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Hu R, Tran B, Li S, Stackpole ML, Zeng W, Zhou Y, Melehy A, Sadeghi S, Finn RS, Zhou XJ, Li W, Agopian VG. Noninvasive prognostication of hepatocellular carcinoma based on cell-free DNA methylation. PLoS One 2025; 20:e0321736. [PMID: 40279344 PMCID: PMC12026916 DOI: 10.1371/journal.pone.0321736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 03/11/2025] [Indexed: 04/27/2025] Open
Abstract
BACKGROUND The current noninvasive prognostic evaluation methods for hepatocellular carcinoma (HCC), which are largely reliant on radiographic imaging features and serum biomarkers such as alpha-fetoprotein (AFP), have limited effectiveness in discriminating patient outcomes. Identification of new prognostic biomarkers is a critical unmet need to improve treatment decision-making. Epigenetic changes in cell-free DNA (cfDNA) have shown promise in early cancer diagnosis and prognosis. Thus, we aim to evaluate the potential of cfDNA methylation as a noninvasive predictor for prognostication in patients with active, radiographically viable HCC. METHODS Using Illumina HumanMethylation450 array data of 377 HCC tumors and 50 adjacent normal tissues obtained from The Cancer Genome Atlas (TCGA), we identified 158 HCC-related DNA methylation markers associated with overall survival (OS). This signature was further validated in 29 HCC tumor tissue samples. Subsequently, we applied the signature to an independent cohort of 52 patients with plasma cfDNA samples by calculating the cfDNA methylation-based risk score (methRisk) via random survival forest models with 10-fold cross-validation for the prognostication of OS. RESULTS The cfDNA-based methRisk showed strong discriminatory power when evaluated as a single predictor for OS (3-year AUC = 0.81, 95% CI: 0.68-0.94). Integrating the methRisk with existing risk indices like Barcelona clinic liver cancer (BCLC) staging significantly improved the noninvasive prognostic assessments for OS (3-year AUC = 0.91, 95% CI: 0.80-1), and methRisk remained an independent predictor of survival in the multivariate Cox model (P = 0.007). CONCLUSIONS Our study serves as a pilot study demonstrating that cfDNA methylation biomarkers assessed from a peripheral blood draw can stratify HCC patients into clinically meaningful risk groups. These findings indicate that cfDNA methylation is a promising noninvasive prognostic biomarker for HCC, providing a proof-of-concept for its potential clinical utility and laying the groundwork for broader applications.
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Affiliation(s)
- Ran Hu
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
- Bioinformatics Interdepartmental Graduate Program, University of California at Los Angeles, Los Angeles, California, United States of America
- Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Benjamin Tran
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Shuo Li
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Mary L. Stackpole
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Weihua Zeng
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Yonggang Zhou
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Andrew Melehy
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Saeed Sadeghi
- Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Richard S. Finn
- Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Xianghong Jasmine Zhou
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
- Institute for Quantitative and Computational Biosciences, University of California at Los Angeles, Los Angeles, California, United States of America
- Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Wenyuan Li
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
| | - Vatche G. Agopian
- Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, United States of America
- Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California, United States of America
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Zhu Z, Wu K, Lu J, Dai S, Xu D, Fang W, Yu Y, Gu W. Gd-EOB-DTPA-enhanced MRI radiomics and deep learning models to predict microvascular invasion in hepatocellular carcinoma: a multicenter study. BMC Med Imaging 2025; 25:105. [PMID: 40165094 PMCID: PMC11956329 DOI: 10.1186/s12880-025-01646-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is an important risk factor for early postoperative recurrence of hepatocellular carcinoma (HCC). Based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) images, we developed a novel radiomics model. It combined bi-regional features and two machine learning algorithms. The aim of this study was to validate its potential value for preoperative prediction of MVI. METHODS This retrospective study included 304 HCC patients (training cohort, 216 patients; testing cohort, 88 patients) from three hospitals. Intratumoral and peritumoral volumes of interest were delineated in arterial phase, portal venous phase, and hepatobiliary phase images. Conventional radiomics (CR) and deep learning radiomics (DLR) features were extracted based on FeAture Explorer software and the 3D ResNet-18 extractor, respectively. Clinical variables were selected using univariate and multivariate analyses. Clinical, CR, DLR, CR-DLR, and clinical-radiomics (Clin-R) models were built using support vector machines. The predictive capacity of the models was assessed by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS The bi-regional CR-DLR model showed more gains and gave better predictive performance than the single-regional models or single-machine learning models. Its AUC, accuracy, sensitivity, and specificity were 0.844, 76.9%, 87.8%, and 69.1% in the training cohort and 0.740, 73.9%, 50%, and 84.5% in the testing cohort. Alpha-fetoprotein (odds ratio was 0.32) and maximum tumor diameter (odds ratio was 1.270) were independent predictors. The AUCs of the clinical model and the Clin-R model were 0.655 and 0.672, respectively. There was no significant difference in the AUCs between all the models (P > 0.005). CONCLUSION Based on Gd-EOB-DTPA-enhanced MRI images, we focused on developing a radiomics model that combines bi-regional features and two machine learning algorithms (CR and DLR). The application of the new model will provide a more accurate and non-invasive diagnostic solution for medical imaging. It will provide valuable information for clinical personalized treatment, thereby improving patient prognosis. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Zhu Zhu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Kaiying Wu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Jian Lu
- Department of Radiology, The Third Affiliated Hospital of Nantong University, The Third People's Hospital of Nantong, Nantong, Jiangsu, 226000, China
| | - Sunxian Dai
- Soochow university, Suzhou, Jiangsu, 215000, China
| | - Dabo Xu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Wei Fang
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China
| | - Yixing Yu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, China.
| | - Wenhao Gu
- Department of Radiology, The First People's Hospital of Taicang, Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215400, China.
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Chiang J, Raman SS, Ramakrishnan A, Keshavarz P, Sayre JW, McWilliams JP, Finn RS, Agopian VG, Choi G, Lu DSK. Correlation of Needle Biopsy-Acquired Histopathologic Grade of Hepatocellular Carcinoma with Outcomes after Thermal Ablation. J Vasc Interv Radiol 2025; 36:50-57. [PMID: 39322178 DOI: 10.1016/j.jvir.2024.09.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 08/11/2024] [Accepted: 09/14/2024] [Indexed: 09/27/2024] Open
Abstract
PURPOSE To correlate preablation needle biopsy-acquired histopathologic grade of Liver Imaging Reporting and Data System (LI-RADS) 5 hepatocellular carcinoma (HCC) with postablation local tumor control rate, intrahepatic distant tumor progression-free survival, and overall survival. MATERIALS AND METHODS This single-center, retrospective cohort study included adult patients with LI-RADS 5 HCC who underwent a preablation core needle biopsy within 3 months prior to thermal ablation from January 2015 to December 2022. Histopathologic grade from the needle biopsy was evaluated as predictor of local tumor control rate, intrahepatic distant tumor progression-free survival, and overall survival. Kaplan-Meier survival curves were compared using the Gehan generalized Wilcoxon test. RESULTS The study group comprised 133 patients (mean age, 67 years [SD ± 10]; 107 men) with LI-RADS 5 confirmed HCC, stratified into 18 poorly differentiated tumors (median follow-up, 27.7 months; interquartile range [IQR], 15.5-55.4 months) and 115 well-differentiated/moderately differentiated tumors (median follow-up, 29.2 months; IQR, 15.4-59.9 months). No difference in local tumor control rate was noted between the 2 cohorts (hazard ratio [HR], 1.16; 95% CI, 0.32-4.23; P = .898). There was significantly lower intrahepatic distant tumor progression-free survival after thermal ablation in the poorly differentiated cohort (HR, 2.54; 95% CI, 0.92-7.05; P < .001). The overall survival in the poorly differentiated cohort was also lower, although this did not reach statistical significance (HR, 1.77; 95% CI, 0.60-5.26; P = .202). CONCLUSIONS Patients with needle biopsy-proven poorly differentiated LI-RADS 5 HCC had significantly lower intrahepatic distant tumor progression-free survival after thermal ablation compared with those with well-differentiated/moderately differentiated HCC.
