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Yang Q, Zhou J, Luo B, Zheng R, Liao J, Tang L, Cheng W, Jing X, Cai W, Cheng Z, Liu F, Han Z, Yu X, Yu J, Liang P. Non-radiomics imaging (US-CEUS) features and clinical text features: correlation with microvascular invasion and tumor grading in hepatocellular carcinoma. Abdom Radiol (NY) 2025; 50:2476-2493. [PMID: 39607454 DOI: 10.1007/s00261-024-04659-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 10/25/2024] [Accepted: 10/26/2024] [Indexed: 11/29/2024]
Abstract
OBJECTIVES To predict microvascular invasion (MVI) status and tumor grading of hepatocellular carcinoma (HCC) by evaluating preoperative non-radiomics ultrasound and contrast-enhanced ultrasound (US-CEUS) features and determine the influences of MVI/tumor grading on the category of CEUS LI-RADS for HCC. METHODS A total of 506 HCC patients who underwent preoperative US-CEUS examinations from 8 hospitals between July 2020 and June 2023 were enrolled. According to the MVI status, all the patients were classified, and HCC differentiation was assessed by using Edmondson-Steiner (ES) grading: MVI-negative (M0) and low-grade ES (GI/II) (MN-L, n = 297) and MVI-positive (M1/M2) and/or high-grade ES (GIII/IV) (MP-H, n = 209). Stratified analysis was performed based on fibrosis stage and tumor size. RESULTS The results proved that MN-L HCC was more frequently classified into the LR-5 category (p = 0.034), while MP-H HCC was more frequently classified into the LR-TIV (p = 0.010). The heterogeneously arterial phase hyperenhancement (APHE) is significantly correlated with MVI(+)/high grade-ES (p = 0.003). Compared with MN-L HCC, the onset of washout was earlier, washout rate was higher, and tumor-invasion border was larger (all p < 0.01) in MP-H HCC. In addition, fibrosis stage and tumor size significantly influenced the onset of washout and washout rate of HCC (all p < 0.01). The tumor-invasion border was only positively correlated with tumor size (p < 0.001) rather than fibrosis stage (p > 0.05). CONCLUSIONS MVI status and tumor grading influence the classification of LR-5 and LR-TIV. Heterogeneous APHE, higher washout rate, earlier onset of washout (≤65 s), larger tumor-invasion border (≥3 mm) and higher alpha fetoprotein level indicate the presence of MVI and/or high-grade ES.
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Affiliation(s)
- Qi Yang
- Chinese PLA General Hospital, Beijing, China
- Peking University Shenzhen Hospital, Shenzhen, China
| | - Jianhua Zhou
- Sun Yat-sen University Cancer Center, Guangzhou, China
- Sun Yat-sen Memorial Hospital, Guangzhou, China
| | - Baoming Luo
- Sun Yat-sen Memorial Hospital, Guangzhou, China
| | - Rongqin Zheng
- Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | | | - Lina Tang
- Fujian Provincial Cancer Hospital, Fuzhou, China
| | - Wen Cheng
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiang Jing
- Tianjin Third Central Hospital, Tianjin, China
| | - Wenjia Cai
- Chinese PLA General Hospital, Beijing, China
| | | | - Fangyi Liu
- Chinese PLA General Hospital, Beijing, China
| | - Zhiyu Han
- Chinese PLA General Hospital, Beijing, China
| | - Xiaoling Yu
- Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Chinese PLA General Hospital, Beijing, China.
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González IA, Pacheco MC. What is New in Pediatric Hepatic Neoplasms. Surg Pathol Clin 2025; 18:281-300. [PMID: 40412827 DOI: 10.1016/j.path.2024.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025]
Abstract
The goal of this review is to provide a practical update on hepatic lesions affecting the pediatric population and is not meant to be an exhaustive summary of each entity. Hepatoblastoma is purposely not discussed as recent comprehensive reviews on this topic are available; instead, a discussion on rhabdoid tumor and the evolving concept of small cell undifferentiated hepatoblastoma and blastemal hepatoblastoma is included.
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Affiliation(s)
- Iván A González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W 11th St., Room 4068, Indianapolis, IN 46202, USA. https://twitter.com/IvanGonzalezMD
| | - Maria C Pacheco
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle Children's Hospital, 4800 Sand Point Way NE, FB 4.521 - Pathology Lab, Seattle, WA 98105, USA.
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Elias-Neto A, Gonzaga APFC, Braga FA, Gomes NBN, Torres US, D'Ippolito G. Imaging Prognostic Biomarkers in Hepatocellular Carcinoma: A Comprehensive Review. Semin Ultrasound CT MR 2024; 45:454-463. [PMID: 39067621 DOI: 10.1053/j.sult.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with its incidence on the rise globally. This paper provides a comprehensive review of prognostic imaging markers in HCC, emphasizing their role in risk stratification and clinical decision-making. We explore quantitative and qualitative criteria derived from imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), which can offer valuable insights into the biological behavior of the tumor. While many of these markers are not yet widely integrated into current clinical guidelines, they represent a promising future direction for approaching this highly heterogeneous cancer. However, standardization and validation of these markers remain important challenges. We conclude by emphasizing the importance of ongoing research to enhance clinical practices and improve outcomes for patients with HCC.
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Affiliation(s)
- Abrahão Elias-Neto
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Ana Paula F C Gonzaga
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Fernanda A Braga
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Natália B N Gomes
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Ulysses S Torres
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; Department of Radiology, Grupo Fleury, São Paulo, São Paulo, Brazil.
| | - Giuseppe D'Ippolito
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; Department of Radiology, Grupo Fleury, São Paulo, São Paulo, Brazil
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Hosseini MS, Bejnordi BE, Trinh VQH, Chan L, Hasan D, Li X, Yang S, Kim T, Zhang H, Wu T, Chinniah K, Maghsoudlou S, Zhang R, Zhu J, Khaki S, Buin A, Chaji F, Salehi A, Nguyen BN, Samaras D, Plataniotis KN. Computational pathology: A survey review and the way forward. J Pathol Inform 2024; 15:100357. [PMID: 38420608 PMCID: PMC10900832 DOI: 10.1016/j.jpi.2023.100357] [Citation(s) in RCA: 22] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 12/21/2023] [Accepted: 12/23/2023] [Indexed: 03/02/2024] Open
Abstract
Computational Pathology (CPath) is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field's future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath. For updated information on this survey review paper and accessing to the original model cards repository, please refer to GitHub. Updated version of this draft can also be found from arXiv.
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Affiliation(s)
- Mahdi S. Hosseini
- Department of Computer Science and Software Engineering (CSSE), Concordia Univeristy, Montreal, QC H3H 2R9, Canada
| | | | - Vincent Quoc-Huy Trinh
- Institute for Research in Immunology and Cancer of the University of Montreal, Montreal, QC H3T 1J4, Canada
| | - Lyndon Chan
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Danial Hasan
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Xingwen Li
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Stephen Yang
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Taehyo Kim
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Haochen Zhang
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Theodore Wu
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Kajanan Chinniah
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Sina Maghsoudlou
- Department of Computer Science and Software Engineering (CSSE), Concordia Univeristy, Montreal, QC H3H 2R9, Canada
| | - Ryan Zhang
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Jiadai Zhu
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Samir Khaki
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
| | - Andrei Buin
- Huron Digitial Pathology, St. Jacobs, ON N0B 2N0, Canada
| | - Fatemeh Chaji
- Department of Computer Science and Software Engineering (CSSE), Concordia Univeristy, Montreal, QC H3H 2R9, Canada
| | - Ala Salehi
- Department of Electrical and Computer Engineering, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
| | - Bich Ngoc Nguyen
- University of Montreal Hospital Center, Montreal, QC H2X 0C2, Canada
| | - Dimitris Samaras
- Department of Computer Science, Stony Brook University, Stony Brook, NY 11794, United States
| | - Konstantinos N. Plataniotis
- The Edward S. Rogers Sr. Department of Electrical & Computer Engineering (ECE), University of Toronto, Toronto, ON M5S 3G4, Canada
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Danzeng A, Guo L, Yang ZH, He ZW, Zeng CL, Ciren P, Lan RH, Jiang XW, Wang C, Zhang BH. Postoperative lenvatinib + PD-1 blockade reduces early tumor recurrence in hepatocellular carcinoma with microvascular invasion (Barcelona Clinic Liver Cancer stage 0 or A): a propensity score matching analysis. J Gastrointest Surg 2024; 28:1104-1112. [PMID: 38723996 DOI: 10.1016/j.gassur.2024.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 04/22/2024] [Accepted: 05/03/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI). METHODS A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses. RESULTS Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022). CONCLUSION Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals.
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Affiliation(s)
- Awang Danzeng
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ling Guo
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Zhen-Hua Yang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng-Wei He
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Cheng-Long Zeng
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Pingcuo Ciren
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Run-Hu Lan
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Xue-Wei Jiang
- Division of Hepato-Pancreato-Biliary Surgery, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China
| | - Chao Wang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Hao Zhang
- Department of Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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6
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Huang XW, Li Y, Jiang LN, Zhao BK, Liu YS, Chen C, Zhao D, Zhang XL, Li ML, Jiang YY, Liu SH, Zhu L, Zhao JM. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma. Open Med (Wars) 2024; 19:20240982. [PMID: 38883336 PMCID: PMC11179385 DOI: 10.1515/med-2024-0982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 05/18/2024] [Accepted: 05/21/2024] [Indexed: 06/18/2024] Open
Abstract
Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.
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Affiliation(s)
- Xiao-Wen Huang
- Medical School of Chinese PLA, Beijing, China
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Yan Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Li-Na Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Bo-Kang Zhao
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, China
| | - Yi-Si Liu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Chun Chen
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Dan Zhao
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Xue-Li Zhang
- Medical School of Chinese PLA, Beijing, China
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Mei-Ling Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Yi-Yun Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Shu-Hong Liu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Li Zhu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Jing-Min Zhao
- Medical School of Chinese PLA, Beijing, China
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
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Tang M, Zhang S, Yang M, Feng R, Lin J, Chen X, Xu Y, Yu R, Liao X, Li Z, Li X, Li M, Zhang Q, Chen S, Qian W, Liu Y, Song L, Li J. Infiltrative Vessel Co-optive Growth Pattern Induced by IQGAP3 Overexpression Promotes Microvascular Invasion in Hepatocellular Carcinoma. Clin Cancer Res 2024; 30:2206-2224. [PMID: 38470497 DOI: 10.1158/1078-0432.ccr-23-2933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 12/26/2023] [Accepted: 03/08/2024] [Indexed: 03/14/2024]
Abstract
PURPOSE Microvascular invasion (MVI) is a major unfavorable prognostic factor for intrahepatic metastasis and postoperative recurrence of hepatocellular carcinoma (HCC). However, the intervention and preoperative prediction for MVI remain clinical challenges due to the absent precise mechanism and molecular marker(s). Herein, we aimed to investigate the mechanisms underlying vascular invasion that can be applied to clinical intervention for MVI in HCC. EXPERIMENTAL DESIGN The histopathologic characteristics of clinical MVI+/HCC specimens were analyzed using multiplex immunofluorescence staining. The liver orthotopic xenograft mouse model and mechanistic experiments on human patient-derived HCC cell lines, including coculture modeling, RNA-sequencing, and proteomic analysis, were used to investigate MVI-related genes and mechanisms. RESULTS IQGAP3 overexpression was correlated significantly with MVI status and reduced survival in HCC. Upregulation of IQGAP3 promoted MVI+-HCC cells to adopt an infiltrative vessel co-optive growth pattern and accessed blood capillaries by inducing detachment of activated hepatic stellate cells (HSC) from the endothelium. Mechanically, IQGAP3 overexpression contributed to HCC vascular invasion via a dual mechanism, in which IQGAP3 induced HSC activation and disruption of the HSC-endothelial interaction via upregulation of multiple cytokines and enhanced the trans-endothelial migration of MVI+-HCC cells by remodeling the cytoskeleton by sustaining GTPase Rac1 activity. Importantly, systemic delivery of IQGAP3-targeting small-interfering RNA nanoparticles disrupted the infiltrative vessel co-optive growth pattern and reduced the MVI of HCC. CONCLUSIONS Our results revealed a plausible mechanism underlying IQGAP3-mediated microvascular invasion in HCC, and provided a potential target to develop therapeutic strategies to treat HCC with MVI.
