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Al Farai A, Sangiuolo F, Albaali D, Ajoub M, Giannone F, Cassese G, Panaro F. The Definition of the Best Margin Cutoff and Related Oncological Outcomes After Liver Resection for Hepatocellular Carcinoma: A Systematic Review. Cancers (Basel) 2025; 17:1759. [PMID: 40507240 PMCID: PMC12153659 DOI: 10.3390/cancers17111759] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2025] [Accepted: 05/16/2025] [Indexed: 06/16/2025] Open
Abstract
Background/Objectives: Different cutoffs have been proposed to be the optimal resection margin of liver resection for hepatocellular carcinoma (HCC). The aim of this study was to perform a systematic review, investigating the different impacts on disease-free survival (DFS) and overall survival (OS) of different margin cutoffs. Methods: The PubMed, Embase, and Cochrane databases were searched for comparative studies evaluating the oncological impacts of different types of liver resection margin for HCC. Results: A total of 48 studies were included in the final analysis. Among them, 36 evaluated the impact of resection margin width on OS and 42 on DFS. The margin cutoffs assessed varied widely, including 20 mm, 10 mm, 5 mm, 4 mm, 2 mm, and 1 mm. While wider margins (≥10 mm) were generally associated with improved outcomes, particularly in high-risk subgroups such as patients with microvascular invasion (MVI), elevated alpha-fetoprotein (AFP) levels, or a non-cirrhotic liver, other studies reported no significant differences. The findings were highly heterogeneous across the studies due to differences in patient populations, tumor biology, and surgical approaches. Consequently, the evidence suggests that the optimal margin is context-dependent rather than universal. Conclusions: Wider resection margins should be considered in select high-risk patients, while a tailored, case-by-case approach remains necessary given the overall heterogeneity of HCC presentations.
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Affiliation(s)
- Abdallah Al Farai
- Surgical Oncology, GI Program, Sultan Qaboos Comprehensive Cancer Care & Research Center, University Medical City, Muscat 123, Oman; (A.A.F.); (D.A.); (M.A.)
| | - Federico Sangiuolo
- Division of Hepato-Pancreato-Biliary, Oncologic and Robotic Surgery, Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; (F.S.); (G.C.); (F.P.)
- Department of Research and Innovation (DAIRI), Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
| | - Dana Albaali
- Surgical Oncology, GI Program, Sultan Qaboos Comprehensive Cancer Care & Research Center, University Medical City, Muscat 123, Oman; (A.A.F.); (D.A.); (M.A.)
| | - Mahmoud Ajoub
- Surgical Oncology, GI Program, Sultan Qaboos Comprehensive Cancer Care & Research Center, University Medical City, Muscat 123, Oman; (A.A.F.); (D.A.); (M.A.)
| | - Fabio Giannone
- Division of Hepato-Pancreato-Biliary, Oncologic and Robotic Surgery, Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; (F.S.); (G.C.); (F.P.)
- Department of Research and Innovation (DAIRI), Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
| | - Gianluca Cassese
- Division of Hepato-Pancreato-Biliary, Oncologic and Robotic Surgery, Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; (F.S.); (G.C.); (F.P.)
- Department of Research and Innovation (DAIRI), Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Department of Health Sciences, School of Medicine, University of Eastern Piedmont “Amedeo Avogadro”, 28100 Alessandria, Italy
| | - Fabrizio Panaro
- Division of Hepato-Pancreato-Biliary, Oncologic and Robotic Surgery, Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy; (F.S.); (G.C.); (F.P.)
- Department of Research and Innovation (DAIRI), Azienda Ospedaliero-Universitaria SS, Antonio e Biagio e Cesare Arrigo, 15121 Alessandria, Italy
- Department of Health Sciences, School of Medicine, University of Eastern Piedmont “Amedeo Avogadro”, 28100 Alessandria, Italy
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Wang Y, Qu Y, Yang C, Wu Y, Wei H, Qin Y, Yang J, Zheng T, Chen J, Cannella R, Vernuccio F, Ronot M, Chen W, Song B, Jiang H. MRI-based prediction of the need for wide resection margins in patients with single hepatocellular carcinoma. Eur Radiol 2025; 35:1772-1784. [PMID: 39235653 PMCID: PMC11913993 DOI: 10.1007/s00330-024-11043-5] [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: 04/29/2024] [Revised: 07/26/2024] [Accepted: 08/07/2024] [Indexed: 09/06/2024]
Abstract
OBJECTIVES To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins. MATERIALS AND METHODS This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN"). Survival outcomes were compared between wide and narrow resection margins in a propensity-score matched cohort for the score-stratified low- and high-risk groups, respectively. RESULTS Four hundred nineteen patients (median age, 54 years; 361 men) were included, 282 (67.3%) undergoing narrow resection margins. In patients with narrow resection margins, age, alpha-fetoprotein (AFP) > 400 ng/mL, protein induced by vitamin K absence or antagonist-II (PIVKA-II) > 200 mAU/mL, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS (p values, 0.002-0.04) and formed the MARGIN score with a testing dataset C-index of 0.75 (95% CI: 0.65-0.84). In the matched cohort, wide resection margin was associated with improved early RFS rate for the high-risk group (MARGIN score ≥ - 1.3; 71.1% vs 41.0%; p = 0.02), but not for the low-risk group (MARGIN score < - 1.3; 79.7% vs 76.1%; p = 0.36). CONCLUSION In patients with single BCLC 0/A HCC, the MARGIN score may serve as promising decision-making to indicate the need for wide resection margins. CLINICAL RELEVANCE STATEMENT The MARGIN score has the potential to identify patients who would benefit more from wide resection margins than narrow resection margins, improving the postoperative survival of patients with single BCLC 0/A hepatocellular carcinoma (HCC). KEY POINTS Age, AFP, PIVKA-II, radiological involvement of liver capsule, and infiltrative appearance were associated with early RFS and formed the MARGIN score. The MARGIN score achieved a testing dataset C-index of 0.75. Wide resection margins were associated with improved early RFS for the high-risk group, but not for the low-risk group.
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Affiliation(s)
- Yanshu Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yali Qu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Chongtu Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yuanan Wu
- Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, China
| | - Hong Wei
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Yun Qin
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Yang
- Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Tianying Zheng
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Roberto Cannella
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Federica Vernuccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy
| | - Maxime Ronot
- Université Paris Cité, UMR 1149, CRI, Paris & Service de Radiologie, Hôpital Beaujon, APHP.Nord, Clichy, France
| | - Weixia Chen
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China
- Department of Radiology, Sanya People's Hospital, Sanya, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
- Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China.
