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Ju S, Duan X, Wang Y, Zhang M, Bai Y, He X, Wang C, Liu J, Yao W, Zhou C, Xiong B, Zheng C. Blocking TGFβR synergistically enhances anti-tumor effects of anti-PD-1 antibody in a mouse model of incomplete thermal ablation. Int Immunopharmacol 2024; 138:112585. [PMID: 38950456 DOI: 10.1016/j.intimp.2024.112585] [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: 04/01/2024] [Revised: 06/20/2024] [Accepted: 06/25/2024] [Indexed: 07/03/2024]
Abstract
The mechanism of early tumor recurrence after incomplete microwave ablation (iMWA) is poorly understood. The anti-programmed cell death protein 1 (anti-PD-1) monotherapy is reported to be ineffective to prevent the progression of residual tumor resulted from iMWA. Transforming growth factor-β (TGFβ) signaling pathway plays an important role in tumorigenesis and development. We assume blocking transforming growth factor-β receptor (TGFβR) after incomplete iMWA may synergistically enhance the effect of anti-PD-1 antibody to prevent the progression of residual tumor. We construct an iMWA model with mice harboring Hepa1-6 derived xenograft. The Tgfb1 expression and phosphorylated-Smad3 protein expression is upregulated in the residual tumor after iMWA. With the application of TGFβR inhibitor SB431542, the cell proliferation potential, the tumor growth, the mRNA expression of epithelial mesenchymal transition (EMT) markers including Cdh2, and Vim, and cancer stem cell marker Epcam, and the infiltrating Treg cells are reduced in the residual tumor tissue. In addition, iMWA combined with TGFβR blocker and anti-PD-1 antibody further decreases the cell proliferation, tumor growth, expression of EMT markers and cancer stem cell marker, and the infiltrating Treg cells in the residual tumor tissue. Blocking TGFβR may alleviate the pro-tumoral effect of tumor microenvironment thereby significantly prevents the progression of residual tumor tissue. Our study indicates that blocking TGFβR may be a novel therapeutic strategy to enhance the effect of anti-PD-1 antibody to prevent residual hepatocellular carcinoma (HCC) progression after iMWA.
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Affiliation(s)
- Shuguang Ju
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xuhua Duan
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China
| | - Yingliang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Mengfan Zhang
- Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450000, China
| | - Yaowei Bai
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Xuelian He
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
| | - Chaoyang Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Jiacheng Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Wei Yao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Chen Zhou
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China
| | - Bin Xiong
- Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China.
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Kulkarni CB, Pullara SK, C S R, Moorthy S. Complications of Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma. Acad Radiol 2024; 31:2987-3003. [PMID: 38092590 DOI: 10.1016/j.acra.2023.11.020] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Revised: 11/11/2023] [Accepted: 11/14/2023] [Indexed: 07/21/2024]
Abstract
Radiofrequency ablation (RFA) is a potentially curative treatment option for early Hepatocellular carcinoma. The RFA is considered safe with a relatively low incidence of complications ranging from 2%-7.9%. Though most of the complications are self-limiting, sometimes they can be life-threatening. The occurrence of the particular complication depends on various factors like tumour location and morphology, underlying disease and ablation technique. A detailed understanding of potential complications along with the associated risk factors will help to employ strategies to prevent them, identify them early and manage them when they occur. This article demonstrates various radiofrequency ablation-related complications and discusses the risk factors and technical strategies to minimise them and achieve complete ablation of the tumour.
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Affiliation(s)
- Chinmay Bhimaji Kulkarni
- Department of Radiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita Lane, Ponekkra. Elamakkara P.O. 682041, Kochi, Kerala, India.
| | - Sreekumar Karumathil Pullara
- Department of Radiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita Lane, Ponekkra. Elamakkara P.O. 682041, Kochi, Kerala, India
| | - Rajsekar C S
- Department of Radiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita Lane, Ponekkra. Elamakkara P.O. 682041, Kochi, Kerala, India
| | - Srikanth Moorthy
- Department of Radiology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita Lane, Ponekkra. Elamakkara P.O. 682041, Kochi, Kerala, India
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Hsiao CY, Ho CM, Ho MC, Cheng HY, Wu YM, Lee PH, Hu RH. Risk factors, patterns, and outcome predictors of late recurrence in patients with hepatocellular carcinoma after curative resection: A large cohort study with long-term follow-up results. Surgery 2024; 176:2-10. [PMID: 38519406 DOI: 10.1016/j.surg.2024.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 01/31/2024] [Accepted: 02/05/2024] [Indexed: 03/24/2024]
Abstract
BACKGROUND Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome. METHODS This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models. RESULTS The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence. CONCLUSION Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence.
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Affiliation(s)
- Chih-Yang Hsiao
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Maw Ho
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Hsinchu Branch, Hsinchu County, Taiwan
| | - Hou-Ying Cheng
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City, Taiwan
| | - Yao-Ming Wu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Surgery, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Po-Huang Lee
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Yunlin Branch, Yunlin County, Taiwan
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Wu Z, Zeng Y, Yuan Y, Shi Y, Qiu J, Li B, Yuan Y, He W. Early recurrence of hepatocellular carcinoma in patients after ablation and resection: A propensity score analysis. Am J Surg 2024; 228:94-101. [PMID: 37580221 DOI: 10.1016/j.amjsurg.2023.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/26/2023] [Accepted: 08/01/2023] [Indexed: 08/16/2023]
Abstract
BACKGROUND Early recurrence (ER, recurrence within 2 years) is common in hepatocellular carcinoma (HCC) patients after ablation and resection. We aimed to compare ER and assess the associated risk factors. METHODS We collected data from patients underwent resection (1,235) or ablation (517) for early HCC (solitary tumor ≤5 cm). Baseline of patients were matched using propensity score matching. RESULTS In the matched cohort of 690 patients, the ablation group had a higher ER rate (37.4% vs. 19.4%; P < .001) than the resection group. Patients with ER had worse overall survival (OS) than those without ER in both the ablation (5-year OS: 60.4% vs. 86.7%) and resection groups (5-year OS: 59.2% vs. 88.1%). Ablation treatment was identified as an independent adverse prognostic factor for ER (hazard ratio: 2.751, P < .001). Resection conferred a significant favorable OS than ablation (2-year: 95.4% vs. 90.9%; 5-years: 83.8% vs. 77.0%). CONCLUSIONS Resection was superior to ablation in minimizing the risk of ER and offering a better OS for patients with early HCC.
