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Rafati I, Destrempes F, Yazdani L, Barat M, Karam E, Fohlen A, Nguyen BN, Castel H, Tang A, Cloutier G. Enhancing Liver Nodule Visibility and Diagnostic Classification Using Ultrasound Local Attenuation Coefficient Slope Imaging. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:807-814. [PMID: 39890529 DOI: 10.1016/j.ultrasmedbio.2025.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 01/03/2025] [Accepted: 01/12/2025] [Indexed: 02/03/2025]
Abstract
OBJECTIVE B-mode ultrasound (US) presents challenges in accurately detecting and distinguishing between benign and malignant liver nodules. This study utilized quantitative US local attenuation coefficient slope (LACS) imaging to address these limitations. MATERIALS AND METHODS This is a prospective, cross-sectional study in adult patients with definable solid liver nodules at US conducted from March 2021 to December 2023. The composite reference standard included histopathology when available or magnetic resonance imaging. LACS images were obtained using a phantom-free method. Nodule visibility was assessed by computing the contrast-to-noise ratio (CNR). Classification accuracy for differentiating benign and malignant lesions was assessed with the area under the receiver operating characteristic curve (AUC), along with sensitivity and specificity. RESULTS The study enrolled 97 patients (age: 62 y ± 13 [standard deviation]), with 57.0% malignant and 43.0% benign observations (size: 26.3 ± 18.9 mm). LACS images demonstrated higher CNR (12.3 dB) compared to B-mode (p < 0.0001). The AUC for differentiating nodules and liver parenchyma was 0.85 (95% confidence interval [CI]: 0.79-0.90), with higher values for malignant (0.93, CI: 0.88-0.97) than benign nodules (0.76, CI: 0.66-0.87). A LACS threshold of 0.94 dB/cm/MHz provided a sensitivity of 0.83 (CI: 0.74-0.89) and a specificity of 0.82 (CI: 0.73-0.88). LACS mean values were higher (p < 0.0001) in malignant (1.28 ± 0.27 dB/cm/MHz) than benign nodules (0.98 ± 0.19 dB/cm/MHz). CONCLUSION LACS imaging improves nodule visibility and provides better differentiation between benign and malignant liver nodules, showing promise as a diagnostic tool.
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Affiliation(s)
- Iman Rafati
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montréal, Québec, Canada; Institute of Biomedical Engineering, University of Montreal, Montréal, Québec, Canada
| | - François Destrempes
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montréal, Québec, Canada
| | - Ladan Yazdani
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montréal, Québec, Canada; Institute of Biomedical Engineering, University of Montreal, Montréal, Québec, Canada
| | - Maxime Barat
- Department of Radiology, University of Montreal Hospital, Montréal, Québec, Canada
| | - Elige Karam
- Department of Radiology, University of Montreal Hospital, Montréal, Québec, Canada
| | - Audrey Fohlen
- Department of Radiology, University of Montreal Hospital, Montréal, Québec, Canada
| | - Bich N Nguyen
- Department of Pathology, University of Montreal Hospital, Montréal, Québec, Canada
| | - Hélène Castel
- Departments of Hepatology and Liver Transplantation, University of Montreal Hospital, Montréal, Québec, Canada
| | - An Tang
- Department of Radiology, University of Montreal Hospital, Montréal, Québec, Canada; Department of Radiology, Radiation Oncology and Nuclear Medicine, University of Montreal, Montréal, Québec, Canada; Laboratory of Clinical Image Processing, University of Montreal Hospital Research Center, Montréal, Québec, Canada.
| | - Guy Cloutier
- Laboratory of Biorheology and Medical Ultrasonics, University of Montreal Hospital Research Center, Montréal, Québec, Canada; Institute of Biomedical Engineering, University of Montreal, Montréal, Québec, Canada; Department of Radiology, Radiation Oncology and Nuclear Medicine, University of Montreal, Montréal, Québec, Canada.
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Chen J, Zhang B, Yan Y, Wei FQ, Lin ZY, Chen J. MR-Guided Microwave Ablation for Patients with Cirrhosis Complicated by Small Hepatocellular Carcinoma. J Vasc Interv Radiol 2025; 36:805-812.e1. [PMID: 39848318 DOI: 10.1016/j.jvir.2025.01.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 12/25/2024] [Accepted: 01/14/2025] [Indexed: 01/25/2025] Open
Abstract
PURPOSE To assess the technical effectiveness and therapeutic outcomes of percutaneous magnetic resonance (MR)-guided microwave ablation (MWA) in the treatment of patients with cirrhosis complicated by small hepatocellular carcinoma (HCC). MATERIALS AND METHODS A single-center, retrospective analysis of consecutive cases involving 1.5T MR-guided MWA for HCC was performed. Fifty-three patients with cirrhosis, harboring 74 HCC lesions with mean diameter of 13.0 mm (SD ± 6.0; range, 6.0-29.0 mm; median, 10.0 mm), were included in this study. Follow-up MR imaging was performed postprocedurally to assess technical effectiveness, whereas local progression-free survival (LPFS) and overall survival (OS) rates were calculated over the study period. RESULTS MR-guided MWA was performed with technical success in all cases with no severe adverse events occurring during the single-session treatment. The mean follow-up duration was 46.1 months (SD ± 17.9; median, 52 months). Local tumor progression was observed in 1 perivascular lesion, accounting for 1.9% of the cases. The mean recurrence-free survival was 31.1 months (SD ± 22.2), with a median of 24.5 months. LPFS rates at 1, 3, and 5 years were 98.1%. The OS rates at 1, 3, and 5 years were 96.2%, 84.9%, and 71.6%, respectively. CONCLUSIONS Percutaneous MR-guided MWA for small HCC in patients with cirrhosis demonstrated high technical success, accurate evaluation of ablation margins, and minimal local tumor progression after a single treatment session, resulting in favorable therapeutic outcomes.
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Affiliation(s)
- Jie Chen
- Department of Interventional Radiology, Sanming Second Hospital, Sanming, China
| | - Bing Zhang
- Department of Interventional Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Yuan Yan
- Department of Interventional Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Fu-Qun Wei
- Department of Interventional Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zheng-Yu Lin
- Department of Interventional Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jin Chen
- Department of Interventional Radiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Department of Interventional Radiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
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Du Z, Fan F, Ma J, Liu J, Yan X, Chen X, Dong Y, Wu J, Ding W, Zhao Q, Wang Y, Zhang G, Yu J, Liang P. Development and validation of an ultrasound-based interpretable machine learning model for the classification of ≤3 cm hepatocellular carcinoma: a multicentre retrospective diagnostic study. EClinicalMedicine 2025; 81:103098. [PMID: 40034568 PMCID: PMC11872562 DOI: 10.1016/j.eclinm.2025.103098] [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: 09/28/2024] [Revised: 01/17/2025] [Accepted: 01/20/2025] [Indexed: 03/05/2025] Open
Abstract
Background Our study aimed to develop a machine learning (ML) model utilizing grayscale ultrasound (US) to distinguish ≤3 cm small hepatocellular carcinoma (sHCC) from non-HCC lesions. Methods A total of 1052 patients with 1058 liver lesions ≤3 cm from 55 hospitals were collected between May 2017 and June 2021, and 756 liver lesions were randomly allocated into train and internal validation cohorts at a 8:2 ratio for the development and evaluation of ML models based on multilayer perceptron (MLP) and extreme gradient boosting (XGBoost) methods (ModelU utilizing US imaging features; ModelUR adding US radiomics features; ModelURC employing clinical features further). The diagnostic performance of three models was assessed in external validation cohort (312 liver lesions from 14 hospitals). The diagnostic efficacy of the optimal model was compared to that of radiologists in external validation cohort. The SHapley Additive exPlanations (SHAP) method was employed to interpret the optimal ML model by ranking feature importance. The study was registered at ClinicalTrials.gov (NCT03871140). Findings ModelURC based XGBoost showed the best performance (AUC = 0.934; 95% CI: 0.894-0.974) in the internal validation cohort. In the external validation cohort, ModelURC also achieved optimal AUC (AUC = 0.899, 95% CI: 0.861-0.931). Upon conducting a subgroup analysis, no statistically significant differences were observed in the diagnostic performance of the ModelURC neither between tumor sizes of ≤2.0 cm and 2.1-3.0 cm nor across different HCC risk stratifications. ModelURC exhibited superior ability compared to all radiologists and ModelURC assistance significantly improved the diagnostic AUC for all radiologists (all P < 0.0001). Interpretation A diagnostic model for sHCC was developed and validated using ML and grayscale US from large cohorts. This model significantly improved the diagnostic performance of grayscale US for sHCC compared with experts. Funding This work was supported by National Key Research and Development Program of China (2022YFC2405500), Major Research Program of the National Natural Science Foundation of China (92159305), National Science Fund for Distinguished Young Scholars (82325027), Key project of National Natural Science Foundation of China (82030047), Military Fund for Geriatric Diseases (20BJZ42), National Natural Science Foundation of China Special Program (82441011). National Natural Science Foundation of China (82402280), National Natural Science Foundation of China (32171363), Key Research and Development Program for Social Development of Yunnan Science and Technology Department (202403AC100014).
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Affiliation(s)
- Zhicheng Du
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer & Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen, China
| | - Fangying Fan
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jun Ma
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jing Liu
- Department of Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xing Yan
- Department of Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xuexue Chen
- Department of Ultrasound, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, China
| | - Yangfang Dong
- Department of Ultrasound, Fuzhou First General Hospital, Fuzhou, China
| | - Jiapeng Wu
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Wenzhen Ding
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Qinxian Zhao
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yuling Wang
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Guojun Zhang
- Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer & Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- Cancer Research Center of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
- The Breast Center and the Cancer Institute, Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Peking University Cancer Hospital Yunnan, Kunming, China
| | - Jie Yu
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
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Shinde S, Bigogno CM, Simmons A, Kathuria N, Ghose A, Apte V, Lapitan P, Makker S, Caglayan A, Boussios S. Precision oncology through next generation sequencing in hepatocellular carcinoma. Heliyon 2025; 11:e42054. [PMID: 39927143 PMCID: PMC11804570 DOI: 10.1016/j.heliyon.2025.e42054] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 01/08/2025] [Accepted: 01/15/2025] [Indexed: 02/11/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer that originates from underlying inflammation, often associated with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infections. Despite the availability of treatments, there are high rates of tumour relapse due to the development of drug resistance in infected cells. Next-Generation Sequencing (NGS) plays a crucial role in overcoming this issue by sequencing both viral and host genomes to identify mutations and genetic heterogeneity. The knowledge gained from sequencing is then utilised to develop countermeasures against these mutants through different combination therapies. Advances in NGS have led to sequencing with higher accuracy and throughput, thereby enabling personalized and effective treatments. The purpose of this article is to highlight how NGS has contributed to precision medicine in HCC and the possible integration of artificial intelligence (AI) to bolster the advancement.
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Affiliation(s)
- Sayali Shinde
- Barts Cancer Institute, Queen Mary University of London, Cancer Research UK Barts Centre, London, UK
| | - Carola Maria Bigogno
- Department of Medical Oncology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, UK
- British Oncology Network for Undergraduate Societies (BONUS), UK
| | - Ana Simmons
- Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- QIAGEN Manchester, Manchester, UK
| | - Nikita Kathuria
- Faculty of Life Sciences and Medicine, King's College London, London, UK
| | - Aruni Ghose
- Department of Medical Oncology, St. Bartholomew's Hospital, Barts Health NHS Trust, London, UK
- Department of Medical Oncology, Medway NHS Foundation Trust, Kent, UK
- Department of Medical Oncology, Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust, London, UK
| | - Vedika Apte
- University College London Medical School, London, UK
- University College London Oncology Society, London, UK
| | - Patricia Lapitan
- School of Medical Sciences, The University of Manchester, Manchester, UK
- Division of Genetics and Epidemiology, The Institute of Cancer Research, Surrey, UK
- University College London Cancer Institute, London, UK
| | - Shania Makker
- University College London Cancer Institute, London, UK
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Barts and the London Oncology Society, London, UK
| | - Aydin Caglayan
- Department of Medical Oncology, Medway NHS Foundation Trust, Kent, UK
| | - Stergios Boussios
- Department of Medical Oncology, Medway NHS Foundation Trust, Kent, UK
- Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, King's College London, Strand, London, UK
- Kent and Medway Medical School, University of Kent, Canterbury, UK
- Faculty of Medicine, Health, and Social Care, Canterbury Christ Church University, Canterbury, UK
- AELIA Organization, 9th Km Thessaloniki–Thermi, 57001 Thessaloniki, Greece
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Tonon F, Grassi C, Tierno D, Biasin A, Grassi M, Grassi G, Dapas B. Non-Coding RNAs as Potential Diagnostic/Prognostic Markers for Hepatocellular Carcinoma. Int J Mol Sci 2024; 25:12235. [PMID: 39596302 PMCID: PMC11594412 DOI: 10.3390/ijms252212235] [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: 10/05/2024] [Revised: 11/04/2024] [Accepted: 11/12/2024] [Indexed: 11/28/2024] Open
Abstract
The increasing incidence of hepatocellular carcinoma (HCC), together with the poor effectiveness of the available treatments, make early diagnosis and effective screening of utmost relevance. Liquid biopsy represents a potential novel approach to early HCC detection and monitoring. The identification of blood markers has many desirable features, including the absence of any significant risk for the patients, the possibility of being used as a screening tool, and the ability to perform multiple tests, thus allowing for the real-time monitoring of HCC evolution. Unfortunately, the available blood markers for HCC have several limitations, mostly related to specificity and sensitivity. In this context, employing non-coding RNAs (ncRNAs) may represent an interesting and novel diagnostic approach. ncRNAs, which include, among others, micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate human gene expression via interactions with their target mRNA. Notably, their expression can be altered in HCC, thus reflecting disease status. In this review, we discuss some notable works that describe the use of miRNAs, lncRNAs, and circRNAs as HCC biomarkers. Despite some open aspects related to ncRNA use, the presented works strongly support the potential effectiveness of these molecules as diagnostic/prognostic markers for HCC.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/blood
- Liver Neoplasms/genetics
- Liver Neoplasms/diagnosis
- Liver Neoplasms/blood
- Biomarkers, Tumor/genetics
- Prognosis
- RNA, Untranslated/genetics
- RNA, Untranslated/blood
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/blood
- RNA, Circular/genetics
- Gene Expression Regulation, Neoplastic
- MicroRNAs/genetics
- MicroRNAs/blood
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Affiliation(s)
- Federica Tonon
- Clinical Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy; (F.T.); (D.T.)
