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Sun Y, Yang H, Li S, Zheng R, Liu B, Lin J, Huang F, Nong W, Luo L, Xie X, Huang G. An Accurate Model for Microvascular Invasion Prediction in Solitary Hepatocellular Carcinoma ≤5 cm Based on CEUS and EOB-MRI: A Retrospective Study with External Validation. Acad Radiol 2025:S1076-6332(25)00361-7. [PMID: 40335335 DOI: 10.1016/j.acra.2025.04.021] [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: 01/06/2025] [Revised: 04/07/2025] [Accepted: 04/09/2025] [Indexed: 05/09/2025]
Abstract
RATIONALE AND OBJECTIVES To develop a model combining contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) for predicting microvascular invasion (MVI) in solitary hepatocellular carcinoma (HCC) ≤5 cm. MATERIALS AND METHODS Patients between December 2019 and May 2024 in one center were retrospectively enrolled and randomly divided into the training cohort and internal validation cohort in a ratio of 7:3. Patients in a separate center were enrolled between January 2022 and December 2023 to be included as the external validation cohort. CEUS and EOB-MRI image features were extracted and used to develop models in the training cohort, and verified in the two validation cohorts. The predictive accuracy and clinical utility of models were evaluated using area under receiver operating characteristic curve (AUROC), Brier score, calibration plot and decision curve analysis (DCA). Net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare different models. RESULTS From the two centers a total of 493 patients, of which 134 were MVI positive, were evaluated. The CEUS+EOB model included seven image features and showed better discrimination ability than the individual CEUS/EOB-MRI model, with AUROCs of 0.92, 0.94, and 0.90 in the training cohort and two validation cohorts, respectively (p<0.05). The lowest Brier score of the combined model indicated the highest predictive precision. DCA also showed that the combined model added more net benefits. Both the NRI and IDI values >0 indicated that the combined model had significantly positive improvement (p<0.05). CONCLUSION The CEUS+EOB model was developed to assist clinicians in evaluating MVI in solitary HCC ≤5 cm.
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Affiliation(s)
- Yueting Sun
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.)
| | - Hong Yang
- Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Guangxi Zhuang Autonomous Region, No. 6, Shuangyong Road, 530021 Nanning, PR China (H.Y.)
| | - Shurong Li
- Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhong Shan Road, Guangzhou 510080, PR China (S.L.)
| | - Ruiying Zheng
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.)
| | - Baoxian Liu
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.)
| | - Jinhua Lin
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.)
| | - Fen Huang
- Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi Zhuang Autonomous Region, No. 3, Foziling Road, 530021 Nanning, PR China (F.H., W.N., L.L., G.H.)
| | - Wanxian Nong
- Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi Zhuang Autonomous Region, No. 3, Foziling Road, 530021 Nanning, PR China (F.H., W.N., L.L., G.H.)
| | - Lan Luo
- Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi Zhuang Autonomous Region, No. 3, Foziling Road, 530021 Nanning, PR China (F.H., W.N., L.L., G.H.)
| | - Xiaoyan Xie
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.)
| | - Guangliang Huang
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhong Shan Road, Guangzhou 510080, PR China (Y.S., R.Z., B.L., J.L., X.X., G.H.); Department of Medical Ultrasonics, Guangxi Hospital Division of the First Affiliated Hospital, Sun Yat-Sen University, Guangxi Zhuang Autonomous Region, No. 3, Foziling Road, 530021 Nanning, PR China (F.H., W.N., L.L., G.H.).
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Zeng Y, Wu H, Zhu Y, Li C, Du D, Song Y, Su S, Qin J, Jiang G. MRI-based intra-tumoral ecological diversity features and temporal characteristics for predicting microvascular invasion in hepatocellular carcinoma. Front Oncol 2025; 15:1510071. [PMID: 40098699 PMCID: PMC11911209 DOI: 10.3389/fonc.2025.1510071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Objective To investigate the predictive value of radiomics models based on intra-tumoral ecological diversity (iTED) and temporal characteristics for assessing microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). Material and Methods We retrospectively analyzed the data of 398 HCC patients who underwent dynamic contrast-enhanced MRI with Gd-EOB-DTPA (training set: 318; testing set: 80). The tumors were segmented into five distinct habitats using case-level clustering and a Gaussian mixture model was used to determine the optimal clusters based on the Bayesian information criterion to produce an iTED feature vector for each patient, which was used to assess intra-tumoral heterogeneity. Radiomics models were developed using iTED features from the arterial phase (AP), portal venous phase (PVP), and hepatobiliary phase (HBP), referred to as MiTED-AP, MiTED-PVP, and MiTED-HBP, respectively. Additionally, temporal features were derived by subtracting the PVP features from the AP features, creating a delta-radiomics model (MDelta). Conventional radiomics features were also extracted from the AP, PVP, and HBP images, resulting in three models: MCVT-AP, MCVT-PVP, and MCVT-HBP. A clinical-radiological model (CR model) was constructed, and two fusion models were generated by combining the radiomics or/and CR models using a stacking algorithm (fusion_R and fusion_CR). Model performance was evaluated using AUC, accuracy, sensitivity, and specificity. Results The MDelta model demonstrated higher sensitivity compared to the MCVT-AP and MCVT-PVP models. No significant differences in performance were observed across different imaging phases for either conventional radiomics (p = 0.096-0.420) or iTED features (p = 0.106-0.744). Similarly, for images from the same phase, we found no significant differences between the performance of conventional radiomics and iTED features (AP: p = 0.158; PVP: p = 0.844; HBP: p = 0.157). The fusion_R and fusion_CR models enhanced MVI discrimination, achieving AUCs of 0.823 (95% CI: 0.816-0.831) and 0.830 (95% CI: 0.824-0.835), respectively. Conclusion Delta radiomics features are temporal and predictive of MVI, providing additional predictive information for MVI beyond conventional AP and PVP features. The iTED features provide an alternative perspective in interpreting tumor characteristics and hold the potential to replace conventional radiomics features to some extent for MVI prediction.
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Affiliation(s)
- Yuli Zeng
- Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Huiqin Wu
- Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China
| | - Yanqiu Zhu
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chao Li
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Dongyang Du
- School of Computer Science, Inner Mongolia University, Inner Mongolia, China
| | - Yang Song
- Magnetic Resonance (MR) Scientific Marketing, Siemens Healthineers Ltd., Shanghai, China
| | - Sulian Su
- Department of Radiology, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, Fujian, China
| | - Jie Qin
- Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guihua Jiang
- Department of Medical Imaging, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, China
- Department of Radiology, Xiamen Humanity Hospital of Fujian Medical University, Xiamen, Fujian, China
- Guangzhou Key Laboratory of Molecular Functional Imaging and Artificial Intelligence for Major Brain Diseases, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China
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Pei J, Wang L, Li H. Development of a Better Nomogram for Prediction of Preoperative Microvascular Invasion and Postoperative Prognosis in Hepatocellular Carcinoma Patients: A Comparison Study. J Comput Assist Tomogr 2025; 49:9-22. [PMID: 38663025 PMCID: PMC11801467 DOI: 10.1097/rct.0000000000001618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 02/26/2024] [Indexed: 01/19/2025]
Abstract
OBJECTIVE Personalized precision medicine can be facilitated by clinically available preoperative microvascular invasion (MVI) prediction models that are reliable and postoperative MVI pathological grade-related recurrence prediction models that are accurate. In this study, we aimed to compare different mathematical models to derive the best preoperative prediction and postoperative recurrence prediction models for MVI. METHODS A total of 143 patients with hepatocellular carcinoma (HCC) whose clinical, laboratory, imaging, and pathological data were available were included in the analysis. Logistic regression, Cox proportional hazards regression, LASSO regression with 10-fold cross-validation, stepwise regression, and random forest methods were used for variable screening and predictive modeling. The accuracy and validity of seven preoperative MVI prediction models and five postoperative recurrence prediction models were compared in terms of C-index, net reclassification improvement, and integrated discrimination improvement. RESULTS Multivariate logistic regression analysis revealed that a preoperative nomogram model with the variables cirrhosis diagnosis, alpha-fetoprotein > 400, and diameter, shape, and number of lesions can predict MVI in patients with HCC reliably. Postoperatively, a nomogram model with MVI grade, number of lesions, capsule involvement status, macrovascular invasion, and shape as the variables was selected after LASSO regression and 10-fold cross-validation analysis to accurately predict the prognosis for different MVI grades. The number and shape of the lesions were the most common predictors of MVI preoperatively and recurrence postoperatively. CONCLUSIONS Our study identified the best statistical approach for the prediction of preoperative MVI as well as postoperative recurrence in patients with HCC based on clinical, imaging, and laboratory tests results. This could expedite preoperative treatment decisions and facilitate postoperative management.
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Birgin E, Nebelung H, Abdelhadi S, Rink JS, Froelich MF, Hetjens S, Rahbari M, Téoule P, Rasbach E, Reissfelder C, Weitz J, Schoenberg SO, Riediger C, Plodeck V, Rahbari NN. Development and validation of a digital biopsy model to predict microvascular invasion in hepatocellular carcinoma. Front Oncol 2024; 14:1360936. [PMID: 39376989 PMCID: PMC11457731 DOI: 10.3389/fonc.2024.1360936] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Accepted: 08/30/2024] [Indexed: 10/09/2024] Open
Abstract
Background Microvascular invasion is a major histopathological risk factor of postoperative recurrence in patients with hepatocellular carcinoma. This study aimed to develop and validate a digital biopsy model using imaging features to predict microvascular invasion before hepatectomy. Methods A total of 217 consecutive patients who underwent hepatectomy for resectable hepatocellular carcinoma were enrolled at two tertiary-care reference centers. An imaging-based digital biopsy model was developed and internally validated using logistic regression analysis with adjustments for age, sex, etiology of disease, size and number of lesions. Results Three imaging features, i.e., non-smoothness of lesion margin (OR = 16.40), ill-defined pseudocapsula (OR = 4.93), and persistence of intratumoral internal artery (OR = 10.50), were independently associated with microvascular invasion and incorporated into a prediction model. A scoring system with 0 - 3 points was established for the prediction model. Internal validation confirmed an excellent calibration of the model. A cutoff of 2 points indicates a high risk of microvascular invasion (area under the curve 0.87). The overall survival and recurrence-free survival stratified by the risk model was significantly shorter in patients with high risk features of microvascular invasion compared to those patients with low risk of microvascular invasion (overall survival: median 35 vs. 75 months, P = 0.027; recurrence-free survival: median 17 vs. 38 months, P < 0.001)). Conclusion A preoperative assessment of microvascular invasion by digital biopsy is reliable, easily applicable, and might facilitate personalized treatment strategies.
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Affiliation(s)
- Emrullah Birgin
- Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
| | - Heiner Nebelung
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Schaima Abdelhadi
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Johann S. Rink
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Matthias F. Froelich
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Svetlana Hetjens
- Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Mohammad Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Patrick Téoule
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Erik Rasbach
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany
| | - Jürgen Weitz
- Department of Visceral-, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Stefan O. Schoenberg
- Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany
| | - Carina Riediger
- Department of Visceral-, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Verena Plodeck
- Department of Radiology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Nuh N. Rahbari
- Department of General and Visceral Surgery, University Hospital Ulm, Ulm, Germany
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Saleh GA, Denewar FA, Ali KM, Saleh M, Ali MA, Shehta A, Mansour M. Inter-observer reliability and predictive values of triphasic computed tomography for microvascular invasion in hepatocellular carcinoma. THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2024; 55:176. [DOI: 10.1186/s43055-024-01354-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 08/28/2024] [Indexed: 02/11/2025] Open
Abstract
Abstract
Background
Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor globally and a leading cause of mortality in cirrhotic patients. Our study aimed to estimate the diagnostic performance of triphasic CT and inter-observer reliability in the preoperative detection of microvascular invasion (MVI) in HCC. Two independent radiologists accomplished a retrospective analysis for 99 patients with HCC to assess the CT features for MVI in each lesion. Postoperative histopathology was considered the gold standard.
Results
Multivariate regression analysis revealed that incomplete or absent tumor capsules, presence of TTPV, and absence of hypodense halo were statistically significant independent predictors of MVI. There was excellent agreement among observers in evaluating peritumoral enhancement, identifying intratumoral arteries, hypodense halo, TTPV, and macrovascular invasion. Also, our results revealed moderate agreement in assessing the tumor margin and tumor capsule.
Conclusion
Triphasic CT features of MVI are reliable imaging predictors that may be helpful for standard preoperative interpretation of HCC.
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Li J, Su X, Xu X, Zhao C, Liu A, Yang L, Song B, Song H, Li Z, Hao X. Preoperative prediction and risk assessment of microvascular invasion in hepatocellular carcinoma. Crit Rev Oncol Hematol 2023; 190:104107. [PMID: 37633349 DOI: 10.1016/j.critrevonc.2023.104107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/22/2023] [Indexed: 08/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and highly lethal tumors worldwide. Microvascular invasion (MVI) is a significant risk factor for recurrence and poor prognosis after surgical resection for HCC patients. Accurately predicting the status of MVI preoperatively is critical for clinicians to select treatment modalities and improve overall survival. However, MVI can only be diagnosed by pathological analysis of postoperative specimens. Currently, numerous indicators in serology (including liquid biopsies) and imaging have been identified to effective in predicting the occurrence of MVI, and the multi-indicator model based on deep learning greatly improves accuracy of prediction. Moreover, several genes and proteins have been identified as risk factors that are strictly associated with the occurrence of MVI. Therefore, this review evaluates various predictors and risk factors, and provides guidance for subsequent efforts to explore more accurate predictive methods and to facilitate the conversion of risk factors into reliable predictors.
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Affiliation(s)
- Jian Li
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Xin Su
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Xiao Xu
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Changchun Zhao
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Ang Liu
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China; Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Liwen Yang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Baoling Song
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Hao Song
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Zihan Li
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou 730000, China
| | - Xiangyong Hao
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China.
