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Zhang X, Zhang X, Luo QK, Fu Q, Liu P, Pan CJ, Liu CJ, Zhang HW, Qin T. Pretreatment radiomic imaging features combined with immunological indicators to predict targeted combination immunotherapy response in advanced hepatocellular carcinoma. World J Clin Oncol 2025; 16:102735. [DOI: 10.5306/wjco.v16.i4.102735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 12/16/2024] [Accepted: 01/23/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Early symptoms of hepatocellular carcinoma (HCC) are not obvious, and more than 70% of which does not receive radical hepatectomy, when first diagnosed. In recent years, molecular-targeted drugs combined with immunotherapy and other therapeutic methods have provided new treatment options for middle and advanced HCC (aHCC). Predicting the effect of targeted combined immunotherapy has become a hot topic in current research.
AIM To explore the relationship between nodule enhancement in hepatobiliary phase and the efficacy of combined targeted immunotherapy for aHCC.
METHODS Data from 56 patients with aHCC for magnetic resonance imaging with gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid were retrospectively collected. Signal intensity of intrahepatic nodules was measured, and the hepatobiliary relative enhancement ratio (RER) was calculated. Progression-free survival (PFS) of patients with high and low reinforcement of HCC nodules was compared. The model was validated using receiver operating characteristic curves. Univariate and multivariate logistic regression and Kaplan-Meier analysis were performed to explore factors influencing the efficacy of targeted immunization and PFS.
RESULTS Univariate and multivariate analyses revealed that the RER, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and prognostic nutritional index were significantly associated with the efficacy of tyrosine kinase inhibitors combined with immunotherapy (P < 0.05). The area under the curve of the RER for predicting the efficacy of tyrosine kinase inhibitors combined with anti-programmed death 1 antibody in patients with aHCC was 0.876 (95% confidence interval: 0.781-0.971, P < 0.05), the optimal cutoff value was 0.904, diagnostic sensitivity was 87.5%, and specificity was 79.2%. Kaplan-Meier analysis showed that neutrophil-to-lymphocyte ratio < 5, platelet-to-lymphocyte ratio < 300, prognostic nutritional index < 45, and RER < 0.9 significantly improved PFS.
CONCLUSION AHCC nodules enhancement in the hepatobiliary stage was significantly correlated with PFS. Imaging information and immunological indicators had high predictive efficacy for targeted combined immunotherapy and were associated with PFS.
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Affiliation(s)
- Xu Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Xu Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Qian-Kun Luo
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Qiang Fu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Pan Liu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Chang-Jie Pan
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Chuan-Jiang Liu
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Hong-Wei Zhang
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Tao Qin
- Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
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Aoki T, Nishida N, Minami Y, Kudo M. The Impact of Normal Hepatobiliary Cell Zonation Programs on the Phenotypes and Functions of Primary Liver Tumors. Liver Cancer 2025; 14:92-103. [PMID: 40144466 PMCID: PMC11936443 DOI: 10.1159/000541077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/21/2024] [Indexed: 03/28/2025] Open
Abstract
Background Traditional tumor classifications have relied on cellular origin, pathological morphological features, gene expression profiles, and more recently, the tumor immune microenvironment. While these classifications provide valuable insights, incorporating physiological classifications focusing on liver metabolic functions may lead to new discoveries. Summary We proposed to reclassify benign and malignant hepatocellular neoplasms based on their physiological functions such as albumin production, bile acid production, glycolysis, glycogenesis, and adipogenesis. We further demonstrated the homology between signal pathways activated by the differentiation program of the normal hepatobiliary cells and those activated by genetic abnormalities in tumors. Specifically, Wnt/β-catenin, RAS, NOTCH, and TGF-β signaling not only contribute to cell differentiation via activation of liver-enriched transcription factors but also determine the tumor traits. Examining the distinctions between hepatocellular carcinomas (HCCs) that maintain or lose metabolic functions can yield valuable insights into the drivers of biological malignancy and tumor plasticity. Key Messages To confirm the homology between the differentiation programs of normal hepatobiliary cells, hepatocellular adenomas (HCA), and HCC we identify liver-specific functions such as catabolism and anabolism within tumors. HCCs and HCAs that have lost these metabolic functions exhibit characteristics such as dedifferentiation, resemblance to biliary cells, or increased glycolysis. Focusing on this underexplored area will likely stimulate active research into new tumor characteristics.
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Affiliation(s)
- Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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Yan Y, Si Z, Chun C, Chao-Qun P, Ke M, Dong Z, Li W. Multiphase MRI-Based Radiomics for Predicting Histological Grade of Hepatocellular Carcinoma. J Magn Reson Imaging 2024; 60:2117-2127. [PMID: 38344854 DOI: 10.1002/jmri.29289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 01/27/2024] [Accepted: 01/29/2024] [Indexed: 10/11/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer. Accurate preoperative prediction of histological grade holds potential for improving clinical management and disease prognostication. PURPOSE To evaluate the performance of a radiomics signature based on multiphase MRI in assessing histological grade in solitary HCC. STUDY TYPE Retrospective. SUBJECTS A total of 405 patients with histopathologically confirmed solitary HCC and with liver gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month of surgery. FIELD STRENGTH/SEQUENCE Contrast-enhanced T1-weighted spoiled gradient echo sequence (LAVA) at 1.5 or 3.0 T. ASSESSMENT Tumors were graded (low/high) according to results of histopathology. Basic clinical characteristics (including age, gender, serum alpha-fetoprotein (AFP) level, history of hepatitis B, and cirrhosis) were collected and tumor size measured. Radiomics features were extracted from Gd-EOB-DTPA-enhanced MRI data. Three feature selection strategies were employed sequentially to identify the optimal features: SelectFromModel (SFM), SelectPercentile (SP), and recursive feature elimination with cross-validation (RFECV). Probabilities of five single-phase radiomics-based models were averaged to generate a radiomics signature. A combined model was built by combining the radiomics signature and clinical predictors. STATISTICAL TESTS Pearson χ2 test/Fisher exact test, Wilcoxon rank sum test, interclass correlation coefficient (ICC), univariable/multivariable logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), DeLong test, calibration curve, Brier score, decision curve, Kaplan-Meier curve, and log-rank test. A P-value <0.05 was considered statistically significant. RESULTS High-grade HCCs were present in 33.8% of cases. AFP levels (odds ratio [OR] 1.89) and tumor size (>5 cm; OR 2.33) were significantly associated with HCC grade. The combined model had excellent performance in assessing HCC grade in the test dataset (AUC: 0.801), and demonstrated satisfactory calibration and clinical utility. DATA CONCLUSION A model that combined a radiomics signature derived from preoperative multiphase Gd-EOB-DTPA-enhanced MRI and clinical predictors showed good performance in assessing HCC grade. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY: Stage 5.
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Affiliation(s)
- Yang Yan
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Zhang Si
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Cui Chun
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Pen Chao-Qun
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Mu Ke
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Zhang Dong
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
| | - Wen Li
- Department of Radiology, XinQiao Hospital, Army Medical University, Chongqing, China
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Qu Q, Liu Z, Lu M, Xu L, Zhang J, Liu M, Jiang J, Gu C, Ma Q, Huang A, Zhang X, Zhang T. Preoperative Gadoxetic Acid-Enhanced MRI Features for Evaluation of Vessels Encapsulating Tumor Clusters and Microvascular Invasion in Hepatocellular Carcinoma: Creating Nomograms for Risk Assessment. J Magn Reson Imaging 2024; 60:1094-1110. [PMID: 38116997 DOI: 10.1002/jmri.29187] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 12/01/2023] [Accepted: 12/02/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Vessels encapsulating tumor cluster (VETC) and microvascular invasion (MVI) have a synergistic effect on prognosis assessment and treatment selection of hepatocellular carcinoma (HCC). Preoperative noninvasive evaluation of VETC and MVI is important. PURPOSE To explore the diagnosis value of preoperative gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI) features for MVI, VETC, and recurrence-free survival (RFS) in HCC. STUDY TYPE Retrospective. POPULATION 240 post-surgery patients with 274 pathologically confirmed HCC (allocated to training and validation cohorts with a 7:3 ratio) and available tumor marker data from August 2014 to December 2021. FIELD STRENGTH/SEQUENCE 3-T, T1-, T2-, diffusion-weighted imaging, in/out-phase imaging, and dynamic contrast-enhanced imaging. ASSESSMENT Three radiologists subjectively reviewed preoperative MRI, evaluated clinical and conventional imaging features associated with MVI+, VETC+, and MVI+/VETC+ HCC. Regression-based nomograms were developed for HCC in the training cohort. Based on the nomograms, the RFS prognostic stratification system was further. Follow-up occurred every 3-6 months. STATISTICAL TESTS Chi-squared test or Fisher's exact test, Mann-Whitney U-test or t-test, least absolute shrinkage and selection operator-penalized, multivariable logistic regression analyses, receiver operating characteristic analysis, Harrell's concordance index (C-index), Kaplan-Meier plots. Significance level: P < 0.05. RESULTS In the training group, 44 patients with MVI+ and 74 patients with VETC+ were histologically confirmed. Three nomograms showed good performance in the training (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.892 vs. 0.848 vs. 0.910) and validation (C-indices: MVI+ vs. VETC+ vs. MVI+/VETC+, 0.839 vs. 0.810 vs. 0.855) cohorts. The median follow-up duration for the training cohort was 43.6 (95% CI, 35.0-52.2) months and 25.8 (95% CI, 16.1-35.6) months for the validation cohort. Patients with either pathologically confirmed or nomogram-estimated MVI, VETC, and MVI+/VETC+ suffered higher risk of recurrence. DATA CONCLUSION GA-enhanced MRI and clinical variables might assist in preoperative estimation of MVI, VETC, and MVI+/VETC+ in HCC. EVIDENCE LEVEL 4 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Qi Qu
- Nantong University, Nantong, Jiangsu, China
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Zixin Liu
- Nantong University, Nantong, Jiangsu, China
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Mengtian Lu
- Nantong University, Nantong, Jiangsu, China
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Lei Xu
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Jiyun Zhang
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Maotong Liu
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Jifeng Jiang
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Chunyan Gu
- Department of Pathology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Qinrong Ma
- Department of Pathology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Aina Huang
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Xueqin Zhang
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
| | - Tao Zhang
- Department of Radiology, Affiliated Nantong Hospital 3 of Nantong University, Nantong Third People's Hospital, Nantong, Jiangsu, China
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Rybczynska D, Markiet K, Pienkowska J, Frydrychowski A. Is there added value of the hepatobiliary phase of MRI with hepatobiliary contrast agents for hepatocellular carcinoma diagnosis? A meta-analysis. Pol J Radiol 2024; 89:e402-e413. [PMID: 39257926 PMCID: PMC11384218 DOI: 10.5114/pjr/189614] [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: 04/22/2024] [Accepted: 06/03/2024] [Indexed: 09/12/2024] Open
Abstract
Purpose So far, there have been published several meta-analyses which focused on hepatocellular carcinoma (HCC) detection with hepatobiliary phase (HBP) contrast agents. However, only a few of them aimed at establishing whether there is any added value of the HBP itself for HCC diagnosis. To answer the question, we performed a systematic literature search with the time limit going back to 2010. Material and methods True positive, false positive, false negative, and true negative values with and without the HBP were extracted from the included studies. Pooled sensitivities and specificities with and without the HBP were calculated and summary receiver operating characteristics curves were drawn to assess the diagnostic performance of the studies with and without the HBP. Results A total of 13 studies were included involving 1184 HCC lesions. In 13 studies without the HBP, the pooled sensitivity, specificity, and area under the curve (AUC) were 0.83, 0.89 and 0.94 respectively. In 13 studies with the HBP, the pooled sensitivity, specificity and AUC were 0.91, 0.85 and 0.98 respectively. Conclusions We found no statistically significant differences in sensitivities between studies with and without the HBP (p = 0.1651).
