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Li L, Burgio MD, Fetzer DT, Ferraioli G, Lyshchik A, Meloni MF, Rafailidis V, Sidhu PS, Vilgrain V, Wilson SR, Zhou J. Contrast-Enhanced Ultrasound for Hepatocellular Carcinoma Diagnosis- AJR Expert Panel Narrative Review. AJR Am J Roentgenol 2025. [PMID: 40434167 DOI: 10.2214/ajr.25.32813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2025]
Abstract
Despite growing clinical use of contrast-enhanced ultrasound (CEUS), inconsistency remains in the modality's role in clinical pathways for hepatocellular carcinoma (HCC) diagnosis and management. This AJR Expert Panel Narrative Review provides practical insights on the use of CEUS for the diagnosis of HCC across populations, including individuals at high risk for HCC, individuals with metabolic dysfunction-associated steatotic liver disease, and remaining individuals not at high risk for HCC. Considerations addressed with respect to high-risk patients include CEUS diagnostic criteria for HCC, use of CEUS for differentiating HCC from non-HCC malignancy, use of CEUS for small (≤2 cm) lesions, use of CEUS for characterizing occult lesions on B-mode ultrasound, and use of CEUS for indeterminate lesions on CT or MRI. Representative literature addressing the use of CEUS for HCC diagnosis as well as gaps in knowledge requiring further investigation are highlighted. Throughout these discussions, the article distinguishes two broad types of ultrasound contrast agents used for liver imaging: pure blood-pool agents and a combined blood-pool and Kupffer-cell agent. Additional topics include the use of CEUS for treatment response assessment after nonradiation therapies and implications of artificial intelligence technologies. The article concludes with a series of consensus statements from the author panel.
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Affiliation(s)
- Lingling Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, China
| | - Marco Dioguardi Burgio
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, F-75018 Paris, France
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110 Clichy, France
| | - David T Fetzer
- Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, E6-230-BF, Dallas, TX 75390-9316, USA
| | - Giovanna Ferraioli
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Campus della Salute c/o Policlinico San Matteo, Viale Golgi 19, Pavia, Italy
| | - Andrej Lyshchik
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Maria Franca Meloni
- Casa di Cura Villa Igea, Department of Interventional Ultrasound, Casa di Cura Igea, Milan, Italy
| | - Vasileios Rafailidis
- Department of Radiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Paul S Sidhu
- Department of Imaging Sciences, School of Biomedical Engineering and Imaging Sciences, Faculty of Life Sciences and Medicine, King's College London, London UK; Department of Radiology, King's College Hospital NHS Foundation Trust, Denmark Hill, London UK
| | - Valerie Vilgrain
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, F-75018 Paris, France
- Department of Radiology, Hôpital Beaujon, AP-HP.Nord, 100 Boulevard du Général Leclerc, 92110 Clichy, France
| | | | - 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, Guangdong 510060, China
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Lee S, Kim YY, Shin J, Shin H, Sirlin CB, Chernyak V. Performance of LI-RADS category 5 vs combined categories 4 and 5: a systemic review and meta-analysis. Eur Radiol 2024; 34:7025-7040. [PMID: 38809263 DOI: 10.1007/s00330-024-10813-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 04/10/2024] [Accepted: 04/16/2024] [Indexed: 05/30/2024]
Abstract
OBJECTIVE Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis. METHODS MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups. CONCLUSIONS Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management. CLINICAL RELEVANCE STATEMENT This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management. KEY POINTS There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yeun-Yoon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jaeseung Shin
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyejung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, CA, USA
| | - Victoria Chernyak
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
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Lee S, Kim YY, Shin J, Roh YH, Choi JY, Chernyak V, Sirlin CB. Liver Imaging Reporting and Data System version 2018 category 5 for diagnosing hepatocellular carcinoma: an updated meta-analysis. Eur Radiol 2024; 34:1502-1514. [PMID: 37656177 DOI: 10.1007/s00330-023-10134-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 05/24/2023] [Accepted: 07/07/2023] [Indexed: 09/02/2023]
Abstract
OBJECTIVE We performed an updated meta-analysis to determine the diagnostic performance of Liver Imaging Reporting and Data System (LI-RADS, LR) 5 category for hepatocellular carcinoma (HCC) using LI-RADS version 2018 (v2018), and to evaluate differences by imaging modalities and type of MRI contrast material. METHODS The MEDLINE and Embase databases were searched for studies reporting the performance of LR-5 using v2018 for diagnosing HCC. A bivariate random-effects model was used to calculate the pooled per-observation sensitivity and specificity. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS Forty-eight studies qualified for the meta-analysis, comprising 9031 patients, 10,547 observations, and 7216 HCCs. The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC were 66% (95% CI, 61-70%) and 91% (95% CI, 89-93%), respectively. In the subgroup analysis, MRI with extracellular agent (ECA-MRI) showed significantly higher pooled sensitivity (77% [95% CI, 70-82%]) than CT (66% [95% CI, 58-73%]; p = 0.023) or MRI with gadoxetate (Gx-MRI) (65% [95% CI, 60-70%]; p = 0.001), but there was no significant difference between ECA-MRI and MRI with gadobenate (gadobenate-MRI) (73% [95% CI, 61-82%]; p = 0.495). Pooled specificities were 88% (95% CI, 80-93%) for CT, 92% (95% CI, 86-95%) for ECA-MRI, 93% (95% CI, 91-95%) for Gx-MRI, and 91% (95% CI, 84-95%) for gadobenate-MRI without significant differences (p = 0.084-0.803). CONCLUSIONS LI-RADS v2018 LR-5 provides high specificity for HCC diagnosis regardless of modality or contrast material, while ECA-MRI showed higher sensitivity than CT or Gx-MRI. CLINICAL RELEVANCE STATEMENT Refinement of the criteria for improving sensitivity while maintaining high specificity of LR-5 for HCC diagnosis may be an essential future direction. KEY POINTS • The pooled per-observation sensitivity and specificity of LR-5 for diagnosing HCC using LI-RADSv2018 were 66% and 91%, respectively. • ECA-MRI showed higher sensitivity than CT (77% vs 66%, p = 0.023) or Gx-MRI (77% vs 65%, p = 0.001). • LI-RADS v2018 LR-5 provides high specificity (88-93%) for HCC diagnosis regardless of modality or contrast material type.