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Affiliation(s)
- Jason Chiang
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California.
| | - Steven S Raman
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Abinaya Ramakrishnan
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Pedram Keshavarz
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - James W Sayre
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California; Department of Informatics, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Justin P McWilliams
- Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Richard S Finn
- Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Vatche G Agopian
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - Gina Choi
- Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
| | - David S K Lu
- Division of Interventional Radiology, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California; Division of Liver and Pancreas Transplantation, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
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Fei X, Zhu L, Han P, Jiang B, Li M, Li N, Jiao Z, Clevert DA, Luo Y. Value of high frame rate contrast-enhanced ultrasound in predicting microvascular invasion of hepatocellular carcinoma. Insights Imaging 2024; 15:273. [PMID: 39546065 PMCID: PMC11568103 DOI: 10.1186/s13244-024-01821-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 09/10/2024] [Indexed: 11/17/2024] Open
Abstract
OBJECTIVES To investigate the value of vascular morphology on high frame rate contrast-enhanced ultrasound (H-CEUS) and CEUS Li-RADS in predicting microvascular invasion (MVI), Ki-67 expression and recurrence of hepatocellular carcinoma (HCC). METHODS This retrospective study enrolled 78 patients with single HCC diagnosed by postoperative pathology between January 1, 2021, and June 30, 2022. All patients underwent ultrasound and H-CEUS examination before operation. H-CEUS image features and CEUS Li-RADS were compared in different MVI status and Ki-67 level. Multiple logistic regression analysis was performed to select independent variables for MVI. Differences in recurrence among different H-CEUS image features, MVI status and Ki-67 level were further analyzed. RESULTS Tumor shape, vascular morphology, LR-M category, necrosis and AFP level were different between the MVI-positive group and MVI-negative group (p < 0.05). Vascular morphology and LR-M category were independent risk factors related to MVI (p < 0.05). Vascular morphology was also different between the high Ki-67 expression group and low Ki-67 expression group (p < 0.05). Vascular morphology, MVI status and Ki-67 expression were different between the recurrence group and no recurrence group (p < 0.05). CONCLUSION The vascular morphology of HCC on H-CEUS can indicate the risk of MVI status, Ki-67 expression and recurrence, which provides a feasible imaging technique for predicting the prognosis before operation. CRITICAL RELEVANCE STATEMENT H-CEUS shows the different vascular morphology of HCC in arterial phase and indicates the risk of MVI, Ki-67 expression and recurrence, which provides a feasible imaging technique for clinician to judge the risk of MVI pre-operation and adopt appropriate treatment. KEY POINTS H-CEUS can clearly show different vascular morphology of HCC in arterial phase. Vascular morphology on H-CEUS is associated with MVI status, Ki-67 expression and HCC recurrence. Preoperative MVI and Ki-67 expression prediction could help surgeons choose a more appropriate treatment plan.
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Affiliation(s)
- Xiang Fei
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Lianhua Zhu
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Peng Han
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Bo Jiang
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Miao Li
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Nan Li
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Ziyu Jiao
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Dirk-André Clevert
- Interdisciplinary Ultrasound-Center University of Munich-Grosshadern Campus, Munich, Germany.
| | - Yukun Luo
- Department of Ultrasound, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
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Alnagar A, Zakeri N, Koilias K, Faulkes RE, Brown R, Cain O, Perera MTPR, Roberts KJ, Sanabria-Mateos R, Bartlett DC, Ma YT, Sivakumar S, Shetty S, Shah T, Dasari BVM. SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation. World J Transplant 2024; 14:95849. [PMID: 39295983 PMCID: PMC11317860 DOI: 10.5500/wjt.v14.i3.95849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/28/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.
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Affiliation(s)
- Amr Alnagar
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nekisa Zakeri
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Konstantinos Koilias
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rosemary E Faulkes
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Owen Cain
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - M Thamara P R Perera
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rebeca Sanabria-Mateos
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shivan Sivakumar
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shishir Shetty
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Bobby V M Dasari
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
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Jiang S, Gao X, Tian Y, Chen J, Wang Y, Jiang Y, He Y. The potential of 18F-FDG PET/CT metabolic parameter-based nomogram in predicting the microvascular invasion of hepatocellular carcinoma before liver transplantation. Abdom Radiol (NY) 2024; 49:1444-1455. [PMID: 38265452 DOI: 10.1007/s00261-023-04166-8] [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: 06/17/2023] [Revised: 06/17/2023] [Accepted: 12/16/2023] [Indexed: 01/25/2024]
Abstract
PURPOSE Microvascular invasion (MVI) is a critical factor in predicting the recurrence and prognosis of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, there is a lack of reliable preoperative predictors for MVI. The purpose of this study is to evaluate the potential of an 18F-FDG PET/CT-based nomogram in predicting MVI before LT for HCC. METHODS 83 HCC patients who obtained 18F-FDG PET/CT before LT were included in this retrospective research. To determine the parameters connected to MVI and to create a nomogram for MVI prediction, respectively, Logistic and Cox regression models were applied. Analyses of the calibration curve and receiver operating characteristic (ROC) curves were used to assess the model's capability to differentiate between clinical factors and metabolic data from PET/CT images. RESULTS Among the 83 patients analyzed, 41% were diagnosed with histologic MVI. Multivariate logistic regression analysis revealed that Child-Pugh stage, alpha-fetoprotein, number of tumors, CT Dmax, and Tumor-to-normal liver uptake ratio (TLR) were significant predictors of MVI. A nomogram was constructed using these predictors, which demonstrated strong calibration with a close agreement between predicted and actual MVI probabilities. The nomogram also showed excellent differentiation with an AUC of 0.965 (95% CI 0.925-1.000). CONCLUSION The nomogram based on 18F-FDG PET/CT metabolic characteristics is a reliable preoperative imaging biomarker for predicting MVI in HCC patients before undergoing LT. It has demonstrated excellent efficacy and high clinical applicability.
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Affiliation(s)
- Shengpan Jiang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), 216 Guanshan Avenue, Wuhan, 430074, China
| | - Xiaoqing Gao
- Clinical Laboratory Department, Wuhan Third Hospital (Tongren Hospital of Wuhan University), 216 Guanshan Avenue, Wuhan, 430074, China
| | - Yueli Tian
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Jie Chen
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yichun Wang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yaqun Jiang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yong He
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China.
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Zheng R, Zhang X, Liu B, Zhang Y, Shen H, Xie X, Li S, Huang G. Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm. Eur Radiol 2023; 33:6462-6472. [PMID: 37338553 DOI: 10.1007/s00330-023-09789-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 03/15/2023] [Accepted: 03/30/2023] [Indexed: 06/21/2023]
Abstract
OBJECTIVES The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.
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Affiliation(s)
- Ruiying Zheng
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaoer Zhang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Baoxian Liu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Yi Zhang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Hui Shen
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiaoyan Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Shurong Li
- Department of Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
| | - Guangliang Huang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
- Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi, China.
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Haque S, Bhushan Raman R, Salam M. Role of Biomarkers in Hepatocellular Carcinoma and Their Disease Progression. LIVER CANCER - GENESIS, PROGRESSION AND METASTASIS 2023. [DOI: 10.5772/intechopen.105856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the third leading and common lethal cancers worldwide. Early detection of tumorigenesis of hepatocellular carcinoma is through ultrasonography, computerized tomography (CT) scans, and magnetic resonance imaging (MRI) scans; however, these methods are not up to the mark, so a search for an efficient biomarker for early diagnosis and treatment of hepatocarcinogenesis is important. Proteomic and genomic approaches aid to develop new promising biomarkers for the diagnosis of HCC at the early stages. These biomarkers not only help in prognosis but also provide better therapeutic intervention against HCC. Among the different biomarker candidates, liquid biopsy [including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)] has recently emerged as a noninvasive detection technique for the characterization of circulating cells, providing a strong basis and early diagnosis for the individualized treatment of patients. This review provides the current understanding of HCC biomarkers that predict the risk of HCC recurrence.
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Pomohaci MD, Grasu MC, Dumitru RL, Toma M, Lupescu IG. Liver Transplant in Patients with Hepatocarcinoma: Imaging Guidelines and Future Perspectives Using Artificial Intelligence. Diagnostics (Basel) 2023; 13:diagnostics13091663. [PMID: 37175054 PMCID: PMC10178485 DOI: 10.3390/diagnostics13091663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 04/26/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023] Open
Abstract
Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival.