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Goetz A, Verloh N, Utpatel K, Fellner C, Rennert J, Einspieler I, Doppler M, Luerken L, Alizadeh LS, Uller W, Stroszczynski C, Haimerl M. Differentiating Well-Differentiated from Poorly-Differentiated HCC: The Potential and the Limitation of Gd-EOB-DTPA in the Presence of Liver Cirrhosis. Diagnostics (Basel) 2024; 14:1676. [PMID: 39125552 PMCID: PMC11311873 DOI: 10.3390/diagnostics14151676] [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: 07/02/2024] [Revised: 07/30/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
This study uses magnetic resonance imaging (MRI) to investigate the potential of the hepatospecific contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in distinguishing G1- from G2/G3-differentiated hepatocellular carcinoma (HCC). Our approach involved analyzing the dynamic behavior of the contrast agent in different phases of imaging by signal intensity (SI) and lesion contrast (C), to surrounding liver parenchyma, and comparing it across distinct groups of patients differentiated based on the histopathological grading of their HCC lesions and the presence of liver cirrhosis. Our results highlighted a significant contrast between well- and poorly-differentiated lesions regarding the lesion contrast in the arterial and late arterial phases. Furthermore, the hepatobiliary phase showed limited diagnostic value in cirrhotic liver parenchyma due to altered pharmacokinetics. Ultimately, our findings underscore the potential of Gd-EOB-DTPA-enhanced MRI as a tool for improving preoperative diagnosis and treatment selection for HCC while emphasizing the need for continued research to overcome the diagnostic complexities posed by the disease.
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Affiliation(s)
- Andrea Goetz
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Niklas Verloh
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | - Kirsten Utpatel
- Department of Pathology, University Regensburg, 93053 Regensburg, Germany
| | - Claudia Fellner
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Janine Rennert
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Ingo Einspieler
- Department of Radiology, University Hospital Regensburg, 93053 Regensburg, Germany
| | - Michael Doppler
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | - Lukas Luerken
- Department of Radiology, Klinikum Würzburg Mitte, 97074 Würzburg, Germany
| | - Leona S. Alizadeh
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, 60596 Frankfurt am Main, Germany
| | - Wibke Uller
- Department of Diagnostic and Interventional Radiology, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, 79085 Freiburg, Germany
| | | | - Michael Haimerl
- Department of Radiology, Klinikum Würzburg Mitte, 97074 Würzburg, Germany
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Song M, Tao Y, He K, Du M, Guo L, Hu C, Zhang W. Clear cell hepatocellular carcinoma: Gd-EOB-DTPA-enhanced MR imaging features and prognosis. Abdom Radiol (NY) 2024; 49:2606-2621. [PMID: 38557768 DOI: 10.1007/s00261-024-04263-2] [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: 11/09/2023] [Revised: 02/17/2024] [Accepted: 02/20/2024] [Indexed: 04/04/2024]
Abstract
PURPOSE To investigate imaging findings on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and prognosis of clear cell hepatocellular carcinoma (CCHCC) comparing with non-otherwise specified hepatocellular carcinoma (NOS-HCC). METHODS The clinical, pathological and MR imaging features of 42 patients with CCHCC and 84 age-matched patients with NOS-HCC were retrospectively analyzed from January 2015 to October 2021. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors for CCHCC. Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan-Meier analysis. RESULTS CCHCC showed fat content more frequently (P < 0.001) and relatively higher Edmondson tumor grade (P = 0.001) compared with NOS-HCC. The lesion-to-muscle ratio (LMR) and lesion-to-liver ratio (LLR) of CCHCC on pre-enhancement T1-weighted imaging (pre-T1WI) (P = 0.001, P = 0.003) and hepatobiliary phase (HBP) (P = 0.007, P = 0.048) were significantly higher than those of NOS-HCC. The area under the curve (AUC) for fat content, LLR on pre-T1WI and their combination with better diagnostic performance in predicting CCHCC were 0.678, 0.666, and 0.750, respectively. There was no statistically significant difference in clinical outcomes between CCHCC and NOS-HCC. Multivariate Cox analysis confirmed that tumor size > 2 cm and enhancing capsule were independent prognostic factors for DFS and OS among CCHCC patients. CONCLUSION Fat content and adjusted lesion signal intensity on pre-T1WI and HBP could be used to differentiate CCHCC from NOS-HCC. CCHCC had similar prognosis with NOS-HCC.
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Affiliation(s)
- Mingyue Song
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Yuhao Tao
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Kuang He
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Mingzhan Du
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Lingchuan Guo
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China
| | - Weiguo Zhang
- Department of Radiology, The Fourth Affiliated Hospital of Soochow University, Suzhou, 215028, China.
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
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Pastor CM, Vilgrain V. New understanding of hepatobiliary MRI. Nat Rev Gastroenterol Hepatol 2024; 21:459-460. [PMID: 38565648 DOI: 10.1038/s41575-024-00926-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/04/2024]
Affiliation(s)
- Catherine M Pastor
- Université Paris-Cité, Paris, France.
- Centre de Recherche sur l'Inflammation, INSERM 1149, Paris, France.
| | - Valérie Vilgrain
- Université Paris-Cité, Paris, France
- Centre de Recherche sur l'Inflammation, INSERM 1149, Paris, France
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Aoki T, Nishida N, Kurebayashi Y, Sakai K, Morita M, Chishina H, Takita M, Hagiwara S, Ida H, Ueshima K, Minami Y, Tsurusaki M, Nakai T, Sakamoto M, Nishio K, Kudo M. Two Distinct Characteristics of Immune Microenvironment in Human Hepatocellular Carcinoma with Wnt/β-Catenin Mutations. Liver Cancer 2024; 13:285-305. [PMID: 38894812 PMCID: PMC11185857 DOI: 10.1159/000533818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 08/22/2023] [Indexed: 06/21/2024] Open
Abstract
Introduction Immunotherapy is becoming a promising approach for unresectable-hepatocellular carcinoma (HCC); the anti-tumor response is affected by the tumor microenvironment (TME). Although Wnt/β-catenin mutations are reported to cause non-inflamed phenotype, their role on TME remains controversial. We aimed to clarify the heterogeneity of immunophenotype in HCC with Wnt/β-catenin mutations. Methods This study includes 152 resected HCCs; mutations in the catenin beta-1, adenomatous polyposis coli, or AXIN1, or AXIN2 genes were defined as Wnt/β-catenin mutations. With hierarchical cluster analyses, TME was classified into inflamed or non-inflamed classes based on the gene expressions associated with T-cell activation. Expression profiles of molecules related to cell differentiation and biliary-stem cell markers were compared between the TME classes to investigate whether differences in tumor traits were associated with TME. Results Forty of 152 (26.3%) HCCs carried the Wnt/β-catenin mutations. Of these, 33 were classified as non-inflamed (33/40, 82.5%) and 7 as inflamed (7/40, 17.5%). Non-inflamed class was characterized by low number of CD3+, CD4+, and CD8+ cells on immunostaining, and high mRNA expressions of AXIN2 and GLUL, which are involved in the canonical Wnt/β-catenin signaling and hepatocyte differentiation, respectively. Non-inflamed tumors showed higher enhancement on the hepatobiliary-phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) compared to inflamed tumors. HCCs classified as inflamed class are revealed to have high numbers of CD3+, CD4+, and CD8+ tumor infiltrating lymphocytes on immunostaining. This class is associated with increased expression of anti-epithelial cell adhesion molecule and FOXM1 accompanied by upregulation of genes related to interferon-gamma signaling, dendritic cell migration, regulatory T cells, and myeloid-derived suppressor cell activation and recognized as low enhancement nodule on Gd-EOB-DTPA-enhanced MRI. Conclusion Heterogeneity of tumor traits and TME was observed in HCC with Wnt/β-catenin mutation. The potential was indicated that tumor traits and TME are determined not only by the activation of the HNF4A but also by FOXM1, both of which are downstream transcription factor of the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Yutaka Kurebayashi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kazuko Sakai
- Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Masahiro Morita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Hirokazu Chishina
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Masahiro Takita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Satoru Hagiwara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Hiroshi Ida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Masakatsu Tsurusaki
- Department of Radiology, Kindai University Faculty of Medicine, Osakasayama, Japan
| | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kazuto Nishio
- Department of Genome Biology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osakasayama, Japan
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Brandi N, Renzulli M. Liver Lesions at Risk of Transformation into Hepatocellular Carcinoma in Cirrhotic Patients: Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement. J Clin Transl Hepatol 2024; 12:100-112. [PMID: 38250460 PMCID: PMC10794268 DOI: 10.14218/jcth.2023.00130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 07/04/2023] [Accepted: 07/25/2023] [Indexed: 01/23/2024] Open
Abstract
Recent technical advances in liver imaging and surveillance for patients at high risk for developing hepatocellular carcinoma (HCC) have led to an increase in the detection of borderline hepatic nodules in the gray area of multistep carcinogenesis, particularly in those that are hypointense at the hepatobiliary phase (HBP) and do not show arterial phase hyperenhancement. Given their potential to transform and advance into hypervascular HCC, these nodules have progressively attracted the interest of the scientific community. To date, however, no shared guidelines have been established for the decision management of these borderline hepatic nodules. It is therefore extremely important to identify features that indicate the malignant potential of these nodules and the likelihood of vascularization. In fact, a more complete knowledge of their history and evolution would allow outlining shared guidelines for their clinical-surgical management, to implement early treatment programs and decide between a preventive curative treatment or a watchful follow-up. This review aims to summarize the current knowledge on hepatic borderline nodules, particularly focusing on those imaging features which are hypothetically correlated with their malignant evolution, and to discuss current guidelines and ongoing management in clinical practice.
