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Zhong H, Zhang Y, Zhu G, Zheng X, Wang J, Kang J, Lin Z, Yue X. Preoperative prediction of microvascular invasion and relapse-free survival in hepatocellular Carcinoma ≥3 cm using CT radiomics: Development and external validation. BMC Med Imaging 2025; 25:141. [PMID: 40312321 PMCID: PMC12046733 DOI: 10.1186/s12880-025-01677-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/15/2025] [Indexed: 05/03/2025] Open
Abstract
OBJECTIVE To preoperatively predict microvascular invasion (MVI) and relapse-free survival (RFS) in hepatocellular carcinoma (HCC) ≥3 cm by constructing and externally validating a combined radiomics model using preoperative enhanced CT images. METHODS This retrospective study recruited adults who underwent surgical resection between September 2016 and August 2020 in our hospital with pathologic confirmation of HCC ≥3 cm and MVI status. For external validation, adults who underwent surgical resection between September 2020 and August 2021 in our hospital were included. Histopathology was the reference standard. The HCC area was segmented on the arterial and portal venous phase CT images to develop a CT radiomics model. A combined model was developed using selected radiomics features, demographic information, laboratory index and radiological features. Analysis of variance and support vector machine were used as features selector and classifier. Receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA) were used to evaluate models' performance. The Kaplan-Meier method and log-rank test were used to evaluate the predictive value for RFS. RESULTS A total of 202 patients were finally enrolled (median age, 59 years, 173 male). Thirteen and 24 features were selected for the CT radiomics model and the combined model, and the area under the ROC curves (AUC) were 0.752 (95 %CI 0.615, 0.889) and 0.890 (95 %CI 0.794, 0.985) in the external validation set, respectively. Calibration curves and DCA showed a higher net clinical benefit of the combined model. The high-risk group (P < 0.001) was an independent predictor for RFS. CONCLUSIONS The combined model showed high accuracy for preoperatively predicting MVI and RFS in HCC ≥3 cm.
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Affiliation(s)
- Hua Zhong
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China
| | - Yan Zhang
- The Second Department of Radiology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian Province, 361021, China
| | - Guanbin Zhu
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China
| | - Xiaoli Zheng
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China
| | - Jinan Wang
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China
| | - Jianghe Kang
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China
| | - Ziying Lin
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China.
| | - Xin Yue
- Department of Radiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, No.201-209 Hubinnan Road, Siming District, Xiamen, Fujian Province, 361004, China.
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Sun J, Xia Y, Shen F, Cheng S. Chinese expert consensus on the diagnosis and treatment of hepatocellular carcinoma with microvascular invasion (2024 edition). Hepatobiliary Surg Nutr 2025; 14:246-266. [PMID: 40342785 PMCID: PMC12057508 DOI: 10.21037/hbsn-24-359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/10/2024] [Indexed: 05/11/2025]
Abstract
Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Surgical resection is the preferred treatment for HCC, but the postoperative recurrence and metastasis rates are high. Current evidence shows that microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis, but there are still many controversies about the diagnosis, classification, prediction, and treatment of MVI worldwide. Methods Systematic literature reviews to identify knowledge gaps and support consensus statements and a modified Delphi method to develop evidence- and expert-based guidelines and finalization of the clinical consensus statements based on recommendations from a panel of experts. Results After many discussions and revisions, the Chinese Association of Liver Cancer of the Chinese Medical Doctor Association organized domestic experts in related fields to form the "Chinese expert consensus on the diagnosis and treatment of hepatocellular carcinoma with microvascular invasion (2024 edition)" which included eight recommendations to better guide the prediction, diagnosis and treatment of HCC patients with MVI. The MVI pathological grading criteria as outlined in the "Guidelines for Pathological Diagnosis of Primary Liver Cancer" and the Eastern Hepatobiliary Surgery Hospital (EHBH) nomogram for predicting MVI are highly recommended. Conclusions We present an expert consensus on the diagnosis and treatment of MVI and potentially improve recurrence-free survival (RFS) and overall survival (OS) for HCC patients with MVI.
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Affiliation(s)
- Juxian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Yong Xia
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatic Surgery IV, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Shuqun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
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Nong HY, Cen YY, Lu SJ, Huang RS, Chen Q, Huang LF, Huang JN, Wei X, Liu MR, Li L, Ding K. Predictive value of a constructed artificial neural network model for microvascular invasion in hepatocellular carcinoma: A retrospective study. World J Gastrointest Oncol 2025; 17:96439. [PMID: 39817122 PMCID: PMC11664629 DOI: 10.4251/wjgo.v17.i1.96439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Revised: 09/06/2024] [Accepted: 11/07/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is a significant risk factor for recurrence and metastasis following hepatocellular carcinoma (HCC) surgery. Currently, there is a paucity of preoperative evaluation approaches for MVI. AIM To investigate the predictive value of texture features and radiological signs based on multiparametric magnetic resonance imaging in the non-invasive preoperative prediction of MVI in HCC. METHODS Clinical data from 97 HCC patients were retrospectively collected from January 2019 to July 2022 at our hospital. Patients were classified into two groups: MVI-positive (n = 57) and MVI-negative (n = 40), based on postoperative pathological results. The correlation between relevant radiological signs and MVI status was analyzed. MaZda4.6 software and the mutual information method were employed to identify the top 10 dominant texture features, which were combined with radiological signs to construct artificial neural network (ANN) models for MVI prediction. The predictive performance of the ANN models was evaluated using area under the curve, sensitivity, and specificity. ANN models with relatively high predictive performance were screened using the DeLong test, and the regression model of multilayer feedforward ANN with backpropagation and error backpropagation learning method was used to evaluate the models' stability. RESULTS The absence of a pseudocapsule, an incomplete pseudocapsule, and the presence of tumor blood vessels were identified as independent predictors of HCC MVI. The ANN model constructed using the dominant features of the combined group (pseudocapsule status + tumor blood vessels + arterial phase + venous phase) demonstrated the best predictive performance for MVI status and was found to be automated, highly operable, and very stable. CONCLUSION The ANN model constructed using the dominant features of the combined group can be recommended as a non-invasive method for preoperative prediction of HCC MVI status.
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Affiliation(s)
- Hai-Yang Nong
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
- Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youiiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Yong-Yi Cen
- Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youiiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
- Department of Radiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
| | - Shan-Jin Lu
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Rui-Sui Huang
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Qiong Chen
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Li-Feng Huang
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Jian-Ning Huang
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Xue Wei
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Man-Rong Liu
- Department of Ultrasound, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Lin Li
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
| | - Ke Ding
- Department of Radiology, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Zhuang Autonomous Region, China
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Huang XW, Li Y, Jiang LN, Zhao BK, Liu YS, Chen C, Zhao D, Zhang XL, Li ML, Jiang YY, Liu SH, Zhu L, Zhao JM. Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma. Transl Oncol 2024; 45:101986. [PMID: 38723299 PMCID: PMC11101742 DOI: 10.1016/j.tranon.2024.101986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 04/22/2024] [Accepted: 05/05/2024] [Indexed: 05/21/2024] Open
Abstract
Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.
