [Accepted: 08/27/2021] [Indexed: 12/12/2022] Open
Abstract
Microvascular invasion (MVI) is a significant risk factor for the recurrence of hepatocellular carcinoma, but it is a histological feature that needs to be confirmed after hepatectomy or liver transplantation. The preoperative prediction of MVI can optimize the treatment plan of HCC, but an easy and widely applicable model is still lacking. The aim of our study was to predict the risk of MVI using objective preoperative factors. We retrospectively collected 1153 patients who underwent liver resection for HCC, and MVI was found to be associated with significantly poor disease-free survival. The patients were randomly split in a 3:1 ratio into training (n = 864) and validation (n = 289) datasets. The multivariate analysis of the training dataset found preoperative total tumor volume (TTV) and alpha-fetoprotein (AFP) to be independent risk factors for MVI. We built a risk score model with cutoff points of TTV at 30, 60, and 300 cm3 and AFP at 160 and 2000 ng/mL, and the model stratified the risk of MVI into low risk (14.1%), intermediate risk (36.4%), and high risk (60.5%). The validation of the risk score model with the validation dataset showed moderate performance (the concordance statistic: 0.731). The model comprised simple and objective preoperative factors with good applicability, which can help to guide treatment plans for HCC and future study design.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Wei-Chen Lee
- Division of Liver and Transplantation Surgery, Department of General Surgery, Linkou Chang-Gung Memorial Hospital, Taoyuan City 333, Taiwan; (J.-C.L.); (H.-C.H.); (Y.-C.W.); (C.-H.C.); (T.-H.W.); (C.-F.L.); (T.-J.W.); (H.-S.C.); (K.-M.C.)
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13
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Tang M, Zhou Q, Huang M, Sun K, Wu T, Li X, Liao B, Chen L, Liao J, Peng S, Chen S, Feng ST. Nomogram development and validation to predict hepatocellular carcinoma tumor behavior by preoperative gadoxetic acid-enhanced MRI. Eur Radiol 2021; 31:8615-8627. [PMID: 33877387 DOI: 10.1007/s00330-021-07941-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 02/18/2021] [Accepted: 03/25/2021] [Indexed: 12/17/2022]
Abstract
OBJECTIVES Pretreatment evaluation of tumor biology and microenvironment is important to predict prognosis and plan treatment. We aimed to develop nomograms based on gadoxetic acid-enhanced MRI to predict microvascular invasion (MVI), tumor differentiation, and immunoscore. METHODS This retrospective study included 273 patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI. Patients were assigned to two groups: training (N = 191) and validation (N = 82). Univariable and multivariable logistic regression analyses were performed to investigate clinical variables and MRI features' associations with MVI, tumor differentiation, and immunoscore. Nomograms were developed based on features associated with these three histopathological features in the training cohort, then validated, and evaluated. RESULTS Predictors of MVI included tumor size, rim enhancement, capsule, percent decrease in T1 images (T1D%), standard deviation of apparent diffusion coefficient, and alanine aminotransferase levels, while capsule, peritumoral enhancement, mean relaxation time on the hepatobiliary phase (T1E), and alpha-fetoprotein levels predicted tumor differentiation. Predictors of immunoscore included the radiologic score constructed by tumor number, intratumoral vessel, margin, capsule, rim enhancement, T1D%, relaxation time on plain scan (T1P), and alpha-fetoprotein and alanine aminotransferase levels. Three nomograms achieved good concordance indexes in predicting MVI (0.754, 0.746), tumor differentiation (0.758, 0.699), and immunoscore (0.737, 0.726) in the training and validation cohorts, respectively. CONCLUSION MRI-based nomograms effectively predict tumor behaviors in HCC and may assist clinicians in prognosis prediction and pretreatment decisions. KEY POINTS • This study developed and validated three nomograms based on gadoxetic acid-enhanced MRI to predict MVI, tumor differentiation, and immunoscore in patients with HCC. • The pretreatment prediction of tumor microenvironment may be useful to guide accurate prognosis and planning of surgical and immunological therapies for individual patients with HCC.
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Affiliation(s)
- Mimi Tang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Qian Zhou
- Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Mengqi Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Kaiyu Sun
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | | | - Xin Li
- GE Healthcare, Shanghai, China
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Lili Chen
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Junbin Liao
- Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Sui Peng
- Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.,Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.,Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China
| | - Shuling Chen
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, China.
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14
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Chen L, Chen S, Zhou Q, Cao Q, Dong Y, Feng S, Xiao H, Wang Y, Liu X, Liao G, Peng Z, Li B, Tan L, Ke Z, Li D, Peng B, Peng S, Zhu L, Liao B, Kuang M. Microvascular Invasion Status and Its Survival Impact in Hepatocellular Carcinoma Depend on Tissue Sampling Protocol. Ann Surg Oncol 2021; 28:6747-6757. [PMID: 33751300 DOI: 10.1245/s10434-021-09673-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/14/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The aim of this work is to explore the impact of the number of sampling sites (NuSS) and sampling location on microvascular invasion (MVI) detection rate and long-term survival of hepatocellular carcinoma (HCC), and determine the minimum NuSS for sufficient MVI detection. PATIENTS AND METHODS From January 2008 to March 2017, 1144 HCC patients who underwent hepatectomy were retrospectively enrolled. Associations between NuSS and MVI positive rates and overall survival were investigated. NuSS thresholds were determined by Chow test and confirmed prospectively in 305 patients from April 2017 to February 2019. In the prospective cohort, the distribution of MVI in different sampling locations and its prognostic effect was evaluated. RESULTS MVI positive rates increased as NuSS increased, steadily reaching a plateau when NuSS reached a threshold. A threshold of four, six, eight, and eight sampling sites within paracancerous parenchyma ≤ 1 cm from tumor was required for detecting MVI in solitary tumors measuring 1.0-3.0, 3.1-4.9, and ≥ 5.0 cm and multiple tumors. Patients with adequate NuSS achieved longer survival than those with inadequate NuSS [hazard ratio (HR) = 0.75, P = 0.043]. For all MVI-positive patients, MVI could be detected positive in paracancerous parenchyma ≤ 1 cm from tumor. Patients with MVI positive in paracancerous parenchyma > 1 cm had higher recurrence risk than those with MVI positive only in parenchyma ≤ 1 cm (HR = 6.05, P < 0.001). CONCLUSIONS Adequate NuSS is associated with higher MVI detection rate and better survival of HCC patients. We recommend four, six, eight, and eight as the cut-points for evaluating MVI sampling quality and patients' prognostic stratification in the subgroups of solitary tumors measuring 1.0-3.0 cm, 3.1-4.9 cm and ≥ 5.0 cm and multiple tumors, respectively.