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Affiliation(s)
- Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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van Rosmalen BV, Visentin M, Furumaya A, van Delden OM, Kazemier G, van Gulik TM, Verheij J, Stieger B. Association Between Gadoxetic Acid-Enhanced Magnetic Resonance Imaging, Organic Anion Transporters, and Farnesoid X Receptor in Benign Focal Liver Lesions. Drug Metab Dispos 2024; 52:118-125. [PMID: 38050024 DOI: 10.1124/dmd.123.001492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 11/21/2023] [Accepted: 11/27/2023] [Indexed: 12/06/2023] Open
Abstract
The organic anion uptake and efflux transporters [organic anion-transporting polypeptide (OATP)1B1, OATP1B3 and multidrug resistance-associated protein (MRP)2 and MRP3] that mediate the transport of the hepatobiliary-specific contrast agent gadoxetate (Gd-EOB-DTPA) are direct or indirect targets of the farnesoid X receptor (FXR), a key regulator of bile acid and lipid homeostasis. In benign liver tumors, FXR expression and activation is not yet characterized. We investigated the expression and activation of FXR and its targets in hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) and their correlation with Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Gd-EOB-DTPA MRI patterns were assessed by an expert radiologist. The intensity of the lesions on the hepatobiliary phase was correlated to mRNA expression levels of OATP1B1, OATP1B3, MRP2, MRP3, FXR, and small heterodimer partner (SHP) in fresh surgical specimens of patients with FNH or HCA subtypes. Normal and tumor sample pairs of 43 HCA and 14 FNH were included. All FNH (14/14) were hyperintense. Of the 34 HCA with available Gd-EOB-DTPA-enhanced MRI, 6 were hyperintense and 28 HCA were hypointense. OATP1B3 was downregulated in the hypointense tumors compared with normal surrounding liver tissue (2.77±3.59 vs. 12.9±15.6, P < 0.001). A significant positive correlation between FXR expression and activation and OATP1B3 expression level was found in the HCA cohort. SHP showed a trend toward downregulation in hypointense HCA. In conclusion, this study suggests that the MRI relative signal in HCA may reflect expression level and/or activity of SHP and FXR. Moreover, our data confirms the pivotal role of OATP1B3 in Gd-EOB-DTPA uptake in HCA. SIGNIFICANCE STATEMENT: FXR represents a valuable target for the treatment of liver disease and metabolic syndrome. Currently, two molecules, ursodeoxycholate and obeticholate, are approved for the treatment of primary biliary cirrhosis and cholestasis, with several compounds in clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease. Because FXR expression and activation is associated with gadoxetate accumulation in HCA, an atypical gadoxetate-enhanced MRI pattern might arise in patients under FXR-targeted therapy, thereby complicating the differential diagnosis.
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Affiliation(s)
- Belle V van Rosmalen
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Michele Visentin
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Alicia Furumaya
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Otto M van Delden
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Geert Kazemier
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Thomas M van Gulik
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Joanne Verheij
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
| | - Bruno Stieger
- Amsterdam UMC Location University of Amsterdam, Department of Surgery, Amsterdam, The Netherlands (B.V.vR., A.F., T.M.vG.); Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands (B.V.vR., A.F., O.M.vD., T.M.vG., J.V.); Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zürich, Switzerland (M.V., B.S.); Amsterdam UMC Location University of Amsterdam, Department of Radiology, Amsterdam, The Netherlands (O.M.vD.); Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Surgery, Amsterdam, The Netherlands (G.K.); Cancer Center Amsterdam, Amsterdam, The Netherlands (G.K.); and Amsterdam UMC Location University of Amsterdam, Department of Pathology, Amsterdam, The Netherlands (J.V.)
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Hagiwara S, Nishida N, Kudo M. Advances in Immunotherapy for Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:2070. [PMID: 37046727 PMCID: PMC10093619 DOI: 10.3390/cancers15072070] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 03/23/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor's immune environment, it is essential to understand the immune environment of hepatocellular carcinoma to select ICI therapeutic indications and develop biomarkers. A network of diverse cellular and humoral factors establishes cancer immunity. By analyzing individual cases and classifying them from the viewpoint of tumor immunity, attempts have been made to select the optimal therapeutic drug for immunotherapy, including ICIs. ICI treatment is discussed from the viewpoints of immune subclass of HCC, Wnt/β-catenin mutation, immunotherapy in NASH-related HCC, the mechanism of HPD onset, and HBV reactivation.
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Affiliation(s)
- Satoru Hagiwara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan
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Song J, Ren T, Duan Y, Guo H, Wang G, Gan Y, Bai M, Dong X, Zhao Z, An J. Near-infrared fluorescence imaging of hepatocellular carcinoma cells regulated by β-catenin signaling pathway. Front Oncol 2023; 13:1140256. [PMID: 37064109 PMCID: PMC10090467 DOI: 10.3389/fonc.2023.1140256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
BackgroundNear-infrared fluorescence (NIRF) imaging has recently emerged as a promising tool for noninvasive cancer imaging. However, lack of tumor sensitivity and specificity restricts the application of NIRF dyes in surgical navigation.MethodsHerein, we investigated the imaging features of NIRF dye MHI-148 and indocyanine green (ICG) in live cell imaging and xenograft nude mice models. TCGA dataset analysis and immunohistochemistry were conducted to investigate the expression of OATPs or ABCGs in hepatocellular carcinoma (HCC) tissues. OATPs or ABCGs were knocked down and overexpressed in HCC cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Further, qRT-PCR ,Western blotting and the use of agonists or inhibitors targeting β-catenin signaling pathway were applied to explore its important role in regulation of OATP2B1 and ABCG2 expression.ResultsHere we demonstrated that NIRF dye MHI-148 was biocompatible as indocyanine green (ICG) but with higher imaging intensity and preferential uptake and retention in hepatocellular carcinoma (HCC) cells and tissues. Moreover, our data indicated that membrane transporters OATP2B1 and ABCG2, which regulated by β-catenin signaling pathway, mediated tumor-specific accumulation and retention of MHI-148 in HCC cells. In addition, the treatment with β-catenin inhibitor significantly enhanced the accumulation of MHI-148 in HCC tissues and improved the efficacy of tumor imaging with MHI-148 in vivo.ConclusionsOur study uncovers a mechanism that links the distribution and expression of the membrane transporters OATP2B1 and ABCG2 to the tumor-specific accumulation of MHI-148, and provides evidence supporting a regulating role of the β-catenin signaling pathway in OATP2B1 and ABCG2- induced retention of MHI-148 inHCC tissues, and strategy targeting key components of MHI-148 transport machinery may be a potential approach to improve HCC imaging.
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Affiliation(s)
- Jian Song
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Tingting Ren
- State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi’an, China
- *Correspondence: Jiaze An, ; Tingting Ren, ; Zheng Zhao,
| | - Yanheng Duan
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Haitao Guo
- State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi’an, China
| | - Gang Wang
- State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi’an, China
| | - Yu Gan
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Mengcai Bai
- State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine, Fourth Military Medical University, Xi’an, China
| | - Xiaotian Dong
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Zheng Zhao
- Third Department of Medical Oncology, Shaanxi Provincial Cancer Hospital, Xi’an, China
- *Correspondence: Jiaze An, ; Tingting Ren, ; Zheng Zhao,
| | - Jiaze An
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- *Correspondence: Jiaze An, ; Tingting Ren, ; Zheng Zhao,
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Minamiguchi K, Nishiofuku H, Saito N, Sato T, Taiji R, Matsumoto T, Maeda S, Chanoki Y, Tachiiri T, Kunichika H, Inoue T, Marugami N, Tanaka T. Quantitative Analysis of Signal Heterogeneity in the Hepatobiliary Phase of Pretreatment Gadoxetic Acid-Enhanced MRI as a Prognostic Imaging Biomarker in Transarterial Chemoembolization for Intermediate-Stage Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15041238. [PMID: 36831582 PMCID: PMC9954181 DOI: 10.3390/cancers15041238] [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: 12/17/2022] [Revised: 02/07/2023] [Accepted: 02/12/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND In the era of local and systemic therapies for intermediate-stage hepatocellular carcinoma (HCC), personalized therapy has become available. The aim of our study was to evaluate the usefulness of quantitative analysis of pretreatment gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) to predict prognosis following transarterial chemoembolization (TACE). METHODS This retrospective study included patients with treatment-naïve intermediate-stage HCC who underwent EOB-MRI before the initial TACE and were treated by initial TACE between February 2007 and January 2016. Signal heterogeneity in the hepatobiliary phase (HBP) of EOB-MRI was quantitatively evaluated by the coefficient of variation (CV). The cutoff CV value was determined using the Classification and Regression Tree algorithm. RESULTS A total of 64 patients were enrolled. In multivariate analysis, High CV (≥0.16) was significantly associated with poor prognosis (p = 0.038). In a subgroup analysis of patients within up-to-7 criteria, MST was significantly shorter in the High CV group than in the Low CV group (37.7 vs. 82.9 months, p = 0.024). In patients beyond up-to-7 criteria, MST was 18.0 and 38.3 months in the High CV and Low CV groups, respectively (p = 0.182). In both groups scanned at 1.5 T or 3.0 T, High CV was significantly associated with poor prognosis (p = 0.001 and 0.003, respectively). CONCLUSION CV of the tumor in the HBP of EOB-MRI is a valuable prognostic factor of TACE.
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Affiliation(s)
- Kiyoyuki Minamiguchi
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
- Correspondence: ; Tel.:+81-744-22-3051
| | - Hideyuki Nishiofuku
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Natsuhiko Saito
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Takeshi Sato
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Ryosuke Taiji
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Takeshi Matsumoto
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Shinsaku Maeda
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Yuto Chanoki
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Tetsuya Tachiiri
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Hideki Kunichika
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Takashi Inoue
- Department of Evidence-Based Medicine, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Nagaaki Marugami
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
| | - Toshihiro Tanaka
- Department of Diagnostic and Interventional Radiology, Nara Medical University, Shijyocho 840, Kashihara City 634-8522, Japan
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Naka T, Kaneko M, Hori H, Minami H. [Investigation of Changing Imaging Contrast Using Compressed Sensing in Gd-EOB-DTPA Hepatocyte Phase]. Nihon Hoshasen Gijutsu Gakkai Zasshi 2022; 78:1445-1450. [PMID: 36351609 DOI: 10.6009/jjrt.2022-1266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
In recent years, gadolinium ethoxybenzyl diethylenetriamine pantaacetic acid (Gd-EOB-DTPA) has been commonly used in magnetic resonance imaging (MRI) for liver contrast studies. The purpose of this study was to investigate the effect of Hyper SENSE factor on contrast in the Gd-EOB-DTPA hepatocyte phase. The subjects were 21 patients [16 males and 5 females, aged 50-94 years (mean age 68±12years)] who underwent hepatic contrast-enhanced MRI with Gd-EOB-DTPA from March 2021 to December 2021. The contrast ratios (CRs) of liver/spleen and liver/tumor were measured when the Hyper SENSE factor was changed to 1.0, 1.4 and 1.8. As a result, there was no statistically significant difference in signal intensity and CR with the change in the Hyper SENSE factor. In this study, the acquisition time can be shortened without decreasing the CR; therefore, it was suggested to improve MR images to avoid motion artifact.