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Affiliation(s)
- Xiao-Wen Huang
- Medical School of Chinese PLA, Beijing, China; Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yan Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li-Na Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bo-Kang Zhao
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, China
| | - Yi-Si Liu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Chun Chen
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Dan Zhao
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xue-Li Zhang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mei-Ling Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yi-Yun Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shu-Hong Liu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li Zhu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jing-Min Zhao
- Medical School of Chinese PLA, Beijing, China; Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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Zhang Z, Jia XF, Chen XY, Chen YH, Pan KH. Radiomics-Based Prediction of Microvascular Invasion Grade in Nodular Hepatocellular Carcinoma Using Contrast-Enhanced Magnetic Resonance Imaging. J Hepatocell Carcinoma 2024; 11:1185-1192. [PMID: 38933179 PMCID: PMC11199320 DOI: 10.2147/jhc.s461420] [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: 01/25/2024] [Accepted: 06/01/2024] [Indexed: 06/28/2024] Open
Abstract
Objective The aim of this study is to develop and verify a magnetic resonance imaging (MRI)-based radiomics model for predicting the microvascular invasion grade (MVI) before surgery in individuals diagnosed with nodular hepatocellular carcinoma (HCC). Methods A total of 198 patients were included in the study and were randomly stratified into two groups: a training group consisting of 139 patients and a test group comprising 59 patients. The tumor lesion was manually segmented on the largest cross-sectional slice using ITK SNAP, with agreement reached between two radiologists. The selection of radiomics features was carried out using the LASSO (Least Absolute Shrinkage and Selection Operator) algorithm. Radiomics models were then developed through maximum correlation, minimum redundancy, and logistic regression analyses. The performance of the models in predicting MVI grade was assessed using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion matrix. Results There were no notable statistical differences in sex, age, BMI (body mass index), tumor size, and location between the training and test groups. The AP and PP radiomic model constructed for predicting MVI grade demonstrated an AUC of 0.83 (0.75-0.88) and 0.73 (0.64-0.80) in the training group and an AUC of 0.74 (0.61-0.85) and 0.62 (0.48-0.74) in test group, respectively. The combined model consists of imaging data and clinical data (age and AFP), achieved an AUC of 0.85 (0.78-0.91) and 0.77 (0.64-0.87) in the training and test groups, respectively. Conclusion A radiomics model utilizing-contrast-enhanced MRI demonstrates strong predictive capability for differentiating MVI grades in individuals with nodular HCC. This model could potentially function as a dependable and resilient tool to support hepatologists and radiologists in their preoperative decision-making processes.
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Affiliation(s)
- Zhao Zhang
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Xiu-Fen Jia
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Xiao-Yu Chen
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Yong-Hua Chen
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Ke-Hua Pan
- Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
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Bosi C, Rimini M, Casadei-Gardini A. Understanding the causes of recurrent HCC after liver resection and radiofrequency ablation. Expert Rev Anticancer Ther 2023; 23:503-515. [PMID: 37060290 DOI: 10.1080/14737140.2023.2203387] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2023]
Abstract
INTRODUCTION Surgical resection and radiofrequency ablation are preferred options for early-stage disease, with 5-year recurrence rates as high as 70% when patients are treated according to guidelines. With increasing availability of therapeutic options, including but not limited to, immune-checkpoint inhibitors (ICI), tyrosine kinase inhibitors, antiangiogenics, and adoptive cell therapies, understanding the causes of recurrence and identifying its predictors should be priorities in the hepatocellular carcinoma (HCC) research agenda. AREAS COVERED Current knowledge of HCC predictors of recurrence is reviewed, and recent insights about its underlying mechanisms are presented. In addition, results from recent clinical trials investigating treatment combinations are critically appraised. EXPERT OPINION HCC recurrence is either due to progressive growth of microscopic residual disease, or to de novo cancer development in the context of a diseased liver, each occurring in an early (<2years) vs. late (≥2 years) fashion. Collectively, morphological, proteomic, and transcriptomic data suggest vascular invasion and angiogenesis as key drivers of HCC recurrence. Agents aimed at blocking either of these two hallmarks should be prioritized at the moment of early-stage HCC clinical trial design. Emerging results from clinical trials testing ICI in early-stage HCC underscore the importance of defining the best treatment sequence and the most appropriate combination strategies. Lastly, as different responses to systemic therapies are increasingly defined according to the HCC etiology, patient enrolment into clinical trials should take into account the biological characteristics of their inherent disease.
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Affiliation(s)
- Carlo Bosi
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Margherita Rimini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
- Vita-Salute San Raffaele University School of Medicine, Milan, 20132, Italy
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Giuliante F, Ratti F, Panettieri E, Mazzaferro V, Guglielmi A, Ettorre GM, Gruttadauria S, Di Benedetto F, Cillo U, De Carlis L, Dalla Valle R, Ferrero A, Santambrogio R, Ardito F, Aldrighetti L. Short and long-term outcomes after minimally invasive liver resection for single small hepatocellular carcinoma: An analysis of 714 patients from the IGoMILS (Italian group of minimally invasive liver surgery) registry. HPB (Oxford) 2023:S1365-182X(23)00046-1. [PMID: 36922259 DOI: 10.1016/j.hpb.2023.02.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Revised: 02/01/2023] [Accepted: 02/10/2023] [Indexed: 03/18/2023]
Abstract
BACKGROUND Widespread use of minimally invasive liver surgery (MILS) contributed to the reduction of surgical risk of liver resection for hepatocellular carcinoma (HCC). Aim of this study was to analyze outcomes of MILS for single ≤3 cm HCC. METHODS Patients who underwent MILS for single ≤3 cm HCC (November 2014 - December 2019) were identified from the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) Registry. RESULTS Of 714 patients included, 641 (93.0%) were Child-Pugh A; 65.7% were limited resections and 2.2% major resections, with a conversion rate of 5.2%. Ninety-day mortality rate was 0.3%. Overall morbidity rate was 22.4% (3.8% major complications). Mean postoperative stay was 5 days. Robotic resection showed longer operative time (p = 0.004) and a higher overall morbidity rate (p < 0.001), with similar major complications (p = 0.431). Child-Pugh B patients showed worse mortality (p = 0.017) and overall morbidity (p = 0.021), and longer postoperative stay (p = 0.005). Five-year overall survival was 79.5%; cirrhosis, satellite micronodules, and microvascular invasion were independently associated with survival. CONCLUSIONS MILS for ≤3 cm HCC was associated with low morbidity and mortality rates, showing high safety, and supporting the increasing indications for surgical resection in these patients.