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Zhu Z, Wu K, Lu J, Dai S, Xu D, Fang W, Yu Y, Gu W. Gd-EOB-DTPA-enhanced MRI radiomics and deep learning models to predict microvascular invasion in hepatocellular carcinoma: a multicenter study. BMC Med Imaging 2025; 25:105. [PMID: 40165094 PMCID: PMC11956329 DOI: 10.1186/s12880-025-01646-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is an important risk factor for early postoperative recurrence of hepatocellular carcinoma (HCC). Based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) images, we developed a novel radiomics model. It combined bi-regional features and two machine learning algorithms. The aim of this study was to validate its potential value for preoperative prediction of MVI. METHODS This retrospective study included 304 HCC patients (training cohort, 216 patients; testing cohort, 88 patients) from three hospitals. Intratumoral and peritumoral volumes of interest were delineated in arterial phase, portal venous phase, and hepatobiliary phase images. Conventional radiomics (CR) and deep learning radiomics (DLR) features were extracted based on FeAture Explorer software and the 3D ResNet-18 extractor, respectively. Clinical variables were selected using univariate and multivariate analyses. Clinical, CR, DLR, CR-DLR, and clinical-radiomics (Clin-R) models were built using support vector machines. The predictive capacity of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS The bi-regional CR-DLR model showed more gains and gave better predictive performance than the single-regional models or single-machine learning models. Its AUC, accuracy, sensitivity, and specificity were 0.844, 76.9%, 87.8%, and 69.1% in the training cohort and 0.740, 73.9%, 50%, and 84.5% in the testing cohort. Alpha-fetoprotein (odds ratio was 0.32) and maximum tumor diameter (odds ratio was 1.270) were independent predictors. The AUCs of the clinical model and the Clin-R model were 0.655 and 0.672, respectively. There was no significant difference in the AUCs between all the models (P > 0.005). CONCLUSION Based on Gd-EOB-DTPA-enhanced MRI images, we focused on developing a radiomics model that combines bi-regional features and two machine learning algorithms (CR and DLR). The application of the new model will provide a more accurate and non-invasive diagnostic solution for medical imaging. It will provide valuable information for clinical personalized treatment, thereby improving patient prognosis. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Zhu Zhu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Kaiying Wu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Jian Lu
- Department of Radiology, The Third Affiliated Hospital of Nantong University, The Third People's Hospital of Nantong, Nantong, Jiangsu, 226000, China
| | - Sunxian Dai
- Soochow university, Suzhou, Jiangsu, 215000, China
| | - Dabo Xu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Wei Fang
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Yixing Yu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
| | - Wenhao Gu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China.
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Zhou XQ, Huang S, Shi XM, Liu S, Zhang W, Shi L, Lv MH, Tang XW. Global trends in artificial intelligence applications in liver disease over seventeen years. World J Hepatol 2025; 17:101721. [PMID: 40177211 PMCID: PMC11959664 DOI: 10.4254/wjh.v17.i3.101721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/01/2025] [Accepted: 02/10/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND In recent years, the utilization of artificial intelligence (AI) technology has gained prominence in the field of liver disease. AIM To analyzes AI research in the field of liver disease, summarizes the current research status and identifies hot spots. METHODS We searched the Web of Science Core Collection database for all articles and reviews on hepatopathy and AI. The time spans from January 2007 to August 2023. We included 4051 studies for further collection of information, including authors, countries, institutions, publication years, keywords and references. VOS viewer, CiteSpace, R 4.3.1 and Scimago Graphica were used to visualize the results. RESULTS A total of 4051 articles were analyzed. China was the leading contributor, with 1568 publications, while the United States had the most international collaborations. The most productive institutions and journals were the Chinese Academy of Sciences and Frontiers in Oncology. Keywords co-occurrence analysis can be roughly summarized into four clusters: Risk prediction, diagnosis, treatment and prognosis of liver diseases. "Machine learning", "deep learning", "convolutional neural network", "CT", and "microvascular infiltration" have been popular research topics in recent years. CONCLUSION AI is widely applied in the risk assessment, diagnosis, treatment, and prognosis of liver diseases, with a shift from invasive to noninvasive treatment approaches.
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Affiliation(s)
- Xue-Qin Zhou
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Shu Huang
- Department of Gastroenterology, Lianshui People' Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian 223499, Jiangsu Province, China
| | - Xia-Min Shi
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Sha Liu
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Wei Zhang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Lei Shi
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Mu-Han Lv
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China
| | - Xiao-Wei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou 646099, Sichuan Province, China.
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Li LJ, Wu CQ, Ye FL, Xuan Z, Zhang XL, Li JP, Zhou J, Su ZZ. Histopathological diagnosis of microvascular invasion in hepatocellular carcinoma: Is it reliable? World J Gastroenterol 2025; 31:98928. [PMID: 39926219 PMCID: PMC11718611 DOI: 10.3748/wjg.v31.i5.98928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 11/05/2024] [Accepted: 12/12/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence, but the reliability of its current pathological diagnosis remains uncertain. AIM To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging (WSI) for better MVI detection. METHODS We utilized 40 New Zealand white rabbits to establish VX2 liver tumor models. The entire tumor-containing liver lobe was subsequently obtained, following which five different sampling protocols (A-E) were employed to evaluate the detection rate, accuracy, quantity, and distribution of MVI, with the aim of identifying the optimal sampling method. RESULTS VX2 liver tumor models were successfully established in 37 rabbits, with an incidence of MVI of 81.1% (30/37). The detection rates [27% (10/37), 43% (16/37), 62% (23/37), 68% (25/37), and 93% (14/15)] and quantity (15, 36, 107, 125, and 395) of MVI increased significantly from protocols A to E. The distribution of MVI showed fewer MVIs farther away from the tumor, but the percentage of MVI detected quantity gradually increased from 6.7% to 48.3% in the distant nonneoplastic liver tissue from protocols A to E. Protocol C was identified as the optimal sampling method by comparing them in sequence. The sampling protocol of three consecutive interval WSIs at the tumor center (WSI3) was further screened to determine the optimal number of WSIs. Protocol A (7-point sampling method) exhibited only 46% accuracy and a high false-negative rate of 67%. Notably, the WSI3 protocol improved the accuracy to 78% and decreased the false-negative rate to 27%. CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI detection. In contrast, the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy, which is crucial for hepatocellular carcinoma diagnosis and treatment planning.
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Affiliation(s)
- Liu-Jun Li
- Department of Ultrasound, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
- Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Chao-Qun Wu
- Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Fei-Le Ye
- Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Zhou Xuan
- Department of Pathology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
| | - Xiao-Li Zhang
- Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
| | - Jian-Ping Li
- Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
| | - Jia Zhou
- Department of Ultrasound, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan Province, China
| | - Zhong-Zhen Su
- Department of Ultrasound, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai 519000, Guangdong Province, China
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Hsu CM, Liu YC, Huang JF. Exploring Circulating Tumor Cells: Detection Methods and Biomarkers for Clinical Evaluation in Hepatocellular Carcinoma. J Clin Transl Hepatol 2024; 12:1020-1042. [PMID: 39649035 PMCID: PMC11622199 DOI: 10.14218/jcth.2024.00230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 09/13/2024] [Accepted: 09/25/2024] [Indexed: 12/10/2024] Open
Abstract
Circulating tumor cells (CTCs), originating from primary neoplastic tissues, infiltrate blood vessels, migrate through the bloodstream, and establish secondary tumor foci. The detection of CTCs holds significant promise for early-stage identification, diagnostic precision, therapeutic monitoring, and prognostic evaluation. It offers a non-invasive approach and has broad clinical relevance in cancer management. This comprehensive review primarily focused on CTCs as biomarkers in the diagnostic, therapeutic, and prognostic surveillance of hepatocellular carcinoma, compared their correlation with key clinical parameters and the identification of gene characteristics. It also highlighted current methodologies in CTC detection. Despite approval by the U.S. Food and Drug Administration for select malignancies, the comprehensive integration of CTCs into routine clinical practice requires procedural standardization and a deeper understanding of the underlying molecular intricacies. The challenges in CTC detection, including limited quantity, technical impediments, and cellular heterogeneity, call for concerted and further investigational efforts to advance precision in cancer diagnostics and prognostication, thus realizing the objectives of precise and personalized medicine.