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Affiliation(s)
- Lili Chen
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuling Chen
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qian Zhou
- Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qinghua Cao
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu Dong
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Han Xiao
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuanqi Wang
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin Liu
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Guanrui Liao
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bin Li
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Li Tan
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zunfu Ke
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Dongming Li
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Baogang Peng
- Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sui Peng
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.,Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Luying Zhu
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
| | - Ming Kuang
- Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. .,Department of Liver Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. .,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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15
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CT Image-Based Texture Analysis to Predict Microvascular Invasion in Primary Hepatocellular Carcinoma. J Digit Imaging 2020; 33:1365-1375. [PMID: 32968880 DOI: 10.1007/s10278-020-00386-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 08/29/2020] [Accepted: 09/14/2020] [Indexed: 12/15/2022] Open
Abstract
The objective of this study was to determine the clinical value of computed tomography (CT) image-based texture analysis in predicting microvascular invasion of primary hepatocellular carcinoma (HCC). CT images of patients with HCC from May 2017 to May 2019 confirmed by surgery and histopathology were retrospectively analyzed. Image features including tumor margin, tumor capsule, peritumoral enhancement, hypoattenuating halo, intratumoral arteries, and tumor-liver differences were assessed. All patients were divided into microvascular invasion (MVI)-negative group (n = 34) and MVI-positive group (n = 68). Preoperative CT images were further imported into MaZda software, where the regions of interest of the lesions were manually delineated. Texture features of lesions based on pre-contrast, arterial, portal, and equilibrium phase CT images were extracted. Thirty optimal texture parameters were selected from each phase by Fisher's coefficient (Fisher), classification error probability combined with average correlation coefficient (POE+ACC), and mutual information (MI). Finally, receiver operating characteristic curve analysis was performed. The results showed that the Edmonson-Steiner grades, tumor size, tumor margin, and intratumoral artery characteristics were significantly different between the two groups (P = 0.012, < 0.001, < 0.001, = 0.003, respectively). There were 58 parameters with significant differences between the MVI-negative and MVI-positive groups (P < 0.001 for all). Among them, 12, 14, 17, and 15 parameters were derived from the pre-contrast phase, arterial phase, portal phase, and equilibrium phase respectively. According to the ROC analysis, optimal texture parameters based on the pre-contrast, arterial, portal, and equilibrium phases were 135dr_GLevNonU (AUC, 0.766; the cutoff value, 1055.00), Vertl_RLNonUni (AUC, 0.764; the cutoff value, 5974.38), 45dgr_GLevNonU (AUC, 0.762; the cutoff value, 924.34), and Vertl_RLNonUni (AUC, 0.754; the cutoff value, 4868.80), respectively. Texture analysis of preoperative CT images may be used as a non-invasive method to predict microvascular invasion in patients with primary hepatocellular carcinomas, and further to guide the treatment and evaluate prognosis. The most valuable parameters were derived from the gray-level run-length matrix.
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16
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A Systematic Review for Variables to Be Collected in a Transplant Database for Improving Risk Prediction. Transplantation 2020; 103:2591-2601. [PMID: 30768569 DOI: 10.1097/tp.0000000000002652] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). METHODS We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. RESULTS Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. CONCLUSIONS Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.
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17
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Zhang T, Pandey G, Xu L, Chen W, Gu L, Wu Y, Chen X. The Value of TTPVI in Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Cancer Manag Res 2020; 12:4097-4105. [PMID: 32581583 PMCID: PMC7276193 DOI: 10.2147/cmar.s245475] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose The objective of our study was to evaluate the value of two-trait predictor of venous invasion (TTPVI) in the prediction of pathological microvascular invasion (pMVI) in patients with hepatocellular carcinoma (HCC) from preoperative computed tomography (CT) and magnetic resonance (MR). Methods A total of 128 preoperative patients with findings of HCC were enrolled. Tumor size, tumor margins, tumor capsule, peritumoral enhancement, and TTPVI was assessed on preoperative CT and MRI images. Histopathological features were reviewed: pathological tumor size, tumor differentiation, pMVI along with alpha-fetoprotein level (AFP). Significant imaging findings and histopathological features were determined with univariate and multivariate logistic regression analysis. Results Univariate analysis revealed that tumor size (p<0.01), AFP level (p=0.043), tumor differentiation (p<0.01), peritumoral enhancement (p=0.003), pathological tumor size (p<0.01), tumor margins (p<0.01) on CT and MRI, and TTPVI (p<0.01) showed statistically significant associations with pMVI. In multivariate logistic regression analysis, tumor size (odds ratio [OR] = 1.294; 95% confidence interval [CI]: 1.155, 1.451; p < 0.001), tumor differentiation (odds ratio [OR] =1.384; 95% confidence interval [CI]: 1.224, 1.564; p < 0.001), and TTPVI (odds ratio [OR] = 4.802; 95% confidence interval [CI]: 1.037, 22.233; p=0.045) were significant independent predictors of pMVI. Using 5.8 as the threshold for size, one could obtain an area-under-curve (AUC) of 0.793, 95% confidence interval [CI]: 0.715 to 0.857. Conclusion Tumor size, tumor differentiation, and TTPVI depicted in preoperative CT and MRI had a statistically significant correlation with pMVI. Hence, TTPVI detected on CT and MRI may be predictive of pMVI in HCC cases.
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Affiliation(s)
- Tao Zhang
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Gaurab Pandey
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Lin Xu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Wen Chen
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Liangrui Gu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Yijun Wu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Xiuwen Chen
- Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
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18
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Park HJ, Park B, Lee SS. Radiomics and Deep Learning: Hepatic Applications. Korean J Radiol 2020; 21:387-401. [PMID: 32193887 PMCID: PMC7082656 DOI: 10.3348/kjr.2019.0752] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 01/05/2020] [Indexed: 12/12/2022] Open
Abstract
Radiomics and deep learning have recently gained attention in the imaging assessment of various liver diseases. Recent research has demonstrated the potential utility of radiomics and deep learning in staging liver fibroses, detecting portal hypertension, characterizing focal hepatic lesions, prognosticating malignant hepatic tumors, and segmenting the liver and liver tumors. In this review, we outline the basic technical aspects of radiomics and deep learning and summarize recent investigations of the application of these techniques in liver disease.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Bumwoo Park
- Health Innovation Big Data Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Al-Ameri AAM, Wei X, Wen X, Wei Q, Guo H, Zheng S, Xu X. Systematic review: risk prediction models for recurrence of hepatocellular carcinoma after liver transplantation. Transpl Int 2020; 33:697-712. [PMID: 31985857 DOI: 10.1111/tri.13585] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 10/10/2019] [Accepted: 01/21/2020] [Indexed: 12/17/2022]
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a significant clinical problem associated with poor surgical outcomes. This study aims to summarize the current evidence on risk prediction models of HCC recurrence after LT. PubMed and EMBASE were searched to May 25, 2019, for relevant articles. Studies originally designed to develop or validate a risk prediction model for HCC recurrence after LT were included. Two independent authors summarized the study characteristics and evaluated the risk of bias and applicability concerns in the included studies. From 26 included studies, 18 original risk prediction models were determined, but only five models were externally validated. The average number of predictors involved in the construction of risk models was three. The most frequently employed predictors were alpha-fetoprotein, tumor size, vascular invasion, tumor number, tumor differentiation, and neutrophil-lymphocyte ratio. Most studies showed good discriminatory performance (AUC >0.75). The overall quality of the included studies was generally low. Most of the original models lacked the highly recommended external and prospective validation in diverse populations. The AFP model was the well-validated preoperative risk model that can stratify patients into high- and low-risk groups.
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Affiliation(s)
- Abdulahad Abdulrab Mohammed Al-Ameri
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xue Wen
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Qiang Wei
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Haijun Guo
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Institution of Organ Transplantation, Zhejiang University, Hangzhou, China.,NHFPC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, Zhejiang Province, China
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Tschuor C, Ferrarese A, Kuemmerli C, Dutkowski P, Burra P, Clavien PA. Allocation of liver grafts worldwide - Is there a best system? J Hepatol 2019; 71:707-718. [PMID: 31199941 DOI: 10.1016/j.jhep.2019.05.025] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Revised: 05/23/2019] [Accepted: 05/27/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. The most frequent principles for allocation policies in liver transplantation are therefore criteria that rely on pre-transplant survival (sickest first policy), post-transplant survival (utility), or on their combination (benefit). However, large differences exist between centers and countries for ethical and legislative reasons. The aim of this study was to report the current worldwide practice of liver graft allocation and discuss respective advantages and disadvantages. METHODS Countries around the world that perform 95 or more deceased donor liver transplantations per year were analyzed for donation and allocation policies, as well as recipient characteristics. RESULTS Most countries use the model for end-stage liver disease (MELD) score, or variations of it, for organ allocation, while some countries opt for center-based allocation systems based on their specific requirements, and some countries combine both a MELD and center-based approach. Both the MELD and center-specific allocation systems have inherent limitations. For example, most countries or allocation systems address the limitations of the MELD system by adding extra points to recipient's laboratory scores based on clinical information. It is also clear from this study that cancer, as an indication for liver transplantation, requires special attention. CONCLUSION The sickest first policy is the most reasonable basis for the allocation of liver grafts. While MELD is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors, predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs. LAY SUMMARY An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. While the model for end-stage liver disease is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs.
