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Hawley J, Tang Y, Sjöström A, Fuentes-Alburo A, Tranquart F. The Clinical Utility of Liver-Specific Ultrasound Contrast Agents During Hepatocellular Carcinoma Imaging. ULTRASOUND IN MEDICINE & BIOLOGY 2025; 51:415-427. [PMID: 39674715 DOI: 10.1016/j.ultrasmedbio.2024.10.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 10/17/2024] [Accepted: 10/21/2024] [Indexed: 12/16/2024]
Abstract
Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancy, with high mortality rates recorded globally. Early detection through clinical biomarkers, medical imaging and histological assessment followed by rapid intervention are integral for positive patient outcomes. Although contrast-enhanced computed tomography scans and magnetic resonance imaging are recognised as the reference standard for the diagnosis and staging of HCC in international guidelines, ultrasound (US) examination is recommended as a screening tool for patients at risk. Contrast-enhanced US (CEUS) elevates the standard of an US examination using US contrast agents (UCAs), capable of diagnosing focal liver lesions with high efficacy. Most UCAs are purely intravascular, offering clinicians a dynamic representation of a lesions' arterial phase vascular kinetics, which is seldom seen in such detail during computed tomography or magnetic resonance imaging assessments. Despite its benefits, there is incongruity between international societies on the role of CEUS in the HCC clinical pathway. The transient nature of pure blood-pool agents is suggested to be insufficient to justify CEUS as a primary modality due to the inability to consistently perform whole liver imaging, alongside disputes regarding its capabilities to differentiate HCC from intrahepatic cholangiocarcinoma. A sinusoidal phase UCA affords clinicians the opportunity to perform whole liver imaging through Kupffer cell uptake in addition to visualising lesion vascular kinetics in the arterial and portal venous phases. Therefore, the purpose of this review was to examine the role of CEUS in the HCC clinical pathway in its current practice and observe how a Kupffer cell sinusoidal phase UCA may supplement contemporary diagnostic techniques through a multi-modality, multi-agent approach.
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Affiliation(s)
- Joshua Hawley
- GE HealthCare Pharmaceutical Diagnostics, Chalfont St. Giles, UK; Chesterfield Royal Hospital Foundation NHS Trust, Chesterfield, UK.
| | - Yongqing Tang
- GE HealthCare Pharmaceutical Diagnostics, Chalfont St. Giles, UK
| | - Anders Sjöström
- GE HealthCare Pharmaceutical Diagnostics, Chalfont St. Giles, UK
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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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Wang T, Han D, Xiao H, Yang H, Chen JY, Tang Y. A Preliminary Study on the Application of Contrast-Enhanced Ultrasonography in Children With Peripheral Neuroblastic Tumors. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:954-960. [PMID: 38575414 DOI: 10.1016/j.ultrasmedbio.2024.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 02/27/2024] [Accepted: 03/04/2024] [Indexed: 04/06/2024]
Abstract
The purpose of this study was to retrospectively analyze the characteristics of contrast-enhanced ultrasound (CEUS) images and quantitative parameters of time-intensity curves (TICs) in children's peripheral neuroblastic tumors (pNTs). By comparing the imaging features and quantitative parameters of the TICs of neuroblastoma (NB) and ganglioneuroblastoma (GNB) patients, we attempted to identify the distinguishing points between NB and GNB. A total of 35 patients confirmed to have pNTs by pathologic examination were included in this study. Each child underwent CEUS with complete imaging data (including still images and at least 3 min of video files). Twenty-four patients were confirmed to have NB, and 11 were considered to have GNB according to differentiation. The CEUS image features and quantitative parameters of the TICs of all lesions were analyzed to determine whether there were CEUS-related differences between the two types of pNT. There was a significant difference in the enhancement patterns of the CEUS features (χ2 = 5.303, p < 0.05), with more "peripheral-central" enhancement in the NB group and more "central-peripheral" enhancement in the GNB group. In the TIC, the rise time and time to peak were significantly different (p < 0.05). The receiver operating characteristic curve showed that the probability of ganglion cell NB increased significantly after RT > 15.29, with a sensitivity of 0.636 and a specificity of 0.958. When the peak time was greater than 16.155, the probability of NB increased significantly, with a sensitivity of 0.636 and a specificity of 0.958. The CEUS features of NB and GNB patients are very similar, and it is difficult to distinguish them. Rise time and time to peak may be useful in identifying GNB and NB, but the sample size of this study was small, and the investigation was only preliminary; a larger sample size is needed to support these conclusions.
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Affiliation(s)
- Ting Wang
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
| | - Dan Han
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
| | - Huan Xiao
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
| | - Hao Yang
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
| | - Jing-Yu Chen
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China
| | - Yi Tang
- Department of Ultrasound, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing, China.
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Kim NR, Bae H, Hwang HS, Han DH, Kim KS, Choi JS, Park MS, Choi GH. Preoperative Prediction of Microvascular Invasion with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Patients with Single Hepatocellular Carcinoma: The Implication of Surgical Decision on the Extent of Liver Resection. Liver Cancer 2024; 13:181-192. [PMID: 38751555 PMCID: PMC11095589 DOI: 10.1159/000531786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 06/26/2023] [Indexed: 05/18/2024] Open
Abstract
Introduction Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical decisions is limited. This study aimed to identify preoperative predictive factors for MVI in HCC and further evaluate oncologic outcomes of different types and extents of hepatectomy according to stratified risk of MVI. Methods Patients with surgically resected single HCC (≤5 cm) who underwent preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) were included in a single-center retrospective study. Two radiologists reviewed the images with no clinical, pathological, or prognostic information. Significant predictive factors for MVI were identified using logistic regression analysis against pathologic MVI and used to stratify patients. In the subgroup analysis, long-term outcomes of the stratified patients were analyzed using the Kaplan-Meier method with log-rank test and compared between anatomical and nonanatomical or major and minor resection. Results A total of 408 patients, 318 men and 90 women, with a mean age of 56.7 years were included. Elevated levels of tumor markers (alpha-fetoprotein [α-FP] ≥25 ng/mL and PIVKA-II ≥40 mAU/mL) and three MRI features (tumor size ≥3 cm, non-smooth tumor margin, and arterial peritumoral enhancement) were independent predictive factors for MVI. As the MVI risk increased from low (no predictive factor) and intermediate (1-2 factors) to high-risk (3-4 factors), recurrence-free and overall survival of each group significantly decreased (p = 0.001). In the high MVI risk group, 5-year cumulative recurrence rate was significantly lower in patients who underwent major compared to minor hepatectomy (26.6 vs. 59.8%, p = 0.027). Conclusion Tumor markers and MRI features can predict the risk of MVI and prognosis after hepatectomy. Patients with high MVI risk had the worst prognosis among the three groups, and major hepatectomy improved long-term outcomes in these high-risk patients.
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Affiliation(s)
- Na Reum Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Seoul, Republic of Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Heejin Bae
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul, Republic of Korea
| | - Hyeo Seong Hwang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Dai Hoon Han
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Seoul, Republic of Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung Sik Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Seoul, Republic of Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin Sub Choi
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Seoul, Republic of Korea
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Mi-Suk Park
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul, Republic of Korea
| | - Gi Hong Choi
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Severance Hospital, Seoul, Republic of Korea
- Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Seoul, Republic of Korea
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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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Zhao CK, Guan X, Pu YY, Zhou BY, Wang LF, Sun YK, Yin HH, Xia HS, Wang X, Han H, Xu HX. Response Evaluation Using Contrast-Enhanced Ultrasound for Unresectable Advanced Hepatocellular Carcinoma Treated With Tyrosine Kinase Inhibitors Plus Anti-PD-1 Antibody Therapy. ULTRASOUND IN MEDICINE & BIOLOGY 2024; 50:142-149. [PMID: 37852872 DOI: 10.1016/j.ultrasmedbio.2023.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 07/21/2023] [Accepted: 09/23/2023] [Indexed: 10/20/2023]
Abstract
OBJECTIVE The aim of the work described here was to evaluate the role of contrast-enhanced ultrasound (CEUS) in response evaluation for unresectable advanced hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors (TKIs) plus anti-programmed cell death protein-1 (PD-1) antibody therapy. METHODS A prospective cohort of consecutive patients with HCC who received combined TKI/anti-PD-1 antibody treatment for unresectable HCC between January 2022 and October 2022 was included in this study. The patients underwent unenhanced ultrasound (US) and CEUS examinations before treatment and at follow-up. Changes in the largest diameters of the target tumor on unenhanced US and the largest diameters of the enhancing target tumors on CEUS were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 with unenhanced US and magnetic resonance imaging/computed tomography (MRI/CT) and modified RECIST (mRECIST) with CEUS and CEMRI/CT were used to assess treatment response. RESULTS A total of 24 HCC patients (23 men and 1 woman; mean age: 56.5 ± 8.5 y; Barcelona Clinic Liver Cancer stage C, 62.5%; 29 intrahepatic target tumors) were studied. Calculations of degree of necrosis in the target tumors revealed no significant differences between CEUS and CEMRI/CT (44.5 ± 36.2% vs. 45.3 ± 36.8%, p = 0.862). As for the differentiation of responders from non-responders, the agreement between RECIST version 1.1 of unenhanced US and mRECIST-CEUS was poor (κ coefficient = 0.233). Meanwhile, there was a high degree of concordance between mRECIST-CEUS and mRECIST-CEMRI/CT (κ coefficient = 0.812). CONCLUSION CEUS proved to be superior to baseline US and is comparable to CEMRI/CT in defining treatment outcome for combined TKI/anti-PD-1 antibody therapy.
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Affiliation(s)
- Chong-Ke Zhao
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China
| | - Xin Guan
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Yin-Ying Pu
- Central Laboratory and Department of Medical Ultrasound, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Bo-Yang Zhou
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Li-Fan Wang
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Yi-Kang Sun
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Hao-Hao Yin
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Han-Sheng Xia
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Xi Wang
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Hong Han
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China; Shanghai Institute of Medical Imaging, Shanghai, China
| | - Hui-Xiong Xu
- Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, Shanghai, China.
