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      Preoperative diagnosis and prediction of hepatocellular carcinoma: Radiomics analysis based on multi-modal ultrasound images

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          Abstract

          Background

          This study aims to establish a radiomics analysis system for the diagnosis and clinical behaviour prediction of hepatocellular carcinoma (HCC) based on multi-parametric ultrasound imaging.

          Methods

          A total of 177 patients with focal liver lesions (FLLs) were included in the study. Every patient underwent multi-modal ultrasound examination, including B-mode ultrasound (BMUS), shear wave elastography (SWE), and shear wave viscosity (SWV) imaging. The radiomics analysis system was built on sparse representation theory (SRT) and support vector machine (SVM) for asymmetric data. Through the sparse regulation from the SRT, the proposed radiomics system can effectively avoid over-fitting issues that occur in regular radiomics analysis. The purpose of the proposed system includes differential diagnosis between benign and malignant FLLs, pathologic diagnosis of HCC, and clinical prognostic prediction. Three biomarkers, including programmed cell death protein 1 (PD-1), antigen Ki-67 (Ki-67) and microvascular invasion (MVI), were included and analysed. We calculated the accuracy (ACC), sensitivity (SENS), specificity (SPEC) and area under the receiver operating characteristic curve (AUC) to evaluate the performance of the radiomics models.

          Results

          A total of 2560 features were extracted from the multi-modal ultrasound images for each patient. Five radiomics models were built, and leave-one-out cross-validation (LOOCV) was used to evaluate the models. In LOOCV, the AUC was 0.94 for benign and malignant classification (95% confidence interval [CI]: 0.88 to 0.98), 0.97 for malignant subtyping (95% CI: 0.93 to 0.99), 0.97 for PD-1 prediction (95% CI: 0.89 to 0.98), 0.94 for Ki-67 prediction (95% CI: 0.87 to 0.97), and 0.98 for MVI prediction (95% CI: 0.93 to 0.99). The performance of each model improved when the viscosity modality was included.

          Conclusions

          Radiomics analysis based on multi-modal ultrasound images could aid in comprehensive liver tumor evaluations, including diagnosis, differential diagnosis, and clinical prognosis.

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          Most cited references31

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          $rm K$-SVD: An Algorithm for Designing Overcomplete Dictionaries for Sparse Representation

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            EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version)

            We present here the first update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography, focused on the assessment of diffuse liver disease. The first part (long version) of these Guidelines and Recommendations deals with the basic principles of elastography and provides an update of how the technology has changed. The practical advantages and disadvantages associated with each of the techniques are described, and guidance is provided regarding optimization of scanning technique, image display, image interpretation, reporting of data and some of the known image artefacts. The second part provides clinical information about the practical use of elastography equipment and the interpretation of results in the assessment of diffuse liver disease and analyzes the main findings based on published studies, stressing the evidence from meta-analyses. The role of elastography in different etiologies of liver disease and in several clinical scenarios is also discussed. All of the recommendations are judged with regard to their evidence-based strength according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. This updated document is intended to act as a reference and to provide a practical guide for both beginners and advanced clinical users.
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              PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients.

              Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of cytotoxic CD8(+) T lymphocytes, the main effector cells in hepatocellular carcinoma (HCC) patients, are not well defined. In this study, we characterized circulating and intratumor PD-1/PD-L1 expression and analyzed their association with disease progression in a cohort of hepatitis B virus-infected patients, including 56 with HCC, 20 with liver cirrhosis (LC) and 20 healthy controls (HC). The frequency of circulating PD-1(+) CD8(+) T cells increased with disease progression from LC to HCC patients versus HC. Furthermore, tumor-infiltrating effector CD8(+) T cells showed a drastic increase in PD-1 expression. These increases in circulating and intratumor PD-1(+) CD8(+) T cells could predict poorer disease progression and postoperative recurrence. Immunohistochemical staining showed that PD-L1 expressing hepatoma cells and apoptotic infiltrating CD8(+) T cells were both enriched in tumor sections. In vitro, CD8(+) T cells induced PD-L1 expression on hepatoma cells in an IFN-γ-dependent manner, which in turn promoted CD8(+) T cells apoptosis, and blocking PD-L1 reversed this effect. Therefore, this study extends our knowledge of the role of the PD-1/PD-L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients. Copyright © 2010 UICC.
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                Author and article information

                Contributors
                17210720167@fudan.edu.cn
                dong.yi@zs-hospital.sh.cn
                16110720102@fudan.edu.cn
                17211210030@fudan.edu.cn
                yang.daohui@zs-hospital.sh.cn
                jhyu@fudan.edu.cn
                puguang61@126.com
                Journal
                BMC Cancer
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                12 November 2018
                12 November 2018
                2018
                : 18
                : 1089
                Affiliations
                [1 ]ISNI 0000 0001 0125 2443, GRID grid.8547.e, Department of Electronic Engineering, , Fudan University, ; No. 220, Handan Road, Yangpu District, Shanghai, 200433 China
                [2 ]ISNI 0000 0004 1755 3939, GRID grid.413087.9, Department of Ultrasound, , Zhongshan Hospital, Fudan University, ; 180 Fenglin Road, Shanghai, 200032 China
                Article
                5003
                10.1186/s12885-018-5003-4
                6233500
                30419849
                94ef11f2-7b9a-41a5-a485-b6ee8e038c77
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 August 2018
                : 28 October 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 61471125
                Award ID: 81571676
                Award ID: 81501471
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Oncology & Radiotherapy
                shear wave dispersion,viscoelasticity,radiomics approach,ultrasound,hepatocellular carcinoma

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