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Affiliation(s)
- Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
| | - Yeun-Yoon Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeseung Shin
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yun Ho Roh
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Victoria Chernyak
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California San Diego, San Diego, CA, USA
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Zeng Q, Xie S, He X, Guo Y, Wu Y, He N, Zhang L, Yu X, Zheng R, Li K. FI-CEUS: a solution to improve the diagnostic accuracy in MRI LI-RADS-indeterminate (LR-3/4) FLLs at risk for HCC. Front Oncol 2024; 13:1225116. [PMID: 38298440 PMCID: PMC10828013 DOI: 10.3389/fonc.2023.1225116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 12/28/2023] [Indexed: 02/02/2024] Open
Abstract
Objective To evaluate the diagnostic accuracy of fusion imaging contrast-enhanced ultrasound (FI-CEUS) of magnetic resonance imaging (MRI) LI-RADS-indeterminate (LR-3/4) and conventional ultrasound undetected focal liver lesions (FLLs) in patients at risk for hepatocellular carcinoma (HCC). Methods Between February 2020 and July 2021, 71 FLLs in 63 patients were registered for diagnostic performance evaluation respectively for ultrasound-guided thermal ablation evaluation in this retrospective study. Diagnostic performance regarding FLLs was compared between FI-CEUS and contrast-enhanced MRI (CE-MRI). Results For diagnostic performance evaluation, among 71 lesions in 63 patients, the diagnostic efficacy of FI-CEUS with LI-RADS was significantly higher than that of CE-MRI (P < 0.05) in both overall and hierarchical comparison (except for the group with lesion diameter ≥2 cm). For malignant lesions, the proportion of arterial phase hyperenhancement (APHE) and washout on FI-CEUS was higher than that on CE-MRI (P < 0.05). Conclusion FI-CEUS has a high value in the precise qualitative diagnosis of small FLLs (<2 cm) of MRI LI-RADS-indeterminate diagnosis (LR-3/4) that are undetected by conventional ultrasound in patients at risk for HCC and can be a good supplementary CE-MRI diagnostic method for thermal ablation evaluation.
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Affiliation(s)
- Qingjing Zeng
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Sidong Xie
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuqi He
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuefei Guo
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuxuan Wu
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Na He
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Meizhou, China
| | - Lanxia Zhang
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Xuan Yu
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Rongqin Zheng
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Kai Li
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Wu Y, Xia C, Chen J, Qin Q, Ye Z, Song B. Diagnostic performance of magnetic resonance imaging and contrast-enhanced ultrasound in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma: a meta-analysis. Abdom Radiol (NY) 2024; 49:34-48. [PMID: 37823913 DOI: 10.1007/s00261-023-04064-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 09/11/2023] [Accepted: 09/13/2023] [Indexed: 10/13/2023]
Abstract
PURPOSE To compare the diagnostic ability between magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in distinguishing intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC). METHODS Original studies reporting the diagnostic accuracy of MRI and CEUS in differentiating ICC from HCC were identified in PubMed and EMBASE databases. Histopathological examination was used as the reference standard for tumor diagnosis. Study quality was assessed using QUADAS-2 scale. Data were extracted to calculate the pooled diagnostic sensitivity, specificity, and diagnostic odds ratio (DOR) using a bivariate random-effects model, as well as the area under the curve (AUC). Sensitivity analysis, subgroup analysis, meta-regression, and investigation of publication bias were also performed. RESULTS A total of 26 studies with 28 data subsets (18 on MRI, 10 on CEUS) were included, consisting of 4169 patients with 1422 ICC lesions and 2747 HCC lesions. Most MRI studies were performed at 3T with hepatobiliary agents, and most CEUS studies used SonoVue as the contrast agent. In MRI, the pooled sensitivity, specificity, DOR, and AUC in distinguishing ICC from HCC were 0.81 (0.79, 0.84), 0.90 (0.88, 0.91), 41.47 (24.07, 71.44), and 0.93 (0.90, 0.96), respectively. The pooled sensitivity, specificity, DOR, and AUC of CEUS were 0.88 (0.84, 0.90), 0.80 (0.78, 0.83), 42.06 (12.38, 133.23), and 0.93 (0.87, 0.99), respectively. Subgroup analysis and meta-regression analysis demonstrated significant heterogeneity among the studies associated with the type of contrast agent in MRI studies. No publication bias was found. CONCLUSION Both MRI and CEUS showed excellent diagnostic performance in differentiating ICC from HCC. CEUS showed higher pooled sensitivity and MRI showed higher pooled specificity.
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Affiliation(s)
- Yingyi Wu
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China
| | - Chunchao Xia
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China
| | - Jie Chen
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China
| | - Qin Qin
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China
| | - Zheng Ye
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China.
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, China.
- Department of Radiology, Sanya People's Hospital, Sanya, Hainan, China.