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Li N, Wang Y, Yang L, Yang C, Zeng M. Hepatobiliary-Phase Hypointense Nodules Without Arterial-Phase Hyperenhancement: Developing a Risk Stratification for Hypervascular Transformation Based on a Real-World Observational Cohort Study. Technol Cancer Res Treat 2024; 23:15330338241299003. [PMID: 39544080 PMCID: PMC11565688 DOI: 10.1177/15330338241299003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 10/01/2024] [Accepted: 10/23/2024] [Indexed: 11/17/2024] Open
Abstract
PURPOSE To develop a risk stratification based on MRI features to predict hypervascular transformation for hepatobiliary-phase (HBP) hypointense nodules without arterial-phase hyperenhancement (APHE). MATERIALS AND METHODS This retrospective observational cohort study included 55 HBP hypointense nodules without APHE in 35 patients with chronic liver disease, cirrhosis, or current hepatocellular carcinoma (HCC) who underwent gadoxetic acid-enhanced MRI. The hypervascular transformation during the follow-up MRI(s) was the primary endpoint analyzed for the nodules. Univariable and multivariable Cox proportional hazard regression analyses were performed to identify risk features predicting transformation and assess their predictive value. RESULTS Among the 55 nodules, 27 developed hypervascular transformation, while 28 did not. Diffusion-weighted imaging (DWI) hyperintensity (hazard ratio [HR], 4.98; 95% confidence interval [CI]: 1.60, 15.54; p = 0.006) and portal venous phase (PVP) hypointensity (HR, 4.08; 95% CI: 1.43, 11.64; p = 0.009) were associated with hypervascular transformation. DWI hyperintensity and PVP hypointensity had 44.4% (95% CI: 26.0%, 64.4%) and 81.9% (95% CI: 61.3%, 93.0%) sensitivity, while their specificity was 78.2% (95% CI: 64.6%, 87.8%) and 67.9 (95% CI: 47.6%, 83.4%), respectively. The specificity of the combination of two features was 100% (95% CI: 85.0%, 100%). The hypervascular transformation rates for nodules with both, either and neither of the risk MRI findings were 100% (10/10), 60.9% (14/23), and 13.6% (3/22), respectively; the median intervals for transformation were 312 (range: 73-838), 409 (range: 50-1643) and 555 (range: 423-968) days, respectively. CONCLUSION The combination of DWI hyperintensity and PVP hypointensity may be used as a high-risk indicator for the hypervascular transformation of HBP hypointense nodules without APHE; nodules without either feature may be treated as low-risk nodules and could adopt an extended interval follow-up schedule.
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Affiliation(s)
- Na Li
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Wang
- Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Li Yang
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chun Yang
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Shanghai Institute of Medical Imaging, Shanghai, China
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Medical Imaging, Shanghai Medical College, Fudan University, Shanghai, China
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Tran VT, Phan TT, Nguyen TB, Le TT, Tran TTT, Nguyen ATT, Nguyen HT, Nguyen NDB, Ho TT, Pho SP, Nguyen TAT, Nguyen HT, Mai HT, Pham BTT, Nguyen KD, Le BT, Nguyen TT, Nguyen ST. The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma. BMC Res Notes 2023; 16:317. [PMID: 37932802 PMCID: PMC10629103 DOI: 10.1186/s13104-023-06600-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 10/26/2023] [Indexed: 11/08/2023] Open
Abstract
OBJECTIVE This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC). RESULTS A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
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Affiliation(s)
- Vinh Thanh Tran
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Thang Thanh Phan
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam.
| | - Tran Bao Nguyen
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Thao Thi Le
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Thanh-Tram Thi Tran
- Department of Clinical Pathology, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Anh-Thu Thi Nguyen
- Department of Clinical Pathology, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Hang Thuy Nguyen
- Department of Clinical Pathology, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Ngoc-Diep Bui Nguyen
- Department of Clinical Pathology, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Toan Trong Ho
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Suong Phuoc Pho
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Thuy-An Thi Nguyen
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Hue Thi Nguyen
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Huyen Thi Mai
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Bich-Tuyen Thi Pham
- The Laboratory D Unit, Cancer Center, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Khoa Dinh Nguyen
- Scientific Research Department, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Binh Thanh Le
- Department of General Director, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Thuc Tri Nguyen
- Department of General Director, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
| | - Son Truong Nguyen
- Department of General Director, Cho Ray Hospital, #201B Nguyen Chi Thanh Street, Dist. 5, Ho Chi Minh City, 700000, Vietnam
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Sakamoto S, Nagasaki A, Shrestha M, Shintani T, Watanabe A, Furusho H, Chayama K, Takata T, Miyauchi M. Porphyromonas gingivalis-odontogenic infection is the potential risk for progression of nonalcoholic steatohepatitis-related neoplastic nodule formation. Sci Rep 2023; 13:9350. [PMID: 37291206 PMCID: PMC10250332 DOI: 10.1038/s41598-023-36553-y] [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: 11/10/2022] [Accepted: 06/06/2023] [Indexed: 06/10/2023] Open
Abstract
Porphyromonas gingivalis (P.g.), a major periodontal pathogen is a known risk factor for various systemic diseases. However, the relationship between P.g. and nonalcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is unclear. Thus, we aimed to elucidate whether P.g.-odontogenic infection promotes NASH-related HCC development/progression and to clarify its mechanism. Using high-fat diet (HFD)-induced NASH mouse model, P.g. was infected odontogenically. After 60 weeks of infection, tumor profiles were examined. Chow diet (CD) groups were also prepared at 60 weeks. Nodule formation was only seen in HFD-mice. P.g.-odontogenic infection significantly increased the mean nodule area (P = 0.0188) and tended to promote histological progression score after 60 weeks (P = 0.0956). Interestingly, P.g. was detected in the liver. HFD-P.g. (+) showed numerous TNF-α positive hepatic crown-like structures and 8-OHdG expression in the non-neoplastic liver. In P.g.-infected hepatocytes, phosphorylation of integrin β1 signaling molecules (FAK/ERK/AKT) was upregulated in vitro. In fact, total AKT in the liver of HFD-P.g. (+) was higher than that of HFD-P.g. (-). P.g.-infected hepatocytes showed increased cell proliferation and migration, and decreased doxorubicin-mediated apoptosis. Integrin β1 knockdown inhibited these phenotypic changes. P.g.-odontogenic infection may promote the progression of neoplastic nodule formation in an HFD-induced NASH mouse model via integrin signaling and TNF-α induced oxidative DNA damage.
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Affiliation(s)
- Shinnichi Sakamoto
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Japan
| | - Atsuhiro Nagasaki
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Madhu Shrestha
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
- Department of Diagnostic Sciences, Texas A&M University School of Dentistry, Dallas, TX, USA
| | - Tomoaki Shintani
- Center of Oral Clinical Examination, Hiroshima University Hospital, Hiroshima, Japan
| | - Atsushi Watanabe
- Laboratory of Research Advancement, National Center for Geriatrics and Gerontology, Research Institute, Obu, Japan
| | - Hisako Furusho
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan
| | - Kazuaki Chayama
- Collaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan
- Research Center for Hepatology and Gastroenterology, Hiroshima University, Hiroshima, Japan
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Takashi Takata
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan.
- Shunan University, 843-4-2 Gakuendai, Shunan, Japan.
| | - Mutsumi Miyauchi
- Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, Hiroshima, 734-8551, Japan.
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Kudo M. Surveillance, Diagnosis, and Treatment Outcome of Hepatocellular Carcinoma in Japan: 2023 Update. Liver Cancer 2023; 12:95-102. [PMID: 37325491 PMCID: PMC10267513 DOI: 10.1159/000530079] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 03/06/2023] [Indexed: 06/17/2023] Open
Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
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11
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Sharma G, Enriquez JS, Armijo R, Wang M, Bhattacharya P, Pudakalakatti S. Enhancing Cancer Diagnosis with Real-Time Feedback: Tumor Metabolism through Hyperpolarized 1- 13C Pyruvate MRSI. Metabolites 2023; 13:606. [PMID: 37233647 PMCID: PMC10224418 DOI: 10.3390/metabo13050606] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/19/2023] [Accepted: 04/23/2023] [Indexed: 05/27/2023] Open
Abstract
This review article discusses the potential of hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) as a noninvasive technique for identifying altered metabolism in various cancer types. Hyperpolarization significantly improves the signal-to-noise ratio for the identification of 13C-labeled metabolites, enabling dynamic and real-time imaging of the conversion of [1-13C] pyruvate to [1-13C] lactate and/or [1-13C] alanine. The technique has shown promise in identifying upregulated glycolysis in most cancers, as compared to normal cells, and detecting successful treatment responses at an earlier stage than multiparametric MRI in breast and prostate cancer patients. The review provides a concise overview of the applications of HP [1-13C] pyruvate MRSI in various cancer systems, highlighting its potential for use in preclinical and clinical investigations, precision medicine, and long-term studies of therapeutic response. The article also discusses emerging frontiers in the field, such as combining multiple metabolic imaging techniques with HP MRSI for a more comprehensive view of cancer metabolism, and leveraging artificial intelligence to develop real-time, actionable biomarkers for early detection, assessing aggressiveness, and interrogating the early efficacy of therapies.
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Affiliation(s)
- Gaurav Sharma
- Department of Cardiovascular & Thoracic Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA;
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | - José S. Enriquez
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA; (J.S.E.); (R.A.); (M.W.); (P.B.)
- Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA
| | - Ryan Armijo
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA; (J.S.E.); (R.A.); (M.W.); (P.B.)
| | - Muxin Wang
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA; (J.S.E.); (R.A.); (M.W.); (P.B.)
| | - Pratip Bhattacharya
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA; (J.S.E.); (R.A.); (M.W.); (P.B.)
- Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA
| | - Shivanand Pudakalakatti
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 75390, USA; (J.S.E.); (R.A.); (M.W.); (P.B.)
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12
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Liao Z, Tang C, Luo R, Gu X, Zhou J, Gao J. Current Concepts of Precancerous Lesions of Hepatocellular Carcinoma: Recent Progress in Diagnosis. Diagnostics (Basel) 2023; 13:diagnostics13071211. [PMID: 37046429 PMCID: PMC10093043 DOI: 10.3390/diagnostics13071211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
The most common cause of hepatocellular carcinoma (HCC) is chronic hepatitis and cirrhosis. It is proposed that precancerous lesions of HCC include all stages of the disease, from dysplastic foci (DF), and dysplastic nodule (DN), to early HCC (eHCC) and progressed HCC (pHCC), which is a complex multi-step process. Accurately identifying precancerous hepatocellular lesions can significantly impact the early detection and treatment of HCC. The changes in high-grade dysplastic nodules (HGDN) were similar to those seen in HCC, and the risk of malignant transformation significantly increased. Nevertheless, it is challenging to diagnose precancerous lesions of HCC. We integrated the literature and combined imaging, pathology, laboratory, and other relevant examinations to improve the accuracy of the diagnosis of precancerous lesions.
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Affiliation(s)
- Ziyue Liao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
| | - Cuiping Tang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
| | - Rui Luo
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
| | - Xiling Gu
- Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
| | - Jun Zhou
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
| | - Jian Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing 400010, China
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Zhang S, Zhong BY, Zhang L, Wang WS, Ni CF. Transarterial chemoembolization failure/refractoriness: A scientific concept or pseudo-proposition. World J Gastrointest Surg 2022; 14:528-537. [PMID: 35979416 PMCID: PMC9258238 DOI: 10.4240/wjgs.v14.i6.528] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 02/08/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
Multi-session transarterial chemoembolization (TACE) is usually needed for the treatment of intermediate-stage hepatocellular carcinoma (HCC), but it may not always have a positive influence on prognosis due to high heterogeneity of HCC. To avoid ineffective repeated TACE, the concept of TACE failure/refractoriness has been proposed by several organizations and is being addressed using tyrosine kinase inhibitors. The concept of TACE failure/refractoriness is controversial due to ambiguous definitions and low evidence-based data. To date, only a few studies have examined the rationality concerning the definition of TACE failure/refractoriness, although the concept has been introduced and applied in many TACE-related clinical trials. This review focuses on some of the issues related to different versions of TACE failure/refractoriness, the rationality of related definitions, and the feasibility of continuing TACE after so-called failure/refractoriness based on published evidence. A suggestion to re-define TAEC failure/refractoriness is also put forward.