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Affiliation(s)
- Zongfeng Wu
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yi Zeng
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yichuan Yuan
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yunxing Shi
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Binkui Li
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Wei He
- State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
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Zhang N, Chen R, Cao X, Wang L. Aberrantly expressed HIF-1α enhances HCC stem cell-like traits via Wnt/β-catenin signaling activation after insufficient radiofrequency ablation. J Cancer Res Ther 2023; 19:1517-1524. [PMID: 38156917 DOI: 10.4103/jcrt.jcrt_1458_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 07/01/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Radiofrequency ablation has become a favorable treatment modality for small hepatocellular carcinoma (HCC) recently; however, insufficient radiofrequency ablation (RFA) was shown to lead to enhanced invasiveness and metastasis of HCC in our previous study, while the underlying molecular mechanism has not been understood. MATERIALS AND METHODS In order to explore the influence of the hypoxic microenvironment on residual cancer and cancer stem cell (CSC)-like characteristics of HCC cells in this process, an in vitro hypoxic model and an insufficient RFA mouse model were established with HCC cancer cell lines. Immunochemistry staining and western blot were used to examine the expression of hypoxia-inducible factor (HIF)-1α and liver CSC markers. The 3D colon formation assay, tumor cell invasion assay, and gene transfection assays were applied to test the change in liver CSC stemness and HCC cell invasion. RESULTS After insufficient RFA treatment, the upregulated HIF-1α expression was associated with an increase in the CSC-like population in residual cancer. In vitro, hypoxic tumor cells showed aggressive CSC-like properties and phenotypes. Wnt/β-catenin signaling activation was shown to be necessary for the acquisition of liver CSC-like characteristics under hypoxic conditions. CONCLUSION Overall, the aberrantly enhanced HIF-1α expression enhanced the liver CSC-like traits via abnormal Wnt/β-catenin signaling activation after insufficient RFA, and the overexpressed HIF-1α would be a vital factor and useful biomarker during the HCC recurrence and metastasis.
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Affiliation(s)
- Ning Zhang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ruoxue Chen
- Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai, China
| | - Xin Cao
- Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai, China
| | - Lu Wang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
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Abdelhamed W, El-Kassas M. Hepatocellular carcinoma recurrence: Predictors and management. LIVER RESEARCH (BEIJING, CHINA) 2023; 7:321-332. [PMID: 39958776 PMCID: PMC11791921 DOI: 10.1016/j.livres.2023.11.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 09/14/2023] [Accepted: 11/17/2023] [Indexed: 02/18/2025]
Abstract
Hepatocellular carcinoma (HCC), the sixth most common cancer globally, is associated with high mortality rates and more than 830,000 annual deaths. Despite advances in the available management options including surgical resection and local ablative therapies, recurrence rates after the initial treatment exceed 50%, even among patients who have undergone curative-intent therapy. Moreover, postsurgical HCC recurrence occurs in about 70% of cases five years postoperatively. The management of recurrent HCC remains undefined. This review discusses different predictors for HCC recurrence after each treatment modality and different approaches available to stratify these patients. More specific guidelines for managing HCC recurrence and strict surveillance protocols for such recurrence after initial HCC management are needed.
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Affiliation(s)
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
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Chen WY, Li C, Liu ZP, Kong QY, Sun LY, Zeng YY, Liang YJ, Zhou YH, Chen TH, Chen ZX, Wang MD, Yao LQ, Lau WY, Pawlik TM, Shen F, Ji JS, Yang T. Novel online calculator to predict reduced risk of early recurrence from adjuvant transarterial chemoembolisation for patients with hepatocellular carcinoma. EGASTROENTEROLOGY 2023; 1:e100008. [PMID: 39944245 PMCID: PMC11770458 DOI: 10.1136/egastro-2023-100008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Accepted: 02/20/2023] [Indexed: 02/20/2025]
Abstract
Background The role of adjuvant transarterial chemoembolisation (TACE) to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma (HCC). Personalised predictive tool to select which patients may benefit from adjuvant TACE is lacking. This study aimed to develop and validate an online calculator for estimating the reduced risk of early recurrence from adjuvant TACE for patients with HCC. Methods From a multi-institutional database, 2590 eligible patients undergoing curative-intent hepatectomy for HCC were enrolled, and randomly assigned to the training and validation cohorts. Independent predictors of early recurrence within 1 year of surgery were identified in the training cohort, and subsequently used to construct a model and corresponding prediction calculator. The predictive performance of the model was validated using concordance indexes (C-indexes) and calibration curves, and compared with conventional HCC staging systems. The reduced risk of early recurrence when receiving adjuvant TACE was used to estimate the expected benefit from adjuvant TACE. Results The prediction model was developed by integrating eight factors that were independently associated with risk of early recurrence: alpha-fetoprotein level, maximum tumour size, tumour number, macrovascular and microvascular invasion, satellite nodules, resection margin and adjuvant TACE. The model demonstrated good calibration and discrimination in the training and validation cohorts (C-indexes: 0.799 and 0.778, respectively), and performed better among the whole cohort than four conventional HCC staging systems (C-indexes: 0.797 vs 0.562-0.673, all p<0.001). An online calculator was built to estimate the reduced risk of early recurrence from adjuvant TACE for patients with resected HCC. Conclusions The proposed calculator can be adopted to assist decision-making for clinicians and patients to determine which patients with resected HCC can significantly benefit from adjuvant TACE.
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Affiliation(s)
- Wei-Yue Chen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research, Department of Interventional Radiology, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Zhi-Peng Liu
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Qing-Yu Kong
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Li-Yang Sun
- Department of General Surgery, Cancer Center, Division of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou, Fujian, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Pu’er, Yunnan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People’s Hospital, Ziyang, Sichuan, China
| | - Zi-Xiang Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
| | - Jian-Song Ji
- The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research, Department of Interventional Radiology, Lishui Hospital of Zhejiang University, Lishui, Zhejiang, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China
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Shi ZR, Duan YX, Cui F, Wu ZJ, Li MP, Song PP, Peng QL, Ye WT, Yin KL, Kang MQ, Yu YX, Yang J, Tang W, Liao R. Integrated proteogenomic characterization reveals an imbalanced hepatocellular carcinoma microenvironment after incomplete radiofrequency ablation. J Exp Clin Cancer Res 2023; 42:133. [PMID: 37231509 PMCID: PMC10210354 DOI: 10.1186/s13046-023-02716-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 05/19/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. METHODS Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. RESULTS Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways. CONCLUSIONS This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA. TRIAL REGISTRATION ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588 .
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Affiliation(s)
- Zheng-Rong Shi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Yu-Xin Duan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Fang Cui
- Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhong-Jun Wu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Mao-Ping Li
- Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Pei-Pei Song
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Qi-Ling Peng
- Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China
| | - Wen-Tao Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Kun-Li Yin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Mei-Qing Kang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Yan-Xi Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Jian Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China
| | - Wei Tang
- National Center for Global Health and Medicine, Tokyo, Japan
| | - Rui Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. Youyi Rd, Chongqing, 400016, China.
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Chen W, Hu S, Liu Z, Sun Y, Wu J, Shen S, Peng Z. Adjuvant anti-PD-1 antibody for hepatocellular carcinoma with high recurrence risks after hepatectomy. Hepatol Int 2023; 17:406-416. [PMID: 36645648 DOI: 10.1007/s12072-022-10478-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 12/27/2022] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND PURPOSE The clinical role of postoperative adjuvant therapy in hepatocellular carcinoma (HCC) is still unclear. The purpose of our study was to explore the clinical value of postoperative adjuvant anti-programed cell death 1 antibody (PA-PD-1) on the prognosis of HCC patients with high relapse risks after surgery. PATIENTS AND METHODS Data of consecutive HCC patients with high recurrence risks treated with liver resection at our center during January 2019 and March 2021 were prospectively collected. Baseline differences were balanced between HCC patients with (PA-PD-1 group) or without PA-PD-1 (non-PD-1 group) after hepatectomy by propensity-score matching (PSM). Between these two groups, we compared overall survival (OS) and recurrence-free survival (RFS). Independent prognostic risk factors for OS and RFS were confirmed by Cox regression analysis, and subgroup analysis was also performed. RESULTS 47 pairs of patients with or without PD-1 treatment after hepatectomy were matched. After PSM, the 1-year and 2-year RFS was 58.4% and 44.1% in the PA-PD-1 group, and 34.0% and 21.3% in the non-PD-1 group (p = 0.008). The OS at 1 year and 2 years was 91.2% and 91.2% in the PA-PD-1 group, compared with 85.1% and 61.7% in the non-PD-1 group (p = 0.024). Multivariable analyses demonstrated that PA-PD-1 was an independent protective predictor associated with RFS and OS. Through subgroup analysis, we concluded that HCC patients with portal venous tumor thrombus (PVTT) or tumor size ≥ 5 cm significantly benefited from PA-PD-1 therapy in RFS and OS. CONCLUSIONS Adjuvant anti-PD-1 antibody can effectively improve the survival outcomes of HCC patients with high relapse risks after hepatectomy in this prospective observational study. This finding should be confirmed by results of the ongoing phase 3 randomized controlled trials.