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Affiliation(s)
- Chin-Mu Hsu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Yi-Chang Liu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
| | - Jee-Fu Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
- Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung
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Wei G, Fang G, Guo P, Fang P, Wang T, Lin K, Liu J. Preoperative prediction of microvascular invasion risk in hepatocellular carcinoma with MRI: peritumoral versus tumor region. Insights Imaging 2024; 15:188. [PMID: 39090456 PMCID: PMC11294513 DOI: 10.1186/s13244-024-01760-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 06/23/2024] [Indexed: 08/04/2024] Open
Abstract
OBJECTIVES To explore the predictive performance of tumor and multiple peritumoral regions on dynamic contrast-enhanced magnetic resonance imaging (MRI), to identify optimal regions of interest for developing a preoperative predictive model for the grade of microvascular invasion (MVI). METHODS A total of 147 patients who were surgically diagnosed with hepatocellular carcinoma, and had a maximum tumor diameter ≤ 5 cm were recruited and subsequently divided into a training set (n = 117) and a testing set (n = 30) based on the date of surgery. We utilized a pre-trained AlexNet to extract deep learning features from seven different regions of the maximum transverse cross-section of tumors in various MRI sequence images. Subsequently, an extreme gradient boosting (XGBoost) classifier was employed to construct the MVI grade prediction model, with evaluation based on the area under the curve (AUC). RESULTS The XGBoost classifier trained with data from the 20-mm peritumoral region showed superior AUC compared to the tumor region alone. AUC values consistently increased when utilizing data from 5-mm, 10-mm, and 20-mm peritumoral regions. Combining arterial and delayed-phase data yielded the highest predictive performance, with micro- and macro-average AUCs of 0.78 and 0.74, respectively. Integration of clinical data further improved AUCs values to 0.83 and 0.80. CONCLUSION Compared with those of the tumor region, the deep learning features of the peritumoral region provide more important information for predicting the grade of MVI. Combining the tumor region and the 20-mm peritumoral region resulted in a relatively ideal and accurate region within which the grade of MVI can be predicted. CLINICAL RELEVANCE STATEMENT The 20-mm peritumoral region holds more significance than the tumor region in predicting MVI grade. Deep learning features can indirectly predict MVI by extracting information from the tumor region and directly capturing MVI information from the peritumoral region. KEY POINTS We investigated tumor and different peritumoral regions, as well as their fusion. MVI predominantly occurs in the peritumoral region, a superior predictor compared to the tumor region. The peritumoral 20 mm region is reasonable for accurately predicting the three-grade MVI.
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Affiliation(s)
- Guangya Wei
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China
| | - Guoxu Fang
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Peng Fang
- Department of Radiology, Henan Province Hospital of TCM, Zhengzhou, China
| | - Tongming Wang
- Department of Radiology, Henan Province Hospital of TCM, Zhengzhou, China
| | - Kecan Lin
- Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China.
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Mondal D, Shinde S, Sinha V, Dixit V, Paul S, Gupta RK, Thakur S, Vishvakarma NK, Shukla D. Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers. Front Mol Biosci 2024; 11:1385238. [PMID: 38770216 PMCID: PMC11103528 DOI: 10.3389/fmolb.2024.1385238] [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: 02/12/2024] [Accepted: 04/08/2024] [Indexed: 05/22/2024] Open
Abstract
Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.
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Affiliation(s)
- Deepankar Mondal
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Sapnita Shinde
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Vibha Sinha
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
| | - Vineeta Dixit
- Department of Botany, Sri Sadguru Jagjit Singh Namdhari College, Garhwa, Jharkhand, India
| | - Souvik Paul
- Department of Surgical Gastroenterology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
| | - Rakesh Kumar Gupta
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India
| | | | | | - Dhananjay Shukla
- Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India
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9
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Zhang ZH, Jiang C, Qiang ZY, Zhou YF, Ji J, Zeng Y, Huang JW. Role of microvascular invasion in early recurrence of hepatocellular carcinoma after liver resection: A literature review. Asian J Surg 2024; 47:2138-2143. [PMID: 38443255 DOI: 10.1016/j.asjsur.2024.02.115] [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: 10/13/2023] [Revised: 12/12/2023] [Accepted: 02/22/2024] [Indexed: 03/07/2024] Open
Abstract
Hepatectomy is widely considered a potential treatment for hepatocellular carcinoma (HCC). Unfortunately, one-third of HCC patients have tumor recurrence within 2 years after surgery (early recurrence), accounting for more than 60% of all recurrence patients. Early recurrence is associated with a worse prognosis. Previous studies have shown that microvascular invasion (MVI) is one of the key factors for early recurrence and poor prognosis in patients with HCC after surgery. This paper reviews the latest literature and summarizes the predictors of MVI, the correlation between MVI and early recurrence, the identification of suspicious nodules or subclinical lesions, and the treatment strategies for MVI-positive HCC. The aim is to explore the management of patients with MVI-positive HCC.
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Affiliation(s)
- Zhi-Hong Zhang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chuang Jiang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ze-Yuan Qiang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yi-Fan Zhou
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jun Ji
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ji-Wei Huang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, China.
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10
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Xu J, Zhao Y, Chen Z, Wei L. Clinical Application of Different Liquid Biopsy Components in Hepatocellular Carcinoma. J Pers Med 2024; 14:420. [PMID: 38673047 PMCID: PMC11051574 DOI: 10.3390/jpm14040420] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/26/2024] [Accepted: 04/04/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, usually occurring in the background of chronic liver disease. HCC lethality rate is in the third highest place in the world. Patients with HCC have concealed early symptoms and possess a high-level of heterogeneity. Once diagnosed, most of the tumors are in advanced stages and have a poor prognosis. The sensitivity and specificity of existing detection modalities and protocols are suboptimal. HCC calls for more sophisticated and individualized therapeutic regimens. Liquid biopsy is non-invasive, repeatable, unaffected by location, and can be monitored dynamically. It has emerged as a useable aid in achieving precision malignant tumor treatment. Circulating tumor cells (CTCs), circulating nucleic acids, exosomes and tumor-educated platelets are the commonest components of a liquid biopsy. It possesses the theoretical ability to conquer the high heterogeneity and the difficulty of early detection for HCC patients. In this review, we summarize the common enrichment techniques and the clinical applications in HCC for different liquid biopsy components. Tumor recurrence after HCC-related liver transplantation is more insidious and difficult to treat. The clinical use of liquid biopsy in HCC-related liver transplantation is also summarized in this review.
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Affiliation(s)
| | | | | | - Lai Wei
- Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China; (J.X.); (Y.Z.); (Z.C.)
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11
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Zhang X, Yu X, Liang W, Zhang Z, Zhang S, Xu L, Zhang H, Feng Z, Song M, Zhang J, Feng S. Deep learning-based accurate diagnosis and quantitative evaluation of microvascular invasion in hepatocellular carcinoma on whole-slide histopathology images. Cancer Med 2024; 13:e7104. [PMID: 38488408 PMCID: PMC10941532 DOI: 10.1002/cam4.7104] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/13/2023] [Accepted: 03/03/2024] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time-consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep-learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. MATERIALS AND METHODS We collected H&E-stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep-learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. RESULTS We successfully developed a MVI artificial intelligence diagnostic model (MVI-AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI-AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. CONCLUSIONS We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.