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Affiliation(s)
- Miaoling Tang
- Department of Oncology, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Shuxia Zhang
- Department of Oncology, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Meisongzhu Yang
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Rongni Feng
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Jinbin Lin
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xiaohong Chen
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yingru Xu
- Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Ruyuan Yu
- Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xinyi Liao
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Ziwen Li
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Xincheng Li
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Man Li
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Qiliang Zhang
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Suwen Chen
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Wanying Qian
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Yuanji Liu
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
| | - Libing Song
- State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jun Li
- Department of Oncology, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
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8
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Kasuga R, Taniki N, Chu PS, Tamura M, Tabuchi T, Yamaguchi A, Hayatsu S, Koizumi J, Ojiro K, Hoshi H, Kaneko F, Morikawa R, Noguchi F, Yamataka K, Usui S, Ebinuma H, Itano O, Hasegawa Y, Abe Y, Kitago M, Inoue M, Nakatsuka S, Jinzaki M, Kitagawa Y, Kanai T, Nakamoto N. Multiple asynchronous recurrence as a predictive factor for refractoriness against locoregional and surgical therapy in patients with intermediate-stage hepatocellular carcinoma. Sci Rep 2024; 14:10896. [PMID: 38740983 DOI: 10.1038/s41598-024-61611-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 05/07/2024] [Indexed: 05/16/2024] Open
Abstract
Development of subclassification of intermediate-stage hepatocellular carcinoma (HCC) by treatment suitability is in demand. We aimed to identify predictors that define treatment refractoriness against locoregional(transarterial chemoembolization(TACE) or thermal ablation) and surgical therapy. This multicenter retrospective study enrolled 1167 HCC patients between 2015 and 2021. Of those, 209 patients were initially diagnosed with intermediate-stage HCC. Treatment refractoriness was defined as clinical settings that meets the following untreatable progressive conditions by TACE (1) 25% increase of intrahepatic tumor, (2) transient deterioration to Child-Pugh class C, (3) macrovascular invasion or extrahepatic spread, within one year. We then analyzed factors contributing to treatment refractoriness. The Child-Pugh score/class, number of tumors, infiltrative radiological type, and recurrence were significant factors. Focusing on recurrence as a predictor, median time to untreatable progression (TTUP) was 17.2 months in the recurrence subgroup whereas 35.5 months in the initial occurrence subgroup (HR, 2.06; 95% CI, 1.44-2.96; P = 0.001). Median TTUP decreased in cases with more later times of recurrence (3-5 recurrences, 17.3 months; ≥ 6 recurrences, 7.7 months). Recurrence, even more at later times, leads to increased treatment refractoriness. Early introduction of multidisciplinary treatment should be considered against HCC patients after multiple recurrent episodes.
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Affiliation(s)
- Ryosuke Kasuga
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Nobuhito Taniki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
| | - Po-Sung Chu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Masashi Tamura
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Takaya Tabuchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Akihiro Yamaguchi
- Division of Gastroenterology, Department of Internal Medicine, National Hospital Organization Saitama National Hospital, Saitama, Japan
| | - Shigeo Hayatsu
- Department of Surgery, National Hospital Organization Saitama National Hospital, Saitama, Japan
| | - Jun Koizumi
- Department of Diagnostic Radiology and Radiation Oncology, School of Medicine, Chiba University, Chiba, Japan
| | - Keisuke Ojiro
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, Chiba, Japan
| | - Hitomi Hoshi
- Department of Gastroenterology and Hepatology, Saitama City Hospital, Saitama, Japan
| | - Fumihiko Kaneko
- Department of Gastroenterology and Hepatology, Saitama City Hospital, Saitama, Japan
| | - Rei Morikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Fumie Noguchi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Karin Yamataka
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Shingo Usui
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Hirotoshi Ebinuma
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
- Department of Gastroenterology, School of Medicine, International University of Health and Welfare, Chiba, Japan
| | - Osamu Itano
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Chiba, Japan
| | - Yasushi Hasegawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yuta Abe
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Minoru Kitago
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masanori Inoue
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Seishi Nakatsuka
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Masahiro Jinzaki
- Department of Radiology, Keio University School of Medicine, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Takanori Kanai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
| | - Nobuhiro Nakamoto
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
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Teufel A, Kudo M, Qian Y, Daza J, Rodriguez I, Reissfelder C, Ridruejo E, Ebert MP. Current Trends and Advancements in the Management of Hepatocellular Carcinoma. Dig Dis 2024; 42:349-360. [PMID: 38599204 DOI: 10.1159/000538815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/08/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains a significant global health burden with a high mortality rate. Over the past 40 years, significant progress has been achieved in the prevention and management of HCC. SUMMARY Hepatitis B vaccination programs, the development of direct acting antiviral drugs for Hepatitis C, and effective surveillance strategies provide a profound basis for the prevention of HCC. Advanced surgery and liver transplantation along with local ablation techniques potentially offer cure for the disease. Also, just recently, the introduction of immunotherapy opened a new chapter in systemic treatment. Finally, the introduction of the BCLC classification system for HCC, clearly defining patient groups and assigning reasonable treatment options, has standardized treatment and become the basis of almost all clinical trials for HCC. With this review, we provide a comprehensive overview of the evolving landscape of HCC management and also touch on current challenges. KEY MESSAGE A comprehensive and multidisciplinary approach is crucial for effective HCC management. Continued research and clinical trials are imperative to further enhance treatment options and will ultimately reduce the global burden of this devastating disease.
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Affiliation(s)
- Andreas Teufel
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health (CPD), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Yuquan Qian
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jimmy Daza
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health (CPD), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Isaac Rodriguez
- Division of Hepatology, Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Clinical Cooperation Unit Healthy Metabolism, Center for Preventive Medicine and Digital Health (CPD), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ-Hector Cancer Institute, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Ezequiel Ridruejo
- Hepatology Section, Department of Medicine, Center for Medical Education and Clinical Research, Buenos Aires, Argentina
| | - Matthias P Ebert
- DKFZ-Hector Cancer Institute, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Molecular Medicine Partnership Unit, EMBL, Heidelberg, Germany
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10
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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-Like Lesions. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:842-946. [DOI: 10.1016/b978-0-7020-8228-3.00013-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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11
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Wu C, Du X, Zhang Y, Zhu L, Chen J, Chen Y, Wei Y, Liu Y. Five machine learning-based radiomics models for preoperative prediction of histological grade in hepatocellular carcinoma. J Cancer Res Clin Oncol 2023; 149:15103-15112. [PMID: 37624395 DOI: 10.1007/s00432-023-05327-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 08/19/2023] [Indexed: 08/26/2023]
Abstract
PURPOSE To compare the efficacy of radiomics models via five machine learning algorithms in predicting the histological grade of hepatocellular carcinoma (HCC) before surgery and to develop the most stable model to classify high-risk HCC patients. METHODS Contrast-enhanced computed tomography (CECT) images of 175 HCC patients before surgery were analysed, and radiomics features were extracted from CECT images (including arterial and portal phases). Five machine learning models, including Bayes, random forest (RF), k-nearest neighbors (KNN), logistic regression (LR), and support vector machine (SVM), were applied to establish the model. The stability of the five models was weighed by the relative standard deviation (RSD), and the lowest RSD value was chosen as the most stable model to predict the histological grade of HCC. The area under the curve (AUC) and Delong tests were devoted to assessing the predictive efficacy of the models. RESULTS High-grade HCC accounted for 28.57% (50/175) of the 175 patients. The RSD value of AUC via the RF machine learning model was the lowest (2.3%), followed by Bayes (3.2%), KNN (6.4%), SVM (8.7%) and LR (31.3%). In addition, the RF model (AUC = 0.995) was better than the other four models in the training set (p < 0.05), as well as obtained good predictive performance in the test set (AUC = 0.837). CONCLUSION Among the five machine learning models, the RF-based radiomics model was the most stable and performed excellently in identifying high histological grade of HCC.
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Affiliation(s)
- Cuiyun Wu
- Cancer Center, Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital),, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, China
| | - Xingyue Du
- Bengbu Medical College, Bengbu, Anhui, China
| | - Yang Zhang
- Cancer Center, Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital),, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, China
| | - Li Zhu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Junfa Chen
- Cancer Center, Department of Radiology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital),, Hangzhou Medical College, 158 Shangtang Road, Hangzhou, Zhejiang, China
| | - Yuan Chen
- Cancer Center, Department of Pathology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yuguo Wei
- Precision Health Institution, General Electric Healthcare, Hangzhou, Zhejiang, China
| | - Yang Liu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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12
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Wang Y, Liu Z, Xu H, Yang D, Jiang J, Asayo H, Yang Z. MRI-based radiomics model and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma. BMC Med Imaging 2023; 23:67. [PMID: 37254089 DOI: 10.1186/s12880-023-01030-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2023] [Accepted: 05/23/2023] [Indexed: 06/01/2023] Open
Abstract
BACKGROUND Prediction of locoregional treatment response is important for further therapeutic strategy in patients with hepatocellular carcinoma. This study aimed to investigate the role of MRI-based radiomics and nomogram for predicting the outcome of locoregional treatment in patients with hepatocellular carcinoma. METHODS The initial postoperative MRI after locoregional treatment in 100 patients with hepatocellular carcinoma was retrospectively analysed. The outcome was evaluated according to mRECIST at 6 months. We delineated the tumour volume of interest on arterial phase, portal venous phase and T2WI. The radiomics features were selected by using the independent sample t test or nonparametric Mann‒Whitney U test and the least absolute shrinkage and selection operator. The clinical variables were selected by using univariate analysis and multivariate analysis. The radiomics model and combined model were constructed via multivariate logistic regression analysis. A nomogram was constructed that incorporated the Rad score and selected clinical variables. RESULTS Fifty patients had an objective response, and fifty patients had a nonresponse. Nine radiomics features in the arterial phase were selected, but none of the portal venous phase or T2WI radiomics features were predictive of the treatment response. The best radiomics model showed an AUC of 0.833. Two clinical variables (hCRP and therapy method) were selected. The AUC of the combined model was 0.867. There was no significant difference in the AUC between the combined model and the best radiomics model (P = 0.573). Decision curve analysis demonstrated the nomogram has satisfactory predictive value. CONCLUSIONS MRI-based radiomics analysis may serve as a promising and noninvasive tool to predict outcome of locoregional treatment in HCC patients, which will facilitate the individualized follow-up and further therapeutic strategies guidance.
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Affiliation(s)
- Yuxin Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Zhenhao Liu
- Department of Radiology, Affiliated Hospital of Changzhi Institute of Traditional Chinese Medicine, Changzhi, 046099, China
| | - Hui Xu
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Dawei Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jiahui Jiang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Himeko Asayo
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Zhenghan Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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13
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Fowler KJ, Chernyak V, Ronot M, Vilgrain V, Kitao A, Lee JM, Motosugi U, Song B, Jiang H, Sirlin CB, Bashir MR. Hepatocellular Carcinoma: It Is Time to Focus on Prognosis. Radiology 2023; 307:e220884. [PMID: 37014249 PMCID: PMC10140632 DOI: 10.1148/radiol.220884] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/05/2022] [Accepted: 07/12/2022] [Indexed: 04/05/2023]
Affiliation(s)
- Kathryn J. Fowler
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Victoria Chernyak
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Maxime Ronot
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Valerie Vilgrain
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Azusa Kitao
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Jeong Min Lee
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Utaroh Motosugi
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Bin Song
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Hanyu Jiang
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Claude B. Sirlin
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
| | - Mustafa R. Bashir
- From the Department of Radiology, University of California San Diego,
6206 Lakewood St, San Diego, CA 92122 (K.J.F., C.B.S.); Department of Radiology,
Beth Israel Deaconess Medical Center, Boston, Mass (V.C.); Department of
Radiology, Université Paris Cité, Paris, France (M.R., V.V.);
Department of Radiology, Hôpital Beaujon, APHP.Nord, Clichy, France
(M.R., V.V.); Department of Radiology, Kanazawa University Graduate School of
Medicine, Kanazawa, Japan (A.K.); Department of Radiology, Seoul National
University College of Medicine, Seoul, Korea (J.M.L.); Department of Radiology,
Kofu Kyoritsu Hospital, Kofu, Japan (U.M.); Department of Radiology, West China
Hospital, Chengdu, China (B.S., H.J.); and Department of Radiology, Duke
University Medical Center, Durham, NC (M.R.B.)