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Kang HJ, Lee JM, Kim SW. Sonazoid-enhanced ultrasonography for noninvasive imaging diagnosis of hepatocellular carcinoma: special emphasis on the 2022 KLCA-NCC guideline. Ultrasonography 2023; 42:479-489. [PMID: 37423603 PMCID: PMC10555687 DOI: 10.14366/usg.23051] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 06/02/2023] [Accepted: 06/09/2023] [Indexed: 07/11/2023] Open
Abstract
Contrast-enhanced ultrasonography (CEUS) is a noninvasive imaging modality used to diagnose hepatocellular carcinoma (HCC) based on specific imaging features, without the need for pathologic confirmation. Two types of ultrasound contrast agents are commercially available: pure intravascular agents (such as SonoVue) and Kupffer agents (such as Sonazoid). Major guidelines recognize CEUS as a reliable imaging method for HCC diagnosis, although they differ depending on the contrast agents used. The Korean Liver Cancer Association-National Cancer Center guideline includes CEUS with either SonoVue or Sonazoid as a second-line diagnostic technique. However, Sonazoid-enhanced ultrasound is associated with several unresolved issues. This review provides a comparative overview of these contrast agents regarding pharmacokinetic features, examination protocols, diagnostic criteria for HCC, and potential applications in the HCC diagnostic algorithm.
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Affiliation(s)
- Hyo-Jin Kang
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea
| | - Se Woo Kim
- Department of Radiology, Armed Forces Daejeon Hospital, Daejeon, Korea
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Lee SW, Kang MK, Zhang X. Sonazoid contrast-enhanced ultrasonography for the diagnosis of hepatocellular carcinoma: strengths and shortcomings. JOURNAL OF LIVER CANCER 2023; 23:238-240. [PMID: 37726895 PMCID: PMC10565547 DOI: 10.17998/jlc.2023.09.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Accepted: 09/12/2023] [Indexed: 09/21/2023]
Affiliation(s)
- Sung Won Lee
- Department of Gastroenterology and Hepatology, College of Medicine, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Min Kyu Kang
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Xiang Zhang
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
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Li L, Mao S, Wang J, Zheng W, Shen J, Clevert DA, Zhou J. Intraindividual Comparison of Contrast-Enhanced Ultrasound Using Perfluorobutane With Modified Criteria Versus CT/MRI LI-RADS Version 2018 for Diagnosing HCC in High-Risk Patients. AJR Am J Roentgenol 2023; 220:682-691. [PMID: 36382914 DOI: 10.2214/ajr.22.28420] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND. Previously proposed modifications to LI-RADS criteria for contrast-enhanced ultrasound (CEUS) performed using perfluorobutane contrast agent yielded increased sensitivity for hepatocellular carcinoma (HCC) without a significant decrease in specificity. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of CEUS with perfluorobutane using modified LI-RADS criteria versus contrast-enhanced CT or MRI using LI-RADS version 2018 (v2018) for characterizing lesions as HCC in high-risk patients. METHODS. This retrospective study included 171 patients (140 men, 31 women; mean age, 54 ± 12 [SD] years) at high-risk for HCC with a pathologically confirmed liver observation evaluated by both CEUS using perfluorobutane and contrast-enhanced CT or MRI between March 2020 and May 2021. A matching algorithm was used to select two patients with HCC for each patient with a non-HCC lesion. Two readers evaluated observations using previously proposed modifications to CEUS LI-RADS version 2017 that classify certain observations as LR-5 rather than as LR-4 or LR-M on the basis of the presence of Kupffer phase defect after perfluorobutane administration; two different readers evaluated observations using CT/MRI LI-RADS v2018. Each reader pair reached consensus. Diagnostic performance was evaluated. RESULTS. A total of 114 patients had HCC, 43 had a non-HCC malignancy, and 14 had a benign lesion. Modified CEUS criteria using perfluorobutane and CT/MRI LI-RADS v2018 showed no significant difference (p > .05) in sensitivity (92.1% vs 89.5%), specificity (87.7% vs 84.2%), or accuracy (90.6% vs 87.7%) of LR-5 for diagnosis of HCC. Of six observations assessed as LR-4 only by CT/MRI LI-RADS v2018, modified CEUS criteria using perfluorobutane assessed one as LR-3 (benign lesion) and five as LR-5 (all HCC). Of seven observations assessed as LR-M only by CT/MRI LI-RADS v2018, modified CEUS criteria using perfluorobutane assessed one as LR-3 (non-HCC malignancy) and six as LR-5 (all HCC). Eight of 12 observations assessed as LR-5 only by CT/MRI LI-RADS v2018 and 11 of 13 observations assessed as LR-5 only by modified CEUS criteria using perfluorobutane were HCC. CONCLUSION. The diagnostic performance of LR-5 for HCC diagnosis was not significantly different between modified CEUS criteria using perfluorobutane and CT/MRI LI-RADS v2018. CLINICAL IMPACT. The findings support the application of modified CEUS criteria using perfluorobutane for diagnosing HCC in high-risk patients.