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Affiliation(s)
- Shen Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Bin-Yan Zhong
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Lei Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Wan-Sheng Wang
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Cai-Fang Ni
- Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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14
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Cheng N, Ren Y, Zhou J, Zhang Y, Wang D, Zhang X, Chen B, Liu F, Lv J, Cao Q, Chen S, Du H, Hui D, Weng Z, Liang Q, Su B, Tang L, Han L, Chen J, Shao C. Deep Learning-Based Classification of Hepatocellular Nodular Lesions on Whole-Slide Histopathologic Images. Gastroenterology 2022; 162:1948-1961.e7. [PMID: 35202643 DOI: 10.1053/j.gastro.2022.02.025] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 12/21/2021] [Accepted: 02/15/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, let alone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). METHODS The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. RESULTS We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. CONCLUSIONS We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.
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Affiliation(s)
- Na Cheng
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yong Ren
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China; Center for Artificial Intelligence in Medicine, Research Institute of Tsinghua, Pearl River Delta, Guangzhou, China
| | - Jing Zhou
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yiwang Zhang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Deyu Wang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaofang Zhang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bing Chen
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital, Meizhou, China
| | - Fang Liu
- Department of Pathology, FoShan First People's Hospital, Foshan, China
| | - Jin Lv
- Department of Pathology, FoShan First People's Hospital, Foshan, China
| | - Qinghua Cao
- Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sijin Chen
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Hong Du
- Department of Pathology, GuangZhou First People's Hospital, Guangzhou, China
| | - Dayang Hui
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zijin Weng
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Qiong Liang
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bojin Su
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Luying Tang
- Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University Lingnan Hospital, Guangzhou, China
| | - Lanqing Han
- Center for Artificial Intelligence in Medicine, Research Institute of Tsinghua, Pearl River Delta, Guangzhou, China.
| | - Jianning Chen
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Chunkui Shao
- Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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15
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Guo HL, Zheng X, Cheng MQ, Zeng D, Huang H, Xie XY, Lu MD, Kuang M, Wang W, Xian MF, Chen LD. Contrast-Enhanced Ultrasound for Differentiation Between Poorly Differentiated Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2022; 41:1213-1225. [PMID: 34423864 DOI: 10.1002/jum.15812] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2021] [Revised: 06/09/2021] [Accepted: 07/19/2021] [Indexed: 12/17/2022]
Abstract
PURPOSE To evaluate the diagnostic performance of LR-5 for diagnosing poorly differentiated hepatocellular carcinoma (p-HCC). To build a contrast-enhanced ultrasound (CEUS) signature for improving the differential diagnostic performance between p-HCC and intrahepatic cholangiocarcinoma (ICC). METHODS The B-mode ultrasound (BUS) and CEUS features of 60 p-HCCs and 56 ICCs were retrospectively analyzed. The CEUS LI-RADS category was assigned according to CEUS LI-RADS v2017. A diagnostic CEUS signature was built based on the independent significant features. An ultrasound (US) signature combining both BUS and CEUS features was also built. The diagnostic performances of the CEUS signature, US signature, and LR-5 were evaluated by receiver operating characteristic (ROC) analysis. RESULTS One (1.7%) p-HCC and 26 (46.4%) ICC patients presented cholangiectasis or cholangiolithiasis (P < .001). Fifty-four (90.0%) p-HCCs and 8 (14.3%) ICCs showed clear boundaries in the artery phase (P < .001). The washout times of p-HCCs and ICCs were 81.0 ± 42.5 s and 34.7 ± 8.6 s, respectively (P < .001). The AUC, sensitivity, and specificity of the CEUS signature, US signature, and LR-5 were 0.955, 91.67%, and 90.57% versus 0.976, 96.67%, and 92.45% versus 0.758, 51.67%, and 100%, respectively. The AUC and sensitivity of CEUS LI-RADS were much lower than those of the CEUS and US signatures (P < .001). CONCLUSION LR-5 had high specificity but low sensitivity in diagnosing p-HCC. When the washout time and tumor boundary were included in the CEUS signature, the sensitivity and AUC were remarkably increased in the differentiation between p-HCC and ICC.
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Affiliation(s)
- Huan-Ling Guo
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xin Zheng
- Department of Medical Ultrasonics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
| | - Mei-Qing Cheng
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dan Zeng
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hui Huang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Yan Xie
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming-De Lu
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Kuang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
- Departments of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wang
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Meng-Fei Xian
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Da Chen
- Department of Medical Ultrasonics, Ultrasomics Artificial Intelligence X-Lab, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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16
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Ye Z, Song B, Lee PM, Ohliger MA, Laustsen C. Hyperpolarized carbon 13 MRI in liver diseases: Recent advances and future opportunities. Liver Int 2022; 42:973-983. [PMID: 35230742 PMCID: PMC9313895 DOI: 10.1111/liv.15222] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 01/20/2022] [Accepted: 02/04/2022] [Indexed: 02/05/2023]
Abstract
Hyperpolarized carbon-13 magnetic resonance imaging (HP 13 C MRI) is a recently translated metabolic imaging technique. With dissolution dynamic nuclear polarization (d-DNP), more than 10 000-fold signal enhancement can be readily reached, making it possible to visualize real-time metabolism and specific substrate-to-metabolite conversions in the liver after injecting carbon-13 labelled probes. Increasing evidence suggests that HP 13 C MRI is a potential tool in detecting liver abnormalities, predicting disease progression and monitoring response treatment. In this review, we will introduce the recent progresses of HP 13 C MRI in diffuse liver diseases and liver malignancies and discuss its future opportunities from a clinical perspective, hoping to provide a comprehensive overview of this novel technique in liver diseases and highlight its scientific and clinical potential in the field of hepatology.
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Affiliation(s)
- Zheng Ye
- Department of RadiologyWest China Hospital, Sichuan UniversityChengduSichuanChina
- The MR Research Center, Department of Clinical MedicineAarhus UniversityAarhusDenmark
| | - Bin Song
- Department of RadiologyWest China Hospital, Sichuan UniversityChengduSichuanChina
| | - Philip M. Lee
- Department of Radiology and Biomedical ImagingUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Michael A. Ohliger
- Department of Radiology and Biomedical ImagingUniversity of CaliforniaSan FranciscoCaliforniaUSA
| | - Christoffer Laustsen
- The MR Research Center, Department of Clinical MedicineAarhus UniversityAarhusDenmark
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Multi-phase contrast-enhanced magnetic resonance image-based radiomics-combined machine learning reveals microscopic ultra-early hepatocellular carcinoma lesions. Eur J Nucl Med Mol Imaging 2022; 49:2917-2928. [PMID: 35230493 PMCID: PMC9206604 DOI: 10.1007/s00259-022-05742-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 02/17/2022] [Indexed: 12/17/2022]
Abstract
Purpose
This study aimed to investigate whether models built from radiomics features based on multiphase contrast-enhanced MRI can identify microscopic pre-hepatocellular carcinoma lesions. Methods We retrospectively studied 54 small hepatocellular carcinoma (SHCC, diameter < 2 cm) patients and 70 patients with hepatocellular cysts or haemangiomas from September 2018 to June 2021. For the former, two MRI scans were collected within 12 months of each other; the 2nd scan was used to confirm the diagnosis. The volumes of interest (VOIs), including SHCCs and normal liver tissues, were delineated on the 2nd scans, mapped to the 1st scans via image registration, and enrolled into the SHCC and internal-control cohorts, respectively, while those of normal liver tissues from patients with hepatocellular cysts or haemangioma were enrolled in the external-control cohort. We extracted 1132 radiomics features from each VOI and analysed their discriminability between the SHCC and internal-control cohorts for intra-group classification and the SHCC and external-control cohorts for inter-group classification. Five radial basis-function, kernel-based support vector machine (SVM) models (four corresponding single-phase models and one integrated from the four-phase MR images) were established. Results Among the 124 subjects, the multiphase models yielded better performance on the testing set for intra-group and inter-group classification, with areas under the receiver operating characteristic curves of 0.93 (95% CI, 0.85–1.00) and 0.97 (95% CI, 0.92–1.00), accuracies of 86.67% and 94.12%, sensitivities of 87.50% and 94.12%, and specificities of 85.71% and 94.12%, respectively. Conclusion The combined multiphase MRI-based radiomics feature model revealed microscopic pre-hepatocellular carcinoma lesions. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-022-05742-8.
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18
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Sheng X, Qin JM. Clinical features and diagnostic and therapeutic strategies of hepatic dysplastic nodules. Shijie Huaren Xiaohua Zazhi 2022; 30:169-181. [DOI: 10.11569/wcjd.v30.i4.169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatic dysplastic nodules (DNs) are a group of neoplastic lesions with a diameter of more than 1 cm that belong to precancerous lesions, with abnormal cytoplasm and cells but without malignant basis in histology. Hepatic DNs lack typical tumor markers and clinical symptoms, and their clinical diagnosis relys mainly on imaging or/and tissue pathological examination. Thanks to the further research on the pathogenesis of hepatic DNs and the development of imaging technology, the combination of medical history, various examinationss, individual tumor markers, and imaging and histopathology techniques can significantly improve the early detection and diagnosis accuracy for hepatic DNs, and reduce the rate of missed and false diagnosis. Due to the potential malignancy risk of hepatic DNs, intervention measures should be carried out on hepatic DNs at all stages, in order to block the transformation process of DNs into hepatocellular carcinoma (HCC), which is of great clinical significance to reduce the incidence and mortality of HCC.
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Affiliation(s)
- Xia Sheng
- Department of Pathology, Minhang Hospital Affiliated to Fudan University, Shanghai 201100, China
| | - Jian-Min Qin
- Department of General Surgery, The Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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19
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Park HJ, Lee TY, Kim SY, Kim MJ, Singal AG, Lee SJ, Won HJ, Byun JH, Lim YS. Hypervascular transformation of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI: long-term follow-up in a surveillance cohort. Eur Radiol 2022; 32:5064-5074. [PMID: 35229195 DOI: 10.1007/s00330-022-08623-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/25/2022] [Accepted: 01/31/2022] [Indexed: 11/27/2022]
Abstract
OBJECTIVES With the increasing use of gadoxetic acid-enhanced MRI for HCC surveillance, hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) are frequently encountered. We investigated the rate of these nodules with hypervascular transformation, which suggests hepatocarcinogenesis, by using a prospectively collected longitudinal surveillance cohort data. METHODS This study included 382 prospectively enrolled patients at high risk for developing HCC who underwent 1-3 rounds of bi-annual surveillance gadoxetic acid-enhanced MRI. MRI was analyzed to detect HBP hypointense nodules without APHE. Follow-up dynamic CTs and MRIs were evaluated to detect hypervascular transformation of the nodules. Cox proportional hazards regression analyses were used to find predictors for hypervascular transformation. RESULTS A total of 76 HBP hypointense nodules without APHE were found in 48 patients, giving a prevalence of 12.6% (48/382). The mean nodule size was 10.8 mm, with 43.4% (33/76) being ≥ 10 mm. Over a median follow-up of 78.6 months, 19 nodules (25.0%) showed hypervascular transformation, all of which demonstrated typical imaging features of HCC. On multivariable Cox-regression analysis, size (≥ 10 mm) was the only independent predictor of hypervascular transformation (hazard ratio, 3.31; 95% confidence interval, 1.21-9.05). The cumulative incidence of hypervascular transformation at 12 and 60 months of nodules ≥ 10 mm was 12.3% and 50.4%, respectively, while that of nodules < 10 mm was 2.5% and 13.9%, respectively. CONCLUSIONS About half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC at 5 years of follow-up, indicating the necessity for cautious monitoring with an augmented and extended follow-up schedule for these nodules. KEY POINTS • The prevalence of HBP hypointense nodules without APHE was 12.6% in a prospectively recruited population at high risk of developing HCC. • Nodule size ≥ 10 mm was significantly associated with hypervascular transformation, and approximately half of the HBP hypointense nodules ≥ 10 mm without APHE transformed to HCC during 5 years of follow-up. • Given the risk of malignant transformation, HBP hypointense nodules ≥ 10 mm without APHE should be closely monitored.