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14
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Talbot T, D'Alessio A, Pinter M, Balcar L, Scheiner B, Marron TU, Jun T, Dharmapuri S, Ang C, Saeed A, Hildebrand H, Muzaffar M, Fulgenzi CAM, Amara S, Naqash AR, Gampa A, Pillai A, Wang Y, Khan U, Lee P, Huang Y, Bengsch B, Bettinger D, Mohamed YI, Kaseb A, Pressiani T, Personeni N, Rimassa L, Nishida N, Kudo M, Weinmann A, Galle PR, Muhammed A, Cortellini A, Vogel A, Pinato DJ. Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study. Liver Int 2023; 43:695-707. [PMID: 36577703 PMCID: PMC10947007 DOI: 10.1111/liv.15502] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 12/11/2022] [Accepted: 12/18/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post-ICI, also appraising treatment strategies. METHODS We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut-off. We evaluated post-progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI). RESULTS Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4-6.9; 271 events). At the data cut-off, 165 patients (45%) received no post-progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21-2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38-3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin-bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09-0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26-0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy. CONCLUSIONS ICI-TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.
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Affiliation(s)
- Thomas Talbot
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
| | - Antonio D'Alessio
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
| | - Matthias Pinter
- Division of Gastroenterology & Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Lorenz Balcar
- Division of Gastroenterology & Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Scheiner
- Division of Gastroenterology & Hepatology, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Thomas U. Marron
- Division of Hematology/Oncology, Department of Medicine, Tisch Cancer InstituteMount Sinai HospitalNew YorkNew YorkUSA
| | | | - Sirish Dharmapuri
- Division of Hematology/Oncology, Department of Medicine, Tisch Cancer InstituteMount Sinai HospitalNew YorkNew YorkUSA
| | - Celina Ang
- Division of Hematology/Oncology, Department of Medicine, Tisch Cancer InstituteMount Sinai HospitalNew YorkNew YorkUSA
| | - Anwaar Saeed
- Division of Medical Oncology, Department of MedicineKansas University Cancer CenterWestwoodKansasUSA
| | - Hannah Hildebrand
- Division of Medical Oncology, Department of MedicineKansas University Cancer CenterWestwoodKansasUSA
| | - Mahvish Muzaffar
- Division of Hematology/OncologyEast Carolina UniversityGreenvilleNorth CarolinaUSA
| | - Claudia A. M. Fulgenzi
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
- Department of Medical OncologyUniversity Campus Bio‐MedicoRomeItaly
| | - Suneetha Amara
- Division of Hematology/OncologyEast Carolina UniversityGreenvilleNorth CarolinaUSA
| | - Abdul Rafeh Naqash
- Division of Hematology/OncologyEast Carolina UniversityGreenvilleNorth CarolinaUSA
- Division of Cancer Treatment and DiagnosisNational Cancer InstituteBethesdaMarylandUSA
| | - Anuhya Gampa
- Section of GastroenterologyHepatology & Nutrition, the University of Chicago MedicineChicagoIllinoisUSA
| | - Anjana Pillai
- Section of GastroenterologyHepatology & Nutrition, the University of Chicago MedicineChicagoIllinoisUSA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology & NutritionThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Uqba Khan
- Division of Hematology and OncologyWeill Cornell Medicine/New York Presbyterian HospitalNew YorkNew YorkUSA
| | - Pei‐Chang Lee
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
| | - Yi‐Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
- Institute of Clinical MedicineNational Yang Ming Chiao Tung University School of MedicineTaipeiTaiwan
| | - Bertram Bengsch
- Department of Medicine II, Faculty of MedicineMedical Center University of Freiburg, University of FreiburgFreiburgGermany
| | - Dominik Bettinger
- Department of Medicine II, Faculty of MedicineMedical Center University of Freiburg, University of FreiburgFreiburgGermany
| | - Yehia I. Mohamed
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Ahmed Kaseb
- Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonTexasUSA
| | - Tiziana Pressiani
- Medical Oncology and Hematology Unit, Humanitas Cancer CenterIRCCS Humanitas Research HospitalMilanItaly
| | - Nicola Personeni
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Medical Oncology and Hematology Unit, Humanitas Cancer CenterIRCCS Humanitas Research HospitalMilanItaly
| | - Lorenza Rimassa
- Department of Biomedical SciencesHumanitas UniversityMilanItaly
- Medical Oncology and Hematology Unit, Humanitas Cancer CenterIRCCS Humanitas Research HospitalMilanItaly
| | - Naoshi Nishida
- Department of Gastroenterology and HepatologyKindai University Faculty of MedicineOsaka‐SayamaJapan
| | - Masatoshi Kudo
- Department of Gastroenterology and HepatologyKindai University Faculty of MedicineOsaka‐SayamaJapan
| | - Arndt Weinmann
- 1st Department of Internal Medicine, Gastroenterology and HepatologyUniversity Medical Center of the Johannes Gutenberg‐University MainzMainzGermany
| | - Peter R. Galle
- 1st Department of Internal Medicine, Gastroenterology and HepatologyUniversity Medical Center of the Johannes Gutenberg‐University MainzMainzGermany
| | - Ambreen Muhammed
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
| | - Alessio Cortellini
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
| | - Arndt Vogel
- Department of Gastroenterology, Hepatology and EndocrinologyHannover Medical SchoolHannoverGermany
| | - David J. Pinato
- Department of Surgery & Cancer, Imperial College LondonHammersmith HospitalLondonUK
- Division of Oncology, Department of Translational MedicineUniversity of Piemonte Orientale “A. Avogadro”NovaraItaly
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15
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Shin SH, Park JY, Hwang C, Lee HJ, Shin DH, Kim JY, Ryu JH, Yang KH, Lee TB, Lee JH. Histological subtypes of hepatocellular carcinoma: Their clinical and prognostic significance. Ann Diagn Pathol 2023; 64:152134. [PMID: 37004359 DOI: 10.1016/j.anndiagpath.2023.152134] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 03/26/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023]
Abstract
Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC.
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Affiliation(s)
- So Hyun Shin
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Joon Young Park
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Chungsu Hwang
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Hyun Jung Lee
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Dong Hoon Shin
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Jee Yeon Kim
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Je Ho Ryu
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Kwang Ho Yang
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Tae Beom Lee
- Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea
| | - Jung Hee Lee
- Department of Pathology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, 20 Geumo-ro, Mulgeum-eup, Yangsan-si, Gyeongsangnam-do 50612, Republic of Korea.
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16
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Xiao Y, Zhou C, Ni X, Huang P, Wu F, Yang C, Zeng M. Preoperative subcategorization based on magnetic resonance imaging in intrahepatic cholangiocarcinoma. Cancer Imaging 2023; 23:15. [PMID: 36782276 PMCID: PMC9926776 DOI: 10.1186/s40644-023-00533-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 02/09/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND Appropriate preoperative identification of iCCA subtype is essential for personalized management, so the aim of this study is to investigate the role of MR imaging features in preoperatively differentiating the iCCA subtype. METHODS Ninety-three patients with mass-forming intrahepatic cholangiocarcinoma (iCCA, 63 small duct type and 30 large duct type) were retrospectively enrolled according to the latest 5th WHO classification (mean age, males vs. females: 60.66 ± 10.53 vs. 61.88 ± 12.82, 50 men). Significant imaging features for differentiating large duct iCCA and small duct iCCA were identified using univariate and multivariate logistic regression analyses, and a regression-based predictive model was then generated. Furthermore, diagnostic performance parameters of single significant imaging features and the predictive model were obtained, and corresponding receiver operating characteristic (ROC) curves were subsequently presented. RESULTS The univariate analysis showed that tumor in vein, arterial phase hypoenhancement, intrahepatic duct dilatation, lack of targetoid restriction and lack of targetoid appearance in T2 were predictors of large duct type iCCA. Arterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction were independent predictors for large duct type iCCA in multivariate analysis. The regression-based predictive model has achieved the best preoperative prediction performance in iCCA subcategorization so far. The area under the ROC curve of the regression-based predictive model was up to 0.91 (95% CI: 0.85, 0.98), and it was significantly higher than every single significant imaging feature. CONCLUSIONS Arterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction could be considered reliable MR imaging indicators of large duct type iCCA. MR imaging features can facilitate noninvasive prediction of iCCA subtype with satisfactory predictive performance.
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Affiliation(s)
- Yuyao Xiao
- grid.8547.e0000 0001 0125 2443Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Changwu Zhou
- grid.8547.e0000 0001 0125 2443Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China ,grid.413087.90000 0004 1755 3939Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Xiaoyan Ni
- grid.8547.e0000 0001 0125 2443Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Peng Huang
- grid.8547.e0000 0001 0125 2443Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Fei Wu
- grid.8547.e0000 0001 0125 2443Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032 China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China.
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, China. .,Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
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17
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Criss CR, Makary MS. Salvage locoregional therapies for recurrent hepatocellular carcinoma. World J Gastroenterol 2023; 29:413-424. [PMID: 36688022 PMCID: PMC9850930 DOI: 10.3748/wjg.v29.i3.413] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/20/2022] [Accepted: 01/02/2023] [Indexed: 01/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide. Despite the advent of screening efforts and algorithms to stratify patients into appropriate treatment strategies, recurrence rates remain high. In contrast to first-line treatment for HCC, which relies on several factors, including clinical staging, tumor burden, and liver function, there is no consensus or general treatment recommendations for recurrent HCC (R-HCC). Locoregional therapies include a spectrum of minimally invasive liver-directed treatments which can be used as either curative or neoadjuvant therapy for HCC. Herein, we provide a comprehensive review of recent evidence using salvage loco-regional therapies for R-HCC after failed curative-intent.
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Affiliation(s)
- Cody R Criss
- Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, United States
| | - Mina S Makary
- Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210, United States
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18
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Miranda J, Horvat N, Fonseca GM, Araujo-Filho JDAB, Fernandes MC, Charbel C, Chakraborty J, Coelho FF, Nomura CH, Herman P. Current status and future perspectives of radiomics in hepatocellular carcinoma. World J Gastroenterol 2023; 29:43-60. [PMID: 36683711 PMCID: PMC9850949 DOI: 10.3748/wjg.v29.i1.43] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Revised: 10/27/2022] [Accepted: 12/14/2022] [Indexed: 01/04/2023] Open
Abstract
Given the frequent co-existence of an aggressive tumor and underlying chronic liver disease, the management of hepatocellular carcinoma (HCC) patients requires experienced multidisciplinary team discussion. Moreover, imaging plays a key role in the diagnosis, staging, restaging, and surveillance of HCC. Currently, imaging assessment of HCC entails the assessment of qualitative characteristics which are prone to inter-reader variability. Radiomics is an emerging field that extracts high-dimensional mineable quantitative features that cannot be assessed visually with the naked eye from medical imaging. The main potential applications of radiomic models in HCC are to predict histology, response to treatment, genetic signature, recurrence, and survival. Despite the encouraging results to date, there are challenges and limitations that need to be overcome before radiomics implementation in clinical practice. The purpose of this article is to review the main concepts and challenges pertaining to radiomics, and to review recent studies and potential applications of radiomics in HCC.