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Affiliation(s)
- Lingling Li
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Rd E, Guangzhou, 510060 China
| | - Siyue Mao
- Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jianwei Wang
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Rd E, Guangzhou, 510060 China
| | - Wei Zheng
- Department of Ultrasound, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Rd E, Guangzhou, 510060 China
| | - Jingxian Shen
- Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Dirk-André Clevert
- Department of Radiology, Interdisciplinary Ultrasound Center, University of Munich Grosshadern Campus, Munich, Germany
| | - 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, 651 Dongfeng Rd E, Guangzhou, 510060 China
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Osama MBS, Ajay MBS, Corinne EWMSMBARDMS, Ji-Bin LMD, John REP, Andrej LMDP. Contrast-Enhanced Ultrasound LI-RADS: A Pictorial Review. ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY 2023; 7:321. [DOI: 10.37015/audt.2023.230041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
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Fraquelli M, Nadarevic T, Colli A, Manzotti C, Giljaca V, Miletic D, Štimac D, Casazza G. Contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease. Cochrane Database Syst Rev 2022; 9:CD013483. [PMID: 36053210 PMCID: PMC9438628 DOI: 10.1002/14651858.cd013483.pub2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer-related deaths. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha-foetoprotein, or both. According to guidelines, a single contrast-enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging. Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real-time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes. OBJECTIVES 1. To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting. 2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results. SEARCH METHODS We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021. SELECTION CRITERIA We included studies assessing the diagnostic accuracy of CEUS 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 We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs). MAIN RESULTS We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants. - CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence). - CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence). The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results. AUTHORS' CONCLUSIONS We found that by using CEUS, as an add-on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.
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Affiliation(s)
- Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - 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
| | - Cristina Manzotti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca´ Granda - Ospedale Maggiore Policlinico, Milan, Italy
| | - Vanja Giljaca
- Department of Gastroenterology, Heart of England NHS Foundation Trust, Birmingham, UK
| | - Damir Miletic
- Department of Radiology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Davor Štimac
- Department of Gastroenterology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Giovanni Casazza
- Department of Clinical Sciences and Community Health - Laboratory of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro", Università degli Studi di Milano, Milan, Italy
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11
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Zhou Y, Qin Z, Ding J, Zhao L, Chen Y, Wang F, Jing X. Risk Stratification and Distribution of Hepatocellular Carcinomas in CEUS and CT/MRI LI-RADS: A Meta-Analysis. Front Oncol 2022; 12:873913. [PMID: 35425706 PMCID: PMC9001845 DOI: 10.3389/fonc.2022.873913] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 02/28/2022] [Indexed: 12/05/2022] Open
Abstract
Background CEUS LI-RADS and CT/MRI LI-RADS have been used in clinical practice for several years. However, there is a lack of evidence-based study to compare the proportion of hepatocellular carcinomas (HCCs) in each category and the distribution of HCCs of these two categorization systems. Purpose The purpose of this study was to compare the proportion of HCCs between corresponding CEUS LI-RADS and CT/MRI LI-RADS categories and the distribution of HCCs and non-HCC malignancies in each category. Methods We searched PubMed, Embase, and Cochrane Central databases from January 2014 to December 2021. The proportion of HCCs and non-HCC malignancies and the corresponding sensitivity, specificity, accuracy, diagnostic odds ratio (DOR), and area under the curve (AUC) of the LR-5 and LR-M categories were determined using a random-effect model. Results A total of 43 studies were included. The proportion of HCCs in CEUS LR-5 was 96%, and that in CECT/MRI LR-5 was 95% (p > 0.05). The proportion of non-HCC malignancy in CEUS LR-M was lower than that of CT/MRI LR-M (35% vs. 58%, p = 0.01). The sensitivity, specificity, and accuracy of CEUS LR-5 for HCCs were 73%, 92%, and 78%, respectively, and of CT/MRI LR-5 for HCCs, 69%, 92%, and 76%, respectively. Conclusion With the upshift of the LI-RADS category, the proportion of HCCs increased. CEUS LR-3 has a lower risk of HCCs than CT/MRI LR-3. CEUS LR-5 and CT/MRI LR-5 have a similar diagnostic performance for HCCs. CEUS LR-M has a higher proportion of HCCs and a lower proportion of non-HCC malignancies compared with CT/MRI LR-M.
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Affiliation(s)
- Yan Zhou
- School of Medicine, Nankai University, Tianjin, China.,Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
| | - Zhengyi Qin
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
| | - Jianmin Ding
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
| | - Lin Zhao
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
| | - Ying Chen
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
| | - Fengmei Wang
- School of Medicine, Nankai University, Tianjin, China.,Department of Gastroenterology and Hepatology, Tianjin Third Central Hospital, Tianjin, China
| | - Xiang Jing
- Department of Ultrasound, Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital, Tianjin, China
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12
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Risk stratification for hepatocellular carcinoma of contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) and the diagnostic performance of LR-5 and LR-M: a systematic review and meta-analysis. Clin Radiol 2022; 77:e280-e286. [PMID: 35164930 DOI: 10.1016/j.crad.2022.01.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 01/06/2022] [Indexed: 11/18/2022]
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13
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Combination of CT/MRI LI-RADS with CEUS can improve the diagnostic performance for HCCs. Eur J Radiol 2022; 149:110199. [PMID: 35196614 DOI: 10.1016/j.ejrad.2022.110199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/29/2022] [Accepted: 02/07/2022] [Indexed: 11/19/2022]
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14
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Shin J, Lee S, Kim YY, Chung YE, Choi JY, Park MS. Contrast-enhanced ultrasound Liver Imaging Reporting and Data System category M: a systematic review and meta-analysis. Ultrasonography 2022; 41:74-82. [PMID: 34289649 PMCID: PMC8696144 DOI: 10.14366/usg.21011] [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: 01/16/2021] [Revised: 05/02/2021] [Accepted: 05/19/2021] [Indexed: 11/03/2022] Open
Abstract
PURPOSE A meta-analysis was conducted to determine the proportion of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System category M (LR-M) in hepatocellular carcinomas (HCCs) and non-HCC malignancies and to investigate the frequency of individual CEUS LR-M imaging features. METHODS The MEDLINE and Embase databases were searched from January 1, 2016 to July 23, 2020 for studies reporting the proportion of CEUS LR-M in HCC and non-HCC malignancies. The meta-analytic pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were calculated. The meta-analytic frequencies of CEUS LR-M imaging features in nonHCC malignancies were also determined. Risk of bias and applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS Twelve studies reporting the diagnostic performance of the CEUS LR-M category were identified, as well as seven studies reporting the frequencies of individual CEUS LR-M imaging features. The pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were 54% (95% confidence interval [CI], 44% to 65%) and 40% (95% CI, 28% to 53%), respectively. The pooled frequencies of individual CEUS LR-M imaging features in non-HCC malignancies were 30% (95% CI, 17% to 45%) for rim arterial phase hyperenhancement, 79% (95% CI, 66% to 90%) for early (<60 s) washout, and 42% (95% CI, 21% to 64%) for marked washout. CONCLUSION In total, 94% of CEUS LR-M lesions were malignancies, with HCCs representing 54% and non-HCC malignancies representing 40%. The frequencies of individual CEUS LR-M imaging features varied; early washout showed the highest frequency for non-HCC malignancies.