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Cai Y, Xie K, Adeeb Alhmoud MN, Lan T, Wan H, Hu D, Lan L, Liu C, Wu H. Effect of PIVKA-II and AFP secretion status on early recurrence of hepatocellular carcinoma after open and laparoscopic surgery. Cancer Med 2023; 12:17866-17877. [PMID: 37596739 PMCID: PMC10523999 DOI: 10.1002/cam4.6422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 06/29/2023] [Accepted: 07/27/2023] [Indexed: 08/20/2023] Open
Abstract
BACKGROUND Prothrombin induced by vitamin K absence-II (PIVKA-II) and Alpha-fetoprotein (AFP) have been widely used as diagnostic markers in hepatocellular carcinoma (HCC), but the prognostic values of the two serum markers and their clinical usefulness in patient selection for different surgical approaches remain largely unclear. METHODS HCC patients received surgical treatment between 2015 and 2019 were included. Patients were divided into four statuses according to the serum PIVKA-II and AFP secretion status: PIVKA-II (-) AFP (-) (status 1); PIVKA-II (+) AFP (-) (status 2); PIVKA-II (-) AFP (+) (status 3); PIVKA-II (+) AFP (+) (status 4). Kaplan-Meier analyses were conducted to compare the survivals of the four groups and the HCC patients received different surgical interventions; time-dependent AUC curves were introduced to evaluate the prognostic value of the PIV-AFP status; Cox regression model was used to identify prognostic indexes for overall survival (OS) and recurrence-free survival (RFS). RESULTS A total of 518 patients were included. Patients with PIVKA-II (+) and APF (+) presented significantly decreased OS and RFS comparing to the other statuses. The areas under ROC curves of PIV-AFP status in predicting OS and RFS were superior to the PIVKA-II or the AFP alone. The HCC patients in early stages with PIVKA-II (+) and APF (+) had worse RFS when received laparoscopic hepatectomy than those who received open hepatectomy, whereas there was no difference in other secretion statuses. The PIVKA-II (+) and AFP (+) secretion status was an independent risk factor for OS, RFS. CONCLUSIONS The PIV-AFP secretion status is of favorable clinical utility in predicting the OS and RFS of the HCC patients; extra caution is needed when applicated the laparoscopic approach in the HCC patients with PIVKA-II (+) and AFP (+).
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Affiliation(s)
- Yunshi Cai
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Kunlin Xie
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Mohammad Natheir Adeeb Alhmoud
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Tian Lan
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Haifeng Wan
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
| | - Die Hu
- Division of Liver Surgery, Department of General SurgeryWest China Hospital, Sichuan UniversityChengduChina
| | - Ling Lan
- Division of Liver Surgery, Department of General SurgeryWest China Hospital, Sichuan UniversityChengduChina
| | - Chang Liu
- Division of Liver Surgery, Department of General SurgeryWest China Hospital, Sichuan UniversityChengduChina
- Department of Minimal Invasive SurgeryShangjin Nanfu HospitalChengduChina
| | - Hong Wu
- Liver Transplant Center, Transplant Center, State Key Laboratory of Biotherapy and Cancer Center, West China HospitalSichuan University and Collaborative Innovation Center of BiotherapyChengduChina
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Tang Y, Lu X, Liu L, Huang X, Lin L, Lu Y, Zhou C, Lai S, Luo N. A Reliable and Repeatable Model for Predicting Microvascular Invasion in Patients With Hepatocellular Carcinoma. Acad Radiol 2023; 30:1521-1527. [PMID: 37002035 DOI: 10.1016/j.acra.2023.02.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 02/26/2023] [Accepted: 02/27/2023] [Indexed: 03/31/2023]
Abstract
RATIONALE AND OBJECTIVES The reproducibility of imaging models for predicting microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains questionable due to inconsistent interpretation of image signs. Our aim was to screen for high-consensus MRI features to develop a repeatable model for predicting MVI. MATERIALS AND METHODS We included 219 patients with HCC who underwent surgical resection, and patients were divided into a training cohort (n = 145) and a validation cohort (n = 74). Morphological characteristics, signal features on hepatobiliary phases, and dynamic enhancement patterns were qualitatively interobserver evaluated. Interobserver agreement was assessed using Cohen's κ for selecting features with high interobserver agreement. Risk factors that were significant in stepwise multivariate analysis and that could be measured with good interobserver agreement were used to construct a predictive model, which was assessed in the validation cohort. The diagnostic performance of the model was evaluated based on area under the receiver operating characteristic curve (AUC). RESULTS Multivariate analysis identified nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery as independent risk factors of MVI. These MRI-based features showed good or nearly perfect interobserver agreement between radiologists (κ > 0.6). The predictive model predicted MVI well in the training (AUC 0.734) and validation cohorts (AUC 0.759) and fitted well to calibration curves. CONCLUSION MRI features included nonsmooth tumor margin, absence of radiologic capsule, and intratumoral artery that can be assessed with high interobserver agreement can predict MVI in HCC patients. The predictive model described here may be useful to radiologists, regardless of experience level.
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Affiliation(s)
- Yunjing Tang
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xinhui Lu
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Lijuan Liu
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xiangyang Huang
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ling Lin
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yixin Lu
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Chuanji Zhou
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Shaolv Lai
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ningbin Luo
- Department of Radiology, Guangxi Medical University Cancer Hospital, Nanning, China.
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Huang J, Li L, Liu FC, Tan BB, Yang Y, Jiang BG, Pan ZY. Prognostic Analysis of Single Large Hepatocellular Carcinoma Following Radical Resection: A Single-Center Study. J Hepatocell Carcinoma 2023; 10:573-586. [PMID: 37056420 PMCID: PMC10086221 DOI: 10.2147/jhc.s404895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 03/28/2023] [Indexed: 04/15/2023] Open
Abstract
Objective To investigate the survival and independent prognostic factors for single large hepatocellular carcinoma (SLHCC) after surgical resection. Methods Patients with SLHCC who underwent radical resection from January 2013 to December 2017 were retrospectively analyzed. The Kaplan-Meier method was used to analyze the overall survival (OS) rate and recurrence-free survival (RFS) rates. Cox forward stepwise regression was performed to analyze the independent prognostic factors. Results A total of 485 cases were included. The average age was 51.2±11.2 years, 88.9% had a history of hepatitis B virus infection, and most patients had normal liver function. The average tumor diameter was 8.8±3.0 cm. The 1-, 3-, and 5-year OS and RFS rates were 76.8%, 56.7%, and 45.7%, and 61.0%, 46.2%, and 34.7%, respectively. Multivariate analysis showed that liver cirrhosis (HR=1.456, P=0.004), total bilirubin (TB) ≥17.1 μmol/L (HR=1.437, P=0.011), glutamyl transferase (GGT) >60 U/L (HR=1.438, P=0.020), lactate dehydrogenase (LDH) >225 U/L (HR=1.442, P=0.007), blood loss ≥400 mL (HR=1.339, P=0.027), microvascular invasion (MVI) (HR=1.492, P=0.004), satellite lesions (HR=1.859, P<0.0001) and Edmondson-Steiner grade III+IV (HR=1.740, P=0.018) were independent risk factors for reduced OS in SLHCC patients. Sex (HR=1.763, P=0.003), liver cirrhosis (HR=1.382, P=0.007), GGT >60 U/L (HR=1.512, P=0.003), LDH >225 U/L (HR=1.480, P=0.002), MVI (HR=1.545, P=0.001), and satellite lesions (HR=1.564, P=0.001) were independent risk factors for reduced RFS. OS and RFS nomograms were constructed using risk factors with C-index values of 0.692 (95% CI: 0.659-0.724) and 0.659 (95% CI: 0.623-0.693), respectively. The Hosmer-Leme test demonstrated the good fit of both nomograms. Conclusion Surgical resection is the standard and effective treatment for SLHCC patients. Sex, liver cirrhosis, TB≥17.1 μmol/L, GGT>60 U/L, LDH>225 U/L, blood loss≥400 mL, MVI, Edmondson-Steiner grade III+IV, and satellite lesions were found to be independent prognostic factors in SLHCC patients following radical resection. The OS and RFS nomograms accurately predicted the prognosis of SLHCC patients.
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Affiliation(s)
- Jian Huang
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Li Li
- Department of Nephrology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Fu-Chen Liu
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Bi-Bo Tan
- Department of Ultrasonic, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Yun Yang
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Bei-Ge Jiang
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
| | - Ze-Ya Pan
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 201805, People’s Republic of China
- Correspondence: Ze-Ya Pan; Bei-Ge Jiang, Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, No. 700, MoYu North Road, Jiading, Shanghai, People’s Republic of China, Tel +86-13391236437; +86-13764561303, Email ;
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10
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Clinical and imaging features preoperative evaluation of histological grade and microvascular infiltration of hepatocellular carcinoma. BMC Gastroenterol 2022; 22:369. [PMID: 35915440 PMCID: PMC9341046 DOI: 10.1186/s12876-022-02449-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 07/21/2022] [Indexed: 11/13/2022] Open
Abstract
Background To predict the histological grade and microvascular invasion (MVI) in patients with HCC. Methods A retrospective analysis was conducted on 175 patients who underwent MRI enhancement scanning (from September 2016.9 to October 2020). They were divided into MVI positive, MVI negative, Grade-high and Grade-low groups. Results The AFP of 175 HCC patients distributed in MVI positive and negative groups, Grade-low and Grade-high groups were statistically significant (P = 0.002 and 0.03, respectively). Multiple HCC lesions were more common in MVI positive and Grade-high groups. Correspondingly, more single lesions were found in MVI negative and Grade-low groups (P = 0.005 and 0.019, respectively). Capsule on MRI was more common in MVI negative and Grade-high groups, and the difference was statistically significant (P = 0.02 and 0.011, respectively). There were statistical differences in the distribution of three MRI signs: artistic rim enhancement, artistic peripheral enhancement, and tumor margin between MVI positive and MVI negative groups (P = 0.001, < 0.001, and < 0.001, respectively). Tumor hypointensity on HBP was significantly different between MVI positive and negative groups (P < 0.001). Conclusions Our research shows that preoperative enhanced imaging can be used to predict MVI and tumor differentiation grade of HCC. The prognosis of MVI-negative group was better than that of MVI-positive group.
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11
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Cai Q, Mao Y, Dai S, Gao F, Xiao Q, Hu W, Qin T, Yang Q, Li Z, Cai D, Zhong ME, Ding K, Wu XJ, Zhang R. The growth pattern of liver metastases on MRI predicts early recurrence in patients with colorectal cancer: a multicenter study. Eur Radiol 2022; 32:7872-7882. [PMID: 35420300 DOI: 10.1007/s00330-022-08774-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 03/22/2022] [Accepted: 03/26/2022] [Indexed: 01/03/2023]
Abstract
OBJECTIVES The multicenter study aimed to explore the relationship between the growth pattern of liver metastases on preoperative MRI and early recurrence in patients with colorectal cancer liver metastases (CRCLM) after surgery. METHODS A total of 348 CRCLM patients from 3 independent centers were enrolled, including 130 patients with 339 liver metastases in the primary cohort and 218 patients in validation cohorts. Referring to the gross classification of hepatocellular carcinoma (HCC), the growth pattern of each liver metastasis on MRI was classified into four types: rough, smooth, focal extranodular protuberant (FEP), and nodular confluent (NC). Disease-free survival (DFS) curve was constructed using the Kaplan-Meier method. RESULTS In primary cohort, 42 (12.4%) of the 339 liver metastases were rough type, 237 (69.9%) were smooth type, 29 (8.6%) were FEP type, and 31 (9.1%) were NC type. Those patients with FEP- and/or NC-type liver metastases had shorter DFS than those without such metastases (p < 0.05). However, there were no significant differences in DFS between patients with rough- and smooth-type liver metastases and those without such metastases. The patients with FEP- and/or NC-type liver metastases also had shorter DFS than those without such metastases in two external validation cohorts. In addition, 40.5% of high-risk-type (FEP and NC) liver metastases converted to low-risk types (rough and smooth) after neoadjuvant chemotherapy. CONCLUSION The FEP- and NC-type liver metastases were associated with early recurrence, which may facilitate the clinical treatment of CRCLM patients. KEY POINTS • In the primary cohort, patients with FEP- and NC-type metastases had shorter disease-free survival (DFS) and a higher intrahepatic recurrence rate than patients without such metastases in the liver. • In the primary cohort, there were no significant differences in DFS or intrahepatic recurrence rate between patients with rough- and smooth-type metastases and those without such metastases in the liver. • High-risk patients had shorter DFS and a higher intrahepatic recurrence rate than low-risk patients in primary and external validation cohorts.
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Affiliation(s)
- Qian Cai
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.,Department of Radiology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Yize Mao
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.,Department of Hepato-biliary-pancreatic Oncology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Siqi Dai
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Zhejiang, 310009, Hangzhou, China
| | - Feng Gao
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, supported by National Key Clinical Discipline, Guangzhou, 510655, China
| | - Qian Xiao
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Zhejiang, 310009, Hangzhou, China
| | - Wanming Hu
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.,Department of Pathology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Tao Qin
- Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 East Yanjiang Road, Guangzhou, 510120, China
| | - Qiuxia Yang
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.,Department of Radiology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, China
| | - Zhaozhou Li
- Department of Astronomy, School of Physics and Astronomy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Shanghai, 200240, China
| | - Du Cai
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, supported by National Key Clinical Discipline, Guangzhou, 510655, China
| | - Min-Er Zhong
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China.,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, supported by National Key Clinical Discipline, Guangzhou, 510655, China
| | - Kefeng Ding
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Zhejiang, 310009, Hangzhou, China. .,Cancer Center, Zhejiang University, Hangzhou, China.
| | - Xiao-Jian Wu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, China. .,Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, supported by National Key Clinical Discipline, Guangzhou, 510655, China.
| | - Rong Zhang
- State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China. .,Department of Radiology, Sun Yat-sen University Cancer Center, No. 651 Dongfeng Road East, Guangzhou, 510060, China.