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Affiliation(s)
| | | | - Hiroki Hori
- FUS Center, Moriyama Cranial Nerves Center Hospital
| | - Hiroaki Minami
- Department of Radiology, Yokohama Minami Kyosai Hospital
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Does hypointense HCC in the Hepatobiliary Phase at Gadoxetate-Enhanced MRI Predict Recurrence After Surgery? A Systematic Review and Meta-analysis. Acad Radiol 2022:S1076-6332(22)00506-2. [DOI: 10.1016/j.acra.2022.09.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 09/11/2022] [Accepted: 09/17/2022] [Indexed: 11/23/2022]
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Zeng F, Dai H, Li X, Guo L, Jia N, Yang J, Huang D, Zeng H, Chen W, Zhang L, Qin G. Preoperative radiomics model using gadobenate dimeglumine-enhanced magnetic resonance imaging for predicting β-catenin mutation in patients with hepatocellular carcinoma: A retrospective study. Front Oncol 2022; 12:916126. [PMID: 36185240 PMCID: PMC9523364 DOI: 10.3389/fonc.2022.916126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 09/05/2022] [Indexed: 11/13/2022] Open
Abstract
Objective To compare and evaluate radiomics models to preoperatively predict β-catenin mutation in patients with hepatocellular carcinoma (HCC). Methods Ninety-eight patients who underwent preoperative gadobenate dimeglumine (Gd-BOPTA)-enhanced MRI were retrospectively included. Volumes of interest were manually delineated on arterial phase, portal venous phase, delay phase, and hepatobiliary phase (HBP) images. Radiomics features extracted from different combinations of imaging phases were analyzed and validated. A linear support vector classifier was applied to develop different models. Results Among all 15 types of radiomics models, the model with the best performance was seen in the RHBP radiomics model. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity of the RHBP radiomics model in the training and validation cohorts were 0.86 (95% confidence interval [CI], 0.75–0.93), 0.75, 1.0, and 0.65 and 0.82 (95% CI, 0.63–0.93), 0.73, 0.67, and 0.76, respectively. The combined model integrated radiomics features in the RHBP radiomics model, and signatures in the clinical model did not improve further compared to the single HBP radiomics model with AUCs of 0.86 and 0.76. Good calibration for the best RHBP radiomics model was displayed in both cohorts; the decision curve showed that the net benefit could achieve 0.15. The most important radiomics features were low and high gray-level zone emphases based on gray-level size zone matrix with the same Shapley additive explanation values of 0.424. Conclusion The RHBP radiomics model may be used as an effective model indicative of HCCs with β-catenin mutation preoperatively and thus could guide personalized medicine.
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Affiliation(s)
- Fengxia Zeng
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hui Dai
- Hospital Office, Ganzhou People’s Hospital, Ganzhou, China
- Hospital Office, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
| | - Xu Li
- School of Biomedical Engineering, Southern Medical University, Guangzhou, China
| | - Le Guo
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ningyang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jun Yang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Danping Huang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hui Zeng
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Weiguo Chen
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ling Zhang
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence: Ling Zhang, ; Genggeng Qin,
| | - Genggeng Qin
- Department of Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Radiology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, China
- *Correspondence: Ling Zhang, ; Genggeng Qin,
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Nolan PE, Catania R, Vendrami CL, Borhani AA, Miller FH. Large Regenerative Nodules and Focal Nodular Hyperplasia-Like Lesions. Radiol Clin North Am 2022; 60:795-808. [DOI: 10.1016/j.rcl.2022.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Öcal O, Rössler D, Gasbarrini A, Berg T, Klümpen HJ, Bargellini I, Peynircioglu B, van Delden O, Schulz C, Schütte K, Iezzi R, Pech M, Malfertheiner P, Sangro B, Ricke J, Seidensticker M. Gadoxetic acid uptake as a molecular imaging biomarker for sorafenib resistance in patients with hepatocellular carcinoma: a post hoc analysis of the SORAMIC trial. J Cancer Res Clin Oncol 2022; 148:2487-2496. [PMID: 34541612 PMCID: PMC9349099 DOI: 10.1007/s00432-021-03803-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/11/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Gadoxetic acid uptake on hepatobiliary phase MRI has been shown to correlate with ß-catenin mutation in patients with HCC, which is associated with resistance to certain therapies. This study aimed to evaluate the prognostic value of gadoxetic acid uptake on hepatobiliary phase MRI in patients with advanced HCC receiving sorafenib. METHODS 312 patients with available baseline hepatobiliary phase MRI images received sorafenib alone or following selective internal radiation therapy (SIRT) within SORAMIC trial. The signal intensity of index tumor and normal liver parenchyma were measured on the native and hepatobiliary phase MRI images, and relative tumor enhancement higher than relative liver enhancement were accepted as high gadoxetic acid uptake, and its prognostic value was assessed using univariate and multivariate Cox proportional hazard models. RESULTS The median OS of the study population was 13.4 (11.8-14.5) months. High gadoxetic acid uptake was seen in 51 (16.3%) patients, and none of the baseline characteristics was associated with high uptake. In univariate analysis, high gadoxetic acid uptake was significantly associated with shorter overall survival (10.7 vs. 14.0 months, p = 0.005). Multivariate analysis confirmed independent prognostic value of high gadoxetic acid uptake (HR, 1.7 [1.21-2.3], p = 0.002), as well as Child-Pugh class (p = 0.033), tumor diameter (p = 0.002), and ALBI grade (p = 0.015). CONCLUSION In advanced HCC patients receiving sorafenib (alone or combined with SIRT), high gadoxetic acid uptake of the tumor on pretreatment MRI, a surrogate of ß-catenin mutation, correlates with shorter survival. Gadoxetic acid uptake status might serve in treatment decision-making process.
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Affiliation(s)
- Osman Öcal
- Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Daniel Rössler
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Antonio Gasbarrini
- Fondazione Policlinico Gemelli IRCCS, Università' Cattolica del Sacro Cuore, Roma, Italy
| | - Thomas Berg
- Klinik Und Poliklinik Für Gastroenterologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Leipzig, Germany
| | - Heinz-Josef Klümpen
- Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Irene Bargellini
- Department of Vascular and Interventional Radiology, University Hospital of Pisa, Pisa, Italy
| | | | - Otto van Delden
- Department of Radiology and Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Christian Schulz
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Kerstin Schütte
- Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von-Guericke University, Magdeburg, Germany
| | - Roberto Iezzi
- Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Di Radiologia, Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica ed Ematologia, Roma, Italy
| | - Maciej Pech
- Departments of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
| | | | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain
| | - Jens Ricke
- Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Max Seidensticker
- Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
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20
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Aoki T, Nishida N, Ueshima K, Morita M, Chishina H, Takita M, Hagiwara S, Ida H, Minami Y, Yamada A, Sofue K, Tsurusaki M, Kudo M. Higher Enhancement Intrahepatic Nodules on the Hepatobiliary Phase of Gd-EOB-DTPA-Enhanced MRI as a Poor Responsive Marker of Anti-PD-1/PD-L1 Monotherapy for Unresectable Hepatocellular Carcinoma. Liver Cancer 2021. [PMID: 34950184 DOI: 10.1159/000518048.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Introduction Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. Methods A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. Results The median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. Conclusion The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
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Affiliation(s)
- Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masahiro Morita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Hirokazu Chishina
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masahiro Takita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Satoru Hagiwara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Hiroshi Ida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Akira Yamada
- Department of Radiology, Shinshu University School of Medicine, Nagano, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masakatsu Tsurusaki
- Department of Radiology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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21
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Ebara M, Shibuya K, Shimada H, Kawashima M, Hirasawa H, Taketomi-Takahashi A, Ohno T, Tsushima Y. Evaluation of Threshold Dose of Damaged Hepatic Tissue After Carbon-Ion Radiation Therapy Using Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging. Adv Radiat Oncol 2021; 6:100775. [PMID: 34934860 PMCID: PMC8655403 DOI: 10.1016/j.adro.2021.100775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/09/2021] [Indexed: 11/25/2022] Open
Abstract
Purpose To evaluate the threshold dose and associated factors using signal-intensity changes in the irradiated area after carbon-ion radiation therapy (C-ion RT) for patients with liver cancer. Methods and Materials Patients treated for the first time with C-ion RT for malignant liver tumors and followed up with 3-Tesla gadoxetic acid (Gd-EOB-DTPA)–enhanced magnetic resonance imaging (MRI) 3 months after treatment completion were retrospectively enrolled. The volume of focal liver reaction (FLR), a low-intensity area in the hepatobiliary phase of Gd-EOB-DTPA after treatment, was measured. Corrected FLR (cFLR) volume, defined as FLR corrected for changes in tumor volume from before to after treatment, was calculated, and the threshold dose was determined by applying the cFLR volume in the dose-volume histogram. To evaluate potential mismatch in fusion images of planning computed tomography and follow-up MRI, the concordance coefficient (CC) was measured, and patients with a CC < 0.7 were excluded. Sixty patients were included. Multiple regression analysis was performed with the threshold dose as the objective variable and the age, dose, number of fractionations, Child-Pugh score, pretreatment liver volume, and pretreatment tumor volume as explanatory variables. The Student t test or Mann-Whitney U test was used as required. Results The median threshold doses for each number of dose fractionations (4 fractions, 12 fractions, and overall) were 51.6, 51.9, and 51.8 Gy (relative biological effectiveness [RBE]), respectively, in patients categorized as Child-Pugh class A and 27.0, 28.8, and 27.0 Gy (RBE), respectively, in patients categorized as Child-Pugh class B. In the multiple-regression analysis, only the Child-Pugh score was significant (P < .001). The number of dose fractionations was not statistically significant. Conclusions Although few patients in the study had decreased liver function, baseline liver function was the only factor significantly associated with the median threshold dose. These findings facilitate appropriate patient selection to receive C-ion RT for malignant hepatic tumors.