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Affiliation(s)
- Jaeseung Shin
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yeun-Yoon Kim
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Eun Chung
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jin-Young Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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15
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Park J, Lee JM, Kim TH, Yoon JH. Imaging Diagnosis of HCC: Future directions with special emphasis on hepatobiliary MRI and contrast-enhanced ultrasound. Clin Mol Hepatol 2021; 28:362-379. [PMID: 34955003 PMCID: PMC9293611 DOI: 10.3350/cmh.2021.0361] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 12/21/2021] [Indexed: 11/16/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a unique cancer entity that can be noninvasively diagnosed using imaging modalities without pathologic confirmation. In 2018, several major guidelines for HCC were updated to include hepatobiliary contrast agent magnetic resonance imaging (HBA-MRI) and contrast-enhanced ultrasound (CEUS) as major imaging modalities for HCC diagnosis. HBA-MRI enables the achievement of high sensitivity in HCC detection using the hepatobiliary phase (HBP). CEUS is another imaging modality with real-time imaging capability, and it is reported to be useful as a second-line modality to increase sensitivity without losing specificity for HCC diagnosis. However, until now, there is an unsolved discrepancy among guidelines on whether to accept “HBP hypointensity” as a definite diagnostic criterion for HCC or include CEUS in the diagnostic algorithm for HCC diagnosis. Furthermore, there is variability in terminology and inconsistencies in the definition of imaging findings among guidelines; therefore, there is an unmet need for the development of a standardized lexicon. In this article, we review the performance and limitations of HBA-MRI and CEUS after guideline updates in 2018 and briefly introduce some future aspects of imaging-based HCC diagnosis.
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Affiliation(s)
- Junghoan Park
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
| | - Tae-Hyung Kim
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University Hospital, Seoul, Republic of Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
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16
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Catania R, Chupetlovska K, Borhani AA, Maheshwari E, Furlan A. Tumor in vein (LR-TIV) and liver imaging reporting and data system (LI-RADS) v2018: diagnostic features, pitfalls, prognostic and management implications. Abdom Radiol (NY) 2021; 46:5723-5734. [PMID: 34519877 DOI: 10.1007/s00261-021-03270-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 09/02/2021] [Accepted: 09/03/2021] [Indexed: 01/27/2023]
Abstract
Vascular invasion by hepatocellular carcinoma (HCC), also known as tumor in vein (TIV), indicates highly invasive tumor behavior and is also associated with poor outcome. Because a diagnosis of TIV precludes liver transplantation, knowledge of the imaging findings to differentiate between TIV and bland thrombus is key for proper patient management. Prior versions of liver imaging reporting and data system (LI-RADS) included presence of TIV as part of LR-5 criteria. However, even if HCC is the most common liver malignancy associated with TIV, other tumors can have vascular invasion and may occur in cirrhotic patients. For these reasons, in LI-RADS v2017 LR-TIV has been introduced as a new different diagnostic category. The aim of this article is to discuss the diagnostic criteria of LR-TIV according to LI-RADS v2018 and analyze potential pitfalls encountered on daily clinical practice. Indeterminate cases and how to manage them will also be discussed.
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Affiliation(s)
- Roberta Catania
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Chicago, IL, 60611, USA.
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA.
| | - Kalina Chupetlovska
- Diagnostic Imaging Department, University Hospital Saint Ivan Rilski, Sofia, Bulgaria
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Amir A Borhani
- Department of Radiology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair Street, Chicago, IL, 60611, USA
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Ekta Maheshwari
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
| | - Alessandro Furlan
- Department of Radiology, Abdominal Imaging Division, University of Pittsburgh, 200 Lothrop St, UPMC Presbyterian Suite 200, Pittsburgh, PA, 15213, USA
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17
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Peng J, Zhang T, Wang H, Ma X. The Value of Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in the Diagnosis of Hepatocellular Carcinoma:: A Meta-Analysis. JOURNAL OF ULTRASOUND IN MEDICINE 2021; 41:1537-1547. [PMID: 34617296 DOI: 10.1002/jum.15837] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 08/30/2021] [Accepted: 09/01/2021] [Indexed: 02/05/2023]
Abstract
OBJECTIVES The aim of this study is to systematically evaluate the diagnostic ability of the contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system (LI-RADS) in hepatocellular carcinoma (HCC). METHODS We searched relevant studies from PubMed, Medline, and Embase database. After literature search, duplicate removal, and data extraction, we calculated and analyzed the pooled sensitivity, pooled specificity, pooled odds ratios of diagnostic, pooled likelihood ratio (LR) of positive and negative, and area under the curve (AUC), accuracy, and F1 score to evaluate the diagnostic value of CEUS LI-RADS for HCC. RESULTS Thirteen studies and 6491 patients were included in this analysis. The pooled sensitivity and pooled specificity were 0.72 (95% confidence interval [CI], 0.70-0.73) and 0.92 (95% CI, 0.91-0.93), respectively. The positive LR was 8.02 (95% CI, 4.93-13.06) and the negative LR was 0.31 (95% CI, 0.27-0.37). The pooled diagnostic odds ratio was 27.91 (95% CI, 15.39-50.63). The overall AUC was 0.8406 and the accuracy was 0.77. CONCLUSIONS CEUS LI-RADS is an effective and promising method to diagnose HCC.
