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Elias-Neto A, Gonzaga APFC, Braga FA, Gomes NBN, Torres US, D'Ippolito G. Imaging Prognostic Biomarkers in Hepatocellular Carcinoma: A Comprehensive Review. Semin Ultrasound CT MR 2024; 45:454-463. [PMID: 39067621 DOI: 10.1053/j.sult.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/30/2024]
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide with its incidence on the rise globally. This paper provides a comprehensive review of prognostic imaging markers in HCC, emphasizing their role in risk stratification and clinical decision-making. We explore quantitative and qualitative criteria derived from imaging studies, such as computed tomography (CT) and magnetic resonance imaging (MRI), which can offer valuable insights into the biological behavior of the tumor. While many of these markers are not yet widely integrated into current clinical guidelines, they represent a promising future direction for approaching this highly heterogeneous cancer. However, standardization and validation of these markers remain important challenges. We conclude by emphasizing the importance of ongoing research to enhance clinical practices and improve outcomes for patients with HCC.
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Affiliation(s)
- Abrahão Elias-Neto
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Ana Paula F C Gonzaga
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Fernanda A Braga
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Natália B N Gomes
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
| | - Ulysses S Torres
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; Department of Radiology, Grupo Fleury, São Paulo, São Paulo, Brazil.
| | - Giuseppe D'Ippolito
- Department of Diagnostic Imaging, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil; Department of Radiology, Grupo Fleury, São Paulo, São Paulo, Brazil
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Ozgul D, Piskin FC, Sozutok S, Balli HT. Validation of functional liver imaging scores derived on gadoxetic acid-enhanced MRI in hepatocellular carcinoma patients. HEPATOLOGY FORUM 2024; 6:41-46. [PMID: 40248681 PMCID: PMC11999903 DOI: 10.14744/hf.2023.2023.0024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 11/04/2023] [Accepted: 12/01/2023] [Indexed: 04/19/2025]
Abstract
Background and Aim To investigate the correlation of the functional liver imaging scores (FLIS) and the scoring system in hepatocellular carcinoma (HCC) patients. Materials and Methods Between April 2015 and December 2022, the HCC patients who underwent gadoxetic acid-enhanced MRI were analyzed. Three parameters on hepatobiliary phase images were evaluated for FLIS: liver parenchymal enhancement, biliary excretion, and signal intensity of the portal vein. The correlation between Child-Turcotte-Pugh (CTP) classification, the albumin-bilirubin (ALBI) grade, and Fibrosis-4 (F-4) score, and FLIS were analyzed. Receiver operating characteristic curve analysis was performed to demonstrate the cut-off value of FLIS for differentiating between CTP classification and ALBI grade. Results We retrospectively analyzed 178 HCC patients (144 men, 34 women; mean age, 65.9 years). A moderate negative correlation was present between CTP classification and ALBI grade, and FLIS (r=-0.596 and r=-0.513, respectively). FLIS ≤3 was determined as the most optimal criterion for differentiating CTP A or B patients from CTP C patients. Conclusion This study showed that the FLIS is a simple, non-invasive imaging marker for the assessment of liver function in HCC patients.
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Affiliation(s)
- Duygu Ozgul
- Department of Radiology, Cukurova University School of Medicine, Balcali Hospital, Adana, Turkiye
| | - Ferhat Can Piskin
- Department of Radiology, Cukurova University School of Medicine, Balcali Hospital, Adana, Turkiye
| | - Sinan Sozutok
- Department of Radiology, Cukurova University School of Medicine, Balcali Hospital, Adana, Turkiye
| | - Huseyin Tugsan Balli
- Department of Radiology, Cukurova University School of Medicine, Balcali Hospital, Adana, Turkiye
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Hu W, Lyu R, Wang D, Gao Z, Sun C, Jia K. Liver imaging reporting and data system diagnostic performance in hepatocellular carcinoma when modifying the definition of "washout" on gadoxetic acid-enhanced magnetic resonance imaging. Arab J Gastroenterol 2024; 25:58-63. [PMID: 38245474 DOI: 10.1016/j.ajg.2023.12.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 08/12/2023] [Accepted: 12/31/2023] [Indexed: 01/22/2024]
Abstract
BACKGROUND AND STUDY AIMS The sensitivity of the Liver Imaging Reporting and Data System (LI-RADS) in the diagnosis of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) was suboptimal. This study evaluated the LI-RADS diagnostic performance in HCC when modifying the definition of washout using the transition phase (TP) or hepatobiliary phase (HBP) hypointensity on EOB-MRI. PATIENTS AND METHODS This retrospective study included patients at high risk of HCC who underwent EOB-MRI from June 2016 to June 2021. Three modified LI-RADS (mLI-RADS) algorithms were formulated according to different definitions of washout as follows: (a) portal venous phase (PVP) or TP hypointensity, (b) PVP or HBP hypointensity, and (c) PVP or TP or HBP hypointensity. Diagnostic performance, including sensitivity, specificity, and accuracy, was compared between mLI-RADS and LI-RADS v2018 using McNemar's test. RESULTS A total of 379 patients with 426 pathologically confirmed hepatic observations (250 HCCs, 88 nonHCC malignancies, and 88 benign lesions) were included in our study. The sensitivity rates of mLI-RADS a-c (80.0 %, 80.8 %, and 80.8 %) were all higher than that of LI-RADS v2018 (74.4 %) (all p < 0.05). The specificity rates of mLI-RADS a-c (86.9 %, 85.8 %, and 85.8 %) were all slightly lower than that of LI-RADS v2018 (88.6 %), although no statistically significant difference was noted (all p > 0.05). The accuracies of the three mLI-RADS algorithms were the same and were all higher than that of LI-RADS v2018 (82.9 % vs. 80.3 %, all p < 0.05). CONCLUSION When the definition of washout appearance was extended to TP or HBP hypointensity on EOB-MRI, the diagnostic sensitivity of LI-RADS for HCC improved without decreasing specificity.
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Affiliation(s)
- Weijuan Hu
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China
| | - Rong Lyu
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China.
| | - Di Wang
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China
| | - Zhongsong Gao
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China
| | - Cheng Sun
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China
| | - Kefeng Jia
- Department of Radiology, The Third Central Hospital of Tianjin, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, No. 83 Jintang Road, Hedong District, Tianjin 300170, China
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Wang L, Liang M, Feng B, Li D, Cong R, Chen Z, Wang S, Ma X, Zhao X. Microvascular invasion-negative hepatocellular carcinoma: Prognostic value of qualitative and quantitative Gd-EOB-DTPA MRI analysis. Eur J Radiol 2023; 168:111146. [PMID: 37832198 DOI: 10.1016/j.ejrad.2023.111146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 09/27/2023] [Accepted: 10/06/2023] [Indexed: 10/15/2023]
Abstract
OBJECTIVES The purpose of this study was to establish a model for predicting the prognosis of patients with microvascular invasion (MVI)-negative hepatocellular carcinoma (HCC) based on qualitative and quantitative analyses of Gd-EOB-DTPA magnetic resonance imaging (MRI). MATERIALS AND METHODS Consecutive patients with MVI-negative HCC who underwent preoperative Gd-EOB-DTPA MRI between January 2015 and December 2019 were retrospectively enrolled.In total, 122 patients were randomly assigned to the training and validation groups at a ratio of 7:3. Univariate and multivariate logistic regression analyses were performed to identify significant clinical parameters and MRI features, including quantitative and qualitative parameters associated with prognosis, which were incorporated into a predictive nomogram. The end-point of this study was recurrence-free survival. Outcomes were compared between groups using the Kaplan-Meier method with the log-rank test. RESULTS During a median follow-up period of 58.86 months, 38 patients (31.15 %) experienced recurrence. Multivariate analysis revealed that lower relative enhancement ratio (RER), hepatobiliary phase hypointensity without arterial phase hyperenhancement, Liver Imaging Reporting and Data System category, mild-moderate T2 hyperintensity, and higher aspartate aminotransferase levels were risk factors associated with prognosis and then incorporated into the prognostic model. C-indices for training and validation groups were 0.732 and 0.692, respectively. The most appropriate cut-off value for RER was 1.197. Patients with RER ≤ 1.197 had significantly higher postoperative recurrence rates than those with RER > 1.197 (p = 0.004). CONCLUSION The model integrating qualitative and quantitative imaging parameters and clinical parameters satisfactorily predicted the prognosis of patients with MVI-negative HCC.
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Affiliation(s)
- Leyao Wang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Meng Liang
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Bing Feng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Rong Cong
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Zhaowei Chen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Sicong Wang
- Sicong Wang, Magnetic Resonance Imaging Research, General Electric Healthcare (China), Beijing 100176, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
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Wang Y, Yuan D, Sun H, Pan X, Lu F, Li H, Huang Y, Tang S. Non-invasive preoperative prediction of Edmondson-Steiner grade of hepatocellular carcinoma based on contrast-enhanced ultrasound using ensemble learning. Front Oncol 2023; 13:1116129. [PMID: 37476377 PMCID: PMC10354515 DOI: 10.3389/fonc.2023.1116129] [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: 12/05/2022] [Accepted: 05/15/2023] [Indexed: 07/22/2023] Open
Abstract
Purpose This study aimed to explore the clinical value of non-invasive preoperative Edmondson-Steiner grade of hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound (CEUS). Methods 212 cases of HCCs were retrospectively included, including 83 cases of high-grade HCCs and 129 cases of low-grade HCCs. Three representative CEUS images were selected from the arterial phase, portal vein phase, and delayed phase and stored in a 3-dimensional array. ITK-SNAP was used to segment the tumor lesions manually. The Radiomics method was conducted to extract high-dimensional features on these contrast-enhanced ultrasound images. Then the independent sample T-test and the Least Absolute Shrinkage and Selection Operator (LASSO) were employed to reduce the feature dimensions. The optimized features were modeled by a classifier based on ensemble learning, and the Edmondson Steiner grading was predicted in an independent testing set using this model. Results A total of 1338 features were extracted from the 3D images. After the dimension reduction, 10 features were finally selected to establish the model. In the independent testing set, the integrated model performed best, with an AUC of 0.931. Conclusion This study proposed an Edmondson-Steiner grading method for HCC with CEUS. The method has good classification performance on independent testing sets, which can provide quantitative analysis support for clinical decision-making.
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Affiliation(s)
- Yao Wang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Dongbo Yuan
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Hang Sun
- School of Information Science and Engineering, Shenyang Ligong University, Shenyang, China
| | - Xiaoguang Pan
- Computer Science and Technology, School of Information and Control Engineering, Liaoning Petrochemical University, Fushun, China
| | - Fangnan Lu
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Hong Li
- College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, China
| | - Ying Huang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Shaoshan Tang
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
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Corallo C, Bell J, Laverty A, Mohsin M, Prasad R, Albazaz R. Suspected focal nodular hyperplasia in male adults: 10-year experience from a large liver centre. Abdom Radiol (NY) 2023; 48:2292-2301. [PMID: 37043025 DOI: 10.1007/s00261-023-03896-z] [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: 01/26/2023] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/13/2023]
Abstract
PURPOSE Focal nodular hyperplasia (FNH) is commonly found in females of reproductive age. In males, the diagnosis is made more cautiously due to its lower incidence and higher incidence of hepatocellular carcinoma, which can have overlapping imaging features. Follow-up or biopsy is sometimes required. This retrospective study aims to assess management of suspected FNH in male adult patients at our institution over a 10-year period. METHODS Male adults (≥ 18 years) suspected of having FNH from January 2010-June 2020 were identified using a departmental radiology information system search. Data was collected from radiology reports and patient pathway manager. RESULTS Of 342 patients with suspected FNH, 62 were male (18.1%; F:M of 4.5:1). We only included patients investigated and followed up by MRI, total of 57 patients. Median age was 40 years (range 18-74 years). Background liver disease present in 21/57 (36.8%), majority with hepatic steatosis. Average number of lesions per patient 1.7. 22/57 (38.6%) had at least one MRI follow-up using liver-specific contrast with 7 lesions demonstrating variation in size (range growth: -3.27 mm/year to + 4 mm/year). In 7 cases, MRI was not definitive; 6 required biopsy and 1 resection. Only 2/7 demonstrated malignancy. Of the total 57 patients, 6 have deceased and none due to a misdiagnosed or mismanaged hepatic lesion. CONCLUSION FNH is relatively uncommon in males, however, our data suggests that lesions with typical MRI characteristics do not require follow-up and diagnosis can be made confidently, similar to females. Any atypical features should prompt a biopsy.