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Affiliation(s)
- Hyo Jung Park
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Tae Young Lee
- Department of Radiology, Ulsan University Hospital, Ulsan, Republic of Korea
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. .,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.
| | - Min-Ju Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Amit G Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - So Jung Lee
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Hyung Jin Won
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.,Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea
| | - Young-Suk Lim
- Liver Cancer Center, Asan Medical Center, Seoul, Republic of Korea.,Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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20
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Xu B, Sun HC. Camrelizumab: an investigational agent for hepatocellular carcinoma. Expert Opin Investig Drugs 2021; 31:337-346. [PMID: 34937475 DOI: 10.1080/13543784.2022.2022121] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Although many approaches have been used to treat hepatocellular carcinoma (HCC), the clinical benefits were limited, particularly for advanced HCC. However, recent treatments with PD-1/PD-L1 inhibitor monotherapy and its combination with other therapies, have demonstrated remarkable results. Camrelizumab, a selective, humanized, high-affinity IgG4 PD-1 monoclonal antibody, has been approved as a second-line treatment in patients with advanced HCC by NMPA in China. AREAS COVERED This paper introduces anti-PD-1/PD-L1 immunotherapies for advanced HCC and progresses to discuss the pharmacology, safety, and efficacy of camrelizumab in the treatment of advanced HCC. It also considers future research directions for camrelizumab in this setting. EXPERT OPINION The PD-1 binding epitope of camrelizumab is different from other PD-1 inhibitors. The IC50 and EC50 of camrelizumab for inhibiting the binding of PD-1 and PD-L1 is similar to pembrolizumab, is significantly lower than other PD-1 inhibitors, and has a higher affinity for PD-1 site. Camrelizumab exhibits a promising antitumor activity and an acceptable safety profile similar to other PD-1 inhibitors in advanced HCC. Apatinib (a VEGFR-2 tyrosine kinase inhibitor) can reduce the incidence of camrelizumab-specific reactive cutaneous capillary endothelial proliferation (RCCEP).
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Affiliation(s)
- Bin Xu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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21
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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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22
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Tamura M, Nakatsuka S, Torikai H, Misu M, Tsukada J, Tamura K, Ito N, Inoue M, Yashiro H, Jinzaki M. Portal Vein Damage after DEB-TACE and Lipiodol-TACE: Based on Evaluation by Computed Tomography during Arterial Portography. INTERVENTIONAL RADIOLOGY 2021; 6:93-101. [PMID: 35912281 PMCID: PMC9327435 DOI: 10.22575/interventionalradiology.2021-0007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 07/01/2021] [Indexed: 11/29/2022]
Abstract
Purpose: To reveal the effect of drug-eluting beads transarterial chemoembolization and Lipiodol transarterial chemoembolization on portal perfusion, and to identify factors predisposing portal vein damage after transarterial chemoembolization, based on evaluation by computed tomography during arterial portography. Material and Methods: This retrospective cohort analysis included 49 patients with hepatocellular carcinoma who underwent transarterial chemoembolization and preprocedural/follow-up computed tomography during arterial portography between October 2013 and April 2015. The preprocedural and follow-up computed tomography during arterial portography were compared to identify the following new changes suggestive of portal vein damage in the follow-up computed tomography during arterial portography: small perfusion defects, large perfusion defects, and narrowing/disappearance or portal vein obstruction. The frequency of portal vein damage after drug-eluting beads transarterial chemoembolization and Lipiodol transarterial chemoembolization was calculated, and relationships between portal vein damage and clinical variables were analyzed. Finally, a multivariate logistic regression analysis with adjustments for potentially confounding factors was performed to identify factors predisposing portal vein damage. Results: The analysis included 24 patients who underwent drug-eluting beads transarterial chemoembolization and 25 who underwent Lipiodol transarterial chemoembolization. Emergence of small perfusion defects and narrowing/disappearance or obstruction of portal vein were observed at a significantly higher frequency following drug-eluting beads transarterial chemoembolization than following Lipiodol transarterial chemoembolization (70.8% [17/24] vs. 20% [5/25]; p < 0.001; 41.7% [10/24] vs. 12% [3/25]; p = 0.019). Drug-eluting beads transarterial chemoembolization and selectivity of transarterial chemoembolization (selective [<subsegmental], segmental or lobar) were significantly associated with portal vein damage (p < 0.001 and p = 0.016, respectively). However, multivariate logistic regression analysis identified drug-eluting beads transarterial chemoembolization as a significant independent predictor of portal vein damage (odds ratio: 34.95; 95% confidence interval: 1.137-1073.99; p = 0.042). Conclusions: Portal vein damage occurred at a significantly higher frequency following drug-eluting beads transarterial chemoembolization than following Lipiodol transarterial chemoembolization, and drug-eluting beads transarterial chemoembolization was an independent predictor of portal vein damage after transarterial chemoembolization.
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Affiliation(s)
- Masashi Tamura
- Department of Radiology, Keio University School of Medicine
| | | | | | - Manabu Misu
- Department of Diagnostic Radiology, Hiratsuka City Hospital
| | - Jitsuro Tsukada
- Department of Radiology, Nihon University School of Medicine
| | - Kentaro Tamura
- Department of Radiology, Toho University School of Medicine Omori Medical Center
| | - Nobutake Ito
- Department of Radiology, Keio University School of Medicine
| | - Masanori Inoue
- Department of Radiology, Keio University School of Medicine
| | - Hideki Yashiro
- Department of Diagnostic Radiology, Hiratsuka City Hospital
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23
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Song M, Park HJ, Lee ES, Ahn HS, Park SB. Value of precontrast and portal venous phases for evaluating atypical hepatocellular carcinoma mimicking arterioportal shunt. Eur J Radiol 2021; 143:109933. [PMID: 34492626 DOI: 10.1016/j.ejrad.2021.109933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 08/19/2021] [Accepted: 08/22/2021] [Indexed: 11/20/2022]
Abstract
PURPOSE To evaluate the value of precontrast phase (PP) and portal venous phase (PVP) for differentiation of small hypervascular hepatocellular carcinomas (HCCs) without delayed washout from arterioportal (AP) shunts in high-risk patients of HCC. METHODS A total of 122 lesions (73 AP shunts and 49 HCCs) detected on quadriphasic CT in 101 patients with chronic liver disease were analyzed. All lesions (≤2 cm) showed arterial enhancement and isodensity on delayed phase (DP) with exclusion of typical features of AP shunts. Lesion morphologic features (size, location, shape, margin) on biphasic CT (arterial phase and DP), Alpha-fetoprotein (AFP) values and coexistent HCC were evaluated. The qualitative and quantitative analyses of lesion attenuation on quadriphasic CT were performed. Diagnostic performances for prediction of AP shunts over HCC were compared among the biphasic CT, triphasic CT (adding PP or PVP) and quadriphasic CT. RESULTS In multivariate analysis, the presence of concomitant HCC (p = 0.0005, odds ratio [OR] = 0.11), visual hypodensity on PP (p = 0.0004, OR = 17.72) and visual hyperdensity on PVP (p = 0.0003, OR = 0.051) were independent predictors for HCCs rather than AP shunts. Additional review of PP and PVP revealed significantly improved diagnostic performance yielding the highest diagnostic performance. CONCLUSIONS Hypodensity on PP and hyperdensity on PVP are significant predictive features in differentiating atypical small hypervascular HCC from AP shunts in patients with high-risk of HCC. Careful evaluation of the PP and PVP may reduce underdiagnosis and lead to earlier diagnosis of atypical small HCCs.
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Affiliation(s)
- Minkyo Song
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Hyun Jeong Park
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
| | - Eun Sun Lee
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Hye Shin Ahn
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Sung Bin Park
- Department of Radiology, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea
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24
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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: 434] [Impact Index Per Article: 108.5] [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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25
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Stocker D, Hectors S, Bane O, Vietti-Violi N, Said D, Kennedy P, Cuevas J, Cunha GM, Sirlin CB, Fowler KJ, Lewis S, Taouli B. Dynamic contrast-enhanced MRI perfusion quantification in hepatocellular carcinoma: comparison of gadoxetate disodium and gadobenate dimeglumine. Eur Radiol 2021; 31:9306-9315. [PMID: 34043055 DOI: 10.1007/s00330-021-08068-5] [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: 02/27/2021] [Revised: 04/22/2021] [Accepted: 05/11/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVES (1) To assess the quality of the arterial input function (AIF) during dynamic contrast-enhanced (DCE) MRI of the liver and (2) to quantify perfusion parameters of hepatocellular carcinoma (HCC) and liver parenchyma during the first 3 min post-contrast injection with DCE-MRI using gadoxetate disodium compared to gadobenate dimeglumine (Gd-BOPTA) in different patient populations. METHODS In this prospective study, we evaluated 66 patients with 83 HCCs who underwent DCE-MRI, using gadoxetate disodium (group 1, n = 28) or Gd-BOPTA (group 2, n = 38). AIF qualitative and quantitative features were assessed. Perfusion parameters (based on the initial 3 min post-contrast) were extracted in tumours and liver parenchyma, including model-free parameters (time-to-peak enhancement (TTP), time-to-washout) and modelled parameters (arterial flow (Fa), portal venous flow (Fp), total flow (Ft), arterial fraction, mean transit time (MTT), distribution volume (DV)). In addition, lesion-to-liver contrast ratios (LLCRs) were measured. Fisher's exact tests and Mann-Whitney U tests were used to compare the two groups. RESULTS AIF quality, modelled and model-free perfusion parameters in HCC were similar between the 2 groups (p = 0.054-0.932). Liver parenchymal flow was lower and liver enhancement occurred later in group 1 vs group 2 (Fp, p = 0.002; Ft, p = 0.001; TTP, MTT, all p < 0.001), while there were no significant differences in tumour LLCR (max. positive LLCR, p = 0.230; max. negative LLCR, p = 0.317). CONCLUSION Gadoxetate disodium provides comparable AIF quality and HCC perfusion parameters compared to Gd-BOPTA during dynamic phases. Despite delayed and decreased liver enhancement with gadoxetate disodium, LLCRs were equivalent between contrast agents, indicating similar tumour conspicuity. KEY POINTS • Arterial input function quality, modelled, and model-free dynamic parameters measured in hepatocellular carcinoma are similar in patients receiving gadoxetate disodium or gadobenate dimeglumine during the first 3 min post injection. • Gadoxetate disodium and gadobenate dimeglumine show similar lesion-to-liver contrast ratios during dynamic phases in patients with HCC. • There is lower portal and lower total hepatic flow and longer hepatic mean transit time and time-to-peak with gadoxetate disodium compared to gadobenate dimeglumine.