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Affiliation(s)
- Jing Peng
- Department of Biotherapy, Cancer Center, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Tao Zhang
- Department of Biotherapy, Cancer Center, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Hang Wang
- Department of Biotherapy, Cancer Center, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center, West China Hospital and State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
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18
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Kang JH, Choi SH, Lee JS, Kim DW, Jang JK. Inter-reader reliability of contrast-enhanced ultrasound Liver Imaging Reporting and Data System: a meta-analysis. Abdom Radiol (NY) 2021; 46:4671-4681. [PMID: 34156509 DOI: 10.1007/s00261-021-03169-7] [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: 04/21/2021] [Revised: 06/05/2021] [Accepted: 06/06/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE To systematically determine the inter-reader reliability of the contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS), with emphasis on its major features for hepatocellular carcinoma (HCC) and LR-M (LI-RADS category M) features for non-HCC malignancy. METHODS MEDLINE, EMBASE, and Cochrane databases were searched from January 2016 to March 2021 to identify original articles reporting the inter-reader reliability of CEUS LI-RADS. Meta-analytic pooled kappa values (κ) were calculated for major features [nonrim arterial-phase hyperenhancement (APHE), mild and late washout], LR-M features (rim APHE, early washout), and LI-RADS categorization using the DerSimonian-Laird random-effects model. Meta-regression analysis was performed to explore any causes of study heterogeneity. RESULTS Twelve studies with a total of 2862 lesions were included. The meta-analytic pooled κ of nonrim APHE, mild and late washout, rim APHE, early washout, and LI-RADS categorization were 0.73 [95% confidence interval (CI), 0.67 - 0.79], 0.69 (95% CI, 0.54-0.84), 0.54 (95% CI, 0.37-0.71), 0.62 (95% CI, 0.45-0.79), and 0.75 (95% CI, 0.64-0.87), respectively. Compared with the major features, LR-M features had a lower meta-analytic pooled κ. Substantial study heterogeneity was noted in the LI-RADS categorization, and lesion size (p = 0.03) and the homogeneity in reader experience (p = 0.03) were significantly associated with study heterogeneity. CONCLUSIONS CEUS LI-RADS showed substantial inter-reader reliability for major features and LI-RADS categorization, but relatively lower reliability was found for LR-M features. In our opinion, the definitions of imaging features require further refinement to improve the inter-reader reliability of CEUS LI-RADS.
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Affiliation(s)
- Ji Hun Kang
- Department of Radiology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea.
| | - Ji Sung Lee
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Clinical Research Center, Asan Medical Center, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong Wook Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
| | - Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul, 05505, Republic of Korea
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Hu YX, Shen JX, Han J, Mao SY, Mao RS, Li Q, Li F, Guo ZX, Zhou JH. Diagnosis of Non-Hepatocellular Carcinoma Malignancies in Patients With Risks for Hepatocellular Carcinoma: CEUS LI-RADS Versus CT/MRI LI-RADS. Front Oncol 2021; 11:641195. [PMID: 33912456 PMCID: PMC8074676 DOI: 10.3389/fonc.2021.641195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 03/10/2021] [Indexed: 12/19/2022] Open
Abstract
Objective Data regarding direct comparison of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) and Computed Tomography/Magnetic Resonance Imaging (CT/MR) LI-RADS in diagnosis of non-hepatocelluar carcinoma (non-HCC) malignancies remain limited. Our study aimed to compare the diagnostic performance of the CEUS LI-RADS version 2017 and CT/MRI LI-RADS v2018 for diagnosing non-HCC malignancies in patients with risks for HCC. Materials and Methods In this retrospective study, 94 liver nodules pathologically-confirmed as non-HCC malignancies in 92 patients at risks for HCC from January 2009 to December 2018 were enrolled. The imaging features and the LI-RADS categories on corresponding CEUS and CT/MRI within 1 month were retrospectively analyzed according to the ACR CEUS LI-RADS v2017 and ACR CT/MRI LI-RADS v2018 by two radiologists in consensus for each algorithm. The sensitivity of LR-M category, inter-reader agreement and inter-modality agreement was compared between these two standardized algorithms. Results Ninety-four nodules in 92 patients (mean age, 54 years ± 10 [standard deviation] with 65 men [54 years ± 11] and 27 women [54 years ± 8]), including 56 intrahepatic cholangiocarcinomas, 34 combined hepatocellular cholangiocarcinomas, two adenosquamous carcinomas of the liver, one primary hepatic neuroendocrine carcinoma and one hepatic undifferentiated sarcoma were included. On CEUS, numbers of lesions classified as LR-3, LR-4, LR-5 and LR-M were 0, 1, 10 and 83, and on CT/MRI, the corresponding numbers were 3, 0, 14 and 77. There was no significant difference in the sensitivity of LR-M between these two standardized algorithms (88.3% of CEUS vs 81.9% of CT/MRI, p = 0.210). Seventy-seven lesions (81.9%) were classified as the same LI-RADS categories by both standardized algorithms (five for LR-5 and 72 for LR-M, kappa value = 0.307). In the subgroup analysis for ICC and CHC, no significant differences were found in the sensitivity of LR-M category between these two standardized algorithms (for ICC, 94.6% of CEUS vs 89.3% of CT/MRI, p = 0.375; for CHC, 76.5% of CEUS vs 70.6% of CT/MRI, p = 0. 649). Conclusion CEUS LI-RADS v2017 and CT/MRI LI-RADS v2018 showed similar value for diagnosing non-HCC primary hepatic malignancies in patients with risks.