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Deng Y, Li J, Xu H, Ren A, Wang Z, Yang D, Yang Z. Diagnostic Accuracy of the Apparent Diffusion Coefficient for Microvascular Invasion in Hepatocellular Carcinoma: A Meta-analysis. J Clin Transl Hepatol 2022; 10:642-650. [PMID: 36062283 PMCID: PMC9396311 DOI: 10.14218/jcth.2021.00254] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/13/2021] [Accepted: 10/27/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND AND AIMS Microvascular invasion (MVI) is a major risk factor for the early recurrence of hepatocellular carcinoma (HCC) and it seriously worsens the prognosis. Accurate preoperative evaluation of the presence of MVI could greatly benefit the treatment management and prognosis prediction of HCC patients. The study aim was to evaluate the diagnostic performance of the apparent diffusion coefficient (ADC), a quantitative parameter for the preoperative diagnosis MVI in HCC patients. METHODS Original articles about diffusion-weighted imaging (DWI) and/or intravoxel incoherent motion (IVIM) conducted on a 3.0 or 1.5 Tesla magnetic resonance imaging (MRI) system indexed through January 17, 2021were collected from MEDLINE/PubMed, Web of Science, EMBASE, and the Cochrane Library. Methodological quality was evaluated using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The pooled sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUROC) were calculated, and meta-regression analysis was performed using a bivariate random effects model through a meta-analysis. RESULTS Nine original articles with a total of 988 HCCs were included. Most studies had low bias risk and minimal applicability concerns. The pooled sensitivity, specificity and AUROC of the ADC value were 73%, 70%, and 0.78, respectively. The time interval between the index test and the reference standard was identified as a possible source of heterogeneity by subgroup meta-regression analysis. CONCLUSIONS Meta-analysis showed that the ADC value had moderate accuracy for predicting MVI in HCC. The time interval accounted for the heterogeneity.
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Affiliation(s)
- Yuhui Deng
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Medical Imaging Division, Heilongjiang Provincial Hospital, Harbin Institute of Technology, Harbin, Heilongjiang, China
| | - Jisheng Li
- Department of Interventional Radiology, Yantai Penglai Traditional Chinese Medicine Hospital, Yantai, Shandong, China
| | - Hui Xu
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Ahong Ren
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Zhenchang Wang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Dawei Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Correspondence to: Dawei Yang and Zhenghan Yang, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, West District, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-1868-2746 (DY) and https://orcid.org/0000-0003-3986-1732 (ZY). Tel: +86-13488676354 (DY) and +86-13910831365 (ZY), Fax: +86-10-63138490, E-mail: (DY) and (ZY)
| | - Zhenghan Yang
- Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- Correspondence to: Dawei Yang and Zhenghan Yang, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, West District, Beijing 100050, China. ORCID: https://orcid.org/0000-0002-1868-2746 (DY) and https://orcid.org/0000-0003-3986-1732 (ZY). Tel: +86-13488676354 (DY) and +86-13910831365 (ZY), Fax: +86-10-63138490, E-mail: (DY) and (ZY)
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13
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Hidaka M, Hara T, Soyama A, Adachi T, Matsushima H, Tanaka T, Ishimaru H, Miyaaki H, Nakao K, Eguchi S. Long‐term outcomes of living‐donor liver transplantation, hepatic resection, and local therapy for hepatocellular carcinoma with three <3‐cm nodules in a single institute. JGH Open 2022; 6:539-546. [PMID: 35928699 PMCID: PMC9344587 DOI: 10.1002/jgh3.12783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 06/06/2022] [Accepted: 06/08/2022] [Indexed: 12/24/2022]
Abstract
Background and Aim Treatment for small hepatocellular carcinoma (HCC) is determined based on the results of a liver function test and the tumor location and spread. The present study compared the outcomes among local therapy, hepatic resection (HR), and living‐donor liver transplantation (LDLT) for small HCC in a single institute. Methods We compared the overall survival, recurrence‐free survival, and cancer‐specific survival rates in patients with three HCC nodules <3 cm in size among local therapy, which included radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), and transarterial chemoembolization (TACE), and surgical treatment (HR and LDLT). Results One hundred and ninety‐seven patients with local therapy (109 RFA, 26 PEI, and 78 TACE), 107 with HR, and 66 with LDLT were enrolled in this study. There was no significant difference in OS among these groups. The recurrence‐free, cancer‐specific survival (CSS) of LDLT was superior to local therapy and HR. The prognostic factors for the survival were Child–Pugh (CP) Grade B and tumor marker for local therapy and multiple tumors and elevated ALT levels for HR. Conclusions For CP grade B patients with HCC of three <3‐cm nodule, LDLT could be considered because it resulted in better survival and CSS rates than local therapy.
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Affiliation(s)
- Masaaki Hidaka
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Takanobu Hara
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Akihiko Soyama
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Tomohiko Adachi
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hajime Matsushima
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Takayuki Tanaka
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hideki Ishimaru
- Department of Radiological Sciences Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Hisamitsu Miyaaki
- Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
| | - Susumu Eguchi
- Department of Surgery Nagasaki University Graduate School of Biomedical Sciences Nagasaki Japan
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14
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Jiang C, Zhao L, Xin B, Ma G, Wang X, Song S. 18F-FDG PET/CT radiomic analysis for classifying and predicting microvascular invasion in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Quant Imaging Med Surg 2022; 12:4135-4150. [PMID: 35919043 PMCID: PMC9338369 DOI: 10.21037/qims-21-1167] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 06/06/2022] [Indexed: 12/24/2022]
Abstract
Background Microvascular invasion (MVI) is a critical risk factor for early recurrence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to explore the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomic features for the preoperative prediction of HCC and ICC classification and MVI. Methods In this retrospective study, 127 (HCC: ICC =76:51) patients with suspected MVI accompanied by either HCC or ICC were included (In HCC group, MVI positive: negative =46:30 in ICC group, MVI positive: negative =31:20). Results-driven feature engineering workflow was used to select the most predictive feature combinations. The prediction model was based on supervised machine learning classifier. Ten-fold cross validation on training cohort and independent test cohort were constructed to ensure stability and generalization ability of models. Results For HCC and ICC classification, radiomics predictors composed of two PET and one CT feature achieved area under the curve (AUC) of 0.86 (accuracy, sensitivity, specificity was 0.82, 0.78, 0.88, respectively) on test cohort. For MVI prediction, in HCC group, our MVI prediction model achieved AUC of 0.88 (accuracy, sensitivity, specificity was 0.78, 0.88, 0.60 respectively) with three PET features associated with tumor stage on test cohort. In ICC group, the phenotype composed of two PET features and carbohydrate antigen 19-9 (CA19-9) achieved AUC of 0.90 (accuracy, sensitivity, specificity was 0.77, 0.75, 0.80, respectively). Conclusions 18F-FDG PET/CT radiomic features integrating clinical factors have potential in HCC and ICC classification and MVI prediction, while PET features have dominant predictive power in model performance. The prediction model has value in providing a non-invasive biomarker for an earlier indication and comprehensive quantification of primary liver cancers.
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Affiliation(s)
- Chunjuan Jiang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Liwei Zhao
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Bowen Xin
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Guang Ma
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Xiuying Wang
- School of Computer Science, The University of Sydney, Sydney, NSW, Australia
| | - Shaoli Song
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
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15
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Preoperative application of systemic inflammatory biomarkers combined with MR imaging features in predicting microvascular invasion of hepatocellular carcinoma. Abdom Radiol (NY) 2022; 47:1806-1816. [PMID: 35267069 DOI: 10.1007/s00261-022-03473-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 02/21/2022] [Accepted: 02/21/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To investigate whether systemic inflammatory biomarkers compared with the imaging features interpreted by radiologists can offer complementary value for predicting the risk of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). METHODS A total of 156 patients with histologically confirmed HCC between Jan 2018 and Dec 2020 were retrospectively enrolled in the primary cohort. Preoperative clinical-inflammatory biomarkers and MR imaging of the patients were recorded and then evaluated as an inflammatory score (Inflam-score) and imaging feature score (Radio-score). Six Inflam-scores and 12 Radio-scores were determined from each patient by univariate analysis. Logistic regression was performed to select risk factors for MVI and establish a predictive nomogram. Decision curve analysis was applied to estimate the incremental value of the Inflam-score to the Radio-score for predicting MVI. RESULTS Four Radio-scores and 2 Inflam-scores, namely, larger tumor size, non-smooth tumor margin, presence of satellite nodules, presence of peritumoral enhance, higher neutrophil-lymphocyte ratio (NLR), and lower prognostic nutritional index (PNI), were significantly associated with MVI (p < 0.05). An MVI risk prediction nomogram was then constructed with an area under the curve (AUC) of 0.868 (95% CI 0.806-0.931). Adding Inflam-scores to Radio-scores improved the sensitivity of the model from 60.9 to 80.4% in receiver operating characteristic (ROC) curve analysis and led to a net benefit in decision curve analysis. CONCLUSION Systemic inflammatory biomarkers are complementary tools that provide additional benefit to conventional imaging estimation for predicting MVI in HCC patients.
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Li X, Han X, Li L, Su C, Sun J, Zhan C, Feng D, Cheng W. Dynamic Contrast-Enhanced Ultrasonography with Sonazoid for Diagnosis of Microvascular Invasion in Hepatocellular Carcinoma. ULTRASOUND IN MEDICINE & BIOLOGY 2022; 48:575-581. [PMID: 34933756 DOI: 10.1016/j.ultrasmedbio.2021.11.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 10/30/2021] [Accepted: 11/08/2021] [Indexed: 06/14/2023]
Abstract
The aim of the present study was to investigate the imaging features observed in pre-operative Sonazoid contrast-enhanced ultrasound (SZ-CEUS) and the correlations with the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. In this single-center retrospective study, 31 patients with surgically and histopathologically confirmed HCC lesions were included. Patients were classified according to the presence of MVI into the MVI-positive group (n = 15) and MVI-negative group (n = 16). The CEUS examinations were performed within 2 or 3 d before surgery. Features, including tumor necrosis and ultrasound contrast agent (UCA) distribution characteristics in the arterial phase (AP), tumor types (single nodular [SN] or non-single nodular [non-SN]) in the post-vascular phase (PVP), wash-in time, wash-in slope, time to peak (TTP) and peak intensity (PI), were assessed. Univariate analysis revealed statistically significant differences between the two groups with respect to tumor necrosis (p = 0.002), inhomogeneous distribution of contrast agent in the AP (p = 0.001) and non-SN type in the PVP (p < 0.001). There was no significant difference in the quantitative parameters. Multivariate analysis revealed that non-SN type in the PVP was a significant independent risk factor for MVI of HCC (odds ratio = 30.51, 95% confidence interval [CI]: 2.335-398.731, p = 0.009). The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.873, 93.3%, 81.3%, 82.4% and 92.9%, respectively. Thus, SZ-CEUS can provide useful information for the diagnosis of MVI in HCC.
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Affiliation(s)
- Xintong Li
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Xue Han
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Lei Li
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Chang Su
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Jianmin Sun
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Chao Zhan
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Di Feng
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China
| | - Wen Cheng
- Department of Ultrasound, Hepatology, and Pathology, Harbin Medical University Cancer Hospital, Nangang District, Harbin, PR China.
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Carr BI, Guerra V, Donghia R, Ince V, Akbulut S, Ersan V, Usta S, Isik B, Samdanci E, Yilmaz S. Microscopic Portal Vein Invasion in Relation to Tumor Focality and Dimension in Patients with Hepatocellular Carcinoma. J Gastrointest Surg 2022; 26:333-340. [PMID: 34506030 DOI: 10.1007/s11605-021-05126-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 08/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Microscopic portal vein invasion (microPVI) and tumor multifocality are hepatocellular carcinoma (HCC) prognosis factors. To investigate whether microPVI and multifocality are directly related to each other. METHODS We retrospectively analyzed the relationships between microPVI, multifocality, and maximum tumor diameter (MTD) in prospectively collected transplanted HCC patients. RESULTS HCCs with 1, 2, or ≥ 3 foci had more microPVI in larger than in smaller HCCs, with microPVI being present in 52.24% of single large foci. Conversely, microPVI patients had similar percentages of single and multifocal lesions. A linear regression model of MTD, showed microPVI best associated with MTD, with 2.49 as coefficient, whereas multifocality had a 0.83 coefficient. A logistic regression model of microPVI showed significant association with tumor multifocality, especially for small HCCs. Trends for microPVI and multifocality in relation to MTD revealed that both increased with MTD but more significantly for microPVI. Survival was similar in patients with small HCCs, with or without microPVI, but was significantly worse in microPVI patients with larger HCCs. No patient survival differences were found in relation to focality. CONCLUSIONS MTD had stronger associations with microPVI than with multifocality. microPVI was associated with worse survival in patients with large HCCs, but survival was not impacted by number of tumor foci. microPVI and multifocality appear weakly related, having different behavior in relation to MTD and survival.