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Affiliation(s)
- Christoph Tschuor
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Alberto Ferrarese
- Multivisceral Transplant Unit - Gastroenterology, Padua University Hospital, Padua, Italy
| | - Christoph Kuemmerli
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Philipp Dutkowski
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland
| | - Patrizia Burra
- Multivisceral Transplant Unit - Gastroenterology, Padua University Hospital, Padua, Italy.
| | - Pierre-Alain Clavien
- Department of Surgery & Transplantation, University Hospital of Zurich, Zurich, Switzerland.
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Feng ST, Jia Y, Liao B, Huang B, Zhou Q, Li X, Wei K, Chen L, Li B, Wang W, Chen S, He X, Wang H, Peng S, Chen ZB, Tang M, Chen Z, Hou Y, Peng Z, Kuang M. Preoperative prediction of microvascular invasion in hepatocellular cancer: a radiomics model using Gd-EOB-DTPA-enhanced MRI. Eur Radiol 2019; 29:4648-4659. [PMID: 30689032 DOI: 10.1007/s00330-018-5935-8] [Citation(s) in RCA: 146] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 11/01/2018] [Accepted: 11/29/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular cancer (HCC) is important for surgery strategy making. We aimed to develop and validate a combined intratumoural and peritumoural radiomics model based on gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in primary HCC patients. METHODS This study included a training cohort of 110 HCC patients and a validating cohort of 50 HCC patients. All the patients underwent preoperative Gd-EOB-DTPA-enhanced MRI examination and curative hepatectomy. The volumes of interest (VOIs) around the hepatic lesions including intratumoural and peritumoural regions were manually delineated in the hepatobiliary phase of MRI images, from which quantitative features were extracted and analysed. In the training cohort, machine-learning method was applied for dimensionality reduction and selection of the extracted features. RESULTS The proportion of MVI-positive patients was 38.2% and 40.0% in the training and validation cohort, respectively. Supervised machine learning selected ten features to establish a predictive model for MVI. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the combined intratumoural and peritumoural radiomics model in the training and validation cohort were 0.85 (95% confidence interval (CI), 0.77-0.93), 88.2%, 76.2%, and 0.83 (95% CI, 0.71-0.95), 90.0%, 75.0%, respectively. CONCLUSIONS We evaluate quantitative Gd-EOB-DTPA-enhanced MRI image features of both intratumoural and peritumoural regions and provide an effective radiomics-based model for the prediction of MVI in HCC patients, and may therefore help clinicians make precise decisions regarding treatment before the surgery. KEY POINTS • An effective radiomics model for prediction of microvascular invasion in HCC patients is established. • The radiomics model is superior to the radiologist in prediction of MVI. • The radiomics model can help clinicians in pretreatment decision making.
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Affiliation(s)
- Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yingmei Jia
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bing Liao
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bingsheng Huang
- National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China
| | - Qian Zhou
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xin Li
- GE Healthcare, Shanghai, China
| | - Kaikai Wei
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lili Chen
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Bin Li
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Shuling Chen
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xiaofang He
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Haibo Wang
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sui Peng
- Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ze-Bin Chen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, 510080, China
| | - Mimi Tang
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhihang Chen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, 510080, China
| | - Yang Hou
- Jinan University, Guangzhou, China
| | - Zhenwei Peng
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, 510080, China.
| | - Ming Kuang
- Department of Medical Ultrasonics, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou, 510080, China.
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Server S, Sabet S, Yaghouti K, Namal E, Inan N, Tokat Y. Value of Imaging Findings in the Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Transplant Proc 2019; 51:2403-2407. [PMID: 31402256 DOI: 10.1016/j.transproceed.2019.01.178] [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: 01/28/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND The purpose of this study was to determine the utility of some imaging findings in predicting microvascular invasion (MVI) and hepatocellular carcinoma (HCC) recurrence risk after liver transplantation. METHOD This retrospective study included 123 patients with histopathologically proven HCC at explant. All HCCs were classified as MVI positive (group I) or negative (group II) based on histopathological findings. In each group, multifocality, largest tumor size, bulging (tumor causing liver capsule expansion), beak sign (the acute angle between the tumor and liver parenchyma), and diffusion restriction on diffusion weighted images (DWI) were evaluated. These findings were compared between the groups by Student's t test. The relation between the parameters and MVI was analyzed by using the Spearman's correlation test. RESULTS Of the total patients, 30.1% had MVI (group I) and 69.9% (group II) did not have MVI. Presence of beak sign (P ≤ .005), bulging sign (P = .002), and diffusion restriction (P = .045) were significantly more frequent in group I than group II. The beak sign, bulging sign, and diffusion restriction were correlated with presence of MVI. Largest tumor size and multifocality were higher in group I than group II, but the differences were not statistically significant. CONCLUSION Radiologists and transplant surgeons should be aware of some clue imaging findings, especially beak and bulging signs because these findings may predict the presence of MVI in HCC. These patients might benefit from histologic confirmation of the tumor characteristics through biopsy and subsequent bridging treatment options before liver transplantation to reduce the risk of recurrence.
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Affiliation(s)
- Sadik Server
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey.
| | - Soheil Sabet
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Kourosh Yaghouti
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Esat Namal
- Department of Medical Oncology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Nagihan Inan
- Department of Radiology, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
| | - Yaman Tokat
- Department of Liver Transplantation, Istanbul Bilim University, Sisli Florence Nightingale Hospital, Istanbul, Turkey
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Thrombospondin-4 expression as a prognostic marker in hepatocellular carcinoma. Gene 2019; 696:219-224. [PMID: 30802535 DOI: 10.1016/j.gene.2019.02.049] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 02/02/2019] [Accepted: 02/06/2019] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS The extracellular calcium-binding protein family member thrombospondin-4 (THBS4) regulates cell migration, proliferation, attachment, adhesion, angiogenesis, neural development, tissue structure, organ development, pain signal transduction, and tumor growth. The aim of this study was to study THBS4 expression in hepatocellular carcinoma (HCC) and determine if it was a prognostic marker for this malignancy. METHODS We used immunohistochemistry and tissue microarrays to evaluate THBS4 expression in 84 HCC and matched para-cancerous tissues. Then, we assessed relationships between THBS4 expression and clinicopathological parameters. RESULTS THBS4 expression was higher in HCCs than in matched para-cancerous tissues (P < 0.001). There was a significant correlation between high THBS4 levels and preoperative serum alanine aminotransferase (P < 0.04). In HCC patients, high THBS4 expression was associated with shorter overall and disease-free survival compared with low THBS4 expression. Additionally, subgroup analysis showed that high THBS4 levels were only associated with poor overall survival for alpha-fetoprotein >40 ng/mL (P = 0.028) and cirrhosis (P = 0.002). Multivariate analysis showed that high THBS4 expression was an independent prognostic factor for both overall and disease-free survival. CONCLUSIONS Our data suggest that THBS4 may play a role in HCC development, and thus may be an independent prognostic marker and/or potential therapeutic target for HCC patients.