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Affiliation(s)
- Masashi Ebara
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Kei Shibuya
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan.,Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.,Gunma University Heavy Ion Medical Center, Gunma, Japan
| | | | | | - Hiromi Hirasawa
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Ayako Taketomi-Takahashi
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Tatsuya Ohno
- Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.,Gunma University Heavy Ion Medical Center, Gunma, Japan
| | - Yoshito Tsushima
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Gunma, Japan
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22
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Quantification of contrast agent uptake in the hepatobiliary phase helps to differentiate hepatocellular carcinoma grade. Sci Rep 2021; 11:22991. [PMID: 34837039 PMCID: PMC8626433 DOI: 10.1038/s41598-021-02499-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 11/10/2021] [Indexed: 12/02/2022] Open
Abstract
This study aimed to assess the degree of differentiation of hepatocellular carcinoma (HCC) using Gd-EOB-DTPA-assisted magnetic resonance imaging (MRI) with T1 relaxometry. Thirty-three solitary HCC lesions were included in this retrospective study. This study's inclusion criteria were preoperative Gd-EOB-DTPA-assisted MRI of the liver and a histopathological evaluation after hepatic tumor resection. T1 maps of the liver were evaluated to determine the T1 relaxation time and reduction rate between the native phase and hepatobiliary phase (HBP) in liver lesions. These findings were correlated with the histopathologically determined degree of HCC differentiation (G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated). There was no significant difference between well-differentiated (950.2 ± 140.2 ms) and moderately/poorly differentiated (1009.4 ± 202.0 ms) HCCs in the native T1 maps. After contrast medium administration, a significant difference (p ≤ 0.001) in the mean T1 relaxation time in the HBP was found between well-differentiated (555.4 ± 140.2 ms) and moderately/poorly differentiated (750.9 ± 146.4 ms) HCCs. For well-differentiated HCCs, the reduction rate in the T1 time was significantly higher at 0.40 ± 0.15 than for moderately/poorly differentiated HCCs (0.25 ± 0.07; p = 0.006). In conclusion this study suggests that the uptake of Gd-EOB-DTPA in HCCs is correlated with tumor grade. Thus, Gd-EOB-DTPA-assisted T1 relaxometry can help to further differentiation of HCC.
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23
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Yasunaka T, Takeuchi Y, Takaki A, Kondo F, Yoshizumi T, Kohashi K, Oyama A, Adachi T, Wada N, Onishi H, Shiraha H, Okada H. A case of focal nodular hyperplasia with hepatic failure treated with liver transplantation. Clin J Gastroenterol 2021; 15:171-176. [PMID: 34807397 DOI: 10.1007/s12328-021-01529-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/30/2021] [Indexed: 12/18/2022]
Abstract
Focal nodular hyperplasia (FNH) is a benign nodular lesion, but because of its feature of portal tract vessel abnormality, it may induce portal hypertension. A 27-year-old woman was admitted with a fever. A large nodule with satellite lesions was found in the liver and cotton wool-like feature of arteries were detected on angiography. Technetium galactosyl serum albumin scintigraphy and diagnostic laparoscopy showed that the tumor site was functional, while the surrounding area was a non-functional fibrotic area. A biopsy specimen indicated that the nodular lesion was an FNH-like lesion. She experienced several instances of variceal rupture and suffered liver failure, receiving liver transplantation. The excised liver showed a centrally scarred area in the nodule, indicating that the diagnosis was FNH. We herein report this case as a rare case of FNH that progressed to liver failure.
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Affiliation(s)
- Tetsuya Yasunaka
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yasuto Takeuchi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Akinobu Takaki
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Fukuo Kondo
- Department of Pathology, School of Medicine, Teikyo University, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Tomoharu Yoshizumi
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Kenichi Kohashi
- Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-Ku, Fukuoka, 812-8582, Japan
| | - Atsushi Oyama
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Takuya Adachi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Nozomu Wada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hideki Onishi
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hidenori Shiraha
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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24
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Kurokawa S, Tanaka T, Yamazaki H, Noguchi S, Wada Y, Nishida H, Akiyoshi H. Comparing the CT and MRI findings for canine primary hepatocellular lesions. Vet Rec 2021; 190:e1083. [PMID: 34751436 DOI: 10.1002/vetr.1083] [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: 03/10/2021] [Revised: 08/24/2021] [Accepted: 10/17/2021] [Indexed: 11/11/2022]
Abstract
BACKGROUND Triple-phase CT and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI have been used to differentiate hepatocellular carcinomas (HCCs) in dogs. METHODS This retrospective case series aimed to compare the CT findings with MRI findings of 20 canine hepatocellular lesions, including eight poorly/moderately-differentiated HCCs, eight well-differentiated HCCs and four hyperplasias. CT data were analysed, and the following parameters were noted: vessel enhancement, enhancement pattern in the equilibrium phase, maximal transverse diameter, the lowest enhancement, and the attenuation values of each hepatocellular lesion in the precontrast and triple-phase series, including the arterial phase, portal phase and equilibrium phase. MRI data were analysed, and the following parameters were noted: signal intensities of each hepatocellular lesion on T2-weighted images and T1-weighted images, and signal intensity ratio of the hepatocellular lesions in the hepatobiliary phase. RESULTS In 62.5% of poorly/moderately-differentiated HCC and 75% of well-differentiated HCC, presumptive necrosis was detected on CT and MRI. In the hepatobiliary phase on MRI, the median signal intensity ratio of poorly/moderately-differentiated HCC (0.54 [range: 0.3-0.71]) was significantly lower than that of well-differentiated HCC (0.75 [range: 0.6-0.96]) and hyperplasia (0.79 [range: 071-0.98]; p = 0.02 and p = 0.02, respectively). CONCLUSION Gd-EOB-DTPA-enhanced MRI may be a superior modality for differentiating hepatocellular origin lesions.
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Affiliation(s)
- Shohei Kurokawa
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Surgery, Osaka Prefecture University, Izumisano, Japan
| | - Toshiyuki Tanaka
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Surgery, Osaka Prefecture University, Izumisano, Japan.,Kinki Animal Medical Training Institute & Veterinary Clinic, Higashiosaka, Japan
| | - Hiroki Yamazaki
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Surgery, Osaka Prefecture University, Izumisano, Japan
| | - Shunsuke Noguchi
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Radiology, Osaka Prefecture University, Izumisano, Japan
| | - Yusuke Wada
- Veterinary Medical Centre, College of Life, Environmental and Advanced Sciences, Osaka Prefecture University, Izumisano, Japan
| | - Hidetaka Nishida
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Surgery, Osaka Prefecture University, Izumisano, Japan
| | - Hideo Akiyoshi
- Department of Graduate School of Life and Environmental Sciences, Laboratory of Veterinary Surgery, Osaka Prefecture University, Izumisano, Japan
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25
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Cannella R, Vernuccio F, Antonucci M, Gagliano DS, Matteini F, Midiri M, Brancatelli G. LI-RADS ancillary features favoring benignity: is there a role in LR-5 observations? Eur Radiol 2021; 32:1804-1812. [PMID: 34545444 DOI: 10.1007/s00330-021-08267-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/29/2021] [Accepted: 08/11/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVES The Liver Imaging Reporting and Data System algorithm allows category downgrade in the presence of ancillary features (AFs) favoring benignity, even in observations categorized as LR-5. This study aims to assess the role of AFs favoring benignity in LR-5 observations and their impact on category downgrade. METHODS This study included high-risk patients with at least one LR-5 observation imaged with gadoxetate disodium MRI. Three readers with different experience levels independently evaluated the presence of AFs favoring malignancy (not hepatocellular carcinoma (HCC) in particular and HCC in particular) and AFs favoring benignity. Category downgrade was considered possible in the presence of ≥ 1 AF favoring benignity and no AF favoring malignancy. Correlation between observations size and number of AFs was assessed using Spearman's rank correlation coefficient. Cohen's kappa (k) test was used to assess inter-reader agreement. RESULTS The final study cohort included 162 LR-5 (mean size: 23 ± 16 mm) in 119 patients. AFs favoring benignity were reported in 9 (5.6%), 20 (12.3%), and 10 (6.2%) LR-5 observations by reader 1, reader 2, and reader 3, respectively. Hepatobiliary phase isointensity was observed in 6 (3.7%), 2 (1.2%), and 7 (4.3%) observations, respectively. Category downgrade was considered possible in only one (0.6%) observation by reader 1 and reader 3. There was a significant correlation between observation size and number of AFs favoring malignancy (p < 0.001), not HCC in particular (p ≤ 0.010), and favoring HCC in particular (p < 0.001). Inter-reader agreement of AFs favoring benignity was poor to moderate (k range: - 0.01, 0.43). CONCLUSIONS AFs favoring benignity are not uncommon in LR-5 observations, but category downgrade is exceptional. KEY POINTS • Ancillary features favoring benignity are encountered in 5.6-12.3% of observations categorized as LR-5. • Category downgrade of LR-5 observations is very rare (0.6% of observations) in the presence of AFs favoring benignity due to the high prevalence (98-99%) of ancillary features favoring malignancy in LR-5 observations. • The inter-reader agreement of ancillary features favoring benignity is poor to moderate (k range: - 0.01, 0.43) in readers with different levels of experience.
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Affiliation(s)
- Roberto Cannella
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy.
- Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127, Palermo, Italy.
| | - Federica Vernuccio
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Michela Antonucci
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Domenico Salvatore Gagliano
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Francesco Matteini
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Massimo Midiri
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
| | - Giuseppe Brancatelli
- Section of Radiology - Department of Biomedicine, Neuroscience and Advanced Diagnostics, BiND, University Hospital "Paolo Giaccone", Via del Vespro 129, 90127, Palermo, Italy
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26
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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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27
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Aoki T, Nishida N, Ueshima K, Morita M, Chishina H, Takita M, Hagiwara S, Ida H, Minami Y, Yamada A, Sofue K, Tsurusaki M, Kudo M. Higher Enhancement Intrahepatic Nodules on the Hepatobiliary Phase of Gd-EOB-DTPA-Enhanced MRI as a Poor Responsive Marker of Anti-PD-1/PD-L1 Monotherapy for Unresectable Hepatocellular Carcinoma. Liver Cancer 2021; 10:615-628. [PMID: 34950184 PMCID: PMC8647075 DOI: 10.1159/000518048] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 06/23/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. METHODS A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. RESULTS The median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. CONCLUSION The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
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Affiliation(s)
- Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan,*Masatoshi Kudo,
| | - Naoshi Nishida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masahiro Morita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Hirokazu Chishina
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masahiro Takita
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Satoru Hagiwara
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Hiroshi Ida
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Akira Yamada
- Department of Radiology, Shinshu University School of Medicine, Nagano, Japan
| | - Keitaro Sofue
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masakatsu Tsurusaki
- Department of Radiology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI. Cancers (Basel) 2021; 13:cancers13143633. [PMID: 34298844 PMCID: PMC8304228 DOI: 10.3390/cancers13143633] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 07/10/2021] [Accepted: 07/16/2021] [Indexed: 12/29/2022] Open
Abstract
Simple Summary HCC with alterations in CTNNB1 (which encodes β-catenin) is resistant to immune checkpoint inhibitors and is associated with HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI in resectable HCC. However, the prevalence, characteristics, mutation profile, and treatment response in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI are not well clarified. In this study, we showed that the prevalence was 13%, and the response to lenvatinib does not differ between HCC with and without iso-high intensity in the hepatobiliary phase of EOB-MRI. We analyzed CTNNB-1 mutations using cell-free DNA, providing support for their association with iso-high intensity in the hepatobiliary phase of EOB-MRI. Abstract In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study’s findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.