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Affiliation(s)
- Xiuming Zhang
- Department of Pathology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
| | - Xiaotian Yu
- Department of Computer Science and TechnologyZhejiang UniversityHangzhouP. R. China
| | - Wenjie Liang
- Department of Radiology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
| | - Zhongliang Zhang
- School of ManagementHangzhou Dianzi UniversityHangzhouP. R. China
| | - Shengxuming Zhang
- Department of Computer Science and TechnologyZhejiang UniversityHangzhouP. R. China
| | - Linjie Xu
- Department of Pathology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
| | - Han Zhang
- Department of Pathology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
| | - Zunlei Feng
- Department of Computer Science and TechnologyZhejiang UniversityHangzhouP. R. China
| | - Mingli Song
- Department of Computer Science and TechnologyZhejiang UniversityHangzhouP. R. China
| | - Jing Zhang
- Department of Pathology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
| | - Shi Feng
- Department of Pathology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouP. R. China
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12
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Herrero A, Toubert C, Bedoya JU, Assenat E, Guiu B, Panaro F, Bardol T, Cassese G. Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations: state of the art and future perspectives. Hepatobiliary Surg Nutr 2024; 13:71-88. [PMID: 38322198 PMCID: PMC10839736 DOI: 10.21037/hbsn-22-579] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 05/02/2023] [Indexed: 02/08/2024]
Abstract
Despite the improvements in surgical and medical therapy for hepatocellular carcinoma (HCC), recurrence still represents a major issue. Up to 70% of patients can experience HCC recurrence after liver resection (LR), as well as 20% of them even after liver transplantation (LT). The patterns of recurrence are different according to both the time and the location. Similarly, the risk factors and the management can change not only according to these patterns, but also according to the underlying liver condition and to the first treatment performed. Deep knowledge of such correlation is fundamental, since prevention and effective management of recurrence are undoubtedly the most important strategies to improve the outcomes of HCC treatment. Without adjuvant therapy, maintaining very close monitoring during the first 2 years in order to diagnose curable recurrence and continue this monitoring beyond 5 years because late recurrences exist, remains our only possibility today. Surgery represents the cornerstone treatment for HCC, including both LT and LR. However, new interesting therapeutic opportunities are coming from immunotherapy that has shown encouraging results also in the adjuvant setting. In such a complex and evolutionary scenario, the aim of this review is to summarize current strategies for the management of HCC recurrence, focusing on the different possible scenarios, as well as on future perspectives.
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Affiliation(s)
- Astrid Herrero
- Department of HPB Surgery and Liver Transplantation, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Cyprien Toubert
- Department of HPB Surgery and Liver Transplantation, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Jose Ursic Bedoya
- Department of Hepatology and Liver Transplantation, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Eric Assenat
- Department of Digestive Oncology, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Boris Guiu
- Department of Radiology, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Fabrizio Panaro
- Department of HPB Surgery and Liver Transplantation, Saint Eloi Hospital, Montpellier University, Montpellier, France
| | - Thomas Bardol
- Laboratory of rare human Circulating Cells (LCCRH), University Medical Center of Montpellier, Montpellier, France
| | - Gianluca Cassese
- Division of Minimally Invasive and Robotic HPB Surgery, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
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13
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Masuda Y, Yeo MHX, Burdio F, Sanchez-Velazquez P, Perez-Xaus M, Pelegrina A, Koh YX, Di Martino M, Goh BKP, Tan EK, Teo JY, Romano F, Famularo S, Ferrari C, Griseri G, Piardi T, Sommacale D, Gianotti L, Molfino S, Baiocchi G, Ielpo B. Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study. Updates Surg 2024; 76:57-69. [PMID: 37839048 DOI: 10.1007/s13304-023-01656-8] [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: 08/06/2023] [Accepted: 09/23/2023] [Indexed: 10/17/2023]
Abstract
Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.
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Affiliation(s)
- Yoshio Masuda
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Ministry of Health Holdings Singapore, Singapore, Singapore
| | - Mark Hao Xuan Yeo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Ministry of Health Holdings Singapore, Singapore, Singapore
| | - Fernando Burdio
- Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain
| | - Patricia Sanchez-Velazquez
- Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain
| | - Marc Perez-Xaus
- Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain
| | - Amalia Pelegrina
- Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain
| | - Ye Xin Koh
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Marcello Di Martino
- Hepatobiliary Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
| | - Brian K P Goh
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Ek Khoon Tan
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Jin Yao Teo
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
- Duke-National University of Singapore Medical School, Singapore, Singapore
| | - Fabrizio Romano
- Department of Surgery, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | - Simone Famularo
- Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | | | - Guido Griseri
- HPB Surgical Unit, San Paolo Hospital, Savona, Italy
| | - Tullio Piardi
- Department of General and Digestive Surgery, Hôpital Robert Debré, Centre Hospitalier Universitaire de Reims, Université de Reims Champagne-Ardenne, Reims, France
| | - Daniele Sommacale
- Department of General and Digestive Surgery, Hôpital Robert Debré, Centre Hospitalier Universitaire de Reims, Université de Reims Champagne-Ardenne, Reims, France
| | - Luca Gianotti
- School of Medicine and Surgery, Milano-Bicocca University and HPB Unit, IRCCS San Gerardo Hospital, Monza, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Gianluca Baiocchi
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Benedetto Ielpo
- Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain.
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14
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Wu J, Chan YT, Lu Y, Wang N, Feng Y. The tumor microenvironment in the postsurgical liver: Mechanisms and potential targets of postoperative recurrence in human hepatocellular carcinoma. Med Res Rev 2023; 43:1946-1973. [PMID: 37102365 DOI: 10.1002/med.21967] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 03/23/2023] [Accepted: 04/13/2023] [Indexed: 04/28/2023]
Abstract
Surgery remains to be the mainstay of treatment for hepatocellular carcinoma (HCC). Nonetheless, its therapeutic efficacy is significantly impaired by postoperative recurrence, which occurs in more than half of cases as a result of intrahepatic metastasis or de novo tumorigenesis. For decades, most therapeutic strategies on inhibiting postoperative HCC recurrence have been focused on the residual tumor cells but satisfying therapeutic outcomes are barely observed in the clinic. In recent years, a better understanding of tumor biology allows us to shift our focus from tumor cells toward the postoperative tumor microenvironment (TME), which is gradually identified to play a pivotal role in tumor recurrence. In this review, we describe various surgical stress and surgical perturbation on postoperative TME. Besides, we discuss how such alternations in TME give rise to postoperative recurrence of HCC. Based on its clinical significance, we additionally highlight the potential of the postoperative TME as a target for postoperative adjuvant therapeutics.
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Affiliation(s)
- Junyu Wu
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yau-Tuen Chan
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yuanjun Lu
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Ning Wang
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yibin Feng
- School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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15
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Wang Y, Chai S, Cai W, Yu J, Liang P. Prognostic and pathological implications of contrast-enhanced ultrasound features in hepatocellular carcinoma. J Cancer Res Ther 2023; 19:1040-1047. [PMID: 37675734 DOI: 10.4103/jcrt.jcrt_1155_23] [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: 09/08/2023]
Abstract
Background Contrast-enhanced ultrasound (CEUS) plays a vital role in diagnosing hepatocellular carcinoma (HCC) and, to some extent, reflects tumor prognosis. This suggests that some pathological features of HCC may be associated with CEUS features. Aim This study aimed to verify the prognostic significance of four CEUS features and further explore their pathological significance. Materials and Methods This study included 243 HCC patients who underwent a preoperative CEUS examination. All pathological diagnoses and immunohistochemical information were obtained from the pathological report. The prognostic significance of four CEUS features, including nodule-in-nodule architecture, mosaic architecture, intratumoral feeding arteries, and peritumoral arterial phase (AP) hyperenhancement, was analyzed. The correlation between prognostic-related features and immunohistochemical information was further analyzed. Results The disease-free survival (DFS) of HCC was significantly affected by mosaic architecture or intratumoral feeding arteries (HR = 1.79; 95% confidence interval (95% CI), 1.09-2.95; P = 0.004; HR = 1.70; 95% CI, 1.07-2.71; P = 0.025, respectively). Intratumoral feeding arteries were positively correlated with the expression of serum alpha-fetoprotein (AFP), microvascular invasion (MVI), differentiation, size, and Ki-67, among which the correlation with size was the strongest, followed by Ki-67 and MVI. The mosaic architecture was positively correlated with serum AFP, MVI, differentiation, and size, among which the correlation with size was strongest, followed by MVI. Conclusion The mosaic architecture and intratumoral feeding arteries of CEUS were closely related to the postoperative progression of HCC. Mosaic architecture had a good correlation with tumor size and MVI, whereas intratumoral feeding arteries were closely associated with tumor size and Ki-67 expression.