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Affiliation(s)
- Yi-Xin Hu
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jing-Xian Shen
- Image and Minimally Invasive Intervention Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jing Han
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Si-Yue Mao
- Image and Minimally Invasive Intervention Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ru-Shuang Mao
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Qing Li
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Fei Li
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Zhi-Xing Guo
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jian-Hua Zhou
- Department of Ultrasound, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Pan J, Chen W, Zhang H, Huang X, Huang X. Contrast-Enhanced Ultrasonography versus Contrast-Enhanced Magnetic Resonance Imaging in the Diagnosis of Mediastinal Tumors. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:261-271. [PMID: 33153806 DOI: 10.1016/j.ultrasmedbio.2020.10.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 09/09/2020] [Accepted: 10/07/2020] [Indexed: 06/11/2023]
Abstract
The aim of the study was to evaluate and compare contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance imaging (CE-MRI) with respect to their value in the differential diagnosis between benign and malignant mediastinal tumors. Forty-two patients with mediastinal tumor underwent CEUS and CE-MRI respectively. The sensitivity, specificity, diagnostic coincidence rate, positive predictive value (PPV) and negative predictive value of the two methods were compared. The value of different enhancement patterns in the differential diagnosis of benign and malignant mediastinal tumors was analyzed. SonoLiver software was used to obtain the dynamic vascular pattern curve (DVPC) of the lesions, and parameters such as arrival time (AT), rise time (RT), time to peak (TTP), maximum intensity/peak intensity (IMAX) and quality of fit (QOF) were extracted from time-intensity curves for quantitative analysis. We found that (i) the specificity of CEUS was higher than that of CE-MRI, and the PPV and diagnostic coincidence rate of CEUS were equal to those of CE-MRI; (ii) the enhancement patterns and DVPC of CEUS differed between the benign and malignant groups, while there was no difference in CE-MRI enhancement intensity; and (iii) AT, RT and TTP in the malignant groups were significantly shorter, while IMAX was significantly higher. In conclusion, the application of quantitative parameters and DVPC of CEUS is worth popularizing. CEUS can be used as an effective alternative and complementary examination for patients who cannot undergo CE-MRI.
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Affiliation(s)
- Juhong Pan
- Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wenwei Chen
- Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Haidong Zhang
- Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xingyue Huang
- Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China
| | - Xin Huang
- Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, China
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Li J, Chen M, Wang ZJ, Li SG, Jiang M, Shi L, Cao CL, Sang T, Cui XW, Dietrich CF. Interobserver agreement for contrast-enhanced ultrasound of liver imaging reporting and data system: A systematic review and meta-analysis. World J Clin Cases 2020; 8:5589-5602. [PMID: 33344549 PMCID: PMC7716336 DOI: 10.12998/wjcc.v8.i22.5589] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 08/11/2020] [Accepted: 09/29/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma is the most common primary liver malignancy. From the results of previous studies, Liver Imaging Reporting and Data System (LI-RADS) on contrast-enhanced ultrasound (CEUS) has shown satisfactory diagnostic value. However, a unified conclusion on the interobserver stability of this innovative ultrasound imaging has not been determined. The present meta-analysis examined the interobserver agreement of CEUS LI-RADS to provide some reference for subsequent related research. AIM To evaluate the interobserver agreement of LI-RADS on CEUS and analyze the sources of heterogeneity between studies. METHODS Relevant papers on the subject of interobserver agreement on CEUS LI-RADS published before March 1, 2020 in China and other countries were analyzed. The studies were filtered, and the diagnostic criteria were evaluated. The selected references were analyzed using the "meta" and "metafor" packages of R software version 3.6.2. RESULTS Eight studies were ultimately included in the present analysis. Meta-analysis results revealed that the summary Kappa value of included studies was 0.76 [95% confidence interval, 0.67-0.83], which shows substantial agreement. Higgins I 2 statistics also confirmed the substantial heterogeneity (I 2 = 91.30%, 95% confidence interval, 85.3%-94.9%, P < 0.01). Meta-regression identified the variables, including the method of patient enrollment, method of consistency testing, and patient race, which explained the substantial study heterogeneity. CONCLUSION CEUS LI-RADS demonstrated overall substantial interobserver agreement, but heterogeneous results between studies were also obvious. Further clinical investigations should consider a modified recommendation about the experimental design.