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Affiliation(s)
- Carmelo Corallo
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK.
| | - Joshua Bell
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Adam Laverty
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Maryam Mohsin
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
| | - Raj Prasad
- Department of Hepatobiliary and Transplant Surgery, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Leeds, UK
| | - Raneem Albazaz
- Department of Radiology, Leeds Teaching Hospitals NHS Trust, St. James's University Hospital, Beckett Street Harehills, Leeds, LS9 7TF, UK
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Ichinohe F, Komatsu D, Yamada A, Aonuma T, Sakai A, Shimizu M, Kurozumi M, Shimizu A, Soejima Y, Uehara T, Fujinaga Y. Classification tree analysis to evaluate the most useful magnetic resonance image type in the differentiation between early and progressed hepatocellular carcinoma. Cancer Med 2023; 12:8018-8026. [PMID: 36683176 PMCID: PMC10134385 DOI: 10.1002/cam4.5589] [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: 05/27/2022] [Revised: 11/30/2022] [Accepted: 12/17/2022] [Indexed: 01/24/2023] Open
Abstract
AIM Using classification tree analysis, we evaluated the most useful magnetic resonance (MR) image type in the differentiation between early and progressed hepatocellular carcinoma (eHCC and pHCC). METHODS We included pathologically proven 214 HCCs (28 eHCCs and 186 pHCCs) in 144 patients. The signal intensity of HCCs was assessed on in-phase (T1in) and opposed-phase T1-weighted images (T1op), ultrafast T2-weighted images (ufT2WI), fat-saturated T2-weighted images (fsT2WI), diffusion-weighted images (DWI), contrast enhanced T1-weighted images in the arterial phase (AP), portal venous phase (PVP), and the hepatobiliary phase. Fat content and washout were also evaluated. Fisher's exact test was performed to evaluate usefulness for the differentiation. Then, we chose MR images using binary logistic regression analysis and performed classification and regression tree analysis with them. Diagnostic performances of the classification tree were evaluated using a stratified 10-fold cross-validation method. RESULTS T1in, ufT2WI, fsT2WI, DWI, AP, PVP, fat content, and washout were all useful for the differentiation (p < 0.05), and AP and T1in were finally chosen for creating classification trees (p < 0.05). AP appeared in the first node in the tree. The area under the curve, sensitivity and specificity for eHCC, and balanced accuracy of the classification tree were 0.83 (95% CI 0.74-0.91), 0.64 (18/28, 95% CI 0.46-0.82), 0.94 (174/186, 95% CI 0.90-0.97), and 0.79 (95% CI 0.70-0.87), respectively. CONCLUSIONS AP is the most useful MR image type and T1in the second in the differentiation between eHCC and pHCC.
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Affiliation(s)
- Fumihito Ichinohe
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Daisuke Komatsu
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Akira Yamada
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Takanori Aonuma
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Ayumi Sakai
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Marika Shimizu
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Masahiro Kurozumi
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Akira Shimizu
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Yuji Soejima
- Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Takeshi Uehara
- Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
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Du L, Yuan J, Gan M, Li Z, Wang P, Hou Z, Wang C. A comparative study between deep learning and radiomics models in grading liver tumors using hepatobiliary phase contrast-enhanced MR images. BMC Med Imaging 2022; 22:218. [DOI: 10.1186/s12880-022-00946-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 12/02/2022] [Indexed: 12/15/2022] Open
Abstract
Abstract
Purpose
To compare a deep learning model with a radiomics model in differentiating high-grade (LR-3, LR-4, LR-5) liver imaging reporting and data system (LI-RADS) liver tumors from low-grade (LR-1, LR-2) LI-RADS tumors based on the contrast-enhanced magnetic resonance images.
Methods
Magnetic resonance imaging scans of 361 suspected hepatocellular carcinoma patients were retrospectively reviewed. Lesion volume segmentation was manually performed by two radiologists, resulting in 426 lesions from the training set and 83 lesions from the test set. The radiomics model was constructed using a support vector machine (SVM) with pre-defined features, which was first selected using Chi-square test, followed by refining using binary least absolute shrinkage and selection operator (LASSO) regression. The deep learning model was established based on the DenseNet. Performance of the models was quantified by area under the receiver-operating characteristic curve (AUC), accuracy, sensitivity, specificity and F1-score.
Results
A set of 8 most informative features was selected from 1049 features to train the SVM classifier. The AUCs of the radiomics model were 0.857 (95% confidence interval [CI] 0.816–0.888) for the training set and 0.879 (95% CI 0.779–0.935) for the test set. The deep learning method achieved AUCs of 0.838 (95% CI 0.799–0.871) for the training set and 0.717 (95% CI 0.601–0.814) for the test set. The performance difference between these two models was assessed by t-test, which showed the results in both training and test sets were statistically significant.
Conclusion
The deep learning based model can be trained end-to-end with little extra domain knowledge, while the radiomics model requires complex feature selection. However, this process makes the radiomics model achieve better performance in this study with smaller computational cost and more potential on model interpretability.
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Liang X, Shi S, Gao T. Preoperative gadoxetic acid-enhanced MRI predicts aggressive pathological features in LI-RADS category 5 hepatocellular carcinoma. Clin Radiol 2022; 77:708-716. [PMID: 35738938 DOI: 10.1016/j.crad.2022.05.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/30/2022] [Accepted: 05/19/2022] [Indexed: 11/09/2022]
Abstract
AIM To investigate whether Liver Imaging Reporting and Data System (LI-RADS) imaging features and non-LI-RADS imaging features can predict aggressive pathological features in adult patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS From February 2018 to September 2021, 236 adult patients with cirrhosis or hepatitis B virus infection in which liver cancer was suspected underwent MRI within 1 month before surgery. Significant MRI findings and alpha-fetoprotein (AFP) level predicted high-grade HCC and microvascular invasion (MVI) by univariate and multivariate logistic regression models. RESULTS The study included 112 patients with histopathologically confirmed liver cancer (≤5 cm), 35 of whom (31.3%) high-grade HCC and 42 of 112 (37.5%) patients had MVI. Mosaic architecture (odds ratio [OR] = 6.031; 95% confidence interval [CI]: 1.366, 26.626; p=0.018), coronal enhancement (OR=5.878; 95% CI: 1.471, 23.489; p=0.012), and intratumoural vessels (OR=5.278; 95% CI: 1.325, 21.020; p=0.018) were significant independent predictors of high-grade HCC. A non-smooth tumour margin (OR=10.237; 95% CI: 1.547, 67.760; p=0.016), coronal enhancement (OR=3.800; 95% CI: 1.152, 12.531; p=0.028), and peritumoural hypointensity on the hepatobiliary phase (HBP; OR=10.322; 95% CI: 2.733, 38.986; p=0.001) were significant independent predictors of MVI. CONCLUSION In high-risk adult patients with single LR-5 HCC (≤5 cm), mosaic architecture, coronal enhancement, and intratumoural vessels are independent predictors of high-grade HCC. Non-smooth tumour margin, coronal enhancement, and peritumoural hypointensity on HBP independently predicted MVI.
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Affiliation(s)
- X Liang
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China
| | - S Shi
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China
| | - T Gao
- Department of Radiology, People's Hospital of Chongqing Banan District, Banan District, Chongqing, China.
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Novel quinoline derivatives as antitumor agents against HepG2 cells: Synthesis, characterization, in silico, in vitro and docking studies. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.132325] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Li S, Xie Y, Wang G, Zhang L, Zhou W. Adaptive multimodal fusion with attention guided deep supervision net for grading hepatocellular carcinoma. IEEE J Biomed Health Inform 2022; 26:4123-4131. [PMID: 35344499 DOI: 10.1109/jbhi.2022.3161466] [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: 11/06/2022]
Abstract
Multimodal medical imaging plays a crucial role in the diagnosis and characterization of lesions. However, challenges remain in lesion characterization based on multimodal feature fusion. First, current fusion methods have not thoroughly studied the relative importance of characterization modals. In addition, multimodal feature fusion cannot provide the contribution of different modal information to inform critical decision-making. In this study, we propose an adaptive multimodal fusion method with an attention-guided deep supervision net for grading hepatocellular carcinoma (HCC). Specifically, our proposed framework comprises two modules: attention-based adaptive feature fusion and attention-guided deep supervision net. The former uses the attention mechanism at the feature fusion level to generate weights for adaptive feature concatenation and balances the importance of features among various modals. The latter uses the weight generated by the attention mechanism as the weight coefficient of each loss to balance the contribution of the corresponding modal to the total loss function. The experimental results of grading clinical HCC with contrast-enhanced MR demonstrated the effectiveness of the proposed method. A significant performance improvement was achieved compared with existing fusion methods. In addition, the weight coefficient of attention in multimodal fusion has demonstrated great significance in clinical interpretation.
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Do transition and hepatobiliary phase hypointensity improve LI-RADS categorization as an alternative washout: a systematic review and meta-analysis. Eur Radiol 2022; 32:5134-5143. [PMID: 35267090 DOI: 10.1007/s00330-022-08665-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 12/30/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The definition of washout in gadoxetate disodium-enhanced MRI (Gd-EOB-MRI) is controversial. The current Liver Imaging Reporting and Data System (LI-RADS) defines washout only in the portal venous phase on Gd-EOB-MRI, leading to low diagnostic sensitivity for HCC. We performed a meta-analysis to compare the diagnostic performance of Gd-EOB-MRI using conventional (cWO) and modified (mWO) definitions of washout. METHODS The PubMed and EMBASE databases were searched to identify studies published between January 1, 2010, and August 1, 2021, that compared the diagnostic performance of cWO and mWO for HCC. The mWOs added transition phase (TP) hypointensity (mWO-1), hepatobiliary phase (HBP) hypointensity (mWO-2), or both (mWO-3). The pooled sensitivity and specificity were calculated using a bivariate random-effects model. Study heterogeneity was explored by subgroup analysis and meta-regression analysis. RESULTS Ten comparative studies with 2391 patients were included. Compared to cWO, the overall mWO yielded significantly higher sensitivity (71% vs. 81%, p = 0.00) and lower specificity (97% vs. 93%, p = 0.01) for diagnosing HCC. The area under the curve (AUC) was 0.90 and 0.94 for the cWO and mWO, respectively. Regarding the three types of mWOs, mWO-2 showed the highest sensitivity (85%) and specificity (96%) for diagnosing HCC. mWO-2 achieved the highest AUC (0.97), followed by mWO-1 (0.90), and mWO-3 (0.89). Average reviewer experience and scanner field strength were significantly associated with study heterogeneity (p < 0.05). CONCLUSIONS Inclusion of TP and HBP hypointensity in the definition of washout improved the sensitivity with slightly lower specificity for diagnosing HCC in LI-RADS. KEY POINTS • Compared to the conventional definition of washout, studies using a modified definition had higher sensitivity (71% vs. 81%) but lower specificity (97% vs. 93%) in LI-RADS for the diagnosis of HCC. • Hepatobiliary phase hypointensity may be a preferred alternative washout for HCC diagnosis with the highest area under the curve. • Studies with experienced reviewer or 3.0T MRI showed higher sensitivity and lower specificity for diagnosing HCC when using modified washout (p < 0.05).