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Affiliation(s)
- Yuling Wang
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Suwan Chai
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Wenjia Cai
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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16
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Abubakar SD, Takaki M, Haeno H. Computational modeling of locoregional recurrence with spatial structure identifies tissue-specific carcinogenic profiles. Front Oncol 2023; 13:1116210. [PMID: 37091178 PMCID: PMC10117647 DOI: 10.3389/fonc.2023.1116210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 03/23/2023] [Indexed: 04/08/2023] Open
Abstract
IntroductionLocal and regional recurrence after surgical intervention is a significant problem in cancer management. The multistage theory of carcinogenesis precisely places the presence of histologically normal but mutated premalignant lesions surrounding the tumor - field cancerization, as a significant cause of cancer recurrence. The relationship between tissue dynamics, cancer initiation and cancer recurrence in multistage carcinogenesis is not well known.MethodsThis study constructs a computational model for cancer initiation and recurrence by combining the Moran and branching processes in which cells requires 3 or more mutations to become malignant. In addition, a spatial structure-setting is included in the model to account for positional relativity in cell turnover towards malignant transformation. The model consists of a population of normal cells with no mutation; several populations of premalignant cells with varying number of mutations and a population of malignant cells. The model computes a stage of cancer detection and surgery to eliminate malignant cells but spares premalignant cells and then estimates the time for malignant cells to re-emerge.ResultsWe report the cellular conditions that give rise to different patterns of cancer initiation and the conditions favoring a shorter cancer recurrence by analyzing premalignant cell types at the time of surgery. In addition, the model is fitted to disease-free clinical data of 8,957 patients in 27 different cancer types; From this fitting, we estimate the turnover rate per month, relative fitness of premalignant cells, growth rate and death rate of cancer cells in each cancer type.DiscussionOur study provides insights into how to identify patients who are likely to have a shorter recurrence and where to target the therapeutic intervention.
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Affiliation(s)
| | - Mitsuaki Takaki
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan
| | - Hiroshi Haeno
- Research Institute for Biomedical Science, Tokyo University of Science, Noda, Japan
- *Correspondence: Hiroshi Haeno,
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17
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Hua Y, Dong J, Hong J, Wang B, Yan Y, Li Z. Clinical applications of circulating tumor cells in hepatocellular carcinoma. Front Oncol 2022; 12:968591. [PMID: 36091119 PMCID: PMC9448983 DOI: 10.3389/fonc.2022.968591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 08/01/2022] [Indexed: 12/09/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a highly malignant tumor and ranked as the fourth cause of cancer-related mortality. The poor clinical prognosis is due to an advanced stage and resistance to systemic treatment. There are no obvious clinical symptoms in the early stage and the early diagnosis rate remains low. Novel effective biomarkers are important for early diagnosis and tumor surveillance to improve the survival of HCC patients. Circulating tumor cells (CTCs) are cancer cells shed from primary or metastatic tumor and extravasate into the blood system. The number of CTCs is closely related to the metastasis of various solid tumors. CTCs escape from blood vessels and settle in target organs, then form micro-metastasis. Epithelial-mesenchymal transformation (EMT) plays a crucial role in distant metastasis, which confers strong invasiveness to CTCs. The fact that CTCs can provide complete cellular biological information, which allows CTCs to be one of the most promising liquid biopsy targets. Recent studies have shown that CTCs are good candidates for early diagnosis, prognosis evaluation of metastasis or recurrence, and even a potential therapeutic target in patients with HCC. It is a new indicator for clinical application in the future. In this review, we introduce the enrichment methods and mechanisms of CTCs, and focus on clinical application in patients with HCC.
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Affiliation(s)
- Yinggang Hua
- Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Jingqing Dong
- Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Jinsong Hong
- Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Bailin Wang
- Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Yong Yan
- Department of General Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China
| | - Zhiming Li
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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18
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Teng PC, Agopian VG, Lin TY, You S, Zhu Y, Tseng HR, Yang JD. Circulating tumor cells: A step toward precision medicine in hepatocellular carcinoma. J Gastroenterol Hepatol 2022; 37:1179-1190. [PMID: 35543075 PMCID: PMC9271591 DOI: 10.1111/jgh.15886] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 05/02/2022] [Indexed: 12/09/2022]
Abstract
Serum alpha-fetoprotein and radiologic imaging are the most commonly used tests for early diagnosis and dynamic monitoring of treatment response in hepatocellular carcinoma (HCC). However, the accuracy of these tests is limited, and they may not reflect the underlying biology of the tumor. Thus, developing highly accurate novel HCC biomarkers reflecting tumor biology is a clinically unmet need. Circulating tumor cells (CTCs) have long been proposed as a noninvasive biomarker in clinical oncology. Most CTC assays utilize immunoaffinity-based, size-based, and/or enrichment-free mechanisms followed by immunocytochemical staining to characterize CTCs. The prognostic value of HCC CTC enumeration has been extensively validated. Subsets of CTCs expressing mesenchymal markers are also reported to have clinical significance. In addition, researchers have been devoting their efforts to molecular characterizations of CTCs (e.g. genetics and transcriptomics) as molecular profiling can offer a more accurate readout and provide biological insights. As new molecular profiling techniques, such as digital polymerase chain reaction, are developed to detect minimal amounts of DNA/RNA, several research groups have established HCC CTC digital scoring systems to quantify clinically relevant gene panels. Given the versatility of CTCs to provide intact molecular and functional data that reflects the underlying tumor, CTCs have great potential as a noninvasive biomarker in HCC. Large-scale, prospective studies for HCC CTCs with a standardized protocol are necessary for successful clinical translation.
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Affiliation(s)
- Pai-Chi Teng
- Department of Education and Research, Taipei City Hospital Renai Branch, Taipei, Taiwan,Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA,California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA
| | - Vatche G. Agopian
- Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA,Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
| | - Ting-Yi Lin
- Doctoral Degree Program of Translational Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taiwan,Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Sungyong You
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yazhen Zhu
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA
| | - Hsian-Rong Tseng
- California NanoSystems Institute, Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA,Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA
| | - Ju Dong Yang
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA,corresponding author (Dr. Ju Dong Yang):
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19
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Xu X, Huang A, Guo DZ, Wang YP, Zhang SY, Yan JY, Wang XY, Cao Y, Fan J, Zhou J, Fu XT, Shi YH. Integration of Inflammation-Immune Factors to Build Prognostic Model Predictive of Prognosis and Minimal Residual Disease for Hepatocellular Carcinoma. Front Oncol 2022; 12:893268. [PMID: 35756674 PMCID: PMC9213691 DOI: 10.3389/fonc.2022.893268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 05/17/2022] [Indexed: 12/24/2022] Open
Abstract
Background Tumor recurrence after hepatectomy is high for hepatocellular carcinoma (HCC), and minimal residual disease (MRD) could be the underlying mechanism. A predictive model for recurrence and presence of MRD is needed. Methods Common inflammation-immune factors were reviewed and selected to construct novel models. The model consisting of preoperative aspartate aminotransferase, C-reactive protein, and lymphocyte count, named ACLR, was selected and evaluated for clinical significance. Results Among the nine novel inflammation-immune models, ACLR showed the highest accuracy for overall survival (OS) and time to recurrence (TTR). At the optimal cutoff value of 80, patients with high ACLR (> 80) had larger tumor size, higher Edmondson’s grade, more vascular invasion, advanced tumor stage, and poorer survival than those with low ACLR (≤ 80) in the training cohort (5-year OS: 43.3% vs. 80.1%, P < 0.0001; 5-year TTR: 74.9% vs. 45.3%, P < 0.0001). Multivariate Cox analysis identified ACLR as an independent risk factor for OS [hazard ratio (HR) = 2.22, P < 0.001] and TTR (HR = 2.36, P < 0.001). Such clinical significance and prognostic value were verified in validation cohort. ACLR outperformed extant models, showing the highest area under receiver operating characteristics curve for 1-, 3-, and 5-year OS (0.737, 0.719, and 0.708) and 1-, 3-, and 5-year TTR (0.696, 0.650, and 0.629). High ACLR correlated with early recurrence (P < 0.001) and extremely early recurrence (P < 0.001). In patients with high ACLR, wide resection margin might confer survival benefit by decreasing recurrence (median TTR, 25.5 vs. 11.4 months; P = 0.037). Conclusions The novel inflammation-immune model, ACLR, could effectively predict prognosis, and the presence of MRD before hepatectomy and might guide the decision on resection margin for patients with HCC.