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Affiliation(s)
- Jun Li
- Department of Medical Ultrasound, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Ming Chen
- Department of Medical Ultrasound, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Zi-Jing Wang
- Department of Medical Ultrasound, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Shu-Gang Li
- Department of Child, Adolescent Health and Maternal Health, School of Public Health, Capital Medical University, Beijing 100069, Beijing, China
| | - Meng Jiang
- Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Long Shi
- Department of Medical Ultrasound, The Second People's Hospital of Jiangmen, Jingmen 448000, Hubei Province, China
| | - Chun-Li Cao
- Department of Medical Ultrasound, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Tian Sang
- Department of Medical Ultrasound, The First Affiliated Hospital of Medical College, Shihezi University, Shihezi 832008, Xinjiang Uygur Autonomous Region, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Sino-German Tongji-Caritas Research Center of Ultrasound in Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Son JH, Choi SH, Kim SY, Lee SJ, Park SH, Kim KW, Won HJ, Shin YM, Kim PN. Accuracy of contrast-enhanced ultrasound liver imaging reporting and data system: a systematic review and meta-analysis. Hepatol Int 2020; 14:1104-1113. [PMID: 33170416 DOI: 10.1007/s12072-020-10102-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 10/22/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM After the introduction of the contrast-enhanced ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS), several studies have reported on its performance, but the reported data vary considerably. Therefore, we performed a systematic review and meta-analysis to determine the diagnostic performance of CEUS LI-RADS in patients at risk for hepatocellular carcinoma (HCC) and investigate the causes of study heterogeneity. METHODS Original studies published until May 30, 2020, investigating the diagnostic performance of CEUS LI-RADS were identified in the MEDLINE, EMBASE, and Cochrane library databases. Study quality was assessed using the QUADAS-2 tool. Meta-analytic summary sensitivity and specificity for the diagnosis of HCC were calculated using a bivariate random-effects model. Meta-regression analysis was performed to explore the causes of study heterogeneity. RESULTS Of the 105 articles screened, eight studies were finally analyzed (5428 hepatic observations). The summary sensitivity and specificity of CEUS LI-RADS category 5 (LR-5) for diagnosing HCC were 73% [95% confidence interval (CI) 65-79%; I2 = 93%] and 95% (95% CI 91-97%; I2 = 89%), respectively. Substantial study heterogeneity was noted in both sensitivity and specificity. Study heterogeneity was significantly associated with the proportion of cases of HCC and the type of reference standard (p ≤ 0.05). CONCLUSION CEUS LI-RADS had high pooled specificity for diagnosing HCC but suboptimal pooled sensitivity. Substantial study heterogeneity was found, which was significantly associated with the proportion of cases of HCC and the type of reference standard.
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Affiliation(s)
- Jung Hee Son
- Department of Radiology, Haeundae Paik Hospital, Inje University College of Medicine, Haeundae-ro 875, Haeundae-gu, Busan, 48108, South Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea.
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Yong Moon Shin
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Pyo-Nyun Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, South Korea
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Shin J, Lee S, Bae H, Chung YE, Choi JY, Huh YM, Park MS. Contrast-enhanced ultrasound liver imaging reporting and data system for diagnosing hepatocellular carcinoma: A meta-analysis. Liver Int 2020; 40:2345-2352. [PMID: 32722894 DOI: 10.1111/liv.14617] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma (HCC). We performed a meta-analysis to determine the diagnostic performance of the CEUS LR-5 for HCC and the pooled proportions of HCCs in each CEUS LI-RADS category. METHODS We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI-RADS. Random-effects model was used to determine summary estimates of the diagnostic performance of CEUS LR-5 and the pooled proportions of HCCs in each CEUS LI-RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per-observation sensitivity and specificity of the CEUS LR-5 for diagnosing HCC were 69% (95% confidence interval [CI], 64%-73%) and 92% (95% CI, 83%-96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0-0%) for LR-1, 1% (95% CI, 0%-4%) for CEUS LR-2, 26% (95% CI, 14%-39%) for CEUS LR-3, 77% (95% CI, 68%-86%) for CEUS LR-4, 97% (95% CI, 95%-98%) for CEUS LR-5, 57% (95% CI, 44%-69%) for CEUS LR-M and 100% (95% CI, 93%-100%) for CEUS LR-5V or TIV. CONCLUSIONS The CEUS LR-5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI-RADS categories.
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Affiliation(s)
| | - Sunyoung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Heejin Bae
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong Eun Chung
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Young Choi
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong-Min Huh
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.,Yonsei Biomedical Research Institute, Yonsei University Health System, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Zhai T, Wang C, Cui L, Du J, Zhou Z, Yang H, Yang S. Hollow Bimetallic Complex Nanoparticles for Trimodality Imaging and Photodynamic Therapy In Vivo. ACS APPLIED MATERIALS & INTERFACES 2020; 12:37470-37476. [PMID: 32814410 DOI: 10.1021/acsami.0c10131] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Hollow nanoparticles have received an enormous amount of attention in the field of nanomedicine. Herein, water-soluble hollow bimetallic complex nanoparticles, holmium(III)/iridium(III) bimetallic complex nanoparticles (Ir-Ho HNPs), were fabricated via a coordination assembly. Owing to the special metal-to-ligand charge transfer (MLCT) and the heavy-atom effect of Ir(III) in an iridium complex, Ir-Ho HNPs exhibited an intense phosphorescence and the generation of singlet oxygen (1O2). With the long electron relaxation time and high magnetic moment of Ho(III), Ir-Ho HNPs presented a high longitudinal relaxivity (r2) value (160.0 mM-1 s-1at 7.0 T). Their unique hollow structure resulted in their strong and stable ultrasound signal in an aqueous solution. As a proof of concept, Ir-Ho HNPs have been developed for the phosphorescence imaging and photodynamic therapy for living cells, ultrasound imaging, and high-field magnetic resonance imaging in vivo. Our work opened up an avenue for novel application of an iridium complex in cancer theranostics.
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Affiliation(s)
- Tianli Zhai
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
| | - Chenchen Wang
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
| | - Lili Cui
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
| | - Jing Du
- Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 201101 P. R China
| | - Zhiguo Zhou
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
| | - Hong Yang
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
| | - Shiping Yang
- The Key Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, P. R China
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