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Affiliation(s)
- Felice Giuliante
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy.
| | - Francesca Ratti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
| | - Elena Panettieri
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Vincenzo Mazzaferro
- Department of Surgery, Division of HPB, General Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy
| | - Alfredo Guglielmi
- Department of Surgery, General and Hepatobiliary Surgery, University of Verona, University Hospital G.B. Rossi, Verona, Italy
| | - Giuseppe M Ettorre
- Department of General Surgery and Liver Transplantation, San Camillo Forlanini Hospital, Rome, Italy
| | - Salvatore Gruttadauria
- Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, IRCCS-Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione, Palermo, Italy
| | - Fabrizio Di Benedetto
- Hepatopancreatobiliary Surgery and Transplant, Modena University Hospital, Modena, Italy
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Unit, Padua University Hospital, Padua, Italy
| | - Luciano De Carlis
- Department of General Surgery and Transplantation, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Raffaele Dalla Valle
- Hepatobiliary Surgery Unit Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Alessandro Ferrero
- Department of General and Oncological Surgery, Umberto I Mauriziano Hospital, Turin, Italy
| | - Roberto Santambrogio
- ASST Fatebenefratelli Sacco, Chirurgia Generale Ospedale Fatebenefratelli, Milan, Italy
| | - Francesco Ardito
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Luca Aldrighetti
- Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy
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Gan L, Ren S, Lang M, Li G, Fang F, Chen L, Liu Y, Han R, Zhu K, Song T. Predictive Value of Preoperative Serum AFP, CEA, and CA19-9 Levels in Patients with Single Small Hepatocellular Carcinoma: Retrospective Study. J Hepatocell Carcinoma 2022; 9:799-810. [PMID: 35990213 PMCID: PMC9384872 DOI: 10.2147/jhc.s376607] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 08/04/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose This study aimed to explore the relationship between the tumor marker score (TMS) and the postoperative recurrence of single small hepatocellular carcinoma (HCC). Patients and Methods A total of 409 patients with one resectable HCC with a diameter of 3 cm or less who visited Tianjin Medical University Cancer Institute & Hospital from January 2010 to December 2014 were included in this study. Their alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) levels were classified into low and high groups using X-tile software. Each patients' TMS was calculated as the sum of each tumor marker (low = 0; high = 1). Results A total of 142 patients were classified as TMS0, 171 as TMS1, and 96 as TMS2. Kaplan–Meier analysis illustrated that TMS could divide the patients into groups with remarkably different prognoses, and the patients with high TMS had worse recurrence-free survival (RFS) than those with low TMS. Multivariate analysis showed that TMS, age, and HBeAg positive were the independent predictors of RFS rate. Subgroup analysis revealed that high TMS was a stable risk factor relative to TMS0. Receiver operating curves showed that the 1-, 3-, and 5-year area under curve (AUC) values of TMS were 0.698, 0.662, and 0.673, respectively. The AUC of TMS was higher than that of other common prognostic models in time-dependent receiver operating curve. Conclusion TMS was an independent prognostic factor for the postoperative recurrence of a single small HCC and can provide a well-discriminated risk stratification, thus contributing to prognostic prediction and adjuvant therapeutic development.
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Affiliation(s)
- Leijuan Gan
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Shaohua Ren
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Mengran Lang
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Guangtao Li
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Feng Fang
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Lu Chen
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Yayue Liu
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Ruyu Han
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Kangwei Zhu
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
| | - Tianqiang Song
- Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China
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Xu C, Jiang D, Tan B, Shen C, Guo J. Preoperative diagnosis and prediction of microvascular invasion in hepatocellularcarcinoma by ultrasound elastography. BMC Med Imaging 2022; 22:88. [PMID: 35562688 PMCID: PMC9107229 DOI: 10.1186/s12880-022-00819-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 05/05/2022] [Indexed: 12/24/2022] Open
Abstract
Background To assess the values of two elastography techniques combined with serological examination and clinical features in preoperative diagnosis of microvascular invasion in HCC patients. Methods A total of 74 patients with single Hepatocellular carcinoma (HCC) were included in this study. Shear wave measurement and real-time tissue elastography were used to evaluate the hardness of tumor-adjacent tissues and tumor tissues, as well as the strain rate ratio per lesion before surgery. According to the pathological results, the ultrasound parameters and clinical laboratory indicators related to microvascular invasion were analyzed, and the effectiveness of each parameter in predicting the occurrence of microvascular invasion was compared. Results 33/74 patients exhibited microvascular invasion. Univariate analysis showed that the hardness of tumor-adjacent tissues (P = 0.003), elastic strain rate ratio (P = 0.032), maximum tumor diameter (P < 0.001), and alpha-fetoprotein (AFP) level (P = 0.007) was significantly different in the patients with and without microvascular invasion. The binary logistic regression analysis showed that the maximum tumor diameter (P = 0.001) was an independent risk factor for predicting microvascular invasion, while the hardness of tumor-adjacent tissues (P = 0.028) was a protective factor. The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of the hardness of tumor-adjacent tissues, the maximum diameter of the tumor, and the predictive model Logit(P) in predicting the occurrence of MVI was 0.718, 0.775 and 0.806, respectively. Conclusion The hardness of tumor-adjacent tissues, maximum tumor diameter, and the preoperative prediction model predict the occurrence of MVI in HCC patients.
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Affiliation(s)
- Chengchuan Xu
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai, China
| | - Dong Jiang
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai, China
| | - Bibo Tan
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai, China
| | - Cuiqin Shen
- Jiading Branch of Shanghai First People's Hospital, Shanghai, China
| | - Jia Guo
- Department of Ultrasound, Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University, Shanghai, China.