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Affiliation(s)
- Brian I Carr
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
| | - Vito Guerra
- National Institute of Digestive Diseases. IRCCS S. de Bellis Research Hospital, Castellana Grotte, Italy
| | - Rossella Donghia
- National Institute of Digestive Diseases. IRCCS S. de Bellis Research Hospital, Castellana Grotte, Italy
| | - Volkan Ince
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
| | - Sami Akbulut
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey.
| | - Veysel Ersan
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
| | - Sertac Usta
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
| | - Burak Isik
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
| | - Emine Samdanci
- Department of Pathology, Faculty of Medicine, Inonu University, 44280, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery, Faculty of Medicine, Liver Transplant Institute, Inonu University, Elazig Yolu 10. Km, 44280, Malatya, Turkey
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Beaufrère A, Caruso S, Calderaro J, Poté N, Bijot JC, Couchy G, Cauchy F, Vilgrain V, Zucman-Rossi J, Paradis V. Gene expression signature as a surrogate marker of microvascular invasion on routine hepatocellular carcinoma biopsies. J Hepatol 2022; 76:343-352. [PMID: 34624411 DOI: 10.1016/j.jhep.2021.09.034] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 09/13/2021] [Accepted: 09/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Microvascular invasion (MVI), a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma (HCC), is only detectable by microscopic examination of the surgical specimen. We aimed to define a transcriptomic signature associated with MVI in HCC than can be applied to formalin-fixed paraffin-embedded (FFPE) biopsies for use in clinical practice. METHODS To identify a gene expression signature related to MVI by using NanoString technology, we selected a set of 200 genes according to the literature and RNA-sequencing data obtained from a cohort of 150 frozen HCC samples previously published. We used 178 FFPE-archived HCC samples, including 109 surgical samples for the training set and 69 paired pre-operative biopsies for the validation set. In 14 cases of the training set, a paired biopsy was available and was also analyzed. RESULTS We identified a 6-gene signature (ROS1, UGT2B7, FAS, ANGPTL7, GMNN, MKI67) strongly associated with MVI in the training set of FFPE surgical HCC samples, with 82% accuracy (sensitivity 82%, specificity 81%, AUC 0.82). The NanoString gene expression was highly correlated in 14 paired surgical/biopsy HCC samples (mean R: 0.97). In the validation set of 69 FFPE HCC biopsies, the 6-gene NanoString signature predicted MVI with 74% accuracy (sensitivity 73%, specificity 76%, AUC 0.74). Moreover, on multivariate analysis, the MVI signature was associated with overall survival in both sets (hazard ratio 2.29; 95% CI 1.03-5.07; p = 0.041). CONCLUSION We defined a 6-gene signature that can accurately predict MVI in FFPE HCC biopsy samples, which is also associated with overall survival, although its survival impact must be confirmed by extensive study with further clinical data. LAY SUMMARY Microvascular invasion, a major risk factor for tumor recurrence after surgery in hepatocellular carcinoma, is only detectable by microscopic examination of a surgical specimen. In this study, we defined a relevant surrogate signature of microvascular invasion in hepatocellular carcinoma that may be applied in clinical practice with routine tumor biopsy and integrated into the therapeutic strategy.
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Affiliation(s)
- Aurélie Beaufrère
- Université de Paris, Paris, France; APHP, Department of Pathology, Hôpital Beaujon, 100 boulevard du Général Leclerc, Clichy, 92110, France; INSERM UMR 1149, Centre de Recherche sur l'Inflammation, 16 rue Henri Huchard, Paris, 75018, France
| | - Stefano Caruso
- Centre de Recherche des Cordeliers, INSERM, Functional Genomics of Solid Tumors laboratory, F-75006 Paris, France
| | - Julien Calderaro
- Department of Pathology, Hôpital Henri Mondor, AP-HP, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, 94010, France
| | - Nicolas Poté
- Université de Paris, Paris, France; Department of Pathology, Hôpital Bichat, AP-HP.Nord, 46 Rue Henri Huchard, Paris, 75018, France
| | - Jean-Charles Bijot
- Université de Paris, Paris, France; Department of Radiology, Hôpital Beaujon, AP-HP, 100 boulevard du Général Leclerc, Clichy, 92110, France
| | - Gabielle Couchy
- Université de Paris, Paris, France; Centre de Recherche des Cordeliers, INSERM, Functional Genomics of Solid Tumors laboratory, F-75006 Paris, France
| | - François Cauchy
- Université de Paris, Paris, France; INSERM UMR 1149, Centre de Recherche sur l'Inflammation, 16 rue Henri Huchard, Paris, 75018, France; Department of HPB and Pancreatic surgery, Beaujon AP-HP, Clichy, 92110, France
| | - Valérie Vilgrain
- Université de Paris, Paris, France; INSERM UMR 1149, Centre de Recherche sur l'Inflammation, 16 rue Henri Huchard, Paris, 75018, France; Department of Radiology, Hôpital Beaujon, AP-HP, 100 boulevard du Général Leclerc, Clichy, 92110, France
| | - Jessica Zucman-Rossi
- Université de Paris, Paris, France; Centre de Recherche des Cordeliers, INSERM, Functional Genomics of Solid Tumors laboratory, F-75006 Paris, France; Department of Oncology, Hopital Européen Georges Pompidou, AP-HP, F-75015, Paris, France
| | - Valérie Paradis
- Université de Paris, Paris, France; APHP, Department of Pathology, Hôpital Beaujon, 100 boulevard du Général Leclerc, Clichy, 92110, France; INSERM UMR 1149, Centre de Recherche sur l'Inflammation, 16 rue Henri Huchard, Paris, 75018, France.
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Du H, Tan X, Cheng L, Zhang B, Wang D. Application and Evaluation of a 64-Slice CT Three-Dimensional Fusion Technique in the Determination of the Effective Ablation Margin after Radiofrequency Ablation of Hepatocellular Carcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:6898233. [PMID: 35126633 PMCID: PMC8813220 DOI: 10.1155/2022/6898233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/02/2021] [Accepted: 12/01/2021] [Indexed: 11/24/2022]
Abstract
Due to the low accuracy of traditional three-dimensional fusion technology in radiofrequency ablation of hepatocellular carcinoma, this paper studies the advantages of three-dimensional CT fusion technology over traditional two-dimensional imaging technology in preoperative visualization and radiofrequency ablation path selection of hepatocellular carcinoma. To study the prognostic differences of hepatocellular carcinoma patients with different ablation margins (AM) in the three groups, so as to explore the best AM value, so as to minimize the liver injury caused by radiofrequency ablation. The selected patients underwent CT plain scan and three-phase enhancement at 1, 3, 6, and 12 months after operation and were rechecked every 6 months. For recurrent patients, CT was rechecked every three months. The images were obtained by GE 64-slice spiral CT. The thickness of the reconstruction layer is 1 mm, and the interval is 1 mm. The reconstructed image is imported into 3D fusion software. The three-dimensional images of tumor focus, hepatic artery, portal vein, and hepatic vein were reconstructed by two experienced doctors by superimposing the saved tumor images, merging the vascular images into the display, and measuring the ablation boundary (AM value). The results showed that the recurrence rate in group A was higher than that in group B (P = 0.041), and there was no significant difference between group B and group C (P = 1.000). Compared with traditional two-dimensional imaging, three-dimensional CT fusion technology can display the anatomical structure and three-dimensional spatial relationship of tumors and blood vessels and select the best radiofrequency ablation path, so as to achieve accurate radiofrequency ablation.
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Affiliation(s)
- Haihao Du
- Department of Radiology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450000, China
| | - Xiongmu Tan
- Department of Radiology, Sichuan Cancer Hospital, Chengdu, Sichuan 640041, China
| | - Liuhui Cheng
- Department of Radiology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450000, China
| | - Baopeng Zhang
- Department of Radiology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450000, China
| | - Daoqing Wang
- Department of Radiology, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan 450000, China
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Jiang C, Ma G, Liu Q, Song S. The value of preoperative 18F-FDG PET metabolic and volumetric parameters in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma. Nucl Med Commun 2022; 43:100-107. [PMID: 34456318 DOI: 10.1097/mnm.0000000000001478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) is very important in the evaluation of hepatocellular carcinoma (HCC), but diagnosis is determined by postoperative pathology; thus, preoperative noninvasive methods will play an active role. The purpose of the study was to assess the performance of metabolic parameters of preoperative 18F-fluorodeoxyglucose PET/computerized tomography (18F-FDG PET/CT) in the prediction of MVI and postoperative recurrence in primary hepatocellular carcinoma. METHODS We retrospectively collected 72 patients with HCC who have performed 18F-FDG PET/CT scan before partial hepatectomy between 2016 and 2019. We used both normal liver tissue and inferior vena cava as the reference background and combined with clinicopathological features, 18F-FDG PET/CT metabolic and volumetric indices to predict MVI and postoperative recurrence of primary HCC before surgery. RESULTS Twenty-one of the 72 patients recurred, in recurrent cases showed higher maximum standard uptake value (SUVmax), TNR (ratio of tumor SUVmax to mean SUV [SUVmean] of the background tissue), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than nonrecurrence cases (P < 0.001). All 18F-FDG PET metabolic and volumetric indices for predicting postoperative HCC recurrence were significant on receiver-operating-characteristic (ROC) curve analyses (P < 0.05). TNRIVC, TNRNL, MTVIVC, MTVNL TLGIVC and TLGNL were significant factors for predicting MVI in HCC (P < 0.05). On multivariate analyses, MVI, SUVmax, TNRIVC, TNRNL, MTVIVC, MTVNL, TLGIVC and TLGNL (P < 0.05) are independent risk factors for predicting postoperative HCC recurrence. TNRIVC is the most relevant PET/CT parameter for predicting MVI in HCC, and MTVIVC is the most valuable for predicting postoperative HCC recurrence. Moreover, the PET/CT parameters are more accurate for prognosis with inferior vena cava as a reference background than with normal liver tissue. CONCLUSION 18F-FDG PET/CT metabolic and volumetric indices are effective predictors, and could noninvasively provide more comprehensive predictive information on MVI and postoperative recurrence of primary HCC before surgery.
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Affiliation(s)
- Chunjuan Jiang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Guang Ma
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Qiufang Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Shaoli Song
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
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21
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Sagar VM, Herring K, Curbishley S, Hodson J, Fletcher P, Karkhanis S, Mehrzad H, Punia P, Shah T, Shetty S, Ma YT. The potential of PIVKA-II as a treatment response biomarker in hepatocellular carcinoma: a prospective United Kingdom cohort study. Oncotarget 2021; 12:2338-2350. [PMID: 34853657 PMCID: PMC8629402 DOI: 10.18632/oncotarget.28136] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 11/10/2021] [Indexed: 11/25/2022] Open
Abstract
Prothrombin induced by vitamin K absence II (PIVKA-II) has recently been validated internationally as a diagnostic biomarker for hepatocellular carcinoma (HCC), as part of the GALAD model. However, its role as a treatment response biomarker has been less well explored. We, therefore, undertook a prospective study at a tertiary centre in the UK to evaluate the role of PIVKA-II as a treatment response biomarker in patients with early, intermediate and advanced stage HCC. In a cohort of 141 patients, we found that PIVKA-II levels tracked concordantly with treatment response in the majority of patients, across a range of different treatment modalities. We also found that rises in PIVKA-II levels almost always predated radiological progression. Among AFP non-secretors, PIVKA-II was found to be informative in 60% of cases. In a small cohort of patients undergoing liver transplantation, pre-transplant PIVKA-II levels predicted for microvascular invasion and poorer differentiation. Our results demonstrate the potential utility of PIVKA-II as a treatment response biomarker and in predicting microvascular invasion, in a Western population. PIVKA-II demonstrated improved performance over AFP but, as a single biomarker, its performance was still limited. Further larger prospective studies are recommended to evaluate PIVKA-II as a treatment response biomarker, within the GALAD model.
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Affiliation(s)
- Vandana M. Sagar
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- These authors contributed equally to this work (joint first authors)
| | - Kathyrn Herring
- The Cancer Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- These authors contributed equally to this work (joint first authors)
| | - Stuart Curbishley
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - James Hodson
- Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Peter Fletcher
- Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
| | - Salil Karkhanis
- Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Homoyon Mehrzad
- Department of Radiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Pankaj Punia
- The Cancer Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Tahir Shah
- The Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Shishir Shetty
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- The Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- These authors contributed equally to this work (joint senior authors)
| | - Yuk Ting Ma
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- The Cancer Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- These authors contributed equally to this work (joint senior authors)
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22
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Lin E, Zou B, Zeng G, Cai C, Li P, Chen J, Li D, Zhang B, Li J. The impact of liver fibrosis on microvascular invasion and prognosis of hepatocellular carcinoma with a solitary nodule: a Surveillance, Epidemiology, and End Results (SEER) database analysis. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1310. [PMID: 34532447 PMCID: PMC8422100 DOI: 10.21037/atm-21-3731] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/06/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND The pathogenesis of non-cirrhotic hepatocellular carcinoma (HCC) with a high recurrence remains controversial, while microvascular invasion (MVI) is highly suggestive of tumor recurrence. This study aimed to investigate the effects of liver fibrosis on MVI and prognosis in HCC. METHODS Based on the data of HCC in the Surveillance, Epidemiology, and End Results (SEER) database [2004-2015], multivariate logistic regression was used for correlation analysis. Survival was analyzed by Log-Rank test and Cox regression, and decision curve analysis and receiver operating characteristic curves were established to evaluate alternative diagnostic and prognostic strategies. RESULTS The study included 1,492 patients with MVI (17.8%) or without MVI (82.2%) for HCC with a solitary nodule. Liver fibrosis was significantly correlated with the occurrence of MVI, and the risk of MVI in patients with a fibrosis score F5-6 was lower than in those with a score of F0-4 (OR =0.651, 95% CI: 0.492-0.860). Combining liver fibrosis could improve the prediction performance of MVI risk models, but liver fibrosis was less associated with survival outcomes in comparison with other tumor characteristics. CONCLUSIONS Lower liver fibrosis correlated with a higher risk of MVI in HCC with a solitary nodule and was a good indicator for improving the performance of MVI risk models. However, it was not a prognostic sensitive indicator.