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Affiliation(s)
- Mihai Dan Pomohaci
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Radiology, The University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
| | - Mugur Cristian Grasu
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Radiology, The University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
| | - Radu Lucian Dumitru
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Radiology, The University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
| | - Mihai Toma
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Radiology, The University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
| | - Ioana Gabriela Lupescu
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
- Department of Radiology, The University of Medicine and Pharmacy "Carol Davila", 050474 Bucharest, Romania
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Cao LL, Peng M, Xie X, Chen GQ, Huang SY, Wang JY, Jiang F, Cui XW, Dietrich CF. Artificial intelligence in liver ultrasound. World J Gastroenterol 2022; 28:3398-3409. [PMID: 36158262 PMCID: PMC9346461 DOI: 10.3748/wjg.v28.i27.3398] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/18/2022] [Accepted: 06/19/2022] [Indexed: 02/06/2023] Open
Abstract
Artificial intelligence (AI) is playing an increasingly important role in medicine, especially in the field of medical imaging. It can be used to diagnose diseases and predict certain statuses and possible events that may happen. Recently, more and more studies have confirmed the value of AI based on ultrasound in the evaluation of diffuse liver diseases and focal liver lesions. It can assess the severity of liver fibrosis and nonalcoholic fatty liver, differentially diagnose benign and malignant liver lesions, distinguish primary from secondary liver cancers, predict the curative effect of liver cancer treatment and recurrence after treatment, and predict microvascular invasion in hepatocellular carcinoma. The findings from these studies have great clinical application potential in the near future. The purpose of this review is to comprehensively introduce the current status and future perspectives of AI in liver ultrasound.
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Affiliation(s)
- Liu-Liu Cao
- Department of Medical Ultrasound, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Mei Peng
- Department of Medical Ultrasound, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Xiang Xie
- Department of Medical Ultrasound, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Gong-Quan Chen
- Department of Medical Ultrasound, Minda Hospital of Hubei Minzu University, Enshi 445000, Hubei Province, China
| | - Shu-Yan Huang
- Department of Medical Ultrasound, The First People's Hospital of Huaihua, Huaihua 418000, Hunan Province, China
| | - Jia-Yu Wang
- Department of Medical Ultrasound, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Fan Jiang
- Department of Medical Ultrasound, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui Province, China
| | - Xin-Wu Cui
- Department of Medical Ultrasound, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Christoph F Dietrich
- Department Allgemeine Innere Medizin, Kliniken Hirslanden Beau Site, Salem und Permanence, Bern 3626, Switzerland
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Salehi O, Vega EA, Kutlu OC, Lunsford K, Freeman R, Ladin K, Alarcon SV, Kazakova V, Conrad C. Poorly differentiated hepatocellular carcinoma: resection is equivalent to transplantation in patients with low liver fibrosis. HPB (Oxford) 2022; 24:1100-1109. [PMID: 34969618 DOI: 10.1016/j.hpb.2021.12.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 11/28/2021] [Accepted: 12/08/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Organ allocation criteria for liver transplantation focus on tumor size and multifocality while tumor differentiation and existing liver damage are omitted. This study analyzes the impact of hepatocellular carcinoma (HCC) grade and liver fibrosis comparing resection (SX) to transplantation (LT). METHODS The National Cancer Database was queried between 2004 and 2016 for solitary HCC meeting Milan criteria undergoing SX vs LT. Two groups were created: low fibrosis (LF) vs high fibrosis (HF) and stratified by grade. Cox multivariable regression models, Kaplan-Meier survival analyses and log-rank tests were performed. RESULTS 1515 patients were identified; 780 had LT and 735 had SX. Median overall survival (mOS) was 39.7 months; LT mOS was 47.9 months vs SX mOS of 34.9 months (P < .001). Multivariate analysis revealed SX, no chemotherapy, longer hospital stays, and age to be associated with worse survival. However, while transplantation conferred survival benefit for well-moderately differentiated tumors, SX vs LT did not impact survival for poorly differentiated HCC in LF patients, independent of tumor size. DISCUSSION HCC differentiation and liver fibrosis, but not size, synergistically determine efficacy of SX vs LT. Therefore, current HCC transplantation criteria should incorporate tumor grade or liver fibrosis for optimal organ allocation.
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Affiliation(s)
- Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Onur C Kutlu
- Department of Surgery, University of Miami Health System, Miller School of Medicine, Miami, FL, USA
| | - Keri Lunsford
- Department of Surgery, Division of Transplant and Hepatobiliary Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Richard Freeman
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Keren Ladin
- Department of Occupational Therapy and Community Health, Tufts University, Boston, MA, USA
| | - Sylvia V Alarcon
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Vera Kazakova
- Department of Medical Oncology, Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Harvard Medical School, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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12
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Zhong X, Long H, Su L, Zheng R, Wang W, Duan Y, Hu H, Lin M, Xie X. Radiomics models for preoperative prediction of microvascular invasion in hepatocellular carcinoma: a systematic review and meta-analysis. Abdom Radiol (NY) 2022; 47:2071-2088. [PMID: 35364684 DOI: 10.1007/s00261-022-03496-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/09/2022] [Accepted: 03/14/2022] [Indexed: 12/17/2022]
Abstract
PURPOSE To assess the methodological quality and to evaluate the predictive performance of radiomics studies for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS Publications between 2017 and 2021 on radiomic MVI prediction in HCC based on CT, MR, ultrasound, and PET/CT were included. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST). Methodological quality was assessed through the radiomics quality score (RQS). Fourteen studies classified as TRIPOD Type 2a or above were used for meta-analysis using random-effects model. Further analyses were performed to investigate the technical factors influencing the predictive performance of radiomics models. RESULTS Twenty-three studies including 4947 patients were included. The risk of bias was mainly related to analysis domain. The RQS reached an average of (37.7 ± 11.4)% with main methodological insufficiencies of scientific study design, external validation, and open science. The pooled areas under the receiver operating curve (AUC) were 0.85 (95% CI 0.82-0.89), 0.87 (95% CI 0.83-0.92), and 0.74 (95% CI 0.67-0.80), respectively, for CT, MR, and ultrasound radiomics models. The pooled AUC of ultrasound radiomics model was significantly lower than that of CT (p = 0.002) and MR (p < 0.001). Portal venous phase for CT and hepatobiliary phase for MR were superior to other imaging sequences for radiomic MVI prediction. Segmentation of both tumor and peritumor regions showed better performance than tumor region. CONCLUSION Radiomics models show promising prediction performance for predicting MVI in HCC. However, improvements in standardization of methodology are required for feasibility confirmation and clinical translation.
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Affiliation(s)
- Xian Zhong
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Haiyi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Liya Su
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Ruiying Zheng
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Wei Wang
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Yu Duan
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Hangtong Hu
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Manxia Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
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Seehofer D, Petrowsky H, Schneeberger S, Vibert E, Ricke J, Sapisochin G, Nault JC, Berg T. Patient Selection for Downstaging of Hepatocellular Carcinoma Prior to Liver Transplantation—Adjusting the Odds? Transpl Int 2022; 35:10333. [PMID: 35529597 PMCID: PMC9069348 DOI: 10.3389/ti.2022.10333] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 02/22/2022] [Indexed: 11/30/2022]
Abstract
Background and Aims: Morphometric features such as the Milan criteria serve as standard criteria for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Since it has been recognized that these criteria are too restrictive and do not adequately display the tumor biology, additional selection parameters are emerging. Methods: Concise review of the current literature on patient selection for downstaging and LT for HCC outside the Milan criteria. Results: The major task in patients outside the Milan criteria is the need for higher granularity with patient selection, since the benefit through LT is not uniform. The recent literature clearly shows that beneath tumor size and number, additional selection parameters are useful in the process of patient selection for and during downstaging. For initial patient selection, the alpha fetoprotein (AFP) level adds additional information to the size and number of HCC nodules concerning the chance of successful downstaging and LT. This effect is quantifiable using newer selection tools like the WE (West-Eastern) downstaging criteria or the Metroticket 2.0 criteria. Also an initial PET-scan and/or tumor biopsy can be helpful, especially in the high risk group of patients outside the University of California San Francisco (UCSF) criteria. After this entry selection, the clinical course during downstaging procedures concerning the tumor and the AFP response is of paramount importance and serves as an additional final selection tool. Conclusion: Selection criteria for liver transplantation in HCC patients are becoming more and more sophisticated, but are still imperfect. The implementation of molecular knowledge will hopefully support a more specific risk prediction for HCC patients in the future, but do not provide a profound basis for clinical decision-making at present.