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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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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: 405] [Impact Index Per Article: 101.3] [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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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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Pilot study of gadoxetate disodium-enhanced mri for localized and metastatic prostate cancers. Sci Rep 2021; 11:5662. [PMID: 33707581 PMCID: PMC7952731 DOI: 10.1038/s41598-021-84960-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 02/18/2021] [Indexed: 11/13/2022] Open
Abstract
OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p < 0.0078). The localized cancer subgroup (n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer.
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Kim JW, Lee CH. [Recent Updates of Abbreviated MRI for Hepatocellular Carcinoma Screening]. TAEHAN YONGSANG UIHAKHOE CHI 2021; 82:280-297. [PMID: 36238735 PMCID: PMC9431949 DOI: 10.3348/jksr.2021.0025] [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: 02/08/2021] [Revised: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 11/15/2022]
Abstract
International guidelines recommended screening with ultrasonography (US) every 6 months for patients at risk for hepatocellular carcinoma (HCC). However, US demonstrates low sensitivity for the early detection of HCC. Magnetic resonance imaging (MRI) plays an important role in the noninvasive diagnosis of HCC, but it is not suitable for surveillance due to its lengthy examination and high cost. Therefore, several studies have been using various abbreviated MRI strategies, including noncontrast abbreviated MRI, dynamic contrast-enhanced abbreviated MRI, and abbreviated MRI using hepatobiliary phase image for HCC surveillance. In this article, we aim to review these various strategies and explore the future direction of HCC surveillance considering the cost-effectiveness aspect.
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Zhou X, Long L, Mo Z, Li Y. OATP1B3 Expression in Hepatocellular Carcinoma Correlates with Intralesional Gd-EOB-DTPA Uptake and Signal Intensity on Gd-EOB-DTPA-Enhanced MRI. Cancer Manag Res 2021; 13:1169-1177. [PMID: 33603462 PMCID: PMC7882717 DOI: 10.2147/cmar.s292197] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/05/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND To evaluate the predictive value of the OATP1B3 expression in hepatocellular carcinoma (HCC) for the gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) uptake and the signal intensity (SI) in the hepatobiliary (HB) phase. METHODS In this retrospective study, we analyzed 69 liver nodules of 64 patients who underwent Gd-EOB-DTPA enhancement magnetic resonance imaging (MRI) before operation. Based on the SI in the HB phase, the patients were categorized into the hypointense HCC and iso- or hyperintense HCC groups. The OATP1B3 expression was detected by polymerase chain reaction (PCR) and immunohistochemistry. The differences between the expression of OATP1B3 and Gd-EOB-DTPA enhanced magnetic resonance imaging between the two groups of hepatocellular carcinoma were compared. The relationship between the OATP1B3 expression and the SI and relative enhancement (RE) was analyzed. RESULTS The examined HCC nodules were 59 hypointense HCC and 10 iso- or hyperintense. The relative expressions of OATP1B3, HB-phase signal, and the RE of the HB phase in iso- or hyperintense were significantly higher than those of the hypointense HCC, while the RE of the HB phase increased with an increase in the OATP1B3 expression (P < 0.05). CONCLUSION The OATP1B3 expression in HCC can predict the uptake of Gd-EOB-DTPA and the SI of the HB phase. We believe that the evaluation of OATP1B3 expression will facilitate the comprehension of imaging performance of HCC in Gd-EOB-DTPA-enhanced MRI.
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Affiliation(s)
- Xiaojiao Zhou
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Liling Long
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Zhiqing Mo
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China
| | - Yajuan Li
- Department of Radiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China
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Kovac JD, Ivanovic A, Milovanovic T, Micev M, Alessandrino F, Gore RM. An overview of hepatocellular carcinoma with atypical enhancement pattern: spectrum of magnetic resonance imaging findings with pathologic correlation. Radiol Oncol 2021; 55:130-143. [PMID: 33544992 PMCID: PMC8042819 DOI: 10.2478/raon-2021-0004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 12/15/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the setting of cirrhotic liver, the diagnosis of hepatocellular carcinoma (HCC) is straightforward when typical imaging findings consisting of arterial hypervascularity followed by portal-venous washout are present in nodules larger than 1 cm. However, due to the complexity of hepatocarcinogenesis, not all HCCs present with typical vascular behaviour. Atypical forms such as hypervascular HCC without washout, isovascular or even hypovascular HCC can pose diagnostic dilemmas. In such cases, it is important to consider also the appearance of the nodules on diffusion-weighted imaging and hepatobiliary phase. In this regard, diffusion restriction and hypointensity on hepatobiliary phase are suggestive of malignancy. If both findings are present in hypervascular lesion without washout, or even in iso- or hypovascular lesion in cirrhotic liver, HCC should be considered. Moreover, other ancillary imaging findings such as the presence of the capsule, fat content, signal intensity on T2-weighted image favour the diagnosis of HCC. Another form of atypical HCCs are lesions which show hyperintensity on hepatobiliary phase. Therefore, the aim of the present study was to provide an overview of HCCs with atypical enhancement pattern, and focus on their magnetic resonance imaging (MRI) features. CONCLUSIONS In order to correctly characterize atypical HCC lesions in cirrhotic liver it is important to consider not only vascular behaviour of the nodule, but also ancillary MRI features, such as diffusion restriction, hepatobiliary phase hypointensity, and T2-weighted hyperintensity. Fat content, corona enhancement, mosaic architecture are other MRI feautures which favour the diagnosis of HCC even in the absence of typical vascular profile.
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Affiliation(s)
- Jelena Djokic Kovac
- Center for Radiology and MRI, Clinical Center Serbia, School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Aleksandar Ivanovic
- Center for Radiology and MRI, Clinical Center Serbia, School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Tamara Milovanovic
- Clinic for Gastroenterology and Hepatology, Clinical Center of Serbia School of Medicine, University of Belgrade; Belgrade, Serbia
| | - Marjan Micev
- Departament of Digestive Pathology, Clinical Center of Serbia, Belgrade, Serbia
| | - Francesco Alessandrino
- Division of Abdominal Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
| | - Richard M. Gore
- Department of Gastrointestinal Radiology, NorthShore University, Evanston, Pritzker School of Medicine at the University of Chicago, ChicagoUSA
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Fan Y, Yu Y, Hu M, Wang X, Du M, Guo L, Hu C. Imaging features based on Gd-EOB-DTPA-enhanced MRI for predicting vessels encapsulating tumor clusters (VETC) in patients with hepatocellular carcinoma. Br J Radiol 2021; 94:20200950. [PMID: 33417489 DOI: 10.1259/bjr.20200950] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE To investigate the non-invasive prediction of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) based on qualitative and quantitative imaging features of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. METHODS 109 patients with pathologically confirmed HCC who underwent Gd-EOB-DTPA enhanced MRI and immunochemical staining for CD34 were retrospectively evaluated in our institution (the first affiliated hospital of Soochow university). Pre-operative imaging features of Gd-EOB-DTPA-enhanced MRI were qualitatively and quantitatively reviewed by radiologists. Significant variables for differentiating the VETC-positive and VETC-negative HCCs were identified in univariate and multivariate analyses. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off values for quantitative variables. The nomogram based on the coefficient of multivariate analysis was constructed to evaluate the probability of VETC-positive HCCs. RESULTS The multivariate analysis showed that the serum AST level >40 U l-1 (p = 0.007), non-rim diffuse and heterogeneous arterial phase hyperenhancement (p = 0.035), tumor-to-liver SI ratio of 1.135 or more on AP images (p = 0.001), and tumor-to-liver SI ratio of 0.585 or less on HBP images (p = 0.002) were significant predictors for predicting VETC-positive HCCs. Combing all four significant variables provided a diagnostic accuracy of 82.6%, sensitivity of 83.9%, specificity of 80.9% for identifying VETC status. The area under the receiver operating characteristics curve value of the logistical regression coefficient-based nomogram was 0.885 (95% confidence intervals, 0.824-0.946). CONCLUSION Qualitative and quantitative imaging features of Gd-EOB-DTPA-enhanced MRI integrating laboratory examination can provide good diagnostic performance. ADVANCES IN KNOWLEDGE VETC is a novel identified microvascular pattern; associations between imaging features and VETC status have not been investigated. Pre-operative diagnosis of VETC status in HCC is essential to help predict the outcome of patients and make a decision for the therapeutic schedule.
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Affiliation(s)
- Yanfen Fan
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Medical Imaging of Soochow University, Suzhou, China
| | - Yixing Yu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Medical Imaging of Soochow University, Suzhou, China
| | - Mengjie Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Medical Imaging of Soochow University, Suzhou, China
| | - Ximing Wang
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Medical Imaging of Soochow University, Suzhou, China
| | - Mingzhan Du
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Lingchuan Guo
- Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chunhong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China.,Institute of Medical Imaging of Soochow University, Suzhou, China
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Vernuccio F, Gagliano DS, Cannella R, Ba-Ssalamah A, Tang A, Brancatelli G. Spectrum of liver lesions hyperintense on hepatobiliary phase: an approach by clinical setting. Insights Imaging 2021; 12:8. [PMID: 33432491 PMCID: PMC7801550 DOI: 10.1186/s13244-020-00928-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/14/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatobiliary MRI contrast agents are increasingly being used for liver imaging. In clinical practice, most focal liver lesions do not uptake hepatobiliary contrast agents. Less commonly, hepatic lesions may show variable signal characteristics on hepatobiliary phase. This pictorial essay reviews a broad spectrum of benign and malignant focal hepatic observations that may show hyperintensity on hepatobiliary phase in various clinical settings. In non-cirrhotic patients, focal hepatic observations that show hyperintensity in the hepatobiliary phase are usually benign and typically include focal nodular hyperplasia. In patients with primary or secondary vascular disorders, focal nodular hyperplasia-like lesions arise as a local hyperplastic response to vascular alterations and tend to be iso- or hyperintense in the hepatobiliary phase. In oncologic patients, metastases and cholangiocarcinoma are hypointense lesions in the hepatobiliary phase; however, occasionally they may show a diffuse, central and inhomogeneous hepatobiliary paradoxical uptake with peripheral rim hypointensity. Post-chemotherapy focal nodular hyperplasia-like lesions may be tricky, and their typical hyperintense rim in the hepatobiliary phase is very helpful for the differential diagnosis with metastases. In cirrhotic patients, hepatocellular carcinoma may occasionally appear hyperintense on hepatobiliary phase.