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Affiliation(s)
- Daniel Stocker
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Institute of Diagnostic and Interventional Radiology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Stefanie Hectors
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Octavia Bane
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Naik Vietti-Violi
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Radiology, Lausanne University Hospital, Lausanne, Switzerland
| | - Daniela Said
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Radiology, Universidad de los Andes, Santiago, Chile
| | - Paul Kennedy
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Jordan Cuevas
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Guilherme M Cunha
- Liver Imaging Group, Radiology, University of California-San Diego, San Diego, CA, USA
| | - Claude B Sirlin
- Liver Imaging Group, Radiology, University of California-San Diego, San Diego, CA, USA
| | - Kathryn J Fowler
- Liver Imaging Group, Radiology, University of California-San Diego, San Diego, CA, USA
| | - Sara Lewis
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA
| | - Bachir Taouli
- BioMedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA.
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26
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Zheng R, Wang L, Wang C, Yu X, Chen W, Li Y, Li W, Yan F, Wang H, Li R. Feasibility of automatic detection of small hepatocellular carcinoma (≤2 cm) in cirrhotic liver based on pattern matching and deep learning. Phys Med Biol 2021; 66. [PMID: 33780910 DOI: 10.1088/1361-6560/abf2f8] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 03/29/2021] [Indexed: 12/13/2022]
Abstract
Background and objective.Early detection of hepatocellular carcinoma (HCC) is crucial for clinical management. Current studies have reported large HCC detections using automatic algorithms, but there is a lack of research on automatic detection of small HCCs (sHCCs). This study is to investigate the feasibility of automatic detection of sHCC (≤2 cm) based on pattern matching and deep learning (PM-DL) model.Materials and methods. A retrospective study included 5376 image sets from 56 cirrhosis patients (28 sHCC patients with 32 pathologically confirmed lesions and 28 non-HCC cirrhosis patients) in the training-validation cohort to build and validate the model through five-fold cross-validation. In addition, an external test cohort including 6144 image sets from 64 cirrhosis patients (32 sHCC patients with 38 lesions and 32 non-HCC cirrhosis patients) was applied to further verify the generalization ability of the model. The proposed PM-DL model consisted of three main steps: 3D co-registration and liver segmentation, screening of suspicious lesions on diffusion-weighted imaging images based on pattern matching algorithm, and identification/segmentation of sHCC lesions on dynamic contrast-enhanced images with convolutional neural network.Results.The PM-DL model achieved a sensitivity of 89.74% and a positive predictive value of 85.00% in the external test cohort for per-lesion analysis. No significant difference was observed in volumes (P= 0.13) and the largest sizes (P= 0.89) between manually delineated and segmented lesions. The DICE coefficient reached 0.77 ± 0.16. Similar performances were identified in the validation cohort. Moreover, the PM-DL model outperformed Liver Imaging Reporting and Data System (LI-RADS) in sensitivity (probable HCCs: LR-5 or LR-4,P= 0.18; definite HCCs: LR-5,P< 0.001), with a similar high specificity for per-patient analysis.Conclusion. The PM-DL model may be feasible for accurate automatic detection of sHCC in cirrhotic liver.
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Affiliation(s)
- Rencheng Zheng
- Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, People's Republic of China.,Department of Radiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China.,Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, People's Republic of China
| | - Luna Wang
- Department of Radiology, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, People's Republic of China.,Department of Radiology, Jinshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Chengyan Wang
- Human Phenome Institute, Fudan University, Shanghai, People's Republic of China
| | - Xuchen Yu
- Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, People's Republic of China
| | - Weibo Chen
- Philips Healthcare, Shanghai, People's Republic of China
| | - Yan Li
- Department of Radiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Weixia Li
- Department of Radiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
| | - He Wang
- Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence (Fudan University), Ministry of Education, People's Republic of China.,Human Phenome Institute, Fudan University, Shanghai, People's Republic of China
| | - Ruokun Li
- Department of Radiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
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27
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Zhong C, Li Y, Yang J, Jin S, Chen G, Li D, Fan X, Lin H. Immunotherapy for Hepatocellular Carcinoma: Current Limits and Prospects. Front Oncol 2021; 11:589680. [PMID: 33854960 PMCID: PMC8039369 DOI: 10.3389/fonc.2021.589680] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 03/10/2021] [Indexed: 12/13/2022] Open
Abstract
Although many approaches have been used to treat hepatocellular carcinoma (HCC), the clinical benefits remain limited, particularly for late stage HCC. In recent years, studies have focused on immunotherapy for HCC. Immunotherapies have shown promising clinical outcomes in several types of cancers and potential therapeutic effects for advanced HCC. In this review, we summarize the immune tolerance and immunotherapeutic strategies for HCC as well as the main challenges of current therapeutic approaches. We also present alternative strategies for overcoming these limitations.
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Affiliation(s)
- Cheng Zhong
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yirun Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Yang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shengxi Jin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Guoqiao Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Duguang Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxiao Fan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,State Key Laboratory of Modern Optical Instrumentations, Centre for Optical and Electromagnetic Research, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University, Hangzhou, China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.,Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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28
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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: 13] [Impact Index Per Article: 3.3] [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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Radiological response to nivolumab in patients with hepatocellular carcinoma: A multicenter analysis of real-life practice. Eur J Radiol 2020; 135:109484. [PMID: 33383399 DOI: 10.1016/j.ejrad.2020.109484] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 12/09/2020] [Accepted: 12/15/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Immune-checkpoint inhibitors are effective in many advanced tumors. However, there is scarce information regarding the radiological response to these agents in hepatocellular carcinoma outside clinical trials. We aimed to describe the radiological response in a retrospective cohort of hepatocellular carcinoma patients treated with nivolumab and to analyze the radiological evolution according to tumor response at first post-treatment radiological assessment. METHODS We reviewed pre-treatment and post-treatment images (CT or MRI) obtained at different time-points in patients with hepatocellular carcinoma treated with nivolumab outside clinical trials at seven Spanish centers, assessing the response according to RECIST 1.1 and iRECIST and registering atypical responses. We also analyzed the imaging findings on subsequent assessments according to tumor status on the first posttreatment imaging assessment. RESULTS From the 118 patients with hepatocellular carcinoma treated with nivolumab, we finally analyzed data from 31 patients (71 % Child-Pugh A; 74 % BCLC-C). Median follow-up was 8.39 months [IQR 5.00-10.92]; median overall survival was 12.82 months (95 %CI 10.92-34.79). According to RECIST 1.1, the objective response rate was 16 % and according to iRECIST, the objective response rate was 22.6 %. Findings at the first post-treatment assessment varied, showing stable disease in 44.8 % of patients; findings during follow-up also varied widely, including 4 hyperprogressions and 3 pseudoprogressions. CONCLUSION Imaging findings during nivolumab treatment are heterogeneous between and within patients. Progression of disease does not always signify treatment failure, and surrogate end-points may not reflect survival outcomes, making the management of hepatocellular carcinoma patients under immunotherapy challenging.
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30
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Ren X, Dong Y, Duan M, Zhang H, Gao P. Abnormal expression of HNRNPA3 in multistep hepatocarcinogenesis. Oncol Lett 2020; 21:46. [PMID: 33281957 PMCID: PMC7709557 DOI: 10.3892/ol.2020.12307] [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: 02/28/2020] [Accepted: 09/08/2020] [Indexed: 12/30/2022] Open
Abstract
Hepatocarcinogenesis is a multistep process involving progression from cirrhosis, to low-grade dysplastic nodule, to high-grade dysplastic nodule (HGDN) and, eventually, to hepatocellular carcinoma (HCC). Early detection of HCC is challenging as the differential diagnosis between HGDN and early HCC (eHCC) is difficult. The aim of the present study was to identify a novel biomarker to specifically differentiate between HGDN and eHCC, which may facilitate early diagnosis of HCC. Immunohistochemistry was performed to determine the expression of heterogeneous nuclear ribonucleoprotein A3 (HNRNPA3) in cirrhosis, dysplastic nodules (DNs), well-differentiated HCC and progressed HCC. The staining was evaluated by assigning a staining intensity score of 0–3 and a percentage of positively stained cells score of 0–4. Receiver operator characteristic (ROC) curve analysis was used to assess the ability of HNRNPA3 expression to differentiate between DNs and HCC. HNRNPA3 expression increased in a stepwise trend in non-tumor hepatic tissue, DNs, eHCC and progressed HCC. ROC curves revealed that HNRNPA3 expression could be used to differentiate between HGDN and eHCC, particularly in combination with glypican 3 (GPC3), with a specificity of 100%. Moreover, HNRNPA3 expression was associated with HCC differentiation. In addition, high expression of HNRNPA3 was found to be associated with poor survival rates in patients with HCC. These findings demonstrated that HNRNPA3 combined with GPC3 is a helpful diagnostic biomarker in the differential diagnosis during the multistep process of hepatocarcinogenesis, particularly in the differential diagnosis between HGDN and eHCC. To the best of our knowledge, this is the first study to report the significance of HNRNPA3 in hepatocarcinogenesis and its potential role in carcinogenesis.
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Affiliation(s)
- Xinlu Ren
- Department of Clinical Medicine, Queen Mary College of Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Yi Dong
- Key Laboratory for Experimental Teratology of The Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Miao Duan
- Key Laboratory for Experimental Teratology of The Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Hui Zhang
- Key Laboratory for Experimental Teratology of The Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Peng Gao
- Key Laboratory for Experimental Teratology of The Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China.,Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
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31
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Garrido A, Djouder N. Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma. Trends Cancer 2020; 7:29-36. [PMID: 32917550 DOI: 10.1016/j.trecan.2020.08.005] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 07/30/2020] [Accepted: 08/18/2020] [Indexed: 02/06/2023]
Abstract
The liver is one of the major metabolic organs in the body, susceptible to injury caused by various factors. In response to injury, sophisticated mechanisms are engaged to repair and regenerate the damaged liver, preventing its failure. When the damage is chronic, regeneration goes awry, impairing liver function and causing cirrhosis. Hence, cirrhosis may rather be a protective response to injury, where wound-healing processes are set to primarily repair the damaged liver. Although cirrhosis is clinically considered a risk factor for hepatocellular carcinoma (HCC), comprehensive population-based studies demonstrate a very modest incidence, refuting the idea that cirrhosis progresses to HCC. Here, we discuss and shed light on the provocative question of whether cirrhosis predisposes to HCC.
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Affiliation(s)
- Amanda Garrido
- Molecular Oncology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain
| | - Nabil Djouder
- Molecular Oncology Programme, Growth Factors, Nutrients and Cancer Group, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid 28029, Spain.