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Affiliation(s)
- Daniel Seehofer
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital, Leipzig, Germany
- *Correspondence: Daniel Seehofer,
| | - Henrik Petrowsky
- Swiss HPB and Transplantation Center, Department of Surgery and Transplantation, University Hospital Zürich, Zurich, Switzerland
| | - Stefan Schneeberger
- Department of Visceral, Transplantation and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Eric Vibert
- Centre Hépato-Biliaire, Hôpital Paul Brousse, Villejuif, France
| | - Jens Ricke
- Department of Radiology, LMU Munich, Munich, Germany
| | - Gonzalo Sapisochin
- Ajmera Transplant Program and HPB Surgical Oncology, Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Jean-Charles Nault
- Service d’Hépatologie, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Université Paris Nord, Paris, France
- INSERM UMR 1138 Functional Genomics of Solid Tumors Laboratory, Paris, France
| | - Thomas Berg
- Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
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Zhong X, Peng J, Xie Y, Shi Y, Long H, Su L, Duan Y, Xie X, Lin M. A nomogram based on multi-modal ultrasound for prediction of microvascular invasion and recurrence of hepatocellular carcinoma. Eur J Radiol 2022; 151:110281. [PMID: 35395542 DOI: 10.1016/j.ejrad.2022.110281] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 03/01/2022] [Accepted: 03/28/2022] [Indexed: 02/08/2023]
Abstract
OBJECTIVE To establish and validate a nomogram based on multi-modal ultrasound for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC), and to assess the ability thereof to stratify recurrence-free survival (RFS). METHODS A total of 287 HCC patients undergoing surgical resection were prospectively enrolled, including 210 patients in the training cohort and 77 patients in the test cohort. All patients underwent conventional ultrasound, contrast-enhanced ultrasonography, and shear wave elastography examinations within one week before surgery. Taking histopathological examination result as the reference standard, independent factors associated with MVI in HCC were determined by logistic regression and a nomogram was established and further evaluated. The Kaplan-Meier method was used to analyze the prognostic value of histologic MVI status and nomogram-predicted MVI status. RESULTS Multivariate analysis showed that tumor diameter, echogenicity, tumor shape, arterial phase peritumoral enhancement and enhancement level in portal venous phase were independent predictors of MVI (all p < 0.05). The nomogram based on these variables showed good discrimination and calibration with the areas under the receiver operating characteristic curve (AUC) of 0.821 (0.762-0.870) and 0.789 (0.681-0.874) in the training and test cohorts. There was a significant difference in RFS between the nomogram-predicted MVI positive and the nomogram-predicted MVI negative groups in training and test cohorts (p < 0.001 and p = 0.004 respectively). CONCLUSIONS The multimodal ultrasound features were effective imaging markers for preoperative prediction of MVI of HCC and the nomogram might be an effective tool to stratify the risk of recurrence and guide the individualized treatment of HCC.
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Affiliation(s)
- Xian Zhong
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Jianyun Peng
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Yuhua Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Yifan Shi
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Haiyi Long
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Liya Su
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Yu Duan
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
| | - Manxia Lin
- Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
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Mao Y, Wang J, Zhu Y, Chen J, Mao L, Kong W, Qiu Y, Wu X, Guan Y, He J. Gd-EOB-DTPA-enhanced MRI radiomic features for predicting histological grade of hepatocellular carcinoma. Hepatobiliary Surg Nutr 2022; 11:13-24. [PMID: 35284527 PMCID: PMC8847875 DOI: 10.21037/hbsn-19-870] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 05/11/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND Prediction models for the histological grade of hepatocellular carcinoma (HCC) remain unsatisfactory. The purpose of this study is to develop preoperative models to predict histological grade of HCC based on gadolinium-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) radiomics. And to compare the performance between artificial neural network (ANN) and logistic regression model. METHODS A total of 122 HCCs were randomly assigned to the training set (n=85) and the test set (n=37). There were 242 radiomic features extracted from volumetric of interest (VOI) of arterial and hepatobiliary phases images. The radiomic features and clinical parameters [gender, age, alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), alanine aminotransferase (ALT), aspartate transaminase (AST)] were selected by permutation test and decision tree. ANN of arterial phase (ANN-AP), logistic regression model of arterial phase (LR-AP), ANN of hepatobiliary phase (ANN-HBP), logistic regression mode of hepatobiliary phase (LR-HBP), ANN of combined arterial and hepatobiliary phases (ANN-AP + HBP), and logistic regression model of combined arterial and hepatobiliary phases (LR-AP + HBP) were built to predict HCC histological grade. Those prediction models were assessed and compared. RESULTS ANN-AP and LR-AP were composed by AST and radiomic features based on arterial phase. ANN-HBP and LR-HBP were composed by AFP and radiomic features based on hepatobiliary phase. ANN-AP + HBP and LR-AP + HBP were composed by AST and radiomic features based on arterial and hepatobiliary phases. The prediction models could distinguish between high-grade tumors [Edmondson-Steiner (E-S) grade III and IV] and low-grade tumors (E-S grade I and II) in both training set and test set. In the test set, the AUCs of ANN-AP, LR-AP, ANN-HBP, LR-HBP, ANN-AP + HBP and LR-AP + HBP were 0.889, 0.777, 0.941, 0.819, 0.944 and 0.792 respectively. The ANN-HBP was significantly superior to LR-HBP (P=0.001). And the ANN-AP + HBP was significantly superior to LR-AP + HBP (P=0.007). CONCLUSIONS Prediction models consisting of clinical parameters and Gd-EOB-DTPA-enhanced MRI radiomic features (based on arterial phase, hepatobiliary phase, and combined arterial and hepatobiliary phases) could distinguish between high-grade HCCs and low-grade HCCs. And the ANN was superior to logistic regression model in predicting histological grade of HCC.
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Affiliation(s)
- Yingfan Mao
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jincheng Wang
- Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yong Zhu
- Department of Radiology, Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Liang Mao
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weiwei Kong
- Department of Oncology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yudong Qiu
- Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaoyan Wu
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yue Guan
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Jian He
- Department of Radiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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Xia W, Peng T, Guan R, Zhou Y, Zeng C, Lin Y, Wu Z, Tan H. Development of a novel prognostic nomogram for the early recurrence of liver cancer after curative hepatectomy. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1541. [PMID: 34790747 PMCID: PMC8576734 DOI: 10.21037/atm-21-4837] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/22/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide. Curative resection is an effective treatment but HCC recurrence rates remain high. This study aimed to establish a novel prognostic nomogram to assess the risk of recurrence in patients following curative resection. METHODS A total of 410 patients undergoing HCC curative resection were recruited from the Guangdong Provincial People's Hospital (GDPH). The cohort was divided into a training group (n=291) and a validation group (n=97). The risk factors for HCC early recurrence within 1 year of curative hepatectomy were identified. Finally, a multivariate prognostic nomogram was developed and validated. RESULTS Age, tumor number, tumor capsule, portal vein tumor thrombi, pathological grade, vascular tumor emboli, activated partial thromboplastin time (APTT), and tumor size were identified as independent prognostic risk factors for HCC early recurrence within 1 year of curative hepatectomy. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.806 [95% confidence interval (CI): 0.755 to 0.857; P<0.001], and no AUC/ROC statistical difference was detected between the training and validation sets. CONCLUSIONS The nomogram effectively predicted postoperative HCC recurrence within 1 year after curative hepatectomy, which may be a useful tool for the postoperative treatment or follow up for HCC patients.