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10
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Cai J, Zhao J, Liu D, Xie H, Qi H, Ma J, Sun Z, Zhao H. Efficacy and Safety of Central Memory T Cells Combined With Adjuvant Therapy to Prevent Recurrence of Hepatocellular Carcinoma With Microvascular Invasion: A Pilot Study. Front Oncol 2021; 11:781029. [PMID: 34926296 PMCID: PMC8679661 DOI: 10.3389/fonc.2021.781029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/08/2021] [Indexed: 01/27/2023] Open
Abstract
Background Postoperative adjuvant transcatheter arterial chemoembolization (TACE) following curative hepatectomy has been reported to improve the clinical outcomes of hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but more endeavors are required to achieve greater clinical benefit. Central memory T-cell (Tcm) self-transfusion has shown superior antitumor activity in several preclinical studies; however, clinical studies are rare. The aim of this study was to evaluate the clinical benefit and safety of combination treatment with Tcm self-transfusion and TACE as adjuvant treatment in HCC patients with MVI after curative hepatectomy. Methods From October 2016 to September 2018, primary HCC patients with histologically confirmed MVI who underwent curative hepatectomy at the Cancer Hospital of the Chinese Academy of Medical Sciences were recruited for this study. The patients were divided into a Tcm group (combined Tcm self-transfusion with TACE treatment) or a control group (TACE treatment alone) according to their willingness. The recurrence-free survival (RFS), quality-of-life (QOL) score, and adverse events of each patient were recorded within 2 years. Results A total of 52 patients were enrolled, and 48 were eligible for the final data analysis. The median follow-up time was 20.5 months (95% CI: 17.05–22.55 months). The median RFS time was 9.5 months in the control group; the cutoff date was not reached in the Tcm group (when the follow-up duration was 12 months, p = 0.049, HR = 0.40; 95% CI: 0.16–0.99). Compared with the control group, 1- and 2-year RFS rates were higher in the Tcm group (72.0% vs. 46.4% and 58.18% vs. 39.14%, respectively). Multivariate analysis did not indicate that Tcm treatment was an independent prognostic factor associated with HCC recurrence (p = 0.107, HR = 2.312; 95% CI: 0.835–6.400), which might be due to the small sample size of this study. Nevertheless, Tcm treatment effectively improved a reduced QOL due to HCC and liver function injury. Finally, the safety profile of Tcm treatment in this study was good, without any serious adverse events. Conclusions This pilot study showed that Tcm self-transfusion combined with TACE treatment might be a beneficial adjuvant therapy with good safety for primary HCC patients with MVI after curative hepatectomy. Trial registration number NCT03575806
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Affiliation(s)
- Jianqiang Cai
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jianjun Zhao
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Defang Liu
- Department of New Drug Registration, Hebei Immune Cell Application Engineering Research Center/Baoding Newish Technology Co., LTD/Newish Technology (Beijing) Co., LTD, Beijing, China
| | - Huangfan Xie
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Hailong Qi
- Department of New Drug Registration, Hebei Immune Cell Application Engineering Research Center/Baoding Newish Technology Co., LTD/Newish Technology (Beijing) Co., LTD, Beijing, China.,School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Junfan Ma
- School of Pharmaceutical Sciences, Tsinghua University, Beijing, China
| | - Zhongjie Sun
- State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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11
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Shinkawa H, Tanaka S, Kabata D, Takemura S, Amano R, Kimura K, Kinoshita M, Kubo S. The Prognostic Impact of Tumor Differentiation on Recurrence and Survival after Resection of Hepatocellular Carcinoma Is Dependent on Tumor Size. Liver Cancer 2021; 10:461-472. [PMID: 34721508 PMCID: PMC8527909 DOI: 10.1159/000517992] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 06/18/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The present study aimed to evaluate the effect of poor differentiation and tumor size on survival outcome after hepatic resection of hepatocellular carcinoma (HCC). METHODS A total of 1,107 patients who underwent initial and curative hepatic resection for HCC without macroscopic vascular invasion participated in the study. Using the multivariable Cox proportional hazards regression model, we evaluated changes in hazard ratios (HRs) for the association between tumor differentiation and survival based on tumor size. RESULTS In patients with poorly (Por) differentiated HCCs, the adjusted HRs of reduced overall survival (OS), recurrence-free survival (RFS), early RFS, and early extrahepatic RFS were 1.31 (95% confidence interval [CI]; 1.07-1.59), 1.07 (95% CI 0.89-1.28), 1.31 (95% CI 1.06-1.62), and 1.81 (95% CI 1.03-3.17), respectively. Moreover, based on an analysis of the effect modification of tumor differentiation according to tumor size, Por HCC was found to be associated with a reduced OS (p = 0.033). The HRs of Por HCCs sharply increased in patients with tumors measuring up to 5 cm. The adjusted HRs of reduced OS in patients with Por HCCs measuring <2, ≥2 and <5, and ≥5 cm were 1.22 (95% CI 0.69-2.14), 1.33 (95% CI 1.02-1.73), and 1.58 (95% CI 1.04-2.42), respectively. The corresponding adjusted HRs of reduced early RFS were 0.85 (95% CI 0.46-1.57), 1.34 (95% CI 1.01-1.8), and 1.57 (95% CI 1.03-2.39), respectively. The adjusted HRs of reduced early extrahepatic RFS were 1.89 (95% CI 0.83-4.3) in patients with tumors measuring ≥2 and <5 cm and 2.33 (95% CI 0.98-5.54) in those with tumors measuring ≥5 cm. CONCLUSIONS Por HCC measuring ≥2 cm was associated with early recurrence. Hence, it had negative effects on OS. After surgery, patients with Por HCC measuring ≥5 cm should be cautiously monitored for early extrahepatic recurrence. These findings will help physicians devise treatment strategies for patients with HCC.
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Affiliation(s)
- Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan,*Hiroji Shinkawa,
| | - Shogo Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Daijiro Kabata
- Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shigekazu Takemura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Ryosuke Amano
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Kenjiro Kimura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masahiko Kinoshita
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
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Song L, Li J, Luo Y. The importance of a nonsmooth tumor margin and incomplete tumor capsule in predicting HCC microvascular invasion on preoperative imaging examination: a systematic review and meta-analysis. Clin Imaging 2021; 76:77-82. [PMID: 33578134 DOI: 10.1016/j.clinimag.2020.11.057] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 11/15/2020] [Accepted: 11/30/2020] [Indexed: 02/05/2023]
Abstract
OBJECTIVES Microvascular invasion (MVI) is a key factor affecting the prognosis of hepatocellular carcinoma (HCC). Preoperative imaging plays an important role in the diagnosis of HCC, treatment planning and treatment evaluation, but it is still difficult to detect MVI directly. Whether the appearance of the tumor margin and the capsule on radiological images can predict MVI is still controversial. The aim of this study is to explore the correlation of the presence of MVI with the smoothness of the tumor margin and the integrity of the capsule in HCC. MATERIALS AND METHODS The PubMed, Embase, Medline, SCI and Cochrane Library databases up to January 2020. Heterogeneity among studies was assessed by sensitivity analysis, subgroup analysis and meta-regression, and the influence of threshold effects was also analyzed. RESULTS Eleven studies with 1618 patients were included. The results of the meta-analysis indicated that there was a significant relationship between MVI and nonsmooth tumor margin (DOR = 4.62 [2.73, 7.81]) and between MVI and incomplete tumor capsule (DOR = 2.25 [1.22, 4.15]); the sensitivity and specificity of these two parameters were 0.757 [0.602, 0.865], 0.597 [0.450, 0.728] and 0.646 [0.455, 0.800], 0.552 [0.419, 0.678], respectively. We drew the receiver operating characteristic (ROC) curves, and the area under curve (AUC) of the nonsmooth tumor margin variable for predicting MVI was 0.72 [0.69, 0.77], and the AUC of the incomplete tumor capsule variable for predicting MVI was 0.62 [0.58, 0.66]. CONCLUSION Nonsmooth tumor margins and incomplete tumor capsules observed by imaging are important for the preoperative prediction of MVI in HCC.
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Affiliation(s)
- Ling Song
- Department of Ultrasound, West China Hospital, Sichuan University, China
| | - Jiawu Li
- Department of Ultrasound, West China Hospital, Sichuan University, China
| | - Yan Luo
- Department of Ultrasound, West China Hospital, Sichuan University, China.