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Affiliation(s)
- Wei Chen
- Center of Hepato-Pancreato- Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.,Department of Pancreaticobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China
| | - Shuifang Hu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Zelong Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Yukun Sun
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China
| | - Jian Wu
- Center of Hepato-Pancreato- Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Shunli Shen
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
| | - Zhenwei Peng
- Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-Sen University, NO.58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China. .,Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. .,Cancer Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China. .,Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.
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10
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Toubert C, Guiu B, Al Taweel B, Assenat E, Panaro F, Souche FR, Ursic-Bedoya J, Navarro F, Herrero A. Prolonged Survival after Recurrence in HCC Resected Patients Using Repeated Curative Therapies: Never Give Up! Cancers (Basel) 2022; 15:232. [PMID: 36612227 PMCID: PMC9818493 DOI: 10.3390/cancers15010232] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/18/2022] [Accepted: 12/26/2022] [Indexed: 01/04/2023] Open
Abstract
Surgical resection is the optimal treatment for HCC, despite a high risk of recurrence. Few data are available on patient’s survival after resection. This is a retrospective study of tumor recurrence occurring after hepatectomy for HCC from 2000 to 2016. Univariate and multivariate analyses were performed to identify prognostic factors of survival after recurrence (SAR). Among 387 patients, 226 recurred (58.4%) with a median SAR of 26 months. Curative treatments (liver transplantation, repeat hepatectomy, thermal ablation) were performed for 44.7% of patients. Independent prognostic factors for SAR were micro-vascular invasion on the primary surgical specimen, size of the initial tumor >5 cm, preoperative AFP, albumin and platelet levels, male gender, number, size and localization of tumors at recurrence, time to recurrence, Child−Pugh score and treatment at recurrence. In subgroup analysis, early recurrence (46%) was associated with a decrease in SAR, by contrast with late recurrence. However, the overall survival (OS) of patients with early recurrence and curative treatment did not significantly differ from that of non-recurring patients. For late recurrence, OS did not significantly differ from that of non-recurring patients, regardless of the proposed treatment. Aggressive and repeat treatments are therefore key to improve prognosis of patients with HCC.
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Affiliation(s)
- Cyprien Toubert
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Boris Guiu
- Department of Digestive Imaging, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Bader Al Taweel
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Eric Assenat
- Department of Digestive Oncology, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Fabrizio Panaro
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - François-Regis Souche
- Department of Minimally Invasive and Oncologic Surgery, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Jose Ursic-Bedoya
- Liver Transplantation Unit, Department of Hepatology, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Francis Navarro
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
| | - Astrid Herrero
- Department of HBP Surgery and Liver Transplantation, Montpellier University Hospital, University of Montpellier, 34295 Montpellier, France
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11
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Late margin recurrence after curative resection for hepatocellular carcinoma – Case report of two cases and review of this enigmatic entity. INTERNATIONAL JOURNAL OF SURGERY OPEN 2022. [DOI: 10.1016/j.ijso.2022.100533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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12
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2450-MHz microwave ablation of liver metastases under 3.0 T wide-bore magnetic resonance guidance: a pilot study. Sci Rep 2022; 12:12640. [PMID: 35879411 PMCID: PMC9314346 DOI: 10.1038/s41598-022-16989-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 07/19/2022] [Indexed: 11/29/2022] Open
Abstract
To investigate the feasibility and effectiveness of 3.0 T wide-bore magnetic resonance (MR)-guided microwave ablation (MA) of liver metastases (LM). From October 2018 to May 2020, 39 patients with 63 LM were treated with 3.0 T wide-bore MR-guided 2450-MHz MA therapy. The procedure parameters, technical success, complications, biochemical index changes, local tumor response, local tumor progression (LTP), 12-month disease-free survival (DFS) and 12-month overall survival (OS) were recorded and analyzed. The mean tumor maximum diameter and total procedure time were 3.0 cm and 55.2 min, respectively. Technical success was 100%, but 5 cases (12.8%) had grade-1 complications. Alanine transaminase, aspartate transaminase and total bilirubin showed a slight transient increase on day 3 (P < 0.05) and returned to normal by day 30 (P > 0.05). The complete ablation rates for ≤ 2.5 and > 2.5 cm lesions were 100% and 92.5%, respectively. During the median follow-up of 12.0 months, the LTP rate was 4.8% (3/63), and the 12-month DFS and OS rates were 61.3% and 92.2%, respectively. 3.0 T wide-bore MR-guided MA for LM is a safe and effective approach, especially for small LM.
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13
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Shen GL, Lu Y, Liang L, Lu WF, Diao YK, Xiao ZQ, Zhang KJ, Zhang JG, Zhang CW, Liu J. Impact of diabetes mellitus on the long-term prognosis of patients with hepatocellular carcinoma after hepatectomy. Expert Rev Gastroenterol Hepatol 2022; 16:473-478. [PMID: 35387530 DOI: 10.1080/17474124.2022.2063837] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy. METHODS The pattern of recurrence for HCC was often stratified into early-stage (<2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis. RESULTS A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036, P = 0.022) and RFS (HR 1.365, 95% CI 1.043-1.787, P = 0.023). CONCLUSION DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.