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Affiliation(s)
- Joao Miranda
- Department of Radiology, University of Sao Paulo, Sao Paulo 05403-010, Brazil
| | - Natally Horvat
- Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States
| | | | | | - Maria Clara Fernandes
- Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States
| | - Charlotte Charbel
- Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States
| | - Jayasree Chakraborty
- Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, United States
| | | | - Cesar Higa Nomura
- Department of Radiology, University of Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Paulo Herman
- Department of Gastroenterology, University of Sao Paulo, Sao Paulo 05403-000, Brazil
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19
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Sim JZT, Hui TCH, Chuah TK, Low HM, Tan CH, Shelat VG. Efficacy of texture analysis of pre-operative magnetic resonance imaging in predicting microvascular invasion in hepatocellular carcinoma. World J Clin Oncol 2022; 13:918-928. [PMID: 36483976 PMCID: PMC9724184 DOI: 10.5306/wjco.v13.i11.918] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 10/13/2022] [Accepted: 11/04/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Presence of microvascular invasion (MVI) indicates poorer prognosis post-curative resection of hepatocellular carcinoma (HCC), with an increased chance of tumour recurrence. By present standards, MVI can only be diagnosed post-operatively on histopathology. Texture analysis potentially allows identification of patients who are considered 'high risk' through analysis of pre-operative magnetic resonance imaging (MRI) studies. This will allow for better patient selection, improved individualised therapy (such as extended surgical margins or adjuvant therapy) and pre-operative prognostication. AIM This study aims to evaluate the accuracy of texture analysis on pre-operative MRI in predicting MVI in HCC. METHODS Retrospective review of patients with new cases of HCC who underwent hepatectomy between 2007 and 2015 was performed. Exclusion criteria: No pre-operative MRI, significant movement artefacts, loss-to-follow-up, ruptured HCCs, previous hepatectomy and adjuvant therapy. Fifty patients were divided into MVI (n = 15) and non-MVI (n = 35) groups based on tumour histology. Selected images of the tumour on post-contrast-enhanced T1-weighted MRI were analysed. Both qualitative (performed by radiologists) and quantitative data (performed by software) were obtained. Radiomics texture parameters were extracted based on the largest cross-sectional area of each tumor and analysed using MaZda software. Five separate methods were performed. Methods 1, 2 and 3 exclusively made use of features derived from arterial, portovenous and equilibrium phases respectively. Methods 4 and 5 made use of the comparatively significant features to attain optimal performance. RESULTS Method 5 achieved the highest accuracy of 87.8% with sensitivity of 73% and specificity of 94%. CONCLUSION Texture analysis of tumours on pre-operative MRI can predict presence of MVI in HCC with accuracies of up to 87.8% and can potentially impact clinical management.
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Affiliation(s)
- Jordan Zheng Ting Sim
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Terrence Chi Hong Hui
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Tong Kuan Chuah
- School of Engineering, Ngee Ann Polytechnic, Singapore 599489, Singapore
| | - Hsien Min Low
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | - Cher Heng Tan
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Vishal G Shelat
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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20
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Sessa A, Mulé S, Brustia R, Regnault H, Galletto Pregliasco A, Rhaiem R, Leroy V, Sommacale D, Luciani A, Calderaro J, Amaddeo G. Macrotrabecular-Massive Hepatocellular Carcinoma: Light and Shadow in Current Knowledge. J Hepatocell Carcinoma 2022; 9:661-670. [PMID: 35923611 PMCID: PMC9342198 DOI: 10.2147/jhc.s364703] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/22/2022] [Indexed: 12/11/2022] Open
Abstract
The subject of this narrative review is macrotrabecular-massive hepatocellular carcinoma (MTM‐HCC). Despite their rarity, these tumours are of general interest because of their epidemiological and clinical features and for representing a distinct model of the interaction between the angiogenetic system and neoplastic cells. The MTM‐HCC subtype is associated with various adverse biological and pathological parameters (the Alfa-foetoprotein (AFP) serum level, tumour size, vascular invasion, and satellite nodules) and is a key determinant of patient prognosis, with a strong and independent predictive value for early and overall tumour recurrence. Gene expression profiling has demonstrated that angiogenesis activation is a hallmark feature of MTM-HCC, with overexpression of both angiopoietin 2 (ANGPT2) and vascular endothelial growth factor A (VEGFA).
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Affiliation(s)
- Anna Sessa
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Correspondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email ;
| | - Sébastien Mulé
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Raffaele Brustia
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Hélène Regnault
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Inserm, U955, Team 18, Créteil, France
| | | | - Rami Rhaiem
- Department of Hepato-Biliary Pancreatic and Digestive Oncological Surgery, Robert Debré University Hospital, Reims, France
- Reims Champagne-Ardenne University, Reims, France
| | - Vincent Leroy
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
| | - Daniele Sommacale
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Digestive and Hepato-Pancreato-Biliary Surgery, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Alain Luciani
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Medical Imaging Department, AP-HP, Henri Mondor University Hospital, Créteil, France
| | - Julien Calderaro
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Department of Pathology, APHP, Henri Mondor University Hospital, Créteil, France
| | - Giuliana Amaddeo
- Hepatology Department, APHP, Henri Mondor University Hospital, Créteil, France
- Université Paris-Est Créteil, Faculté de Médecine, Créteil, France
- Inserm, U955, Team 18, Créteil, France
- Correspondence: Giuliana Amaddeo; Anna Sessa, Hepatology Department, APHP, Henri Mondor University Hospital, 1 rue Gustave Eiffel, Créteil, 94000, France, Tel +33 149812353, Email ;
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21
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Zhang S, Zhong BY, Zhang L, Wang WS, Ni CF. Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition. World J Gastrointest Surg 2022; 14:528-537. [PMID: 35979416 PMCID: PMC9258238 DOI: 10.4240/wjgs.v14.i6.528] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/08/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.
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Affiliation(s)
- Shen Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Lei Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Wan-Sheng Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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22
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Liang X, Shi S, Gao T. Preoperative gadoxetic acid-enhanced MRI predicts aggressive pathological features in LI-RADS category 5 hepatocellular carcinoma. Clin Radiol 2022; 77:708-716. [PMID: 35738938 DOI: 10.1016/j.crad.2022.05.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/30/2022] [Accepted: 05/19/2022] [Indexed: 11/09/2022]
Abstract
AIM To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features and non-LI-RADS imaging features can predict aggressive pathological features in adult patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS From February 2018 to September 2021, 236 adult patients with cirrhosis or hepatitis B virus infection in which liver cancer was suspected underwent MRI within 1 month before surgery. Significant MRI findings and alpha-fetoprotein (AFP) level predicted high-grade HCC and microvascular invasion (MVI) by univariate and multivariate logistic regression models. RESULTS The study included 112 patients with histopathologically confirmed liver cancer (≤5 cm), 35 of whom (31.3%) high-grade HCC and 42 of 112 (37.5%) patients had MVI. Mosaic architecture (odds ratio [OR] = 6.031; 95% confidence interval [CI]: 1.366, 26.626; p=0.018), coronal enhancement (OR=5.878; 95% CI: 1.471, 23.489; p=0.012), and intratumoural vessels (OR=5.278; 95% CI: 1.325, 21.020; p=0.018) were significant independent predictors of high-grade HCC. A non-smooth tumour margin (OR=10.237; 95% CI: 1.547, 67.760; p=0.016), coronal enhancement (OR=3.800; 95% CI: 1.152, 12.531; p=0.028), and peritumoural hypointensity on the hepatobiliary phase (HBP; OR=10.322; 95% CI: 2.733, 38.986; p=0.001) were significant independent predictors of MVI. CONCLUSION In high-risk adult patients with single LR-5 HCC (≤5 cm), mosaic architecture, coronal enhancement, and intratumoural vessels are independent predictors of high-grade HCC. Non-smooth tumour margin, coronal enhancement, and peritumoural hypointensity on HBP independently predicted MVI.
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Affiliation(s)
- X Liang
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China
| | - S Shi
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China
| | - T Gao
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China.
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Mao Y, Wang J, Zhu Y, Chen J, Mao L, Kong W, Qiu Y, Wu X, Guan Y, He J. Gd-EOB-DTPA-enhanced MRI radiomic features for predicting histological grade of hepatocellular carcinoma. Hepatobiliary Surg Nutr 2022; 11:13-24. [PMID: 35284527 PMCID: PMC8847875 DOI: 10.21037/hbsn-19-870] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 05/11/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND Prediction models for the histological grade of hepatocellular carcinoma (HCC) remain unsatisfactory. The purpose of this study is to develop preoperative models to predict histological grade of HCC based on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) radiomics. And to compare the performance between artificial neural network (ANN) and logistic regression model. METHODS A total of 122 HCCs were randomly assigned to the training set (n=85) and the test set (n=37). There were 242 radiomic features extracted from volumetric of interest (VOI) of arterial and hepatobiliary phases images. The radiomic features and clinical parameters [gender, age, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), alanine aminotransferase (ALT), aspartate transaminase (AST)] were selected by permutation test and decision tree. ANN of arterial phase (ANN-AP), logistic regression model of arterial phase (LR-AP), ANN of hepatobiliary phase (ANN-HBP), logistic regression mode of hepatobiliary phase (LR-HBP), ANN of combined arterial and hepatobiliary phases (ANN-AP + HBP), and logistic regression model of combined arterial and hepatobiliary phases (LR-AP + HBP) were built to predict HCC histological grade. Those prediction models were assessed and compared. RESULTS ANN-AP and LR-AP were composed by AST and radiomic features based on arterial phase. ANN-HBP and LR-HBP were composed by AFP and radiomic features based on hepatobiliary phase. ANN-AP + HBP and LR-AP + HBP were composed by AST and radiomic features based on arterial and hepatobiliary phases. The prediction models could distinguish between high-grade tumors [Edmondson-Steiner (E-S) grade III and IV] and low-grade tumors (E-S grade I and II) in both training set and test set. In the test set, the AUCs of ANN-AP, LR-AP, ANN-HBP, LR-HBP, ANN-AP + HBP and LR-AP + HBP were 0.889, 0.777, 0.941, 0.819, 0.944 and 0.792 respectively. The ANN-HBP was significantly superior to LR-HBP (P=0.001). And the ANN-AP + HBP was significantly superior to LR-AP + HBP (P=0.007). CONCLUSIONS Prediction models consisting of clinical parameters and Gd-EOB-DTPA-enhanced MRI radiomic features (based on arterial phase, hepatobiliary phase, and combined arterial and hepatobiliary phases) could distinguish between high-grade HCCs and low-grade HCCs. And the ANN was superior to logistic regression model in predicting histological grade of HCC.
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Affiliation(s)
- Yingfan Mao
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yong Zhu
- Department of Radiology, Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Liang Mao
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weiwei Kong
- Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yudong Qiu
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoyan Wu
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yue Guan
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Byun D, Lee SG, Kim H, You Y, Jung J, Jang JH, Lee MS, Kim CN, Cho BS, Kang YJ, on behalf of the Korean Liver Cancer Association. Prognostic value of preoperative protein-induced vitamin K absence or antagonist II after liver resection for hepatitis B-related hepatocellular carcinoma: a nationwide multicenter study. Ann Surg Treat Res 2022; 103:271-279. [DOI: 10.4174/astr.2022.103.5.271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 08/18/2022] [Accepted: 09/01/2022] [Indexed: 11/12/2022] Open
Affiliation(s)
- Dahn Byun
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Seul Gi Lee
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Hyeyoung Kim
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Yunghun You
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Jaehag Jung
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Je Ho Jang
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Moon-Soo Lee
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Chang-Nam Kim
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Byung Sun Cho
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
| | - Yoon-Jung Kang
- Department of Surgery, Daejeon Eulji Medical Center, Eulji University College of Medicine, Daejeon, Korea
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Zheng Z, Guan R, Jianxi W, Zhao Z, Peng T, Liu C, Lin Y, Jian Z. Microvascular Invasion in Hepatocellular Carcinoma: A Review of Its Definition, Clinical Significance, and Comprehensive Management. JOURNAL OF ONCOLOGY 2022; 2022:9567041. [PMID: 35401743 PMCID: PMC8986383 DOI: 10.1155/2022/9567041] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 02/28/2022] [Accepted: 03/14/2022] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of malignancies in the world, and most HCC patients undergoing liver resection relapse within five years. Microvascular invasion (MVI) is an independent factor for both the disease-free survival and overall survival of HCC patients. At present, the definition of MVI is still controversial, and a global consensus on how to evaluate MVI precisely is needed. Moreover, this review summarizes the current knowledge and clinical significance of MVI for HCC patients. In terms of management, antiviral therapy, wide surgical margins, and postoperative transcatheter arterial chemoembolization (TACE) could effectively reduce the incidence of MVI or improve the disease-free survival and overall survival of HCC patients with MVI. However, other perioperative management practices, such as anatomical resection, radiotherapy, targeted therapy and immune therapy, should be clarified in future investigations.