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Affiliation(s)
- Federica Vernuccio
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Via del Vespro, 129, 90127, Palermo, Italy. .,University Paris Diderot, Sorbonne Paris Cité, Paris, France. .,I.R.C.C.S. Centro Neurolesi Bonino Pulejo, Contrada Casazza, SS113, 98124, Messina, Italy. .,Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital of Palermo, Via del Vespro 129, 90127, Palermo, Italy.
| | - Domenico Salvatore Gagliano
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Roberto Cannella
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Via del Vespro, 129, 90127, Palermo, Italy.,Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital of Palermo, Via del Vespro 129, 90127, Palermo, Italy
| | - Ahmed Ba-Ssalamah
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, General Hospital of Vienna (AKH), Waehringer Guertel 18-20, 1090, Vienna, Austria
| | - An Tang
- Department of Radiology, Centre Hospitalier de l'Université de Montréal (CHUM), Montreal, QC, Canada.,Centre de Recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.,Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, Montreal, Canada
| | - Giuseppe Brancatelli
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital of Palermo, Via del Vespro 129, 90127, Palermo, Italy
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Li Y, Chen J, Weng S, Yan C, Ye R, Zhu Y, Wen L, Cao D, Hong J. Hepatobiliary phase hypointensity on gadobenate dimeglumine-enhanced magnetic resonance imaging may improve the diagnosis of hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:55. [PMID: 33553348 PMCID: PMC7859813 DOI: 10.21037/atm.2020.02.38] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background To determine the clinical value of hepatobiliary phase (HBP) hypointensity for noninvasive diagnosis of hepatocellular carcinoma (HCC). Methods A total of 246 high-risk patients with 263 selected nodules (126 HCCs, 137 non-HCCs) undergoing gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) were included in the study. Imaging-based diagnoses of small (≤3 cm) and large (>3 cm) HCCs were made using the following 4 criteria: (I) non-rim arterial phase hyper-enhancement (APHE) plus hypointensity on the portal venous phase (PVP); (II) non-rim APHE plus hypointensity on the PVP and/or transitional phase (TP); (III) non-rim APHE plus hypointensity on the PVP and/or TP and/or HBP; (IV) criterion 3 plus non-LR-1/2/M. Based on typical imaging features, LR-1, LR-2, or LR-M (if definitely benign, probably benign, malignant but not HCC specific, respectively) were defined according to the Liver Imaging Reporting and Data System (LI-RADS). Sensitivities and specificities of imaging criteria were calculated and compared using McNemar’s test. Results Among the diagnostic criteria for small HCCs, criterion 3 and 4, which included HBP hypointensity, showed significantly higher sensitivities (96.4% and 94.6%, respectively) than criterion 1 (58.9%, P<0.001 for both). Moreover, criterion 4, which included HBP hypointensity and ancillary features, showed significantly higher specificity (94.7%) than criterion 3 (66.7%, P<0.001) and comparable specificity to criterion 1 (97.4%, P=0.375), achieving the highest accuracies (94.7%). The diagnostic performance of criterion 4 for large HCCs was similar to that for small HCCs. Conclusions HBP hypointensity acquired from Gd-BOPTA-MRI can improve sensitivity and maintain high specificity in the diagnosis of both small and large HCCs after excluding benignities or non-HCC malignancies according to characteristic imaging features.
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Affiliation(s)
- Yueming Li
- 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.,Department of Radiology, Fujian Provincial Cancer Hospital, Fuzhou, China
| | - Shuping Weng
- Department of Radiology, Fujian Provincial Maternity and Child Health Hospital, Fuzhou, China
| | - Chuan Yan
- 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
| | - Dairong Cao
- 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; Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
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Zhou IY, Catalano OA, Caravan P. Advances in functional and molecular MRI technologies in chronic liver diseases. J Hepatol 2020; 73:1241-1254. [PMID: 32585160 PMCID: PMC7572718 DOI: 10.1016/j.jhep.2020.06.020] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 06/11/2020] [Accepted: 06/15/2020] [Indexed: 02/06/2023]
Abstract
MRI has emerged as the most comprehensive non-invasive diagnostic tool for liver diseases. In recent years, the value of MRI in hepatology has been significantly enhanced by a wide range of contrast agents, both clinically available and under development, that add functional information to anatomically detailed morphological images, or increase the distinction between normal and pathological tissues by targeting molecular and cellular events. Several classes of contrast agents are available for contrast-enhanced hepatic MRI, including i) conventional non-specific extracellular fluid contrast agents for assessing tissue perfusion; ii) hepatobiliary-specific contrast agents that are taken up by functioning hepatocytes and excreted through the biliary system for evaluating hepatobiliary function; iii) superparamagnetic iron oxide particles that accumulate in Kupffer cells; and iv) novel molecular contrast agents that are biochemically targeted to specific molecular/cellular processes for staging liver diseases or detecting treatment responses. The use of different functional and molecular MRI methods enables the non-invasive assessment of disease burden, progression, and treatment response in a variety of liver diseases. A high diagnostic performance can be achieved with MRI by combining imaging biomarkers.
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Affiliation(s)
- Iris Y Zhou
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; Harvard Medical School, Boston, MA, USA; Institute for Innovation in Imaging (i(3)), Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
| | - Onofrio A Catalano
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; Harvard Medical School, Boston, MA, USA; Division of Abdominal Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States
| | - Peter Caravan
- Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States; Harvard Medical School, Boston, MA, USA; Institute for Innovation in Imaging (i(3)), Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA.
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Shimada S, Kamiyama T, Kakisaka T, Orimo T, Nagatsu A, Asahi Y, Sakamoto Y, Abo D, Kamachi H, Taketomi A. Impact of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging on the prognosis of hepatocellular carcinoma after surgery. JGH OPEN 2020; 5:41-49. [PMID: 33490612 PMCID: PMC7812518 DOI: 10.1002/jgh3.12444] [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: 06/30/2020] [Revised: 09/18/2020] [Accepted: 10/19/2020] [Indexed: 12/24/2022]
Abstract
Background and Aim Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI) has been recognized as a useful imaging technique to distinguish the biological behavior of hepatocellular carcinoma (HCC). Methods We analyzed 217 hepatectomy recipients with HCCs measuring 10 cm or less. We divided the patients into a decreased intensity (DI) group (n = 189, 87%) and an increased or neutral intensity (INI) group (n = 28, 13%) according to the ratio of tumor intensity to liver intensity during the hepatobiliary phase (HBP). According to the ratio of the maximum tumor diameter (including peritumoral hypointensity) between HBP images and precontrast T1-weighted images (RHBPP), we divided the patients as follows: The group whose RHBPP was ≥1.036 was the high RHBPP group (n = 60, 28%), and the group whose RHBPP was <1.036 was the low RHBPP group (n = 157, 72%). We investigated the prognoses and clinicopathological characteristics of these patients. Results DI versus INI was not a prognostic factor for either survival or recurrence; however, a high RHBPP was an independent predictor of unfavorable survival and recurrence in patients. In addition, the INI group showed significantly lower α-fetoprotein (AFP) levels and higher rates of well-differentiated HCC and ICGR15 ≥15% than the DI group. The high RHBPP group showed significantly higher rates of vascular invasion and poorly differentiated HCC than the low RHBPP group. Conclusions A high RHBPP by EOB-MRI is a preoperative predictor of vascular invasion and an unfavorable prognostic factor for survival and recurrence. These patients might be considered for highly curative operations such as anatomical liver resection.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Yoh Asahi
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Yuzuru Sakamoto
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Daisuke Abo
- Department of Diagnostic Imaging Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Sapporo Japan
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Kudo M. Gd-EOB-DTPA-MRI Could Predict WNT/β-Catenin Mutation and Resistance to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma. Liver Cancer 2020. [PMID: 33083276 DOI: 10.1159/000509554.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
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Kudo M. Gd-EOB-DTPA-MRI Could Predict WNT/β-Catenin Mutation and Resistance to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma. Liver Cancer 2020; 9:479-490. [PMID: 33083276 PMCID: PMC7548850 DOI: 10.1159/000509554] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2020] [Accepted: 06/18/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Masatoshi Kudo
- *Masatoshi Kudo, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 337-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan),
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Li XQ, Wang X, Zhao DW, Sun J, Liu JJ, Lin DD, Yang G, Liu H, Xia ZY, Jia CY, Li HJ. Application of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in hepatocellular carcinoma. World J Surg Oncol 2020; 18:219. [PMID: 32828123 PMCID: PMC7443289 DOI: 10.1186/s12957-020-01996-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, and its morbidity and mortality have been increasing in recent years. The early diagnosis and prompt treatment of small HCC are crucial to improve the prognosis and quality of life of patients. In China, hepatitis B virus infection is the main cause. HCC with a single tumor nodule of ≤ 3 cm in diameter, or HCC with a number of nodules, in which each nodule is ≤ 2 cm in diameter, with a total diameter of ≤ 3 cm, is considered as small HCC. The MRI liver-specific contrast agent can detect small HCC at the early stage. This has important clinical implications for improving the survival rate of patients. MAIN BODY Gd-EOB-DTPA-enhanced MRI can significantly improve the sensitivity and specificity of the detection of HBV-related small hepatocellular carcinoma, providing an important basis for the clinical selection of appropriate personalized treatment. Gd-EOB-DTPA-enhanced MRI can reflect the degree of HCC differentiation, and the evaluation of HCC on Gd-EOB-DTPA-enhanced MRI would be helpful for the selection of the treatment and prognosis of HCC patients. The present study reviews the progress of the application of Gd-EOB-DTPA in the early diagnosis of small HCC, its clinical treatment, the prediction of the degree of differentiation, and the assessment of recurrence and prognosis of HCC, including the pharmacoeconomics and application limitations of Gd-EOB-DTPA. The value of the application of HCC with the Gd-EOB-DTPA was summarized to provide information for improving the quality of life and prolonging the survival of patients. CONCLUSION Gd-EOB-DTPA-enhanced MRI has the diagnostic capability for small HCC with a diameter of ≤ 2 cm. This will have a broader application prospect in the early diagnosis of small liver cancer with a diameter of ≤ 1 cm in the future. The relationship between GD-EOB-DTPA-MRI and the degree of HCC differentiation has a large research space, and Gd-EOB-DTPA is expected to become a potential tool for the preoperative prediction and postoperative evaluation of HCC, which would be beneficial for more appropriate treatments for HCC patients.