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Affiliation(s)
- Wuzheng Xia
- Department of Organ Transplant, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Tianyi Peng
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Shantou University Medical College, Shantou, China
| | - Renguo Guan
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yu Zhou
- Department of Pancreatic Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Cong Zeng
- Department of General Practice, Hospital of South China Normal University, Guangzhou, China
| | - Ye Lin
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhongshi Wu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hongmei Tan
- Day Operating Room, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Liu W, Rong D, Zhu J, Xiao Y, Zhang L, Deng Y, Chen J, Yin M, Venkatesh SK, Ehman RL, Wang J. Diagnostic accuracy of 3D magnetic resonance elastography for assessing histologic grade of hepatocellular carcinoma: comparison of three methods for positioning region of interest. Abdom Radiol (NY) 2021; 46:4601-4609. [PMID: 34085091 DOI: 10.1007/s00261-021-03150-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 05/23/2021] [Accepted: 05/24/2021] [Indexed: 12/11/2022]
Abstract
PURPOSE To assess the influence of region of interest (ROI) placement on the predictive value of 3D MRE in differentiating the histologic grade of HCC. METHODS 85 patients with pathologically confirmed HCCs were analyzed using 3D MRE imaging, two radiologists measured the tumor stiffness with three different ROI positioning methods. Intraclass correlation coefficient (ICC) was expressed in terms of inter- and intra-observer agreements. Kruskal-Wallis rank test or one-way ANOVA was used to compare the difference in MRE stiffness across the three-ROI positioning methods. Receiver operating characteristic curve analysis (ROC) was performed, and the area under curve (AUC) was measured to evaluate the diagnostic performance. RESULTS There were 64 (75%) well-or-moderately differentiated HCCs and 21(25%) poorly differentiated HCCs included finally. Almost excellent inter- and intra-observer agreements (all ICC > 0.82) were observed for all three-ROI methods, the volumetric method has the highest values (inter-observer ICC 0.967, intra-observer ICC 0.919, 0.926, respectively). The mean stiffnesses of poorly differentiated HCC obtained by two readers were significantly higher than well-or-moderately differentiated HCC with volumetric method (7.07 ± 1.57 Kpa, 5.00 ± 1.49 Kpa, and 6.85 ± 1.49 Kpa, 4.94 ± 1.48 Kpa, respectively) and three-ROI method (6.14 ± 1.71 Kpa, 4.91 ± 1.56 Kpa and 5.94 ± 1.61 Kpa, 4.84 ± 1.54 Kpa, respectively) but not on single-ROI method (p > 0.005), for the diagnostic performance, the highest area under the curve (AUC) with a value of 0.837, 0.812 by using the volumetric method, followed by the three-ROI method (0.713, 0.754) and single-ROI method. CONCLUSION Different ROI positioning methods significantly affect HCC tumor stiffness measurements. The whole tumor volumetric analysis is superior to ROI-based methods for predicting the grade of HCC.
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Affiliation(s)
- Weimin Liu
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Dailin Rong
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Jie Zhu
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Yuanqiang Xiao
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Linqi Zhang
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Ying Deng
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China
| | - Jun Chen
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Meng Yin
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Sudhakar K Venkatesh
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Richard L Ehman
- Department of Radiology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Jin Wang
- Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China.
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Pelizzaro F, Gambato M, Gringeri E, Vitale A, Cillo U, Farinati F, Burra P, Russo FP. Management of Hepatocellular Carcinoma Recurrence after Liver Transplantation. Cancers (Basel) 2021; 13:4882. [PMID: 34638365 PMCID: PMC8508053 DOI: 10.3390/cancers13194882] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 09/19/2021] [Accepted: 09/24/2021] [Indexed: 02/06/2023] Open
Abstract
Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT), occurring in 10-15% of cases, is a major concern. A lot of work has been done in order to refine the selection of LT candidates with HCC and to improve the outcome of patients with recurrence. Despite this, the prognosis of these patients remains poor, partly due to the several areas of uncertainty in their management. Even if surveillance for HCC recurrence is crucial for early detection, there is currently no evidence to support a specific and cost-effective post-LT surveillance strategy. Concerning preventive measures, consensus on the best immunosuppressive drugs has not been reached and not enough data to support adjuvant therapy are present. Several therapeutic approaches (surgical, locoregional and systemic treatments) are available in case of recurrence, but there are still few data in the post-LT setting. Moreover, the use of immune checkpoint inhibitors is controversial in transplant recipients considered the risk of rejection. In this paper, the available evidence on the management of HCC recurrence after LT is comprehensively reviewed, considering pre- and post-transplant risk stratification, post-transplant surveillance, preventive strategies and treatment options.
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Affiliation(s)
- Filippo Pelizzaro
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Martina Gambato
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Enrico Gringeri
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (E.G.); (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
| | - Patrizia Burra
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
| | - Francesco Paolo Russo
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy; (F.P.); (M.G.); (F.F.); (P.B.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35128 Padova, Italy
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Jing M, Cao Y, Zhang P, Zhang B, Lin X, Deng L, Han T, Zhou J. The Benefit of Apparent Diffusion Coefficient in Evaluating the Invasiveness of Hepatocellular Carcinoma. Front Oncol 2021; 11:719480. [PMID: 34504795 PMCID: PMC8423087 DOI: 10.3389/fonc.2021.719480] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 08/05/2021] [Indexed: 12/14/2022] Open
Abstract
Background This study aimed to evaluate hepatocellular carcinoma (HCC) invasiveness using the apparent diffusion coefficient (ADC). Methods Eighty-one patients with HCC confirmed by pathology and examined by preoperative magnetic resonance imaging diffusion-weighted imaging from January 2015 to September 2020 were retrospectively analyzed. Clinical and pathological data were recorded. The minimum ADC (ADCmin), average ADC (ADCmean), and the ratio of ADCmean to normal-appearing hepatic parenchyma ADC (ADCnahp) were assessed. The associations between clinical information, ADC value, and HCC invasiveness (microvascular invasion [MVI], tumor differentiation, and Ki-67 expression) were evaluated statistically. Independent risk factors related to HCC invasiveness were screened using binary logistic regression, and the diagnostic efficiency was evaluated by the receiver operating characteristic curve and its area under the curve (AUC) value. Results Tumor size was related to HCC MVI and tumor differentiation (P < 0.05). HCC MVI was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P < 0.05) with AUC values of 0.860, 0.860, and 0.909, respectively. If these were combined with tumor size, the AUC value increased to 0.912. The degree of tumor differentiation was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P < 0.05) with AUC values of 0.719, 0.708, and 0.797, respectively. If these were combined with tumor size, the AUC value increased to 0.868. Ki-67 expression was associated with ADCmin, ADCmean, and the ADCmean-to-ADCnahp ratio (all P < 0.05) with AUC values of 0.731, 0.747, and 0.746, respectively. Combined them, the AUC value increased to 0.763. Conclusions The findings indicated that the ADC value has significant potential for the non-invasive preoperative evaluation of HCC invasiveness.
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Affiliation(s)
- Mengyuan Jing
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
| | - Yuntai Cao
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China.,Department of Radiology, Affiliated Hospital of Qinghai University, Xining, China
| | - Peng Zhang
- Department of Pathology, Lanzhou University Second Hospital, Lanzhou, China
| | - Bin Zhang
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
| | - Xiaoqiang Lin
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
| | - Liangna Deng
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
| | - Tao Han
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
| | - Junlin Zhou
- Department of Radiology, Lanzhou University Second Hospital, Lanzhou, China.,Second Clinical School, Lanzhou University, Lanzhou, China.,Key Laboratory of Medical Imaging of Gansu Province, Lanzhou, China
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20
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Wang W, Wu SS, Zhang JC, Xian MF, Huang H, Li W, Zhou ZM, Zhang CQ, Wu TF, Li X, Xu M, Xie XY, Kuang M, Lu MD, Hu HT. Preoperative Pathological Grading of Hepatocellular Carcinoma Using Ultrasomics of Contrast-Enhanced Ultrasound. Acad Radiol 2021; 28:1094-1101. [PMID: 32622746 DOI: 10.1016/j.acra.2020.05.033] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 05/12/2020] [Accepted: 05/15/2020] [Indexed: 02/07/2023]
Abstract
RATIONALE AND OBJECTIVES To develop an ultrasomics model for preoperative pathological grading of hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound (CEUS). MATERIAL AND METHODS A total of 235 HCCs were retrospectively enrolled, including 65 high-grade and 170 low-grade HCCs. Representative images of four-phase CEUS were selected from the baseline sonography, arterial, portal venous, and delayed phase images. Tumor ultrasomics features were automatically extracted using Ultrasomics-Platform software. Models were built via the classifier support vector machine, including an ultrasomics model using the ultrasomics features, a clinical model using the clinical factors, and a combined model using them both. Model performances were tested in the independent validation cohort considering efficiency and clinical usefulness. RESULTS A total of 1502 features were extracted from each image. After the reproducibility test and dimensionality reduction, 25 ultrasomics features and 3 clinical factors were selected to build the models. In the validation cohort, the combined model showed the best predictive power, with an area under the curve value of 0.785 (95% confidence interval [CI] 0.662-0.909), compared to the ultrasomics model of 0.720 (95% CI 0.576-0.864) and the clinical model of 0.665 (95% CI 0.537-0.793). Decision curve analysis suggested that the combined model was clinically useful, with a corresponding net benefit of 0.760 compared to the other two models. CONCLUSION We presented an ultrasomics-clinical model based on multiphase CEUS imaging and clinical factors, which showed potential value for the preoperative discrimination of HCC pathological grades.