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Affiliation(s)
- Zehao Zheng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Renguo Guan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
| | - Wang Jianxi
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhen Zhao
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Department of General Surgery, School of Medicine, Southern China University of Technology, Guangzhou, China
| | - Tianyi Peng
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chunsheng Liu
- Shantou University Medical College, Shantou, China
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ye Lin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhixiang Jian
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Cai J, Zhao J, Liu D, Xie H, Qi H, Ma J, Sun Z, Zhao H. Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study. Front Oncol 2021; 11:781029. [PMID: 34926296 PMCID: PMC8679661 DOI: 10.3389/fonc.2021.781029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/08/2021] [Indexed: 01/27/2023] Open
Abstract
Background Postoperative adjuvant transcatheter arterial chemoembolization (TACE) following curative hepatectomy has been reported to improve the clinical outcomes of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but more endeavors are required to achieve greater clinical benefit. Central memory T-cell (Tcm) self-transfusion has shown superior antitumor activity in several preclinical studies; however, clinical studies are rare. The aim of this study was to evaluate the clinical benefit and safety of combination treatment with Tcm self-transfusion and TACE as adjuvant treatment in HCC patients with MVI after curative hepatectomy. Methods From October 2016 to September 2018, primary HCC patients with histologically confirmed MVI who underwent curative hepatectomy at the Cancer Hospital of the Chinese Academy of Medical Sciences were recruited for this study. The patients were divided into a Tcm group (combined Tcm self-transfusion with TACE treatment) or a control group (TACE treatment alone) according to their willingness. The recurrence-free survival (RFS), quality-of-life (QOL) score, and adverse events of each patient were recorded within 2 years. Results A total of 52 patients were enrolled, and 48 were eligible for the final data analysis. The median follow-up time was 20.5 months (95% CI: 17.05–22.55 months). The median RFS time was 9.5 months in the control group; the cutoff date was not reached in the Tcm group (when the follow-up duration was 12 months, p = 0.049, HR = 0.40; 95% CI: 0.16–0.99). Compared with the control group, 1- and 2-year RFS rates were higher in the Tcm group (72.0% vs. 46.4% and 58.18% vs. 39.14%, respectively). Multivariate analysis did not indicate that Tcm treatment was an independent prognostic factor associated with HCC recurrence (p = 0.107, HR = 2.312; 95% CI: 0.835–6.400), which might be due to the small sample size of this study. Nevertheless, Tcm treatment effectively improved a reduced QOL due to HCC and liver function injury. Finally, the safety profile of Tcm treatment in this study was good, without any serious adverse events. Conclusions This pilot study showed that Tcm self-transfusion combined with TACE treatment might be a beneficial adjuvant therapy with good safety for primary HCC patients with MVI after curative hepatectomy. Trial registration number NCT03575806
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Affiliation(s)
- Jianqiang Cai
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Defang Liu
- Department of New Drug Registration, Hebei Immune Cell Application Engineering Research Center/Baoding Newish Technology Co., LTD/Newish Technology (Beijing) Co., LTD, Beijing, China
| | - Huangfan Xie
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Hailong Qi
- Department of New Drug Registration, Hebei Immune Cell Application Engineering Research Center/Baoding Newish Technology Co., LTD/Newish Technology (Beijing) Co., LTD, Beijing, China.,School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Junfan Ma
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Zhongjie Sun
- State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Byun J, Kim SY, Kim JH, Kim MJ, Yoo C, Shim JH, Lee SS. Prediction of transarterial chemoembolization refractoriness in patients with hepatocellular carcinoma using imaging features of gadoxetic acid-enhanced magnetic resonance imaging. Acta Radiol 2021; 62:1548-1558. [PMID: 33197329 DOI: 10.1177/0284185120971844] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Repeated transarterial chemoembolization (TACE) can be associated with loss of its efficacy and subsequent tumor progression. PURPOSE To identify features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) associated with TACE refractoriness and to develop a prediction model for estimating the risk of TACE refractoriness. MATERIAL AND METHODS Among 1025 patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent TACE as a first-line treatment during 2010-2017, 427 patients who underwent preoperative gadoxetic acid-enhanced MRI were analyzed. According to the date of initial TACE, patients were divided into the development cohort (n = 211) and the test cohort (n = 216). TACE refractoriness was determined according to the Japan Society of Hepatology guidelines. Univariable and multivariable analyses were performed to investigate the association between clinical/MRI features and TACE refractoriness. The performance of the prediction model was internally and externally assessed using the C-index of discrimination and a Hosmer-Lemeshow goodness-of-fit test for calibration. RESULTS By analyzing 427 patients, we constructed a prediction model with the following independent features associated with TACE refractoriness: maximum tumor size; tumor number; peritumoral hypointensity on hepatobiliary phase (HBP); and the presence of non-hypervascular hypointense nodule on HBP. This system enabled the prediction of TACE refractoriness in the development cohort (C-index, 0.796) and the test cohort (C-index, 0.738) with good discrimination and calibration abilities. CONCLUSION The prediction model based on gadoxetic acid-enhanced MRI features in addition to the known predictors including tumor size and number can be used to estimate the risk of TACE refractoriness in patients with intermediate-stage HCC.
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Affiliation(s)
- Jieun Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Radiology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Changhoon Yoo
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Catania R, Chupetlovska K, Borhani AA, Maheshwari E, Furlan A. Tumor in vein (LR-TIV) and liver imaging reporting and data system (LI-RADS) v2018: diagnostic features, pitfalls, prognostic and management implications. Abdom Radiol (NY) 2021; 46:5723-5734. [PMID: 34519877 DOI: 10.1007/s00261-021-03270-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Vascular invasion by hepatocellular carcinoma (HCC), also known as tumor in vein (TIV), indicates highly invasive tumor behavior and is also associated with poor outcome. Because a diagnosis of TIV precludes liver transplantation, knowledge of the imaging findings to differentiate between TIV and bland thrombus is key for proper patient management. Prior versions of liver imaging reporting and data system (LI-RADS) included presence of TIV as part of LR-5 criteria. However, even if HCC is the most common liver malignancy associated with TIV, other tumors can have vascular invasion and may occur in cirrhotic patients. For these reasons, in LI-RADS v2017 LR-TIV has been introduced as a new different diagnostic category. The aim of this article is to discuss the diagnostic criteria of LR-TIV according to LI-RADS v2018 and analyze potential pitfalls encountered on daily clinical practice. Indeterminate cases and how to manage them will also be discussed.
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Affiliation(s)
- Roberta Catania
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Chicago, IL, 60611, USA.
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA.
| | - Kalina Chupetlovska
- Diagnostic Imaging Department, University Hospital Saint Ivan Rilski, Sofia, Bulgaria
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Amir A Borhani
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Chicago, IL, 60611, USA
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Ekta Maheshwari
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Alessandro Furlan
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
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Zhang D, Wei Q, Wu GG, Zhang XY, Lu WW, Lv WZ, Liao JT, Cui XW, Ni XJ, Dietrich CF. Preoperative Prediction of Microvascular Invasion in Patients With Hepatocellular Carcinoma Based on Radiomics Nomogram Using Contrast-Enhanced Ultrasound. Front Oncol 2021; 11:709339. [PMID: 34557410 PMCID: PMC8453164 DOI: 10.3389/fonc.2021.709339] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/13/2021] [Indexed: 01/27/2023] Open
Abstract
PURPOSE This study aimed to develop a radiomics nomogram based on contrast-enhanced ultrasound (CEUS) for preoperatively assessing microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. METHODS A retrospective dataset of 313 HCC patients who underwent CEUS between September 20, 2016 and March 20, 2020 was enrolled in our study. The study population was randomly grouped as a primary dataset of 192 patients and a validation dataset of 121 patients. Radiomics features were extracted from the B-mode (BM), artery phase (AP), portal venous phase (PVP), and delay phase (DP) images of preoperatively acquired CEUS of each patient. After feature selection, the BM, AP, PVP, and DP radiomics scores (Rad-score) were constructed from the primary dataset. The four radiomics scores and clinical factors were used for multivariate logistic regression analysis, and a radiomics nomogram was then developed. We also built a preoperative clinical prediction model for comparison. The performance of the radiomics nomogram was evaluated via calibration, discrimination, and clinical usefulness. RESULTS Multivariate analysis indicated that the PVP and DP Rad-score, tumor size, and AFP (alpha-fetoprotein) level were independent risk predictors associated with MVI. The radiomics nomogram incorporating these four predictors revealed a superior discrimination to the clinical model (based on tumor size and AFP level) in the primary dataset (AUC: 0.849 vs. 0.690; p < 0.001) and validation dataset (AUC: 0.788 vs. 0.661; p = 0.008), with a good calibration. Decision curve analysis also confirmed that the radiomics nomogram was clinically useful. Furthermore, the significant improvement of net reclassification index (NRI) and integrated discriminatory improvement (IDI) implied that the PVP and DP radiomics signatures may be very useful biomarkers for MVI prediction in HCC. CONCLUSION The CEUS-based radiomics nomogram showed a favorable predictive value for the preoperative identification of MVI in HCC patients and could guide a more appropriate surgical planning.
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Affiliation(s)
- Di Zhang
- Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, China
| | - Qi Wei
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ge-Ge Wu
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xian-Ya Zhang
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wen-Wu Lu
- Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, China
| | - Wen-Zhi Lv
- Department of Artificial Intelligence, Julei Technology Company, Wuhan, China
| | - Jin-Tang Liao
- Department of Diagnostic Ultrasound, Xiang Ya Hospital, Central South University, Changsha, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xue-Jun Ni
- Department of Medical Ultrasound, Affiliated Hospital of Nantong University, Nantong, China
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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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Liu J, Kuang S, Zheng Y, Liu M, Wang L. Prognostic and predictive significance of the tumor microenvironment in hepatocellular carcinoma. Cancer Biomark 2021; 32:99-110. [PMID: 34092607 DOI: 10.3233/cbm-203003] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Identification of molecular markers that reflect the characteristics of the tumor microenvironment (TME) may be beneficial to predict the prognosis of post-operative hepatocellular carcinoma (HCC) patients. OBJECTIVE AND METHODS A total of 100 tissue samples from HCC patients were separately stained by immunohistochemistry to examine the expression levels of CD56, CD8α, CD68, FoxP3, CD31 and pan-Keratin. The prognostic values were analyzed by Cox regression and the Kaplan-Meier method. RESULTS Univariate and multivariate logistic analysis showed that FoxP3 was the independent factor associated with microvascular invasion (MVI), tumor size and envelop invasion; CD68 was associated with envelope invasion and AFP. Kaplan-Meier survival curves revealed that CD68 and FoxP3 expression were significantly associated with relapse free survival (RFS) of HCC patients (P< 0.05). The ROC curve indicated that the combination of tumor number, MVI present and CD68 expression yielded a ROC curve area of 82.3% (86.36% specificity, 68.75% sensitivity) to evaluate the prognosis of HCC patients, which was higher than the classifier established by the combination of tumor number and MVI (78.8% probability, 63.64% specificity and 85.42% sensitivity). CONCLUSIONS Our study indicated that CD68 and FoxP3 are associated with prognosis of HCC patients, and CD68 can be considered as a potential prognostic and predictive biomarker.