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Multi-phase contrast-enhanced magnetic resonance image-based radiomics-combined machine learning reveals microscopic ultra-early hepatocellular carcinoma lesions. Eur J Nucl Med Mol Imaging 2022; 49:2917-2928. [PMID: 35230493 PMCID: PMC9206604 DOI: 10.1007/s00259-022-05742-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/17/2022] [Indexed: 12/17/2022]
Abstract
Purpose
This study aimed to investigate whether models built from radiomics features based on multiphase contrast-enhanced MRI can identify microscopic pre-hepatocellular carcinoma lesions. Methods We retrospectively studied 54 small hepatocellular carcinoma (SHCC, diameter < 2 cm) patients and 70 patients with hepatocellular cysts or haemangiomas from September 2018 to June 2021. For the former, two MRI scans were collected within 12 months of each other; the 2nd scan was used to confirm the diagnosis. The volumes of interest (VOIs), including SHCCs and normal liver tissues, were delineated on the 2nd scans, mapped to the 1st scans via image registration, and enrolled into the SHCC and internal-control cohorts, respectively, while those of normal liver tissues from patients with hepatocellular cysts or haemangioma were enrolled in the external-control cohort. We extracted 1132 radiomics features from each VOI and analysed their discriminability between the SHCC and internal-control cohorts for intra-group classification and the SHCC and external-control cohorts for inter-group classification. Five radial basis-function, kernel-based support vector machine (SVM) models (four corresponding single-phase models and one integrated from the four-phase MR images) were established. Results Among the 124 subjects, the multiphase models yielded better performance on the testing set for intra-group and inter-group classification, with areas under the receiver operating characteristic curves of 0.93 (95% CI, 0.85–1.00) and 0.97 (95% CI, 0.92–1.00), accuracies of 86.67% and 94.12%, sensitivities of 87.50% and 94.12%, and specificities of 85.71% and 94.12%, respectively. Conclusion The combined multiphase MRI-based radiomics feature model revealed microscopic pre-hepatocellular carcinoma lesions. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-022-05742-8.
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Mao Y, Wang J, Zhu Y, Chen J, Mao L, Kong W, Qiu Y, Wu X, Guan Y, He J. Gd-EOB-DTPA-enhanced MRI radiomic features for predicting histological grade of hepatocellular carcinoma. Hepatobiliary Surg Nutr 2022; 11:13-24. [PMID: 35284527 PMCID: PMC8847875 DOI: 10.21037/hbsn-19-870] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 05/11/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND Prediction models for the histological grade of hepatocellular carcinoma (HCC) remain unsatisfactory. The purpose of this study is to develop preoperative models to predict histological grade of HCC based on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) radiomics. And to compare the performance between artificial neural network (ANN) and logistic regression model. METHODS A total of 122 HCCs were randomly assigned to the training set (n=85) and the test set (n=37). There were 242 radiomic features extracted from volumetric of interest (VOI) of arterial and hepatobiliary phases images. The radiomic features and clinical parameters [gender, age, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), alanine aminotransferase (ALT), aspartate transaminase (AST)] were selected by permutation test and decision tree. ANN of arterial phase (ANN-AP), logistic regression model of arterial phase (LR-AP), ANN of hepatobiliary phase (ANN-HBP), logistic regression mode of hepatobiliary phase (LR-HBP), ANN of combined arterial and hepatobiliary phases (ANN-AP + HBP), and logistic regression model of combined arterial and hepatobiliary phases (LR-AP + HBP) were built to predict HCC histological grade. Those prediction models were assessed and compared. RESULTS ANN-AP and LR-AP were composed by AST and radiomic features based on arterial phase. ANN-HBP and LR-HBP were composed by AFP and radiomic features based on hepatobiliary phase. ANN-AP + HBP and LR-AP + HBP were composed by AST and radiomic features based on arterial and hepatobiliary phases. The prediction models could distinguish between high-grade tumors [Edmondson-Steiner (E-S) grade III and IV] and low-grade tumors (E-S grade I and II) in both training set and test set. In the test set, the AUCs of ANN-AP, LR-AP, ANN-HBP, LR-HBP, ANN-AP + HBP and LR-AP + HBP were 0.889, 0.777, 0.941, 0.819, 0.944 and 0.792 respectively. The ANN-HBP was significantly superior to LR-HBP (P=0.001). And the ANN-AP + HBP was significantly superior to LR-AP + HBP (P=0.007). CONCLUSIONS Prediction models consisting of clinical parameters and Gd-EOB-DTPA-enhanced MRI radiomic features (based on arterial phase, hepatobiliary phase, and combined arterial and hepatobiliary phases) could distinguish between high-grade HCCs and low-grade HCCs. And the ANN was superior to logistic regression model in predicting histological grade of HCC.
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Affiliation(s)
- Yingfan Mao
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yong Zhu
- Department of Radiology, Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Liang Mao
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weiwei Kong
- Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yudong Qiu
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoyan Wu
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yue Guan
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Toyoda H, Yasuda S, Shiota S, Kumada T. Long-term persistence of hepatocarcinogenic potential of a non-hypervascular hypointense nodule on EOB-MRI after the eradication of hepatitis C virus. Hepatol Res 2022; 52:128-132. [PMID: 34472681 DOI: 10.1111/hepr.13707] [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: 07/01/2021] [Revised: 08/11/2021] [Accepted: 08/22/2021] [Indexed: 02/08/2023]
Abstract
Non-hypervascular hypointense nodules (NHHNs) on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have a high likelihood of hypervascularization progressing to typical hypervascular hepatocellular carcinoma (HCC). NHHNs that were present before the start of anti-hepatitis C virus (HCV) therapy is a risk marker for HCC development after achieving sustained virologic response (SVR). In this report, we show a patient without a previous history of HCC in whom HCC developed by hypervascularization of NHHN after SVR. This patient achieved SVR more than 8 years before NHHN developed into HCC, and during this time NHHN had been present but had remained unchanged in size and imaging features as shown by repeated EOB-MRI. Hepatocarcinogenic potential of NHHNs persist for a long time after SVR, despite the eradication of HCV.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shohei Shiota
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Abstract
Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; Gadoxetic acid; Gadoxetate disodium) is a hepatocyte-specific MR contrast agent. It acts as an extracellular contrast agent in the early phase after intravenous injection, and then is taken up by hepatocytes later. Using this contrast agent, we can evaluate the hemodynamics of the liver and liver tumors, and can therefore improve the detection and characterization of hepatocellular carcinoma (HCC). Gd-EOB-DTPA helps in the more accurate detection of hypervascular HCC than by other agents. In addition, Gd-EOB-DTPA can detect hypovascular HCC, which is an early stage of the multi-stage carcinogenesis, with a low signal in the hepatobiliary phase. In addition to tumor detection and characterization, Gd-EOB-DTPA contrast-enhanced MR imaging can be applied for liver function evaluation and prognoses evaluation. Thus, Gd-EOB-DTPA plays an important role in the diagnosis of HCC. However, we have to employ optimal imaging techniques to improve the diagnostic ability. In this review, we aimed to discuss the characteristics of the contrast media, optimal imaging techniques, diagnosis, and applications.
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Affiliation(s)
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine
| | - Masatoshi Hori
- Department of Radiology, Kobe University Graduate School of Medicine
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Inadequate Ultrasound Examination in Hepatocellular Carcinoma Surveillance: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:jcm10163535. [PMID: 34441831 PMCID: PMC8397222 DOI: 10.3390/jcm10163535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 12/24/2022] Open
Abstract
We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence of inadequate US was calculated using a random effects model, and subgroup analyses were performed. The pooled odds ratio (OR) was calculated for each risk factor for inadequate US. Six eligible articles were identified from 756 screened articles (4250 patients). The pooled incidence of inadequate US was 21.5%. Significantly higher rates of inadequate US were noted in studies including patients with and without hepatic observations compared with those evaluating only patients with hepatic observations (23.2% vs. 18.8%), studies using US alone compared with US plus alpha-fetoprotein (28.0% vs. 20.8%), and those using pathology and imaging as a reference standard compared with imaging only (23.2% vs. 17.9%). Nonalcoholic steatohepatitis (OR = 2.3 (1.07–4.84)), Child–Pugh B cirrhosis (OR = 2.2 (1.10–4.37)), and high body mass index (OR = 2.2 (1.12–4.24)) were significant risk factors for inadequate US (p ≤ 0.04). In patients at risk of HCC, 21.5% of US surveillance was inadequate. An alternative surveillance modality might be considered in patients with risk factors.
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Xiong J, Luo J, Bian J, Wu J. Overall diagnostic accuracy of different MR imaging sequences for detection of dysplastic nodules: a systematic review and meta-analysis. Eur Radiol 2021; 32:1285-1296. [PMID: 34357448 DOI: 10.1007/s00330-021-08022-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 03/24/2021] [Accepted: 04/27/2021] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN). METHODS PubMed, Cochrane Library, and Web of Science were systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T2WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73-0.87), 0.90 (95%CI, 0.86-0.93), 7.04 (95%CI, 4.49-11.04), and 0.24 (95%CI, 0.17-0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84-0.93), 0.75 (0.72-0.79), 3.72 (2.51-5.51), and 0.17 (0.12-0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72-0.83), 0.60 (0.55-0.65), 2.19 (1.55-3.10), and 0.36 (0.23-0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71-0.82), 0.92 (0.89-0.94), 8.74 (5.91-12.92), and 0.24 (0.14-0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN. CONCLUSION MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN. KEY POINTS • MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma. • Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before. • Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.
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Affiliation(s)
- Jingtong Xiong
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China
| | - Jiawen Luo
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China.
| | - Jie Bian
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China
| | - Jianlin Wu
- Department of Radiology, Affiliated Zhongshan Hospital of Dalian University, No. 6, Jiefang Road, Zhongshan District, Dalian, 116001, Liaoning Province, China
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Chen R, Bai Y, Liu T, Zhang G, Han Y, Chen L, Gao H, Wei W, Wang M. Evaluation of Glypican-3 Expression in Hepatocellular Carcinoma by Using IDEAL IQ Magnetic Resonance Imaging. Acad Radiol 2021; 28:e227-e234. [PMID: 32540197 DOI: 10.1016/j.acra.2020.05.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 05/14/2020] [Accepted: 05/14/2020] [Indexed: 12/11/2022]
Abstract
RATIONALE AND OBJECTIVES To investigate the value of iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL IQ) and gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for evaluating Glypican-3 (GPC3) expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS Seventy-six patients with histopathologic diagnosis of HCC were retrospectively included in this study. In all patients IDEAL IQ and Gd-EOB-DTPA-enhanced MRI were performed preoperatively using a 3 T MRI system. For an identical slice through the liver of each patient a region of interest was drawn on the tumor in the hepatobiliary phase image and copied to the R2* map and fat fraction map produced by IDEAL IQ. A Mann-Whitney U test was used to compare the region of interest values of R2*, fat fraction and uptake of Gd-EOB-DTPA values between patients with positive and negative GPC3 expression HCC. Receiver operating characteristic analysis was used to determine the diagnostic performances of each of the MRI parameters in evaluating GPC3 expression and histological grade in HCC. RESULTS R2* value was significantly higher in cases of positive than negative GPC3 expression HCCs (p < 0.001), whereas there were no significant differences in fat fraction and uptake of Gd-EOB-DTPA between the 2 groups (both p > 0.05). R2* value had higher areas under receiver operating characteristic (0.881), sensitivity (85.96%), and specificity (84.21%) compared to the fat fraction and uptake of Gd-EOB-DTPA. CONCLUSION R2* value yielded from IDEAL IQ could reliably predict GPC3 expression in HCC prior to surgery.
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Affiliation(s)
- Rushi Chen
- Academy of Medical Sciences & the People's Hospital of Zhengzhou University, Zhengzhou, China
| | - Yan Bai
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Taiyuan Liu
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Ge Zhang
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Yanhong Han
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Lijuan Chen
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Haiyan Gao
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Wei Wei
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China
| | - Meiyun Wang
- Department of Medical Imaging, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou, 450003, China.