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21
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Wang P, Nie F, Dong T, Wang G, Wang L, Fan X. Study on correlation between two-dimensional ultrasound, contrast-enhanced ultrasound and microvascular invasion in hepatocellular carcinoma. Clin Hemorheol Microcirc 2021; 80:97-106. [PMID: 34057142 DOI: 10.3233/ch-211190] [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: 12/22/2022]
Abstract
OBJECTIVE To explore the correlation between two-dimensional ultrasound (2D-US), contrast-enhanced ultrasound (CEUS) and microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS In this retrospective study, 56 patients with surgically pathologically confirmed HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n = 17) and MVI negative group (n = 39). 2D-US and CEUS examinations were performed within two weeks before surgery. The 2D-US and CEUS features were analyzed for correlation with MVI. Statistically significant parameters of ultrasound characteristic were scored, and the results of the scores were analyzed by ROC curve. RESULTS There were statistically significant differences in tumor shape, boundary, capsule, CEUS portal phase and delayed phase enhancement pattern, time to wash out, and tumor margin after enhancement (P < 0.05), while there were no statistically significant differences in tumor location and size, CEUS arterial phase enhancement pattern, initial time, time to peak, and peritumor enhancement (P > 0.05). When diagnosing the presence of MVI in HCC patients with cut-off value of the score combined 2D-US and CEUS features≥3, the maximum Jorden index was 0.58, and its diagnostic sensitivity and specificity were 94.10%and 64.1%, respectively, meaning that the total score≥3 was highly suspicious of the presence of MVI. CONCLUSIONS 2D-US and CEUS are feasible methods for preoperative prediction of MVI in HCC, and can provide some theoretical basis for individualized clinical treatment.
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Affiliation(s)
- Peihua Wang
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Fang Nie
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Tiantian Dong
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Guojuan Wang
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Lan Wang
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
| | - Xiao Fan
- Department of Ultrasound, Lanzhou University Second Hospital, Lanzhou, Gansu, China
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22
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Zhou Y, Yang G, Gong XQ, Tao YY, Wang R, Zheng J, Yang C, Peng J, Yang L, Li JD, Zhang XM. A study of the correlations between IVIM-DWI parameters and the histologic differentiation of hepatocellular carcinoma. Sci Rep 2021; 11:10392. [PMID: 34001962 PMCID: PMC8129092 DOI: 10.1038/s41598-021-89784-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/30/2021] [Indexed: 02/07/2023] Open
Abstract
The present study aimed to investigate the value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) in the preoperative prediction of the histologic differentiation of hepatocellular carcinoma (HCC). Seventy HCC patients were scanned with a 3.0 T magnetic resonance scanner. The values of apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and the fraction of the fast apparent diffusion coefficient (f) were measured. Analysis of variance was used to compare the differences in parameters between groups with different degrees of histologic differentiation. p < 0.05 was considered statistically significant. Receiver operating characteristic (ROC) curves were used to analyse the efficacy of IVIM-DWI parameters for predicting the histologic differentiation of HCC. The ADC and D values for well, moderately and poorly differentiated HCC were 1.35 ± 0.17 × 10-3 mm2/s, 1.16 ± 0.17 × 10-3 mm2/s, 0.98 ± 0.21 × 10-3 mm2/s, and 1.06 ± 0.15 × 10-3 mm2/s, 0.88 ± 0.16 × 10-3 mm2/s, 0.76 ± 0.18 × 10-3 mm2/s, respectively, and all differences were significant. The D* and f values of the three groups were 32.87 ± 14.70 × 10-3 mm2/s, 41.68 ± 17.90 × 10-3 mm2/s, 34.54 ± 18.60 × 10-3 mm2/s and 0.22 ± 0.07, 0.23 ± 0.08, 0.18 ± 0.07, respectively, with no significant difference. When the cut-off values of ADC and D were 1.25 × 10-3 mm2/s and 0.97 × 10-3 mm2/s, respectively, their diagnostic sensitivities and specificities for distinguishing well differentiated HCC from moderately differentiated and poorly differentiated HCC were 73.3%, 85.5%, 86.7%, and 78.2%, and their areas under the ROC curve were 0.821 and 0.841, respectively. ADC and D values can be used preoperatively to predict the degree of histologic differentiation in HCC, and the D value has better diagnostic value.
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Affiliation(s)
- Yi Zhou
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
- Department of Radiology, People's Hospital of Deyang City, Deyang, 618000, Sichuan, People's Republic of China
| | - Gang Yang
- Institute of Hepato-Biliary-Intestinal Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Xue-Qin Gong
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Yun-Yun Tao
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Ran Wang
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Jing Zheng
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Cui Yang
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Juan Peng
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Lin Yang
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China.
| | - Jing-Dong Li
- Institute of Hepato-Biliary-Intestinal Disease, Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
| | - Xiao-Ming Zhang
- Medical Imaging Key Laboratory of Sichuan Province, Medical Research Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, Sichuan, People's Republic of China
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23
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Court CM, Hou S, Liu L, Winograd P, DiPardo BJ, Liu SX, Chen PJ, Zhu Y, Smalley M, Zhang R, Sadeghi S, Finn RS, Kaldas FM, Busuttil RW, Zhou XJ, Tseng HR, Tomlinson JS, Graeber TG, Agopian VG. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells. NPJ Precis Oncol 2020; 4:16. [PMID: 32637655 PMCID: PMC7331695 DOI: 10.1038/s41698-020-0123-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 05/07/2020] [Indexed: 12/12/2022] Open
Abstract
Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. Sequencing of 18 CTC samples (median: 4 CTCs/sample) from 10 HCC patients using a low-resolution whole-genome sequencing strategy (median: 0.88 million reads/sample) revealed frequent SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/44 (73%) CTCs from 12/16 (75%) patients with different cancer types.
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Affiliation(s)
- Colin M. Court
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- Department of Surgery, Veteran’s Health Administration, Greater Los Angeles, Los Angeles, CA USA
- Department of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA USA
| | - Shuang Hou
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
| | - Lian Liu
- PacGenomics, llc, Los Angeles, CA USA
| | - Paul Winograd
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- Department of Surgery, Veteran’s Health Administration, Greater Los Angeles, Los Angeles, CA USA
| | - Benjamin J. DiPardo
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- Department of Surgery, Veteran’s Health Administration, Greater Los Angeles, Los Angeles, CA USA
| | - Sean X. Liu
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
| | - Pin-Jung Chen
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
| | - Yazhen Zhu
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
| | - Matthew Smalley
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
| | - Ryan Zhang
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
| | - Saeed Sadeghi
- Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA USA
| | - Richard S. Finn
- Department of Medicine, Division of Hematology/Oncology, University of California, Los Angeles, Los Angeles, CA USA
| | - Fady M. Kaldas
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
| | - Ronald W. Busuttil
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA USA
| | - Xianghong J. Zhou
- Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA USA
| | - Hsian-Rong Tseng
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
- California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA USA
| | - James S. Tomlinson
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- Department of Surgery, Veteran’s Health Administration, Greater Los Angeles, Los Angeles, CA USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA USA
| | - Thomas G. Graeber
- Department of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA USA
- Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA USA
- California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA USA
| | - Vatche G. Agopian
- Department of Surgery, University of California, Los Angeles, Los Angeles, CA USA
- Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA USA
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24
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Mehta N, Bhangui P, Yao FY, Mazzaferro V, Toso C, Akamatsu N, Durand F, Ijzermans J, Polak W, Zheng S, Roberts JP, Sapisochin G, Hibi T, Kwan NM, Ghobrial M, Soin A. Liver Transplantation for Hepatocellular Carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference. Transplantation 2020; 104:1136-1142. [PMID: 32217938 DOI: 10.1097/tp.0000000000003174] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT) offers excellent long-term outcome for certain patients with hepatocellular carcinoma (HCC), with a push to not simply rely on tumor size and number. Selection criteria should also consider tumor biology (including alpha-fetoprotein), probability of waitlist and post-LT survival (ie, transplant benefit), organ availability, and waitlist composition. These criteria may be expanded for live donor LT (LDLT) compared to deceased donor LT though this should not adversely affect the double equipoise in LDLT, namely ensuring both acceptable recipient outcomes and donor safety. HCC patients with compensated liver disease and minimal tumor burden have low urgency for LT, especially after local-regional therapy with complete response, and do not appear to derive the same benefit from LT as other waitlist candidates. These guidelines were developed to assist in selecting appropriate HCC patients for both deceased donor LT and LDLT.