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13
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Hepatocellular carcinoma: metastatic pathways and extra-hepatic findings. Abdom Radiol (NY) 2021; 46:3698-3707. [PMID: 34091729 DOI: 10.1007/s00261-021-03151-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/21/2021] [Accepted: 05/24/2021] [Indexed: 01/10/2023]
Abstract
Although a small portion of patients with hepatocellular carcinoma (HCC) have radiologically evident extrahepatic disease at the initial presentation, a larger number of them develop metastatic disease later during the course of treatment or after definitive treatment. Furthermore, early metastatic disease could be overlooked by imaging due to small size and non-specificity of findings. Extrahepatic spread of HCC occurs via different pathways and is directly fueled by tumor biology and its molecular characteristics. Early and accurate detection of extrahepatic disease in patients with HCC has significant impact on management and selection of treatment options. Additionally, precise staging of disease will allow for better prediction of survival and outcome. Different pathways of regional and systemic spread of HCC with their proposed mechanisms and relevant underlying molecular derangement will be discussed in this article. Potential roles in management of patients with HCC will be discussed and reviewed in this article.
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14
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Zhou Z, Qi L, Mo Q, Liu Y, Zhou X, Zhou Z, Liang X, Feng S, Yu H. Effect of surgical margin on postoperative prognosis in patients with solitary hepatocellular carcinoma: A propensity score matching analysis. J Cancer 2021; 12:4455-4462. [PMID: 34149909 PMCID: PMC8210564 DOI: 10.7150/jca.57896] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Accepted: 05/13/2021] [Indexed: 12/24/2022] Open
Abstract
Objective: The effect of surgical margin (SM) on the postoperative prognosis of patients with solitary hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the effect of SM on the postoperative prognosis of patients with solitary HCC by using propensity score matching (PSM). Methods: Patients with solitary HCC who underwent liver resection were divided into a wide margin group (1.0 cm or more, group W) and a narrow margin group (< 1.0 cm, group N). Progression-free survival (PFS) and overall survival (OS) associated with the SM status and the factors influencing postoperative prognosis were evaluated. Results: Before PSM, the indicators were not balanced between the two groups. PFS and OS were significantly lower in group N than group W. The factors affecting postoperative prognosis were international normalized ratio (INR), AST, capsule integrity, microvascular invasion, tumour embolus and tumour size. After PSM, data of both groups were balanced and comparable, and no significant differences in OS or PFS between the two groups. The INR in the above affecting factors was excluded. Conclusion: For solitary HCC patients with negative SMs, SM size does not affect prognosis. INR, AST, capsule integrity, microvascular invasion, tumour embolus and tumour size are independent factors influencing the postoperative prognosis of solitary HCC patients.
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Affiliation(s)
- Zewen Zhou
- Guangxi Medical University Cancer Hospital, Nanning 530021, China.,School of Public Health, Guangxi Medical University, Nanning 530021, China
| | - Lunan Qi
- Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Qiuyan Mo
- Guangxi Medical University Cancer Hospital, Nanning 530021, China.,School of Public Health, Guangxi Medical University, Nanning 530021, China
| | - Yingchun Liu
- Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xianguo Zhou
- Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Zihan Zhou
- Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Xiumei Liang
- Guangxi Medical University Cancer Hospital, Nanning 530021, China
| | - Shixiong Feng
- Guangxi Medical University Cancer Hospital, Nanning 530021, China.,School of Public Health, Guangxi Medical University, Nanning 530021, China
| | - Hongping Yu
- Guangxi Medical University Cancer Hospital, Nanning 530021, China.,School of Public Health, Guangxi Medical University, Nanning 530021, China
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15
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Liu P, Tan XZ, Zhang T, Gu QB, Mao XH, Li YC, He YQ. Prediction of microvascular invasion in solitary hepatocellular carcinoma ≤ 5 cm based on computed tomography radiomics. World J Gastroenterol 2021; 27:2015-2024. [PMID: 34007136 PMCID: PMC8108034 DOI: 10.3748/wjg.v27.i17.2015] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 02/22/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Liver cancer is one of the most common malignant tumors, and ranks as the fourth leading cause of cancer death worldwide. Microvascular invasion (MVI) is considered one of the most important factors for recurrence and poor prognosis of liver cancer. Thus, accurately identifying MVI before surgery is of great importance in making treatment strategies and predicting the prognosis of patients with hepatocellular carcinoma (HCC). Radiomics as an emerging field, aims to utilize artificial intelligence software to develop methods that may contribute to cancer diagnosis, treatment improvement and evaluation, and better prediction. AIM To investigate the predictive value of computed tomography radiomics for MVI in solitary HCC ≤ 5 cm. METHODS A total of 185 HCC patients, including 122 MVI negative and 63 MVI positive patients, were retrospectively analyzed. All patients were randomly assigned to the training group (n = 124) and validation group (n = 61). A total of 1351 radiomic features were extracted based on three-dimensional images. The diagnostic performance of the radiomics model was verified in the validation group, and the Delong test was applied to compare the radiomics and MVI-related imaging features (two-trait predictor of venous invasion and radiogenomic invasion). RESULTS A total of ten radiomics features were finally obtained after screening 1531 features. According to the weighting coefficient that corresponded to the features, the radiomics score (RS) calculation formula was obtained, and the RS score of each patient was calculated. The radiomics model exhibited a better correction and identification ability in the training and validation groups [area under the curve: 0.72 (95% confidence interval: 0.58-0.86) and 0.74 (95% confidence interval: 0.66-0.83), respectively]. Its prediction performance was significantly higher than that of the image features (P < 0.05). CONCLUSION Computed tomography radiomics has certain predictive value for MVI in solitary HCC ≤ 5 cm, and the predictive ability is higher than that of image features.
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Affiliation(s)
- Peng Liu
- Department of Radiology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
| | - Xian-Zhen Tan
- Department of Radiology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
| | - Ting Zhang
- Department of Radiology, Hunan Children's Hospital, Changsha 410000, Hunan Province, China
| | - Qian-Biao Gu
- Department of Radiology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
| | - Xian-Hai Mao
- Department of Hepatological Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
| | - Yan-Chun Li
- Department of Pathology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
| | - Ya-Qiong He
- Department of Radiology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan Province, China
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16
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Meng ZW, Cai XR, Lin CZ, Chen YL, Liu S. The Islanding effect - a special method of percutaneous peritumor ethanol injection for hepatocellular carcinoma: 15-year follow-up outcome. Medicine (Baltimore) 2021; 100:e24365. [PMID: 33546073 PMCID: PMC7837841 DOI: 10.1097/md.0000000000024365] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 12/19/2020] [Indexed: 12/28/2022] Open
Abstract
Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study.Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database.The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child-Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child-Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival.Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.