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Wang W, Wu SS, Zhang JC, Xian MF, Huang H, Li W, Zhou ZM, Zhang CQ, Wu TF, Li X, Xu M, Xie XY, Kuang M, Lu MD, Hu HT. Preoperative Pathological Grading of Hepatocellular Carcinoma Using Ultrasomics of Contrast-Enhanced Ultrasound. Acad Radiol 2021; 28:1094-1101. [PMID: 32622746 DOI: 10.1016/j.acra.2020.05.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 05/12/2020] [Accepted: 05/15/2020] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To develop an ultrasomics model for preoperative pathological grading of hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound (CEUS). MATERIAL AND METHODS A total of 235 HCCs were retrospectively enrolled, including 65 high-grade and 170 low-grade HCCs. Representative images of four-phase CEUS were selected from the baseline sonography, arterial, portal venous, and delayed phase images. Tumor ultrasomics features were automatically extracted using Ultrasomics-Platform software. Models were built via the classifier support vector machine, including an ultrasomics model using the ultrasomics features, a clinical model using the clinical factors, and a combined model using them both. Model performances were tested in the independent validation cohort considering efficiency and clinical usefulness. RESULTS A total of 1502 features were extracted from each image. After the reproducibility test and dimensionality reduction, 25 ultrasomics features and 3 clinical factors were selected to build the models. In the validation cohort, the combined model showed the best predictive power, with an area under the curve value of 0.785 (95% confidence interval [CI] 0.662-0.909), compared to the ultrasomics model of 0.720 (95% CI 0.576-0.864) and the clinical model of 0.665 (95% CI 0.537-0.793). Decision curve analysis suggested that the combined model was clinically useful, with a corresponding net benefit of 0.760 compared to the other two models. CONCLUSION We presented an ultrasomics-clinical model based on multiphase CEUS imaging and clinical factors, which showed potential value for the preoperative discrimination of HCC pathological grades.
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Toyoda H, Yasuda S, Shiota S. Editorial: is there a 'precursor' HCC lesion and can it be detected by hepatobiliary contrast-enhanced magnetic resonance imaging? Authors' reply. Aliment Pharmacol Ther 2021; 54:204-205. [PMID: 34170540 DOI: 10.1111/apt.16466] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shohei Shiota
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
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22
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Vutien P, Ioannou GN. Editorial: is there a 'precursor' HCC lesion and can it be detected by hepatobiliary contrast-enhanced magnetic resonance imaging? Aliment Pharmacol Ther 2021; 54:202-203. [PMID: 34170532 DOI: 10.1111/apt.16455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Philip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA.,Department of Medicine Veterans Affairs Puget Sound Healthcare System, University of Washington, Seattle, WA, USA
| | - George N Ioannou
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA.,Department of Medicine Veterans Affairs Puget Sound Healthcare System, University of Washington, Seattle, WA, USA
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Gupta P, Soundararajan R, Patel A, Kumar-M P, Sharma V, Kalra N. Abbreviated MRI for hepatocellular carcinoma screening: A systematic review and meta-analysis. J Hepatol 2021; 75:108-119. [PMID: 33548385 DOI: 10.1016/j.jhep.2021.01.041] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND & AIMS Biannual ultrasound has poor sensitivity for hepatocellular carcinoma (HCC) screening. MRI is accurate for the detection of HCC, but a complete MRI is not feasible as a screening tool. Abbreviated MRI (AMRI) is an acceptable alternative. The diagnostic performance of different AMRI protocols is not known. We performed a systematic review to determine the diagnostic accuracy of AMRI for HCC screening. METHODS We searched the MEDLINE and EMBASE databases for studies reporting the diagnostic accuracy of AMRI for HCC screening. The pooled sensitivity and specificity of different AMRI protocols were calculated based on a random intercept logistic regression model. The diagnostic performance of AMRI was compared with ultrasound. Study quality was assessed using the QUADAS-2 tool. RESULTS Of the 11,327 studies screened by titles, 15 studies (3 prospective and 12 retrospective: 2,807 patients, 917 with HCC) were included in the final analysis. The pooled per-patient sensitivity and specificity were 86% (95% CI 84-88%, I2 0%) and 94% (95% CI 91-96%, I2 83%), respectively. Pooled per-lesion sensitivity was 77% (95% CI 74-81%, I2 8%). There was no influence of study type, screening setting, reference standard, and presence and etiology of cirrhosis on the performance of AMRI. The sensitivity of AMRI for detection of HCC <2 cm was lower than that for HCC ≥2 cm (69% vs. 86%). The sensitivity and specificity of non-contrast AMRI were comparable to contrast-enhanced AMRI (86% and 94% vs. 87% and 94%, respectively). The diagnostic performance of different non-contrast AMRI and contrast-enhanced AMRI protocols was comparable. The sensitivity of ultrasound was lower than AMRI (53% vs. 82%). CONCLUSIONS AMRI has high sensitivity and specificity for HCC screening. Different AMRI protocols have comparable diagnostic performance. LAY SUMMARY Abbreviated MRI (AMRI) has been suggested as an alternative to ultrasound and complete MRI for hepatocellular carcinoma (HCC) screening. Our study results showed that AMRI has a high per-patient and per-lesion sensitivity for HCC. Although the sensitivity of AMRI for detection of HCC <2 cm is considerably lower than for HCC ≥2 cm, it is substantially higher than ultrasound, making it a potential alternative for HCC screening in high-risk populations.
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Affiliation(s)
- Pankaj Gupta
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012.
| | - Raghuraman Soundararajan
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012
| | - Ankur Patel
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012
| | - Praveen Kumar-M
- Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012
| | - Vishal Sharma
- Gastroenterology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012
| | - Naveen Kalra
- Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India-160012
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Kim H, Choi J, Yu DY, Choi HJ. Expression of Organic Anion Transporting Polypeptides in an H-Ras 12V Transgenic Mouse Model of Spontaneous Hepatocellular Carcinoma. Yonsei Med J 2021; 62:622-630. [PMID: 34164960 PMCID: PMC8236347 DOI: 10.3349/ymj.2021.62.7.622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/29/2021] [Accepted: 04/06/2021] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Expression of organic anion transporting polypeptides (OATPs) 1B1/1B3 in hepatocellular carcinoma (HCC) induces a paradoxical enhancement of gadoxetic acid on liver magnetic resonance imaging (MRI). We examined the expression profile of OATPs with regard to tumor differentiation in a genetically modified H-Ras 12V mouse model of spontaneous HCC that undergoes multistep hepatocarcinogenesis with minimal inter-individual variation. MATERIALS AND METHODS Tumor nodules were harvested from transgenic H-Ras 12V mice. Hematoxylin and eosin-stained slides were examined for tumor differentiation and high-grade pathological components (tumor necrosis, thickened trabeculae, or vascular invasion). Immunohistochemistry of OATP 1B1/1B3 was performed, and OATP expression was assessed. RESULTS We examined well-differentiated HCCs (n=59) in which high-grade pathological components were absent (n=49) or present (n=10). Among the well-differentiated HCCs without high-grade pathological components (n=49), OATP expression was negative, weak positive, and moderate positive in 23, 17, and nine cases, respectively. Among the well-differentiated HCCs with high-grade pathological components (n=10), OATP expression was negative, weak positive, and moderate positive in one, two, and seven cases, respectively. The ratio of positive OATP 1B1/1B3 expressing tumors was higher in HCCs with high-grade pathological components than in those without high-grade pathological components (p=0.004). CONCLUSION Our findings support those of previous clinical studies that have reported the frequent appearance of gadoxetic acid-enhanced MRI in moderately differentiated HCC.
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Affiliation(s)
- Honsoul Kim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea
| | - Junjeong Choi
- Department of Pharmacy, College of Pharmacy, Yonsei Institute of Pharmaceutical Science, Yonsei University, Incheon, Korea
| | - Dae Yeul Yu
- Genome Editing Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea
| | - Hye Jin Choi
- Division of Oncology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
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Toyoda H, Yasuda S, Shiota S, Sone Y, Maeda A, Kaneoka Y, Kumada T, Tanaka J. Pretreatment non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of hepatocellular carcinoma development after sustained virologic response in HCV infection. Aliment Pharmacol Ther 2021; 53:1309-1316. [PMID: 33896023 DOI: 10.1111/apt.16382] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2021] [Revised: 02/27/2021] [Accepted: 04/08/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Identification of risk factors for the development of hepatocellular carcinoma (HCC) after a sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection is urgently needed for HCC surveillance. AIMS To evaluate whether the presence of non-hypervascular hypointense nodules (NHHNs) depicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) before direct-acting antivirals (DAAs) therapy is a risk factor for de novo HCC development after SVR. METHODS The presence of NHHNs was examined with EOB-MRI before the start of DAA therapy in 383 patients with HCV infection who achieved SVR. The incidence of de novo HCC after SVR was compared between patients with versus without NHHNs. RESULTS NHHNs were detected before DAA therapy in 32 patients (8.4%). The incidence of de novo HCC after SVR was significantly higher in patients with NHHNs than in those without (1-, 3-, 5-year incidence, 9.8%, 24.2% and 41.6% vs. 0%, 1.2% and 4.4%, P < 0.0001). The presence of NHHNs before DAA therapy (adjusted HR, 10.86; 95% CI, 4.03-31.64) and cirrhosis (adjusted HR, 7.23; 95% CI, 1.88-35.85) were independently associated with a higher incidence of HCC after SVR. A higher incidence of de novo HCC after SVR remained after adjustment for age, gender, regular alcohol intake, diabetes, cirrhosis, FIB-4 index and serum alpha-foetoprotein with inverse probability of treatment weighting. CONCLUSIONS This study confirmed that the presence of NHHNs before DAA therapy is a strong risk factor for the development of de novo HCC after SVR.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Shohei Shiota
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
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Wang F, Numata K, Okada M, Chuma M, Nihonmatsu H, Moriya S, Nozaki A, Ogushi K, Luo W, Ruan L, Nakano M, Otani M, Inayama Y, Maeda S. Comparison of Sonazoid contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid MRI for the histological diagnosis of hepatocellular carcinoma. Quant Imaging Med Surg 2021; 11:2521-2540. [PMID: 34079721 DOI: 10.21037/qims-20-685] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Background This study aimed to compare the value of Sonazoid contrast-enhanced ultrasound (SCEUS) with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid magnetic resonance imaging (EOB-MRI) for histological grading diagnosis, especially for early hepatocellular carcinoma (eHCC). Methods A total of 163 histopathologically confirmed HCC lesions were retrospectively collected, including 71 eHCCs (27 hypervascular, 44 non-hypervascular) and 92 advanced HCCs (adHCC) (73 hypervascular, 19 non-hypervascular). We performed SCEUS to evaluate the lesions' vascularity during the portal phase (PP) and the echogenicity during the post-vascular phase (PVP). EOB-MRI was used to determine the signal intensity between lesions and the surrounding liver parenchyma on unenhanced T1-weighted images (pre-contrast ratio) in the hepatobiliary phase (HBP) (post-contrast ratio). Results For the PP and PVP of SCEUS (for all lesions), the pre-and post-contrast ratios of EOB-MRI (for all hypervascular lesions) showed statistical differences in the diagnosis of some (but not all) histological grades. For the diagnosis of eHCC, isoechogenicity in the PVP achieved the best diagnostic efficacy [area under the receiver operating characteristic curve (AUC) =0.892]. Whether used independently or in a combination of any form, all indicators failed to produce a higher diagnostic efficacy than PVP. Post- (≥0.610) and pre-contrast ratios (≥0.981) yielded acceptable diagnostic efficacy, with, respectively, accuracy levels of 69.3% and 75.5% and AUC values of 0.719 and 0.736. For eHCC diagnosis, the post-contrast ratio (≥0.625) and combined diagnosis using pre- (≥0.907) and post-contrast ratios (≥0.609) revealed the highest sensitivity (92.6%) for hypervascular lesions and perfect specificity (100%) for non-hypervascular lesions. Conclusions Unenhanced T1-weighted images and the HBP of EOB-MRI [regardless of the vascularity in the arterial phase (AP)], and the PP and PVP of SCEUS showed their value in the histological grading diagnosis of HCC. In particular, isoechogenicity in the PVP may have promising diagnostic utility for eHCC.