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Affiliation(s)
- Guo-Liang Shen
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yi Lu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Lei Liang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.,Department of Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Hangzhou, China
| | - Wen-Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, Zhejiang, China
| | - Yong-Kang Diao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Zun-Qiang Xiao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Kang-Jun Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jun-Gang Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Cheng-Wu Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Junwei Liu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
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14
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Comparison of the Efficacy Among Transcatheter Arterial Chemoembolization (TACE)-Radiofrequency Ablation Plus Apatinib, TACE Plus Apatinib, and TACE Alone for Hepatocellular Carcinoma: A Retrospective Study. Cardiovasc Intervent Radiol 2022; 45:780-790. [PMID: 35410405 DOI: 10.1007/s00270-022-03141-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 03/28/2022] [Indexed: 11/02/2022]
Abstract
BACKGROUND This study aimed to investigate the efficacy and safety of apatinib plus transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) in the therapy of hepatocellular carcinoma (HCC) patients. METHODS From December 2015 to June 2018, 175 eligible participants were included in our research. Twenty-four patients who received apatinib plus TACE and RFA were categorized as the TACE + RFA-A group, 82 patients who received apatinib plus TACE were categorized as the TACE-A group, and 69 patients who received TACE alone were categorized as the TACE group. Treatment complications, treatment response, overall survival (OS), and time to progression (TTP) were recorded. Survival analyses were compared. Univariate and multivariate Cox analyses were conducted to investigate the predictive factors for OS and TTP. A subgroup analysis was carried out. RESULTS The median TTP was 8.0 months (95% CI 6.7-9.3) in the TACE + RFA-A, which was longer than the TACE-A group (6.0 months, 95% CI 4.8-7.2) and TACE group (3.0 months, 95% CI 2.3-3.7); the difference was statistically significant (P < 0.001). The median OS was 23.0 months (95% CI 12.6-33.4) in the TACE + RFA-A group, 18.0 months (95% CI 16.2-19.8) in the TACE-A group, and 8.0 months (95% CI 5.3-10.7) in the TACE group; the difference was statistically significant (P < 0.001). The objective response rate (ORR) was higher in TACE + RFA-A t group (M1, 70.8% vs 65.9% vs. 46.4%, P = 0.023; M3, 58.3% vs. 53.7% vs. 26.1%, P = 0.001). Multivariate Cox analysis demonstrated that treatment strategy and tumor size were independent prognostic factors for the OS and TTP, whereas the Child-Pugh stage was predictive factor of OS. No treatment-related death was observed. The toxicity was comparable between the two groups. CONCLUSION TACE combined with RFA plus apatinib is a safe three-modality treatment for the intermediate or advanced HCC, and it demonstrated better efficacy than TACE plus apatinib or TACE alone.
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15
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Xia S, Li X, Xu S, Ni X, Zhan W, Zhou W. Sublethal heat treatment promotes breast cancer metastasis and its molecular mechanism revealed by quantitative proteomic analysis. Aging (Albany NY) 2022; 14:1389-1406. [PMID: 35150481 PMCID: PMC8876919 DOI: 10.18632/aging.203884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Accepted: 10/03/2021] [Indexed: 11/30/2022]
Abstract
Radiofrequency ablation (RFA) is a frequently used thermal ablation technique for breast tumors. The study aimed to identify the effect of sublethal heat treatment on biological function of breast cancer cells and reveal its potential molecular mechanism. The expression profile of dysregulated proteins in sublethal heat treated breast cancer cells was analyzed by quantitative proteomic analysis. The differentially expressed proteins in the sublethal heat treated breast cancer were identified. The potential biological functions of these proteins were evaluated. The proliferation and invasion ability of breast cancer cells were enhanced after sublethal heat treatment. The expression profile of proteins in sublethal heat treated breast cancer cells was abundant, and most of which were newly discovered. A total of 206 differentially expressed proteins were identified. Among them, 101 proteins were downregulated while 105 proteins were upregulated. GO and KEGG analysis indicated that various systems were involved in the process of sublethal heat treatment including cancer, immune system, et al. Immunohistochemistry staining showed that the expression of Heat shock protein 1B, NOB1 and CRIP1 was highly expressed while the expression of BCLAF1 was lower in sublethal heat treated group. The proliferation and invasion ability of breast cancer cells were enhanced after sublethal heat treatment. Sublethal heat treatment caused gene alterations in cancer and immune system. Heat shock protein 1B, NOB1 and CRIP1 were upregulated while BCLAF1 was downregulated in breast cancer after sublethal heat treatment.
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Affiliation(s)
- Shujun Xia
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyu Li
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shangyan Xu
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaofeng Ni
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiwei Zhan
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Zhou
- Department of Ultrasound, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Department of Ultrasound, Ruijin Hospital Luwan Branch, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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16
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Chu W, Li P, Wu X, Zhang P, Zhou H, Niu B. Risk factors for recurrence beyond Milan criteria after radiofrequency ablation in transplantable small hepatocellular carcinoma. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:580-585. [PMID: 35042367 DOI: 10.17235/reed.2022.8592/2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
This study aims to determine the risk factors of recurrence beyond Milan criteria in patients with transplantable early hepatocellular carcinoma (HCC) after the first Radiofrequency ablation (RFA). 95 patients with newly diagnosed transplantable small HCC with single ≤ 3 cm were analyzed retrospectively. During the 39-month median follow-up period, 12 (21.8%) patients with HCC < 2 cm and 22 (56.4%) patients with HCC ≥ 2 cm relapsed beyond Milan criteria (p = 0.001). The 1- and 3-year recurrence rates beyond Milan criteria were 6.3% and 14.7% in HCC < 2 cm group, compared with 24.1% and 55.6% in HCC ≥ 2 cm group(p < 0.0001).HCC ≥ 2 cm, red blood cell distribution width-to-lymphocyte ratio (RLR) ≥ 18.3, alpha-fetoprotein (AFP) > 15 ng/ml and early recurrence after RFA were independent predictors of recurrence exceeding Milan criteria. For patients with transplantable early single small HCC whose tumor diameter ≥ 2cm and have higher RLR and AFP levels before first RFA and early recurrence after RFA (recurrence within 2 years), close follow-up and early liver transplantation should be initiated to obtain the best survival benefit.
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Affiliation(s)
- Weike Chu
- School of Graduates, Tianjin Medical University, China
| | - Ping Li
- Hepatology, Tianjin City Second People's Hospital, China
| | - Xue Wu
- School of Graduates, Tianjin Medical University, China
| | - Peng Zhang
- School of Graduates, Tianjin Medical University, China
| | - Hui Zhou
- School of Graduates, Tianjin Medical University, China
| | - Bin Niu
- School of Graduates, Tianjin Medical University, China
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17
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Cao S, Lyu T, Fan Z, Guan H, Song L, Tong X, Wang J, Zou Y. Long-term outcome of percutaneous radiofrequency ablation for periportal hepatocellular carcinoma: tumor recurrence or progression, survival and clinical significance. Cancer Imaging 2022; 22:2. [PMID: 34983650 PMCID: PMC8725335 DOI: 10.1186/s40644-021-00442-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 12/08/2021] [Indexed: 02/08/2023] Open
Abstract
Background/aim Recent studies have suggested that periportal location of percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered as one of the independent risk factors for local tumor progression (LTP). However, the long-term therapeutic outcomes of percutaneous RFA as the first-line therapy for single periportal HCCand corresponding impacts on tumor recurrence or progression are still unclear. Materials and methods From February 2011 to October 2020, a total of 233 patients with single nodular HCC ≤ 5 cm who underwent RFA ± transarterial chemoembolization (TACE) as first-line therapy was enrolled and analyzed, including 56 patients in the periportal group and 177 patients in the nonperiportal group. The long-term therapeutic outcomes between the two groups were compared, risk factors of tumor recurrence or progression were evaluated. Results The LTP rates at 1, 3, and 5 years were significantly higher in the periportal group than those in the nonperiportal group (15.7, 33.7, and 46.9% vs 6.0, 15.7, and 28.7%, respectively, P = 0.0067). The 1-, 3- and 5-year overall survival (OS) rates in the periportal group were significantly worse than those in the nonperiportal group (81.3, 65.1 and 42.9% vs 99.3, 90.4 and 78.1%, respectively, P<0.0001). In the subgroup of single HCC ≤ 3 cm, patients with periportal HCC showed significantly worse LTP P = 0.0006) and OS (P<0.0001) after RFA than patients with single nonperiportal HCC; The univariate and multivariate analyses revealed that tumor size, periportal HCC and AFP ≥ 400ug/ml were independent prognostic factors for tumor progression after RFA. Furthermore, patients with single periportal HCC had significantly higher risk for IDR(P = 0.0012), PVTT(P<0.0001) and extrahepatic recurrence(P = 0.0010) after RFA than those patients with single nonperiportal HCC. . Conclusion The long-term therapeutic outcomes of RFA as the first-line therapy for single periportal HCC were worse than those for single nonperiportal HCC, an increased higher risk of tumor recurrence or progression after RFA was significantly associated with periportal HCC. Supplementary Information The online version contains supplementary material available at 10.1186/s40644-021-00442-2.