| | - Chiara Grassi
- Degree Course in Medicine, University of Trieste, 34127 Trieste, Italy;
| | - Domenico Tierno
- Clinical Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy; (F.T.); (D.T.)
| | - Alice Biasin
- Department of Engineering and Architecture, University of Trieste, Via Valerio 6, 34127 Trieste, Italy; (A.B.); (M.G.)
| | - Mario Grassi
- Department of Engineering and Architecture, University of Trieste, Via Valerio 6, 34127 Trieste, Italy; (A.B.); (M.G.)
| | - Gabriele Grassi
- Clinical Department of Medical, Surgical and Health Sciences, Cattinara University Hospital, University of Trieste, Strada di Fiume 447, 34149 Trieste, Italy; (F.T.); (D.T.)
| | - Barbara Dapas
- Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy;
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Shanbhogue K, Chandarana H. Imaging of Cirrhosis and Hepatocellular Carcinoma: Current Evidence. Radiol Clin North Am 2024; 62:1013-1023. [PMID: 39393847 DOI: 10.1016/j.rcl.2024.04.004] [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: 10/13/2024]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Early detection of HCC is a key factor in enabling curative therapies and improving overall survival. Worldwide, several guidelines are available for surveillance of at-risk populations and diagnosis of HCC. This article provides a current comprehensive update on screening and diagnosis of HCC.
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Affiliation(s)
- Krishna Shanbhogue
- Department of Radiology, NYU Langone Health, 660 1st Avenue, 3rd Floor, New York, NY 10016, USA.
| | - Hersh Chandarana
- Department of Radiology, NYU Langone Health, 660 1st Avenue, 3rd Floor, New York, NY 10016, USA
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Zhou W, Li X, Zabihollahy F, Lu DS, Wu HH. Deep learning-based automatic pipeline for 3D needle localization on intra-procedural 3D MRI. Int J Comput Assist Radiol Surg 2024; 19:2227-2237. [PMID: 38520646 PMCID: PMC11541278 DOI: 10.1007/s11548-024-03077-3] [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: 10/19/2023] [Accepted: 02/09/2024] [Indexed: 03/25/2024]
Abstract
PURPOSE Accurate and rapid needle localization on 3D magnetic resonance imaging (MRI) is critical for MRI-guided percutaneous interventions. The current workflow requires manual needle localization on 3D MRI, which is time-consuming and cumbersome. Automatic methods using 2D deep learning networks for needle segmentation require manual image plane localization, while 3D networks are challenged by the need for sufficient training datasets. This work aimed to develop an automatic deep learning-based pipeline for accurate and rapid 3D needle localization on in vivo intra-procedural 3D MRI using a limited training dataset. METHODS The proposed automatic pipeline adopted Shifted Window (Swin) Transformers and employed a coarse-to-fine segmentation strategy: (1) initial 3D needle feature segmentation with 3D Swin UNEt TRansfomer (UNETR); (2) generation of a 2D reformatted image containing the needle feature; (3) fine 2D needle feature segmentation with 2D Swin Transformer and calculation of 3D needle tip position and axis orientation. Pre-training and data augmentation were performed to improve network training. The pipeline was evaluated via cross-validation with 49 in vivo intra-procedural 3D MR images from preclinical pig experiments. The needle tip and axis localization errors were compared with human intra-reader variation using the Wilcoxon signed rank test, with p < 0.05 considered significant. RESULTS The average end-to-end computational time for the pipeline was 6 s per 3D volume. The median Dice scores of the 3D Swin UNETR and 2D Swin Transformer in the pipeline were 0.80 and 0.93, respectively. The median 3D needle tip and axis localization errors were 1.48 mm (1.09 pixels) and 0.98°, respectively. Needle tip localization errors were significantly smaller than human intra-reader variation (median 1.70 mm; p < 0.01). CONCLUSION The proposed automatic pipeline achieved rapid pixel-level 3D needle localization on intra-procedural 3D MRI without requiring a large 3D training dataset and has the potential to assist MRI-guided percutaneous interventions.
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Affiliation(s)
- Wenqi Zhou
- Department of Radiological Sciences, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B119, Los Angeles, CA, 90095, USA
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA
| | - Xinzhou Li
- Department of Radiological Sciences, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B119, Los Angeles, CA, 90095, USA
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA
| | - Fatemeh Zabihollahy
- Department of Radiological Sciences, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B119, Los Angeles, CA, 90095, USA
- Joint Department of Medical Imaging, Sinai Health System and University of Toronto, Toronto, Canada
| | - David S Lu
- Department of Radiological Sciences, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B119, Los Angeles, CA, 90095, USA
| | - Holden H Wu
- Department of Radiological Sciences, University of California Los Angeles, 300 UCLA Medical Plaza, Suite B119, Los Angeles, CA, 90095, USA.
- Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA.
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Somnay K, Wadgaonkar P, Sridhar N, Roshni P, Rao N, Wadgaonkar R. Liver Fibrosis Leading to Cirrhosis: Basic Mechanisms and Clinical Perspectives. Biomedicines 2024; 12:2229. [PMID: 39457542 PMCID: PMC11505165 DOI: 10.3390/biomedicines12102229] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/20/2024] [Accepted: 09/23/2024] [Indexed: 10/28/2024] Open
Abstract
Liver fibrosis is the pathological deposition of extracellular matrix rich in fibrillar collagen within the hepatocytes in response to chronic liver injury due to various causes. As the condition advances, it can progress to cirrhosis, the late stages of which are irreversible. Multiple pathophysiological mechanisms and cell types are responsible for the progression of liver fibrosis and cirrhosis. Hepatic stellate cells and myofibroblast activation represent a key event in fibrosis. Capillarization of liver sinusoidal endothelial cells further contributes to extracellular matrix deposition and an increase in portal pressure. Macrophages and neutrophils produce inflammatory cytokines and participate in activating hepatic stellate cells. Although initially believed to be irreversible, early stages of fibrosis are now found to be reversible. Furthermore, advances in noninvasive imaging and serum studies have changed and improved how cirrhosis can be evaluated and monitored. Although there are currently no specific approved therapies to reverse liver fibrosis, management of underlying diseases has been found to halt the progression, and to an extent, even reverse liver fibrosis, preventing further liver injury and cirrhosis-related complications.
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Affiliation(s)
- Kaumudi Somnay
- New York Presbyterian Hospital, Queens, New York, NY 11355, USA
- New York Digestive Disease Center, Queens, New York, NY 11355, USA
| | | | | | - Prarath Roshni
- New York Digestive Disease Center, Queens, New York, NY 11355, USA
| | - Nachiketh Rao
- New York Digestive Disease Center, Queens, New York, NY 11355, USA
| | - Raj Wadgaonkar
- SUNY Downstate Medical Center, Brooklyn, New York, NY 11203, USA;
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Yalcin S, Lacin S, Kaseb AO, Peynircioğlu B, Cantasdemir M, Çil BE, Hurmuz P, Doğrul AB, Bozkurt MF, Abali H, Akhan O, Şimşek H, Sahin B, Aykan FN, Yücel İ, Tellioğlu G, Selçukbiricik F, Philip PA. A Post-International Gastrointestinal Cancers' Conference (IGICC) Position Statements. J Hepatocell Carcinoma 2024; 11:953-974. [PMID: 38832120 PMCID: PMC11144653 DOI: 10.2147/jhc.s449540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/14/2024] [Indexed: 06/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.
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Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Sahin Lacin
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Ahmed Omar Kaseb
- Department of Gastrointestinal Medical Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA
| | - Bora Peynircioğlu
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | | | - Barbaros Erhan Çil
- Department of Radiology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Pervin Hurmuz
- Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Ahmet Bülent Doğrul
- Department of General Surgery, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Murat Fani Bozkurt
- Department of Nuclear Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Hüseyin Abali
- Department of Medical Oncology, Bahrain Oncology Center, Muharraq, Bahrain
| | - Okan Akhan
- Department of Radiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Halis Şimşek
- Department of Gastroenterology, Hacettepe University Faculty of Medicine, Ankara, Turkey
| | - Berksoy Sahin
- Department of Medical Oncology, Cukurova University Faculty of Medicine, Adana, Türkiye
| | - Faruk N Aykan
- Department of Medical Oncology, Istinye University Faculty of Medicine Bahçeşehir Liv Hospital, İstanbul, Turkey
| | - İdris Yücel
- Medicana International Hospital Samsun, Department of Medical Oncology, Samsun, Turkey
| | - Gürkan Tellioğlu
- Department of General Surgery, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Fatih Selçukbiricik
- Department of Medical Oncology, Koç University Faculty of Medicine, İstanbul, Turkey
| | - Philip A Philip
- Department of Medicine, Division of Hematology-Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA
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11
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Lai YW, Chung CH. Epidemiology of Hepatocellular Carcinoma in Taiwan. Clin Pract 2024; 14:570-578. [PMID: 38666802 PMCID: PMC11048999 DOI: 10.3390/clinpract14020044] [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: 01/22/2024] [Revised: 03/14/2024] [Accepted: 03/19/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research. METHODS From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied. RESULTS The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021. CONCLUSIONS The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.
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Affiliation(s)
- Yu-Wei Lai
- General Education Center, University of Taipei, Taipei 104, Taiwan;
- Division of Urology, Taipei City Hospital Renai Branch, Taipei 106, Taiwan
| | - Ching-Hu Chung
- Department of Medicine, Mackay Medical College, New Taipei City 252, Taiwan
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12
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McGillen K, Aljabban N, Wu R, Shin B, Schreibman I, Luke F, Birkholz J. Addition of contrast in ultrasound screening for hepatocellular carcinoma. RESEARCH IN DIAGNOSTIC AND INTERVENTIONAL IMAGING 2024; 9:100039. [PMID: 39076583 PMCID: PMC11265193 DOI: 10.1016/j.redii.2023.100039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 12/26/2023] [Indexed: 07/31/2024]
Abstract
Objective Screening ultrasound for hepatocellular carcinoma (HCC) identifies lesions which require further characterization by a contrast-enhanced exam to non-invasively diagnose HCC. While ultrasound is recommended in screening, some HCC can be occult on grayscale imaging. The purpose of this study was to determine if the addition of ultrasound contrast (sulfahexafluoride) to screening ultrasound for HCC can identify more HCC lesions than grayscale sonographic imaging alone. Methods All HCC screening ultrasounds that also had contrast were evaluated in this retrospective study. Patients with a focal lesion seen only after administration of contrast (OAC) were noted, as well as any follow-up imaging or pathology results. Additional variables collected included patient demographics, cirrhosis type, and laboratory values. Results 230 unique patients were included, of which 160 had imaging or pathology follow-up. 18 of these patients had an OAC lesion, of which 17 had follow-up. Among these OACs, there was one LIRADS M lesion (1/18, 5.6 %) and one bland portal vein thrombus identified, which were both confirmed on follow-up imaging. All LIRADS 4 OAC lesions were downgraded. No additional HCC were identified on follow-up imaging or pathology of these patients. Conclusion Addition of contrast to screening ultrasound did identify additional lesions, portal vein thrombus, and high grade malignancy. However, as the incidence of OAC lesions was low (7.8 %, 18/230) and most of the lesions were not malignant, addition of post contrast sweeps through the liver is of low value in the low to medium at-risk cirrhotic population in identifying occult HCC.
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Affiliation(s)
- Kathryn McGillen
- Penn State Health Milton S Hershey Medical Center, Department of Radiology, 500 University Drive, Hershey, PA 17033, USA
| | - Nabeal Aljabban
- Penn State Health Milton S Hershey Medical Center, Department of Medicine, 500 University Drive, Hershey, PA 17033, USA
| | - Robert Wu
- Rutgers Robert Wood Johnson Medical School, Department of Radiology, MEB #404, 1 Robert Wood Johnson Place, New Brunswick, NJ 08901, USA
| | - Benjamin Shin
- George Washington University Hospital, Department of Radiology, 900 23rd St NW 2nd Floor, Washington DC 20037, USA
| | - Ian Schreibman
- Penn State Health Milton S Hershey Medical Center, Department of Medicine, 500 University Drive, Hershey, PA 17033, USA
| | - Franklin Luke
- Penn State Health Milton S Hershey Medical Center, Department of Radiology, 500 University Drive, Hershey, PA 17033, USA
| | - James Birkholz
- Penn State Health Milton S Hershey Medical Center, Department of Radiology, 500 University Drive, Hershey, PA 17033, USA
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Wang Y, Sun Y, Zeng X, Zhuang R, Huang J, Zhang X, Guo Z, Li Y. 68Ga-Labeled TMTP1 Modified with d-Amino Acid for Positron Emission Tomography Diagnosis of Highly Metastatic Hepatocellular Carcinoma. J Med Chem 2024; 67:2165-2175. [PMID: 38270637 DOI: 10.1021/acs.jmedchem.3c02090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2024]
Abstract
TMTP1 (NVVRQ) has been proven to selectively target various highly metastatic tumor cells. Nonetheless, existing TMTP1 probes encounter challenges such as rapid blood clearance, limited tumor uptake, and inadequate suitability for therapeutic interventions. To overcome these constraints, we designed and synthesized eight peptide probes, employing innovative chemical modification strategies involving d-amino acid modification and retro-inverso isomerization. Notably, [68Ga]TV2 exhibited particularly impressive performance, displaying an 88.88, 76.90, and 90.32% improvement in uptake at 15, 30, and 60 min, respectively, while maintaining a high target-to-nontarget ratio. Further research has demonstrated that [68Ga]TV2 also exhibits remarkable diagnostic potential for detecting in situ microtumors in the liver. The results suggest that through the implementation of innovative chemical modification strategies, we successfully developed a peptide precursor, NOTA-G-NVvRQ, with specific affinity for highly metastatic tumors, enhanced in vivo pharmacokinetic profile, and heightened stability in vivo, rendering it well suited for prospective investigations in combination therapy studies.