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Affiliation(s)
- Feiqian Wang
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.,Ultrasound Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Masahiro Okada
- Department of Radiology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Hiromi Nihonmatsu
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Katsuaki Ogushi
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Wen Luo
- Department of Ultrasound, Xijing Hospital, Air Force Military Medical University, Xi'an, China
| | - Litao Ruan
- Ultrasound Department, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Masayuki Nakano
- Tokyo Central Pathology Laboratory, Utsukimachi, Hachioji, Japan
| | - Masako Otani
- Division of Diagnostic Pathology, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Yoshiaki Inayama
- Division of Diagnostic Pathology, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan
| | - Shin Maeda
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
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Kudo M, Kawamura Y, Hasegawa K, Tateishi R, Kariyama K, Shiina S, Toyoda H, Imai Y, Hiraoka A, Ikeda M, Izumi N, Moriguchi M, Ogasawara S, Minami Y, Ueshima K, Murakami T, Miyayama S, Nakashima O, Yano H, Sakamoto M, Hatano E, Shimada M, Kokudo N, Mochida S, Takehara T. Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update. Liver Cancer 2021; 10:181-223. [PMID: 34239808 PMCID: PMC8237791 DOI: 10.1159/000514174] [Citation(s) in RCA: 423] [Impact Index Per Article: 105.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 12/23/2020] [Indexed: 02/06/2023] Open
Abstract
The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other's work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan,*Masatoshi Kudo,
| | | | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuya Kariyama
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Yasuharu Imai
- Department of Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Namiki Izumi
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Michihisa Moriguchi
- Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takamichi Murakami
- Department of Radiology, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shiro Miyayama
- Department of Diagnostic Radiology, Fukui-ken Saiseikai Hospital, Fukui, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan
| | - Hirohisa Yano
- Department of Pathology, Kurume University School of Medicine, Kurume, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Etsuro Hatano
- Department of Gastroenterological Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Tetsuo Takehara
- Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
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Wang F, Numata K, Chuma M, Nihonmatsu H, Moriya S, Nozaki A, Ogushi K, Fukuda H, Okada M, Ruan L, Luo W, Koizumi N, Nakano M, Otani M, Inayama Y, Maeda S. The value of hepatobiliary phase in EOB-MRI in predicting hypervascularization outcome of non-hypervascular hypointense lesions in high-risk patients for hepatocellular carcinoma. Abdom Radiol (NY) 2021; 46:2527-2539. [PMID: 33388895 DOI: 10.1007/s00261-020-02881-0] [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: 10/02/2020] [Revised: 11/20/2020] [Accepted: 11/25/2020] [Indexed: 11/24/2022]
Abstract
PURPOSE To estimate the role of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI (EOB-MRI) in predicting hypervascularization outcome of non-hypervascular hypointense hepatic lesions in high-risk patients for hepatocellular carcinoma (HCC). METHODS Under the premise of non-hyperenhance in arterial phase (AP) and hypointensity in hepatobiliary phase (HBP) of EOB-MRI, 29 fresh lesions from 22 patients with chronic viral hepatitis (median (range) age: 69(57-82) years) were prospectively enrolled. During continuously followed-up by EOB-MRI, lesional vascularity in AP, the signal intensity (SI) ratios of lesions-to-parenchyma in HBP images (post-contrast ratio) and adjusted enhancement with reference of unenhanced images (EOB enhancement ratio) were examined. RESULTS After 644 (220-2912) days of follow-up, 20 lesions changed into hyperenhancement in AP of EOB-MRI (hypervascularized group), while nine remained non-hyperenhanced (maintained non-hypervascular group). There is no statistical difference of post-contrast ratio at the initial detection. The post-contrast ratios in hypervascularized group were different between each follow-up time point when followed-up ≥ three (P < 0.01) and four (P < 0.05) times, and exposed a linear downward trend with time. Between the hypervascularized and maintained non-hypervascular groups, there were significant differences in the post-contrast ratio at endpoint for three-times' follow-up (P < 0.001); and at the second (P = 0.037), third follow-up time points (P = 0.005), endpoint (P = 0.005) for four-times' follow-up. EOB enhancement ratio showed inter-group difference only at endpoint for three-times' follow-up (P = 0.008). CONCLUSION For non-hypervascular, HBP hypointense hepatic lesions, decreasing trend of SI in HBP may early predict unfavorable hypervascularized outcome.
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Affiliation(s)
- Feiqian Wang
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
- Ultrasound Department, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan.
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Hiromi Nihonmatsu
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Satoshi Moriya
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Katsuaki Ogushi
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Hiroyuki Fukuda
- Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Masahiro Okada
- Department of Radiology, Nihon University School of Medicine, 30-1 Oyaguchi kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Litao Ruan
- Ultrasound Department, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277 West Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Wen Luo
- Department of Ultrasound, Xijing Hospital, Air Force Military Medical University, No. 127 Changle West Road, Xi'an, 710032, Shaanxi, People's Republic of China
| | - Norihiro Koizumi
- Department of Mechanical and Intelligent Systems Engineering, Graduate School of Informatics and Engineering, The University of Electro-Communications, Choufu, 182-8585, Japan
| | - Masayuki Nakano
- Tokyo Central Pathology Laboratory, 838-1, Utsukimachi, Hachioji, 192-0024, Japan
| | - Masako Otani
- Division of Diagnostic Pathology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Yoshiaki Inayama
- Division of Diagnostic Pathology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa, 232-0024, Japan
| | - Shin Maeda
- Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
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Morisaka H, Motosugi U, Ichikawa S, Ichikawa T, Kondo T, Onishi H. Uptake of gadoxetic acid in hepatobiliary phase magnetic resonance imaging and transporter expression in hypovascular hepatocellular nodules. Eur J Radiol 2021; 138:109669. [PMID: 33770738 DOI: 10.1016/j.ejrad.2021.109669] [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: 10/29/2020] [Revised: 03/04/2021] [Accepted: 03/10/2021] [Indexed: 11/30/2022]
Abstract
AIMS To evaluate the association between contrast patterns on gadoxetic acid-enhanced hepatobiliary phase (HBP) MR images and transporter expression in surgically resected hypovascular hepatocellular nodules including early hepatocellular carcinomas (HCCs). METHODS Forty-two hypovascular hepatic nodules and 43 hypervascular HCCs as a control were included in this retrospective study. Contrast of the nodules on HBP images was graded as hypo-, iso-, or hyperintense. Histopathological assessment was performed in the context of multistep hepatocarcinogenesis. Immunohistochemical staining of organic anion transporter 1B3 (OATP1B3) and multidrug resistance protein 2 (MRP2) was performed. Cramer's coefficient was used to determine the linear relationship between contrast grades and transporter expression, and the Cochran-Armitage trend test was used to determine the relationship between transporter expression and progression of multistep hepatocarcinogenesis. RESULTS Moderate linear relationships between contrast grades and OATP1B3 expression were observed for both hypo- and hypervascular nodules. OATP1B3 expression was negatively correlated with the progression of multistep hepatocarcinogenesis. MRP2 expression was not associated with the contrast grades or histopathological results. CONCLUSION OATP1B3 expression was associated with contrast grades of hepatocellular nodules observed in HBP image of gadoxetic acid-enhanced MRI in the hypovascular hepatocellular nodules and was negatively correlated with hepatocarcinogenesis.
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Affiliation(s)
- Hiroyuki Morisaka
- Department of Radiology, University of Yamanashi, 409-3898, Shimokato, Chuo, Yamanashi, Japan.
| | - Utaroh Motosugi
- Department of Radiology, University of Yamanashi, 409-3898, Shimokato, Chuo, Yamanashi, Japan; Department of Radiology, Kofu-Kyoritsu Hospital, 400-0034, Takara, Kofu, Yamanashi, Japan
| | - Shintaro Ichikawa
- Department of Radiology, University of Yamanashi, 409-3898, Shimokato, Chuo, Yamanashi, Japan
| | - Tomoaki Ichikawa
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University, 371-8511, Showa, Maebashi, Gunma, Japan
| | - Tetsuo Kondo
- Department of Human Pathology, University of Yamanashi, 409-3898, Shimokato, Chuo, Yamanashi, Japan
| | - Hiroshi Onishi
- Department of Radiology, University of Yamanashi, 409-3898, Shimokato, Chuo, Yamanashi, Japan
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30
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Weng S, Xu X, Li Y, Yan C, Chen J, Ye R, Zhu Y, Wen L, Hong J. Quantitative analysis of multiphase magnetic resonance images may assist prediction of histopathological grade of small hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:1023. [PMID: 32953823 PMCID: PMC7475488 DOI: 10.21037/atm-20-2874] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Background The aim of the study was to investigate whether preoperative quantitative analysis of multiphase magnetic resonance images may assist in predicting the pathological grade of small hepatocellular carcinoma (HCC). Methods A total of 49 patients with small HCCs (≤3 cm) underwent multiphase magnetic resonance imaging (MRI) and were retrospectively reviewed. Routine unenhanced and post gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI were preoperatively performed. Signal intensity (SI) was measured within the designated region of interest (ROI) including those of the lesion and paraspinous muscles. The lesion-to-paraspinous muscle relative contrast ratio (RCR) on T2-weighted (T2W) imaging, diffusion-weighted (DW) imaging, and dynamic phase Gd-BOPTA-enhanced T1W (T1-weighted) imaging were calculated, and statistical analysis was performed to determine the predictive power for the histological grade. Results In all, 49 cases were included comprising 3 well-differentiated (WD) HCCs, 36 moderately differentiated (MD) HCCs, and 10 poorly differentiated (PD) HCCs. There was a negative correlation between the RCR and pathological grade of small HCC in the arterial phase [correlation coefficient (ρ)=-0.305, P<0.05]. However, there was no correlation between RCR in other phases and pathological grade (P>0.05 for all). There was also no correlation between tumor margin, tumor location, cystic/necrotic change, intratumoral fat, enhancement pattern, tumor capsule, tumor boundary or tumor size, and any of the differentiation categories (P>0.05 for all). Conclusions The lesion-to-paraspinous muscle RCR on arterial phase Gd-BOPTA-enhanced T1W imaging may be useful for the prediction of the histological characteristics of small HCC.
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Affiliation(s)
- Shuping Weng
- Department of Radiology, Fujian Maternity and Child Health Hospital, Fuzhou, China
| | - Xuru Xu
- Department of Radiology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, China.,Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yueming Li
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China.,Key Laboratory of Radiation Biology (Fujian Medical University), Fujian Province University, Fuzhou
| | - Chuan Yan
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jianwei Chen
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Rongping Ye
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Yuemin Zhu
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Liting Wen
- Department of Radiology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Jinsheng Hong
- Key Laboratory of Radiation Biology (Fujian Medical University), Fujian Province University, Fuzhou.,Department of Radiation Oncology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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31
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Feng M, Zhang M, Liu Y, Jiang N, Meng Q, Wang J, Yao Z, Gan W, Dai H. Texture analysis of MR images to identify the differentiated degree in hepatocellular carcinoma: a retrospective study. BMC Cancer 2020; 20:611. [PMID: 32605628 PMCID: PMC7325565 DOI: 10.1186/s12885-020-07094-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 06/19/2020] [Indexed: 01/02/2023] Open
Abstract
Background To explore the clinical value of texture analysis of MR images (multiphase Gd-EOB-DTPA-enhanced MRI and T2 weighted imaging (T2WI) to identify the differentiated degree of hepatocellular carcinoma (HCC). Method One hundred four participants were enrolled in this retrospective study. Each participant performed preoperative Gd-EOB-DTPA-enhanced MR scanning. Texture features were analyzed by MaZda, and B11 program was used for data analysis and classification. The diagnosis efficiencies of texture features and conventional imaging features in identifying the differentiated degree of HCC were assessed by receiver operating characteristic analysis. The relationship between texture features and differentiated degree of HCC was evaluated by Spearman’s correlation coefficient. Results The grey-level co-occurrence matrix -based texture features were most frequently extracted and the nonlinear discriminant analysis was excellent with the misclassification rate ranging from 3.33 to 14.93%. The area under the curve (AUC) of the combined texture features between poorly- and well-differentiated HCC, poorly- and moderately-differentiated HCC, moderately- and well-differentiated HCC was 0.812, 0.879 and 0.808 respectively, while the AUC of tumor size was 0.649, 0.660 and 0.517 respectively. The tumor size was significantly different between poorly- and moderately-HCC (p = 0.014). The COMBINE AUC values were not increased with tumor size combined. Conclusions Texture analysis of Gd-EOB-DTPA-enhanced MRI and T2WI was valuable and might be a promising method in identifying the differentiated degree of HCC. The poorly-differentiated HCC was more heterogeneous than well- and moderately-differentiated HCC.