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Affiliation(s)
- En Lin
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Baojia Zou
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Guifang Zeng
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Chaonong Cai
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Peiping Li
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jiafan Chen
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Decheng Li
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Baimeng Zhang
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jian Li
- Department of Hepatobiliary Surgery and Liver Transplantation Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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23
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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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Usta S, Kayaalp C. Tumor Diameter for Hepatocellular Carcinoma: Why Should Size Matter? J Gastrointest Cancer 2021; 51:1114-1117. [PMID: 32851543 DOI: 10.1007/s12029-020-00483-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE There are two main goals in hepatocellular carcinoma management, the first is long term survival and the second is the low recurrence rate after the treatment. Therefore, a lot of selection criteria defined for each treatment method and tumor size is one of the most important parameter in almost all of them. METHODS In this review, importance of diamater in hepatocellular carcinoma is reviewed. RESULTS Many reports showed a significant association between increase in maximum tumor diameter and microvascular invasion. Patients with larger tumors are more likely to have poorly differentiated tumors. Increased regional and distant metastasis of tumors were observed in the larger size hepatocellular carcinoma. Liver transplantation represents the best treatment option for patients with decompensated liver cirrhosis and hepatocellular carcinoma. CONCLUSIONS Combined with biological, inflammatory, radiological, pathological and genetic markers that predict the biological behavior of the tumor, today, tumor size is one of the best aggressiveness markers until new markers are found. So, tumor size is matter.
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Affiliation(s)
- Sertac Usta
- Department of Surgery, Liver Transplantation Institute, Inonu University, 44315, Malatya, Turkey.
| | - Cuneyt Kayaalp
- Department of Surgery, Liver Transplantation Institute, Inonu University, 44315, Malatya, Turkey
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25
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Hong SB, Choi SH, Kim SY, Shim JH, Lee SS, Byun JH, Park SH, Kim KW, Kim S, Lee NK. MRI Features for Predicting Microvascular Invasion of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver Cancer 2021; 10:94-106. [PMID: 33981625 PMCID: PMC8077694 DOI: 10.1159/000513704] [Citation(s) in RCA: 92] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 12/08/2020] [Indexed: 02/04/2023] Open
Abstract
PURPOSE Microvascular invasion (MVI) is an important prognostic factor in patients with hepatocellular carcinoma (HCC). However, the reported results of magnetic resonance imaging (MRI) features for predicting MVI of HCC are variable and conflicting. Therefore, this meta-analysis aimed to identify the significant MRI features for MVI of HCC and to determine their diagnostic value. METHODS Original studies reporting the diagnostic performance of MRI for predicting MVI of HCC were identified in MEDLINE and EMBASE up until January 15, 2020. Study quality was assessed using QUADAS-2. A bivariate random-effects model was used to calculate the meta-analytic pooled diagnostic odds ratio (DOR) and 95% confidence interval (CI) for each MRI feature for diagnosing MVI in HCC. The meta-analytic pooled sensitivity and specificity were calculated for the significant MRI features. RESULTS Among 235 screened articles, we found 36 studies including 4,274 HCCs. Of the 15 available MRI features, 7 were significantly associated with MVI: larger tumor size (>5 cm) (DOR = 5.2, 95% CI [3.0-9.0]), rim arterial enhancement (4.2, 95% CI [1.7-10.6]), arterial peritumoral enhancement (4.4, 95% CI [2.8-6.9]), peritumoral hypointensity on hepatobiliary phase imaging (HBP) (8.2, 95% CI [4.4-15.2]), nonsmooth tumor margin (3.2, 95% CI [2.2-4.4]), multifocality (7.1, 95% CI [2.6-19.5]), and hypointensity on T1-weighted imaging (T1WI) (4.9, 95% CI [2.5-9.6]). Both peritumoral hypointensity on HBP and multifocality showed very high meta-analytic pooled specificities for diagnosing MVI (91.1% [85.4-94.8%] and 93.3% [74.5-98.5%], respectively). CONCLUSIONS Seven MRI features including larger tumor size, rim arterial enhancement, arterial peritumoral enhancement, peritumoral hypointensity on HBP, nonsmooth margin, multifocality, and hypointensity on T1WI were significant predictors for MVI of HCC. These MRI features predictive of MVI can be useful in the management of HCC.
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Affiliation(s)
- Seung Baek Hong
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Sang Hyun Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea,*Sang Hyun Choi, Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympicro 43-gil, Songpa-gu, Seoul 05505 (Republic of Korea),
| | - So Yeon Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seong Ho Park
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyung Won Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Suk Kim
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
| | - Nam Kyung Lee
- Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea
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Wang W, Guo Y, Zhong J, Wang Q, Wang X, Wei H, Li J, Xiu P. The clinical significance of microvascular invasion in the surgical planning and postoperative sequential treatment in hepatocellular carcinoma. Sci Rep 2021; 11:2415. [PMID: 33510294 PMCID: PMC7843639 DOI: 10.1038/s41598-021-82058-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and most lethal malignant tumors in the world. Microvascular invasion (MVI) is a major risk factor for survival outcomes and intrahepatic metastasis after resection in patients with HCC. Relevant English literatures retrieved using PubMed on the research progress of MVI in patients with HCC were reviewed. For HCC patients, especially those with MVI, it is very important to develop a comprehensive and sequential treatment plan to support the long-term survival of patients. This manuscript reviewed and analyzed the risk factors for MVI; the preoperative prediction of MVI, which informs the selection of surgical strategies; and the current situation and future direction of comprehensive postoperative treatment strategies; to provide a basis for the comprehensive treatment of HCC patients with MVI. For HCC patients with MVI, the preoperative prediction of MVI may play a certain guiding role in planning procedures, and the comprehensive sequential postoperative pathological detection of HCC MVI may provide a basis for treatment decisions.
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Affiliation(s)
- Wentao Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Yaxun Guo
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jingtao Zhong
- Department of Hepatobiliary Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Qi Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
| | - Xin Wang
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Honglong Wei
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Jie Li
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China
| | - Peng Xiu
- Department of General Surgery, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, Shandong, China.
- Department of General Surgery, Shandong Provincial Qianfoshan Hospital, the First Hospital Affiliated With Shandong First Medical University, Jinan, China.
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Eguchi S, Hidaka M, Kugiyama T, Soyama A, Hara T, Nagakawa K, Adachi T, Tanaka T, Yoshimoto T, Hamada T, Matsushima H, Ito S, Kanetaka K. Changes in the Role and Mode of Liver Resection for Hepatocellular Carcinoma Over 20 Years: A Single-Center Analysis. World J Surg 2021; 45:1152-1158. [PMID: 33491142 DOI: 10.1007/s00268-020-05914-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/05/2020] [Indexed: 12/01/2022]
Abstract
INTRODUCTION The aim of this study was to analyze changes in characteristics of HCC and the modes of LR over 20 years in order to show the impact of those changes in the outcome of LR. In addition, BCLC staging was used to assess the limitations of this classification system and changes over the decade. PATIENTS AND METHODS In our department, 500 liver resections (LR) were performed for hepatocellular carcinoma (HCC) over the 20 years between January 2000 and February 2020. The 208 cases performed through 2009 were designated as Era 1, and the 292 cases between 2010 and February 2020 were termed Era 2. We analyzed changes in the characteristics of HCC and mode of LR (Study 1), and final outcomes of LR are shown according to the BCLC staging classifications and eras using data from the 5 years after LR (Study 2). RESULTS In Era 1, the mean age of the patients was 68, while in Era 2 the mean age was 71, which was significantly older than the patients in Era 1. HCC that developed from non-B, non-C liver cirrhosis was significantly increased in Era 2 (45%) as compared to that in Era 1 (34%). Laboratory data were all comparable between the eras in patients undergoing LR for HCC. The size and numbers of the HCC as well as tumor markers were similar between the eras. As to the mode of LR, although the extent of LR was similar between the eras, the laparoscopic method was significantly increased in Era 2. Blood loss was significantly lower in Era 2 (mean 519 g) than in Era 1 (1,085 g). Patient survival and recurrence-free survival (RFS) were similar between the two eras, while RFS at 5 years after LR was better in Era 2. Even in the BCLC A category, only patients with a single HCC less than 5 cm showed best results, while patients with HCC within the rest of BCLC A and BCLC B showed a dismal outcome. There was no difference in OS and RFS between the eras after stratification by BCLC. CONCLUSION There are conspicuous changes in the baseline characteristics and mode of LR over 20 years, which should be taken into account for patient care and informed consent for patients undergoing LR going forward.
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Affiliation(s)
- Susumu Eguchi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
| | - Masaaki Hidaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tota Kugiyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Akihiko Soyama
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takanobu Hara
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kantoku Nagakawa
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomohiko Adachi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takayuki Tanaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Tomoko Yoshimoto
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takashi Hamada
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Hajime Matsushima
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Sinichiro Ito
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kengo Kanetaka
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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Maebayashi T, Ishibashi N, Aizawa T, Sakaguchi M, Okada M. Stereotactic radiotherapy for hepatocellular carcinoma induced by hepatitis C and the relationships of changes in carbohydrate antigen 19-9 with AFP and PIVKA-II. Cancer Radiother 2021; 25:242-248. [PMID: 33455875 DOI: 10.1016/j.canrad.2020.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 11/26/2022]
Abstract
PURPOSE Assessing the therapeutic effects of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) takes time. Purpose of our study was to explore the relationships of changes in carbohydrate antigen 19-9 (CA 19-9) with those in the existing markers alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II). PATIENTS AND METHODS The subjects were 16 patients who underwent SBRT for solitary HCC ≤3cm induced by hepatitis C between June 2016 and July 2019. Observation periods ranged from 8-43 (median: 28) months, ages from 59-85 (median: 65) years. RESULTS Changes in CA 19-9 levels after SBRT were categorised into three patterns: 1) a transient elevation followed by a decline (75%); 2) a transient decline followed by an elevation (18.8%); and 3) no change (6.3%). Among patients showing a transient CA 19-9 elevation followed by a decline, which was the most frequent pattern, 75% showed these changes in synchronisation with AFP and preceded the changes in PIVKA-II, while in the other 25%, CA 19-9 changes were in synchronisation with PIVKA-II and preceded those in AFP. At the time of recurrence, 62.5% showed a continuous CA 19-9 elevation, either in synchronisation with other markers or by itself. CONCLUSIONS This is the first investigation of changes in CA 19-9 levels after SBRT for HCC induced by hepatitis C. Characteristic changes in CA 19-9, AFP, and PIVKA-II levels were observed as responses after treatment. As for its correlations with tumour markers, the acute responses of PIVKA-II tended to be slower than those of CA 19-9 and AFP. Although the sample size was small, our findings raise the possibility that measuring these 3 biomarkers after SBRT may be useful for monitoring patients for HCC recurrence.
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Affiliation(s)
- T Maebayashi
- Department of Radiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho Itabashi-ku, 173-8610 Tokyo, Japan.
| | - N Ishibashi
- Department of Radiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho Itabashi-ku, 173-8610 Tokyo, Japan.
| | - T Aizawa
- Department of Radiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho Itabashi-ku, 173-8610 Tokyo, Japan.
| | - M Sakaguchi
- Department of Radiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho Itabashi-ku, 173-8610 Tokyo, Japan.
| | - M Okada
- Department of Radiology, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho Itabashi-ku, 173-8610 Tokyo, Japan.
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Jin H, Zhang M, Jia K, Huang L. Efficacy of Raman spectroscopy in the diagnosis of hepatocellular carcinoma: A protocol for systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e23884. [PMID: 33350784 PMCID: PMC7769366 DOI: 10.1097/md.0000000000023884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Accepted: 11/24/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND To comprehensively analyze the relative effectiveness of Raman spectroscopy (RS) in the diagnosis of suspected hepatocellular carcinoma (HCC). METHODS We will perform a complete systematic review based on studies from PubMed/Medline, EMBASE, Web of Science, Ovid, Web of Knowledge, Cochrane Library and CNKI. We plan to identify over 2000 spectra with strict criteria in several individual studies published between January 2008 and November 2020 in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We are going to summarize the test performance using random effects models. RESULTS This study will provide solid evidence and data on the sensitivity, specificity and accuracy of RS in the diagnosis of HCC. CONCLUSION Through this meta-analysis, we intend to provide the pooled sensitivity, specificity and diagnostic accuracy of RS in the diagnosis of suspected HCC. Other parameters like positive LR, negative LR, DOR and AUC of the SROC curve will also be calculated and drawn to help illustrate the efficacy of RS in the diagnosis of HCC.
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Affiliation(s)
- Hongyu Jin
- Department of Liver Surgery & Liver Transplantation Center, West China Hospital, Sichuan University
| | - Man Zhang
- Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University; Key Laboratory of Obstetric & Gynecologic and Pediatric Disease and Birth Defects of Ministry of Education
| | | | - Libin Huang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
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Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer 2020; 9:682-720. [PMID: 33442540 PMCID: PMC7768108 DOI: 10.1159/000509424] [Citation(s) in RCA: 527] [Impact Index Per Article: 105.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 06/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. SUMMARY Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition) in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition (2019 Edition) was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. KEY MESSAGES Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People's Republic of China in December 2019.