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32
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Lu D, Bai X, Zou Q, Gan Z, Lv Y. Identification of the association between HMMR expression and progression of hepatocellular carcinoma via construction of a co-expression network. Oncol Lett 2020; 20:2645-2654. [PMID: 32765791 PMCID: PMC7403633 DOI: 10.3892/ol.2020.11844] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 01/04/2020] [Indexed: 02/06/2023] Open
Abstract
The aim of the present study was to identify key genes involved in the progression of hepatocellular carcinoma (HCC). According to the theory of the multistep process of hepatocarcinogenesis and weighted gene co-expression network analysis, hub genes associated with the progression of HCC were identified using the gene expression profiles of patients with normal to chronic hepatitis/cirrhosis and dysplastic nodules to HCC. An independent dataset was used to verify the association between hub gene and clinical phenotype. The diagnostic and prognostic value of hub genes regarding HCC were evaluated. Gene set enrichment analysis (GSEA) was performed to explore the function of hub genes. A co-expression gene module positively associated with HCC progression was identified. Combined with a protein-protein interaction (PPI) network, a total of 10 common hub genes common to both the module of interest and the PPI network were selected as hub genes. Hyaluronan mediated motility receptor (HMMR) was selected as the candidate gene and was significantly upregulated in HCC at the mRNA and protein expression levels. HMMR is a promising diagnostic biomarker for HCC, and is also associated with its progression. The expression of HMMR was positively correlated with HCC tumor grade, pathological stage, tumor stage and Ishak score. The expression of HMMR was an independent prognostic factor compared with clinicopathological features. Patients with high expression levels of HMMR exhibited a less favorable prognosis. GSEA identified 6 representative gene sets that were associated with cancer. Overall, HMMR may serve an important role in HCC and may have potential as a biomarker of HCC diagnosis and progression.
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Affiliation(s)
- Donglan Lu
- Department of Medical Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541199, P.R. China
| | - Xue Bai
- Department of Medical Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Zhuang Autonomous Region 541199, P.R. China
| | - Qiyuan Zou
- Department of Medicine 1, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Zuhuan Gan
- Department of Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
| | - Yufeng Lv
- Department of Oncology, Affiliated Langdong Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
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33
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Muraoka M, Maekawa S, Suzuki Y, Sato M, Tatsumi A, Matsuda S, Miura M, Nakakuki N, Shindo H, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Inoue T, Sato T, Yamashita A, Moriishi K, Matsuda M, Enomoto N. Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings. Hepatol Res 2020; 50:1071-1082. [PMID: 32510681 DOI: 10.1111/hepr.13529] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 04/28/2020] [Accepted: 05/17/2020] [Indexed: 02/07/2023]
Abstract
AIM The landscape of cancer-related genetic aberrations in hepatocellular carcinoma (HCC) has gradually become clear through recent next-generation sequencing studies. However, it remains unclear how genetic aberrations correlate with imaging and histological findings. METHODS Using 117 formalin-fixed paraffin-embedded specimens of primary liver tumors, we undertook targeted next-generation sequencing of 50 cancer-related genes and digital polymerase chain reaction of hTERT. After classifying tumors into several imaging groups by hierarchal clustering with the information from gadoxetic acid enhanced magnetic resonance imaging, contrast-enhanced computed tomography, contrast-enhanced ultrasound, and diffusion-weighted imaging magnetic resonance imaging, the correlation between genetic aberrations and imaging and histology were investigated. RESULTS Most frequent mutations were hTERT (61.5%), followed by TP53 (42.7%), RB1 (24.8%), and CTNNB1 (18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence of hTERT mutations tended to increase with the advancement of imaging/histological grades (P = 0.026 and 0.13, respectively), whereas no such tendency was evident for TP53 mutation (P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) of hTERT did not change (P = 0.36 and 0.14, respectively) in association with imaging/histological grades, TP53 VF increased significantly (P = 0.004 and <0.001, respectively). In multivariate analysis, stage III or IV (hazard ratio, 3.64; P = 0.003), TP53 VF ≥ 50% (hazard ratio, 3.79; P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. CONCLUSIONS Increased prevalence of hTERT mutation and increased TP53 mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.
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Affiliation(s)
- Masaru Muraoka
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Shinya Maekawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Yuichiro Suzuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Mitsuaki Sato
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Akihisa Tatsumi
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Shuya Matsuda
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Mika Miura
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Natsuko Nakakuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Hiroko Shindo
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Fumitake Amemiya
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Shinichi Takano
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Mitsuharu Fukasawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Yasuhiro Nakayama
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Tatsuya Yamaguchi
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Taisuke Inoue
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Tadashi Sato
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
| | - Atsuya Yamashita
- Department of Microbiology, University of Yamanashi, Chuo, Japan
| | - Kohji Moriishi
- Department of Microbiology, University of Yamanashi, Chuo, Japan
| | - Masanori Matsuda
- Department of Surgery, Fujiyoshida Municipal Hospital, Fujiyoshida, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Japan
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34
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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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35
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Shi Q, Chen D, Zhou C, Liu J, Huang S, Yang C, Xiong B. Drug-Eluting Beads versus Lipiodol Transarterial Chemoembolization for the Treatment of Hypovascular Hepatocellular Carcinoma: A Single-Center Retrospective Study. Cancer Manag Res 2020; 12:5461-5468. [PMID: 32753963 PMCID: PMC7351634 DOI: 10.2147/cmar.s255960] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 05/28/2020] [Indexed: 12/25/2022] Open
Abstract
Purpose To evaluate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in treating hypovascular hepatocellular carcinoma (HCC). Materials and Methods The medical records based on HCC patients who underwent TACE from January 2016 to June 2019 were reviewed in the study. The diagnosis of hypovascular HCC was conducted by two senior radiologists according to imaging. We evaluated the adverse events (AEs), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) in the study. Results A total of 98 patients with hypovascular HCC were included in the study. 46 patients underwent DEB-TACE treatment, and 52 patients underwent C-TACE treatment. The PFS of DEB-TACE group and C-TACE group was 12.0 months and 7.0 months (P < 0.001), and OS was 21.0 months and 14.0 months (P = 0.035), respectively. In addition, DEB-TACE group had better ORR (76.1% vs 40.4%, P < 0.001) and DCR (91.3% vs 75.0%, P = 0.033) compared to C-TACE group. The occurrence rate of AEs showed no difference between the two groups (67.3% vs 57.7%, P = 0.323). Furthermore, we found that DEB-TACE can be identified as a positive independent prognostic factor for improved PFS and OS. Conclusion DEB-TACE, as an effective treatment, can yield better objective response rate, similar safety profile and improved survival for hypovascular HCC patients compared to C-TACE.
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Affiliation(s)
- Qin Shi
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
| | - Dandan Chen
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China.,Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China
| | - Chen Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
| | - Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
| | - Songjiang Huang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
| | - Chongtu Yang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
| | - Bin Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.,Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, People's Republic of China
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36
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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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Afaloniati H, Angelopoulou K, Giakoustidis A, Hardas A, Pseftogas A, Makedou K, Gargavanis A, Goulopoulos T, Iliadis S, Papadopoulos V, Papalois A, Mosialos G, Poutahidis T, Giakoustidis D. HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice. Onco Targets Ther 2020; 13:5575-5588. [PMID: 32606772 PMCID: PMC7304783 DOI: 10.2147/ott.s250233] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 05/27/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi). The aim of the present study was to investigate the effect of HDAC1/2 inhibitor Romidepsin in the well-established mouse model of diethylnitrosamine (DEN)-induced HCC. MATERIALS AND METHODS C56BL/6 mice were treated with Romidepsin at the critical point of 10 months after DEN challenge and their livers were examined 2 months later using histopathology and morphometry. Protein levels were assessed in serum using ELISA and in liver tissues using Western blot and immunohistochemistry (in-situ detection). Gene expression was quantified using real-time PCR. RESULTS Romidepsin suppressed cancer progression. This effect was associated with decreased proliferation and increased apoptosis of cancer cells. The cell cycle regulator CK2a, the anti-inflammatory molecule PPAR-γ, and the tumor suppressors PTEN and CYLD were upregulated in treated HCC. By contrast, the expression of PI3K, NF-κB p65 and c-Jun was reduced. In line with this result, the levels of two major apoptosis regulators, ie, BAD and the multifunctional protein c-Met, were lower in the blood serum of treated mice compared to the untreated mice with HCC. CONCLUSION These findings suggest that Romidepsin, a drug currently used in the treatment of lymphoma, could also be considered in the management of early-stage HCC.
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Affiliation(s)
- Hara Afaloniati
- Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Katerina Angelopoulou
- Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Alexander Giakoustidis
- First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
| | - Alexandros Hardas
- Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios Pseftogas
- School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Kali Makedou
- Department of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Athanasios Gargavanis
- First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
| | - Thomas Goulopoulos
- First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
| | - Stavros Iliadis
- Department of Biological Chemistry, Medical School, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasileios Papadopoulos
- First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
| | - Apostolos Papalois
- Experimental, Educational and Research Center, ELPEN, Pikermi, Attica, Greece
| | - George Mosialos
- School of Biology, Faculty of Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Theofilos Poutahidis
- Laboratory of Pathology, School of Veterinary Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Giakoustidis
- First Department of Surgery, Medical School, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
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Shimizu Y, Arai K, Yamashita T, Yamashita T, Shimakami T, Kawaguchi K, Kitamura K, Sakai Y, Mizukoshi E, Honda M, Kitao A, Kozaka K, Kobayashi S, Kaneko S. Direct-Acting Antiviral Agents Reduce the Risk of Malignant Transformation of Hepatobiliary Phase-Hypointense Nodule without Arterial Phase Hyperenhancement to Hepatocellular Carcinoma on Gd-EOB-DPTA-Enhanced Imaging in the Hepatitis C Virus-Infected Liver. Liver Cancer 2020; 9:261-274. [PMID: 32647630 PMCID: PMC7325122 DOI: 10.1159/000504889] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Accepted: 10/26/2019] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND AND AIMS Hepatobiliary phase-hypointense nodules without arterial phase hyperenhancement (HHNs without APHE) on gadolinium-ethoxybenzyl-diethylenetriamine-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) are considered to be dysplastic nodules or early hepatocellular carcinoma (HCC) and have high risk of undergoing malignant transformation and progression to hypervascular HCC. The aim of this study was to evaluate the clinical outcome of HHNs without APHE diagnosed by Gd-EOB-DTPA-enhanced MRI before the eradication of HCV by direct-acting antiviral agents (DAAs). METHODS We retrospectively investigated 221 consecutive patients with HCV infection who were treated with DAAs. Thirty patients with 65 HHNs without APHE were enrolled in a sustained virologic response (SVR) cohort and 22 with 43 HHNs without APHE who did not receive DAAs or had failed HCV eradication therapy were enrolled in a non-SVR cohort. Fifty-seven percent of patients in the SVR group and 64% of those in the non-SVR group had a history of HCC. The primary endpoint of this study was the development of hypervascular HCC from HHNs without APHE detected on imaging. The cumulative incidence and relative risk of progression to hypervascular HCC in relation to clinical characteristics were compared between the two cohorts. RESULTS The 2-year cumulative incidence of progression to hypervascular HCC was 8.5 and 21.9% in the SVR and non-SVR cohorts, respectively. There was a significant reduction in progression of HHNs without APHE to HCC after the eradication of HCV (p = 0.022, log-rank test). Multivariate Cox regression analysis identified hyperintensity on T2-weighted images (relative risk 14.699, p < 0.001) and achieving SVR (relative risk 0.290, p = 0.043) as independent factors associated with the risk of HCC. During follow-up, 6 (9.2%) of the HHNs without APHE in the SVR cohort became undetectable on hepatocyte-phase images. CONCLUSIONS Eradication of HCV by DAAs could reduce the hypervascularization rate of HHNs without APHE, and some of these nodules disappeared.