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17
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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 X, Ruan S, Xiao W, Shao J, Tian W, Liu W, Zhang Z, Wan D, Huang J, Huang Q, Yang Y, Yang H, Ding Y, Liang W, Bai X, Liang T. Contrast-enhanced CT radiomics for preoperative evaluation of microvascular invasion in hepatocellular carcinoma: A two-center study. Clin Transl Med 2020; 10:e111. [PMID: 32567245 PMCID: PMC7403665 DOI: 10.1002/ctm2.111] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 06/04/2020] [Accepted: 06/05/2020] [Indexed: 12/24/2022] Open
Abstract
Background The present study constructed and validated the use of contrast‐enhanced computed tomography (CT)‐based radiomics to preoperatively predict microvascular invasion (MVI) status (positive vs negative) and risk (low vs high) in patients with hepatocellular carcinoma (HCC). Methods We enrolled 637 patients from two independent institutions. Patients from Institution I were randomly divided into a training cohort of 451 patients and a test cohort of 111 patients. Patients from Institution II served as an independent validation set. The LASSO algorithm was used for the selection of 798 radiomics features. Two classifiers for predicting MVI status and MVI risk were developed using multivariable logistic regression. We also performed a survival analysis to investigate the potentially prognostic value of the proposed MVI classifiers. Results The developed radiomics signature predicted MVI status with an area under the receiver operating characteristic curve (AUC) of .780, .776, and .743 in the training, test, and independent validation cohorts, respectively. The final MVI status classifier that integrated two clinical factors (age and α‐fetoprotein level) achieved AUC of .806, .803, and .796 in the training, test, and independent validation cohorts, respectively. For MVI risk stratification, the AUCs of the radiomics signature were .746, .664, and .700 in the training, test, and independent validation cohorts, respectively, and the AUCs of the final MVI risk classifier‐integrated clinical stage were .783, .778, and .740, respectively. Survival analysis showed that our MVI status classifier significantly stratified patients for short overall survival or early tumor recurrence. Conclusions Our CT radiomics‐based models were able to predict MVI status and MVI risk of HCC and might serve as a reliable preoperative evaluation tool.
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Affiliation(s)
- Xiuming Zhang
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shijian Ruan
- College of Information Science and Electronic Engineering, Zhejiang University, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiayuan Shao
- College of Information Science and Electronic Engineering, Zhejiang University, Hangzhou, China
| | - Wuwei Tian
- College of Information Science and Electronic Engineering, Zhejiang University, Hangzhou, China
| | - Weihai Liu
- Department of Radiology, The People's Hospital of Beilun District, Ningbo, China
| | - Zhao Zhang
- Department of Radiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Dalong Wan
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiacheng Huang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiang Huang
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yunjun Yang
- Department of Radiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China
| | - Hanjin Yang
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yong Ding
- College of Information Science and Electronic Engineering, Zhejiang University, Hangzhou, China
| | - Wenjie Liang
- Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Innovation Center for the Study of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Innovation Center for the Study of Pancreatic Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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Dasari BV, Kamarajah SK, Hodson J, Pawlik TM, Vauthey JN, Ma YT, Punia P, Coldham C, Abradelo M, Roberts KJ, Marudanayagam R, Sutcliffe RP, Muiesan P, Mirza DF, Isaac J. Development and validation of a risk score to predict the overall survival following surgical resection of hepatocellular carcinoma in non-cirrhotic liver. HPB (Oxford) 2020; 22:383-390. [PMID: 31416786 DOI: 10.1016/j.hpb.2019.07.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Revised: 06/08/2019] [Accepted: 07/19/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND The aim of this study was to develop and validate a risk score to predict overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma in non-cirrhotic liver (NC-HCC). METHODS Patients who underwent resection for NC-HCC between 2004 and 2013 were identified from the SEER database. A derivation set of 75% of this cohort was used to develop a risk score. This was then internally validated on the remaining patients, and externally validated using a cohort of patients from The HPB Unit, Birmingham, UK. RESULTS A total of 3897 patients were included from the SEER database, with a median post-diagnosis survival of 59 months. In the derivation set, multivariable analyses identified male sex, increasing tumour size, the presence of multiple tumours, bilobar tumours and major vascular invasion as adverse prognostic factors. A risk score generated from these factors was significantly predictive of OS, and was used to classify patients into low, medium and high-risk groups. These groups had a five-year OS of 69%, 51% and 19% in the internal, and 73%, 50% and 45% in the external validation sets. CONCLUSION The proposed risk score is useful in the selection, pre-operative consenting and counselling of patients for surgery and to allow patients to make an informed decision regarding treatment.
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Affiliation(s)
- Bobby Vm Dasari
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom.
| | - Sivesh K Kamarajah
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - James Hodson
- Institute of Translational Medicine, Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom
| | - Timothy M Pawlik
- Wexner Medical Centre, The Ohio State University, Birmingham, B15 2TH, United Kingdom
| | - Jean-Nicholas Vauthey
- Department of Surgical Oncology, M.D. Anderson Medical Centre, Birmingham, B15 2TH, United Kingdom
| | - Yuk T Ma
- Department of Oncology, Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom
| | - Pankaj Punia
- Department of Oncology, Queen Elizabeth Hospital, Birmingham, B15 2TH, United Kingdom
| | - Chris Coldham
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Manuel Abradelo
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Keith J Roberts
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Ravi Marudanayagam
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Robert P Sutcliffe
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Paolo Muiesan
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - Darius F Mirza
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
| | - John Isaac
- Department of Hepatobiliary and Pancreatic Surgery, Queen Elizabeth Hospital, Birmingham, B15 2WB, United Kingdom
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20
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Sun SW, Liu QP, Xu X, Zhu FP, Zhang YD, Liu XS. Direct Comparison of Four Presurgical Stratifying Schemes for Prediction of Microvascular Invasion in Hepatocellular Carcinoma by Gadoxetic Acid-Enhanced MRI. J Magn Reson Imaging 2020; 52:433-447. [PMID: 31943465 DOI: 10.1002/jmri.27043] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 12/17/2019] [Accepted: 12/18/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Microvascular invasion (MVI) is implicated in the poor prognosis of hepatocellular carcinoma (HCC). Presurgical stratifying schemes have been proposed for HCC-MVI but lack external validation. PURPOSE To perform external validation and comparison of four presurgical stratifying schemes for the prediction of MVI using gadoxetic acid-based MRI in a cohort of HCC patients. STUDY TYPE Retrospective. SUBJECTS Included were 183 surgically resected HCCs from patients who underwent pretreatment MRI. FIELD STRENGTH/SEQUENCE This includes 1.5-3.0 T with T2 , T1 , diffusion-weighted imaging (DWI), and dynamic gadoxetic acid contrast-enhancement imaging sequences. ASSESSMENT A two-trait predictor of venous invasion (TTPVI), Lei model, Lee model, and Xu model were compared. We relied on preoperative characteristics and imaging findings via four independent radiologists who were blinded to histologic results, as required by the tested tools. STATISTICAL TEST Tests of accuracy between predicted and observed HCC-MVI rates using receiver operating characteristic (ROC) curve and decision curve analysis. The intraclass correlation coefficient (ICC) and Cronbach's alpha statistics were used to evaluate reproducibility. RESULTS HCC-MVI was identified in 52 patients (28.4%). The average ROC curves (AUCs) for HCC-MVI predictions were 0.709-0.880, 0.714-0.828, and 0.588-0.750 for the Xu model, Lei model, and Lee model, respectively. The rates of accuracy were 60.7-81.4%, 69.9-75.9%, and 65.6-73.8%, respectively. Decision curve analyses indicated a higher benefit for the Xu and Lei models compared to the Lee model. The ICC and Cronbach's alpha index were highest in the Lei model (0.896/0.943), followed by the Xu model (0.882/0.804), and the Lee model (0.769/0.715). The TTPVI resulted in a Cronbach's alpha index of 0.606 with a sensitivity of 34.6-61.5% and a specificity of 76.3-91.6%. DATA CONCLUSION Stratifying schemes relying on gadoxetic acid-enhanced MRI provide an additional insight into the presence of preoperative MVI. The Xu model outperformed the other models in terms of accuracy when performed by an experienced radiologist. Conversely, the Lei model outperformed the other models in terms of reproducibility. LEVEL OF EVIDENCE 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:433-447.