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Affiliation(s)
- Yanjie Wang
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Yuan Sun
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xueyuan Zeng
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Rongqiang Zhuang
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Jinxiong Huang
- Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
| | - Xianzhong Zhang
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
- Theranostics and Translational Research Center, Institute of Clinical Medicine, Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
| | - Zhide Guo
- State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Yesen Li
- Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361003, China
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14
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Decharatanachart P, Pan-ngum W, Peeraphatdit T, Tanpowpong N, Tangkijvanich P, Treeprasertsuk S, Rerknimitr R, Chaiteerakij R. Cost-Utility Analysis of Non-Contrast Abbreviated Magnetic Resonance Imaging for Hepatocellular Carcinoma Surveillance in Cirrhosis. Gut Liver 2024; 18:135-146. [PMID: 37560799 PMCID: PMC10791494 DOI: 10.5009/gnl230089] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/01/2023] [Accepted: 05/23/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND/AIMS Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. METHODS Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. RESULTS aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. CONCLUSIONS Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.
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Affiliation(s)
| | - Wirichada Pan-ngum
- Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Thoetchai Peeraphatdit
- Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Natthaporn Tanpowpong
- Department of Radiology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Pisit Tangkijvanich
- Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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15
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Yang Q, Zheng R, Zhou J, Tang L, Zhang R, Jiang T, Jing X, Liao J, Cheng W, Zhao C, Liu C, Dietrich CF, Cui X, Cai W, Wu J, Yu F, Cheng Z, Liu F, Han Z, Yu X, Yu J, Liang P. On-Site Diagnostic Ability of CEUS/CT/MRI for Hepatocellular Carcinoma (2019-2022): A Multicenter Study. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:2825-2838. [PMID: 37713625 DOI: 10.1002/jum.16321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 08/05/2023] [Accepted: 08/07/2023] [Indexed: 09/17/2023]
Abstract
OBJECTIVES To compare the on-site diagnostic performance of contrast-enhanced ultrasound (CEUS), computed tomography (CECT), and magnetic resonance imaging (CEMRI) for hepatocellular carcinoma (HCC) across diverse practice settings. METHODS Between May 2019 and April 2022, a total of 2085 patients with 2320 pathologically confirmed focal liver lesions (FLLs) were enrolled. Imaging reports were compared with results from pathology analysis. Diagnostic performance was analyzed in defined size, high-risk factors for HCC, and hospital volume categories. RESULTS Three images achieved similar diagnostic performance in classifying HCC from 16 types of FLLs, including HCC ≤2.0 cm. For HCC diagnosis at low-volume hospitals and HCC with high-risk factors, the accuracy and specificity of CEUS were comparable to CECT and CEMRI, while the sensitivity of CEUS (77.4 and 89.5%, respectively) was inferior to CEMRI (87.0 and 92.8%, respectively). The diagnostic accuracy of CEUS + CEMRI and CEUS + CECT increased by 7.8 and 6.2% for HCC ≤2.0 cm, 8.0 and 5.0% for HCC with high-risk factors, and 7.4 and 5.5% for HCC at low-volume hospitals, respectively, compared with CEMRI/CECT alone. CONCLUSIONS Compared with CECT and CEMRI, CEUS provides adequate diagnostic performance in clinical first-line applications at high-volume hospitals. Moreover, a higher diagnostic performance for HCC is achieved by combining CEUS with CECT/CEMRI compared with any single imaging technique.
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Affiliation(s)
- Qi Yang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
- Department of Medical Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
| | - Rongqin Zheng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jianhua Zhou
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Lina Tang
- Department of Diagnostic Ultrasound, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Ruifang Zhang
- Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Tianan Jiang
- Department of Ultrasound Medicine, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiang Jing
- Department of Ultrasound, Tianjin Third Central Hospital, Tianjin, China
| | - Jintang Liao
- Department of Diagnostic Ultrasound, Xiangya Hospital Central South University, Changsha, China
| | - Wen Cheng
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Cheng Zhao
- Department of Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cun Liu
- Department of Ultrasound, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Chirstoph F Dietrich
- Department Allgemeine Innere Medizin (DAIM), Kliniken Hirslanden Beau Site, Bern, Switzerland
| | - Xinwu Cui
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenjia Cai
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - JiaPeng Wu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Fei Yu
- Department of Medical Ultrasound, Peking University Shenzhen Hospital, Shenzhen, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Zhiyu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
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16
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Shahbazian H, Birnbaum J, Burns PJ, Shabanan SH, Kanmaniraja D, Reinus J, Kamel I, Sirlin CB, Chernyak V. Prevalence of different LI-RADS v2018 categories in high-risk patients undergoing CT- or MRI-based screening for hepatocellular carcinoma. Abdom Radiol (NY) 2023; 48:3696-3702. [PMID: 37725110 DOI: 10.1007/s00261-023-04040-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 08/22/2023] [Accepted: 08/24/2023] [Indexed: 09/21/2023]
Abstract
PURPOSE To estimate the prevalence of Liver Imaging Reporting and Data System (LI-RADS, LR) v2018 categories reported on CT or MRI performed for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS This retrospective study included all reports for CT and MRI exams performed for HCC screening patients between 8/2018 and 4/2020. Patients with ultrasound, CT, or MRI of the abdomen within two years of the index exam were excluded. From each radiology report, we extracted number of reported liver observations, and LI-RADS v2018 category for each observation. RESULTS There were 329 patients (170 [52%] male, mean age 59 years [SD 12]), of whom 177 (54%) had MRI with gadoxetate, 72 (22%) had MRI with extracellular contrast, 7 (2%) had MRI with unspecified contrast, and 73 (22%) had CT. Of 329 patients, 199 (60%) had no reported observations; 130 patients had 166 reported observations: 114 (68.7%) LR-1, 8 (4.8%) LR-2, 21 (12.6%) LR-3, 6 (3.6%) LR-4, 13 (7.8%) LR-5, 3 (1.8%) LR-M, and 1 (0.6%) LR-TIV. Of 114 LR-1 observations, 78 (68%) were cysts, 17 (15%) were hemangiomas, 12 (11%) were vascular shunts, 3 (3%) were focal nodular hyperplasia, 2 (2%) were siderotic nodules, 1 (1%) was a lipoma, and 1 (1%) was biliary hamartoma. There were 23 observations with probably or definitely malignant categories (LR-4, LR-5, LR-M or LR- TIV), reported in 20/329 (6%) of patients. CONCLUSION In a cohort of at-risk patients undergoing contrast-enhanced CT/MRI for HCC screening, 60% of had no liver observations, and 6 % had probably or definitely malignant observations. IMPLICATIONS FOR PATIENT CARE The prevalence of LI-RADS v2018 categories on CT or MR exams used for HCC screening can help develop screening criteria and assess cost-effectiveness of surveillance strategies with CT and MRI.
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Affiliation(s)
- Haneyeh Shahbazian
- Department of Radiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Jason Birnbaum
- Department of Radiology, Montefiore Medical Center, Bronx, NY, USA
- Department of Radiology, Mount Sinai Hospital, New York, NY, USA
| | - Patricia J Burns
- Liver Imaging Group, University of California San Diego, San Diego, CA, USA
| | | | | | - John Reinus
- Department of Hepatology, Montefiore Medical Center, Bronx, NY, USA
| | - Ihab Kamel
- Department of Radiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Claude B Sirlin
- Liver Imaging Group, University of California San Diego, San Diego, CA, USA
| | - Victoria Chernyak
- Department of Radiology, Montefiore Medical Center, Bronx, NY, USA.
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Singh S, Hoque S, Zekry A, Sowmya A. Radiological Diagnosis of Chronic Liver Disease and Hepatocellular Carcinoma: A Review. J Med Syst 2023; 47:73. [PMID: 37432493 PMCID: PMC10335966 DOI: 10.1007/s10916-023-01968-7] [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: 10/18/2022] [Accepted: 07/02/2023] [Indexed: 07/12/2023]
Abstract
Medical image analysis plays a pivotal role in the evaluation of diseases, including screening, surveillance, diagnosis, and prognosis. Liver is one of the major organs responsible for key functions of metabolism, protein and hormone synthesis, detoxification, and waste excretion. Patients with advanced liver disease and Hepatocellular Carcinoma (HCC) are often asymptomatic in the early stages; however delays in diagnosis and treatment can lead to increased rates of decompensated liver diseases, late-stage HCC, morbidity and mortality. Ultrasound (US) is commonly used imaging modality for diagnosis of chronic liver diseases that includes fibrosis, cirrhosis and portal hypertension. In this paper, we first provide an overview of various diagnostic methods for stages of liver diseases and discuss the role of Computer-Aided Diagnosis (CAD) systems in diagnosing liver diseases. Second, we review the utility of machine learning and deep learning approaches as diagnostic tools. Finally, we present the limitations of existing studies and outline future directions to further improve diagnostic accuracy, as well as reduce cost and subjectivity, while also improving workflow for the clinicians.
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Affiliation(s)
- Sonit Singh
- School of CSE, UNSW Sydney, High St, Kensington, 2052, NSW, Australia.
| | - Shakira Hoque
- Gastroenterology and Hepatology Department, St George Hospital, Hogben St, Kogarah, 2217, NSW, Australia
| | - Amany Zekry
- St George and Sutherland Clinical Campus, School of Clinical Medicine, UNSW, High St, Kensington, 2052, NSW, Australia
- Gastroenterology and Hepatology Department, St George Hospital, Hogben St, Kogarah, 2217, NSW, Australia
| | - Arcot Sowmya
- School of CSE, UNSW Sydney, High St, Kensington, 2052, NSW, Australia
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Lee JH, Kim YK, Min JH, Cha D, Hwang JA, Ahn S. Comparison of noncontrast, dynamic, and hepatobiliary phase abbreviated MRI protocols for detection of hepatic malignancies. Clin Imaging 2023; 101:206-214. [PMID: 37421716 DOI: 10.1016/j.clinimag.2023.05.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 05/12/2023] [Accepted: 05/31/2023] [Indexed: 07/10/2023]
Abstract
BACKGROUND Abbreviated MRI for surveillance in patients at risk for hepatocellular carcinoma (HCC) has recently gained interest. PURPOSE To compare the performance among the three types of abbreviated MRI protocols for the detection of hepatic malignancies in patients at risk for HCC. MATERIAL AND METHODS This retrospective review using data from a prospective-registry study included 221 patients with one or more hepatic nodules detected during surveillance for chronic liver disease. Patients underwent MRI with extracellular contrast agents (ECA-MRI) and MRI with hepatobiliary agents (HBA-MRI) before surgery. Sequences from each MRI were extracted to create three simulated abbreviated MRI (aMRI) sets: noncontrast aMRI (NC-aMRI), dynamic aMRI (Dyn-aMRI), and hepatobiliary phase aMRI (HBP-aMRI). Two readers evaluated each set and reported the probability of malignancy and possibility of non-HCC malignancy per lesion. Using the pathology report as reference, the diagnostic performance of each aMRI was compared. RESULTS This study included 289 observations (219 HCCs, 22 non-HCC malignancies, and 48 benign lesions). Defining category definite malignancy as test positive, the performance of each aMRI was as follows: sensitivity, 94.6%, 88.8%, and 92.5%; and specificity, 83.3%, 91.7%, and 85.4% for HBP-aMRI, Dyn-aMRI, and NC-aMRI, respectively. Pairwise comparison revealed higher sensitivity of HBP-aMRI than both Dyn-aMRI (P = 0.003) and NC-aMRI (P = 0.025), and higher specificity of Dyn-aMRI than HBP-aMRI (P = 0.046). CONCLUSION HBP-aMRI showed better sensitivity than Dyn-aMRI or NC-aMRI, whereas the sensitivity of NC-aMRI was comparable to Dyn-aMRI in the detection of malignancy in high-risk patients. Dyn-aMRI showed better specificity than HBP-aMRI.
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Affiliation(s)
- Jeong Hyun Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Young Kon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
| | - Ji Hye Min
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dongik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jeong Ah Hwang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Soohyun Ahn
- Department of Mathematics, Ajou University, Suwon, Republic of Korea
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19
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Wang Z, Qin H, Liu S, Sheng J, Zhang X. Precision diagnosis of hepatocellular carcinoma. Chin Med J (Engl) 2023; 136:1155-1165. [PMID: 36939276 PMCID: PMC10278703 DOI: 10.1097/cm9.0000000000002641] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Indexed: 03/21/2023] Open
Abstract
ABSTRACT Hepatocellular carcinoma (HCC) is the most common type of primary hepatocellular carcinoma (PHC). Early diagnosis of HCC remains the key to improve the prognosis. In recent years, with the promotion of the concept of precision medicine and more in-depth analysis of the biological mechanism underlying HCC, new diagnostic methods, including emerging serum markers, liquid biopsies, molecular diagnosis, and advances in imaging (novel contrast agents and radiomics), have emerged one after another. Herein, we reviewed and analyzed scientific advances in the early diagnosis of HCC and discussed their application and shortcomings. This review aimed to provide a reference for scientific research and clinical practice of HCC.