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Affiliation(s)
- Yoshiaki Shimizu
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kuniaki Arai
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan,*Kuniaki Arai, MD, PhD, Department of Gastroenterology, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641 (Japan), E-Mail , Taro Yamashita, MD, PhD, Department of General Medicine, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641 (Japan), E-Mail
| | - Taro Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Tatsuya Yamashita
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Tetsuro Shimakami
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kazunori Kawaguchi
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kazuya Kitamura
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Yoshio Sakai
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Eishiro Mizukoshi
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Masao Honda
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
| | - Azusa Kitao
- Department of Radiology, Kanazawa University Hospital, Kanazawa, Japan
| | - Kazuto Kozaka
- Department of Radiology, Kanazawa University Hospital, Kanazawa, Japan
| | - Satoshi Kobayashi
- Department of Radiology, Kanazawa University Hospital, Kanazawa, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan
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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: 2] [Impact Index Per Article: 0.4] [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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40
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Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, Park MS, Kudo N, Lee MW, Kamata K, Iijima H, Kim SY, Numata K, Sugimoto K, Maruyama H, Sumino Y, Ogawa C, Kitano M, Joo I, Arita J, Liang JD, Lin HM, Nolsoe C, Gilja OH, Kudo M. The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid. Ultrasonography 2020; 39:191-220. [PMID: 32447876 PMCID: PMC7315291 DOI: 10.14366/usg.20057] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Accepted: 04/27/2020] [Indexed: 12/11/2022] Open
Abstract
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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Affiliation(s)
- Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Byung Ihn Choi
- Department of Radiology, Chung Ang University Hospital, Seoul, Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yi-Hong Chou
- Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan.,Department of Radiology, National Yang Ming University, Taipei, Taiwan
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nobuki Kudo
- Laboratory of Biomedical Engineering, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Hiroko Iijima
- Department of Ultrasound, Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - So Yeon Kim
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Yasukiyo Sumino
- Department of Gastroenterology and Hepatology, Toho University Medical Center, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Masayuki Kitano
- Department of Gastroenterology and Hepatology, Wakayama Medical University Hospital, Wakayama, Japan
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ja-Der Liang
- Department of Gastroenterology and Hepatology, National Taiwan University, Taipei, Taiwan
| | - Hsi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung University, Taipei, Taiwan
| | - Christian Nolsoe
- Ultrasound Section, Division of Surgery, Department of Gastroenterology, Herlev Hospital, Copenhagen Academy for Medical Education and Simulation, University of Copenhagen, Copenhagen, Denmark
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway.,Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
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Satiya J, Schwartz I, Tabibian JH, Kumar V, Girotra M. Ablative therapies for hepatic and biliary tumors: endohepatology coming of age. Transl Gastroenterol Hepatol 2020; 5:15. [PMID: 32258519 PMCID: PMC7063520 DOI: 10.21037/tgh.2019.10.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 12/12/2022] Open
Abstract
Ablative therapies refer to minimally invasive procedures performed to destroy abnormal tissue that may arise with many conditions, and can be achieved clinically using chemical, thermal, and other techniques. In this review article, we explore the different ablative therapies used in the management of hepatic and biliary malignancies, namely hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), with a particular focus on radiofrequency ablation (RFA) and photodynamic therapy (PDT) techniques.
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Affiliation(s)
- Jinendra Satiya
- Internal Medicine, University of Miami/JFK Medical Center Palm Beach Regional GME Consortium, West Palm Beach, FL, USA
| | - Ingrid Schwartz
- Internal Medicine, University of Miami Miller School of Medicine/Jackson Memorial Hospital, Miami, FL, USA
| | - James H. Tabibian
- Geffen School of Medicine, University of California, Los Angeles, CA, USA
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Vivek Kumar
- Gastroenterology and Hepatology, UPMC Susquehanna, Williamsport, PA, USA
| | - Mohit Girotra
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Miami, FL, USA
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42
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Lee JY, Minami Y, Choi BI, Lee WJ, Chou YH, Jeong WK, Park MS, Kudo N, Lee MW, Kamata K, Iijima H, Kim SY, Numata K, Sugimoto K, Maruyama H, Sumino Y, Ogawa C, Kitano M, Joo I, Arita J, Liang JD, Lin HM, Nolsoe C, Gilja OH, Kudo M. The AFSUMB Consensus Statements and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound using Sonazoid. J Med Ultrasound 2020; 28:59-82. [PMID: 32874864 PMCID: PMC7446696 DOI: 10.4103/jmu.jmu_124_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 02/09/2020] [Accepted: 02/17/2020] [Indexed: 12/13/2022] Open
Abstract
The first edition of the guidelines for the use of ultrasound contrast agents was published in 2004, dealing with liver applications. The second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some nonliver applications. The third edition of the contrast-enhanced ultrasound (CEUS) guidelines was the joint World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology (WFUMB-EFSUMB) venture in conjunction with other regional US societies such as Asian Federation of Societies for Ultrasound in Medicine and Biology, resulting in a simultaneous duplicate on liver CEUS in the official journals of both WFUMB and EFSUMB in 2013. However, no guidelines were described mainly for Sonazoid due to limited clinical experience only in Japan and Korea. The new proposed consensus statements and recommendations provide general advice on the use of Sonazoid and are intended to create standard protocols for the use and administration of Sonazoid in hepatic and pancreatobiliary applications in Asian patients and to improve patient management.
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Affiliation(s)
- Jae Young Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Yasunori Minami
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Byung Ihn Choi
- Department of Radiology, Chung Ang University Hospital, Seoul, Korea
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yi-Hong Chou
- Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan
- Department of Radiology, National Yang Ming University, Taipei, Taiwan
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Mi-Suk Park
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Nobuki Kudo
- Laboratory of Biomedical Engineering, Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ken Kamata
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
| | - Hiroko Iijima
- Department of Ultrasound, Hepatobiliary and Pancreatic Disease, Hyogo College of Medicine, Nishinomiya, Japan
| | - So Yeon Kim
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Katsutoshi Sugimoto
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, Tokyo, Japan
| | - Yasukiyo Sumino
- Department of Gastroenterology and Hepatology, Toho University Medical Center, Tokyo, Japan
| | - Chikara Ogawa
- Department of Gastroenterology and Hepatology, Takamatsu Red Cross Hospital, Takamatsu, Japan
| | - Masayuki Kitano
- Department of Gastroenterology and Hepatology, Wakayama Medical University Hospital, Wakayama, Japan
| | - Ijin Joo
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ja-Der Liang
- Department of Gastroenterology and Hepatology, National Taiwan University, Taipei, Taiwan
| | - Hsi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung University, Taipei, Taiwan
| | - Christian Nolsoe
- Ultrasound Section, Division of Surgery, Department of Gastroenterology, Herlev Hospital, Copenhagen Academy for Medical Education and Simulation, University of Copenhagen, Copenhagen, Denmark
| | - Odd Helge Gilja
- National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Kindai University, Higashi-Osaka, Japan
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Ogasawara N, Saitoh S, Denpou H, Kinowaki K, Akuta N, Suzuki F, Hashimoto M, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Kobayashi M, Suzuki Y, Arase Y, Ikeda K, Fujii T, Kumada H. Poorly Differentiated Hepatocellular Carcinoma in a Low-risk Patient with an Otherwise Normal Liver. Intern Med 2020; 59:365-372. [PMID: 31619599 PMCID: PMC7028417 DOI: 10.2169/internalmedicine.3577-19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
We herein report a 48-year-old healthy woman who visited our hospital to investigate a 25-mm space-occupying lesion in the liver. The tumor was irregularly shaped and exhibited heterogeneous enhancement on dynamic computed tomography (CT). Whole-body positron emission tomography-CT showed an abnormal fluorodeoxyglucose uptake in the liver tumor, with a maximum standardized uptake value of 12.82. During the ensuing three months, the tumor grew rapidly and the serum alpha-fetoprotein levels also rose; partial hepatectomy was therefore performed. Microscopic findings revealed a moderately-to-poorly differentiated hepatocellular carcinoma in the normal liver.
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Affiliation(s)
| | | | - Hideyuki Denpou
- Department of Clinical Laboratory, Toranomon Hospital, Japan
| | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Japan
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Huang JY, Li JW, Lu Q, Luo Y, Lin L, Shi YJ, Li T, Liu JB, Lyshchik A. Diagnostic Accuracy of CEUS LI-RADS for the Characterization of Liver Nodules 20 mm or Smaller in Patients at Risk for Hepatocellular Carcinoma. Radiology 2020; 294:329-339. [PMID: 31793849 DOI: 10.1148/radiol.2019191086] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background American College of Radiology contrast agent-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) was developed to improve the accuracy of hepatocellular carcinoma (HCC) diagnosis at contrast agent-enhanced US. However, to the knowledge of the authors, the diagnostic accuracy of the system in characterization of liver nodules 20 mm or smaller has not been fully evaluated. Purpose To evaluate the diagnostic accuracy of CEUS LI-RADS in diagnosing HCC in liver nodules 20 mm or smaller in patients at risk for HCC. Materials and Methods Between January 2015 and February 2018, consecutive patients at risk for HCC presenting with untreated liver nodules 20 mm or less were enrolled in this retrospective double-reader study. Each nodule was categorized according to the CEUS LI-RADS and World Federation for Ultrasound in Medicine and Biology (WFUMB)-European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) criteria. Diagnostic performance of CEUS LI-RADS and WFUMB-EFSUMB characterization was evaluated by using tissue histologic analysis, multiphase contrast-enhanced CT and MRI, and imaging follow-up as reference standard and compared by using McNemar test. Results The study included 175 nodules (mean diameter, 16.1 mm ± 3.4) in 172 patients (mean age, 51.8 years ± 10.6; 136 men). The sensitivity of CEUS LR-5 versus WFUMB-EFSUMB criteria in diagnosing HCC was 73.3% (95% confidence interval [CI]: 63.8%, 81.5%) versus 88.6% (95% CI: 80.9%, 94%), respectively (P < .001). The specificity of CEUS LR-5 versus WFUMB-EFSUMB criteria was 97.1% (95% CI: 90.1%, 99.7%) versus 87.1% (95% CI: 77%, 94%), respectively (P = .02). No malignant lesions were found in CEUS LR-1 and LR-2 categories. Only two nodules (of 41; 5%, both HCC) were malignant in CEUS LR-3 category. The incidences of HCC in CEUS LR-4, LR-5, and LR-M were 48% (11 of 23), 98% (77 of 79), and 75% (15 of 20), respectively. Two of 175 (1.1%) histologic analysis-confirmed intrahepatic cholangiocarcinomas were categorized as CEUS LR-M by CEUS LI-RADS and misdiagnosed as HCC by WFUMB-EFSUMB criteria. Conclusion The contrast-enhanced US Liver Imaging Reporting and Data System (CEUS LI-RADS) algorithm was an effective tool for characterization of small (≤20 mm) liver nodules in patients at risk for hepatocellular carcinoma (HCC). Compared with World Federation for Ultrasound in Medicine and Biology-European Federation of Societies for Ultrasound in Medicine and Biology criteria, CEUS LR-5 demonstrated higher specificity for diagnosing small HCCs with lower sensitivity. Published under a CC BY 4.0 license. See also the editorial by Crocetti in this issue.