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Affiliation(s)
- Jibing Liu
- Department of Interventional Surgical Oncology, Cancer Hospital of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China.,Department of Interventional Surgical Oncology, Cancer Hospital of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Shuwen Kuang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Interventional Surgical Oncology, Cancer Hospital of Shandong Province, Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Yiling Zheng
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mei Liu
- Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liming Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Kim M, Kim T, Lee HY, Hong SY, Wang HJ, Kim BW. Risk Factors for Beyond Milan Recurrence After Hepatic Resection for Single Hepatocellular Carcinoma No Larger Than 5 Centimeters. Liver Transpl 2021; 27:1116-1129. [PMID: 33835642 DOI: 10.1002/lt.26070] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 03/29/2021] [Accepted: 03/30/2021] [Indexed: 12/22/2022]
Abstract
Hepatic resection (HR) is considered a treatment of choice for a single hepatocellular carcinoma (HCC) ≤5 cm in patients with preserved liver function. However, it is possible for these patients to develop a severe form of recurrence (beyond Milan recurrence [BMR] criteria). This recurrence could have been avoided if liver transplantation (LT) was performed primarily, as LT is believed to yield a more favorable oncological outcome compared with HR. The aim of this study was to determine the risk factors for BMR after HR and to verify whether primary LT can provide a more favorable outcome in patients with BMR risk factors. Data from 493 patients who underwent HR for HCC ≤5 cm between 1995 and 2016 were analyzed. Among them, 74 patients (15%) experienced BMR. The 10-year survival rate of patients with BMR was significantly low compared with that of patients without BMR (22.6% versus 79.8%; P < 0.01). In multivariate analysis, calculated hepatic venous pressure gradient ≥7 mm Hg and microvascular invasion were identified as the risk factors for BMR (P < 0.05). During the same period, 63 eligible patients underwent LT as a primary treatment for HCC ≤5 cm. No significant difference in long-term survival rate was observed when no risk factor for BMR was present in the HR and LT groups (85.5% versus 100%; P = 0.39). However, 10-year survival was poorer in the HR group in the presence of risk factors for BMR (60.6% versus 91.8%; P < 0.001). Among the patients with HCCs ≤5 cm, which are resectable and transplantable, LT is indicated when calculated hepatic venous pressure gradient ≥7 mm Hg and/or microvascular invasion is present.
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Affiliation(s)
- Mina Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Taegyu Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Young Lee
- Clinical Trial Center, Ajou University School of Medicine, Suwon, Korea
| | - Sung Yeon Hong
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Hee-Jung Wang
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
| | - Bong-Wan Kim
- Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Korea
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Kumar D, Hafez O, Jain D, Zhang X. Can primary hepatocellular carcinoma histomorphology predict extrahepatic metastasis? Hum Pathol 2021; 113:39-46. [PMID: 33905775 DOI: 10.1016/j.humpath.2021.04.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 04/10/2021] [Accepted: 04/19/2021] [Indexed: 02/07/2023]
Abstract
Studies comparing the histomorphologic features and phenotypic heterogeneity between primary and its corresponding metastatic hepatocellular carcinoma (HCC) are lacking. The aim of this study was to assess and compare the histomorphologic features and heterogeneity between primary and metastatic HCC. A total of 39 cases with both primary and metastatic tissues were identified from pathology archives (2000-2019). The common sites of metastasis included lung (28.21%), abdominal cavity (25.64%), lymph nodes (20.51%), bone (17.95%), soft tissue (15.38%), and adrenal gland (10.26%). Both the primary and metastatic tumors showed heterogeneity in intratumoral histologic patterns (87.18% and 76.92%, respectively). The most common histologic pattern was solid in both primary (61.54%) and metastases (56.41%), followed by macrotrabecular in primary (17.95%) and metastases (10.26%). Among HCC-subtypes, macrotrabecular-massive HCC was the most common subtype in both primary and metastases (28.21% each). Primary tumors in noncirrhotic livers were more likely to have larger size and microvascular invasion than those in cirrhotic livers. The histomorphology (histologic pattern, subtype, and grade) between the primary and metastases was discordant in about 50% cases (48.72%, 48.72%, and 51.28%, respectively). Our findings exhibit significant intratumoral heterogeneity and histomorphologic discordance between primary and metastatic HCCs. The solid and macrotrabecular histologic patterns and the macrotrabecular-massive subtype were the most common histomorphologic features seen in primary tumors associated with metastasis. Further studies to identify and explore different pathways that promote HCC metastasis and to compare the differences between primary and metastatic tumors on a larger cohort are needed to better understand the pathogenesis of metastasis.
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Affiliation(s)
- Deepika Kumar
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States
| | - Omeed Hafez
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States
| | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States
| | - Xuchen Zhang
- Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, United States.
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34
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Renne SL, Sarcognato S, Sacchi D, Guido M, Roncalli M, Terracciano L, Di Tommaso L. Hepatocellular carcinoma: a clinical and pathological overview. Pathologica 2021; 113:203-217. [PMID: 34294938 PMCID: PMC8299323 DOI: 10.32074/1591-951x-295] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 04/26/2021] [Indexed: 02/07/2023] Open
Abstract
HCC incidence rates have been rising in the past 3 decades and by 2025 > 1 million individuals will be affected annually. High-throughput sequencing technologies led to the identification of several molecular HCC subclasses that can be broadly grouped into 2 major subgroups, each characterized by specific morphological and phenotypical features. It is likely that this increasing knowledge and a more appropriate characterization of HCC at the pathological level will impact HCC patient management.
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Affiliation(s)
- Salvatore Lorenzo Renne
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Samantha Sarcognato
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Diana Sacchi
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
| | - Maria Guido
- Department of Pathology, Azienda ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Medicine - DIMED, University of Padova, Padova, Italy
| | - Massimo Roncalli
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luigi Terracciano
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Luca Di Tommaso
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
- IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
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35
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Vij M, Calderaro J. Pathologic and molecular features of hepatocellular carcinoma: An update. World J Hepatol 2021; 13:393-410. [PMID: 33959223 PMCID: PMC8080551 DOI: 10.4254/wjh.v13.i4.393] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/27/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Morphological diversity and several new distinct pathologic subtypes of hepatocellular carcinoma (HCC) are now well-recognized. Recent advances in tumor genomics and transcriptomics have identified several recurrent somatic/genetic alterations that are closely related with histomorphological subtypes and have therefore, greatly improved our understanding of HCC pathogenesis. Pathologic subtyping allows for a diagnosis which is clinically helpful and can have important implication in patient prognostication as some of these subtypes are extremely aggressive with vascular invasion, early recurrence, and worst outcomes. Several targeted treatments are now being considered in HCC, and the reporting of subtypes may be quite useful for personalized therapeutic purpose. This manuscript reviews the recently identified histomorphological subtypes and molecular alterations in HCC.
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Affiliation(s)
- Mukul Vij
- Department ofPathology, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India.
| | - Julien Calderaro
- Department of Pathology, Groupe Hospitalier Henri Mondor, Creteil F-94010, France
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Lin SH, Eng HL, Liu YW, Lin CC, Yong CC, Wang CC, Chen CL, Kuo FY, Cheng YF, Wang JH, Yen YH, Liu TT, Li WF, Chen CH. Characteristics and prognosis of patients with large well-differentiated hepatocellular carcinoma who have undergone resection. Am J Surg 2021; 223:339-345. [PMID: 33840448 DOI: 10.1016/j.amjsurg.2021.03.065] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/11/2021] [Accepted: 03/30/2021] [Indexed: 01/10/2023]
Abstract
BACKGROUND Large well-differentiated hepatocellular carcinoma (HCC) ≥ 3 cm (defined as atypical HCC) is uncommon. We evaluated the characteristics and outcomes of atypical HCC patients underwent liver resection (LR). METHODS This retrospective study enrolled patients who underwent LR for HCC from 2007 to 2017. Patient characteristics and overall survival (OS) were compared between patients with atypical HCC and patients with typical HCC (moderate-to-undifferentiated HCC ≥ 3 cm). RESULTS Among 598 patients, 51 (8.5%) had atypical HCC. Patients with atypical HCC had higher rates of non-hepatitis B or C infections (p = 0.02) and American Joint Committee on Cancer T1 pathology (p < 0.001), a lower rate of alpha-fetoprotein >20 ng/ml (p < 0.001) and a longer OS (p < 0.001) than those with typical HCC. Multivariate analysis showed that atypical HCC was associated with OS (HR = 0.50, 95% CI = 0.27-0.91, p = 0.02). CONCLUSIONS Patients with atypical HCC have a higher rate of non-hepatitis B or C infections and a lower rate of aggressive tumor biologic behavior. Atypical HCC is an independent predictor of OS.
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Affiliation(s)
- Shu-Hsien Lin
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Hock-Liew Eng
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yueh-Wei Liu
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Che Lin
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chee-Chien Yong
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chao-Long Chen
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Fang-Ying Kuo
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Yu-Fan Cheng
- Liver Transplantation Center, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Ting-Ting Liu
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Department of Medical Laboratory Science, I-Shou University, Kaohsiung, Taiwan
| | - Wei-Feng Li
- Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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Rastogi A, Maiwall R, Ramakrishna G, Modi S, Taneja K, Bihari C, Kumar G, Patil N, Thapar S, Choudhury AK, Mukund A, Pamecha V, Sarin SK. Hepatocellular carcinoma: Clinicopathologic associations amidst marked phenotypic heterogeneity. Pathol Res Pract 2021; 217:153290. [PMID: 33307344 DOI: 10.1016/j.prp.2020.153290] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is characterized by marked phenotypic and molecular heterogeneity. Clinico-morphologic phenotypes and associations are important surrogate markers of molecular aberrations; therefore have immense relevance for targeted therapy. There is paucity of published literature on critical analysis of HCC heterogeneity and morphological alliance. AIMS To assess the heterogeneity and dominance of histomorphological features, and to explore clinicopathological associations in HCC. METHODS Retrospective cross-sectional study of 217 HCC tissue specimens was performed for the assessment of prevalence of major histological patterns, cytological features, and clinicopathological correlation. RESULTS Homogeneous architecture with a single dominant histological pattern was a rarity. Single pattern constituting ≥50 % of the tumour was found in less than 1/5th of the cases. Macrotrabecular HCC represented 9.2 % of cases. The simultaneous presence of 2-3 patterns or atypical variants and/ or cytological characteristics was recorded in 25 % and 30 % respectively. Significant clinicopathological associations: Pseudoglandular with microtrabecular pattern-cholestasis, showed better differentiation and early-stage; macrotrabecular pattern frequently occurred with pleomorphic giant cells, higher tumour stage, higher AFP levels; solid pattern often showed clear cells. Noticeable mutual exclusions were MD bodies with microtrabecular and pseudoglandular patterns; Compact pattern with neutrophilic clusters and cholestasis. Larger tumours were significantly more heterogeneous; however, heterogeneity did not correlate with outcome CONCLUSIONS: HCC displays immense heterogeneity with an amalgamation of different histomorphological patterns and features; nevertheless, there are certain reproducible associations and omissions. Tumor biopsies agree fairly well with large specimens. Characterization of phenotypic heterogeneity, dominance, associations, and exclusions in individual patients provides vital information.
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Affiliation(s)
- Archana Rastogi
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Rakhi Maiwall
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Gayatri Ramakrishna
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Shilpi Modi
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Kanika Taneja
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Chhagan Bihari
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Guresh Kumar
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Nilesh Patil
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Shalini Thapar
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | | | - Amar Mukund
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
| | - Viniyendra Pamecha
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India
| | - Shiv K Sarin
- Institute of Liver & Biliary Sciences, D-1 Vasant Kunj, Delhi, 110070, India.
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Wu B, Yeh MM. Pathology of Hepatitis B Virus (HBV) Infection and HBV-Related Hepatocellular Carcinoma. HEPATITIS B VIRUS AND LIVER DISEASE 2021:99-122. [DOI: 10.1007/978-981-16-3615-8_5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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40
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Torbenson MS. Hepatocellular carcinoma: making sense of morphological heterogeneity, growth patterns, and subtypes. Hum Pathol 2020; 112:86-101. [PMID: 33387587 DOI: 10.1016/j.humpath.2020.12.009] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 12/18/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinomas are not a homogenous group of tumors but have multiple layers of heterogeneity. This heterogeneity has been studied for many years with the goal to individualize care for patients and has led to the identification of numerous hepatocellular carcinoma subtypes, defined by morphology and or molecular methods. This article reviews both gross and histological levels of heterogeneity within hepatocellular carcinoma, with a focus on histological findings, reviewing how different levels of histological heterogeneity are used as building blocks to construct morphological hepatocellular carcinoma subtypes. The current best practice for defining a morphological subtype is outlined. Then, the definition for thirteen distinct hepatocellular carcinoma subtypes is reviewed. For each of these subtypes, unresolved issues regarding their definitions are highlighted, including recommendations for these problematic areas. Finally, three methods for improving the research on hepatocellular carcinoma subtypes are proposed: (1) Use a systemic, rigorous approach for defining hepatocellular carcinoma subtypes (four-point model); (2) Once definitions for a subtype are established, it should be followed in research studies, as this common denominator enhances the ability to compare results between studies; and (3) Studies of subtypes will be more effective when morphological and molecular results are used in synergistic and iterative study designs where the results of one approach are used to refine and sharpen the results of the other. These and related efforts to better understand heterogeneity within hepatocellular carcinoma are the most promising avenue for improving patient care by individualizing patient care.