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Menyhárt O, Nagy Á, Győrffy B. Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. ROYAL SOCIETY OPEN SCIENCE 2018; 5:181006. [PMID: 30662724 PMCID: PMC6304123 DOI: 10.1098/rsos.181006] [Citation(s) in RCA: 337] [Impact Index Per Article: 48.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 11/08/2018] [Indexed: 05/03/2023]
Abstract
Background: Potential prognostic biomarker candidates for hepatocellular carcinoma (HCC) are abundant, but their generalizability is unexplored. We cross-validated markers of overall survival (OS) and vascular invasion in independent datasets. Methods: The literature search yielded 318 genes related to survival and 52 related to vascular invasion. Validation was performed in three datasets (RNA-seq, n = 371; Affymetrix arrays, n = 91; Illumina gene chips, n = 135) by uni- and multivariate Cox regression and Mann-Whitney U-test, separately for Asian and Caucasian patients. Results: One hundred and eighty biomarkers remained significant in Asian and 128 in Caucasian subjects at p < 0.05. After multiple testing correction BIRC5 (p = 1.9 × 10-10), CDC20 (p = 2.5 × 10-9) and PLK1 (p = 3 × 10-9) endured as best performing genes in Asian patients; however, none remained significant in the Caucasian cohort. In a multivariate analysis, significance was reached by stage (p = 0.0018) and expression of CENPH (p = 0.0038) and CDK4 (p = 0.038). KIF18A was the only gene predicting vascular invasion in the Affymetrix and Illumina cohorts (p = 0.003 and p = 0.025, respectively). Conclusion: Overall, about half of biomarker candidates failed to retain prognostic value and none were better than stage predicting OS. Impact: Our results help to eliminate biomarkers with limited capability to predict OS and/or vascular invasion.
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Affiliation(s)
- Otília Menyhárt
- 2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary
- MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary
| | - Ádám Nagy
- 2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary
- MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary
| | - Balázs Győrffy
- 2nd Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary
- MTA TTK Lendület Cancer Biomarker Research Group, Institute of Enzymology, Hungarian Academy of Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary
- Author for correspondence: Balázs Győrffy e-mail:
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Pavel M, Sanchez Cabus S, Crespo G, Ferrer J, Fondevila C, Fuster J, Garcia-Valdecasas J. Role of Adult Living Donor Liver Transplantation in the Treatment of Hepatocellular Carcinoma Within and Beyond Milan Criteria: A Comparative Study. Transplant Proc 2018; 50:1386-1395. [DOI: 10.1016/j.transproceed.2018.02.093] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 02/17/2018] [Indexed: 02/07/2023]
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Lam A, Bui K, Hernandez Rangel E, Nguyentat M, Fernando D, Nelson K, Abi-Jaoudeh N. Radiogenomics and IR. J Vasc Interv Radiol 2018; 29:706-713. [PMID: 29551544 DOI: 10.1016/j.jvir.2017.11.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Revised: 11/21/2017] [Accepted: 11/21/2017] [Indexed: 12/17/2022] Open
Abstract
Radiogenomics involves the integration of mineable data from imaging phenotypes with genomic and clinical data to establish predictive models using machine learning. As a noninvasive surrogate for a tumor's in vivo genetic profile, radiogenomics may potentially provide data for patient treatment stratification. Radiogenomics may also supersede the shortcomings associated with genomic research, such as the limited availability of high-quality tissue and restricted sampling of tumoral subpopulations. Interventional radiologists are well suited to circumvent these obstacles through advancements in image-guided tissue biopsies and intraprocedural imaging. Comprehensive understanding of the radiogenomic process is crucial for interventional radiologists to contribute to this evolving field.
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Affiliation(s)
- Alexander Lam
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868.
| | - Kevin Bui
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
| | - Eduardo Hernandez Rangel
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
| | - Michael Nguyentat
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
| | - Dayantha Fernando
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
| | - Kari Nelson
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
| | - Nadine Abi-Jaoudeh
- University of California, Irvine, School of Medicine, Department of Radiological Sciences, 101 The City Drive South, Orange, CA, 92868
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Zhu R, Weng D, Lu S, Lin D, Wang M, Chen D, Lv J, Li H, Lv F, Xi L, Zhou J, Ma D, Li N. Double-Dose Adenovirus-Mediated Adjuvant Gene Therapy Improves Liver Transplantation Outcomes in Patients with Advanced Hepatocellular Carcinoma. Hum Gene Ther 2018; 29:251-258. [PMID: 29446997 DOI: 10.1089/hum.2017.114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Affiliation(s)
- Ruidong Zhu
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Danhui Weng
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Shichun Lu
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Dongdong Lin
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Menglong Wang
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Dongdong Chen
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Jun Lv
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Hongjun Li
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Fudong Lv
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
| | - Ling Xi
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Jianfeng Zhou
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Ding Ma
- 2 Tumor Molecular Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, P.R. China
| | - Ning Li
- 1 Beijing YouAn Hospital affiliated with Capital Medical University , Beijing, P.R. China
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Prediction of Microvascular Invasion in Hepatocellular Carcinoma: Preoperative Gd-EOB-DTPA-Dynamic Enhanced MRI and Histopathological Correlation. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:9674565. [PMID: 29606926 PMCID: PMC5828041 DOI: 10.1155/2018/9674565] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2017] [Revised: 11/26/2017] [Accepted: 12/20/2017] [Indexed: 12/16/2022]
Abstract
Objective To investigate the imaging features observed in preoperative Gd-EOB-DTPA-dynamic enhanced MRI and correlated with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. Methods 66 HCCs in 60 patients with preoperative Gd-EOB-DTPA-dynamic enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, peritumor enhancement during mid-arterial phase, peritumor hypointensity during hepatobiliary phase, signal intensity ratio on DWI and apparent diffusion coefficients (ADC), T1 relaxation times, and the reduction rate between pre- and postcontrast enhancement images were assessed. Correlation between these features and histopathological presence of MVI was analyzed to establish a prediction model. Results Histopathology confirmed that MVI were observed in 17 of 66 HCCs. Univariate analysis showed tumor size (p = 0.003), margin (p = 0.013), peritumor enhancement (p = 0.001), and hypointensity during hepatobiliary phase (p = 0.004) were associated with MVI. A multiple logistic regression model was established, which showed tumor size, margin, and peritumor enhancement were combined predictors for the presence of MVI (α = 0.1). R2 of this prediction model was 0.353, and the sensitivity and specificity were 52.9% and 93.0%, respectively. Conclusion Large tumor size, irregular tumor margin, and peritumor enhancement in preoperative Gd-EOB-DTPA-dynamic enhanced MRI can predict the presence of MVI in HCC.
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Muaddi H, Al-Adra DP, Beecroft R, Ghanekar A, Moulton CA, Doyle A, Selzner M, Wei A, McGilvray ID, Gallinger S, Grant DR, Cattral MS, Greig PD, Kachura J, Cleary SP, Sapisochin G. Liver Transplantation is Equally Effective as a Salvage Therapy for Patients with Hepatocellular Carcinoma Recurrence Following Radiofrequency Ablation or Liver Resection with Curative Intent. Ann Surg Oncol 2018; 25:991-999. [PMID: 29327179 DOI: 10.1245/s10434-017-6329-x] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND Liver resection (LR) and radiofrequency ablation (RFA) are curative-intent therapies for early stages of hepatocellular carcinoma (HCC). If HCC recurs, salvage liver transplant (SLT) may constitute a treatment option. OBJECTIVE We aimed to compare the outcomes of patients transplanted for recurrent HCC after curative-intent therapies with those transplanted as initial therapy. METHODS We conducted a matched-control (1:1) cohort study comparing patients with HCC treated with primary liver transplant (PLT) with SLT after HCC recurrence. Matching was performed according to the size and number of viable tumors at explant pathology following liver transplant. RESULTS Between November 1999 and December 2014, 687 patients with HCC were listed for transplant at our institution. A total of 559 patients were transplanted; 509 patients were treated with PLT and 50 patients were treated with SLT for HCC recurrence after primary treatment with LR (n = 25) or RFA (n = 25). The median length of follow-up from transplant was 64 months (0.5-195), and the median time from curative-intent treatment of HCC with RFA or LR to recurrence was 9.5 months (1-36) and 14.5 months (3-143), respectively (p = 0.04). The matched cohort was composed of 48 SLT patients (23 LR and 25 RFA) and 48 PLT patients. The 5-year risk of recurrence after LT was 22% in the PLT group versus 32% in the SLT group (p = 0.53), while the 5-year actuarial patient survival after PLT was 69% versus 70% in the SLT group (p = 1). CONCLUSION Liver transplant is an effective treatment for patients with HCC recurrence following RFA or LR. Outcomes are similar in both groups.