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Affiliation(s)
- Zhenxiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, Jilin 130041, China
| | - Hanjiao Qin
- Department of Radiotherapy, Second Hospital of Jilin University, Changchun, Jilin 130041, China
| | - Shui Liu
- Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, Jilin 130041, China
| | - Jiyao Sheng
- Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, Jilin 130041, China
| | - Xuewen Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, Jilin 130041, China
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20
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Eletreby R, Elsharkawy M, Taha AA, Hassany M, Abdelazeem A, El-Kassas M, Soliman A. Evaluation of GALAD Score in Diagnosis and Follow-up of Hepatocellular Carcinoma after Local Ablative Therapy. J Clin Transl Hepatol 2023; 11:334-340. [PMID: 36643039 PMCID: PMC9817041 DOI: 10.14218/jcth.2022.00013] [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: 01/07/2022] [Revised: 04/21/2022] [Accepted: 07/04/2022] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND AND AIMS Strategies for detection of early hepatocellular carcinoma (HCC) are still limited. The GALAD score is a serum biomarker-based model designed to predict the probability of having HCC. We aimed to assess the ability of GALAD score to diagnose early HCC and its validity to follow patients after local ablation therapy. METHODS This multicenter prospective study included 108 patients in two groups, 58 HCC patients (67 focal lesions) with local ablative therapy (study group), and a control group of 50 patients with liver cirrhosis. The GALAD scores of the study and control groups, and of the HCC patients before and after ablative therapy were compared. RESULTS Most patients were men (74.1% in study group and 76% in controls) with hepatitis C virus infection (98.30% in the study group, and 94% in controls). GALAD scores were significantly higher in HCC patients than in those with benign cirrhosis (2.65 vs. -0.37, p=0.001). Ablative therapy was successful in 94.4% of focal lesions <2 cm, and in 86.10% of 2-5 cm lesions. The GALAD score was also significantly lower at 1 month after ablation in patients with well-ablated tumors (2.19 vs. 0.98, p=0.001). The best cutoff values of GALAD score for diagnosis of early HCC, and for prediction of well ablation of HCC were 0.74 and ≤3.31 (areas under the curve of 0.92 and 0.75, sensitivities of 84.48% and 76.19%, specificities of 89.13% and 83.33%, positive predictive values of 90.74% and 94.1%, and negative predictive values of 82% and 35.7% respectively). CONCLUSION The GALAD score was effective for the diagnosis of early HCC and for follow-up after ablative therapy.
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Affiliation(s)
- Rasha Eletreby
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Marwa Elsharkawy
- Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Alaa Awad Taha
- Hepatogastroenterology Department, Theodore Bilharz Research Institute, Giza, Egypt
| | - Mohamed Hassany
- Hepatogastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Amr Abdelazeem
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Ahmed Soliman
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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21
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Huang D, Wen B, Zhang H, Liu H, Wang W, Shen H, Kong W. Ultrasound fusion imaging for improving diagnostic and therapeutic strategies of focal liver lesions: A preliminary study. JOURNAL OF CLINICAL ULTRASOUND : JCU 2023. [PMID: 37098104 DOI: 10.1002/jcu.23467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/27/2023] [Accepted: 04/05/2023] [Indexed: 06/19/2023]
Abstract
PURPOSE To assess the effect of ultrasound (US) fusion imaging on the clinical diagnostic and therapeutic strategies of focal liver lesions, which are difficult to detect or diagnose by conventional US. METHODS From November 2019 to June 2022, 71 patients with invisible or undiagnosed focal liver lesions who underwent fusion imaging combining US with CT or MR were included in this retrospective study. The reasons for US fusion imaging were as follows: (1) lesions that were undetectable or inconspicuous on B-mode US; (2) post-ablation lesions that could not be assessed accurately by B-mode US; (3) to evaluate whether the lesions detected by B-mode US that were consistent with those presented on MRI/CT images. RESULTS Of the 71 cases, 43 cases were single lesions, and 28 cases were multiple lesions. Among the 46 cases which were invisible on conventional US, the display rate of lesions using US-CT/MRI fusion imaging was 30.8%, and that combined with CEUS was 76.9%. US-guided biopsy was performed in 30 patients after the detection and localization determined by fusion imaging, with a positive rate of 73.3%. Six patients with recurrence after ablation therapy were all detected and located accurately after fusion imaging, and 4 of them successfully underwent ablation therapy again. CONCLUSION Fusion imaging contributes to the understanding of the anatomical relationship between lesion location and blood vessels. Additionally, fusion imaging can improve the diagnostic confidence, be helpful to guide interventional operations, and hence be conducive to clinical therapeutic strategies.
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Affiliation(s)
- Danqing Huang
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Baojie Wen
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Han Zhang
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Han Liu
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haiyun Shen
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Wentao Kong
- Department of Ultrasound, Nanjing DrumTower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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22
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Low dose of contrast agent and low radiation liver computed tomography with deep-learning-based contrast boosting model in participants at high-risk for hepatocellular carcinoma: prospective, randomized, double-blind study. Eur Radiol 2023; 33:3660-3670. [PMID: 36934202 DOI: 10.1007/s00330-023-09520-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Revised: 12/18/2022] [Accepted: 02/03/2023] [Indexed: 03/20/2023]
Abstract
OBJECTIVE To investigate the image quality and lesion conspicuity of a deep-learning-based contrast-boosting (DL-CB) algorithm on double-low-dose (DLD) CT of simultaneous reduction of radiation and contrast doses in participants at high-risk for hepatocellular carcinoma (HCC). METHODS Participants were recruited and underwent four-phase dynamic CT (NCT04722120). They were randomly assigned to either standard-dose (SD) or DLD protocol. All CT images were initially reconstructed using iterative reconstruction, and the images of the DLD protocol were further processed using the DL-CB algorithm (DLD-DL). The primary endpoint was the contrast-to-noise ratio (CNR), the secondary endpoint was qualitative image quality (noise, hepatic lesion, and vessel conspicuity), and the tertiary endpoint was lesion detection rate. The t-test or repeated measures analysis of variance was used for analysis. RESULTS Sixty-eight participants with 57 focal liver lesions were enrolled (20 with HCC and 37 with benign findings). The DLD protocol had a 19.8% lower radiation dose (DLP, 855.1 ± 254.8 mGy·cm vs. 713.3 ± 94.6 mGy·cm, p = .003) and 27% lower contrast dose (106.9 ± 15.0 mL vs. 77.9 ± 9.4 mL, p < .001) than the SD protocol. The comparative analysis demonstrated that CNR (p < .001) and portal vein conspicuity (p = .002) were significantly higher in the DLD-DL than in the SD protocol. There was no significant difference in lesion detection rate for all lesions (82.7% vs. 73.3%, p = .140) and HCCs (75.7% vs. 70.4%, p = .644) between the SD protocol and DLD-DL. CONCLUSIONS DL-CB on double-low-dose CT provided improved CNR of the aorta and portal vein without significant impairment of the detection rate of HCC compared to the standard-dose acquisition, even in participants at high risk for HCC. KEY POINTS • Deep-learning-based contrast-boosting algorithm on double-low-dose CT provided an improved contrast-to-noise ratio compared to standard-dose CT. • The detection rate of focal liver lesions was not significantly differed between standard-dose CT and a deep-learning-based contrast-boosting algorithm on double-low-dose CT. • Double-low-dose CT without a deep-learning algorithm presented lower CNR and worse image quality.
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23
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Sabeti S, Ternifi R, Larson NB, Olson MC, Atwell TD, Fatemi M, Alizad A. Morphometric analysis of tumor microvessels for detection of hepatocellular carcinoma using contrast-free ultrasound imaging: A feasibility study. Front Oncol 2023; 13:1121664. [PMID: 37124492 PMCID: PMC10134399 DOI: 10.3389/fonc.2023.1121664] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 03/21/2023] [Indexed: 05/02/2023] Open
Abstract
Introduction A contrast-free ultrasound microvasculature imaging technique was evaluated in this study to determine whether extracting morphological features of the vascular networks in hepatic lesions can be beneficial in differentiating benign and malignant tumors (hepatocellular carcinoma (HCC) in particular). Methods A total of 29 lesions from 22 patients were included in this work. A post-processing algorithm consisting of clutter filtering, denoising, and vessel enhancement steps was implemented on ultrasound data to visualize microvessel structures. These structures were then further characterized and quantified through additional image processing. A total of nine morphological metrics were examined to compare different groups of lesions. A two-sided Wilcoxon rank sum test was used for statistical analysis. Results In the malignant versus benign comparison, six of the metrics manifested statistical significance. Comparing only HCC cases with the benign, only three of the metrics were significantly different. No statistically significant distinction was observed between different malignancies (HCC versus cholangiocarcinoma and metastatic adenocarcinoma) for any of the metrics. Discussion Obtained results suggest that designing predictive models based on such morphological characteristics on a larger sample size may prove helpful in differentiating benign from malignant liver masses.
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Affiliation(s)
- Soroosh Sabeti
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Redouane Ternifi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Nicholas B. Larson
- Department of Quantitative Health Sciences, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Michael C. Olson
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Thomas D. Atwell
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Mostafa Fatemi
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
| | - Azra Alizad
- Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- Department of Radiology, Mayo Clinic College of Medicine and Science, Rochester, MN, United States
- *Correspondence: Azra Alizad,
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24
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Cheng C, Cai J, Teng W, Zheng Y, Huang Y, Wang Y, Peng C, Tang Y, Lee W, Yeh T, Xiao J, Lu L, Liao C, Harrison AP. A flexible three-dimensional heterophase computed tomography hepatocellular carcinoma detection algorithm for generalizable and practical screening. Hepatol Commun 2022; 6:2901-2913. [PMID: 35852311 PMCID: PMC9512477 DOI: 10.1002/hep4.2029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 04/13/2022] [Accepted: 05/29/2022] [Indexed: 11/26/2022] Open
Abstract
Hepatocellular carcinoma (HCC) can be potentially discovered from abdominal computed tomography (CT) studies under varied clinical scenarios (e.g., fully dynamic contrast-enhanced [DCE] studies, noncontrast [NC] plus venous phase [VP] abdominal studies, or NC-only studies). Each scenario presents its own clinical challenges that could benefit from computer-aided detection (CADe) tools. We investigate whether a single CADe model can be made flexible enough to handle different contrast protocols and whether this flexibility imparts performance gains. We developed a flexible three-dimensional deep algorithm, called heterophase volumetric detection (HPVD), that can accept any combination of contrast-phase inputs with adjustable sensitivity depending on the clinical purpose. We trained HPVD on 771 DCE CT scans to detect HCCs and evaluated it on 164 positives and 206 controls. We compared performance against six clinical readers, including two radiologists, two hepatopancreaticobiliary surgeons, and two hepatologists. The area under the curve of the localization receiver operating characteristic for NC-only, NC plus VP, and full DCE CT yielded 0.71 (95% confidence interval [CI], 0.64-0.77), 0.81 (95% CI, 0.75-0.87), and 0.89 (95% CI, 0.84-0.93), respectively. At a high-sensitivity operating point of 80% on DCE CT, HPVD achieved 97% specificity, which is comparable to measured physician performance. We also demonstrated performance improvements over more typical and less flexible nonheterophase detectors. Conclusion: A single deep-learning algorithm can be effectively applied to diverse HCC detection clinical scenarios, indicating that HPVD could serve as a useful clinical aid for at-risk and opportunistic HCC surveillance.
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Affiliation(s)
- Chi‐Tung Cheng
- Department of Trauma and Emergency SurgeryChang Gung Memorial Hospital at LinkouChang Gung UniversityLinkouTaiwan, Republic of China
| | | | - Wei Teng
- Department of Gastroenterology and HepatologyChang Gung Memorial Hospital, Linkou Medical CenterLinkouTaiwan, Republic of China
| | - Youjing Zheng
- Virginia Polytechnic Institute and State UniversityBlacksburgVirginiaUSA
| | - Yu‐Ting Huang
- Department of Diagnostic RadiologyChang Gung Memorial Hospital at Keelung, Chang Gung UniversityKeelungTaiwan, Republic of China
| | - Yu‐Chao Wang
- Department of General SurgeryChang Gung Memorial HospitalLinkouTaiwan, Republic of China
| | - Chien‐Wei Peng
- Department of Gastroenterology and HepatologyChang Gung Memorial Hospital, Linkou Medical CenterLinkouTaiwan, Republic of China
| | | | - Wei‐Chen Lee
- Department of General SurgeryChang Gung Memorial HospitalLinkouTaiwan, Republic of China
| | - Ta‐Sen Yeh
- Department of General SurgeryChang Gung Memorial HospitalLinkouTaiwan, Republic of China
| | | | - Le Lu
- PAII Inc.BethesdaMarylandUSA
| | - Chien‐Hung Liao
- Department of Trauma and Emergency SurgeryChang Gung Memorial Hospital at LinkouChang Gung UniversityLinkouTaiwan, Republic of China
- Center for Artificial Intelligence in MedicineChang Gung Memorial HospitalLinkou, TaiwanTaiwan, Republic of China
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25
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Huang YM, Wang TE, Chen MJ, Lin CC, Chang CW, Tai HC, Hsu SM, Chen YJ. Radiomics-based nomogram as predictive model for prognosis of hepatocellular carcinoma with portal vein tumor thrombosis receiving radiotherapy. Front Oncol 2022; 12:906498. [PMID: 36203419 PMCID: PMC9530279 DOI: 10.3389/fonc.2022.906498] [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: 03/28/2022] [Accepted: 08/26/2022] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND This study aims to establish and validate a predictive model based on radiomics features, clinical features, and radiation therapy (RT) dosimetric parameters for overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with RT for portal vein tumor thrombosis (PVTT). METHODS We retrospectively reviewed 131 patients. Patients were randomly divided into the training (n = 105) and validation (n = 26) cohorts. The clinical target volume was contoured on pre-RT computed tomography images and 48 textural features were extracted. The least absolute shrinkage and selection operator regression was used to determine the radiomics score (rad-score). A nomogram based on rad-score, clinical features, and dosimetric parameters was developed using the results of multivariate regression analysis. The predictive nomogram was evaluated using Harrell's concordance index (C-index), area under the curve (AUC), and calibration curve. RESULTS Two radiomics features were extracted to calculate the rad-score for the prediction of OS. The radiomics-based nomogram had better performance than the clinical nomogram for the prediction of OS, with a C-index of 0.73 (95% CI, 0.67-0.79) and an AUC of 0.71 (95% CI, 0.62-0.79). The predictive accuracy was assessed by a calibration curve. CONCLUSION The radiomics-based predictive model significantly improved OS prediction in HCC patients treated with RT for PVTT.