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Affiliation(s)
- Xin Xu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ao Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - De-Zhen Guo
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yu-Peng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shi-Yu Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia-Yan Yan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xin-Yu Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ya Cao
- Cancer Research Institute, Xiangya School of Medicine, Central South University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Xiangya Hospital, Central South University, Changsha, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Xiu-Tao Fu
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ying-Hong Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University and Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, China.,Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
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20
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Zhang Q, Xia F, Gao H, Wu Z, Cao W, Xiang Q, Guan Z, Su Y, Zhang W, Chen W, Mo A, Li S. Circulating Tumor Cells as an Indicator of Treatment Options for Hepatocellular Carcinoma Less Than or Equal to 3 cm in Size: A Multi-Center, Retrospective Study. Front Surg 2022; 9:895426. [PMID: 35795230 PMCID: PMC9251203 DOI: 10.3389/fsurg.2022.895426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 05/31/2022] [Indexed: 12/24/2022] Open
Abstract
Background The status of circulating tumor cells (CTCs) is related to the recurrence of hepatocellular carcinoma (HCC), which is also one of the reasons for the poor prognosis of HCC. The purpose of this study was to explore whether CTCs can help guide the choice of treatment methods for HCC. Methods This study is a multicenter retrospective study, including 602 patients with HCC. CTCs were detected in the overall cohort before operation. There were 361 patients in the training cohort and 241 patients in the validation cohort. Patients were divided into CTC-negative group (CTCs = 0/5 mL) and the CTC-positive group (CTCs ≥ 1/5 mL) according to CTCs status. Subgroup analysis was performed according to CTCs status. We compared overall survival, and recurrence outcomes for HCC patients with different CTC statuses after undergoing radiofrequency ablation (RFA) or surgical resection (SR). Results There was no significant difference in overall survival (OS) and recurrence-free survival (RFS) between the RFA group and SR group for CTC-negative patients in both the training cohort and the validation cohort (P > 0.05). However, among CTC-positive patients, the clinical outcome of patients in the SR group was significantly better than those in the RFA group. CTC-positive patients who underwent RFA had increased early recurrence compared to those who underwent SR. RFA is an independent risk factor for survival and recurrence in CTC-positive HCC patients. Conclusions The CTC status could serve as an indicator to guide the choice between surgical resection or radiofrequency ablation for early hepatocellular carcinoma. Surgical resection is recommended for CTC-positive patients.
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Affiliation(s)
- Qiao Zhang
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
| | - Feng Xia
- Department of Hepatic Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Hengyi Gao
- Department of Hepatic Vascular Surgery, Xiaogan Central Hospital, Xiaogan, China
| | - Zhenheng Wu
- Department of Hepatobiliary Surgery, Union Hospital Affiliated to Fujian Medical University, Fuzhou, China
| | - Wenjing Cao
- Southern Medical University Graduate School, Guangzhou, China
| | - Qingfeng Xiang
- The First Department of General Surgery, Qingyuan People’s Hospital, Qingyuan, China
| | - Zhifeng Guan
- Department of Gastrointestinal Surgery, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
| | - Yang Su
- Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, China
| | | | - Weiqiang Chen
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
| | - Ali Mo
- Department of Hepatobiliary Surgery, Zhongshan Hospital Affiliated to Sun Yat-Sen University, Zhongshan, China
| | - Shuqun Li
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, China
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21
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Ding WZ, Liu S, Liu F, Cheng Z, Yu X, Han ZY, Yu J, Liang P. Are all local tumour progressions of HCC related to thermal ablation? A study of the causes and classification of local tumour progression. Eur Radiol 2022; 32:8518-8526. [PMID: 35704110 DOI: 10.1007/s00330-022-08913-1] [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: 12/28/2021] [Revised: 05/26/2022] [Accepted: 05/30/2022] [Indexed: 11/30/2022]
Abstract
OBJECTIVES Local tumour progression (LTP) is believed to be a negative consequence of imperfect thermal ablation, but we wondered if all LTP is truly due to imperfect ablation. METHODS This study included 185 LTPs occurring within 1 cm of the ablation zone (AZ) after clinical curative thermal ablation for ≤ 5 cm hepatocellular carcinoma between 2010 and 2019. The AZ was divided into 8 quadrants by coronal, sagittal, and horizontal planes. Two methods, visual assessment through pre- and post-MRI (VA) and tumour mapping for 3D visualisation pre- and post-MRI fusion (MF), were used to assess which AZ quadrant included the shortest ablation margin (AM) by three doctors. LTP subclassification was based on whether LTP contacted the AZ margin (contacted LTP and dissociated-type LTP) and occurrence at different time points (12, 18, and 24 months). RESULTS Fleiss's Kappa of VA and MF was 0.769 and 0.886, respectively. Cohen's Kappa coefficient between VA and MF was 0.830. For all LTPs, 98/185 (53.0%) occurred in the shortest AM quadrant, which showed a significant central tendency (p < 0.001). However, only 8/51 (15.7%) dissociated - type LTPs and 6/39 (15.4%) LTPs after 24 months occurred in the shortest AM quadrant, which showed no evenly distributed difference (p = 0.360 and 0.303). CONCLUSIONS MF is an accurate and convenient method to assess the shortest AM quadrant. LTP is a central tendency in the shortest AM quadrant, but dissociated-type and LTPs after 24 months are not, and these LTP types could be considered nonablation-related LTPs. KEY POINTS • LTPs are not evenly distributed around the AZ. More than half of LTPs occur in the shortest AM quadrant. • Subgroup analysis showed that the occurrence of contacted-type LTPs (tumour margin has direct contact with the AZ) within 24 months after ablation indeed had a high proportion in the shortest AM quadrant, and they could be called ablation-related LTPs. • However, the dissociated-type LTPs (tumour margin adjacent to but not in contact with the AZ) or LTPs occurring beyond 24 months after ablation were evenly distributed around the AZ, and they could be called nonablation-related LTPs.
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Affiliation(s)
- Wen-Zhen Ding
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Sisi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Zhi-Yu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, China.