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Affiliation(s)
- Michael S Torbenson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, 55905, USA.
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41
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Min JH, Lee MW, Park HS, Lee DH, Park HJ, Lim S, Choi SY, Lee J, Lee JE, Ha SY, Cha DI, Carriere KC, Ahn JH. Interobserver Variability and Diagnostic Performance of Gadoxetic Acid-enhanced MRI for Predicting Microvascular Invasion in Hepatocellular Carcinoma. Radiology 2020; 297:573-581. [PMID: 32990512 DOI: 10.1148/radiol.2020201940] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Background Accurate identification of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment is critical for selecting a proper treatment strategy. Purpose To evaluate the interobserver agreement and the diagnostic performance of the MRI assessment of MVI in HCC according to the level of radiologist experience. Materials and Methods This retrospective study included 100 patients with surgically confirmed HCCs smaller than 5 cm who underwent gadoxetic acid-enhanced MRI between 2013 and 2016. Eight postfellowship radiologists (four with 7-13 years of experience [more experienced] and four with 3-6 years of experience [less experienced]) evaluated four imaging features (nonsmooth tumor margin, irregular rim-like enhancement in the arterial phase, peritumoral arterial phase hyperenhancement, peritumoral hepatobiliary phase hypointensity) and assigned the possibility of MVI. Interobserver agreement was determined by using Fleiss κ statistics according to reviewer experience and tumor size (≤3 cm vs >3 cm). With reference standards of histopathologic specimens, the diagnostic performance in the identification of MVI was assessed by using receiver operating characteristic curve analysis. Results In 100 patients (mean age, 58 years ± 10 [standard deviation]; 70 men) with 100 HCCs (mean size, 2.8 cm ± 0.9), 39 (39%) HCCs had MVI. The overall interobserver agreement was fair to moderate for the imaging features and their combinations (κ = 0.38-0.47) and MVI probability (κ = 0.41; 95% confidence interval: 0.33, 0.45). More experienced reviewers demonstrated higher agreement in MVI probability than less experienced reviewers (κ = 0.55 vs 0.36, respectively; P = .002). Diagnostic performance of each reviewer was modest for MVI prediction (area under the receiver operating characteristic curve [AUC] range, 0.60-0.74). The AUCs for the diagnosis of MVI were lower for HCCs larger than 3 cm (range, 0.55-0.69) than for those less than or equal to 3 cm (range, 0.59-0.75). Conclusion Considerable interobserver variability exists in the assessment of microvascular invasion in hepatocellular carcinoma using MRI, even for more experienced radiologists. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Tang in this issue.
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Affiliation(s)
- Ji Hye Min
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Min Woo Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Hee Sun Park
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Dong Ho Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Hyun Jeong Park
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Sanghyeok Lim
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Seo-Youn Choi
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Jisun Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Ji Eun Lee
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Sang Yun Ha
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Dong Ik Cha
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Keumhee Chough Carriere
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
| | - Joong Hyun Ahn
- From the Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro Gangnam-gu, Seoul 06351, Republic of Korea (J.H.M., M.W.L., D.I.C.); Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea (M.W.L.); Department of Radiology, Konkuk University School of Medicine, Seoul, Republic of Korea (H.S.P.); Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea (D.H.L.); Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea (H.J.P.); Department of Radiology, Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea (S.L.); Department of Radiology, Soonchunhyang University College of Medicine, Bucheon Hospital, Bucheon, Republic of Korea (S.Y.C., J.E.L.); Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea (J.L.); Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea (S.Y.H.); Department of Mathematical and Statistical Sciences University of Alberta, Edmonton, Canada (K.C.C.); Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea (J.H.A.)
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Isik B, Gonultas F, Sahin T, Yilmaz S. Microvascular Venous Invasion in Hepatocellular Carcinoma: Why Do Recurrences Occur? J Gastrointest Cancer 2020; 51:1133-1136. [PMID: 32839943 DOI: 10.1007/s12029-020-00487-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Hepatocellular carcinoma is the most common primary cancer of the liver. It is almost always associated with cirrhosis and it is usually diagnosed in later stages of the disease. Furthermore, recurrence rate following liver transplantation ranges between 15 and 30%. The most important factor determining the recurrence is vascular invasion. METHODS In this review, the issue of microvascular invasion causing hepatocellular carcinoma recurrence is reviewed. Macroscopic vascular invasion is almost easy to diagnose on radiologic evaluation. However, microscopic vascular invasion is almost always diagnosed with pathologic evaluation. On the other hand, microscopic vascular invasion is associated with early recurrences and reduced disease-free survival. The type of vessel that is invaded determines the nature of the spread of the tumor cells. Invasion of the hepatic venous tributaries leads to systemic metastasis whereas portal venous invasions lead to intrahepatic spread of the tumor. Microscopic vascular invasion should be diagnosed before liver transplantation or liver resection in order to deliver the appropriate therapy to the patients. RESULTS Yet, there is no ideal marker to suggest microscopic vascular invasion before any intervention. Markers such as alpha-fetoprotein, des carboxy prothrombin, or gamma-glutamyl transferase have been found to be correlated with microscopic vascular invasion. These parameters are not very efficient to be used in routine clinical practice. CONCLUSION Therefore, further research is needed to define ideal marker associated with microscopic vascular invasion.
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Affiliation(s)
- Burak Isik
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Fatih Gonultas
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Tolga Sahin
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey.
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, 44280, Malatya, Turkey.
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Fung AK, Cheng NM, Chong CC, Lee KF, Wong J, Cheung SY, Lok HT, Lai PB, Ng KK. Single-center experience on actual mid-term (≥5 years) and long-term (≥10 years) survival outcome in patients with hepatocellular carcinoma after curative hepatectomy: A bimodal distribution. Medicine (Baltimore) 2020; 99:e23358. [PMID: 33235106 PMCID: PMC7710257 DOI: 10.1097/md.0000000000023358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Analysis for actual mid-term (≥5 years) and long-term (≥10 years) survivors with hepatocellular carcinoma (HCC) following curative hepatectomy are rarely reported in the literature.This retrospective study aims to study the mid- and long-term survival outcome and associated prognostic factors following curative hepatectomy for HCC in a tertiary referral center.The clinical data of 325 patients who underwent curative hepatectomy for HCC were reviewed. They were stratified into 3 groups for comparison (Group 1, overall survival <5 years; Group 2, overall survival ≥5, and <10 years; Group 3, overall survival ≥10 years). Favorable independent prognostic factors for mid- and long-term survival were analyzed.A bimodal distribution of actual survival outcome was observed, with short-term (<5 years) survival of 52.7% (n = 171), mid-term survival of 18.1% (n = 59), and long-term survival of 29.2% (n = 95). Absence of microvascular invasion (OR 3.690, 95% CI: 1.562-8.695) was independent good prognostic factor for mid-term survival. Regarding long-term overall survival, young age (OR 1.050, 95% CI: 0.920-0.986), ASA grade ≤2 (OR 3.746, 95% CI: 1.325-10.587), high albumin level (OR 1.008, 95% CI: 0.920-0.986), solitary tumor (OR 3.289, 95% CI: 1.149-7.625) and absence of microvascular invasion (OR 4.926, 95% CI: 2.192-11.111) were independent good prognostic factors.Curative hepatectomy results in bimodal actual survival outcome with favorable long-term survival rate of 29.2%. Favorable independent prognostic factors (age, ASA grade, albumin level, tumor number, and microvascular invasion) are identified for overall survival.
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Affiliation(s)
- Andrew K.Y. Fung
- Department of Surgery, Prince of Wales Hospital, New Territories
| | | | - Charing C.N. Chong
- Department of Surgery, Prince of Wales Hospital, New Territories
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong
| | - Kit-Fai Lee
- Department of Surgery, Prince of Wales Hospital, New Territories
| | - John Wong
- Department of Surgery, Prince of Wales Hospital, New Territories
| | | | - Hon-Ting Lok
- Department of Surgery, Prince of Wales Hospital, New Territories
| | - Paul B.S. Lai
- Department of Surgery, Prince of Wales Hospital, New Territories
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong
| | - Kelvin K.C. Ng
- Department of Surgery, Prince of Wales Hospital, New Territories
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong
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Wei H, Jiang H, Liu X, Qin Y, Zheng T, Liu S, Zhang X, Song B. Can LI-RADS imaging features at gadoxetic acid-enhanced MRI predict aggressive features on pathology of single hepatocellular carcinoma? Eur J Radiol 2020; 132:109312. [PMID: 33022551 DOI: 10.1016/j.ejrad.2020.109312] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/16/2020] [Accepted: 09/24/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features at preoperative gadoxetic acid-enhanced MRI can predict microvascular invasion (MVI) and histologic grade of hepatocellular carcinoma (HCC) and to evaluate their associations with recurrence after curative resection of single HCC. MATERIALS AND METHODS From July 2015 to September 2018, 111 consecutive patients with pathologically confirmed HCC who underwent gadoxetic acid-enhanced MRI within 1 month before surgery were included in this retrospective study. Significant MRI findings and clinical parameters for predicting MVI, high-grade HCCs and postoperative recurrence were identified by logistic regression model and Cox proportional hazards model. RESULTS Twenty-six of 111 (23.4 %) patients had MVI and 36 of 111 (32.4 %) patients had high-grade HCCs, whereas 44 of 95 (46.3 %) patients experienced recurrence. Tumor size > 5 cm (OR = 9.852; p < 0.001) and absence of nodule-in-nodule architecture (OR = 8.302; p = 0.001) were independent predictors of MVI. Enhancing capsule (OR = 4.396; p = 0.004) and corona enhancement (OR = 3.765; p = 0.021) were independent predictors of high-grade HCCs. Blood products in mass (HR = 2.275; p = 0.009), corona enhancement (HR = 4.332; p < 0.001), and serum AFP level > 400 ng/mL (HR = 2.071; p = 0.023) were independent predictors of recurrence. CONCLUSION LI-RADS imaging features can be used as potential biomarkers for predicting aggressive pathologic features and recurrence of HCC. The identification of prognostic LI-RADS imaging features may facilitate the selection of surgical candidates and optimize the management of HCC patients.
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Affiliation(s)
- Hong Wei
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Xijiao Liu
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Yun Qin
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Tianying Zheng
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | | | | | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
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Affiliation(s)
- An Tang
- From the Department of Radiology, Radio-oncology and Nuclear Medicine, Université de Montréal, Montréal, Canada; Department of Radiology, Centre Hospitalier de l'Université de Montréal (CHUM), 1000 rue Saint-Denis, Montréal, QC, Canada H2X 0C2; and Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
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Weng S, Xu X, Li Y, Yan C, Chen J, Ye R, Zhu Y, Wen L, Hong J. Quantitative analysis of multiphase magnetic resonance images may assist prediction of histopathological grade of small hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1023. [PMID: 32953823 PMCID: PMC7475488 DOI: 10.21037/atm-20-2874] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Background The aim of the study was to investigate whether preoperative quantitative analysis of multiphase magnetic resonance images may assist in predicting the pathological grade of small hepatocellular carcinoma (HCC). Methods A total of 49 patients with small HCCs (≤3 cm) underwent multiphase magnetic resonance imaging (MRI) and were retrospectively reviewed. Routine unenhanced and post gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI were preoperatively performed. Signal intensity (SI) was measured within the designated region of interest (ROI) including those of the lesion and paraspinous muscles. The lesion-to-paraspinous muscle relative contrast ratio (RCR) on T2-weighted (T2W) imaging, diffusion-weighted (DW) imaging, and dynamic phase Gd-BOPTA-enhanced T1W (T1-weighted) imaging were calculated, and statistical analysis was performed to determine the predictive power for the histological grade. Results In all, 49 cases were included comprising 3 well-differentiated (WD) HCCs, 36 moderately differentiated (MD) HCCs, and 10 poorly differentiated (PD) HCCs. There was a negative correlation between the RCR and pathological grade of small HCC in the arterial phase [correlation coefficient (ρ)=-0.305, P<0.05]. However, there was no correlation between RCR in other phases and pathological grade (P>0.05 for all). There was also no correlation between tumor margin, tumor location, cystic/necrotic change, intratumoral fat, enhancement pattern, tumor capsule, tumor boundary or tumor size, and any of the differentiation categories (P>0.05 for all). Conclusions The lesion-to-paraspinous muscle RCR on arterial phase Gd-BOPTA-enhanced T1W imaging may be useful for the prediction of the histological characteristics of small HCC.