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Affiliation(s)
- Hala Muaddi
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - David P Al-Adra
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Rob Beecroft
- Department of Radiology, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Anand Ghanekar
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Carol-Anne Moulton
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Adam Doyle
- Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Markus Selzner
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Alice Wei
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Ian D McGilvray
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Steven Gallinger
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - David R Grant
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Mark S Cattral
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Paul D Greig
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - John Kachura
- Department of Radiology, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Sean P Cleary
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Department of Surgery, University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada. .,Department of Surgery, Multi-Organ Transplant. University Health Network-Toronto General Hospital, University of Toronto, Toronto, ON, Canada.
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Costentin CE, Amaddeo G, Decaens T, Boudjema K, Bachellier P, Muscari F, Salamé E, Bernard PH, Francoz C, Dharancy S, Vanlemmens C, Radenne S, Dumortier J, Hilleret MN, Chazouillères O, Pageaux GP, Calderaro J, Laurent A, Roudot-Thoraval F, Duvoux C. Prediction of hepatocellular carcinoma recurrence after liver transplantation: Comparison of four explant-based prognostic models. Liver Int 2017; 37:717-726. [PMID: 28199760 DOI: 10.1111/liv.13388] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Accepted: 02/08/2017] [Indexed: 12/17/2022]
Abstract
AIM Discordance between pre-LT imaging and explanted liver findings have been reported after liver transplantation (LT) for hepatocellular carcinoma (HCC), suggesting the need of reassessing the risk of HCC recurrence post-LT. Our aims were to compare pre-LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. METHODS Staging according to pre-LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. RESULTS Pre-LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the "Up to seven" (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the "Up to seven" model was superior to the Decaens model (P=.034), which was superior to the Chan model (P=.0041) but not to the Iwatsuki model (P=.17). CONCLUSION Pre-LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based "Up to seven" and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT.
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Affiliation(s)
| | | | - Thomas Decaens
- Service d'hépatologie, CHU Grenoble Alpes, Grenoble, France
| | - Karim Boudjema
- Service de Chirurgie digestive, Hôpital Pontchaillou, Rennes, France
| | | | - Fabrice Muscari
- Service de Chirurgie digestive, Hôpital Rangueil, Toulouse, France
| | - Ephrem Salamé
- Service de Chirurgie digestive, CHU de Tours, Chambray-lès-Tours, France
| | | | | | | | | | - Sylvie Radenne
- Service d'hépatologie, Hôpital Lyon Croix Rousse, Lyon, France
| | - Jérôme Dumortier
- Service d'hépatologie, Hospices Civiles de Lyon, Hôpital Edouard Herriot, Lyon, France
| | | | | | | | - Julien Calderaro
- Département de Pathologie, Hôpital Henri Mondor, Créteil, France
| | - Alexis Laurent
- Service de Chirurgie digestive, Hôpital Henri Mondor, Créteil, France
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Reginelli A, Vanzulli A, Sgrazzutti C, Caschera L, Serra N, Raucci A, Urraro F, Cappabianca S. Vascular microinvasion from hepatocellular carcinoma: CT findings and pathologic correlation for the best therapeutic strategies. Med Oncol 2017; 34:93. [PMID: 28401484 DOI: 10.1007/s12032-017-0949-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 04/04/2017] [Indexed: 12/13/2022]
Abstract
Recurrence of HCC reduces survival rates in patients treated with surgery, and one of the most relevant risk factors for tumour recurrence is microvascular invasion (mVI). The identification of mVI on preoperative examinations could improve surgical planning's and techniques so as to reduce the risk of tumour recurrence. During our study, we have revised 101 CT examinations of the liver performed on patients diagnosed with solitary HCC who had surgical treatment and pathological analysis of the specimens for mVI in order to detect CT signs which could be reliable in mVI prediction. On CT examinations, the tumours were evaluated for margins, capsule, size, contrast enhancement, halo sign and Thad. From our statistical analysis, we found out that irregularity in tumour margins and defects in peritumoural capsule are the most significant characteristics predicting mVI in HCC. Every report on CT examinations performed on surgical candidate patients should include suggestions about mVI probability in order to tailor procedures, reduce tumour recurrence risk and improve survival rates.
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Affiliation(s)
- Alfonso Reginelli
- Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy.
| | - Angelo Vanzulli
- Niguarda Cancer Center - ASST Grande Ospedale Metropolitano, University of Milano, Niguarda, Milan, Italy
| | - Cristiano Sgrazzutti
- Niguarda Cancer Center - ASST Grande Ospedale Metropolitano, University of Milano, Niguarda, Milan, Italy
| | - Luca Caschera
- Niguarda Cancer Center - ASST Grande Ospedale Metropolitano, University of Milano, Niguarda, Milan, Italy
| | - Nicola Serra
- Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy
| | - Antonio Raucci
- Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy
| | - Fabrizio Urraro
- Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy
| | - Salvatore Cappabianca
- Department of Internal and Experimental Medicine, Second University of Naples, Naples, Italy
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Liver transplantation for hepatocellular carcinoma: outcomes and novel surgical approaches. Nat Rev Gastroenterol Hepatol 2017; 14:203-217. [PMID: 28053342 DOI: 10.1038/nrgastro.2016.193] [Citation(s) in RCA: 322] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Liver transplantation for hepatocellular carcinoma (HCC) is the best treatment option for patients with early-stage tumours and accounts for ∼20-40% of all liver transplantations performed at most centres worldwide. The Milan criteria are the most common criteria to select patients with HCC for transplantation but they can be seen as too restrictive. Several proposals have been made for a moderate expansion of the criteria, which result in good outcomes but with an increase in the risk of tumour recurrence. In this Review, we provide a comprehensive overview of the outcomes after liver transplantation for HCC, focusing on tumour recurrence in terms of surveillance, prevention and treatment. Additionally, novel surgical techniques have been developed to increase the available pool of organs for liver transplantation (such as living donor liver transplantation, donation after circulatory death and split livers), but the effect of these techniques on patients with HCC is still under debate. Thus, we will describe these techniques and expose the benefits and disadvantages of each surgical approach. Finally, we will comment on the limitations of the current priority policies for liver transplantation and the need to further refine them to better serve the population.