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Affiliation(s)
- Yu-Ming Huang
- Department of Radiation Oncology, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tsang-En Wang
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
| | - Ming-Jen Chen
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
| | - Ching-Chung Lin
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
| | - Ching-Wei Chang
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
| | - Hung-Chi Tai
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shih-Ming Hsu
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Jen Chen
- Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
- Department of Artificial Intelligence and Medical Application, MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan
- Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
- Department of Medical Research, China Medical University Hospital, Taichung, Taiwan
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Park HJ, Kim SY, Singal AG, Lee SJ, Won HJ, Byun JH, Choi SH, Yokoo T, Kim MJ, Lim YS. Abbreviated magnetic resonance imaging vs ultrasound for surveillance of hepatocellular carcinoma in high-risk patients. Liver Int 2022; 42:2080-2092. [PMID: 34817921 DOI: 10.1111/liv.15110] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 09/30/2021] [Accepted: 11/20/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS We aimed to compare the performance of gadoxetic acid-enhanced abbreviated MRI (AMRI)-based surveillance and ultrasound-only surveillance in high-risk patients for hepatocellular carcinoma (HCC). METHODS Prospectively recruited high-risk patients (>5% annual risk of HCC) who underwent one to three rounds of complete gadoxetic acid-enhanced MRI (CMRI) and ultrasound at 6-months intervals were retrospectively analysed. AMRI consisted of diffusion-weighted, T2-weighted, and hepatobiliary phase imaging. The sensitivity, specificity, and accuracy of CMRI followed by AMRI (CAA), AMRI-only (AAA), and ultrasound-only (US) were compared using generalized estimating equations. Image quality was assessed. RESULTS In 382 patients, HCC was diagnosed in 43 (11.3%), including 42 with early-stage HCCs. The sensitivities of CAA (90.7%, 39/43) and AAA (86.0%, 37/43) were higher than US (27.9% [12/43]; P < 0.001), whereas the sensitivities of the two MRI approaches did not significantly differ (P = 0.56). The specificity of CAA (97.1%, 983/1012) was higher than AAA (95.6% [967/1012]; P = 0.01) and not significantly different from US (96.3% [975/1012]; P = 0.59). The CAA approach had the best accuracy of 96.9% (1022/1055), higher than the AAA approach (95.2% [1004/1055]; P = 0.01) and the US approach (93.6% [987/1055]; P = 0.01). Image quality was inadequate in 33.7% (356/1055) of US examinations but in only 10.0% (105/1055) of the AAA and 11.1% (117/1055) of the CAA approach. CONCLUSIONS In high-risk patients, AMRI-based surveillance approaches had higher sensitivities than ultrasound-only surveillance for early-stage HCC. A sequential MRI approach of CMRI followed by AMRIs showed superior accuracy than the AMRI-only or ultrasound-only approach.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Takeshi Yokoo
- Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Suk Lim
- Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.,Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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27
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Jia X, Sun Z, Mi Q, Yang Z, Yang D. A Multimodality-Contribution-Aware TripNet for Histologic Grading of Hepatocellular Carcinoma. IEEE/ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS 2022; 19:2003-2016. [PMID: 33974545 DOI: 10.1109/tcbb.2021.3079216] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Hepatocellular carcinoma (HCC) is a type of primary liver malignant tumor with a high recurrence rate and poor prognosis even undergoing resection or transplantation. Accurate discrimination of the histologic grades of HCC plays a critical role in the management and therapy of HCC patients. In this paper, we discuss a deep learning-based diagnostic model for HCC histologic grading with multimodal Magnetic Resonance Imaging (MRI) images to overcome the problem of limited well-annotated data and extract the discriminated fusion feature referring to the clinical diagnosis experience of radiologists. Accordingly, we propose a novel Multimodality-Contribution-Aware TripNet (MCAT) based on the metric learning and the attention-aware weighted multimodal fusion. The novelty of the method lies in the multimodality small-shot learning architecture designation and the multimodality adaptive weighted computing scheme. The comprehensive experiments are done on the clinic dataset with the well-annotation of lesion location by the professional radiologist. The experimental results show that our proposed MCAT is not only able to achieve acceptable quantitative measuring of HCC histologic grading based on the MRI sequences with small cases but also outperforms previous models in HCC histologic grading, reaching an accuracy of 84 percent, a sensitivity of 87 percent and precision of 89 percent.
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Wu X, Meng X, Chang TS, Feng S, Lee M, Jaiswal S, Choi EYK, Tran L, Jiang H, Wang TD. Multi-modal imaging for uptake of peptide ligand specific for CD44 by hepatocellular carcinoma. PHOTOACOUSTICS 2022; 26:100355. [PMID: 35479192 PMCID: PMC9035732 DOI: 10.1016/j.pacs.2022.100355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 03/25/2022] [Accepted: 04/08/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early cancer detection and image-guided surgery. METHODS We used a structural model to optimize the peptide sequence. Specific binding was validated in vitro with knockdown, competition, and co-localization assays. Multi-modal imaging was performed to validate specific binding in vivo in orthotopically-implanted human xenograft tumors. RESULTS Binding properties of WKGWSYLWTQQA were characterized by an apparent dissociation constant of kd = 43 nM, and an apparent association time constant of k = 0.26 min-1. The target-to-background ratio was significantly higher for the target versus control for both modalities. Ex-vivo evaluation using human HCC specimens supported the ability of the peptide to distinguish HCC from other liver pathologies. CONCLUSIONS We have identified a peptide specific for CD44 with properties that are promising for clinical translation to image HCC in vivo.
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Affiliation(s)
- Xiaoli Wu
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Xiaoqing Meng
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Tse-Shao Chang
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
| | - Shuo Feng
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Miki Lee
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Sangeeta Jaiswal
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Eun-Young K. Choi
- Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
| | - Lam Tran
- Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Hui Jiang
- Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
| | - Thomas D. Wang
- Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
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Calderaro J, Seraphin TP, Luedde T, Simon TG. Artificial intelligence for the prevention and clinical management of hepatocellular carcinoma. J Hepatol 2022; 76:1348-1361. [PMID: 35589255 PMCID: PMC9126418 DOI: 10.1016/j.jhep.2022.01.014] [Citation(s) in RCA: 127] [Impact Index Per Article: 42.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/26/2021] [Accepted: 01/14/2022] [Indexed: 12/13/2022]
Abstract
Hepatocellular carcinoma (HCC) currently represents the fifth most common malignancy and the third-leading cause of cancer-related death worldwide, with incidence and mortality rates that are increasing. Recently, artificial intelligence (AI) has emerged as a unique opportunity to improve the full spectrum of HCC clinical care, by improving HCC risk prediction, diagnosis, and prognostication. AI approaches include computational search algorithms, machine learning (ML) and deep learning (DL) models. ML consists of a computer running repeated iterations of models, in order to progressively improve performance of a specific task, such as classifying an outcome. DL models are a subtype of ML, based on neural network structures that are inspired by the neuroanatomy of the human brain. A growing body of recent data now apply DL models to diverse data sources - including electronic health record data, imaging modalities, histopathology and molecular biomarkers - to improve the accuracy of HCC risk prediction, detection and prediction of treatment response. Despite the promise of these early results, future research is still needed to standardise AI data, and to improve both the generalisability and interpretability of results. If such challenges can be overcome, AI has the potential to profoundly change the way in which care is provided to patients with or at risk of HCC.
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Affiliation(s)
- Julien Calderaro
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Pathology, Créteil, France; Inserm U955 and Univ Paris Est Creteil, INSERM, IMRB, 94010, Creteil, France
| | - Tobias Paul Seraphin
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Medical Faculty at Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Duesseldorf, Medical Faculty at Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany
| | - Tracey G. Simon
- Liver Center, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA, USA
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Nadarevic T, Colli A, Giljaca V, Fraquelli M, Casazza G, Manzotti C, Štimac D, Miletic D. Magnetic resonance imaging for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 2022; 5:CD014798. [PMID: 35521901 PMCID: PMC9074390 DOI: 10.1002/14651858.cd014798.pub2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths. In clinical practice, magnetic resonance imaging (MRI) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-fetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study (computed tomography (CT) or MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is considered valid to diagnose hepatocellular carcinoma. The detection of hepatocellular carcinoma amenable to surgical resection could improve the prognosis. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma may, therefore, be missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of MRI may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of MRI in people with chronic liver disease who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma. OBJECTIVES Primary: to assess the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease. Secondary: to assess the diagnostic accuracy of MRI for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease, and to identify potential sources of heterogeneity in the results. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test of Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, and three other databases to 9 November 2021. We manually searched articles retrieved, contacted experts, handsearched abstract books from meetings held during the last 10 years, and searched for literature in OpenGrey (9 November 2021). Further information was requested by e-mails, but no additional information was provided. No data was obtained through correspondence with investigators. We applied no language or document-type restrictions. SELECTION CRITERIA Studies assessing the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. DATA COLLECTION AND ANALYSIS At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and we tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses. MAIN RESULTS We included 34 studies, with 4841 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time interval between the index test and the reference standard was rarely defined. Regarding applicability, we judged 15% (5/34) of studies to be at low concern and 85% (29/34) of studies to be at high concern mostly owing to characteristics of the participants, most of whom were on waiting lists for orthotopic liver transplantation, and due to pathology of the explanted liver being the only reference standard. MRI for hepatocellular carcinoma of any size and stage: sensitivity 84.4% (95% CI 80.1% to 87.9%) and specificity 93.8% (95% CI 90.1% to 96.1%) (34 studies, 4841 participants; low-certainty evidence). MRI for resectable hepatocellular carcinoma: sensitivity 84.3% (95% CI 77.6% to 89.3%) and specificity 92.9% (95% CI 88.3% to 95.9%) (16 studies, 2150 participants; low-certainty evidence). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results. AUTHORS' CONCLUSIONS We found that using MRI as a second-line imaging modality to diagnose hepatocellular carcinoma of any size and stage, 16% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 16% of people with resectable hepatocellular carcinoma would improperly not be resected, while 7% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.
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Affiliation(s)
- Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Vanja Giljaca
- Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham, UK
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Giovanni Casazza
- Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, Milan, Italy
| | - Cristina Manzotti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Damir Miletic
- Department of Radiology , Clinical Hospital Centre Rijeka, Rijeka, Croatia
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Lysdahlgaard S. Comparing Radiomics features of tumour and healthy liver tissue in a limited CT dataset: A machine learning study. Radiography (Lond) 2022; 28:718-724. [PMID: 35428570 DOI: 10.1016/j.radi.2022.03.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 03/07/2022] [Accepted: 03/29/2022] [Indexed: 10/18/2022]
Abstract
INTRODUCTION Liver cancer lesions on Computed Tomography (CT) withholds a great amount of data, which is not visible to the radiologists and radiographer. Radiomics features can be extracted from the lesions and used to train Machine Learning (ML) algorithms to predict between tumour and liver tissue. The purpose of this study was to investigate and classify Radiomics features extracted from liver tumours and normal liver tissue in a limited CT dataset. METHODS The Liver Tumour Segmentation Benchmark (LiTS) dataset consisting of 131 CT scans of the liver with segmentations of tumour tissue and healthy liver was used to extract Radiomic features. Extracted Radiomic features included size, shape, and location extracted with morphological and statistical techniques according to the International Symposium on Biomedical Imaging manual. Relevant features was selected with chi2 correlation and principal component analysis (PCA) with tumour and healthy liver tissue as outcome according to a consensus between three experienced radiologists. Logistic regression, random forest and support vector machine was used to train and validate the dataset with a 10-fold cross-validation method and the Grid Search as hyper-parameter tuning. Performance was evaluated with sensitivity, specificity and accuracy. RESULTS The performance of the ML algorithms achieved sensitivities, specificities and accuracy ranging from 96.30% (95% CI: 81.03%-99.91%) to 100.00% (95% CI: 86.77%-100.00%), 91.30% (95% CI: 71.96%-98.93%) to 100.00% (95% CI: 83.89%-100.00%)and 94.00% (95% CI: 83.45%-98.75%) to 100.00% (95% CI: 92.45%-100.00%), respectively. CONCLUSION ML algorithms classifies Radiomics features extracted from healthy liver and tumour tissue with perfect accuracy. The Radiomics signature allows for a prognostic biomarker for hepatic tumour screening on liver CT. IMPLICATIONS FOR PRACTICE Differentiation between tumour and liver tissue with Radiomics ML algorithms have the potential to increase the diagnostic accuracy, assist in the decision-making of supplementary multiphasic enhanced medical imaging, as well as for developing novel prognostic biomarkers for liver cancer patients.
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Affiliation(s)
- S Lysdahlgaard
- Department of Radiology and Nuclear Medicine, Hospital of South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark; Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark; Imaging Research Initiative Southwest (IRIS), Hospital of South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark.