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Affiliation(s)
- Shu-Wen Sun
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qiu-Ping Liu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xun Xu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fei-Peng Zhu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yu-Dong Zhang
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xi-Sheng Liu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Ahn KS, Kang KJ. Appropriate treatment modality for solitary small hepatocellular carcinoma: Radiofrequency ablation vs. resection vs. transplantation? Clin Mol Hepatol 2019; 25:354-359. [PMID: 31006225 PMCID: PMC6933127 DOI: 10.3350/cmh.2018.0096] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/10/2019] [Indexed: 12/12/2022] Open
Abstract
There has been controversy regarding the first-line treatment modality for the patients who have small solitary hepatocellular carcinoma (HCC); radiofrequency ablation (RFA) or percutaneous ethanol injection (PEI), surgical hepatic resection (HR) and liver transplantation (LT). For selection of treatment modality of HCC, it should be considered of hepatic reservoir function as well as the tumor stage. If the liver function is good enough, HR may be the first choice regardless of the tumor size. However, recent studies comparing RFA with resection showed comparable outcome and similar survival rates. RFA, HR and LT provide good outcome for patients who have small HCCs. RFA would be desired in patients who have below 3.0 cm in size and low alpha-fetoprotein (<200 ng/mL). However, in small HCC with high tumor marker, HR should be considered. Better patient selection for the 'resection first' approach and early detection of recurrence can achieve better outcomes of the salvage LT strategy. Another benefit of resection first strategy is that it make possible to do enlist of LT for patients before recurrence at high risk of HCC recurrence after resection on the basis of pathologic aggressiveness, microvascular invasion and/or satellites nodule. They should be applied appropriately according to the tumor size, location, tumor markers and underlying liver parenchymal disease.
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Affiliation(s)
- Keun Soo Ahn
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea
| | - Koo Jeong Kang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Keimyung University Dongsan Medical Center, Daegu, Korea
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22
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Fang Q, Xie QS, Chen JM, Shan SL, Xie K, Geng XP, Liu FB. Long-term outcomes after hepatectomy of huge hepatocellular carcinoma: A single-center experience in China. Hepatobiliary Pancreat Dis Int 2019; 18:532-537. [PMID: 31543313 DOI: 10.1016/j.hbpd.2019.09.001] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Currently, hepatectomy remains the first-line therapy for hepatocellular carcinoma (HCC). However, surgery for patients with huge (>10 cm) HCCs is controversial. This retrospective study aimed to explore long-term survival after hepatectomy for patients with huge HCC. METHODS The records of 188 patients with pathologically confirmed HCC who underwent curative hepatectomy between 2007 and 2017 were reviewed; patients were divided into three groups according to tumor size: huge (>10 cm; n = 84), large (5-10 cm; n = 51) and small (<5 cm; n = 53) HCC. Kaplan-Meier analysis was used to assess overall survival (OS) and disease-free survival (DFS), and log-rank analysis was performed for pairwise comparisons among the three groups. Risk factors for survival and recurrence were analyzed using the Cox proportional hazard model. RESULTS The median follow-up period was 20 months. Although the prognosis of small HCC was better than that of huge and large HCC, OS and DFS were not significantly different between huge and large HCC (P = 0.099 and P = 0.831, respectively). A family history of HCC, poor Child-Pugh class, vascular invasion, diolame, pathologically positive margins, and operative time ≥240 min were identified as independent risk factors for OS and DFS in a multivariate model. Tumor size (>10 cm) had significant effect on OS, and postoperative antiviral therapy and postoperative complications also had significant effects on DFS. CONCLUSIONS Huge HCC is not a contraindication of hepatectomy. Although most of these patients experienced recurrence after surgery, OS and DFS were not significantly different from those of patients with large HCC after resection.
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Affiliation(s)
- Qiang Fang
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Qing-Song Xie
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Jiang-Ming Chen
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Shen-Liang Shan
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Kun Xie
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Xiao-Ping Geng
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China
| | - Fu-Bao Liu
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
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Deng G, Yao L, Zeng F, Xiao L, Wang Z. Nomogram For Preoperative Prediction Of Microvascular Invasion Risk In Hepatocellular Carcinoma. Cancer Manag Res 2019; 11:9037-9045. [PMID: 31695495 PMCID: PMC6816236 DOI: 10.2147/cmar.s216178] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Accepted: 09/10/2019] [Indexed: 12/24/2022] Open
Abstract
Objective To preoperatively predict the microvascular invasion (MVI) risk in hepatocellular carcinoma (HCC) using nomogram. Methods A retrospective cohort of 513 patients with HCC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent risk factors for MVI. Based on the independent risk factors, nomogram was established to preoperatively predict the MVI risk in HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). Results Tumor size (OR=1.17, 95% CI: 1.11–1.23, p<0.001), preoperative AFP level greater than 155 ng/mL (OR=1.65, 95% CI: 1.13–2.39, p=0.008) and NLR (OR=1.14, 95% CI: 1.00–1.29, p=0.042) were the independent risk factors for MVI. Incorporating these 3 factors, nomogram was established with the concordance index of 0.71 (95% CI, 0.66–0.75) and well-fitted calibration curves. DCA confirmed that using this nomogram added more benefit compared with the measures that treat all patients or treat none patients. At the cutoff value of predicted probability ≥0.44, the model demonstrated sensitivity of 61.64%, specificity of 71.53%, positive predictive value (PPV) of 64.13%, and negative predictive value (NPV) of 69.31%. Conclusion Nomogram was established for preoperative prediction of the MVI risk in HCC patients, and better therapeutic choice will be made if it was applied in clinical practice.