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Affiliation(s)
- Shoujin Cao
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Tianshi Lyu
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Zeyang Fan
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Haitao Guan
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Li Song
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Xiaoqiang Tong
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China
| | - Jian Wang
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
| | - Yinghua Zou
- Department of Interventional and Vascular Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
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18
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Wang X, Liu G, Chen S, Bi H, Xia F, Feng K, Ma K, Ni B. Combination therapy with PD-1 blockade and radiofrequency ablation for recurrent hepatocellular carcinoma: a propensity score matching analysis. Int J Hyperthermia 2021; 38:1519-1528. [PMID: 34702122 DOI: 10.1080/02656736.2021.1991011] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND This study aimed to evaluate whether combined therapy with PD-1 blockade (anti-PD-1) and radiofrequency ablation (RFA) is superior to RFA monotherapy for recurrent hepatocellular carcinoma (HCC). METHODS A total of 127 patients who underwent anti-PD-1 plus RFA treatment (n = 41) or RFA alone (n = 86) for recurrent HCC were included in this retrospective study. A matched cohort comprising 40 patients from each group was selected after propensity score matching analysis. Clinical data including post-RFA HCC recurrence (primary endpoint), overall survival (OS) (secondary endpoint), adverse events, and toxic effects were retrospectively analyzed. RESULTS The 1-year recurrence-free survival rates for the anti-PD-1 plus RFA and RFA groups were 32.5% and 10.0% after propensity score matching. There were statistically significant differences between the two groups in terms of the recurrence-free survival rate (p = 0.001) and OS rate (p = 0.016). Tumor number, tumor-node metastasis (TNM) stage, antiviral therapy, and anti-PD-1 treatment were demonstrated to be important factors associated with 1-year recurrence-free survival probability by univariate and multivariate analyses. Univariate and multivariate analyses demonstrated that tumor number, TNM stage and anti-PD-1 treatment were significant prognostic factors for OS. RFA treatment-related adverse events included pleural effusions that require drainage and a mild or moderate increase in body temperature. Grade 3 or higher events related to anti-PD-1 treatment occurred in 12.8% (6) of patients and were infrequent. CONCLUSIONS Combination therapy with anti-PD-1 plus RFA was superior to RFA alone in improving survival in patients with recurrent HCC.
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Affiliation(s)
- Xiaofei Wang
- Department of Pathophysiology, Third Military Medical University, Chongqing, China
| | - Guo Liu
- Department of Dermatology, Qionglai Hospital of Traditional Chinese Medicine, Qionglai, China
| | - Shu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Huaqiang Bi
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kai Feng
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Kuansheng Ma
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Bing Ni
- Department of Pathophysiology, Third Military Medical University, Chongqing, China
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19
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Paknahad AA, Kerr L, Wong DA, Kolios MC, Tsai SSH. Biomedical nanobubbles and opportunities for microfluidics. RSC Adv 2021; 11:32750-32774. [PMID: 35493576 PMCID: PMC9042222 DOI: 10.1039/d1ra04890b] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 09/19/2021] [Indexed: 12/17/2022] Open
Abstract
The use of bulk nanobubbles in biomedicine is increasing in recent years, which is attributable to the array of therapeutic and diagnostic tools promised by developing bulk nanobubble technologies. From cancer drug delivery and ultrasound contrast enhancement to malaria detection and the diagnosis of acute donor tissue rejection, the potential applications of bulk nanobubbles are broad and diverse. Developing these technologies to the point of clinical use may significantly impact the quality of patient care. This review compiles and summarizes a representative collection of the current applications, fabrication techniques, and characterization methods of bulk nanobubbles in biomedicine. Current state-of-the-art generation methods are not designed to create nanobubbles of high concentration and low polydispersity, both characteristics of which are important for several bulk nanobubble applications. To date, microfluidics has not been widely considered as a tool for generating nanobubbles, even though the small-scale precision and real-time control offered by microfluidics may overcome the challenges mentioned above. We suggest possible uses of microfluidics for improving the quality of bulk nanobubble populations and propose ways of leveraging existing microfluidic technologies, such as organ-on-a-chip platforms, to expand the experimental toolbox of researchers working to develop biomedical nanobubbles. The use of bulk nanobubbles in biomedicine is increasing in recent years. This translates into new opportunities for microfluidics, which may enable the generation of higher quality nanobubbles that lead to advances in diagnostics and therapeutics.![]()
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Affiliation(s)
- Ali A Paknahad
- Department of Mechanical and Industrial Engineering, Ryerson University 350 Victoria Street Toronto Ontario M5B 2K3 Canada .,Institute for Biomedical Engineering, Science and Technology (iBEST), A Partnership Between Ryerson University and St. Michael's Hospital 209 Victoria Street Toronto Ontario M5B 1T8 Canada.,Keenan Research Centre for Biomedical Science, Unity Health Toronto 209 Victoria Street Toronto Ontario M5B 1W8 Canada
| | - Liam Kerr
- Department of Mechanical and Industrial Engineering, Ryerson University 350 Victoria Street Toronto Ontario M5B 2K3 Canada .,Institute for Biomedical Engineering, Science and Technology (iBEST), A Partnership Between Ryerson University and St. Michael's Hospital 209 Victoria Street Toronto Ontario M5B 1T8 Canada.,Keenan Research Centre for Biomedical Science, Unity Health Toronto 209 Victoria Street Toronto Ontario M5B 1W8 Canada
| | - Daniel A Wong
- Institute for Biomedical Engineering, Science and Technology (iBEST), A Partnership Between Ryerson University and St. Michael's Hospital 209 Victoria Street Toronto Ontario M5B 1T8 Canada.,Keenan Research Centre for Biomedical Science, Unity Health Toronto 209 Victoria Street Toronto Ontario M5B 1W8 Canada.,Department of Electrical, Computer, and Biomedical Engineering, Ryerson University 350 Victoria Street Toronto Ontario M5B 2K3 Canada
| | - Michael C Kolios
- Institute for Biomedical Engineering, Science and Technology (iBEST), A Partnership Between Ryerson University and St. Michael's Hospital 209 Victoria Street Toronto Ontario M5B 1T8 Canada.,Keenan Research Centre for Biomedical Science, Unity Health Toronto 209 Victoria Street Toronto Ontario M5B 1W8 Canada.,Department of Physics, Ryerson University Toronto Ontario M5B 2K3 Canada
| | - Scott S H Tsai
- Department of Mechanical and Industrial Engineering, Ryerson University 350 Victoria Street Toronto Ontario M5B 2K3 Canada .,Institute for Biomedical Engineering, Science and Technology (iBEST), A Partnership Between Ryerson University and St. Michael's Hospital 209 Victoria Street Toronto Ontario M5B 1T8 Canada.,Keenan Research Centre for Biomedical Science, Unity Health Toronto 209 Victoria Street Toronto Ontario M5B 1W8 Canada.,Graduate Program in Biomedical Engineering, Ryerson University 350 Victoria Street Toronto Ontario M5B 2K3 Canada
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20