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Du YQ, Bai XM, Yang W, Zhang ZY, Wang S, Wu W, Yan K, Chen MH. Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma. Int J Hyperthermia 2022; 39:517-524. [PMID: 35311422 DOI: 10.1080/02656736.2022.2048907] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Affiliation(s)
- Yu-qing Du
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiu-mei Bai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhong-yi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Song Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wei Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Kun Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
| | - Min-hua Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Ultrasound, Peking University Cancer Hospital & Institute, Beijing, China
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Cheung ALY, Zhang L, Liu C, Li T, Cheung AHY, Leung C, Leung AKC, Lam SK, Lee VHF, Cai J. Evaluation of Multisource Adaptive MRI Fusion for Gross Tumor Volume Delineation of Hepatocellular Carcinoma. Front Oncol 2022; 12:816678. [PMID: 35280780 PMCID: PMC8913492 DOI: 10.3389/fonc.2022.816678] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 01/27/2022] [Indexed: 12/22/2022] Open
Abstract
Purpose Tumor delineation plays a critical role in radiotherapy for hepatocellular carcinoma (HCC) patients. The incorporation of MRI might improve the ability to correctly identify tumor boundaries and delineation consistency. In this study, we evaluated a novel Multisource Adaptive MRI Fusion (MAMF) method in HCC patients for tumor delineation. Methods Ten patients with HCC were included in this study retrospectively. Contrast-enhanced T1-weighted MRI at portal-venous phase (T1WPP), contrast-enhanced T1-weighted MRI at 19-min delayed phase (T1WDP), T2-weighted (T2W), and diffusion-weighted MRI (DWI) were acquired on a 3T MRI scanner and imported to in-house-developed MAMF software to generate synthetic MR fusion images. The original multi-contrast MR image sets were registered to planning CT by deformable image registration (DIR) using MIM. Four observers independently delineated gross tumor volumes (GTVs) on the planning CT, four original MR image sets, and the fused MRI for all patients. Tumor contrast-to-noise ratio (CNR) and Dice similarity coefficient (DSC) of the GTVs between each observer and a reference observer were measured on the six image sets. Inter-observer and inter-patient mean, SD, and coefficient of variation (CV) of the DSC were evaluated. Results Fused MRI showed the highest tumor CNR compared to planning CT and original MR sets in the ten patients. The mean ± SD tumor CNR was 0.72 ± 0.73, 3.66 ± 2.96, 4.13 ± 3.98, 4.10 ± 3.17, 5.25 ± 2.44, and 9.82 ± 4.19 for CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively. Fused MRI has the minimum inter-observer and inter-patient variations as compared to original MR sets and planning CT sets. GTV delineation inter-observer mean DSC across the ten patients was 0.81 ± 0.09, 0.85 ± 0.08, 0.88 ± 0.04, 0.89 ± 0.08, 0.90 ± 0.04, and 0.95 ± 0.02 for planning CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively. The patient mean inter-observer CV of DSC was 3.3%, 3.2%, 1.7%, 2.6%, 1.5%, and 0.9% for planning CT, T1WPP, T2W, DWI, T1WDP, and fused MRI, respectively. Conclusion The results demonstrated that the fused MRI generated using the MAMF method can enhance tumor CNR and improve inter-observer consistency of GTV delineation in HCC as compared to planning CT and four commonly used MR image sets (T1WPP, T1WDP, T2W, and DWI). The MAMF method holds great promise in MRI applications in HCC radiotherapy treatment planning.
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Affiliation(s)
- Andy Lai-Yin Cheung
- Department of Clinical Oncology, Queen Mary Hospital, Hong Kong, Hong Kong SAR, China.,Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Lei Zhang
- Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States.,Medical Physics Graduate Program, Duke University, Durham, NC, United States.,Medical Physics Graduate Program, Duke Kunshan University, Kunshan, China
| | - Chenyang Liu
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Tian Li
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Anson Ho-Yin Cheung
- Radiotherapy and Oncology Centre, Hong Kong Baptist Hospital, Hong Kong, Hong Kong SAR, China
| | - Chun Leung
- Radiotherapy and Oncology Centre, Hong Kong Baptist Hospital, Hong Kong, Hong Kong SAR, China
| | | | - Sai-Kit Lam
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China
| | - Victor Ho-Fun Lee
- Department of Clinical Oncology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jing Cai
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China.,Department of Radiation Oncology, Duke University Medical Center, Durham, NC, United States
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Tran L, Jung J, Feldman R, Riley T. Disparities in the quality of care for chronic hepatitis C among Medicare beneficiaries. PLoS One 2022; 17:e0263913. [PMID: 35271617 PMCID: PMC8912154 DOI: 10.1371/journal.pone.0263913] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 01/29/2022] [Indexed: 12/09/2022] Open
Abstract
Purpose
Chronic hepatitis C virus (HCV) infection is an important public health concern. Limited information exists on disparities in the quality of HCV care. We examine disparities in genotype or quantitative HCV ribonucleic acid testing before and after starting HCV treatment, and screening for hepatocellular carcinoma (HCC) in HCV patients with cirrhosis.
Methods
This national study included Medicare beneficiaries with HCV between 2014 and 2017. We used bivariate probit to estimate the probability of receiving recommended tests before and after HCV treatment by patient race/ethnicity, urban/rural residence, and socioeconomic status. We used multivariate logistic regression to estimate adjusted odds ratios (aOR) of HCC screening among beneficiaries with cirrhosis by patient factors.
Findings
Of 41,800 Medicare patients with HCV treatment, 93.47% and 84.99% received pre- and post-treatment testing. Patients in racial minority groups had lower probabilities of pre- and post-treatment testing than whites. Rural residents were less likely to receive a post-treatment test (Coef. = -0.06, 95% CI: -0.11, -0.01). Among HCV patients with cirrhosis, 40% (24,021) received at least one semi-annual HCC screening during the study period. The odds of HCC screening were 14% lower in rural than in urban patients (aOR = 0.86, 95% CI: 0.80, 0.92), lower in African Americans (aOR = 0.93, 95% CI: 0.90, 0.96), but higher among Hispanics than in whites (aOR = 1.09, 95% CI: 1.04, 1.15). There was no significant association between ZIP-level income or education and HCC screening.
Conclusions
Disparities in the quality of HCV care existed by patient race/ethnicity, urban/rural residence, and socioeconomic status. Continued efforts are needed to improve the quality of care for all HCV patients—especially rural patients and racial/ethnic minorities.
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Affiliation(s)
- Linh Tran
- Department of Health Policy and Administration, College of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania, United States of America
- * E-mail:
| | - Jeah Jung
- Department of Health Policy and Administration, College of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Roger Feldman
- Division of Health Policy and Management, School of Public Health, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Thomas Riley
- Department of Medicine, College of Medicine, Pennsylvania State University, Hershey, Pennsylvania, United States of America
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Rich NE, Singal AG. Overdiagnosis of hepatocellular carcinoma: Prevented by guidelines? Hepatology 2022; 75:740-753. [PMID: 34923659 PMCID: PMC8844206 DOI: 10.1002/hep.32284] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 11/27/2021] [Accepted: 12/04/2021] [Indexed: 12/13/2022]
Abstract
Overdiagnosis refers to detection of disease that would not otherwise become clinically apparent during a patient's lifetime. Overdiagnosis is common and has been reported for several cancer types, although there are few studies describing its prevalence in HCC surveillance programs. Overdiagnosis can have serious negative consequences including overtreatment and associated complications, financial toxicity, and psychological harms related to being labeled with a cancer diagnosis. Overdiagnosis can occur for several different reasons including inaccurate diagnostic criteria, detection of premalignant or very early malignant lesions, detection of indolent tumors, and competing risks of mortality. The risk of overdiagnosis is partly mitigated, albeit not eliminated, by several guideline recommendations, including definitions for the at-risk population in whom surveillance should be performed, surveillance modalities, surveillance interval, recall procedures, and HCC diagnostic criteria. Continued research is needed to further characterize the burden and trends of overdiagnosis as well as identify strategies to reduce overdiagnosis in the future.
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Affiliation(s)
- Nicole E Rich
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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Qiong L, Jie Z, Zhong Z, Wen S, Jun Z, Liping L, Jinkui C. Detection of hepatocellular carcinoma in a population at risk: iodine-enhanced multidetector CT and/or gadoxetic acid-enhanced 3.0 T MRI. BMJ Open 2022; 12:e058461. [PMID: 35177466 PMCID: PMC8860074 DOI: 10.1136/bmjopen-2021-058461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVE To evaluate the diagnostic performance of iodine-enhanced multidetector CT and gadoxetic acid-enhanced 3.0 Tesla (T) MRI for detection of hepatocellular carcinoma of patients. DESIGN Retrospective, multicentre cohort study. SETTING The Gong'an County People's Hospital, Gong'an County, China and the First People's Hospital of Jingzhou City, China. PARTICIPANTS Reports of CT, MRI and liver biopsies/histopathology data of a total of 815 patients who at risk were reviewed. PRIMARY AND SECONDARY OUTCOME MEASURES The lesions that possessed detection in the plain scan phase, enhanced arterial phase and/or enhanced portal phase of CT images and the lesions that possessed enhancements in the plain scan phase, enhanced arterial phase, enhanced portal phase and/or hepatobiliary phases of MRI were considered hepatocellular carcinoma. The decision of hepatocellular carcinoma was made based on the current Liver Imaging and Data Reporting System for diagnosing hepatocellular carcinoma. RESULTS True positive hepatocellular carcinoma (563 vs 521, p=0.0314), true negative hepatocellular carcinoma (122 vs 91, p=0.0275), false positive hepatocellular carcinoma (88 vs 123, p=0.0121), false negative hepatocellular carcinoma (42 vs 80, p=0.0005), specificity (58.10 vs 42.52, p=0.0478) and negative clinical utility (0.1 vs 0.073, p=0.0386) were superior for gadoxetic acid-enhanced 3.0 T MRI than those of iodine-enhanced multidetector CT. Sensitivity and accuracy for gadoxetic acid-enhanced 3.0 T MRI were 93.06% and 77.40 %, respectively, and those for iodine-enhanced multidetector CT were 86.69% and 75.09 %, respectively. Likelihood to detect hepatocellular carcinoma for gadoxetic acid-enhanced 3.0 T MRI was 0-0.894 diagnostic confidence/lesion, and that for iodine-enhanced multidetector CT was 0-0.887 diagnostic confidence/lesion. CONCLUSION Gadoxetic acid-enhanced 3.0 T MRI facilitates the confidence of initiation of treatment of hepatocellular carcinoma. LEVEL OF EVIDENCE III. TECHNICAL EFFICACY STAGE 4.
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Affiliation(s)
- Lan Qiong
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zhao Jie
- Department of Rehabilitation, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zheng Zhong
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Sheng Wen
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Zhao Jun
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Lu Liping
- Department of Radiology Imaging, Gong'an County People's Hospital, Gong'an County, Hubei, China
| | - Cheng Jinkui
- Department of Ophthalmology, The First People's Hospital of Jingzhou, Jingzhou, Hubei, China
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Clinical versus radiographical factors associated with hepatocellular carcinoma diagnosis in high-risk patients: sizes matter. Future Sci OA 2022; 8:FSO785. [PMID: 35369275 PMCID: PMC8965803 DOI: 10.2144/fsoa-2021-0108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 01/19/2022] [Indexed: 11/23/2022] Open
Abstract
Aim: This study aimed to evaluate if clinical or radiographic findings can be used for hepatocellular carcinoma (HCC) diagnosis particularly in high-risk patients. Methods: This was a prospective study and evaluated factors associated with HCC. Results: There were 260 patients met the study criteria: 219 patients (84.23%) were HCC. Two factors significantly associated with HCC: portal vein invasion and the largest mass size. The cutoff point for the largest mass size of 2 cm or over gave sensitivity and specificity for HCC of 83.56 and 87.80%, respectively. Conclusion: Portal vein invasion and the largest liver mass of 2 cm or over may be diagnostic factors for HCC in high-risk patients, while clinical factors were not suggestive for HCC. Radiographic findings are suggestive for liver cancer and can be used to diagnose liver cancer in patients at risk for liver cancer.
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Luo B, Ma F, Liu H, Hu J, Rao L, Liu C, Jiang Y, Kuangzeng S, Lin X, Wang C, Lei Y, Si Z, Chen G, Zhou N, Liang C, Jiang F, Liu F, Dai W, Liu W, Gao Y, Li Z, Li X, Zhou G, Li B, Zhang Z, Nian W, Luo L, Liu X. Cell-free DNA methylation markers for differential diagnosis of hepatocellular carcinoma. BMC Med 2022; 20:8. [PMID: 35027051 PMCID: PMC8759185 DOI: 10.1186/s12916-021-02201-3] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/24/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Aberrant DNA methylation may offer opportunities in revolutionizing cancer screening and diagnosis. We sought to identify a non-invasive DNA methylation-based screening approach using cell-free DNA (cfDNA) for early detection of hepatocellular carcinoma (HCC). METHODS Differentially, DNA methylation blocks were determined by comparing methylation profiles of biopsy-proven HCC, liver cirrhosis, and normal tissue samples with high throughput DNA bisulfite sequencing. A multi-layer HCC screening model was subsequently constructed based on tissue-derived differentially methylated blocks (DMBs). This model was tested in a cohort consisting of 120 HCC, 92 liver cirrhotic, and 290 healthy plasma samples including 65 hepatitis B surface antigen-seropositive (HBsAg+) samples, independently validated in a cohort consisting of 67 HCC, 111 liver cirrhotic, and 242 healthy plasma samples including 56 HBsAg+ samples. RESULTS Based on methylation profiling of tissue samples, 2321 DMBs were identified, which were subsequently used to construct a cfDNA-based HCC screening model, achieved a sensitivity of 86% and specificity of 98% in the training cohort and a sensitivity of 84% and specificity of 96% in the independent validation cohort. This model obtained a sensitivity of 76% in 37 early-stage HCC (Barcelona clinical liver cancer [BCLC] stage 0-A) patients. The screening model can effectively discriminate HCC patients from non-HCC controls, including liver cirrhotic patients, asymptomatic HBsAg+ and healthy individuals, achieving an AUC of 0.957(95% CI 0.939-0.975), whereas serum α-fetoprotein (AFP) only achieved an AUC of 0.803 (95% CI 0.758-0.847). Besides detecting patients with early-stage HCC from non-HCC controls, this model showed high capacity for distinguishing early-stage HCC from a high risk population (AUC=0.934; 95% CI 0.905-0.963), also significantly outperforming AFP. Furthermore, our model also showed superior performance in distinguishing HCC with normal AFP (< 20ng ml-1) from high risk population (AUC=0.93; 95% CI 0.892-0.969). CONCLUSIONS We have developed a sensitive blood-based non-invasive HCC screening model which can effectively distinguish early-stage HCC patients from high risk population and demonstrated its performance through an independent validation cohort. TRIAL REGISTRATION The study was approved by the ethic committee of The Second Xiangya Hospital of Central South University (KYLL2018072) and Chongqing University Cancer Hospital (2019167). The study is registered at ClinicalTrials.gov(# NCT04383353 ).