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22
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Zhang Q, Xia F, Mo A, He W, Chen J, Zhang W, Chen W. Guiding Value of Circulating Tumor Cells for Preoperative Transcatheter Arterial Embolization in Solitary Large Hepatocellular Carcinoma: A Single-Center Retrospective Clinical Study. Front Oncol 2022; 12:839597. [PMID: 35664772 PMCID: PMC9159764 DOI: 10.3389/fonc.2022.839597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 04/15/2022] [Indexed: 12/07/2022] Open
Abstract
Background Large hepatocellular carcinoma (LHCC) is highly malignant and prone to recurrence, leading to a poor long-term prognosis for patients. There is an urgent need for measures to intervene in postoperative recurrence. Preoperative Transcatheter Arterial Embolization (TACE) is an effective treatment. However, there is a lack of reliable preoperative indicators to guide the application of preoperative TACE. We, therefore, investigated whether the preoperative status of circulating tumor cells (CTCs) could be used to guide preoperative TACE for HCC treatment. Methods This study recruited 361 HCC patients and compared recurrence-free survival (RFS) and overall survival (OS) in patients treated with TACE prior to surgery and those not treated with TACE. Patients were divided into CTC-positive group and CTC-negative group according to CTC status, and the effect of preoperative TACE on RFS and OS was compared in each subgroup. Results In CTC-positive patients, preoperative TACE reduces early recurrence and improves long-term survival. However, HCC patients did not benefit from preoperative TACE for the overall population and CTC-negative patients. Conclusions Preoperative CTC testing is a reliable indicator of whether HCC patients received TACE preoperatively. CTC positivity was associated with early tumor recurrence, and preoperative TACE could reduce early recurrence and long-term prognosis in CTC-positive patients.
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Affiliation(s)
- Qiao Zhang
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Feng Xia
- Department of Hepatic Surgery Center, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Ali Mo
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiming He
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Jiazhen Chen
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiqiao Zhang
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
| | - Weiqiang Chen
- Zhongshan People's Hospital, Guangdong Medical University, Zhongshan, China
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23
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Chen Q, Xiao H, Gu Y, Weng Z, Wei L, Li B, Liao B, Li J, Lin J, Hei M, Peng S, Wang W, Kuang M, Chen S. Deep learning for evaluation of microvascular invasion in hepatocellular carcinoma from tumor areas of histology images. Hepatol Int 2022; 16:590-602. [PMID: 35349075 PMCID: PMC9174315 DOI: 10.1007/s12072-022-10323-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 02/16/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) is essential for the management of hepatocellular carcinoma (HCC). However, MVI is hard to evaluate in patients without sufficient peri-tumoral tissue samples, which account for over a half of HCC patients. METHODS We established an MVI deep-learning (MVI-DL) model with a weakly supervised multiple-instance learning framework, to evaluate MVI status using only tumor tissues from the histological whole slide images (WSIs). A total of 350 HCC patients (2917 WSIs) from the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU cohort) were divided into a training and test set. One hundred and twenty patients (504 WSIs) from Dongguan People's Hospital and Shunde Hospital of Southern Medical University (DG-SD cohort) formed an external test set. Unsupervised clustering and class activation mapping were applied to visualize the key histological features. RESULTS In the FAHSYSU and DG-SD test set, the MVI-DL model achieved an AUC of 0.904 (95% CI 0.888-0.920) and 0.871 (95% CI 0.837-0.905), respectively. Visualization results showed that macrotrabecular architecture with rich blood sinus, rich tumor stroma and high intratumor heterogeneity were identified as the key features associated with MVI ( +), whereas severe immune infiltration and highly differentiated tumor cells were associated with MVI (-). In the simulation of patients with only one WSI or biopsies only, the AUC of the MVI-DL model reached 0.875 (95% CI 0.855-0.895) and 0.879 (95% CI 0.853-0.906), respectively. CONCLUSION The effective, interpretable MVI-DL model has potential as an important tool with practical clinical applicability in evaluating MVI status from the tumor areas on the histological slides.
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Affiliation(s)
- Qiaofeng Chen
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Han Xiao
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China
| | - Yunquan Gu
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Zongpeng Weng
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Lihong Wei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bin Li
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Bing Liao
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jiali Li
- Department of Liver and Pancreatobiliary Surgery, Dongguan People's Hospital, Dongguan, Guangdong, China
| | - Jie Lin
- Department of Liver and Pancreatobiliary Surgery, Shunde Hospital of Southern Medical University, Shunde, Guangdong, China
| | - Mengying Hei
- Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Sui Peng
- Department of Gastroenterology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
- Clinical Trials Unit, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Ming Kuang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
- Department of Liver Surgery, Cancer Center, Institute of Precision Medicine, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
| | - Shuling Chen
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, the First Affiliated Hospital of Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, China.
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24
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Wang Z, Zhong Y, Zhang Z, Zhou K, Huang Z, Yu H, Liu L, Liu S, Yang H, Zhou J, Fan J, Wu L, Sun Y. Characteristics and Clinical Significance of T-Cell Receptor Repertoire in Hepatocellular Carcinoma. Front Immunol 2022; 13:847263. [PMID: 35371059 PMCID: PMC8965762 DOI: 10.3389/fimmu.2022.847263] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 02/09/2022] [Indexed: 11/13/2022] Open
Abstract
Several studies have demonstrated that the T-cell receptor (TCR) repertoire is associated with prognosis and immune therapy response in several types of cancer. However, the comprehensive features of TCR repertoire in tumor-infiltrating and circulating T cells, as well as its clinical significance of diagnosis in hepatocellular carcinoma (HCC) patients, are still unknown. In this study, we perform paired tumor/peritumoral tissues and peripheral blood samples from 58 patients with HCC and sequenced them with high-throughput TCR to comprehensively analyze the characteristics of TCR and the clinical significance of peripheral TCR sequence. By exploring the abundance and diversity of TCR repertoires, we observe that there was a significantly higher TCR diversity in peripheral blood than in tumoral and peritumoral tissues, while tumoral and peritumoral tissues showed similar TCR diversity. A substantial difference in the usage frequencies of several Vβ, Jβ genes, and TCRβ VJ pairings was found among three types of tissues. Moreover, we reveal that HCC patients have a unique profile of TCR repertoire in peripheral blood in contrast to healthy individuals. We further establish an HCC diagnostic model based on TCRβ VJ pairing usage in peripheral blood, which yields a best-fit area under the curve (AUC) of 0.9746 ± 0.0481 (sensitivity = 0.9675 ± 0.0603, specificity = 0.9998 ± 0.0007, average of 100 repeats) in the test set. Our study describes the characteristics of tissue infiltration and circulating T-cell bank in patients with HCC and shows the potential of using circulating TCR sequence as a biomarker for the non-invasive diagnosis of patients with HCC.
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Affiliation(s)
- Zifei Wang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
| | - Yu Zhong
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
| | - Zefan Zhang
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Kaiqian Zhou
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Zhihao Huang
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
| | - Hao Yu
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
| | - Longqi Liu
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
- Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Shiping Liu
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
- Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Huanming Yang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
| | - Jian Zhou
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Liang Wu
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
- Beijing Genomics Institute at Shenzhen, Shenzhen, China
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
- Shenzhen Key Laboratory of Single-Cell Omics, BGI-Shenzhen, Shenzhen, China
| | - Yunfan Sun
- Zhong-Hua Precision Medical Center, Zhongshan Hospital, Fudan University-BGI, Shanghai, China
- Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
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25
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Lin Y, Xu J, Hong J, Si Y, He Y, Zhang J. Prognostic Impact of Surgical Margin in Hepatectomy on Patients With Hepatocellular Carcinoma: A Meta-Analysis of Observational Studies. Front Surg 2022; 9:810479. [PMID: 35223977 PMCID: PMC8863846 DOI: 10.3389/fsurg.2022.810479] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 01/13/2022] [Indexed: 12/14/2022] Open
Abstract
Objective This study aims to comprehensively evaluate the prognostic impact of the surgical margin in hepatectomy on patients diagnosed with hepatocellular carcinoma (HCC). Methods A comprehensive and systematic search for eligible articles published in English before July 2021 was conducted across PubMed, Cochrane Library, Web of Science, and Embase electronic databases. The overall survival (OS) and disease-free survival (DFS) were the primary endpoints. Results In total, 37 observational studies with 12,295 cases were included in this meta-analysis. The results revealed that a wide surgical margin (≥1 cm) was associated with better OS (hazard ration (HR), 0.70; 95% confidence interval (CI), 0.63–0.77) and DFS (HR, 0.66; 95% CI, 0.61–0.71) compared to a narrow surgical margin (<1 cm). Subgroup analyses were conducted based on median follow-up time, gender, country, hepatitis B surface antigen (HBsAg) status, tumor number, and liver cirrhosis. The prognostic benefit of a wide surgical margin was consistent in most subgroups, however, analysis of studies from Western countries showed that margin width was not associated with prognosis. Conclusion In summary, a surgical margin wider than 1 cm prolongs the long-term prognosis of HCC patients compared to a surgical margin narrower than 1 cm.