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Affiliation(s)
- Mengmeng Feng
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Mengchao Zhang
- Department of Radiology, the China-Japan Union Hospital of Jilin University, Changchun city, Jilin province, 130033, P.R. China
| | - Yuanqing Liu
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Nan Jiang
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Qian Meng
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Jia Wang
- Department of Hepatobiliary Surgery Department, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Ziyun Yao
- Department of Pathology Department, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Wenjuan Gan
- Department of Pathology Department, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China
| | - Hui Dai
- Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China. .,Institute of Medical Imaging, Soochow University, Suzhou city, Jiangsu province, 215000, P.R. China.
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Kim TH, Yoon JH, Lee JM. Emerging Role of Hepatobiliary Magnetic Resonance Contrast Media and Contrast-Enhanced Ultrasound for Noninvasive Diagnosis of Hepatocellular Carcinoma: Emphasis on Recent Updates in Major Guidelines. Korean J Radiol 2020; 20:863-879. [PMID: 31132813 PMCID: PMC6536788 DOI: 10.3348/kjr.2018.0450] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2018] [Accepted: 02/03/2019] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) can be noninvasively diagnosed on the basis of its characteristic imaging findings of arterial phase enhancement and portal/delayed “washout” on computed tomography (CT) and magnetic resonance imaging (MRI) in cirrhotic patients. However, different specific diagnostic criteria have been proposed by several countries and major academic societies. In 2018, major guideline updates were proposed by the Association for the Study of Liver Diseases, European Association for the Study of the Liver (EASL), Korean Liver Cancer Association and National Cancer Center (KLCA-NCC) of Korea. In addition to dynamic CT and MRI using extracellular contrast media, these new guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as the first-line diagnostic test, while the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound (CEUS) as the second-line diagnostic test. Therefore, hepatobiliary MR contrast media and CEUS will be increasingly used for the noninvasive diagnosis and staging of HCC. In this review, we discuss the emerging role of hepatobiliary phase MRI and CEUS for the diagnosis of HCC and also review the changes in the HCC diagnostic criteria in major guidelines, including the KLCA-NCC practice guidelines version 2018. In addition, we aimed to pay particular attention to some remaining issues in the noninvasive diagnosis of HCC.
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Affiliation(s)
- Tae Hyung Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Hee Yoon
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jeong Min Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.,Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul, Korea.
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Low expression of organic anion-transporting polypeptide 1B3 predicts a poor prognosis in hepatocellular carcinoma. World J Surg Oncol 2020; 18:127. [PMID: 32534581 PMCID: PMC7293789 DOI: 10.1186/s12957-020-01891-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 05/20/2020] [Indexed: 12/24/2022] Open
Abstract
Objective To detect the expression level of organic anion-transporting polypeptide 1B3 (OATP1B3) in hepatocellular carcinoma (HCC) and to determine the relationship between OATP1B3 expression, clinicopathological features, and prognosis. Methods Immunohistochemical (IHC) staining was performed to detect the expression of OATP1B3 in 131 HCC specimens and in 89 adjacent nontumorous tissues. Moreover, the expression levels of OATP1B3 in 30 pairs of tumor and matched adjacent nontumorous tissues were detected by quantitative real-time polymerase chain reaction, and 34 pairs of tumor and matched adjacent nontumorous tissues were detected by Western blotting. The χ2 test was applied to analyze the correlation between OATP1B3 expression and the clinical parameters of HCC patients. The prognostic value of OATP1B3 in HCC patients was estimated by Kaplan-Meier survival analysis and the Cox stepwise proportional hazards model. Results Compared with that in adjacent nontumorous tissues (25.8%, 23/89), OATP1B3 expression was significantly downregulated in tumor tissues (59.5%, 78/131) (P < 0.0001). Moreover, OATP1B3 expression was markedly correlated with tumor size, recurrence, tumor differentiation, and tumor node metastasis (TNM) stage (P < 0.05 for each). However, age, sex, tumor capsule status, HBsAg, cirrhosis, tumor number, vascular invasion, and serum alpha fetoprotein were not associated with OATP1B3 expression. The overall survival (OS) and disease-free survival (DFS) of HCC patients who had high expression of OATP1B3 were significantly longer than those of patients with low expression (33.0% vs 12.9%, P = 0.001; 18.8% vs 5.3%, P < 0.0001). Cox multivariate analysis showed that OATP1B3, invasion, and TNM stage (P < 0.05 for each) were independent prognostic factors of OS in HCC patients and that OATP1B3 and TNM stage (both P < 0.05) were independent prognostic factors of DFS in HCC patients. Conclusions The expression of OATP1B3 in HCC patients was significantly lower than that in adjacent nontumorous tissues. OATP1B3 expression may be a potential prognostic marker in HCC patients.
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Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background. Eur Radiol 2020; 30:3438-3447. [PMID: 32064560 DOI: 10.1007/s00330-020-06687-y] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 01/03/2020] [Accepted: 01/29/2020] [Indexed: 02/07/2023]
Abstract
Gadoxetic acid-enhanced magnetic resonance imaging (MRI) plays important roles in diagnosis of hepatic lesions because of its superiority in the detectability of small lesions, its differentiation ability, and its utility for the early diagnosis of hepatocellular carcinoma (HCC). In HCC, expression of organic anion transporting polypeptide (OATP) 1B3 correlates with the enhancement ratio in the hepatobiliary phase. Gadoxetic acid-enhanced MRI, an indirect molecular imaging method, reflects OATP1B3 expression in HCC. OATP1B3 expression gradually decreases from the dysplastic nodule stage to advanced HCC. Decreased expression is a sensitive marker of multistep hepatocarcinogenesis, especially in the early stages. Hypervascular HCCs commonly show hypointensity in the hepatobiliary phase corresponding to a decrease in OATP1B3; however, approximately 10% of HCCs show hyperintensity due to OATP1B3 overexpression. This hyperintense HCC shows less aggressive biological features and has a better prognosis than hypointense HCC. Hyperintense HCC can be classified into a genetic subtype of HCC with a mature hepatocyte-like molecular expression. OATP1B3 expression and the less aggressive nature of hyperintense HCC are regulated by the molecular interaction of β-catenin signaling and hepatocyte nuclear factor 4α, a tumor suppressor factor. Gadoxetic acid-enhanced MR imaging has the potential to be an imaging biomarker for HCC. KEY POINTS: • The hepatobiliary phase is a sensitive indirect indicator of organic anion transporting polypeptide1B3 (OATP1B3) expression in hepatocellular carcinoma (HCC). • The OATP1B3 expression, namely, enhancement in the hepatobiliary phase, decreases from the very early stage of hepatocarcinogenesis, contributing to early diagnosis of HCC. • HCC showing hyperintensity on the hepatobiliary phase is a peculiar genetic subtype of HCC with OATP1B3 overexpression, a less aggressive nature, and mature hepatocyte-like molecular/genetic features.
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Ye Z, Cao L, Wei Y, Chen J, Zhang Z, Yao S, Duan T, Song B. Preoperative prediction of hepatocellular carcinoma with highly aggressive characteristics using quantitative parameters derived from hepatobiliary phase MR images. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:85. [PMID: 32175378 PMCID: PMC7049034 DOI: 10.21037/atm.2020.01.04] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 12/20/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND To prospectively determine whether the quantitative imaging parameters derived from the hepatobiliary phase (HBP) can be used for the preoperative prediction of hepatocellular carcinoma (HCC) with highly aggressive characteristics. METHODS One hundred and three patients with surgical-proven HCC were included from July 2015 to June 2018. Two independent reviewers measured signal intensity (SI) of liver and tumor, and quantitative parameters, including relative tumor enhancement (RTE), tumor to liver contrast ratio (TLR), tumor enhancement index (TEI), and relative enhancement ratio (RER) were calculated. The aggressive characteristics of HCC were identified by using the Ki-67 labeling index (LI), and patients were classified into low aggressive (Ki-67 LI ≤10%) and high aggressive (Ki-67 LI >10%) groups. The difference of quantitative parameters between two groups was assessed, and the correlation between quantitative parameters and Ki-67 LI was explored. Receiver operating characteristic analyses was used to evaluate the predictive performance of quantitative parameters. RESULTS The values of RTE, TLR, TEI, and RER, were significantly lower in the highly aggressive group than low aggressive group (P<0.05), and negative correlations were obtained between these quantitative parameters and Ki-67 LI (r ranges from -0.41 to -0.22, P<0.05). TLR demonstrated the highest predictive performance with the area under curve (AUC) of 0.83 [95% confidence interval (CI): 0.75-0.90], sensitivity of 89.0% and specificity of 63.3%, and subsequent with RER, TEI, and RTE with AUC of 0.78 (95% CI: 0.68-0.85), 0.74 (95% CI: 0.64-0.82) and 0.68 (95% CI: 0.58-0.77), respectively. Good inter-observer and intra-observer agreement were found in all parameters. CONCLUSIONS TLR showed the highest predictive performance in highly aggressive HCC. Quantitative parameters based on HBP could preoperatively predict the aggressiveness of HCC.
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Affiliation(s)
- Zheng Ye
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Likun Cao
- West China School of Medicine, Sichuan University, Chengdu 610041, China
- Department of Radiology, Peking Union Medical College Hospital (Dongdan Campus), Beijing 100730, China
| | - Yi Wei
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Jie Chen
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Zhen Zhang
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Shan Yao
- West China School of Medicine, Sichuan University, Chengdu 610041, China
| | - Ting Duan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, China
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Zhong X, Tang H, Lu B, You J, Piao J, Yang P, Li J. Differentiation of Small Hepatocellular Carcinoma From Dysplastic Nodules in Cirrhotic Liver: Texture Analysis Based on MRI Improved Performance in Comparison Over Gadoxetic Acid-Enhanced MR and Diffusion-Weighted Imaging. Front Oncol 2020; 9:1382. [PMID: 31998629 PMCID: PMC6966306 DOI: 10.3389/fonc.2019.01382] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 11/22/2019] [Indexed: 12/30/2022] Open
Abstract
Background: Accurate characterization of small (3 cm) hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in cirrhotic liver is challenging. We aimed to investigate whether texture analysis (TA) based on T2-weighted images (T2WI) is superior to qualitative diagnosis using gadoxetic acid-enhanced MR imaging (Gd-EOB-MRI) and diffusion-weighted imaging (DWI) for distinguishing sHCC from DNs in cirrhosis. Materials and methods: Sixty-eight patients with 73 liver nodules (46 HCCs, 27 DNs) pathologically confirmed by operation were included. For imaging diagnosis, three sets of images were reviewed by two experienced radiologists in consensus: a Gd-EOB-MRI set, a DWI set, and a combined set (combination of Gd-EOB-MRI and DWI). For TA, 279 texture features resulting from T2WI were extracted for each lesion. The performance of each approach was evaluated by a receiver operating characteristic analysis. The area under the receiver operating characteristic curve (Az), sensitivity, specificity, and accuracy were determined. Results: The performance of TA (Az = 0.96) was significantly higher than that of imaging diagnosis using Gd-EOB-MRI set (Az = 0.86) or DWI set (Az = 0.80) alone in differentiation of sHCC from DNs (P = 0.008 and 0.025, respectively). The combination of Gd-EOB-MRI and DWI showed a greater sensitivity (95.6%) but reduced specificity (66.7%). The specificity of TA (92.6%) was significantly higher than that of the combined set (P < 0.001), but no significant difference was observed in sensitivity (97.8 vs. 95.6%, P = 0.559). Conclusion: TA-based T2WI showed a better classification performance than that of qualitative diagnosis using Gd-EOB-MRI and DW imaging in differentiation of sHCCs from DNs in cirrhotic liver. TA-based MRI may become a potential imaging biomarker for the early differentiation HCCs from DNs in cirrhosis.