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Lv X, Chen M, Kong C, Shu G, Meng M, Ye W, Cheng S, Zheng L, Fang S, Chen C, Wu F, Weng Q, Tu J, Zhao Z, Ji J. Construction of a novel radiomics nomogram for the prediction of aggressive intrasegmental recurrence of HCC after radiofrequency ablation. Eur J Radiol 2021; 144:109955. [PMID: 34600237 DOI: 10.1016/j.ejrad.2021.109955] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 08/18/2021] [Accepted: 09/15/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To construct a precise prediction model of preoperative magnetic resonance imaging (MRI)-based nomogram for aggressive intrasegmental recurrence (AIR) of hepatocellular carcinoma (HCC) patients treated with radiofrequency ablation (RFA). METHODS Among 891 patients with HCC treated by RFA, 22 patients with AIR and 36 patients without AIR (non-AIR) were finally enrolled in our study, and each patient was followed up for more than 6 months to determine the occurrence of AIR. The laboratory indicators and MRI features were compared and assessed. Preoperative contrast-enhanced T1-weighted images (CE-T1WI) were used for radiomics analysis. The selected clinical indicators and texture features were finally screened out to generate the novel prediction nomogram. RESULTS Tumor shape, ADC Value, DWI signal intensity and ΔSI were selected as the independent factors of AIR by univariate and multivariate logistic regression analysis. Meanwhile, two radiomics features were selected from 396 candidate features by LASSO (P < 0.05), which were further used to calculate the Rad-score. The selected clinical factors were further integrated with the Rad-score to construct the predictive model, and the AUCs were 0.941 (95% CI: 0.876-1.000) and 0.818 (95% CI: 0.576-1.000) in the training (15 AIR and 25 non-AIR) and validation cohorts (7 AIR and 11 non-AIR), respectively. The AIR predictive model was further converted into a novel radiomics nomogram, and decision curve analysis showed good agreement. CONCLUSIONS The predictive nomogram integrated with clinical factors and CE-T1WI -based radiomics signature could accurately predict the occurrence of AIR after RFA, which could greatly help individualized evaluation before treatment.
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Affiliation(s)
- Xiuling Lv
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Minjiang Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Chunli Kong
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Gaofeng Shu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Miaomiao Meng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Weichuan Ye
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Shimiao Cheng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China
| | - Liyun Zheng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Shiji Fang
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Chunmiao Chen
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Fazong Wu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Qiaoyou Weng
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Jianfei Tu
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Zhongwei Zhao
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China
| | - Jiansong Ji
- Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, the Fifth Affiliated Hospital of Wenzhou Medical University/Lishui Hospital of Zhejiang University, Lishui 323000, China; Department of Radiology, Lishui Central Hospital of Zhejiang Province, Lishui 323000, China.
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21
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Yan X, Ning ZY, Wang P, Zhuang LP, Xu LT, Zhu ZF, Sheng J, Shen YH, Hua YQ, Meng ZQ. Combined ablation-chemotherapy versus chemotherapy alone for pancreatic cancer with liver metastasis: a propensity score matching study. Expert Rev Gastroenterol Hepatol 2021; 15:1047-1056. [PMID: 33356652 DOI: 10.1080/17474124.2021.1869937] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Objectives: To retrospectively assess the efficacy of combined ablation-chemotherapy in comparison to that of chemotherapy alone in patients with liver metastasized pancreatic ductal adenocarcinoma (lmPDAC).Methods: In total 104 patients with hepatic oligo metastasized PDAC were identified; among them, 74 patients underwent combined thermal ablation-chemotherapy, and 30 patients underwent chemotherapy alone. Through propensity score matching, 1:1 matching of the combined ablation-chemotherapy group and chemotherapy group was achieved. The primary endpoint of this study was overall survival (OS). Clinical and tumor-related factors affecting OS were also analyzed through univariate and multivariate analyses using the Cox risk model.Results: For patients treated with combined ablation-chemotherapy, the median OS was 10.77 months, while it was 5.77 months for patients treated with chemotherapy alone (P = 0.011). The survival benefit for patients treated with combined ablation-chemotherapy was still preserved in the matched cohort, with a median OS of 8.17 months compared to 5.77 months in the chemotherapy group. Univariate and multivariate analyses in the matched population also showed treatment with combined ablation-chemotherapy was an independent prognostic factor (P < 0.05).Conclusions: For patients with liver metastases from pancreatic cancer, the combined use of thermal ablation and systemic chemotherapy offers a chance for a better survival outcome.
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Affiliation(s)
- Xia Yan
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhou-Yu Ning
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Peng Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Li-Ping Zhuang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Li-Tao Xu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhen-Feng Zhu
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jie Sheng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ye-Hua Shen
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yong-Qiang Hua
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Zhi-Qiang Meng
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Cancer minimally invasive treatment center, Fudan University Shanghai Cancer Center, Shanghai, China
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22
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Huang J, Huang W, Guo Y, Cai M, Zhou J, Lin L, Zhu K. Risk Factors, Patterns, and Long-Term Survival of Recurrence After Radiofrequency Ablation With or Without Transarterial Chemoembolization for Hepatocellular Carcinoma. Front Oncol 2021; 11:638428. [PMID: 34123790 PMCID: PMC8191459 DOI: 10.3389/fonc.2021.638428] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 04/13/2021] [Indexed: 12/12/2022] Open
Abstract
Objectives To classify hepatocellular carcinoma (HCC) recurrence patterns after radiofrequency ablation (RFA) or transarterial chemoembolization (TACE) combined with RFA (TACE-RFA) and analyze their risk factors and impacts on survival. Methods We retrospectively evaluated the medical records of HCC patients who underwent RFA or TACE-RFA from January 2006 to December 2016. HCC recurrences were classified into four patterns: local tumor progression (LTP), intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence. Risk factors, overall survival (OS), and post-recurrence survival of each pattern were evaluated. Results A total of 249 patients with a single, hepatitis-B virus (HBV)-related HCC ≤ 5.0 cm who underwent RFA (HCC ≤ 3.0 cm) or TACE-RFA (HCC of 3.1-5.0 cm) were included. During follow-up (median, 53 months), 163 patients experienced HCC recurrence: 40, 43, 62 and 18 patients developed LTP, intra-segmental recurrence, extra-segmental recurrence, and aggressive recurrence, respectively; the median post-recurrence survival was 49, 37, 25 and 15 months, respectively (P < .001); the median OS was 65, 56, 58 and 28 months, respectively (P < .001). Independent risk factors for each pattern were as follows: tumor sized 2.1-3.0 cm undergoing RFA alone and insufficient ablative margin for LTP, periportal tumor and non-smooth tumor margin for intra-segmental recurrence, HBV-DNA ≥ 2000 IU/mL for extra-segmental recurrence, and periportal tumor and α-fetoprotein ≥ 100 ng/mL for aggressive recurrence. Recurrence pattern (P < .001) and Child-Pugh class B (P = .025) were independent predictors for OS. Conclusions Based on our classification, each recurrence pattern had different recurrence risk factors, OS, and post-recurrence survival.