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Donat M, Alonso S, Pereira F, Ferrero E, Carrión L, Acin-Gándara D, Moreno E. Impact of Histological Factors of Hepatocellular Carcinoma on the Outcome of Liver Transplantation. Transplant Proc 2017; 48:1968-77. [PMID: 27569930 DOI: 10.1016/j.transproceed.2016.04.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 04/10/2016] [Accepted: 04/27/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND The aim of this study was to identify predictors of overall survival (OS), disease-free survival (DFS), and recurrence in a cohort of 151 patients with hepatocellular carcinoma (HCC) and cirrhosis who were treated by liver transplantation (LT). PATIENTS AND METHODS A retrospective database of patients undergoing LT for radiologically diagnosed HCC at "12 de Octubre" Hospital, Madrid during 1986-2006 was analyzed. RESULTS The median follow-up was 67.44 months (SD = 55.7 months). Overall 1-, 3-, 5-, and 10-year survival was 87.5%, 73.7%, 64.1% and 43.4%, respectively. The 5-year OS of patients beyond the Milan criteria was 47.14%, whereas that of patients within the Milan criteria was 70.13% (P = .011). The 5-year OS of patients beyond the Milan criteria and with microvascular invasion (MVI) was 27.27%, whereas that of patients beyond the Milan criteria and without MVI criteria was 57.89% (P = .003). Multivariate analysis of prognostic factors revealed MVI and G3 to be independent and statistically significant factors affecting OS (P < .0001 and P = .045, respectively), DFS (P < .0001 and P = .004, respectively), and recurrence (P = .0002 and P = .028, respectively). Multivariate analysis of prognostic factors also revealed preoperative fine-needle aspiration (FNA) to be an independent negative statistically significant factor affecting recurrence (P = .0022). Multivariate analysis of predictive MVI factors revealed preoperative α-fetoprotein (AFP) levels >200 ng/mL to be an independent positive and statistically significant predictor of MVI (P = .0004). CONCLUSION MVI and G3 are independent negative factors affecting OS, DFS, and recurrence. The presence of MVI or AFP levels >200 ng/mL represent a contraindication for LT, as long as the patient is beyond the Milan criteria.
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Affiliation(s)
- M Donat
- Department of General and Visceral Surgery, Infanta Leonor Hospital, Madrid, Spain
| | - S Alonso
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain.
| | - F Pereira
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - E Ferrero
- Department of General and Visceral Surgery, "12 de Octubre" University Hospital, Madrid, Spain
| | - L Carrión
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - D Acin-Gándara
- Department of General and Visceral Surgery, Fuenlabrada University Hospital, Madrid, Spain
| | - E Moreno
- Department of General and Visceral Surgery, "12 de Octubre" University Hospital, Madrid, Spain
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Feng J, Wu J, Zhu R, Feng D, Yu L, Zhang Y, Bu D, Li C, Zhou Y, Si L, Liu Y, Liang Z, Xu J, Wu T. Simple Risk Score for Prediction of Early Recurrence of Hepatocellular Carcinoma within the Milan Criteria after Orthotopic Liver Transplantation. Sci Rep 2017; 7:44036. [PMID: 28276470 PMCID: PMC5343663 DOI: 10.1038/srep44036] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 01/31/2017] [Indexed: 12/23/2022] Open
Abstract
Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604-0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. In the training cohort, the AUC value of the model was 0.767 (95% CI = 0.645-0.890, P < 0.001), which was the highest among all the elements. The model's performance was then assessed using a validation cohort. In the validation cohort, the AUC value of the model was 0.843 (95% CI = 0.720-0.966, P < 0.001) which was higher than any other elements. The results indicated that model had high performance with good discrimination ability and significantly improved the predictive capacity for the recurrence of HCC patients within MC after OLT.
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Affiliation(s)
- Jiliang Feng
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Jushan Wu
- General Surgical Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Ruidong Zhu
- General Surgical Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Dezhao Feng
- College of Life Science, Sichuan University, Sichuan, China
| | - Lu Yu
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Yan Zhang
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Dayu Bu
- Medical Record Statistics Management Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Chenlei Li
- Medical Record Statistics Management Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Yuyan Zhou
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Lianghao Si
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Yuhan Liu
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Ziwei Liang
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Jianing Xu
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
| | - Tianjun Wu
- Clinical-Pathology Center, Bejing You-An Hospital, Capital Medical University, Beijing, China
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Wang Z, Wang W, Liu GJ, Yang Z, Chen LD, Huang Y, Li W, Xie XY, Lu MD, Kuang M. The role of quantitation of real-time 3-dimensional contrast-enhanced ultrasound in detecting microvascular invasion: an in vivo study. Abdom Radiol (NY) 2016; 41:1973-9. [PMID: 27277527 DOI: 10.1007/s00261-016-0804-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE This study was to evaluate the role of quantitative perfusion analysis of 3-dimensional (3D) contrast-enhanced ultrasound (CEUS) in detecting microvascular invasion (MVI) of liver tumor in vivo. METHODS VX2 tumors were implanted in the livers of sixteen New Zealand rabbits. On day 10, real-time 3D CEUS was performed, and the real-time dynamic images were analyzed using online quantification software. The animals were sacrificed and sent for pathology examinations. According to the gold standard of pathology, the animals were divided into an MVI group and a group without MVI (non-MVI group). Time-intensity curves (TICs) were obtained for the VX2 tumors and the surrounding liver parenchyma, and the parameters peak intensity (PI), mean transit time (MTT), and time to peak (TTP) were compared within and between the MVI and non-MVI groups. RESULTS The TTP and MTT of the VX2 tumors were significantly faster than those of the surrounding liver parenchyma in both MVI and non-MVI groups. The PI of the VX2 tumors was significantly lower than that of the surrounding liver parenchyma in the non-MVI group but not the MVI group. The TTP and MTT of the VX2 tumors and surrounding liver parenchyma were not significantly different in the MVI group compared with the non-MVI group, whereas the ΔPI (the PI ratio between the VX2 liver tumors and the reference liver parenchyma) of the VX2 tumors in the MVI group was larger than that in the non-MVI group. VX2 tumors with MVI present different hemodynamic parameters, with a larger ΔPI than tumors without MVI. CONCLUSIONS Our data suggest that quantitative perfusion analysis of 3D CEUS might be a promising method for predicting MVI in liver tumors.
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Piñero F, Marciano S, Anders M, Orozco Ganem F, Zerega A, Cagliani J, Andriani O, de Santibañes E, Gil O, Podestá LG, McCormack L, Gadano A, Silva M. Identifying patients at higher risk of hepatocellular carcinoma recurrence after liver transplantation in a multicenter cohort study from Argentina. Eur J Gastroenterol Hepatol 2016; 28:421-427. [PMID: 26684693 DOI: 10.1097/meg.0000000000000551] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The Up-to-7 criteria on the basis of the explanted liver features categorize patients at higher risk of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). The aim of this study was to propose a novel pretransplant scoring system to predict recurrence including pre-LT data. PATIENTS AND METHODS From 763 consecutive adult patients who underwent transplantation in four LT centers from Argentina, 124 patients with HCC were included. A scoring system was developed in 87 patients from pre-LT risk factors for recurrence as determined by hazard ratios (HRs) from a multivariate Cox regression analysis. RESULTS Overall survival and recurrence rates at 5 years were 63.3 and 13.7%, respectively, during a follow-up period of 3.5±2.2 years. Variables associated with HCC recurrence on multivariate analysis were α-fetoprotein more than 100 ng/ml (HR=5.6, P=0.001) and tumor beyond Up-to-7 imaging criteria (HR=6.3, P=0.001). Bootstrap validation showed that overfitting was negligible. Scoring points were assigned as follows (0-2 points): pre-LT α-fetoprotein more than 100 ng/ml (presence=1 point, absence=0 point), and tumor beyond Up-to-7 imaging criteria (presence=1 point, absence=0 point). AUROC curve indicated a c-statistic of 0.74 (0.58-0.88, P=0.003). Two distinct subgroups of patients were identified with a cut-off more than or equal to 1 point (62% sensitivity and 82% specificity): low risk (0 point) and high risk (1-2 points). The 5-year recurrence rate was 9.4 and 44.5% (P=0.0001) and the 5-year overall survival was 78.1 and 34.8% (P=0.0001) in the low-risk and high-risk groups, respectively. CONCLUSION This scoring model may be a useful additional tool for HCC recurrence risk stratification before LT. Prospective studies are needed to evaluate our model.