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Affiliation(s)
- Shuping Weng
- Department of Radiology, Fujian Maternity and Child Health Hospital, Fuzhou, China
| | - Xuru Xu
- Department of Radiology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.,Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yueming Li
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Key Laboratory of Radiation Biology (Fujian Medical University), Fujian Province University, Fuzhou
| | - Chuan Yan
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jianwei Chen
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Rongping Ye
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yuemin Zhu
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Liting Wen
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinsheng Hong
- Key Laboratory of Radiation Biology (Fujian Medical University), Fujian Province University, Fuzhou.,Department of Radiation Oncology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Sun Y, Bai H, Xia W, Wang D, Zhou B, Zhao X, Yang G, Xu L, Zhang W, Liu P, Xu J, Meng S, Liu R, Gao X. Predicting the Outcome of Transcatheter Arterial Embolization Therapy for Unresectable Hepatocellular Carcinoma Based on Radiomics of Preoperative Multiparameter MRI. J Magn Reson Imaging 2020; 52:1083-1090. [PMID: 32233054 DOI: 10.1002/jmri.27143] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 03/04/2020] [Accepted: 03/04/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND In unresectable hepatocellular carcinoma (HCC), methods to predict patients at increased risk of progression are required. PURPOSE To investigate the feasibility of radiomics model in predicting early progression of unresectable HCC after transcatheter arterial chemoembolization (TACE) therapy using preoperative multiparametric magnetic resonance imaging (MP-MRI). STUDY TYPE Retrospective. POPULATION A total of 84 patients with BCLC B stage HCC from one medical center. According to the modified response evaluation criteria in solid tumors, patients who progressed at 6 months after TACE therapy were assigned as the progressive disease (PD) group (n = 32). Patients whose MRI was performed on four devices were divided into a training cohort (n = 67). Patients whose MRI was performed on other than the previous four devices were used as the testing set (n = 17). FIELD STRENGTH/SEQUENCE 3.0T, 1.5T axial T2 -weighted imaging (T2 WI), diffusion-weighted imaging (DWI, b = 0, 500 s/mm2 ), and apparent diffusion coefficient (ADC) ASSESSMENT: PD was confirmed via imaging studies with MRI. Risk factors, including age, alpha fetoprotein (AFP), size, and radiomic-related features of PD were assessed. In addition, the discrimination ability of each radiomics signature was tested on an independent testing set. STATISTICAL TESTS The area under the receiver-operator characteristic (ROC) curve (AUC) was used to evaluate the predictive accuracy of the radiomic signature in both the training and testing sets. The results indicated that the MP-MRI model achieved the greatest benefit. RESULTS In the testing set, the model based on DWI features presented an AUC of (b = 0, 0.786; b = 500, 0.729), followed by T2 WI features (0.729) and ADC (0.714). The AUC of the MP-MRI signature was increased to 0.800 compared to any single MRI signature. The multivariate logistic analysis identified the radiomics signature as independent parameters of PD, while clinical information such as age, AFP, size, etc., had no significance in the PD group. DATA CONCLUSION Preoperative MP-MRI has the potential to predict the outcome of TACE therapy for unresectable HCC. In addition, these image features may be complementary to the current staging systems of HCC patients. LEVEL OF EVIDENCE 2. TECHNICAL EFFICACY STAGE 3. J. Magn. Reson. Imaging 2020;52:1083-1090.
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Affiliation(s)
- Yuejun Sun
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Honglin Bai
- University of Science and Technology of China, Hefei, China.,Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Beijing, China
| | - Wei Xia
- Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Beijing, China
| | - Dong Wang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Bo Zhou
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xingyu Zhao
- University of Science and Technology of China, Hefei, China.,Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Beijing, China
| | - Guowei Yang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ligang Xu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Wei Zhang
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Pingping Liu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jiacheng Xu
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Siyu Meng
- Department of Electro-Optical Engineering, Changchun University of Science and Technology, Changchun, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Institution of Medical Imaging, Shanghai, China
| | - Xin Gao
- Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Beijing, China
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Abstract
OBJECTIVE To investigate whether subclassification of microscopic vascular invasion (MiVI) affects the long-term outcome after curative surgical resection or liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA The most important factor for TNM staging in HCC is MiVI, which includes all vascular invasions detected on microscopic examination. However, there is a broad spectrum of current definitions for MiVI. METHODS In total, 412 consecutive patients with HCC who underwent curative surgical resection without any preoperative treatment or gross vascular invasion were histologically evaluated for MiVI. Patients with MiVI were subclassified into 2 groups: microvessel invasion (MI; n = 164) only and microscopic portal vein invasion (MPVI; n = 36). Clinicopathologic features were compared between 2 groups (MI vs MPVI), whereas disease-free survival (DFS) and overall survival (OS) after resection were analyzed among 3 groups (no vascular invasion [NVI] vs MI vs MPVI). These subclassifications were validated in a cohort of 197 patients with HCC who underwent LT. RESULTS The MPVI group showed more aggressive tumor characteristics, such as higher tumor marker levels (alpha-fetoprotein, P = 0.006; protein induced by vitamin K absence-II, P = 0.001) and poorer differentiation (P = 0.011), than the MI group. In multivariate analysis, both MI and MPVI were independent prognostic factors for DFS (P = 0.001 and <0.001, respectively) and OS (P = 0.005 and <0.001, respectively). In the validation cohort, 5-year DFS was 89%, 67.9%, and 0% in the NVI, MI, and MPVI groups, respectively (P < 0.001), whereas 5-year OS was 79.1%, 55.0%, and 15.4%, respectively (P < 0.001). CONCLUSIONS Based on subclassification of MiVI in HCC, MPVI was associated with more aggressive clinicopathologic characteristics and poorer survival than MI only. Therefore, the original MiVI classification should be divided into MI and MPVI.
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Liao H, Xiong T, Peng J, Xu L, Liao M, Zhang Z, Wu Z, Yuan K, Zeng Y. Classification and Prognosis Prediction from Histopathological Images of Hepatocellular Carcinoma by a Fully Automated Pipeline Based on Machine Learning. Ann Surg Oncol 2020; 27:2359-2369. [PMID: 31916093 DOI: 10.1245/s10434-019-08190-1] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVE The aim of this study was to develop quantitative feature-based models from histopathological images to distinguish hepatocellular carcinoma (HCC) from adjacent normal tissue and predict the prognosis of HCC patients after surgical resection. METHODS A fully automated pipeline was constructed using computational approaches to analyze the quantitative features of histopathological slides of HCC patients, in which the features were extracted from the hematoxylin and eosin (H&E)-stained whole-slide images of HCC patients from The Cancer Genome Atlas and tissue microarray images from West China Hospital. The extracted features were used to train the statistical models that classify tissue slides and predict patients' survival outcomes by machine-learning methods. RESULTS A total of 1733 quantitative image features were extracted from each histopathological slide. The diagnostic classifier based on 31 features was able to successfully distinguish HCC from adjacent normal tissues in both the test [area under the receiver operating characteristic curve (AUC) 0.988] and external validation sets (AUC 0.886). The random-forest prognostic model using 46 features was able to significantly stratify patients in each set into longer- or shorter-term survival groups according to their assigned risk scores. Moreover, the prognostic model we constructed showed comparable predicting accuracy as TNM staging systems in predicting patients' survival at different time points after surgery. CONCLUSIONS Our findings suggest that machine-learning models derived from image features can assist clinicians in HCC diagnosis and its prognosis prediction after hepatectomy.
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Affiliation(s)
- Haotian Liao
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tianyuan Xiong
- Department of Cardiology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiajie Peng
- School of Computer Science, Northwestern Polytechnical University, Xi'an, China
| | - Lin Xu
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Mingheng Liao
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Zhen Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Zhenru Wu
- Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Kefei Yuan
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
| | - Yong Zeng
- Department of Liver Surgery and Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
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Zhang Y, Kuang S, Shan Q, Rong D, Zhang Z, Yang H, Wu J, Chen J, He B, Deng Y, Roberts N, Shen J, Venkatesh SK, Wang J. Can IVIM help predict HCC recurrence after hepatectomy? Eur Radiol 2019; 29:5791-5803. [PMID: 30972544 DOI: 10.1007/s00330-019-06180-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 01/30/2019] [Accepted: 02/08/2019] [Indexed: 12/16/2022]
Abstract
PURPOSE To determine the diagnostic performance of intravoxel incoherent motion (IVIM) parameters to predict tumor recurrence after hepatectomy in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). MATERIALS AND METHODS One hundred and fifty-seven patients (mean age 52.54 ± 11.32 years, 87% male) with surgically and pathologically confirmed HCC were included. Regions of interests were drawn including the tumors by two independent radiologists. ADC and IVIM-derived parameters (true diffusion coefficient [D]; pseudodiffusion coefficient [D*]; pseudodiffusion fraction [f]) were obtained preoperatively. The Cox proportional hazards model was used to analyze the predictors associated with tumor recurrence after hepatectomy. RESULTS Forty-seven of 157 (29.9%) patients experienced tumor recurrence. The multivariate Cox proportional hazards model revealed that a D value < 0.985 × 10-3 mm2/s (hazard ratio (HR), 0.190; p = 0.023) was a risk factor for tumor recurrence. Additional risk factors included younger age (HR, 0.328; p = 0.034) and higher serum alpha-fetoprotein (AFP) level (HR, 2.079; p = 0.013). Further, receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of the obtained Cox regression model improved from 0.68 for the combination of AFP and age alone to 0.724 for the combination of D value, AFP, and age. CONCLUSION The D value derived from the IVIM model is a potential biomarker for the preoperative prediction of recurrence after hepatectomy in patients with HCC. When combined with age and AFP levels, D can improve the predictive performance for tumor recurrence. KEY POINTS • The recurrence rate of HCC after hepatectomy was higher in patients with ADC, D, and f values that were lower than the optimal cutoff values. • The optimal cutoff values of ADC, D, D*, and f for predicting recurrence in HBV associated HCC were 0.858 × 10-3 mm2/s, 0.985 × 10-3 mm2/s, 12.5 × 10-3 mm2/s, and 23.4%, respectively. • The D value derived from IVIM diffusion-weighted imaging may be a useful biomarker for preoperative prediction of recurrence after hepatectomy in patients with HCC. When combined with age and AFP levels, D can improve the predictive performance for tumor recurrence.
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Affiliation(s)
- Yao Zhang
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Sichi Kuang
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Qungang Shan
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Dailin Rong
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Zhongping Zhang
- Philips Intergrated Solution Center, Guangzhou, People's Republic of China
| | - Hao Yang
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Jun Wu
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Jingbiao Chen
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Bingjun He
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Ying Deng
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China
| | - Neil Roberts
- Edinburgh Imaging, School of Clinical Sciences, University of Edinburgh, Edinburgh, EH16 4TJ, UK
| | - Jun Shen
- Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (SYSU), No 107, Yanjiang Road, West, Guangzhou, 510120, People's Republic of China
| | - Sudhakar K Venkatesh
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Jin Wang
- Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University (SYSU), No 600, Tianhe Road, Guangzhou, 510630, People's Republic of China.
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