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Affiliation(s)
- Jian Zhou
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Huichuan Sun
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenming Cong
- Department of Pathology, The Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianhua Wang
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ping Bie
- Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Lianxin Liu
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Guohong Han
- Department of Liver Diseases and Digestive Interventional Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Maoqiang Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China
| | - Ruibao Liu
- Department of Interventional Radiology, The Tumor Hospital of Harbin Medical University, Harbin, China
| | - Ligong Lu
- Department of Interventional Oncology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhengang Ren
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Minshan Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Zhaochong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Changhong Liang
- Department of Radiology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Min Chen
- Editorial Department of Chinese Journal of Digestive Surgery, Chongqing, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Wenping Wang
- Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jingping Yun
- Department of Pathology, Tumor Prevention and Treatment Center, Sun Yat-sen University, Guangzhou, China
| | - Dingfang Cai
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongjun Chen
- Department of Hematology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenwu Cheng
- Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shuqun Cheng
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Spleenary Surgery, The Affiliated Shengjing Hospital, China Medical University, Shenyang, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Baojin Hua
- Graduate School, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaowu Huang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Weidong Jia
- Department of Hepatic Surgery, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China
| | - Yaming Li
- Department of Nuclear Medicine, The First Hospital of China Medical University, Shenyang, China
| | - Yexiong Li
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Tianshu Liu
- Department of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guoyue Lv
- Department of General Surgery, The First Hospital of Jilin University, Jilin, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Weixin Ren
- Department of Interventional Radiology The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Guoming Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoying Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiming Wang
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Bangde Xiang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Baocai Xing
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital and Institute, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, China
| | - Jiamei Yang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jianyong Yang
- Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yefa Yang
- Department of Hepatic Surgery & Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yunke Yang
- Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shenglong Ye
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhengyu Yin
- Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, Hubing South Road, Xiamen, China
| | - Bixiang Zhang
- Department of Surgery, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Boheng Zhang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Leida Zhang
- Department of Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yongfu Zhao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, ZhengZhou, China
| | - Honggang Zheng
- Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rong Liu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yinghong Shi
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yongsheng Xiao
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhi Dai
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gaojun Teng
- Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - Jianqiang Cai
- Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Feng Shen
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shukui Qin
- Department of Medical Oncology, PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China
| | - Jiahong Dong
- Department of Hepatobiliary and Pancreas Surgery, Beijing Tsinghua Changgung Hospital (BTCH), School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Jia Fan
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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Isik B, Gonultas F, Sahin T, Yilmaz S. Microvascular Venous Invasion in Hepatocellular Carcinoma: Why Do Recurrences Occur? J Gastrointest Cancer 2020; 51:1133-1136. [PMID: 32839943 DOI: 10.1007/s12029-020-00487-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE Hepatocellular carcinoma is the most common primary cancer of the liver. It is almost always associated with cirrhosis and it is usually diagnosed in later stages of the disease. Furthermore, recurrence rate following liver transplantation ranges between 15 and 30%. The most important factor determining the recurrence is vascular invasion. METHODS In this review, the issue of microvascular invasion causing hepatocellular carcinoma recurrence is reviewed. Macroscopic vascular invasion is almost easy to diagnose on radiologic evaluation. However, microscopic vascular invasion is almost always diagnosed with pathologic evaluation. On the other hand, microscopic vascular invasion is associated with early recurrences and reduced disease-free survival. The type of vessel that is invaded determines the nature of the spread of the tumor cells. Invasion of the hepatic venous tributaries leads to systemic metastasis whereas portal venous invasions lead to intrahepatic spread of the tumor. Microscopic vascular invasion should be diagnosed before liver transplantation or liver resection in order to deliver the appropriate therapy to the patients. RESULTS Yet, there is no ideal marker to suggest microscopic vascular invasion before any intervention. Markers such as alpha-fetoprotein, des carboxy prothrombin, or gamma-glutamyl transferase have been found to be correlated with microscopic vascular invasion. These parameters are not very efficient to be used in routine clinical practice. CONCLUSION Therefore, further research is needed to define ideal marker associated with microscopic vascular invasion.
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Affiliation(s)
- Burak Isik
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Fatih Gonultas
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Tolga Sahin
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey
| | - Sezai Yilmaz
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, 244280, Malatya, Turkey.
- Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, 44280, Malatya, Turkey.
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Si YQ, Wang XQ, Fan G, Wang CY, Zheng YW, Song X, Pan CC, Chu FL, Liu ZF, Lu BR, Lu ZM. Value of AFP and PIVKA-II in diagnosis of HBV-related hepatocellular carcinoma and prediction of vascular invasion and tumor differentiation. Infect Agent Cancer 2020; 15:70. [PMID: 33292429 PMCID: PMC7684907 DOI: 10.1186/s13027-020-00337-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 11/13/2020] [Indexed: 02/06/2023] Open
Abstract
Background To explore the value of alpha fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in diagnosis of HBV-related hepatocellular carcinoma (HCC) and their relationship with vascular invasion, tumor differentiation and size. Methods A total of 433 participants were enrolled in this study including 266 cases with HBV-related HCC, 87 cases with HBV DNA positive benign liver disease and 80 healthy individuals. Then we explored the correlation between AFP, PIVKA-II serum level and several pathological features such as vascular invasion, tumor differentiation and size. The value of these two markers used singly or jointly in diagnosing HBV-related HCC was evaluated by receiver operating characteristic (ROC) curve. The ROC curve was also plotted to identify AFP, PIVKA-II serum cut-off values that would best distinguish HBV-related HCC patients with and without vascular invasion. Results The level of AFP and PIVKA-II in HBV-related HCC group was significantly higher (Z was 7.428, 11.243 respectively, all P < 0.01). When AFP and PIVKA-II were used as the individual tumor marker, the areas under the ROC curve (AUC) of HBV-related HCC diagnosis were 0.765 (95% CI, 0.713 ~ 0.8170) for AFP, 0.901 (95% CI, 0.868 ~ 0.935) for PIVKA-II, and 0.917 (95% CI, 0.886 ~ 0.948) for AFP and PIVKA-II simultaneously. The serum levels of AFP and PIVKA-II were positively correlated with tumor differentiation and size. High AFP and PIVKA-II expression was significantly associated with the presence of vascular invasion (P was 0.007 and 0.014 respectively). The AFP level > 64.4 ng/ml or PIVKA-II level > 957.61mAU/ml was the best critical value to predict the presence of vascular invasion. Conclusion Our results validate that AFP and PIVKA-II play a significant role in the diagnosis of HBV-related HCC. The diagnostic value of AFP and PIVKA-II combined detection or single assay of PIVKA-II is higher than that of separate assay of AFP. Moreover, their concentration has important clinical value in judging tumor size, tumor cell differentiation and vascular invasion.
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Affiliation(s)
- Yuan-Quan Si
- Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, PR China.,Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Xiu-Qin Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Gang Fan
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Chang-Yin Wang
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Yuan-Wen Zheng
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Xie Song
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Cui-Cui Pan
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Fu-Lu Chu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Zhan-Feng Liu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Bing-Ru Lu
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China
| | - Zhi-Ming Lu
- Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, Shandong, PR China. .,Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, PR China.
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CT Image-Based Texture Analysis to Predict Microvascular Invasion in Primary Hepatocellular Carcinoma. J Digit Imaging 2020; 33:1365-1375. [PMID: 32968880 DOI: 10.1007/s10278-020-00386-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Revised: 08/29/2020] [Accepted: 09/14/2020] [Indexed: 12/15/2022] Open
Abstract
The objective of this study was to determine the clinical value of computed tomography (CT) image-based texture analysis in predicting microvascular invasion of primary hepatocellular carcinoma (HCC). CT images of patients with HCC from May 2017 to May 2019 confirmed by surgery and histopathology were retrospectively analyzed. Image features including tumor margin, tumor capsule, peritumoral enhancement, hypoattenuating halo, intratumoral arteries, and tumor-liver differences were assessed. All patients were divided into microvascular invasion (MVI)-negative group (n = 34) and MVI-positive group (n = 68). Preoperative CT images were further imported into MaZda software, where the regions of interest of the lesions were manually delineated. Texture features of lesions based on pre-contrast, arterial, portal, and equilibrium phase CT images were extracted. Thirty optimal texture parameters were selected from each phase by Fisher's coefficient (Fisher), classification error probability combined with average correlation coefficient (POE+ACC), and mutual information (MI). Finally, receiver operating characteristic curve analysis was performed. The results showed that the Edmonson-Steiner grades, tumor size, tumor margin, and intratumoral artery characteristics were significantly different between the two groups (P = 0.012, < 0.001, < 0.001, = 0.003, respectively). There were 58 parameters with significant differences between the MVI-negative and MVI-positive groups (P < 0.001 for all). Among them, 12, 14, 17, and 15 parameters were derived from the pre-contrast phase, arterial phase, portal phase, and equilibrium phase respectively. According to the ROC analysis, optimal texture parameters based on the pre-contrast, arterial, portal, and equilibrium phases were 135dr_GLevNonU (AUC, 0.766; the cutoff value, 1055.00), Vertl_RLNonUni (AUC, 0.764; the cutoff value, 5974.38), 45dgr_GLevNonU (AUC, 0.762; the cutoff value, 924.34), and Vertl_RLNonUni (AUC, 0.754; the cutoff value, 4868.80), respectively. Texture analysis of preoperative CT images may be used as a non-invasive method to predict microvascular invasion in patients with primary hepatocellular carcinomas, and further to guide the treatment and evaluate prognosis. The most valuable parameters were derived from the gray-level run-length matrix.
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Zhang Z, Chen J, Jiang H, Wei Y, Zhang X, Cao L, Duan T, Ye Z, Yao S, Pan X, Song B. Gadoxetic acid-enhanced MRI radiomics signature: prediction of clinical outcome in hepatocellular carcinoma after surgical resection. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:870. [PMID: 32793714 PMCID: PMC7396783 DOI: 10.21037/atm-20-3041] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 05/15/2020] [Indexed: 02/05/2023]
Abstract
BACKGROUND This study aimed to evaluate the efficiency of gadoxetic acid-enhanced MRI-based radiomics features for prediction of overall survival (OS) in hepatocellular carcinoma (HCC) patients after surgical resection. METHODS This prospective study approved by the Institutional Review Board enrolled 120 patients with pathologically confirmed HCC. Radiomics signatures (rad-scores) were built from radiomics features in 3 different regions of interest (ROIs) with the least absolute shrinkage and selection operator (LASSO) cox regression analysis. Preoperative clinical characteristics and semantic imaging features potentially associated with patient survival were evaluated to develop a clinic-radiological model. The radiomics features and clinic-radiological predictors were integrated into a joint model using multivariable Cox regression analysis. Kaplan-Meier analysis and log-rank tests were performed to compare the discriminative performance and evaluated on the validation cohort. RESULTS The radiomics signatures showed a significant association with patient survival in both cohorts (all P<0.001). The BCLC (Barcelona clinic liver cancer) stage, non-smooth tumor margin, and the combined rad-score were independently associated with OS. Moreover, the combined model incorporating with clinic-radiological and radiomics features showed an improved predictive performance with C-index of 0.92 [95% confidence interval (CI): 0.87-0.97], compared to the clinic-radiological model (C-index, 0.86, 95% CI: 0.79-0.94; P=0.039) or the combined rad-score (C-index, 0.88, 95% CI: 0.81-0.95; P=0.016). CONCLUSIONS Radiomics features along with clinic-radiological predictors can efficiently aid in preoperative HCC prognosis prediction after surgical resection and enable a step forward precise medicine.
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Affiliation(s)
- Zhen Zhang
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Hanyu Jiang
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Yi Wei
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Xin Zhang
- GE Healthcare, MR Research China, Beijing, China
| | - Likun Cao
- Department of Radiology, Peking Union Medical College Hospital (Dongdan campus), Beijing, China
| | - Ting Duan
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Ye
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Shan Yao
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Xuelin Pan
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital of Sichuan University, Chengdu, China
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Zhang T, Pandey G, Xu L, Chen W, Gu L, Wu Y, Chen X. The Value of TTPVI in Prediction of Microvascular Invasion in Hepatocellular Carcinoma. Cancer Manag Res 2020; 12:4097-4105. [PMID: 32581583 PMCID: PMC7276193 DOI: 10.2147/cmar.s245475] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose The objective of our study was to evaluate the value of two-trait predictor of venous invasion (TTPVI) in the prediction of pathological microvascular invasion (pMVI) in patients with hepatocellular carcinoma (HCC) from preoperative computed tomography (CT) and magnetic resonance (MR). Methods A total of 128 preoperative patients with findings of HCC were enrolled. Tumor size, tumor margins, tumor capsule, peritumoral enhancement, and TTPVI was assessed on preoperative CT and MRI images. Histopathological features were reviewed: pathological tumor size, tumor differentiation, pMVI along with alpha-fetoprotein level (AFP). Significant imaging findings and histopathological features were determined with univariate and multivariate logistic regression analysis. Results Univariate analysis revealed that tumor size (p<0.01), AFP level (p=0.043), tumor differentiation (p<0.01), peritumoral enhancement (p=0.003), pathological tumor size (p<0.01), tumor margins (p<0.01) on CT and MRI, and TTPVI (p<0.01) showed statistically significant associations with pMVI. In multivariate logistic regression analysis, tumor size (odds ratio [OR] = 1.294; 95% confidence interval [CI]: 1.155, 1.451; p < 0.001), tumor differentiation (odds ratio [OR] =1.384; 95% confidence interval [CI]: 1.224, 1.564; p < 0.001), and TTPVI (odds ratio [OR] = 4.802; 95% confidence interval [CI]: 1.037, 22.233; p=0.045) were significant independent predictors of pMVI. Using 5.8 as the threshold for size, one could obtain an area-under-curve (AUC) of 0.793, 95% confidence interval [CI]: 0.715 to 0.857. Conclusion Tumor size, tumor differentiation, and TTPVI depicted in preoperative CT and MRI had a statistically significant correlation with pMVI. Hence, TTPVI detected on CT and MRI may be predictive of pMVI in HCC cases.