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Affiliation(s)
- Jingjun Huang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Wensou Huang
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yongjian Guo
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mingyue Cai
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jingwen Zhou
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Liteng Lin
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kangshun Zhu
- Department of Minimally Invasive Interventional Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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23
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Winkelmann MT, Gohla G, Kübler J, Weiß J, Clasen S, Nikolaou K, Hoffmann R. MR-Guided High-Power Microwave Ablation in Hepatic Malignancies: Initial Results in Clinical Routine. Cardiovasc Intervent Radiol 2020; 43:1631-1638. [PMID: 32699978 PMCID: PMC7591402 DOI: 10.1007/s00270-020-02584-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 06/26/2020] [Indexed: 12/15/2022]
Abstract
PURPOSE Evaluation of technique effectiveness, patient safety and ablation parameters of MR-guided microwave ablation in hepatic malignancies using an MR-conditional high-power microwave ablation system. MATERIALS AND METHODS Institutional review board approval and informed patient consent were obtained. Patients who underwent MR-guided microwave ablation of hepatic malignancies in a 1.5T wide-bore scanner using a perfusion-cooled high-power microwave ablation system with a maximum generator power of 150 W were included. Ablation parameters comprising procedure durations, net ablation duration, applicator positions and ablation zone dimensions were recorded. Adverse events were classified according to the CIRSE classification system. Technique effectiveness was assessed after 1 month. Follow-up was conducted with contrast-enhanced MRI and ranged from 1 to 20 months (mean: 6.1 ± 5.4 months). RESULTS Twenty-one consecutive patients (age: 63.4 ± 10.5 years; 5 female) underwent 22 procedures for 28 tumours (9 hepatocellular carcinomas, 19 metastases) with a mean tumour diameter of 14.6 ± 5.4 mm (range: 6-24 mm). Technique effectiveness was achieved in all lesions. Tumours were treated using 1.7 ± 0.7 applicator positions (range: 1-3). Mean energy and ablation duration per tumour were 75.3 ± 35.4 kJ and 13.3 ± 6.2 min, respectively. Coagulation zone short- and long-axis diameters were 29.1 ± 6.4 mm and 39.9 ± 7.4 mm, respectively. Average procedure duration was 146.4 ± 26.2 min (range: 98-187 min). One minor complication was reported. Five patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed during initial follow-up. CONCLUSION MR-guided high-power microwave ablation provides safe and effective treatment of hepatic malignancies with short ablation times and within acceptable procedure durations.
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Affiliation(s)
- Moritz T Winkelmann
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Georg Gohla
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Jens Kübler
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Jakob Weiß
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Stephan Clasen
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Konstantin Nikolaou
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Rüdiger Hoffmann
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.
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24
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Xing H, Zhang WG, Cescon M, Liang L, Li C, Wang MD, Wu H, Lau WY, Zhou YH, Gu WM, Wang H, Chen TH, Zeng YY, Schwartz M, Pawlik TM, Serenari M, Shen F, Wu MC, Yang T. Defining and predicting early recurrence after liver resection of hepatocellular carcinoma: a multi-institutional study. HPB (Oxford) 2020; 22:677-689. [PMID: 31607637 DOI: 10.1016/j.hpb.2019.09.006] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/12/2019] [Accepted: 09/14/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND A clear definition of "early recurrence" after hepatocellular carcinoma (HCC) resection is still lacking. This study aimed to determine the optimal cutoff between early and late HCC recurrence, and develop nomograms for pre- and postoperative prediction of early recurrence. METHODS Patients undergoing HCC resection were identified from a multi-institutional Chinese database. Minimum P-value approach was adopted to calculate optimal cut-off to define early recurrence. Pre- and postoperative risk factors for early recurrence were identified and further used for nomogram construction. The results were externally validated by a Western cohort. RESULTS Among 1501 patients identified, 539 (35.9%) were recurrence-free. The optimal length to distinguish between early (n = 340, 35.3%) and late recurrence (n = 622, 64.7%) was 8 months. Multivariable logistic regression analyses identified 5 preoperative and 8 postoperative factors for early recurrence, which were further incorporated into preoperative and postoperative nomograms (C-index: 0.785 and 0.834). The calibration plots for the probability of early recurrence fitted well. The nomogram performance was maintained using the validation dataset (C-index: 0.777 for preoperative prediction and 0.842 for postoperative prediction). CONCLUSIONS An interval of 8 months was the optimal threshold for defining early HCC recurrence. The two web-based nomograms have been published to allow accurate pre- and postoperative prediction of early recurrence. These may offer useful guidance for individual treatment or follow up for patients with resectable HCC.
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Affiliation(s)
- Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Guang Zhang
- Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
| | - Matteo Cescon
- Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Italy
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong Special Administrative Region
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, The Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People's Hospital, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People's Hospital, Sichuan, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Myron Schwartz
- Liver Cancer Program, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, United States
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, United States
| | - Matteo Serenari
- Department of Medical and Surgical Sciences, General Surgery and Transplantation Unit, University of Bologna, Italy
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
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25
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Huang Q, Zeng Q, Long Y, Tan L, Zheng R, Xu E, Li K. Fusion imaging techniques and contrast-enhanced ultrasound for thermal ablation of hepatocellular carcinoma - A prospective randomized controlled trial. Int J Hyperthermia 2020; 36:1207-1215. [PMID: 31813295 DOI: 10.1080/02656736.2019.1687945] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Objectives: This randomized controlled trial (RCT) aims to compare the clinical application values of contrast-enhanced ultrasound (CEUS), computed tomography/magnetic resonance-CEUS (CT/MR-CEUS), and three-dimensional ultrasound-CEUS (3DUS-CEUS) Fusion imaging (FI) techniques in the assistance of thermal ablation for hepatocellular carcinoma (HCC).Methods: A RCT was conducted on 374 patients with 456 HCCs between January 2016 and September 2017. CEUS, CT/MR-CEUS, and 3DUS-CEUS FI techniques were randomly used to assist HCC ablation. All lesions were ablated according to a previously determined plan, and FI groups required a 5-mm ablative margin. The primary endpoints were technical efficacy of thermal ablation and local tumor progression (LTP).Results: According to randomization, 153 (18.8 ± 8.0 cm), 153 (18.3 ± 6.6 cm) and 150 (19.1 ± 6.9 cm) HCCs were assigned to CT/MR-CEUS, 3DUS-CEUS and CEUS groups respectively. Technical efficacy rates (99.3% vs. 100% vs. 100%) were achieved in the three groups, showing no statistical differences (p = 1.000). The median follow-up time was 24 (1-37) months. LTP rates at 1 and 2 years were 3.4%, 12.2% for CT/MR-CEUS FI, 4.8%, 9.0% for 3DUS-CEUS FI, and 8.6%, 19.9% for CEUS, respectively (p = .105). The results of subgroup analysis for LTP were statistically significant when patients with albumin-bilirubin (ALBI) grade 2 and 3 (p = .000), and tumor located at risky positions (p = .042). In addition, the p value in group of multiple tumors was close to .05 (p = .052).Conclusions: All the three techniques are feasible for intraoperative HCC thermal ablation. Compared with CEUS, FI techniques are more suitable in patients with ALBI grade 2 and 3, multiple tumors, and in tumors at risky locations.