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Affiliation(s)
- Xi Zhong
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Bingui Lu
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jia You
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jinsong Piao
- Department of Pathology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Peiyu Yang
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
| | - Jiansheng Li
- Department of Radiology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China
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Toyoda H, Tada T, Yasuda S, Mizuno K, Sone Y, Kaneoka Y, Maeda A, Akita T, Tanaka J, Kumada T. The emergence of non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI in patients with chronic hepatitis C. Aliment Pharmacol Ther 2019; 50:1232-1238. [PMID: 31588590 DOI: 10.1111/apt.15490] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Revised: 04/17/2019] [Accepted: 08/12/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Intrahepatic non-hypervascular hypointense nodules (NHHNs) detected during the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) have the potential to transition into typical hypervascular hepatocellular carcinoma (HCC). However, the incidence and risk factors for the emergence of these nodules in patients with chronic hepatitis C virus (HCV) infection are unknown. AIM To investigate the incidence and risk factors for NHHNs in patients with chronic HCV infection in a longitudinal follow-up study METHODS: EOB-MRI was performed in 608 patients with chronic HCV infection and no history of HCC. The characteristics of patients with and without NHHNs were compared. In patients without NHHNs at baseline, the incidence of NHHN emergence and associated risk factors were analysed. RESULTS NHHNs were detected at baseline in 93 of 608 patients (15.3%). Among 515 patients without NHHNs at baseline, the 1-year, 3-year and 5-year incidence of NHHN emergence was 1.8%, 9.8% and 16.4%, respectively. Only FIB-4 index was independently associated with the emergence of NHHNs in multivariate analyses. Whereas NHHNs emerged in 24.1% of patients with FIB-4 index ≥ 3.25 at 5 years, none emerged in patients with FIB-4 index < 1.45. CONCLUSION In patients with chronic HCV infection, advanced liver fibrosis is an important risk factor for the presence or emergence of NHHNs.
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yuji Kaneoka
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Atsuyuki Maeda
- Department of Surgery, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Takashi Kumada
- Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Qin X, Yang T, Huang Z, Long L, Zhou Z, Li W, Gao Y, Wang M, Zhang X. Hepatocellular carcinoma grading and recurrence prediction using T 1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging. Oncol Lett 2019; 18:2322-2329. [PMID: 31404322 PMCID: PMC6676719 DOI: 10.3892/ol.2019.10557] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 05/23/2019] [Indexed: 12/13/2022] Open
Abstract
The aim of the present study was to explore the value of T1 mapping on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for grading hepatocellular carcinoma (HCC) and predicting its recurrence rate. A retrospective study was performed that included 75 patients (66 men and 9 women; mean age, 52.89 years; age range, 23-79 years) with HCC who had undergone Gd-EOB-DTPA-enhanced MRI with T1 mapping before surgery. The T1 relaxation time of the 81 lesions and non-tumorous liver parenchyma in 75 patients with HCC were measured before Gd-EOB-DTPA was injected and then at 5, 10 and 20 min after administration, respectively. T1[lesion (L)-hepatic parenchyma (H)]/H (%) was calculated as the increment rate of the T1 value in the lesions relative to the non-tumorous liver parenchyma. One-way analysis of variance and Spearman's correlation analysis was used to compare the differences and relationship of T1 mapping values among the three grades of HCC. A total of 81 lesions were divided into well-differentiated HCC (grades I; n=21), moderately differentiated HCC (grades II; n=40) and poorly differentiated HCC (grades III; n=20) according to the histopathology. The T1(L-H)/H (%) value among grades I, II and III HCC on pre-contrast results and on post-contrast results at the 5-, 10- and 20-min hepatobiliary phase (HBP) were significantly different (P<0.05), and T1(L-H)/H (%) was correlated with the histological grade of HCC at each time point (r=0.637, r=0.554, r=0.499 and r=0.560, respectively, P<0.001). A total of 41 recurrence cases [grade I (n=5), grade II (n=23) and grade III (n=13)] were verified by imaging (CT, MRI or ultrasound) or reoperation. Patients with grade III and grade II HCC had higher recurrence rates compared with that in patients with grade I HCC (P<0.05; median recurrence times were 258 days, 605 days and undefined, respectively). According to the optimal cut-off point for the T1(L-H)/H (%) of the three grades of HCC, patients with HCC in the low T1(L-H)/H (%) value group (≤155.15%) had lower cumulative recurrence rates compared with that in the medium (T1(L-H)/H (%) >155.15% and T1(L-H)/H (%) ≤241.20%) and high (T1(L-H)/H (%) >241.20%) value groups at the 20-min HBP (P<0.05; median recurrence times were undefined, 530 days and 447 days, respectively). These results indicate that the parameters of T1 mapping would be beneficial for predicting the grading and recurrence of HCC.
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Affiliation(s)
- Xiali Qin
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Tengfei Yang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhongkui Huang
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Liling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhipeng Zhou
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Wenmei Li
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yinjuan Gao
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Mengzhu Wang
- Department of Magnetic Resonance Scientific Marketing, Siemens Healthineers, Guangzhou, Guangdong 510620, P.R. China
| | - Xiaoyong Zhang
- Department of Magnetic Resonance Scientific Marketing, Siemens Healthineers, Guangzhou, Guangdong 510620, P.R. China
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Gyoda Y, Imamura H, Ichida H, Yoshimoto J, Ishizaki Y, Kuwatsuru R, Kawasaki S. Significance of hypovascular lesions on dynamic computed tomography and/or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma. J Gastroenterol Hepatol 2019; 34:1242-1248. [PMID: 30345571 DOI: 10.1111/jgh.14510] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 09/29/2018] [Accepted: 10/05/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND AND AIM The natural course and clinical implications of hypovascular lesions on dynamic computed tomography and/or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging were investigated. METHODS We followed the patients with hepatocellular carcinoma (HCC) who underwent hepatectomy between April 2009 and August 2012 to determine whether new classical HCCs developed from these unresected borderline lesions or emerged in different areas. RESULTS One hundred and eleven patients with HCC were identified to have undergone examinations using both imaging methods before hepatic resection. A total of 54 hypovascular lesions were detected. Gadolinium ethoxybenzyl-enhanced magnetic resonance imaging detected 51 lesions, while dynamic computed tomography identified 21 lesions. Eleven lesions were resected at the time of the hepatectomy together with the main HCCs. Classical HCCs had developed from 52.5% of the 43 unresected lesions at 3 years after hepatic resection. Subsequently, we conducted a patient-by-patient analysis to compare the development of classical HCC from these hypovascular lesions and the emergence of de novo classical HCC in other areas. The 3-year occurrence rate was 62.2% for the former group and 55.0% for the latter group (P = 0.83). Thus, although 52.2% of these hypovascular lesions had developed into classical HCCs at 3 years after the initial hepatectomy, de novo HCCs also occurred at other sites. Furthermore, new hypovascular lesions emerged after hepatectomy in 18-29% of patients irrespective of the presence or absence of hypovascular lesions at hepatectomy. CONCLUSIONS It remains uncertain whether these hypovascular lesions should be resected together with the main tumors at the time of hepatectomy.
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Affiliation(s)
- Yu Gyoda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Jiro Yoshimoto
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoichi Ishizaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Ryohei Kuwatsuru
- Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
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40
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Chernyak V, Fowler KJ, Heiken JP, Sirlin CB. Use of gadoxetate disodium in patients with chronic liver disease and its implications for liver imaging reporting and data system (LI-RADS). J Magn Reson Imaging 2019; 49:1236-1252. [PMID: 30609194 DOI: 10.1002/jmri.26540] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 01/04/2025] Open
Abstract
Use of gadoxetate disodium, a hepatobiliary gadolinium-based agent, in patients with chronic parenchymal liver disease offers the advantage of improved sensitivity for detecting hepatocellular carcinoma (HCC). Imaging features of liver observations on gadoxetate-enhanced MRI may also serve as biomarkers of recurrence-free and overall survival following definitive treatment of HCC. A number of technical and interpretative pitfalls specific to gadoxetate exist, however, and needs to be recognized when protocoling and interpreting MRI exams with this agent. This article reviews the advantages and pitfalls of gadoxetate use in patients at risk for HCC, and the potential impact on Liver Imaging Reporting and Data System (LI-RADS) imaging feature assessment and categorization. Level of Evidence: 5 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:1236-1252.
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Affiliation(s)
- Victoria Chernyak
- Department of Radiology, Montefiore Medical Center, Bronx, New York, USA
| | - Kathryn J Fowler
- Liver Imaging Group, Department of Radiology, University of California - San Diego, California, USA
| | - Jay P Heiken
- Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA
| | - Claude B Sirlin
- Liver Imaging Group, Department of Radiology, University of California - San Diego, California, USA
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41
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Inoue-Shinomiya E, Murakawa M, Asahina Y, Nakagawa M, Tsuchiya J, Sato A, Tsunoda T, Miyoshi M, Nitta S, Kawai-Kitahata F, Itsui Y, Azuma S, Kakinuma S, Murata K, Mizokami M, Watanabe M. Association of serum interferon-λ3 levels with hepatocarcinogenesis in chronic hepatitis C patients treated with direct-acting antiviral agents. Hepatol Res 2019; 49:500-511. [PMID: 30623518 DOI: 10.1111/hepr.13307] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 12/10/2018] [Accepted: 12/28/2018] [Indexed: 02/08/2023]
Abstract
AIM Although the efficacy of hepatitis C virus (HCV) treatment is improved dramatically by direct-acting antiviral agents (DAAs), the assessment of hepatocellular carcinoma (HCC) remains important. Interferon lambda 3 (IFN-λ3) is associated with liver fibrosis and inflammation in chronic hepatitis C (CHC) patients, but its impact on carcinogenesis remains controversial and little is known about its effects after viral clearance. To determine the contribution of IFN-λ3 to hepatocarcinogenesis after HCV clearance, we analyzed IFNL3 genotypes and serial serum IFN-λ3 levels in CHC patients who achieved sustained virologic responses (SVR). METHODS This study comprised 201 CHC patients treated with DAAs. Serum samples were collected sequentially and IFN-λ3 levels were quantified by chemiluminescence enzyme immunoassay. The IFNL3 polymorphism (rs8099917) was genotyped in 195 patients. RESULTS One hundred and twenty-five patients were rs8099917 T/T and 70 were non-T/T. Serum IFN-λ3 levels did not differ significantly with IFNL3 genotype, dropped markedly by 1 week and remained low up to 24 weeks after the end of treatment. Interferon-λ3 levels were significantly higher after viral clearance in patients who developed HCC and were associated with a higher potential for hepatocarcinogenesis, such as a higher frequency of non-hypervascular hypointensive nodules (P = 0.046), higher stages of liver fibrosis (P < 0.001), and higher post-treatment levels of Wisteria floribunda agglutinin positive Mac-2 binding protein (P < 0.001) and alanine aminotransferase (P < 0.001). CONCLUSIONS Serum IFN-λ3 levels after HCV clearance are associated with the potential for HCC development. Interferon-λ3 could be helpful for elucidating the relationships among immunologic status, liver fibrosis, liver inflammation, and hepatocarcinogenesis, after achieving SVR.