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Affiliation(s)
- Biyuan Luo
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Fang Ma
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Hao Liu
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Jixiong Hu
- Department of General Surgery, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Le Rao
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Chun Liu
- Department of Hepatopancreatobiliary Surgery, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Yongfang Jiang
- Department of Infectious Disease, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Shuyu Kuangzeng
- Department of Oncology, 331 Hospital of Zhuzhou, Zhuzhou, 412002, Hunan Province, China
| | - Xuan Lin
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Chenyang Wang
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Yiyu Lei
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Zhongzhou Si
- Center of Organ Transplantation, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Guangshun Chen
- Center of Organ Transplantation, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Ning Zhou
- Department of Hepatobiliary Surgery, Hunan Provincial Hospital, Hunan Normal University, No. 61 Jiafang West Road, Changsha, Hunan Province, China
| | - Chengbai Liang
- Department of Gastroenterology, The Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Fangqing Jiang
- Department of Infectious Disease, The First Hospital of Changsha, No. 311, Yingpan Road, Changsha, 410005, Hunan Province, China
| | - Fenge Liu
- Department of Infectious Disease, The First Hospital of Changsha, No. 311, Yingpan Road, Changsha, 410005, Hunan Province, China
| | - Weidong Dai
- Department of General Surgery, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Wei Liu
- Department of Hepatopancreatobiliary Surgery, The Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Yawen Gao
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China
| | - Zhihong Li
- Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Changsha, 410011, China
| | - Xi Li
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Guangyu Zhou
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Bingsi Li
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Zhihong Zhang
- Burning Rock Biotech, Guangzhou, 510300, Guangdong, China
| | - Weiqi Nian
- Chongqing University Cancer Hospital, No.181, Hangyu Road, Shapingba District, Chongqing, China
| | - Lihua Luo
- Department of Oncology, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, 445000, Hubei Province, People's Republic of China
| | - Xianling Liu
- Department of Oncology, The Second XiangYa Hospital of Central South University, 139 Renmin Middle Road, Changsha, 410011, Hunan Province, China.
- Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Changsha, 410011, China.
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Ho CL, Chen S. Oncology: Hepatic cancer. Nucl Med Mol Imaging 2022. [DOI: 10.1016/b978-0-12-822960-6.00109-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
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Dharia A, Boulet J, Sridhar VS, Kitchlu A. Cancer Screening in Solid Organ Transplant Recipients: A Focus on Screening Liver, Lung, and Kidney Recipients for Cancers Related to the Transplanted Organ. Transplantation 2022; 106:e64-e65. [PMID: 33795594 DOI: 10.1097/tp.0000000000003773] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Over the last few decades, the life expectancy of solid organ transplant recipients (SOTRs) has improved significantly. With SOTRs living longer, more recipients are dying from cancer. There is a reported 2- to 3-fold increased risk of cancer-specific mortality in SOTRs compared with the general population. Cancer in an SOTR can be de novo, recurrent, or donor-derived. Cancer screening in this population is crucial, as early detection and treatment may improve outcomes. In the absence of randomized controlled trials dedicated to SOTRs, clinicians rely on clinical practice guidelines from regional and national transplant societies; however, these may vary considerably across jurisdictions and transplanted organ. At present, no widely accepted consensus exists for cancer screening protocols in SOTRs, particularly with regard to screening for malignancy related to transplanted organ. Some SOTRs may be at higher risk of malignancies within the allograft. This is particularly the case in lung and liver recipients, though less common in kidney recipients who are at increased risk of developing renal cell cancer in their native kidneys. This increased risk has not been uniformly incorporated into screening recommendations for SOTRs. In this review, we summarize the cancer screening recommendations for SOTRs from various transplant organizations based on transplanted organ. This review also discusses the complexity and controversies surrounding screening of cancer in the allograft and future avenues to improve cancer detection in this context. More studies specific to SOTRs are required to form generalizable and evidence-based cancer screening guidelines, particularly with respect to cancer screening in the allograft.
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Affiliation(s)
- Atit Dharia
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Jacinthe Boulet
- Division of Cardiology, Department of Medicine, Montreal Heart Institute, Montreal, QC, Canada
| | - Vikas S Sridhar
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
| | - Abhijat Kitchlu
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, ON, Canada
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Chan MV, Huo YR, Trieu N, Mitchelle A, George J, He E, Lee AU, Chang J, Yang J. Noncontrast MRI for Hepatocellular Carcinoma Detection: A Systematic Review and Meta-analysis - A Potential Surveillance Tool? Clin Gastroenterol Hepatol 2022; 20:44-56.e2. [PMID: 33662596 DOI: 10.1016/j.cgh.2021.02.036] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 02/17/2021] [Accepted: 02/22/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS This meta-analysis investigates the diagnostic performance of non-contrast magnetic resonance imaging (MRI) for the detection of hepatocellular carcinoma (HCC). METHODS A systematic review was performed to May 2020 for studies which examined the diagnostic performance of non-contrast MRI (multi-sequence or diffusion-weighted imaging (DWI)- alone) for HCC detection in high risk patients. The primary outcome was accuracy for the detection of HCC. Random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio (LR) and negative LR. Subgroup analyses for cirrhosis and size of the lesion were performed. RESULTS Twenty-two studies were included involving 1685 patients for per-patient analysis and 2128 lesions for per-lesion analysis. Multi-sequence non-contrast MRI (NC-MRI) using T2+DWI±T1 sequences had a pooled per-patient sensitivity of 86.8% (95%CI:83.9-89.4%), specificity of 90.3% (95%CI:87.3-92.7%), and negative LR of 0.17 (95%CI:0.14-0.20). DWI-only MRI (DW-MRI) had a pooled sensitivity of 79.2% (95%CI:71.8-85.4%), specificity of 96.5% (95%CI:94.3-98.1%) and negative LR of 0.24 (95%CI:1.62-0.34). In patients with cirrhosis, NC-MRI had a pooled per-patient sensitivity of 87.3% (95%CI:82.7-91.0%) and specificity of 81.6% (95%CI:75.3-86.8%), whilst DWI-MRI had a pooled sensitivity of 71.4% (95%CI:60.5-80.8%) and specificity of 97.1% (95%CI:91.9-99.4%). For lesions <2 cm, the pooled per-lesion sensitivity was 77.1% (95%CI:73.8-80.2%). For lesions >2 cm, pooled per-lesion sensitivity was 88.5% (95%CI:85.0-91.5%). CONCLUSION Non-contrast MRI has a moderate negative LR and high specificity with acceptable sensitivity for the detection of HCC, even in patients with cirrhosis and with lesions <2 cm. Prospective trials to validate if non-contrast MRI can be used for HCC surveillance is warranted.
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Affiliation(s)
- Michael Vinchill Chan
- Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia; Concord Hospital Clinical School, The University of Sydney, Sydney, Australia
| | - Ya Ruth Huo
- Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia; Concord Hospital Clinical School, The University of Sydney, Sydney, Australia
| | - Nelson Trieu
- Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia; Concord Hospital Clinical School, The University of Sydney, Sydney, Australia
| | - Amer Mitchelle
- Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Institute for Medical Research and Department of Gastroenterology and Hepatology, Westmead Hospital, University of Sydney, Sydney, Australia
| | - Emily He
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Alice Unah Lee
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Jeff Chang
- Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, Australia
| | - Jessica Yang
- Department of Radiology, Concord Repatriation General Hospital, Sydney, Australia; Concord Hospital Clinical School, The University of Sydney, Sydney, Australia.
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Mettikanont P, Kalluri A, Bittermann T, Phillips N, Loza BL, Rosen M, Siegelman E, Furth E, Abt P, Olthoff K, Shaked A, Hoteit M, Reddy KR. The Course of LIRADS 3 and 4 Hepatic Abnormalities as Correlated With Explant Pathology: A Single Center Experience. J Clin Exp Hepatol 2022; 12:1048-1056. [PMID: 35814502 PMCID: PMC9257948 DOI: 10.1016/j.jceh.2022.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 02/23/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS The Liver Reporting and Data System (LI-RADS) is the standard classification of imaging findings of hepatic abnormalities for hepatocellular carcinoma (HCC) surveillance. We aimed to study the course of LI-RADS 3 and 4 (LR-3 and LR-4) abnormalities through correlations with explant pathology. METHODS A single center retrospective study of liver transplant recipients between January 2016 and September 2019 with HCC on explant pathology was conducted. Eligible patients were divided into three subgroups based on their LI-RADS classification: LR-3/4, LR-5 only, and combination of LR-3/4/5. RESULTS There were 116 eligible patients with 99 LR-3/4 observations (60 LR-3 and 39 LR-4); the rest had LR-5 lesions. LR-4 more often than LR-3 observations progressed to LR-5 (36% vs 12%) and with shorter duration during follow-up (median 175 days and 196 days). Mean size growth of LR-3 and LR-4 abnormalities were 2.6 and 3.8 mm; median growth rates were 0.2 and 0.4 mm/month, respectively. Numbers of HCC lesions per explant, largest HCC lesion size, and cumulative size were higher in LR-3/4/5 subgroup than LR-5 subgroup (P = 0.007, 0.007 and 0.006, respectively); 68% of LR-3 and 82% of LR-4 abnormalities were confirmed HCC on explant (P = 0.09). CONCLUSION Compared to LR-3, more LR-4 abnormalities progressed to LR-5 (12% and 36%, respectively) in a shorter time and with faster growth rate. A high proportion of LR-3 and LR-4 lesions (68% and 82%, respectively) were confirmed HCC on explant, raising the question of whether excluding HCC based on radiologic criteria alone is adequate in those with LR-3/4 abnormalities.
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Key Words
- AFP, alpha-fetoprotein
- BMI, body mass index
- CT, computed tomography
- HBV, hepatitis b virus
- HCC, hepatocellular carcinoma
- HCV, hepatitis c virus
- LI-RADS, liver reporting and data system
- LIRADS classification
- LR-3, LI-RADS 3
- LR-4, LI-RADS4
- LR-5, LI-RADS 5
- LT, liver transplantation
- MELD-Na, model for end stage liver disease sodium
- MRI, magnetic resonance imaging
- explant pathology
- hepatocellular carcinoma
- liver transplant
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | - K. Rajender Reddy
- Address for correspondence: K. Rajender Reddy, Professor of Medicine, Director of Hepatology, University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Philadelphia, PA, 19104, United States.
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Kim JH, Kang SH, Lee M, Choi HS, Jun BG, Kim TS, Choi DH, Suk KT, Kim MY, Kim YD, Cheon GJ, Baik SK, Kim DJ. Individualized surveillance of chronic hepatitis B patients according to hepatocellular carcinoma risk based on PAGE-B scores. Eur J Gastroenterol Hepatol 2021; 33:1564-1572. [PMID: 32804840 DOI: 10.1097/meg.0000000000001870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIMS Current guidelines for chronic hepatitis B (CHB) patients are to undergo surveillance for hepatocellular carcinoma (HCC) with 6-month ultrasonography. We aimed to compare detection rates of very-early-stage HCC in two groups: group A, undergoing 6-month ultrasonography versus group B, undergoing 6-month ultrasonography alternating with dynamic computed tomography (CT). METHODS This retrospective study assessed 2151 CHB patients under entecavir/tenofovir therapy from 2007 to 2016. Detection rates of very-early-stage HCC were compared between groups A/B at intermediate/high risk based on platelets, age, gender-hepatitis B scores. The primary endpoint was the proportion of patients in each group with very-early-stage HCC. Cox proportional hazards model was used to assess the effect of surveillance modalities to detect very-early-stage HCC. RESULTS Five-year cumulative HCC incidence rates in group A were 15.0% not significantly different from 18.2% in group B at high risk (P = 0.17). Detection rates of very-early-stage HCC were significantly higher in group B than in group A (P < 0.001), and surveillance using CT alternating with ultrasonography was significantly associated with detection of very-early-stage HCC (hazard ratio 3.89, P < 0.001). Among intermediate-risk patients, difference between detection rates of very-early-stage HCC in groups A and B was not significant (P = 0.30), and surveillance using CT alternating with ultrasonography was not significantly associated with detection of very-early-stage HCC (hazard ratio 1.61, P = 0.23). CONCLUSION In high-risk CHB patients, surveillance using CT alternating with ultrasonography led to higher detection rates of very-early-stage HCC compared to surveillance using ultrasonography.