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Affiliation(s)
- Neil Mehta
- Department of Medicine, University of California San Francisco, San Francisco, CA
| | - Prashant Bhangui
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
| | - Francis Y Yao
- Department of Medicine, University of California San Francisco, San Francisco, CA
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Vincenzo Mazzaferro
- Department of Surgery, GI Surgery and Liver Transplantation, Istituto Nazionale Tumori, Milan, Italy
| | - Christian Toso
- Division of Abdominal Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | | | - Francois Durand
- Service d'Hépatologie & Réanimation Hépatodigestive, Université Paris VII Hôpital Beaujon, Paris, France
| | - Jan Ijzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Wojciech Polak
- Department of Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Shusen Zheng
- Department of Surgery, First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - John P Roberts
- Department of Surgery, University of California San Francisco, San Francisco, CA
| | - Gonzalo Sapisochin
- Multi-Organ Transplant and HPB Surgical Oncology, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Taizo Hibi
- Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Nancy Man Kwan
- Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Mark Ghobrial
- J C Walter Jr Transplant Center, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Avi Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta, The Medicity, Gurgaon, India
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25
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De Martin E, Rayar M, Golse N, Dupeux M, Gelli M, Gnemmi V, Allard MA, Cherqui D, Sa Cunha A, Adam R, Coilly A, Antonini TM, Guettier C, Samuel D, Boudjema K, Boleslawski E, Vibert E. Analysis of Liver Resection Versus Liver Transplantation on Outcome of Small Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma in the Setting of Cirrhosis. Liver Transpl 2020; 26:785-798. [PMID: 32090444 DOI: 10.1002/lt.25737] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 12/09/2019] [Accepted: 12/26/2019] [Indexed: 02/07/2023]
Abstract
This multicenter study compares the outcomes of patients with cirrhosis undergoing liver transplantation (LT) or liver resection (LR) between January 2002 and July 2015 who had intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA) found incidentally in the native liver. A total of 49 (65%) LT and 26 (35%) LR patients with cirrhosis and histologically confirmed iCCA/cHCC-CCA ≤5 cm were retrospectively analyzed. LT patients had significantly lower tumor recurrence (18% versus 46%; P = 0.01), for which the median diameter of the largest nodule (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.02-1.12]; P = 0.006) and tumor differentiation (HR, 3.74; 95% CI 1.71-8.17; P = 0.001) were independently predictive. The LT group had significantly higher 5-year recurrence-free survival (RFS; 75% versus 36%; P = 0.004). In patients with tumors >2 cm but ≤5 cm, LT patients had a lower recurrence rate (21% versus 48%; P = 0.06) and a higher 5-year RFS (74% versus 40%; P = 0.06). Independent risk factors for recurrence were LT (protective; HR, 0.23; 95% CI, 0.07-0.82; P = 0.02), the median diameter of the largest nodule (HR, 1.10; 95% CI, 1.02-1.73; P = 0.007), and tumor differentiation (HR, 4.16; 95% CI, 1.37-12.66; P = 0.01). In the LT group, 5-year survival reached 69% and 65% (P = 0.40) in patients with tumors ≤2 cm and >2-5 cm, respectively, and survival was also comparable between iCCA and cHCC-CCA patients (P = 0.29). LT may offer a benefit for highly selected patients with cirrhosis and unresectable iCCA/cHCC-CCA having tumors ≤5 cm. Efforts should be made to evaluate tumor differentiation, and these results need to be confirmed prospectively in a larger population.
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Affiliation(s)
- Eleonora De Martin
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Michael Rayar
- Service de Chirurgie Hépatobiliaire et Digestive, Hôpital Pontchaillou, Rennes, France.,Université de Rennes 1, Rennes, France
| | - Nicolas Golse
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Margot Dupeux
- Laboratoire Anatomie Pathologique, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, U1193, INSERM, Orsay, France
| | | | - Viviane Gnemmi
- Département de Chirurgie, Institut Gustave-Roussy, Université Paris-Saclay, Saint-Aubin, France
| | - Marc Antoine Allard
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Daniel Cherqui
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Antonio Sa Cunha
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Rene Adam
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Audrey Coilly
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Teresa Maria Antonini
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Catherine Guettier
- Laboratoire Anatomie Pathologique, AP-HP Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,Université Paris-Saclay, U1193, INSERM, Orsay, France
| | - Didier Samuel
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
| | - Karim Boudjema
- Service de Chirurgie Hépatobiliaire et Digestive, Hôpital Pontchaillou, Rennes, France.,Université de Rennes 1, Rennes, France
| | - Emmanuel Boleslawski
- Service de Chirurgie Digestive et Transplantation, Centre Hospitalier Regional Universitaire de Lille, Hôpital Huriez, Lille, France
| | - Eric Vibert
- Centre Hépato-Biliaire, AP-HP Hôpital Paul-Brousse, Villejuif, France.,Département Hospitalo-Universitaire Hepatinov, Université Paris-Saclay, Unités Mixtes de Recherche en Santé 1193, INSERM, Villejuif, France
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26
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Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma. Ann Surg 2020; 271:616-624. [PMID: 30870180 DOI: 10.1097/sla.0000000000003253] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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27
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Verna EC, Patel YA, Aggarwal A, Desai AP, Frenette C, Pillai AA, Salgia R, Seetharam A, Sharma P, Sherman C, Tsoulfas G, Yao FY. Liver transplantation for hepatocellular carcinoma: Management after the transplant. Am J Transplant 2020; 20:333-347. [PMID: 31710773 DOI: 10.1111/ajt.15697] [Citation(s) in RCA: 96] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 10/03/2019] [Accepted: 10/21/2019] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.
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Affiliation(s)
- Elizabeth C Verna
- Center for Liver Disease and Transplantation, Columbia University, New York, New York, USA
| | - Yuval A Patel
- Division of Gastroenterology, Department of Medicine, Duke University, Durham, North Carolina, USA
| | - Avin Aggarwal
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Tuscon, Arizona, USA
| | - Archita P Desai
- Division of Gastroenterology, Department of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Catherine Frenette
- Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California, USA
| | - Anjana A Pillai
- Center for Liver Diseases, University of Chicago Medicine, Chicago, Illinois, USA
| | - Reena Salgia
- Department of Gastroenterology/Hepatology, Henry Ford Hospital, Detroit, Michigan, USA
| | - Anil Seetharam
- Transplant Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | - Pratima Sharma
- Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Courtney Sherman
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
| | - Georgios Tsoulfas
- Department of Surgery, Aristotle University School of Medicine, Thessaloniki, Greece
| | - Francis Y Yao
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA
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28
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Filgueira NA. Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation. World J Hepatol 2019; 11:261-272. [PMID: 30967904 PMCID: PMC6447422 DOI: 10.4254/wjh.v11.i3.261] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/06/2019] [Accepted: 03/16/2019] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation is the best treatment option for cirrhotic patients with early-stage hepatocellular carcinoma, but it faces the problem of scarcity of donors and the risk of tumor recurrence, which affects between 15% and 20% of the cases, despite the use of restrictive criteria. The risk of recurrence depends on a number of factors, related to the tumor, the patient, and the treatment, which are discussed in this review. Some of these factors are already well established, such as the histopathological characteristics of the tumor, Alpha-fetoprotein (AFP) levels, and waiting time. Other factors related to the biological behavior of the tumor and treatment should be recognized because they can be used in the refinement of the selection criteria of transplant candidates and in an attempt to reduce recurrence. This review also discusses the clinical presentation of recurrence and its prognosis, contributing to the identification of a subgroup of patients who may have better survival, if they are timely identified and treated. Development of recurrence after the first year, with AFP levels ≤ 100 ng/mL, and single site capable of locoregional therapy are associated with better survival after recurrence.