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Affiliation(s)
- Emi Inoue-Shinomiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Miyako Murakawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Clinical Laboratory, Medical Hospital of Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Asahina
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Mina Nakagawa
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Jun Tsuchiya
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ayako Sato
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Tomoyuki Tsunoda
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Masato Miyoshi
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sayuri Nitta
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fukiko Kawai-Kitahata
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yasuhiro Itsui
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seishin Azuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Sei Kakinuma
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.,Department of Liver Disease Control, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kazumoto Murata
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan.,Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Nasushiobara, Japan
| | - Masashi Mizokami
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Mamoru Watanabe
- Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan
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42
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Huang K, Dong Z, Cai H, Huang M, Peng Z, Xu L, Jia Y, Song C, Li ZP, Feng ST. Imaging biomarkers for well and moderate hepatocellular carcinoma: preoperative magnetic resonance image and histopathological correlation. BMC Cancer 2019; 19:364. [PMID: 30999947 PMCID: PMC6472074 DOI: 10.1186/s12885-019-5574-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 04/03/2019] [Indexed: 12/20/2022] Open
Abstract
Background Our aim of the study is to investigate the feasibility of preoperative prediction for hepatocellular carcinoma (HCC) histological grading using gadoxetic acid-enhanced magnetic resonance imaging (MRI). Methods This study included one hundred and fifty-six patients with solitary HCC. Preoperative gadoxetic acid-enhanced MRI findings were retrospectively analyzed. MRI qualitative features such as tumor size, margin, capsule status, signal homogeneity, intratumoral vessels, peritumoral enhancement during mid-arterial phase, peritumoral hypointensity during the hepatobiliary phase (HBP) were investigated. Apparent diffusion coefficients (ADCs), T1 reduction ratio of pre- and post-contrast enhanced images of the tumors were calculated. HCC histological grading in surgical specimens were confirmed by Edmonson’s criteria. Correlations between these MRI features and HCC histological grading were analyzed using multivariate logistic regression. The receiver operating characteristic (ROC) curve was used to assess the predictive efficacy of the model. Results Univariate analysis showed that maximum tumor diameter (p = 0.004), tumor margin (p = 0.006), intratumoral vessels (p = 0.001) and peritumoral hypointensity during HBP (p = 0.000), were significantly correlated with HCC histological grading. There was no relationship between capsule, tumor signal, venous thrombosis, peritumoral enhancement during mid-arterial phase, ADC value, T1 reduction ratio, and HCC histological grading. Multivariate logistic regression analysis demonstrated that the maximum tumor diameter (p = 0.012, odds ratio = 1.002, 95% confidence interval: 1.007–1.046)) was an independent risk factor for high grade HCC. Conclusions Greater tumor size, a more irregular margin, presence of intratumoral vessels, and peritumoral hypointensity during HBP were indicators for high grade HCC. The maximum tumor diameter was an independent risk factor for high grade HCC. Electronic supplementary material The online version of this article (10.1186/s12885-019-5574-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Kun Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.,Department of Radiology, Guizhou Provincial People's Hospital, No. 83 East, Zhongshan Road, Guiyang, 550002, Guizhou, China
| | - Zhi Dong
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Huasong Cai
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Mengqi Huang
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Zhenpeng Peng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Ling Xu
- Faculty of Medicine and Dentistry, University of Western Australia, Perth, Australia
| | - Yingmei Jia
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Chenyu Song
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China
| | - Zi-Ping Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.
| | - Shi-Ting Feng
- Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, 510080, Guangdong, China.
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43
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Navin PJ, Venkatesh SK. Hepatocellular Carcinoma: State of the Art Imaging and Recent Advances. J Clin Transl Hepatol 2019; 7:72-85. [PMID: 30944823 PMCID: PMC6441649 DOI: 10.14218/jcth.2018.00032] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 12/31/2018] [Accepted: 01/04/2019] [Indexed: 02/07/2023] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing, with this trend expected to continue to the year 2030. Hepatocarcinogenesis follows a predictable course, which makes adequate identification and surveillance of at-risk individuals central to a successful outcome. Moreover, imaging is central to this surveillance, and ultimately to diagnosis and management. Many liver study groups throughout Asia, North America and Europe advocate a surveillance program for at-risk individuals to allow early identification of HCC. Ultrasound is the most commonly utilized imaging modality. Many societies offer guidelines on how to diagnose HCC. The Liver Image Reporting and Data System (LIRADS) was introduced to standardize the acquisition, interpretation, reporting and data collection of HCC cases. The LIRADS advocates diagnosis using multiphase computed tomography or magnetic resonance imaging (MRI) imaging. The 2017 version also introduces contrast-enhanced ultrasound as a novel approach to diagnosis. Indeed, imaging techniques have evolved to improve diagnostic accuracy and characterization of HCC lesions. Newer techniques, such as T1 mapping, intravoxel incoherent motion analysis and textural analysis, assess specific characteristics that may help grade the tumor and guide management, allowing for a more personalized approach to patient care. This review aims to analyze the utility of imaging in the surveillance and diagnosis of HCC and to assess novel techniques which may increase the accuracy of imaging and determine optimal treatment strategies.
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Toyoda H, Kumada T, Tada T, Mizuno K, Sone Y, Akita T, Tanaka J, Johnson PJ. The impact of HCV eradication by direct-acting antivirals on the transition of precancerous hepatic nodules to HCC: A prospective observational study. Liver Int 2019; 39:448-454. [PMID: 30312003 DOI: 10.1111/liv.13987] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 09/25/2018] [Accepted: 10/05/2018] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS It remains controversial whether the eradication of hepatitis C virus (HCV) by interferon (IFN)-free anti-HCV therapy using direct-acting antivirals (DAAs) suppresses or promotes hepatocellular carcinoma (HCC) development. We investigated the influence of HCV eradication by DAA therapy on HCC development, by observing changes of non-hypervascular hypointense nodules (NHHNs) by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI). METHODS A total of 401 patients treated with DAA therapy who did not have a history of HCC were enrolled in this prospective cohort study. All patients underwent EOB-MRI prior to the start of DAA therapy and were followed up periodically after therapy. The progression of NHHNs detected at baseline to typical HCC, as indicated by hypervascularization and the incidence of newly emergent NHHNs, was analyzed. RESULTS In comparison of patients who achieved sustained virologic response (SVR) with propensity score-matched patients with persistent HCV infection, there was no difference in the incidence of hypervascularization of NHHNs to typical HCC among patients who had NHHNs at baseline. Among patients who did not have NHHNs at baseline, the incidence of the new emergence of NHHNs did not differ between study patients and propensity score-matched patients with persistent HCV infection. CONCLUSIONS During a 2-year observation period after SVR, the eradication of HCV by IFN-free DAA therapy did not suppress or enhance HCC development. (UMIN000017020).
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Affiliation(s)
- Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Takashi Kumada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kazuyuki Mizuno
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yasuhiro Sone
- Department of Radiology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Tomoyuki Akita
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Philip J Johnson
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
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Kim TH, Kim SY, Tang A, Lee JM. Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update. Clin Mol Hepatol 2019; 25:245-263. [PMID: 30759967 PMCID: PMC6759428 DOI: 10.3350/cmh.2018.0090] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 11/07/2018] [Indexed: 12/11/2022] Open
Abstract
The goal of this review is to present the similarities and differences among the latest guidelines for noninvasive diagnosis of hepatocellular carcinoma (HCC) of American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), Liver Imaging Reporting and Data System (LI-RADS), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) of Korea. In 2018, major guideline updates have been proposed by the AASLD, EASL and KLCA-NCC; AASLD newly incorporated LI-RADS into their HCC diagnostic algorithm. The AASLD and EASL guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as a first-line diagnostic test in addition to dynamic computed tomography and MRI using extracellular contrast media and the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound as a second-line diagnostic test. We will comprehensively review the HCC surveillance and diagnostic algorithms and compare and highlight key features for each guideline. We also address limitations of current systems for the noninvasive diagnosis of HCC.
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Affiliation(s)
- Tae-Hyung Kim
- Department of Radiology, Seoul National University Hospital, Seoul, Korea.,Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - An Tang
- Department of Radiology, Centre hospitalier de l'Université de Montréal (CHUM), Québec, Canada
| | - 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
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Low HM, Choi JY, Tan CH. Pathological variants of hepatocellular carcinoma on MRI: emphasis on histopathologic correlation. Abdom Radiol (NY) 2019; 44:493-508. [PMID: 30145629 DOI: 10.1007/s00261-018-1749-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is a unique tumor because it is one of the few cancers which can be treated based on imaging alone. Magnetic resonance imaging (MRI) carries higher sensitivity and specificity for the diagnosis of HCC than either computed tomography (CT) or ultrasound. MRI is imaging modality of choice for the evaluation of complex liver lesions and HCC because of its inherent ability to depict cellularity, fat, and hepatocyte composition with high soft tissue contrast. The imaging features of progressed HCC are well described. However, many HCC tumors do not demonstrate classical imaging features, posing a diagnostic dilemma to radiologists. Some of these can be attributed to variations in tumor biology and histology, which result in radiological features that differ from the typical progressed HCC. This pictorial review seeks to demonstrate the appearance of different variants of HCC on MRI imaging, in relation to their histopathologic features.
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Affiliation(s)
- Hsien Min Low
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore
| | - Jin Young Choi
- Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Cher Heng Tan
- Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11, Jalan Tan Tock Seng, Singapore, 308433, Singapore.
- Lee Kong Chian School of Medicine, 11, Mandalay Road, Singapore, 308232, Singapore.
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Orabi AS, Abou El-Nour KM, Ahmed SA, El-Falouji AI. Novel gold and silver-Sarcophine complexes as antitumor agents against MCF7 and HepG2 cells: Synthesis, characterization, in Silico, in Vitro and docking studies. J Mol Liq 2019. [DOI: 10.1016/j.molliq.2018.10.058] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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48
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Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation. Eur Radiol 2018; 29:2272-2282. [DOI: 10.1007/s00330-018-5882-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 10/19/2018] [Accepted: 11/09/2018] [Indexed: 01/15/2023]
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49
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Predicting the grade of hepatocellular carcinoma based on non-contrast-enhanced MRI radiomics signature. Eur Radiol 2018; 29:2802-2811. [PMID: 30406313 DOI: 10.1007/s00330-018-5787-2] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 09/01/2018] [Accepted: 09/21/2018] [Indexed: 12/12/2022]
Abstract
PURPOSE This study was conducted in order to investigate the value of magnetic resonance imaging (MRI)-based radiomics signatures for the preoperative prediction of hepatocellular carcinoma (HCC) grade. METHODS Data from 170 patients confirmed to have HCC by surgical pathology were divided into a training group (n = 125) and a test group (n = 45). The radiomics features of tumours based on both T1-weighted imaging (WI) and T2WI were extracted by using Matrix Laboratory (MATLAB), and radiomics signatures were generated using the least absolute shrinkage and selection operator (LASSO) logistic regression model. The predicted values of pathological HCC grades using radiomics signatures, clinical factors (including age, sex, tumour size, alpha fetoprotein (AFP) level, history of hepatitis B, hepatocirrhosis, portal vein tumour thrombosis, portal hypertension and pseudocapsule) and the combined models were assessed. RESULTS Radiomics signatures could successfully categorise high-grade and low-grade HCC cases (p < 0.05) in both the training and test datasets. Regarding the performances of clinical factors, radiomics signatures and the combined clinical and radiomics signature (from the combined T1WI and T2WI images) models for HCC grading prediction, the areas under the curve (AUCs) were 0.600, 0.742 and 0.800 in the test datasets, respectively. Both the AFP level and radiomics signature were independent predictors of HCC grade (p < 0.05). CONCLUSIONS Radiomics signatures may be important for discriminating high-grade and low-grade HCC cases. The combination of the radiomics signatures with clinical factors may be helpful for the preoperative prediction of HCC grade. KEY POINTS • The radiomics signature based on non-contrast-enhanced MR images was significantly associated with the pathological grade of HCC. • The radiomics signatures based on T1WI or T2WI images performed similarly at predicting the pathological grade of HCC. • Combining the radiomics signature and clinical factors (including age, sex, tumour size, AFP level, history of hepatitis B, hepatocirrhosis, portal vein tumour thrombosis, portal hypertension and pseudocapsule) may be helpful for the preoperative prediction of HCC grade.
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50
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Cerny M, Chernyak V, Olivié D, Billiard JS, Murphy-Lavallée J, Kielar AZ, Elsayes KM, Bourque L, Hooker JC, Sirlin CB, Tang A. LI-RADS Version 2018 Ancillary Features at MRI. Radiographics 2018; 38:1973-2001. [DOI: 10.1148/rg.2018180052] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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