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Affiliation(s)
- Jia-Yan Huang
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Jia-Wu Li
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Qiang Lu
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Yan Luo
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Ling Lin
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Yu-Jun Shi
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Tao Li
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Ji-Bin Liu
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
| | - Andrej Lyshchik
- From the Department of Medical Ultrasound (J.Y.H., J.W.L., Q.L., Y.L., L.L.), Laboratory of Pathology (Y.J.S.), and Department of Anesthesiology (T.L.), West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan Province, China; and Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pa (J.B.L., A.L.)
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Purcell Y, Sartoris R, Paradis V, Vilgrain V, Ronot M. Influence of pretreatment tumor growth rate on objective response of hepatocellular carcinoma treated with transarterial chemoembolization. J Gastroenterol Hepatol 2020; 35:305-313. [PMID: 31369166 DOI: 10.1111/jgh.14816] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 07/15/2019] [Accepted: 07/29/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The study aims to assess the influence of pretreatment tumor growth rate (TGR) on modified response evaluation criteria in solid tumors (mRECIST) objective response (OR) after a first session of selective transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). METHODS One hundred fifteen patients (101 men [88%], mean 65.1 ± 10.5 years [range 26-87]) with 169 tumors (mean 34.2 ± 29.3 mm [10-160]), undergoing a first session of selective TACE for the treatment of HCC between 2011 and 2016, were included. TGR was calculated as the percentage change in tumor volume per month (%/month) on imaging before treatment. TGR cut-off for prediction of OR was identified by receiver operating characteristic curve analysis. RESULTS Overall 88/189 (52%) and 46/189 (27%) tumors showed complete response (CR) and partial response (PR) (OR rate 79%), while 32/189 (19%) showed stable disease (SD), and 3/189 (2%) were progressive disease (PD) on computed tomography at 1-month post-TACE. The mean pretreatment TGR was 12.0 ± 15.4 (-3.2-90.4) %/month. TGR of tumors showing CR, PR, SD, and PD was a mean 13.2 ± 16.4%, 12.1 ± 15.1%, 5.3 ± 4.5%, and 44.8 ± 20.4%, respectively (P < 0.001). The three tumors showing PD had TGR values > 20%/month. TGR was significantly higher in tumors with OR (12.8 ± 15.9% vs 5.3 ± 4.5% in SD, P = 0.009). A cut-off value of 6.5%/month had the highest predictive value of OR (AUROC 0.65 ± 0.05, P = 0.009). CONCLUSION Pretreatment TGR is highly variable in HCC before TACE with a U-shaped distribution for the prediction of tumor response. It provides insight into tumor biology that may be used during pretreatment workup to help stratify patients.
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Affiliation(s)
- Yvonne Purcell
- Department of Radiology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France
| | - Riccardo Sartoris
- Department of Radiology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France
| | - Valérie Paradis
- University Paris Diderot, Sorbonne Paris Cité, Paris, France.,Department of Pathology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France
| | - Valérie Vilgrain
- Department of Radiology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France.,University Paris Diderot, Sorbonne Paris Cité, Paris, France.,Department of Pathology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France
| | - Maxime Ronot
- Department of Radiology, APHP, University Hospitals Paris-Nord-Val-de-Seine, Beaujon, Clichy, France.,University Paris Diderot, Sorbonne Paris Cité, Paris, France.,INSERM U1149, CRI, Paris, France
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Chen J, Wu Z, Xia C, Jiang H, Liu X, Duan T, Cao L, Ye Z, Zhang Z, Ma L, Song B, Shi Y. Noninvasive prediction of HCC with progenitor phenotype based on gadoxetic acid-enhanced MRI. Eur Radiol 2020; 30:1232-1242. [PMID: 31529254 DOI: 10.1007/s00330-019-06414-2] [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] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 07/26/2019] [Accepted: 08/07/2019] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To explore the noninvasive prediction of hepatocellular carcinoma (HCC) with progenitor phenotype based on gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS This retrospective study included 115 surgery-proven HCCs with preoperative gadoxetic acid-enhanced MRI from August 2015 to September 2018. Image features were reviewed. Quantitative image analysis was performed using histogram analysis. HCC with progenitor phenotype was defined as positive for either cytokeratin 19 (CK19) or epithelial cell adhesion molecule (EpCAM) expression. Statistically significant variables for identifying HCCs with progenitor phenotype were determined at multivariate analyses. ROC analyses were used to determined cutoff values and the diagnostic performance of significant variables and combinations. Prediction nomogram was constructed based on multivariate analysis. RESULTS At multivariate regression analyses, AFP ≥ 155.25 ng/mL (p < 0.001), skewness on T2WI ≤ 1.10 (p = 0.024), uniformity on pre-T1WI ≤ 0.91 (p = 0.024), irregular tumor margin (p = 0.006), targetoid appearance (p = 0.001), and the absence of mosaic architecture (p = 0.014) were significant predictors of HCCs expressing progenitor cell markers. Combing any three of those significant variables, it provides a diagnostic accuracy of 0.86 (95% CI 0.78-0.92) with sensitivity of 0.97 (95% CI 0.86-1.00), and specificity of 0.74 (95% CI 0.63-0.83). The C-index of the regression coefficient-based nomogram was 0.94 (95% CI 0.91-0.98). CONCLUSIONS Noninvasive prediction of HCCs with progenitor phenotype can be achieved with high accuracy by integrated interpretation of biochemical and radiological information, representing a handy tool for precise patient management and the prediction of prognosis. KEY POINTS • Qualitative image features of irregular tumor margin, targetoid appearance, and the absence of mosaic architecture are significant predictors of hepatocellular carcinoma with progenitor phenotype. • Quantitative analyses using whole-lesion histogram analysis provides additional information for the prediction of hepatocellular carcinoma with progenitor phenotype. • Noninvasive prediction of hepatocellular carcinoma with progenitor phenotype can be achieved with high accuracy by integrated interpretation of clinical information and qualitative and quantitative imaging analyses.
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Affiliation(s)
- Jie Chen
- West China School of Medicine, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Zhenru Wu
- Laboratory of Pathology, West China Hospital, Sichuan University, B2 Building, No. 88, South Ke Yuan Road, Chengdu, 610041, China
| | - Chunchao Xia
- Department of Radiology, West China Hospital, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Hanyu Jiang
- West China School of Medicine, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Xijiao Liu
- Department of Radiology, West China Hospital, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Ting Duan
- Department of Radiology, West China Hospital, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Likun Cao
- West China School of Medicine, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Zheng Ye
- West China School of Medicine, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Zhen Zhang
- West China School of Medicine, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China
| | - Ling Ma
- Application Advanced Team, GE Healthcare, Shanghai, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Guoxue Xiang, No. 37, Chengdu, 610041, China.
| | - Yujun Shi
- Laboratory of Pathology, West China Hospital, Sichuan University, B2 Building, No. 88, South Ke Yuan Road, Chengdu, 610041, China.
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Ueno A, Masugi Y, Yamazaki K, Kurebayashi Y, Tsujikawa H, Effendi K, Ojima H, Sakamoto M. Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma. Pathol Int 2020; 70:140-154. [PMID: 31908112 DOI: 10.1111/pin.12895] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 12/11/2019] [Indexed: 12/25/2022]
Abstract
Outcomes for patients with hepatocellular carcinoma (HCC) remain poor because the condition is often unresponsive to the available treatments. Consequently, the early and precise diagnosis of HCC is crucial to achieve improvements in prognosis. For patients with chronic liver disease, the assessment of liver fibrosis is also important to ascertain both the staging of fibrosis and the risk of HCC occurrence. Early HCC was first described in 1991 in Japan and was defined internationally in 2009. As the concept of early HCC spread, the multistage hepatocarcinogenesis process became accepted. Consequently, improvements in imaging technology made the early diagnosis of HCC possible. At present, the most appropriate therapeutic strategy for HCC is determined using an integrated staging system that assesses the tumor burden, the degree of liver dysfunction and the patient performance status; however, pathological and molecular features are not taken into account. The recent introduction of several new therapeutic agents will change the treatment strategy for HCC. Against this background, HCC subclassification based on tumor cellular and microenvironmental characteristics will become increasingly important. In this review, we give an overview of how pathological analysis contributes to understanding the development and progression of HCC and establishing a precision diagnosis of HCC.
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Affiliation(s)
- Akihisa Ueno
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Yohei Masugi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Ken Yamazaki
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Yutaka Kurebayashi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Hanako Tsujikawa
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Kathryn Effendi
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Hidenori Ojima
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
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Vychytilova-Faltejskova P, Slaby O. MicroRNA-215: From biology to theranostic applications. Mol Aspects Med 2019; 70:72-89. [PMID: 30904345 DOI: 10.1016/j.mam.2019.03.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 03/10/2019] [Accepted: 03/17/2019] [Indexed: 02/07/2023]
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Cai QY, Jiang JH, Jin RM, Jin GZ, Jia NY. The clinical significance of lipopolysaccharide binding protein in hepatocellular carcinoma. Oncol Lett 2019; 19:159-166. [PMID: 31897126 PMCID: PMC6924111 DOI: 10.3892/ol.2019.11119] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Accepted: 09/17/2019] [Indexed: 12/15/2022] Open
Abstract
Lipopolysaccharide binding protein (LBP) has been reported to be associated with prognosis in colorectal carcinoma and renal cell carcinoma; however, the clinical significance of LBP in human primary hepatocellular carcinoma (HCC) is inconclusive. We aimed to investigate the clinical significance and prognostic value of LBP in human primary HCC. In the present study, 346 patients with HCC who underwent curative resection were retrospectively analyzed. LBP protein expression was evaluated using western blot analysis and immunohistochemistry. LBP scores collected from immunohistochemical analysis were obtained by multiplying staining intensity and the percentage of positive cells. An outcome-based best cutoff-point was calculated by X-tile software. Moreover, Kaplan-Meier curves and Cox regressions were used for prognosis evaluation. LBP was frequently overexpressed in HCC compared with that in peritumor tissues (five pairs by western blot analysis, P=0.0533; 77 pairs by immunohistochemistry, P=0.0171), and LBP expression was positively associated with tumor-node-metastasis stage and tumor differentiation. Patients who had high LBP expression had decreased overall survival and time to recurrence compared with patients with low LBP expression. Furthermore, patients who were both serum α-fetoprotein positive and had high LBP expression had poor prognoses. Univariate and multivariate Cox analyses indicated that this combination was an independent prognostic factor [overall survival: Hazard ratio (HR), 1.458; 95% confidence interval (CI), 1.158–1.837; P=0.001; time to recurrence: HR,1.382; 95% Cl, 1.124–1.700; P=0.002]. In conclusion, LBP is highly expressed in HCC, and high LBP expression combined with serum α-fetoprotein may predict poor outcomes in patients with HCC following curative resection.
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Affiliation(s)
- Quan-Yu Cai
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
| | - Jing-Hua Jiang
- Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
| | - Ri-Ming Jin
- Department of Hepatic Surgery I, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
| | - Guang-Zhi Jin
- Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
| | - Ning-Yang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
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Cannella R, Calandra A, Cabibbo G, Midiri M, Tang A, Brancatelli G. Hyperintense nodule-in-nodule on hepatobiliary phase arising within hypovascular hypointense nodule: Outcome and rate of hypervascular transformation. Eur J Radiol 2019; 120:108689. [PMID: 31563835 DOI: 10.1016/j.ejrad.2019.108689] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 09/04/2019] [Accepted: 09/18/2019] [Indexed: 02/06/2023]
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