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Affiliation(s)
- Federico Piñero
- aHepatology and Liver Transplant Unit, Hospital Universitario Austral bLiver Transplant Unit, Hospital Italiano de Buenos Aires cLiver Transplant Unit, Hospital Alemán, Buenos Aires dSchool of Medicine, University of Buenos Aires, Buenos Aires eLiver Transplant Unit, Hospital Allende, Córdoba, Argentina
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Cillo U, Giuliani T, Polacco M, Herrero Manley LM, Crivellari G, Vitale A. Prediction of hepatocellular carcinoma biological behavior in patient selection for liver transplantation. World J Gastroenterol 2016; 22:232-252. [PMID: 26755873 PMCID: PMC4698488 DOI: 10.3748/wjg.v22.i1.232] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 08/14/2015] [Accepted: 11/09/2015] [Indexed: 02/06/2023] Open
Abstract
Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as 18F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.
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Wang L, Wang J, Zhang X, Li J, Wei X, Cheng J, Ling Q, Xie H, Zhou L, Xu X, Zheng S. Diagnostic Value of Preoperative Needle Biopsy for Tumor Grading Assessment in Hepatocellular Carcinoma. PLoS One 2015; 10:e0144216. [PMID: 26658912 PMCID: PMC4682812 DOI: 10.1371/journal.pone.0144216] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 10/19/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Needle core biopsy (NCB) is one of the most widely used and accepted methods for the diagnosis of focal hepatic lesions. Although many studies have assessed the diagnostic accuracy of NCB in predicting the tumor grade, it is still under debate. OBJECTIVE To identify the influence of number of biopsies on NCB diagnostic accuracy. METHODS 153 patients with HCC were selected from patients who received preoperative NCB under the guidance of ultrasonography in our hospital. The diagnostic reference standard was the surgical pathologic diagnosis. RESULTS Using a 3-tier grading scheme (well, moderate and poor), the accuracy of NCB has no significant differences among different number of passes in HCC ≤5 cm. For HCC >5≤8 cm, the increasing number of passes could increase the diagnostic accuracy (63.3%, 81.8%, and 84.8% for passes one, two, and three, respectively). While in HCC>8 cm, the diagnostic accuracy of passes one, two, and three were 62.1%, 69%, and 75.8%, respectively. CONCLUSIONS The accuracy of NCB in assessing tumor grading associated with tumor size and number of passes. Meanwhile, a minimum of two passes should be performed to get better accuracy in patients with HCC >5 cm.
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Affiliation(s)
- Lijun Wang
- Department of Pathology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianguo Wang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Xuanyu Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Jie Li
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Xuyong Wei
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Jun Cheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Qi Ling
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
| | - Haiyang Xie
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lin Zhou
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | - Xiao Xu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, Zhejiang, China
- Collaborative innovation center for diagnosis and treatment of infectious diseases, Zhejiang University, Hangzhou, Zhejiang, China
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Liver Computed Tomographic Perfusion in the Assessment of Microvascular Invasion in Patients With Small Hepatocellular Carcinoma. Invest Radiol 2015; 50:188-94. [DOI: 10.1097/rli.0000000000000098] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Liver Transplantation for Hepatocellular Carcinoma. CURRENT TRANSPLANTATION REPORTS 2014. [DOI: 10.1007/s40472-014-0028-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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41
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Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation. AJR Am J Roentgenol 2014; 203:W253-9. [PMID: 25148181 DOI: 10.2214/ajr.13.10595] [Citation(s) in RCA: 127] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The objective of our study was to prospectively investigate whether nonsmooth margins detected on multiphasic CT images correlate with the presence and location of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). SUBJECTS AND METHODS A total of 102 patients with preoperative CT findings of solitary HCC were prospectively enrolled. Tumor size, tumor capsule, tumor margins, and peritumoral enhancement on preoperative CT images were assessed. Histopathologic results including the following were also recorded: tumor differentiation; liver fibrosis score; presence or absence of MVI; and, if present, the location of MVI. Correlation between tumor margin on preoperative CT images and histopathologic location of MVI was determined. RESULTS Pathologic examination revealed MVI in 60 of the 102 HCC specimens. Although the results of the univariate analysis showed that tumor size, higher Edmondson-Steiner grade, and nonsmooth tumor margins were associated with MVI, multivariate analysis revealed that only nonsmooth margins correlated with the presence of MVI in HCC (p < 0.001). Of the 60 HCC specimens with histopathologic evidence of MVI, 40 exhibited focal nonsmooth margins. In addition, the locations of the nonsmooth margins and MVI were similar in 36 of the 40 specimens. CONCLUSION Nonsmooth tumor margins correlated with the histopathologic presence and location of MVI. Therefore, nonsmooth margins detected on multiphasic CT may be predictive of MVI in HCC.
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Menon KV, Hakeem AR, Heaton ND. Review article: liver transplantation for hepatocellular carcinoma - a critical appraisal of the current worldwide listing criteria. Aliment Pharmacol Ther 2014; 40:893-902. [PMID: 25155143 DOI: 10.1111/apt.12922] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 01/16/2014] [Accepted: 07/27/2014] [Indexed: 12/08/2022]
Abstract
BACKGROUND Liver transplantation (LT) plays an important role in the management of patients with hepatocellular carcinoma (HCC). Although early results following LT for HCC were poor, since the introduction of the Milan criteria in 1996 morphological criteria have since been well established. Thereafter, various expansions of the Milan criteria were introduced worldwide. Listing criteria for LT for HCC in the United Kingdom (UK) initially conformed to the Milan criteria but were re-defined in 2009 by expansion of the Milan criteria. AIMS To look at the evidence in literature on listing criteria and management of HCC worldwide in comparison with the UK. Secondly, we aim to review worldwide vs. UK literature on prioritisation models, loco-regional therapy protocols and role of alpha-fetoprotein (AFP) in LT for HCC. METHODS An electronic literature search with Medline was carried out to identify articles related to LT for HCC. RESULTS Although various expansions of the Milan criteria have been described, they remain the gold standard against which other criteria are measured. The UK criteria are an expansion of the Milan criteria that go beyond Milan and University of California, San Francisco (UCSF) criteria. The current UK listing criteria for LT for HCC when compared to the worldwide criteria have a worse survival benefit (projected 5-year survival between 35-50%) when plotted on the metroticket calculator. CONCLUSIONS In keeping with most transplant centres worldwide, the UK have adopted expansions to Milan to allow more patients to benefit from LT. However, currently, as it stands the UK criteria when plotted in the modification of the Metroticket model project worse survival that would seem unjustified.
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Affiliation(s)
- K V Menon
- Institute of Liver Studies, Kings College Hospital, London, UK
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Itri JN, Heller MT, Tublin ME. Hepatic transplantation: postoperative complications. ACTA ACUST UNITED AC 2014; 38:1300-33. [PMID: 23644931 DOI: 10.1007/s00261-013-0002-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Advances in surgical techniques and immunosuppression have made orthotopic liver transplantation a first-line treatment for many patients with end-stage liver disease. The early detection and treatment of postoperative complications has contributed significantly to improved graft and patient survival with imaging playing a critical role in detection. Complications that can lead to graft failure or patient mortality include vascular abnormalities, biliary abnormalities, allograft rejection, and recurrent or post-transplant malignancy. Vascular abnormalities include stenosis and thrombosis of the hepatic artery, portal vein, and inferior vena cava, as well as hepatic artery pseudoaneurysm, arteriovenous fistula, and celiac stenosis. Biliary abnormalities include strictures, bile leak, obstruction, recurrent disease, and infection. While imaging is not used to diagnose allograft rejection, it plays an important role in identifying complications that can mimic rejection. Ultrasound is routinely performed as the initial imaging modality for the detection and follow-up of both early and delayed complications. Cholangiography and magnetic resonance cholangiopancreatography are used to characterize biliary complications and computed tomography is used to confirm abnormal findings on ultrasound or for the evaluation of postoperative collections. The purpose of this article is to describe and illustrate the imaging appearances and management of complications associated with liver transplantation.