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Affiliation(s)
- Tao Zhang
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Gaurab Pandey
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Lin Xu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Wen Chen
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Liangrui Gu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Yijun Wu
- Department of Radiology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
| | - Xiuwen Chen
- Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China
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Prediction of HCC microvascular invasion with gadobenate-enhanced MRI: correlation with pathology. Eur Radiol 2020; 30:5327-5336. [PMID: 32367417 DOI: 10.1007/s00330-020-06895-6] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Revised: 03/04/2020] [Accepted: 04/14/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To assess the accuracy of gadobenate-enhanced MRI for predicting microvascular invasion (MVI) in patients operated for hepatocellular carcinoma (HCC). METHODS The 164 patients who met the inclusion criteria were assigned to one of two groups: the MVI-positive group and the MVI-negative group. Imaging results were compared between the two groups using the Kruskal test, chi-square test, independent sample t test, and logistic regression analysis. RESULTS Differences in the capsule (p = 0.037) and margin (p = 0.004) of the tumor, rim enhancement (p = 0.002), peritumoral enhancement in the arterial phase (p < 0.001), and peritumoral hypointensity in the hepatobiliary phase (HBP) (p < 0.001) were statistically significant. The results of multivariate analysis identified rim enhancement in the arterial phase (odds ratio (OR) = 2.115; 95% confidence interval (CI), 1.002-4.464; p = 0.049) and peritumoral hypointensity in the HBP (OR = 5.836; 95% CI, 2.442-13.948; p < 0.001) as independent risk factors for MVI. Use of the two predictors in combination identified 32.79% (20/61) of HCCs with MVI with a specificity of 95.15% (98/103). CONCLUSIONS Rim enhancement in the arterial phase and peritumoral hypointensity in the HBP were identified as independent risk factors for MVI in patients with HCC. KEY POINTS • Rim enhancement in the arterial phase and peritumoral hypointensity in the hepatobiliary phase were independent risk factors for microvascular invasion in patients with HCC. • Use of the two predictors in combination had a sensitivity of 32.79% and a specificity of 95.15% for predicting microvascular invasion.
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Wang P, Xu LL, Zheng XB, Hu YT, Zhang JF, Ren SS, Hao XY, Li L, Zhang M, Xu MQ. Correlation between the expressions of circular RNAs in peripheral venous blood and clinicopathological features in hepatocellular carcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:338. [PMID: 32355782 PMCID: PMC7186655 DOI: 10.21037/atm.2020.02.134] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background Recent studies have reported that circular RNAs (circRNAs) are involved in the development of hepatocellular carcinoma (HCC). This study evaluated the expression of preoperative peripheral venous blood circRNAs in HCC patients and their predictive ability for microvascular invasion (MVI). Methods Seven circRNAs (circMTO1, circ-10720, circZKSCAN1, cSMARCA5, circHIPK3, circSETD3 and ciRS-7) were screened from the literature as circRNAs with reported biological functions in HCC. The expression levels of seven circRNAs in preoperative blood samples and HCC tissues were detected by quantitative reverse transcription polymerase chain reaction. The correlations between the circRNA expressions in blood and the clinicopathological factors of HCC patients were analyzed. The risk factors of MVI were analyzed by univariate and multivariate logistic regression. The functional role of circSETD3 in cell migration and invasion was evaluated by wound healing and Transwell assays in vitro. Results The expressions of all seven circRNAs were measured in peripheral venous blood samples. The venous expression levels of circHIPK3 and circMTO1 were significantly associated with gender, while circ-10720 and circMTO1 levels were significantly correlated with gross vascular invasion. Furthermore, circMTO1 and cSMARCA5 levels were significantly associated with alpha-fetoprotein level and ciRS-7 was significantly associated with satellite nodules. Importantly, low venous circSETD3 expression was significantly associated with prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) level, MVI, gross vascular invasion, and liver capsule. Furthermore, venous circSETD3 expression had predictive ability for MVI. Knockdown of circSETD3 promoted cell invasion and metastasis in vitro. Conclusions CircRNAs were stably present in peripheral venous blood and associated with multiple clinicopathological characteristics of HCC patients. Venous circSETD3 was an independent risk factor of MVI and shows ability to predict MVI in HCC patients before surgery.
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Affiliation(s)
- Peng Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Liang-Liang Xu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiao-Bo Zheng
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yi-Tao Hu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Jin-Fu Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Sheng-Sheng Ren
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiang-Yong Hao
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.,Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China
| | - Lian Li
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Ming Zhang
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.,Department of General Surgery, Mianzhu Hospital of West China Hospital, Sichuan University, Mianzhu 618200, China
| | - Ming-Qing Xu
- Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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Sun J, Zhang A, Li W, Wang Q, Wang J, Fan Y, Sun Y, Li D, Zhang D, Duan X. CyberKnife Stereotactic Body Radiation Therapy as an Effective Treatment for Hepatocellular Carcinoma Patients With Decompensated Cirrhosis. Front Oncol 2020; 10:100. [PMID: 32158688 PMCID: PMC7052044 DOI: 10.3389/fonc.2020.00100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/20/2020] [Indexed: 12/24/2022] Open
Abstract
Purpose: The aim of our study was to evaluate the curative effect and safety of CyberKnife stereotactic body radiation therapy in treating decompensated cirrhosis hepatocellular carcinoma (HCC) patients. Methods: From March 2011 to December 2015, 32 HCC patients who refused or were ineligible for other treatments were treated with CyberKnife stereotactic body radiation therapy. Among these patients, 17 were Child-Pugh score 7 (53.13%), 7 were Child-Pugh score 8 (21.87%), 4 were Child-Pugh score 9 (12.50%), and 4 were Child-Pugh score 10 (12.50%). A total dose of 45-54 Gy in 5-10 fractions was given according to the location of lesions. Results: The median follow-up period was 30 months (8-46 months). By July 2019, the tumors were recurrent or metastasized in 17 patients. The overall survival rates of 1, 2, and 3 years were 84.4, 61.8, and 46.0%, respectively. After 1, 2, and 3 years, the local control rates were 92.9%. The progression-free survival rates of the 1, 2, and 3-year treatments were 73.8, 44.6, and 33.4%, respectively. Conclusions: CyberKnife stereotactic body radiation therapy was an effective option for HCC patients with decompensated cirrhosis. The liver injury occurrence rate was acceptable in our study.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Xuezhang Duan
- Radiation Oncology Center, The Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), Beijing, China
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Zhang H, Zhou Y, Li Y, Qin W, Zi Y, Liu Y, Qiu X, Xu H, Liao W, Huang Z. Predictive value of gamma-glutamyl transpeptidase to lymphocyte count ratio in hepatocellular carcinoma patients with microvascular invasion. BMC Cancer 2020; 20:132. [PMID: 32070301 PMCID: PMC7029459 DOI: 10.1186/s12885-020-6628-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 02/11/2020] [Indexed: 12/24/2022] Open
Abstract
Background Microvascular invasion (MVI) is an independent risk factor for poor prognosis in hepatocellular carcinoma (HCC). However, there is still a lack of preoperative markers to predict MVI in HCC. This study intends to explore the potential application value of the gamma-glutamyl transpeptidase (GGT) to lymphocyte count ratio (GLR) in predicting MVI in HCC and provide guidance for clinical diagnosis and treatment. Methods From March 2010 to December 2015, 230 HCC patients who underwent surgical treatment in the Affiliated Hospital of Guilin Medical University were selected. Clinicopathological parameters between the MVI group (n = 115) and the non-MVI group (n = 115) were comparatively analyzed. The GLR was used as the potential risk factor for HCC with MVI, and its optimal cut-off value was estimated by using the receiver operating characteristic (ROC) curve. The Kaplan-Meier method was used to analyze the survival of HCC patients, and univariate and multivariate Cox regression analyses were used to establish independent predictors affecting postoperative HCC patients. Results The GLR levels in the MVI group and non-MVI group were 84.83 ± 61.84 and 38.42 ± 33.52 (p < 0.001), respectively. According to ROC curve analysis, the optimal cut-off value of GLR was 56.0, and the area under the ROC curve (AUC) was 0.781 (95% CI, 0.719–0.833) for the risk prediction of MVI in HCC patients. Multivariate analysis showed that tumor size > 5 cm, HCC combined with MVI and GLR > 56.0 were independent risk factors for poor prognosis in HCC patients. In addition, compared with the non-MVI group, patients in the MVI group had shorter progression-free survival (PFS) and overall survival (OS). Conclusion GLR could be a predictive biomarker of HCC after operation and a potential predictor of HCC combined with MVI.
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Affiliation(s)
- Hongxing Zhang
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Yu Zhou
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Yicheng Li
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.,Second clinical medical college, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China
| | - Wanying Qin
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Yunhua Zi
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Yulan Liu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Xiaoying Qiu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Hongyuan Xu
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Weijia Liao
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
| | - Zhaoquan Huang
- Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China. .,Department of Pathology, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
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Qin JM. Postoperative recurrent factors and therapeutic and preventive strategies for hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2019; 27:1407-1418. [DOI: 10.11569/wcjd.v27.i23.1407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The recurrence rate is about 50% at 3 years and over 70% at 5 years after hepatectomy for HCC. The high recurrence rate seriously affects the curative effect and long-term survival of patients with HCC, and is the primary cause of death after operation. Postoperative recurrence of HCC is a complex multi-step, multi-factorial process involving three factors: the body, microenvironment, and tumor tissue, which include body immunity, local pH value, interstitial pressure, vascular osmotic pressure, inflammatory reaction, tumor cell adhesion, extracellular matrix degradation, cell migration, cell proliferation, and tumor angiogenesis. HCC recurrence is closely related to abnormal gene expression and related molecular function changes, but the molecular mechanism has not been fully elucidated. How to treat the recurrence of HCC after operation directly affects the prognosis of patients with HCC, and treatments include reoperation, liver transplantation, local minimally invasive treatment, radiotherapy, molecular targeted drugs, immunotherapy, and traditional Chinese medicine treatment. It is difficult to cure or control tumor progression by a single therapy. Two or more therapeutic methods need to be combined organically to achieve a synergistic therapeutic effect. According to the specific situation of patients with HCC, it is key to analyze the individual characteristics of patients, to combine the clinical experience of clinicians and the best evidence, to adopt the individualized treatment plan, and to choose the appropriate treatment methods. For HCC patients with high-risk factors for recurrence, selecting the appropriate treatment is important to reduce the recurrence of HCC after operation and prolong the survival of patients.
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Affiliation(s)
- Jian-Min Qin
- Department of General Surgery, the Third Hospital Affiliated to Naval Military Medical University, Shanghai 201805, China
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Nomogram to Assist in Surgical Plan for Hepatocellular Carcinoma: a Prediction Model for Microvascular Invasion. J Gastrointest Surg 2019; 23:2372-2382. [PMID: 30820799 DOI: 10.1007/s11605-019-04140-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 01/23/2019] [Indexed: 01/31/2023]
Abstract
BACKGROUND Microvascular invasion (MVI) relates to poor survival in hepatocellular carcinoma (HCC) patients. In this study, we aim at developing a nomogram for MVI prediction and potential assistance in surgical planning. METHODS A total of 357 patients were assigned to training (n = 257) and validation (n = 100) cohort. Univariate and multivariate analyses were used to reveal preoperative predictors for MVI. A nomogram incorporating independent predictors was constructed and validated. Disease-free survival was compared between patients, and the potential of the predicted MVI in making surgical procedure was also explored. RESULTS Pathological examination confirmed MVI in 140 (39.2%) patients. Imaging features including larger tumor, intra-tumoral artery, tumor type, and higher serum AFP independently correlated with MVI. The nomogram showed desirable performance with an AUROC of 0.803 (95% CI, 0.746-0.860) and 0.814 (95% CI, 0.720-0.908) in the training and validation cohorts, respectively. Good calibration were also revealed by calibration curve in both cohorts. The decision curve analysis indicated that the prediction nomogram was of promising usefulness in clinical work. In addition, survival analysis revealed that patients with positive-predicted MVI suffered a higher risk of early recurrence (P < 0.01). There was no difference in disease-free survival between anatomic or non-anatomic resection in large HCC or small HCC without nomogram-predicted MVI. However, anatomic resection improved disease-free survival in small HCC with nomogram-predicted MVI. CONCLUSIONS The nomogram obtained desirable results in predicting MVI. Patients with predicted MVI were associated with early recurrence and anatomic resection was recommended for small HCC patients with predicted MVI.
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Song W, Yu X, Guo D, Liu H, Tang Z, Liu X, Zhou J, Zhang H, Liu Y, Liu X. MRI-Based Radiomics: Associations With the Recurrence-Free Survival of Patients With Hepatocellular Carcinoma Treated With Conventional Transcatheter Arterial Chemoembolization. J Magn Reson Imaging 2019; 52:461-473. [PMID: 31675174 DOI: 10.1002/jmri.26977] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 10/05/2019] [Accepted: 10/07/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Preoperative estimation of hepatocellular carcinoma (HCC) recurrence after conventional transcatheter arterial chemoembolization (c-TACE) is crucial for subsequent follow-up and therapy decisions. PURPOSE To evaluate the associations of radiomics models based on pretreatment contrast-enhanced MRI, a clinical-radiological model and a combined model with the recurrence-free survival (RFS) of patients with HCC after c-TACE, and to develop a radiomics nomogram for individual RFS estimations and risk stratification. STUDY TYPE Retrospective. POPULATION In all, 184 consecutive HCC patients. FIELD STRENGTH/SEQUENCE 1.5T or 3.0T, including T2 WI, T1 WI, and contrast-enhanced T1 WI. ASSESSMENT All HCC patients were randomly divided into the training (n = 110) and validation datasets (n = 74). Radiomics signatures capturing intratumoral and peritumoral expansion (1, 3, and 5 mm) were constructed, and the radiomics models were set up using least absolute shrinkage and selection operator (LASSO) Cox regression. Clinical-radiological features were identified by univariate and multivariate Cox regression. The clinical-radiological model and the combined model fusing the radiomics signature with the clinical-radiological risk factors were developed by a multivariate Cox proportional hazard model. A radiomics nomogram derived from the combined model was established. STATISTICAL TESTS LASSO Cox regression, univariate and multivariate Cox regression, Kaplan-Meier analysis were performed. The discrimination performance of each model was quantified by the C-index. RESULTS Among the different peritumoral expansion models, only the 3-mm peritumoral expansion model (C-index, 0.714) showed a comparable performance (P = 0.4087) to that of the portal venous phase intratumoral model (C-index, 0.727). The combined model showed the best performance and the C-index was 0.802. Kaplan-Meier analysis showed that the cutoff values of the combined model relative to a median value (1.7426) perfectly stratified these patients into high-risk and low-risk subgroups. DATA CONCLUSION The combined model is more valuable than the clinical-radiological model or radiomics model alone for evaluating the RFS of HCC patients after c-TACE, and the radiomics nomogram can be used to preoperatively and individually estimate RFS. LEVEL OF EVIDENCE 3 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;52:461-473.