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Affiliation(s)
- Xue-Qin Li
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Xing Wang
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Da-Wei Zhao
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Jun Sun
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Jiao-Jiao Liu
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Dong-Dong Lin
- Department of Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Guang Yang
- Department of Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Hui Liu
- Department of Pathology,Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Zhen-Ying Xia
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Cui-Yu Jia
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
| | - Hong-Jun Li
- Department of Radiology, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
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Tanaka T, Nishida H, Mie K, Yamazaki H, Lin LS, Akiyoshi H. Assessment of hepatitis and fibrosis using Gd-EOB-DTPA MRI in dogs. Vet Rec Open 2020; 7:e000371. [PMID: 32818058 PMCID: PMC7401995 DOI: 10.1136/vetreco-2019-000371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 07/01/2020] [Accepted: 07/03/2020] [Indexed: 01/27/2023] Open
Abstract
Background Gadoxetate sodium (Gd-EOB-DTPA) is taken into hepatocytes and excreted into the bile. Hepatocytes with reduced function or dysfunction due to hepatocellular carcinoma (HCC), hepatitis or hepatic fibrosis show impaired Gd-EOB-DTPA uptake. The purpose of the present retrospective case series was to assess the relationship between liver function and contrast enhancement using Gd-EOB-DTPA MRI. Methods Sixteen dogs with a histopathological diagnosis of liver disease, including six with HCC, three with nodular hyperplasia, two with hepatocellular adenoma, two with liver fibrosis and three with hepatitis were included in the study along with three dogs with suspected liver disease but no histopathological diagnosis of liver disease. Relative signal intensities (RSI) of the common bile duct and gall bladder were calculated, and their relationship with the following serum biochemical parameters was assessed: total bilirubin, alanine transaminase, alkaline phosphatase and albumin (Alb). To assess anatomical liver function, relative contrast enhancement indices (RCEI) of the liver were calculated, and differences were assessed between normal and diseased liver. Results RSI showed no significant differences between dogs without and with a histopathological diagnosis of liver disease (P=0.88) although they were significantly correlated with Alb (ρ=0.57, P=0.02) in dogs with a histopathological diagnosis of liver disease. RCEI was significantly higher in normal liver tissue than that in livers with hepatitis/fibrosis (P=0.048) and HCC (P=0.03) but not nodular hyperplasia/hepatocellular adenoma (P=0.51). Conclusions Gd-EOB-DTPA MRI may be potentially useful in the assessment of anatomical liver function in dogs with liver disease.
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Affiliation(s)
- Toshiyuki Tanaka
- Laboratory of Veterinary Surgery, Department of Veterinary Clinical Medicine, Graduate School of Life and Environmental Sciences, Osaka Prefecture University - Rinku Campus, Izumisano, Osaka, Japan.,Kinki Animal Medical Training Institute & Veterinary Clinic, Higashiosaka, Osaka, Japan
| | - Hidetaka Nishida
- Laboratory of Veterinary Surgery, Department of Veterinary Clinical Medicine, Graduate School of Life and Environmental Sciences, Osaka Prefecture University - Rinku Campus, Izumisano, Osaka, Japan
| | - Keiichiro Mie
- Laboratory of Veterinary Surgery, Department of Veterinary Clinical Medicine, Graduate School of Life and Environmental Sciences, Osaka Prefecture University - Rinku Campus, Izumisano, Osaka, Japan
| | - Hiroki Yamazaki
- Laboratory of Veterinary Surgery, Department of Veterinary Clinical Medicine, Graduate School of Life and Environmental Sciences, Osaka Prefecture University - Rinku Campus, Izumisano, Osaka, Japan
| | - Lee-Shuan Lin
- Laboratory of Veterinary Diagnostic Imaging, Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan
| | - Hideo Akiyoshi
- Laboratory of Veterinary Surgery, Department of Veterinary Clinical Medicine, Graduate School of Life and Environmental Sciences, Osaka Prefecture University - Rinku Campus, Izumisano, Osaka, Japan
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Kumada T. Editorial: impact of the introduction of direct-acting antiviral drugs on hepatocarcinogenesis-a prospective serial follow-up MRI study. Author's reply. Aliment Pharmacol Ther 2020; 52:737-738. [PMID: 32886360 DOI: 10.1111/apt.15939] [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)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
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Kumada T, Toyoda H, Yasuda S, Tada T, Ogawa S, Takeshima K, Tanaka J, Chayama K, Johnson PJ. Impact of the introduction of direct-acting anti-viral drugs on hepatocarcinogenesis: a prospective serial follow-up MRI study. Aliment Pharmacol Ther 2020; 52:359-370. [PMID: 32519782 DOI: 10.1111/apt.15825] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2020] [Revised: 04/17/2020] [Accepted: 05/10/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND We conducted a prospective study using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-MRI) to determine whether sustained virological response (SVR) by direct-acting anti-viral (DAA) drugs suppresses hepatocarcinogenesis in patients with hepatitis C virus (HCV) infection. AIM To use serial Gd-EOB-MRI to assess the impact of DAAs on hepatocarcinogenesis. METHODS Between February 2008 and December 2018, 1083 consecutive patients with HCV infection underwent Gd-EOB-MRI. Of these, 719 patients were enrolled, including 210 patients in the 'Non-DAA group', who did not receive DAAs before the introduction of DAAs, and 509 patients in the 'DAA group', who achieved SVR after the introduction of DDAs. Factors associated with hepatocarcinogenesis were analysed by a Cox proportional hazard model. In addition, hepatocarcinogenesis was classified into two types, 'multistep' and 'de novo', on the basis of Gd-EOB-MRI findings. Factors associated with each type were analysed by Fine and Gray proportional hazards models. RESULTS Hepatocarcinogenesis was observed in 67 of 719 (9.3%) patients. Factors associated with hepatocarcinogenesis were male gender, albumin-bilirubin (ALBI) grade 2 or 3, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) ≥5%, the presence of nonhypervascular hypointense nodules (NHHNs) and Non-DAA group. Of 67 patients, multistep hepatocarcinogenesis occurred in 58 patients (86.6%) and de novo hepatocarcinogenesis occurred in nine patients (13.4%). Factors associated with multistep hepatocarcinogenesis were male gender and Non-DAA group. CONCLUSION The eradication of HCV by DAA therapy reduces multistep hepatocarcinogenesis.
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Affiliation(s)
- Takashi Kumada
- Department of Nursing, Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Satoshi Yasuda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Toshifumi Tada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Sadanobu Ogawa
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Kenji Takeshima
- Department of Imaging Diagnosis, Ogaki Municipal Hospital, Ogaki, Japan
| | - Junko Tanaka
- Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Institute of Biomedical and Health Sciences, Hiroshima University Hospital, Hiroshima, Japan
| | - Philip J Johnson
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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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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Detection of Hepatocellular Carcinoma in Contrast-Enhanced Magnetic Resonance Imaging Using Deep Learning Classifier: A Multi-Center Retrospective Study. Sci Rep 2020; 10:9458. [PMID: 32527998 PMCID: PMC7289813 DOI: 10.1038/s41598-020-65875-4] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Accepted: 05/09/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a leading cause of cancer-related death worldwide. We propose a fully automated deep learning model to detect HCC using hepatobiliary phase magnetic resonance images from 549 patients who underwent surgical resection. Our model used a fine-tuned convolutional neural network and achieved 87% sensitivity and 93% specificity for the detection of HCCs with an external validation data set (54 patients). We also confirmed whether the lesion detected by our deep learning model is a true lesion using a class activation map.
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Takatsu Y, Nakamura M, Kobayashi S, Miyati T. Prediction of Sufficient Liver Enhancement on the Gadoxetate Disodium-enhanced Hepatobiliary Phase Imaging Using Transitional Phase Images and Albumin-bilirubin Grade. Magn Reson Med Sci 2020; 20:152-159. [PMID: 32461506 PMCID: PMC8203475 DOI: 10.2463/mrms.mp.2020-0050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Purpose: To investigate whether the contrast enhancement effect in hepatobiliary phase (HBP) images can be predicted using transitional phase (3-min delay) images on liver magnetic resonance imaging (MRI) based on the quantitative liver–spleen contrast ratio (Q-LSC) and albumin–bilirubin (ALBI) grade. Methods: Overall, 212 patients (124 men and 88 women; mean age 66.7 ± 11.1 years) who underwent blood tests (assessed within 1 month of performing MRI) were included; patients with diffuse tumor, hepatectomy, splenectomy, Gamna–Gandy bodies in the spleen, and movement artifacts were excluded. Q-LSC was calculated using the signal intensity of the liver divided that of the spleen. Q-LSC > 1.5 (cut-off value) indicates a relatively higher sensitivity for detecting of hepatic lesions. To predict the contrast enhancement effect in HBP using Q-LSC of 3-min delay images, Q-LSC of 10- and 15-min delay images were compared for each ALBI grade based on Q-LSC of 3-min delay images. Furthermore, to verify the accuracy of this prediction, the proportion of cases with Q-LSC > 1.5 in 10- and 15 min delay images was calculated based on Q-LSC on 3-min delay images. Results: The higher the Q-LSC on the 3-min delay image, the higher was the Q-LSC on its 10- and 15-min delay images. The proportion of cases with Q-LSC > 1.5 in 10- and 15-min delay images was higher for ALBI grade 1 than for ALBI grades 2 and 3 even in the same Q-LSC on 3-min delay images. Q-LSC was <1 in a 3-min delay image and <1.5 in a 15-min delay image in 62.2% of patients with ALBI grade 1 and 82.1% of patients with ALBI grades 2 and 3. Conclusion: The liver contrast enhancement effect in HBP images could be predicted using a 3-min delay image based on Q-LSC and ALBI grade.
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Affiliation(s)
- Yasuo Takatsu
- Department of Radiological Technology, Faculty of Health and Welfare, Tokushima Bunri University.,Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University
| | | | - Satoshi Kobayashi
- Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University
| | - Tosiaki Miyati
- Division of Health Sciences, Graduate School of Medical Sciences, Kanazawa University
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Kovac JD, Milovanovic T, Dugalic V, Dumic I. Pearls and pitfalls in magnetic resonance imaging of hepatocellular carcinoma. World J Gastroenterol 2020; 26:2012-2029. [PMID: 32536771 PMCID: PMC7267693 DOI: 10.3748/wjg.v26.i17.2012] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 04/20/2020] [Accepted: 04/24/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy, which usually arises in cirrhotic liver. When the typical enhancement pattern, consisting of late arterial hyperenhancement followed by washout, is present in nodules larger than 1 cm, HCC can be confidently diagnosed without the need for tissue biopsy. Nevertheless, HCC can display an atypical enhancement pattern, either as iso or hypovascular lesion, or hypervascular lesion without washout. Not only the enhancement pattern of HCC could be atypical, but also a variety of histological types of HCC, such as steatotic, scirrhous, fibrolamellar, or combined hepatocellular-cholangiocellular carcinoma could raise diagnostic dilemmas. In addition, distinct morphological types of HCC or different growth pattern can occur. Awareness of these atypical and rare HCC presentations on magnetic resonance imaging is important for accurate differentiation from other focal liver lesions and timely diagnosis, which allows optimal treatment of patients.
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Affiliation(s)
- Jelena Djokic Kovac
- Departament of Radiology, Clinical Center Serbia, Belgrade 11000, Serbia
- School of Medicine, Belgrade University, Belgrade 11000, Serbia
| | - Tamara Milovanovic
- Departament of Hepatology, Clinical Center Serbia, Belgrade 11000, Serbia
- School of Medicine, Belgrade University, Belgrade 11000, Serbia
| | - Vladimir Dugalic
- Departament of Surgery, Clinical Center Serbia, Belgrade 11000, Serbia
- School of Medicine, Belgrade University, Belgrade 11000, Serbia
| | - Igor Dumic
- Divison of Hospital Medicine, Mayo Clinic College of Medicine and Sciences, Mayo Clinic Health System, New York, NY 10029, United States
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