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Affiliation(s)
- Jason N Itri
- University of Pittsburgh Medical Center, 200 Lothrop Street Presby South Tower, Suite 4896, Pittsburgh, PA, USA,
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Zhou J, Hu Z, Li Z, Yu P, Wu J, Zheng S. The role of liver cancer stem cells in donor liver allocation for patients with hepatocellular carcinoma. Postgrad Med 2013; 125:24-30. [PMID: 24200758 DOI: 10.3810/pgm.2013.11.2709] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Previous criteria for liver transplantation in patients with hepatocellular carcinoma (HCC) has predominantly emphasized the size and number of existent tumors; however, criteria have not included tumor biology, which may comprise a critical factor for predicting patient prognosis. This issue has been recognized in the Hangzhou criteria, which take tumor histopathologic grade and pre-transplant α-fetoprotein (AFP) level into consideration. However, neither histopathologic grading nor AFP level are precise enough to adequately represent tumor biology in patients with HCC. Recent research has indicated that the development and progression of HCC are driven by a subpopulation of liver cells with stem cell features (cancer stem cells, [CSCs]). Liver CSCs with cluster of differentiation (CD)133 antigen positivity show a high tumorigenic capacity, and the increase in the percentage of CD133+ liver cancer cells is consistent with increased levels of serum AFP. In addition, the number of CD90+ cells increases with the tumorigenicity of HCC, and a positive correlation between the number of circulating CD90+ liver CSCs and disease progression has been observed. As liver CSCs can be detected using the CD profile and could more accurately represent tumor biology in HCC, we hypothesized that liver CSCs with specific phenotypes could be used for modifying the Hangzhou criteria, thereby providing valuable guidance for the development of more accurate prognosis prediction algorithms for patients with HCC being considered for liver transplantation. We provide reliable evidence supporting this hypothesis, and offer proposals for future applications in transplant practice.
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Affiliation(s)
- Jie Zhou
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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Evaluation of safety parameters and changes in serum concentration in liver transplant recipients treated with doxorubicin during the anhepatic period. Cancer Chemother Pharmacol 2013; 72:1325-33. [PMID: 24121480 DOI: 10.1007/s00280-013-2311-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 09/25/2013] [Indexed: 12/22/2022]
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Truong BX, Yano Y, VAN VT, Seo Y, Nam NH, Trach NK, Utsumi T, Azuma T, Hayashi Y. Clinical utility of protein induced by vitamin K absence in patients with chronic hepatitis B virus infection. Biomed Rep 2012; 1:122-128. [PMID: 24648907 DOI: 10.3892/br.2012.4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2012] [Accepted: 08/20/2012] [Indexed: 12/16/2022] Open
Abstract
Hepatitis B virus (HBV) is a leading cause of hepatocellular carcinoma (HCC). α-fetoprotein (AFP) is a common tumor marker for the diagnosis of HCC, although not for protein induced by the absence of vitamin K or antagonist-II (PIVKA-II). The present study aimed to evaluate the role of PIVKA-II in the diagnosis of HCC in HBV-infected Vietnamese patients. A total of 166 consecutive HBV-infected Vietnamese patients were enrolled, including 41 HCC, 43 liver cirrhosis (LC), 26 chronic hepatitis (CH) and 56 asymptomatic carriers (ASC). AFP was examined using ELISA, while PIVKA-II was analyzed using Eitest PIVKA-II. The cut-off level of AFP and PIVKA-II was 20 ng/ml and 40 mAU/ml, respectively. Although the markers, AFP (344±356 ng/ml) and PIVKA-II (16,200±25,386 mAU/ml), were the highest in the HCC groups, only PIVKA-II in HCC was significantly higher compared to the other groups (P<0.001). The univariate analysis demonstrated that age over 50, male, genotype C, AFP and PIVKA-II were risk factors of LC and HCC. Results of the receiver operating characteristics (ROC) analysis showed that PIVKA-II was more sensitive to HCC compared to AFP. Moreover, PIVKA-II was strongly correlated with the portal venous thrombosis in HCC, as opposed to AFP. Results of the multivariate analysis demonstrated that PIVKA-II was the strongest independent risk factor of LC and HCC. In conclusion, PIVKA-II is likely to be a better marker for the diagnosis of HCC in chronic HBV-infected Vietnamese patients.
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Affiliation(s)
- Bui Xuan Truong
- Vinmec International Hospital; ; Department of Gastroenterology
| | - Yoshihiko Yano
- Department of Gastroenterology; ; Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
| | | | | | | | | | - Takako Utsumi
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan ; ; Indonesia-Japan Collaborative Research Center for Emerging and Reemerging Infectious Diseases, Research Institute for Tropical Medicine, Airlangga University, Surabaya, Indonesia
| | | | - Yoshitake Hayashi
- Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan
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Tsoulfas G, Mekras A, Agorastou P, Kiskinis D. Surgical treatment for large hepatocellular carcinoma: does size matter? ANZ J Surg 2012; 82:510-517. [PMID: 22548726 DOI: 10.1111/j.1445-2197.2012.06079.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Despite significant progress in the management of hepatocellular carcinoma (HCC), patients with large HCC (defined as >10 cm) continue to present a significant challenge. The goal of this paper is to review the existing literature regarding large HCC, with emphasis on identifying the issues and challenges involved in approaching these tumours surgically. A computerized search was made of the Medline database from January 1992 to December 2010. The MESH heading 'large' or 'huge' in combination with the keyword 'hepatocellular carcinoma' was used. After excluding further studies that identified 'large' HCC as less than 10 cm and/or sequential publications with overlapping patient populations, the search produced a study population of 22 non-duplicated papers, reporting on a total of 5223 patients with HCC tumours >10 cm. Regarding resection for large HCC, the overall 5-year survival in these studies ranged from 25% to 45%, with few outliers on both sides, whereas in most studies, the 5-year disease-free survival ranged between 15% and 35%, with the only exception being studies with patients with single lesions and no cirrhosis showing disease-free survival of 41% and 56%, respectively. Risk factors identified included vascular invasion, cirrhosis, high level of alpha-fetoprotein and the presence of multiple lesions. Finally, liver transplantation, although an attractive concept, did not appear to offer a survival benefit in any of the studies. In conclusion, identifying the risk factors that affect the outcome in patients undergoing surgery for large HCC is critical. The reason is that surgical resection can have excellent outcomes in carefully selected patients.
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Affiliation(s)
- Georgios Tsoulfas
- Department of Surgery, Aristoteleion University of Thessaloniki, 66 Tsimski St., Thessaloniki, Greece.
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Liver transplantation for hepatocellular carcinoma: how far can the selection criteria be expanded? Hepatol Int 2012. [PMID: 26201470 DOI: 10.1007/s12072-012-9351-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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Zhang M, Yin F, Chen B, Li B, Li YP, Yan LN, Wen TF. Mortality risk after liver transplantation in hepatocellular carcinoma recipients: A nonlinear predictive model. Surgery 2012; 151:889-97. [DOI: 10.1016/j.surg.2011.12.034] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2011] [Accepted: 12/22/2011] [Indexed: 12/12/2022]
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Maggs JRL, Suddle AR, Aluvihare V, Heneghan MA. Systematic review: the role of liver transplantation in the management of hepatocellular carcinoma. Aliment Pharmacol Ther 2012; 35:1113-34. [PMID: 22432733 DOI: 10.1111/j.1365-2036.2012.05072.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Revised: 09/18/2011] [Accepted: 03/02/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage. AIM To review systematically the role of liver transplantation in the management of HCC in current clinical practice. METHODS An electronic literature search using PUBMED (1980-2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation. RESULTS Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra-hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco-regional therapies have a role in the bridging treatment of HCC by minimising wait-list drop-out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down-staged tumours. Post-liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important. CONCLUSIONS Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait-list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.
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Affiliation(s)
- J R L Maggs
- Institute of Liver Studies, King's College Hospital, London, UK
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