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Affiliation(s)
- Guangtong Deng
- General Surgery Department, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Lei Yao
- General Surgery Department, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Furong Zeng
- Xiangya School of Medicine, Central South University, Changsha, People's Republic of China
| | - Liang Xiao
- General Surgery Department, Xiangya Hospital, Central South University, Changsha, People's Republic of China
| | - Zhiming Wang
- General Surgery Department, Xiangya Hospital, Central South University, Changsha, People's Republic of China
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Chen ZH, Zhang XP, Wang H, Chai ZT, Sun JX, Guo WX, Shi J, Cheng SQ. Effect of microvascular invasion on the postoperative long-term prognosis of solitary small HCC: a systematic review and meta-analysis. HPB (Oxford) 2019; 21:935-944. [PMID: 30871805 DOI: 10.1016/j.hpb.2019.02.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 01/26/2019] [Accepted: 02/04/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND The effect of microvascular invasion (MVI) on the postoperative long-term prognosis of solitary small hepatocellular carcinoma remains controversial. We compared the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma. METHODS The PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare the long-term outcomes of MVI-positive and MVI-negative groups of patients with solitary small hepatocellular carcinoma from inception to November 1, 2018. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors. RESULTS Fourteen studies involving 3033 patients were evaluated. A meta-analysis of all 14 studies suggested that the OS of the MVI-positive group was significantly worse than that of the MVI-negative group (HR = 2.39, 95% CI = 2.02-2.84, I2 = 22.8%; P < 0.001). Twelve studies were included in the meta-analysis of DFS, and MVI showed a worse prognosis (HR = 1.79, 95% CI = 1.59-2.02, I2 = 25.3%; P < 0.001). Subgroup analysis demonstrated that MVI still showed a negative effect on the long-term OS and DFS of patients with solitary small HCC measuring up to 2 cm, 3 cm, or 5 cm. CONCLUSION Microvascular invasion was a risk factor for poorer prognosis for solitary small hepatocellular carcinoma.
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Affiliation(s)
- Zhen-Hua Chen
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hang Wang
- Company 8 of Student Bridge, Second Military Medical University, Shanghai, China
| | - Zong-Tao Chai
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ju-Xian Sun
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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Erstad DJ, Tanabe KK. Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma. Ann Surg Oncol 2019; 26:1474-1493. [PMID: 30788629 DOI: 10.1245/s10434-019-07227-9] [Citation(s) in RCA: 281] [Impact Index Per Article: 46.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a morbid condition for which surgical and ablative therapy are the only options for cure. Nonetheless, over half of patients treated with an R0 resection will develop recurrence. Early recurrences within 2 years after resection are thought to be due to the presence of residual microscopic disease, while late recurrences > 2 years after resection are thought to be de novo metachronous HCCs arising in chronically injured liver tissue. Microvascular invasion (MVI) is defined as the presence of micrometastatic HCC emboli within the vessels of the liver, and is a critical determinant of early recurrence and survival. In this review, we summarize the pathogenesis and clinical relevance of MVI, which correlates with adverse biological features, including high grade, large tumor size, and epithelial-mesenchymal transition. Multiple classification schemas have been proposed to capture the heterogeneous features of MVI that are associated with prognosis. However, currently, MVI can only be determined based on surgical specimens, limiting its clinical applicability. Going forward, advances in axial imaging technologies, molecular characterization of biopsy tissue, and novel serum biomarkers hold promise as future methods for non-invasive MVI detection. Ultimately, MVI status may be used to help clinicians determine treatment plans, particularly with respect to surgical intervention, and to provide more accurate prognostication.
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Affiliation(s)
- Derek J Erstad
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Kenneth K Tanabe
- Division of Surgical Oncology, Massachusetts General Hospital, Boston, MA, USA.
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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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Microvascular Invasion in HCC: The Molecular Imaging Perspective. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:9487938. [PMID: 30402046 PMCID: PMC6193341 DOI: 10.1155/2018/9487938] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 09/20/2018] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma represents the most frequent primary liver tumor; curative options are only surgical resection and liver transplantation. From 1996, Milan Criteria are applied in consideration of patients with cirrhosis and hepatocellular for liver transplantation; nonetheless, more recently, Milan Criteria have been criticized because they appear over conservative. Apart from number and size of lesions and biomarker levels, which already have been associated with poorer prognosis, overall survival and recurrence rates after transplantation are affected also by the presence of vascular invasion. Microvascular invasion suggests a poor prognosis but it is often hard to detect before transplant. Diagnostic imaging and tumor markers may play an important role and become the main tools to define microvascular invasion. In particular, a possible role could be found for computed tomography, magnetic resonance imaging, and positron emission tomography. In this paper, we analyze the possible role of positron emission tomography as a preoperative imaging biomarker capable of predicting microvascular invasion in patients with hepatocellular carcinoma and thus selecting optimal candidates for liver transplantation.
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Li C, Zhang XY, Peng W, Wen TF, Yan LN, Li B, Yang JY, Wang WT, Xu MQ, Chen LP. Preoperative albumin-bilirubin grade plus platelet-to-lymphocyte ratio predict the outcomes of patients with BCLC stage A hepatocellular carcinoma after liver resection. Medicine (Baltimore) 2018; 97:e11599. [PMID: 30024565 PMCID: PMC6086466 DOI: 10.1097/md.0000000000011599] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
There is little information regarding the predictive ability of albumin-bilirubin grades (ALBI) plus platelet-to-lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) following liver resection. In this study, we aimed to evaluate the prognostic power of the ALBI-PLR score in patients with hepatitis B virus-related (HBV-related) HCC within Barcelona Clinic Liver Cancer (BCLC) stage A after liver resection.Around 475 patients were included in this study. Patients with preoperative ALBI grades 1, 2, or 3 were allocated a score of 0, 1, or 2, respectively. Patients with preoperative PLR >150 or ≤150 were allocated a score of 0 or 1, respectively. The ALBI-PLR score was the summary of the ALBI and PLR scores.During the follow-up period, 256 patients experienced recurrence, and 150 patients died. Multivariate analysis revealed tumor size, multiple tumors, positive HBV-DNA load, cirrhosis, and ALBI-PLR score as being independently associated with postoperative recurrence, whereas tumor size, high preoperative α-fetoprotein level, and ALBI-PLR score were independent risk factors for postoperative mortality. HCC patients with high ALBI-PLR score had poor recurrence-free and overall survival.The preoperative ALBI-PLR score is a surrogate marker for predicting HBV-related HCC patient's prognosis after liver resection. A high ALBI-PLR score is associated with a high incidence of postoperative recurrence and mortality.
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Affiliation(s)
| | | | | | | | | | - Bo Li
- Department of Liver Surgery
| | | | | | | | - Li-Ping Chen
- Department of General Surgery, West China Hospital of Sichuan University, Chengdu, China
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Reply to: "Detecting microvascular invasion in HCC with contrast-enhanced MRI: Is it a good idea?". J Hepatol 2018; 68:863-864. [PMID: 29288752 DOI: 10.1016/j.jhep.2017.12.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 12/20/2017] [Indexed: 01/02/2023]
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