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Affiliation(s)
- Wenlong Song
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiangling Yu
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dajing Guo
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | | | - Zhuoyue Tang
- Department of Radiology, Chongqing General Hospital, Chongqing, China
| | - Xinjie Liu
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jun Zhou
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haiping Zhang
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yangyang Liu
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xi Liu
- Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Lim C, Salloum C, Chalaye J, Lahat E, Costentin CE, Osseis M, Itti E, Feray C, Azoulay D. 18F-FDG PET/CT predicts microvascular invasion and early recurrence after liver resection for hepatocellular carcinoma: A prospective observational study. HPB (Oxford) 2019; 21:739-747. [PMID: 30401520 DOI: 10.1016/j.hpb.2018.10.007] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 09/17/2018] [Accepted: 10/10/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND This study assessed the prognostic value of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) in the prediction of MVI and early recurrence following resection. METHOD This prospective study (ClinicalTrials.gov ID: NCT02145013) included 78 consecutive HCC patients who underwent 18F-FDG PET/CT before curative-intent resection from 2014 to 2017. Prognostic factors available before surgery for predicting MVI and early recurrence (≤2 years) were identified by univariate and multivariate analyses. RESULTS The 18F-FDG PET/CT result was positive in 30 (38%) patients. MVI was present in 33% (26/78) of specimens. Early recurrence occurred in 19% (14/74) of surviving patients. PET/CT positivity was the sole independent predictor of MVI (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-11.2; p = 0.03), with a specificity and sensitivity for predicting MVI of 73% and 62%, respectively. Analysis of variables available before surgery showed that PET/CT positivity (hazard ratio [HR] = 5.8, 95% CI = 1.6-20.4; p = 0.006) and the male sex (HR = 6.6; 95% CI = 1.8-24.2; p = 0.005) were independent predictors of early recurrence. CONCLUSION 18F-FDG PET/CT predicts MVI and early recurrence after surgery for HCC and could be used to select patients for neoadjuvant treatment.
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Affiliation(s)
- Chetana Lim
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Chady Salloum
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Julia Chalaye
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Eylon Lahat
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | | | - Michael Osseis
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France
| | - Emmanuel Itti
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Cyrille Feray
- Department of Nuclear Medicine, Henri Mondor Hospital, Créteil APHP, France
| | - Daniel Azoulay
- Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil APHP, France.
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Clinical significance of glypican-3-positive circulating tumor cells of hepatocellular carcinoma patients: A prospective study. PLoS One 2019; 14:e0217586. [PMID: 31141571 PMCID: PMC6541303 DOI: 10.1371/journal.pone.0217586] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 05/14/2019] [Indexed: 12/15/2022] Open
Abstract
The utility of glypican-3 (GPC3) expression for the detection of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients has not been elucidated. The aim of this study was to identify associations between the presence of GPC3-positive CTCs and clinicopathological factors of these patients, furthermore, to evaluate whether CTC can predict microscopic portal vein invasion (mPVI). This study was done on 85 patients who underwent hepatectomy as the first-line treatment and whose preoperative imaging showed no evidence of macroscopic PVI and distant metastases. Peripheral blood was collected from all patients immediately before surgery. Cells were purified initially by density gradient centrifugation followed by immunomagnetic positive enrichment based upon the expression of GPC3. The numbers of CTCs contained in the enriched samples were enumerated via flow cytometry. Protocol validation using HepG2 cells spiked into 8.0 mL of blood from a healthy volunteer indicated that we were able to recover 12.1% of the tumor cells. A median number of 3 CTCs (range: 0-27) was detected in the 8.0 mL of peripheral blood of the 85 analyzed HCC patients. Thirty-three patients had CTCs ≥5, and these patients had a higher incidence of mPVI (p < 0.001), a lower disease-free survival (p = 0.015), and a lower overall survival (p = 0.047) than those with CTCs <5. Multivariate analysis identified CTCs ≥5 as an independent predictor of mPVI (p < 0.001). In conclusion, preoperative GPC3-positive CTCs ≥5 was a risk factor of mPVI and poor prognosis, and therefore may be a useful biomarker for HCC patient outcomes.
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Shimada S, Kamiyama T, Yokoo H, Orimo T, Nagatsu A, Ohata T, Kamachi H, Taketomi A. Prognoses and Clinicopathological Characteristics for Hepatocellular Carcinoma Originating from the Caudate Lobe After Surgery. World J Surg 2019; 43:1085-1093. [PMID: 30478681 DOI: 10.1007/s00268-018-4869-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND The aim was to evaluate the prognoses and clinicopathological characteristics of solitary hepatocellular carcinoma (HCC) originating from the caudate lobe (HCC-CL). METHODS We analyzed 584 patients with a solitary tumor <10 cm from January 1990 to November 2014. Patients were classified into a caudate lobe group (CL; n = 39) and a non-caudate lobe group (NCL; n = 545). We investigated the prognoses and clinicopathological characteristics of solitary HCC-CL. We compared the surgical procedures performed in these cases. RESULTS HCC-CL had a similar rate of portal venous invasion (PVI) as HCC-NCL (21% vs. 19%); however, the frequency of tumor thrombus at the first branch of the portal vein (PV) or extension to the trunk or the opposite side of the PV was significantly higher in HCC-CL (8% vs. 2%). HCC-CL had similar OS rates compared to HCC-NCL; however, HCC-CL showed significantly poorer RFS. Although there were no significant differences among the three surgical procedures, blood loss and complication rates tended to be higher in cases who underwent an isolated caudate lobectomy. Tumor size ≥5 cm, PVI, and liver fibrosis or cirrhosis (LF or LC) were independent unfavorable factors for both OS and RFS. PIVKA-II ≥120 mAU/ml was an independent unfavorable factor for RFS. CONCLUSION HCC-CL presented a poorer RFS rate. Patients with a tumor size ≥5 cm, PIVKA-II ≥120 mAU/ml, portal venous invasion, and LF or LC should be diligently followed up as these cases have a high risk of recurrence.
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Affiliation(s)
- Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Hideki Yokoo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takanori Ohata
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, North 15-West 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan
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Ke RS, Cai QC, Chen YT, Lv LZ, Jiang Y. Diagnosis and treatment of microvascular invasion in hepatocellular carcinoma. Eur Surg 2019. [DOI: 10.1007/s10353-019-0573-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Abstract
We discuss various imaging features that have been reported to be associated with the prognosis of hepatocellular carcinoma (HCC) but not included in the current staging systems: findings related with microvascular invasion, tumor encapsulation, intratumoral fat, presence of satellite nodules, peritumoral hypointensity on hepatobiliary phase images of gadoxetic-acid enhanced MRI, restricted diffusion, and irregular rim-like hyperenhancement. Current evidence suggests that larger (> 2 cm) tumor size, presence of satellite nodules, presence of irregular rim-like hyperenhancement of a tumor, peritumoral parenchymal enhancement in the arterial phase, and peritumoral hypointensity observed on hepatobiliary phase images are independent imaging features to portend a worse prognosis in patients with hepatocellular carcinoma.
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Rungsakulkij N, Mingphruedhi S, Suragul W, Tangtawee P, Muangkaew P, Aeesoa S. Platelet-to-Lymphocyte Ratio and Large Tumor Size Predict Microvascular Invasion after Resection for Hepatocellular Carcinoma. Asian Pac J Cancer Prev 2018; 19:3435-3441. [PMID: 30583666 PMCID: PMC6428560 DOI: 10.31557/apjcp.2018.19.12.3435] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: Recurrence after curative resection of hepatocellular carcinoma (HCC) is associated with early death and poor prognosis. Microvascular invasion (mVI) is strongly associated with disease recurrence. Although many studies have examined the relationship between various serum inflammatory indices and post-treatment prognosis, little is known about preoperative predictors of microvascular invasion in HCC. Methods: Patients who underwent curative hepatic resection for HCC at our institute from January 2006 to December 2016 were retrospectively reviewed. The associations between mVI and various potential risk factors, including tumor size, hepatitis B and C virus infection, Child–Pugh scores, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio, were analyzed. Optimal cut-off values were determined using receiver operating characteristic curves. Results: A total of 330 HCC patients were enrolled in this study, of whom 74 (22.4%) had tumors with mVI. After univariate analysis, two parameters were significantly associated with mVI after hepatic resection: platelet-to-lymphocyte ratio ≥102 (odds ratio [OR] 2.385, p = 0.001) and tumor size ≥5 cm (OR 4.29, p < 0.001). Both variables remained significant risk factors for mVI after multivariate analysis: platelet-to-lymphocyte ratio ≥102 (OR 1.831, p = 0.034) and tumor size ≥5 cm (OR 3.791, p < 0.001). Conclusions: Large tumor size (≥5 cm) and high platelet-to-lymphocyte ratio (≥102) are independent predictive factors for mVI in HCC.
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Affiliation(s)
- Narongsak Rungsakulkij
- Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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Lu JB, Cai SH, Pan YH, Yun JP. Altered epidermal fatty acid-binding protein expression in hepatocellular carcinoma predicts unfavorable outcomes. Cancer Manag Res 2018; 10:6275-6284. [PMID: 30538573 PMCID: PMC6260128 DOI: 10.2147/cmar.s181555] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective Hepatocellular carcinoma (HCC) is a rapidly proliferating malignancy that requires large amounts of fatty acids to synthesize cellular membranes and provide energy. Epidermal fatty acid-binding protein (EFABP) is uniquely expressed in epidermal cells, but its role and expression in HCC are not clear. Subjects and methods A total of 804 HCC specimens were collected to construct a tissue microarray (TMA) and for immunohistochemistry (IHC) analysis. The relationship between EFABP expression and clinical features of patients with HCC was analyzed. Results The EFABP IHC score for HCC tissue was 0.76±0.69, being significantly higher than that for matched nontumorous tissue (0.48±0.55; P<0.001). Using the median IHC score (ie, 0.8) in the tumorous tissue, a high level of EFABP expression was found in 57.3% (461/804) of the cases. Patients with HCC displaying high EFABP expression had poorer tumor differentiation (P=0.029), more vascular invasion (P=0.006), and a higher proportion of late TNM stage disease (P=0.042). Kaplan-Meier analysis revealed that the patients with high EFABP expression had significantly worse outcomes in terms of overall survival (P=0.003), worse disease-free survival (P=0.021), and a higher probability of recurrence (P=0.014). Multivariate analysis indicated that EFABP expression was an independent prognostic variable for overall survival (P=0.021) and disease-free survival (P=0.044). For HCC recurrence, only vascular invasion (P=0.020) and EFABP expression (P=0.026) were independent risk factors. Conclusion Our data revealed that EFABP expression was increased in HCC samples. High EFABP expression was correlated with shorter survival times in patients with HCC and served as an independent factor for worse outcomes. Our study therefore provides a promising bio-marker for the prognostic prediction of HCC and a potential therapeutic target for the disease.
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Affiliation(s)
- Jia-Bin Lu
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China, .,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China,
| | - Shao-Hang Cai
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China, .,Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Ying-Hua Pan
- Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510060, China
| | - Jing-Ping Yun
- Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China, .,Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China,
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Okamura Y, Sugiura T, Ito T, Yamamoto Y, Ashida R, Aramaki T, Uesaka K. The Predictors of Microscopic Vessel Invasion Differ Between Primary Hepatocellular Carcinoma and Hepatocellular Carcinoma with a Treatment History. World J Surg 2018; 42:3694-3704. [PMID: 29872870 DOI: 10.1007/s00268-018-4658-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Previous studies have shown that microscopic vessel invasion (MVI) occurs in hepatocellular carcinoma (HCC) with a treatment history due to its poorer malignant behavior in comparison with primary HCC. The aim of the present study was to determine the predictors of MVI and overall survival in HCC patients with a treatment history. METHODS This retrospective study included 580 patients who underwent hepatectomy and whose preoperative imaging showed no evidence of macroscopic vessel invasion. The patients were classified into two groups: primary HCC (n = 425) and HCC with a treatment history (n = 155). MVI was defined as the presence of either microscopic portal vein invasion or venous invasion, which was invisible on preoperative imaging. RESULTS MVI was identified in 34 (21.9%) patients with a treatment history. A multivariate analysis showed that a high des-gamma-carboxy prothrombin (odds ratio [OR] 5.16, P = 0.002) and a large tumor diameter (OR 2.57, P = 0.030) were the significant predictor of MVI in HCC with a treatment history. Moreover, the presence of MVI (hazard ratio [HR] 2.27, P = 0.001) and tumor diameter >27 mm (HR 2.04, P = 0.006) remained significant predictors of the overall survival in HCC with a treatment history. The tumor diameter cutoff value for predicting MVI (27 mm) in HCC with a treatment history was smaller than in primary HCC (37 mm). CONCLUSIONS The presence of MVI was a significant predictor in the HCC patients with a treatment history. The tumor diameter is an important factor that can be used to predict the presence of MVI, especially in HCC with a treatment history.
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Affiliation(s)
- Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
| | - Takeshi Aramaki
- Division of Diagnostic Radiology, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, 1007, Shimo-Nagakubo, Sunto-Nagaizumi, Shizuoka, 411-8777, Japan
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