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Affiliation(s)
- Yeting Lin
- Anesthesiology Department, Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| | - Jiaxuan Xu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuexiu Si
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yujing He
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jinhang Zhang
- Surgery Department, Fenghua Hospital of Traditional Chinese Medicine, Ningbo, China
- *Correspondence: Jinhang Zhang
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Espejo-Cruz ML, González-Rubio S, Zamora-Olaya J, Amado-Torres V, Alejandre R, Sánchez-Frías M, Ciria R, De la Mata M, Rodríguez-Perálvarez M, Ferrín G. Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal. Int J Mol Sci 2021; 22:13073. [PMID: 34884878 PMCID: PMC8657934 DOI: 10.3390/ijms222313073] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/27/2021] [Accepted: 11/30/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and a major cause of cancer-related death worldwide. There is no ideal biomarker allowing early diagnosis of HCC and tumor surveillance in patients receiving therapy. Liquid biopsy, and particularly circulating tumor cells (CTCs), have emerged as a useful tool for diagnosis and monitoring therapeutic responses in different tumors. In the present manuscript, we evaluate the current evidence supporting the quantitative and qualitative assessment of CTCs as potential biomarkers of HCC, as well as technical aspects related to isolation, identification, and classification of CTCs. Although the dynamic assessment of CTCs in patients with HCC may aid the decision-making process, there are still many uncertainties and technical caveats to be solved before this methodology has a true impact on clinical practice guidelines. More studies are needed to identify the optimal combination of surface markers, to increase the efficiency of ex-vivo expansion of CTCs, or even to target CTCs as a potential therapeutic strategy to prevent HCC recurrence after surgery or to hamper tumor progression and extrahepatic spreading.
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Affiliation(s)
- María Lola Espejo-Cruz
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
| | - Sandra González-Rubio
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
| | - Javier Zamora-Olaya
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Víctor Amado-Torres
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Rafael Alejandre
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
| | - Marina Sánchez-Frías
- Department of Pathology, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain;
| | - Rubén Ciria
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatobiliary Surgery and Liver Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
| | - Manuel De la Mata
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Manuel Rodríguez-Perálvarez
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Department of Hepatology and Liver Transplantation, Reina Sofía University Hospital, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
| | - Gustavo Ferrín
- Maimónides Institute of Biomedical Research (IMIBIC), University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; (M.L.E.-C.); (S.G.-R.); (J.Z.-O.); (V.A.-T.); (R.A.); (R.C.); (M.D.l.M.); (G.F.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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Lin D, Shen L, Luo M, Zhang K, Li J, Yang Q, Zhu F, Zhou D, Zheng S, Chen Y, Zhou J. Circulating tumor cells: biology and clinical significance. Signal Transduct Target Ther 2021; 6:404. [PMID: 34803167 PMCID: PMC8606574 DOI: 10.1038/s41392-021-00817-8] [Citation(s) in RCA: 474] [Impact Index Per Article: 118.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/06/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.
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Affiliation(s)
- Danfeng Lin
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lesang Shen
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Meng Luo
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kun Zhang
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinfan Li
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qi Yang
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Fangfang Zhu
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Zhou
- Department of Surgery, Traditional Chinese Medical Hospital of Zhuji, Shaoxing, China
| | - Shu Zheng
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yiding Chen
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Jiaojiao Zhou
- Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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Wan C, Zhou B. Research progress on circulating tumor cells of hepatocellular carcinoma. J Interv Med 2021; 4:181-183. [PMID: 35586377 PMCID: PMC8947999 DOI: 10.1016/j.jimed.2021.10.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 10/07/2021] [Accepted: 10/08/2021] [Indexed: 12/24/2022] Open
Abstract
Circulating tumor cells (CTCs) are the cells released from the primary tumor and found in the peripheral blood, which can colonize and develop at a distance through blood circulation. At present, the commonly used separation and detection methods of CTCs are mainly divided into physical methods, biological methods, and microfluidic chip-based methods. Monitoring CTC count and cell phenotype is of great significance for early screening and diagnosis of hepatocellular carcinoma (HCC). Moreover, the CTC count and cell phenotype are related to assessing the clinical efficacy of the treatment of HCC and the clinical stage of HCC patients. The CTCs count is also closely related to the overall survival, progression-free survival, and postoperative recurrence of patients with HCC.
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He RQ, Li JD, Du XF, Dang YW, Yang LJ, Huang ZG, Liu LM, Liao LF, Yang H, Chen G. LPCAT1 overexpression promotes the progression of hepatocellular carcinoma. Cancer Cell Int 2021; 21:442. [PMID: 34419067 PMCID: PMC8380368 DOI: 10.1186/s12935-021-02130-4] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2021] [Accepted: 07/30/2021] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) remains one of the most common malignant neoplasms. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role in the lipid remodelling and is correlated with various neoplasms. Nonetheless, the biological functions and molecular mechanisms of LPCAT1 underlying HCC remain obscure. METHODS In the present study, we investigated the role of LPCAT1 in the progression of HCC. In-house RT-qPCR, tissue microarrays, and immunohistochemistry were performed to detect the expression levels and the clinical value of LPCAT1 in HCC. External datasets were downloaded to confirm the results. Proliferation, migration, invasiveness, cell cycle, and apoptosis assays were conducted to reveal the biological effects LPCAT1 has on SMMC-7721 and Huh7 cells. HCC differentially expressed genes and LPCAT1 co-expressed genes were identified to explore the molecular mechanisms underlying HCC progression. RESULTS LPCAT1 showed upregulated expression in 3715 HCC specimens as opposed to 3105 non-tumour specimens. Additionally, LPCAT1 might be an independent prognostic factor for HCC. LPCAT1-knockout hampered cellular proliferation, migration, and metastasis in SMMC-7721 and Huh7 cells. More importantly, the cell cycle and chemical carcinogenesis were the two most enriched signalling pathways. CONCLUSIONS The present study demonstrated that increased LPCAT1 correlated with poor prognosis in HCC patients and fuelled HCC progression by promoting cellular growth, migration, and metastasis.
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Affiliation(s)
- Rong-Quan He
- Department of Oncology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Jian-Di Li
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Xiu-Fang Du
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Yi-Wu Dang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Lin-Jie Yang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Zhi-Guang Huang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Li-Min Liu
- Department of Toxicology, College of Pharmacy, Guangxi Medical University, No. 22 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Liu-Feng Liao
- Department of Pharmacy, Guangxi Medical University Cancer Hospital, No. 71 Hedi Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Hong Yang
- The Ultrasonics Division of Radiology Department, The First Affiliated Hospital of Guangxi Medical University, No. 6. Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China
| | - Gang Chen
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Rd, Guangxi Zhuang Autonomous Region, Nanning, 530021, People's Republic of China.
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