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Affiliation(s)
- Norma Arteiro Filgueira
- Department of Internal Medicine, Universidade Federal de Pernambuco, Recife, Pernambuco 50670-901, Brazil
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29
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Wei Y, Gao F, Wang M, Huang Z, Tang H, Li J, Wang Y, Zhang T, Wei X, Zheng D, Song B. Intravoxel incoherent motion diffusion-weighted imaging for assessment of histologic grade of hepatocellular carcinoma: comparison of three methods for positioning region of interest. Eur Radiol 2019; 29:535-544. [PMID: 30027411 DOI: 10.1007/s00330-018-5638-1] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 06/13/2018] [Accepted: 06/28/2018] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To prospectively compare the diagnostic performances of three methods of region of interest (ROI) placement for the measurements of intravoxel incoherent motion (IVIM) diffusion-weighted MR imaging in differentiating the histologic grade of hepatocellular carcinoma (HCC). METHODS Eighty-seven patients with 91 newly diagnosed HCCs were studied using IVIM imaging. Two attending radiologists separately identified the selection of tumour tissue for ROI positioning. Three different ROI positioning methods, namely the whole tumour volume (WTV) method, three-ROI method and one-section method, were used for the measurement. Kruskal-Wallis rank test or one-way ANOVA was used to compare the difference in IVIM parameters and ADC across the three different ROI positioning methods. Spearman correlation analysis was used to determine the correlation between each parameter and Edmondson-Steiner (E-S) grade. Receiver operating characteristics (ROC) curve analyses were performed to evaluate the diagnostic performance. RESULTS For the ADC and ADCslow, the mean value measured by using the WTV method was significant higher than the one-section and three-ROI methods (all p < 0.01). For the ADCslow, the highest area under curve (AUC) with a value of 0.969 was obtained by using the WTV method, followed by the one-section method (AUC = 0.938) and three-ROI method (AUC = 0.873). Additionally, for the ADC, AUC values were 0.861 for WTV method, 0.840 for one-section method and 0.806 for three-ROI method. CONCLUSIONS Different ROI positioning methods used significantly affect the IVIM parameters and ADC measurements. Measurements of ADCslow value derived from WTV method entailed the highest diagnostic performance in grading HCC. KEY POINTS • Diffusion MRI is useful for non-invasively differentiating the histologic grade of hepatocellular carcinoma. • Different ROI positioning methods used significantly affect the IVIM parameters and ADC measurements. • IVIM model is advantageous over mono-exponential model for assessing the histologic grade of hepatocellular carcinoma.
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Affiliation(s)
- Yi Wei
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Feifei Gao
- Department of Radiology, Henan Provincial People's Hospital, Zhengzhou, China
| | - Min Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Zixing Huang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Hehan Tang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jiaxing Li
- Department of Liver surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Wang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Tong Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | | | | | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China.
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30
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Citores MJ, Lucena JL, de la Fuente S, Cuervas-Mons V. Serum biomarkers and risk of hepatocellular carcinoma recurrence after liver transplantation. World J Hepatol 2019; 11:50-64. [PMID: 30705718 PMCID: PMC6354126 DOI: 10.4254/wjh.v11.i1.50] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 11/13/2018] [Accepted: 12/05/2018] [Indexed: 02/06/2023] Open
Abstract
Liver transplantation (LT) is the only potentially curative treatment for selected patients with cirrhosis and hepatocellular carcinoma (HCC) who are not candidates for resection. When the Milan criteria are strictly applied, 75% to 85%of 3- to 4-year actuarial survival rates are achieved, but up to 20% of the patients experience HCC recurrence after transplantation. The Milan criteria are based on the preoperative tumor macromorphology, tumor size and number on computed tomography or magnetic resonance imaging that neither correlate well with posttransplant histological study of the liver explant nor accurately predict HCC recurrence after LT, since they do not include objective measures of tumor biology. Preoperative biological markers, including alpha-fetoprotein, des-gamma-carboxiprothrombin or neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio, can predict the risk for HCC recurrence after transplantation. These biomarkers have been proposed as surrogate markers of tumor differentiation and vascular invasion, with varied risk magnitudes depending on the defined cutoffs. Different studies have shown that the combination of one or several biomarkers integrated into prognostic models predict the risk of HCC recurrence after LT more accurately than Milan criteria alone. In this review, we focus on the potential utility of these serum biological markers to improve the performance of Milan criteria to identify patients at high risk of tumoral recurrence after LT.
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Affiliation(s)
- Maria J Citores
- Department of Internal Medicine, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Majadahonda 28222, Spain.
| | - Jose L Lucena
- Liver Transplantation Unit, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Sara de la Fuente
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
| | - Valentin Cuervas-Mons
- Department of Internal Medicine, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda 28222, Spain
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31
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Lunsford KE, Court C, Seok Lee Y, Lu DS, Naini BV, Harlander-Locke MP, Busuttil RW, Agopian VG. Propensity-Matched Analysis of Patients with Mixed Hepatocellular-Cholangiocarcinoma and Hepatocellular Carcinoma Undergoing Liver Transplantation. Liver Transpl 2018; 24:1384-1397. [PMID: 29573187 DOI: 10.1002/lt.25058] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 04/30/2018] [Accepted: 03/13/2018] [Indexed: 12/13/2022]
Abstract
Mixed hepatocellular-cholangiocarcinomas (HCC-CCAs) are rare tumors with both hepatocellular and biliary differentiation. While liver transplantation (LT) is the gold standard treatment for patients with unresectable hepatocellular carcinoma (HCC), it is contraindicated in known HCC-CCA because of concerns of poor prognosis. We sought to compare posttransplant oncologic outcomes for HCC-CCA and a matched cohort of HCC LT recipients. A retrospective, single-center analysis (1984-2015) identified 12 patients with mixed HCC-CCA who were matched 1:3 to patients with HCC on both pretransplant (radiologic diameter and alpha-fetoprotein) and explant (pathologic diameter, grade/differentiation, and vascular invasion) tumor characteristics. Compared with HCC patients matched on pretransplant characteristics (n = 36), HCC-CCA had higher explant tumor grade, more poorly differentiated tumors, but similar T stage and vascular invasion. HCC-CCA recipients trended toward inferior recurrence-free survival at 5 years (28% versus 61%; P = 0.12) and greater recurrence (HCC-CCA: 50%, median time to recurrence 297 days versus HCC: 22%, median time to recurrence 347 days; P = 0.07). However, when matched to a separate HCC cohort with similar explant pathology, HCC-CCA had similar 5-year recurrence-free survival (42% versus 44%; P = 0.45) and posttransplant recurrence (50% versus 27%; P = 0.13). All 6 HCC-CCA recurrences occurred with poorly differentiated tumors (median survival 21.3 months), without a single recurrence in 5 of the 12 HCC-CCA patients with well-moderately differentiated tumors (median survival 60.2 months). Mixed HCC-CCA tumors are more likely poorly differentiated tumors compared with HCC with similar pretransplant characteristics. However, compared with HCC with similar pathologic characteristics, they display similar recurrence-free survival and are not inherently more aggressive tumors. Low-grade, well-moderately differentiated HCC-CCAs have excellent survival with a low risk for post-LT recurrence, and they should not be excluded from LT. Improved pretransplant identification of pathologic characteristics in HCC-CCA may allow for successful utilization of LT in this subset of patients.
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Affiliation(s)
- Keri E Lunsford
- J.C. Walter Center for Transplantation, Department of Surgery, Weill Cornell Medical College, Houston Methodist Hospital and Research Institute, Houston, TX
| | - Colin Court
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Yong Seok Lee
- Radiology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - David S Lu
- Radiology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Bita V Naini
- Pathology, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Michael P Harlander-Locke
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Ronald W Busuttil
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
| | - Vatche G Agopian
- Division of Liver and Pancreas Transplantation, Departments of Surgery, David Geffen School of Medicine at University of California, Los Angeles, CA
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