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Affiliation(s)
- Ji Hyun Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Seong Hee Kang
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju
| | - Minjong Lee
- Department of Internal Medicine, Ewha Womans University College of Medicine, Ewha Womans University Seoul Hospital, Seoul
| | - Hoon Sung Choi
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Baek Gyu Jun
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung
| | - Tae Suk Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Dae Hee Choi
- Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon
| | - Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea
| | - Moon Young Kim
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju
| | - Young Don Kim
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung
| | - Gab Jin Cheon
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung
| | - Soon Koo Baik
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea
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Ahmad S, Hossain MN, Ahmadi S, Kerman K, Kraatz HB. Electrochemical distinction of neuronal and neuroblastoma cells via the phosphorylation of the cellular extracellular membrane. Anal Biochem 2021; 645:114434. [PMID: 34785194 DOI: 10.1016/j.ab.2021.114434] [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: 09/01/2020] [Revised: 10/10/2021] [Accepted: 10/21/2021] [Indexed: 11/20/2022]
Abstract
In this contribution we establish a proof of concept method for monitoring, quantifying and differentiating the extracellular phosphorylation of Human SHSY5Y undifferentiated neuronal cells and neuroblastoma cells by three prominent ectokinases PKA, PKC and Src. Herein it is demonstrated that a combination of different experimental techniques, including fluroesence microscopy, quartz crystal microscopy (QCM) and electrochemistry, can be used to detect extracellular phosphorylation levels of neuronal and neuroblastoma cells. Phosphorylation profiles of the three ectokinases, PKA, PKC and Src, were investigated using fluorescence microscopy and the number of phosphorylation sites per kinase was estimated using QCM. Finally, the phosphorylation of the extracellular membrane was determined using electrochemistry. Our results clearly demonstrate that the extracellular phosphorylation of neuronal cells differs significantly in terms of its phosphorylation profile from diseased neuroblastoma cells and the strength of surface electrochemical techniques in the differentiation process. We reveal that using electrochemistry, the percent compositions of neuronal and neuroblastoma cells can also be identified.
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Affiliation(s)
- S Ahmad
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Canada
| | - M N Hossain
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Canada
| | - S Ahmadi
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Canada
| | - K Kerman
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Canada
| | - H-B Kraatz
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, M1C 1A4, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6, Canada.
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Tan P, Grundy L, Makary P, Eng KH, Ramsay G, Bekheit M. The value of liquid biopsy in the diagnosis and staging of hepatocellular carcinoma: a systematic review. Transl Gastroenterol Hepatol 2021; 6:54. [PMID: 34805576 PMCID: PMC8573369 DOI: 10.21037/tgh.2020.01.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 01/18/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC). METHODS This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators. The primary outcome was the sensitivity and specificity of HCC detection with tumour specific single gene methylation alteration. Secondary outcomes were the comparison using specific assay methods and the effect of early vs. late stages on CTC positivity. We included patients with HCC who had samples taken from peripheral blood and had sufficient data to assess the outcome data. ASSIA, Cochrane library, EMbase, Medline, PubMed and the knowledge network Scotland were systematically searched with appropriate Mesh terms employed. The quality assessment of diagnostic accuracy studies (QUADAS) was used to ensure quality of data. Statistical analysis was performed using the 'Rev Man' meta-analysis soft ward for Windows. RESULTS The review included 36 studies, with a total of 5,853 patients. Here, we found that AFP has the highest overall diagnostic performance. The average Youden index amongst all CTC was 0.46 with a mode and median of 0.5 with highest of 0.87 and lowest of 0.01. CONCLUSIONS The available literature provides weak evidence that there is potential in the use of CTC, however the lack of a standardised procedure in the study of CTC contribute to the lack of consensus of use. Future research should include large scaled, standardized studies for the diagnostic accuracy of CTCs.
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Affiliation(s)
- Poh Tan
- Department of General Surgery, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Lisa Grundy
- Department of General Surgery, Aberdeen Royal Infirmary, Aberdeen, UK
| | - Peter Makary
- Department of General Surgery, Aberdeen Royal Infirmary, Aberdeen, UK
| | | | - George Ramsay
- Rowette institute of Health Sciences, Medical School, University of Aberdeen, Aberdeen, UK
| | - Mohamed Bekheit
- Department of General Surgery, Aberdeen Royal Infirmary, Aberdeen, UK
- Department of Surgery, El Kabbary Hospital, Alexandria, Egypt
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Nadarevic T, Giljaca V, Colli A, Fraquelli M, Casazza G, Miletic D, Štimac D. Computed tomography for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 2021; 10:CD013362. [PMID: 34611889 PMCID: PMC8493329 DOI: 10.1002/14651858.cd013362.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and fourth in terms of cancer deaths. In clinical practice, computed tomography (CT) is used as a second-line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha-foetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast-enhanced imaging study CT or magnetic resonance imaging (MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is valid to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma is, therefore, missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of CT may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CT in people with chronic liver disease, who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma. OBJECTIVES Primary: to assess the diagnostic accuracy of multidetector, multiphasic contrast-enhanced CT for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, either in a surveillance programme or in a clinical setting. Secondary: to assess the diagnostic accuracy of CT for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease. SEARCH METHODS We searched the Cochrane Hepato-Biliary Trials Register, Cochrane Hepato-Biliary Diagnostic-Test-Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index - Science until 4 May 2021. We applied no language or document-type restrictions. SELECTION CRITERIA Studies assessing the diagnostic accuracy of CT for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. DATA COLLECTION AND ANALYSIS At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS-2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and tabulated the results. We used a hierarchical meta-analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double-checked all data extractions and analyses. MAIN RESULTS We included 21 studies, with a total of 3101 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time-interval between the index test and the reference standard was rarely defined. Regarding applicability in the patient selection domain, we judged 14% (3/21) of studies to be at low concern and 86% (18/21) of studies to be at high concern owing to characteristics of the participants who were on waiting lists for orthotopic liver transplantation. CT for hepatocellular carcinoma of any size and stage: sensitivity 77.5% (95% CI 70.9% to 82.9%) and specificity 91.3% (95% CI 86.5% to 94.5%) (21 studies, 3101 participants; low-certainty evidence). CT for resectable hepatocellular carcinoma: sensitivity 71.4% (95% CI 60.3% to 80.4%) and specificity 92.0% (95% CI 86.3% to 95.5%) (10 studies, 1854 participants; low-certainty evidence). In the three studies at low concern for applicability (861 participants), we found sensitivity 76.9% (95% CI 50.8% to 91.5%) and specificity 89.2% (95% CI 57.0% to 98.1%). The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results. AUTHORS' CONCLUSIONS In the clinical pathway for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, CT has roles as a confirmatory test for hepatocellular carcinoma lesions, and for staging assessment. We found that using CT in detecting hepatocellular carcinoma of any size and stage, 22.5% of people with hepatocellular carcinoma would be missed, and 8.7% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 28.6% of people with resectable hepatocellular carcinoma would improperly not be resected, while 8% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.
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Affiliation(s)
- Tin Nadarevic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Vanja Giljaca
- Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham, UK
| | - Agostino Colli
- Department of Transfusion Medicine and Haematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Giovanni Casazza
- Dipartimento di Scienze Biomediche e Cliniche "L. Sacco", Università degli Studi di Milano, Milan, Italy
| | - Damir Miletic
- Department of Radiology , Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
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Choi HH, Rodgers SK, Fetzer DT, Wasnik AP, Millet JD, Morgan TA, Dawkins A, Gabriel H, Kamaya A. Ultrasound Liver Imaging Reporting and Data System (US LI-RADS): An Overview with Technical and Practical Applications. Acad Radiol 2021; 28:1464-1476. [PMID: 32718745 DOI: 10.1016/j.acra.2020.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 06/01/2020] [Accepted: 06/01/2020] [Indexed: 12/12/2022]
Abstract
The Ultrasound Liver Imaging Reporting and Data System (US LI-RADS), introduced in 2017 by the American College of Radiology, standardizes the technique, interpretation, and reporting of screening and surveillance ultrasounds intended to detect hepatocellular carcinoma in high-risk patients. These include patients with cirrhosis of any cause as well as subsets of patients with chronic hepatitis B viral infection. The US LI-RADS scheme is composed of an ultrasound category and a visualization score: ultrasound categories define the exam as negative, subthreshold, or positive and direct next steps in management; visualization scores denote the expected sensitivity of the exam, based on adequacy of liver visualization with ultrasound. Since its introduction, multiple institutions across the United States have implemented US LI-RADS. This review includes a background of hepatocellular carcinoma and US LI-RADS, definition of screening/surveillance population, recommendations and tips for technique, interpretation, and reporting, and preliminary outcomes analysis.
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Affiliation(s)
- Hailey H Choi
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 1001 Potrero Ave. Building 5, 1st floor, San Francisco, CA 94110.
| | - Shuchi K Rodgers
- Department of Radiology, Einstein Medical Center, Philadelphia, Pennsylvania
| | - David T Fetzer
- Department of Radiology, UT Southwestern Medical Center, Dallas Texas
| | - Ashish P Wasnik
- Department of Radiology, Michigan Medicine, University of Michigan, Arbor, Michigan
| | - John D Millet
- Department of Radiology, Michigan Medicine, University of Michigan, Arbor, Michigan
| | - Tara A Morgan
- Department of Radiology and Biomedical Imaging, University of California San Francisco, 1001 Potrero Ave. Building 5, 1st floor, San Francisco, CA 94110
| | - Adrian Dawkins
- Department of Radiology, University of Kentucky, Lexington, Kentucky
| | - Helena Gabriel
- Department of Radiology, Northwestern University, Chicago, Illinois
| | - Aya Kamaya
- Department of Radiology, Stanford University Medical Center, Stanford, California
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Adeniji N, Dhanasekaran R. Current and Emerging Tools for Hepatocellular Carcinoma Surveillance. Hepatol Commun 2021; 5:1972-1986. [PMID: 34533885 PMCID: PMC8631096 DOI: 10.1002/hep4.1823] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2021] [Revised: 08/04/2021] [Accepted: 08/30/2021] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related mortality worldwide. Early detection of HCC enables patients to avail curative therapies that can improve patient survival. Current international guidelines advocate for the enrollment of patients at high risk for HCC, like those with cirrhosis, in surveillance programs that perform ultrasound every 6 months. In recent years, many studies have further characterized the utility of established screening strategies and have introduced new promising tools for HCC surveillance. In this review, we provide an overview of the most promising new imaging modalities and biomarkers for the detection of HCC. We discuss the role of imaging tools like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) in the early detection of HCC, and describe recent innovations which can potentially enhance their applicability, including contrast enhanced ultrasound, low‐dose CT scans, and abbreviated MRI. Next, we outline the data supporting the use of three circulating biomarkers (i.e., alpha‐fetoprotein [AFP], AFP lens culinaris agglutinin‐reactive fraction, and des‐gamma‐carboxy prothrombin) in HCC surveillance, and expand on multiple emerging liquid biopsy biomarkers, including methylated cell‐free DNA (cfDNA), cfDNA mutations, extracellular vesicles, and circulating tumor cells. These promising new imaging modalities and biomarkers have the potential to improve early detection, and thus improve survival, in patients with HCC.
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Affiliation(s)
- Nia Adeniji
- Stanford School of Medicine, Stanford, CA, USA
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Lin XC, Yan Y, Lin L, Lin QF, Chen J, Lin ZY, Chen J. Magnetic resonance-guided thermal ablation for small liver malignant tumor located on segment II or IVa abutting the heart: a retrospective cohort study. Int J Hyperthermia 2021; 38:1359-1365. [PMID: 34505553 DOI: 10.1080/02656736.2021.1976851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVE This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart. METHOD The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated. RESULTS The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40-140 min), and mean follow-up time was 31.5 ± 22.2 months (6-92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively. CONCLUSION MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.
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Affiliation(s)
- Xin-Chen Lin
- Department of Interventional Radiology, People's Hospital Affiliated of Fujian Traditional Chinese Medical University, Fuzhou, China
| | - Yuan Yan
- Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Lin Lin
- Department of Operation, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Qing-Feng Lin
- Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jian Chen
- Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Zheng-Yu Lin
- Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
| | - Jin Chen
- Department of Interventional Radiology, First Affiliated Hospital of Fujian Medical University; Molecular Oncology Research Institute, First Affiliated Hospital, Fujian Medical University, Fuzhou, China
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A Radiomics Approach to Predict the Emergence of New Hepatocellular Carcinoma in Computed Tomography for High-Risk Patients with Liver Cirrhosis. Diagnostics (Basel) 2021; 11:diagnostics11091650. [PMID: 34573991 PMCID: PMC8471809 DOI: 10.3390/diagnostics11091650] [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: 07/05/2021] [Revised: 09/07/2021] [Accepted: 09/08/2021] [Indexed: 01/02/2023] Open
Abstract
Liver cirrhosis poses a major risk for the development of hepatocellular carcinoma (HCC). This retrospective study investigated to what extent radiomic features allow the prediction of emerging HCC in patients with cirrhosis in contrast-enhanced computed tomography (CECT). A total of 51 patients with liver cirrhosis and newly detected HCC lesions (n = 82) during follow-up (FU-CT) after local tumor therapy were included. These lesions were not to have been detected by the radiologist in the chronologically prior CECT (PRE-CT). For training purposes, segmentations of 22 patients with liver cirrhosis but without HCC-recurrence were added. A total of 186 areas (82 HCCs and 104 cirrhotic liver areas without HCC) were analyzed. Using univariate analysis, four independent features were identified, and a multivariate logistic regression model was trained to classify the outlined regions as "HCC probable" or "HCC improbable". In total, 60/82 (73%) of segmentations with later detected HCC and 84/104 (81%) segmentations without HCC were classified correctly (AUC of 81%, 95% CI 74-87%), yielding a sensitivity of 72% (95% CI 57-83%) and a specificity of 86% (95% CI 76-96%). In conclusion, the model predicted the occurrence of new HCCs within segmented areas with an acceptable sensitivity and specificity in cirrhotic liver tissue in CECT.
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