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Affiliation(s)
- Qiannan Huang
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Qingjing Zeng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Yinglin Long
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Lei Tan
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Rongqin Zheng
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Erjiao Xu
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
| | - Kai Li
- Department of Ultrasound, Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, PR China
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Biondetti P, Fumarola EM, Ierardi AM, Coppola A, Gorga G, Maggi L, Valconi E, Angileri SA, Carrafiello G. Percutaneous US-guided MWA of small liver HCC: predictors of outcome and risk factors for complications from a single center experience. Med Oncol 2020; 37:39. [PMID: 32239295 DOI: 10.1007/s12032-020-01365-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Accepted: 03/17/2020] [Indexed: 12/17/2022]
Abstract
The aim of the present study was to identify predictors of outcome and complications in patients with small hepatocellular carcinoma (HCC) treated by percutaneous microwave ablation (MWA). Patients with non-previously treated small (≤ 3 cm) HCCs who underwent ultrasound (US)-guided percutaneous MWA between July 2016 and January 2019 were included. For each patient, the following variables were registered: age, sex, albumin, platelet count, INR/PT, PTT ratio, total bilirubin, liver status, etiology of liver disease, Child-Pugh classification, tumor dimension, margin, and hepatic segment, tumor subcapsular, perihilar or perivascular location, HCC focality, ascites. During follow-up, complications and outcomes were registered. Variables were then analyzed in relation to both outcomes and complications. 74 patients were included. Mean CT follow-up was 6.2 months (range 1-24 months). At least one complication occurred in 48% of patients, the majority being asymptomatic imaging findings not requiring intervention. One major complication was registered (duodenal perforation: 1.3%). The occurrence of complications was associated with HCC multifocality and abnormal INR/PT, duodenal wall edema with tumor dimension, portal vein thrombosis with Child Pugh score, perihepatic free fluid with abnormal platelet count and comorbidities. Incomplete response rate at 1 month was 18.9%. Local tumor progression and new HCC nodules rates were 13.5% and 27%, respectively. Incomplete response at 1 month was associated with both alcoholic etiology of liver disease and II segment tumor location, new HCC nodules with PBC. Despite the small series analyzed, significant factors related with complications and outcomes may be kept in mind when planning the best treatment for each patient.
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Affiliation(s)
| | | | - Anna Maria Ierardi
- Diagnostic and Interventional Radiology, ASST Santi Paolo e Carlo, Milan, Italy
| | | | - Giovanna Gorga
- Postgraduate School in Radiology, University of Milan, Milan, Italy
| | - Luca Maggi
- Postgraduate School in Radiology, University of Milan, Milan, Italy
| | - Elena Valconi
- Postgraduate School in Radiology, University of Milan, Milan, Italy
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Guo X, Gai Y, Du F, Wang Q, Sun L, Ding X, Zeng D, Wu Z. Thermally sensitive fluorescence imaging system for radiofrequency ablation guidance. Int J Hyperthermia 2020; 37:308-315. [PMID: 32228185 DOI: 10.1080/02656736.2020.1742934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
Abstract
Radiofrequency ablation (RFA) has been clinically used as a minimally invasive procedure for the treatment of many solid tumors. However, the current imaging techniques have some shortages in RFA guidance, especially for the assessment of the margin of ablation. Herein, we developed a novel optical imaging platform to guide RFA utilizing fluorescence resonance energy transfer from a thermally sensitive fluorescent protein conjugated to a near-infrared fluorescent dye. Additionally, attaching receptor-targeting ligands further equipped the system with high specificity to tumors overexpressing the targeted receptor.
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Affiliation(s)
- Xiaoxia Guo
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yongkang Gai
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Fang Du
- Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingbing Wang
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lingyi Sun
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Xiaoyi Ding
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dexing Zeng
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Zhiyuan Wu
- Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Shi L, Wang J, Ding N, Zhang Y, Zhu Y, Dong S, Wang X, Peng C, Zhou C, Zhou L, Li X, Shi H, Wu W, Long X, Wu C, Liao W. Inflammation induced by incomplete radiofrequency ablation accelerates tumor progression and hinders PD-1 immunotherapy. Nat Commun 2019; 10:5421. [PMID: 31780645 PMCID: PMC6883042 DOI: 10.1038/s41467-019-13204-3] [Citation(s) in RCA: 188] [Impact Index Per Article: 31.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 10/28/2019] [Indexed: 02/07/2023] Open
Abstract
Radiofrequency ablation (RFA) promotes tumor antigen-specific T cell responses and enhances the effect of immunotherapy in preclinical settings. Here we report that the existence of remnant tumor masses due to incomplete RFA (iRFA) is associated with earlier new metastases and poor survival in patients with colorectal cancer liver metastases (CRCLM). Using mouse models, we demonstrate that iRFA promotes tumor progression and hinders the efficacy of anti-PD-1 therapy. Immune analysis reveals that iRFA induces sustained local inflammation with predominant myeloid suppressor cells, which inhibit T cell function in tumors. Mechanistically, tumor cell-derived CCL2 is critical for the accumulation of monocytes and tumor-associated macrophages (TAMs). The crosstalk between TAMs and tumor cells enhances the CCL2 production by tumor cells. Furthermore, we find that administration of a CCR2 antagonist or the loss of CCL2 expression in tumor cells enhances the antitumor activity of PD-1 blockade, providing a salvage alternative for residual tumors after iRFA. Radiofrequency ablation is used to treat metastatic colorectal cancer. In this study, the authors show that incomplete ablation of tumours results in metastases and show in mouse models that the chemokine CCL2 recruits myeloid cells to the partially ablated tumours, which can block T cell function.
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Affiliation(s)
- Liangrong Shi
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Junjun Wang
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Nianhua Ding
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Yi Zhang
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Yibei Zhu
- Institute of Biotechnology, Key Laboratory of Clinical Immunology of Jiangsu Province, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Shunli Dong
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Xiaohui Wang
- Dept. of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Changli Peng
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Chunhui Zhou
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Ledu Zhou
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Xiaodong Li
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Hongbing Shi
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China
| | - Wei Wu
- National Clinical Research Center for Geriatric Disorder, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Xueyin Long
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China
| | - Changping Wu
- Department of Oncology, the Third Affiliated Hospital, Soochow University, Changzhou, 213003, Jiangsu, China.
| | - Weihua Liao
- Radiological Intervention Center, Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China. .,Center for Molecular Imaging, Xiangya Hospital, Central South University, Changsha, 410005, Hunan, China.
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Microwave Ablation (MWA) of Pulmonary Neoplasms: Clinical Performance of High-Frequency MWA With Spatial Energy Control Versus Conventional Low-Frequency MWA. AJR Am J Roentgenol 2019; 213:1388-1396. [PMID: 31593520 DOI: 10.2214/ajr.18.19856] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE. The objective of our study was to evaluate the clinical performance of a new high-frequency (HF) microwave ablation (MWA) technology with spatial energy control for treatment of lung malignancies in comparison with a conventional low-frequency (LF) MWA technology. MATERIALS AND METHODS. In this retrospective study, 59 consecutive patients (mean age, 58.9 ± 12.6 [SD] years) were treated in 71 sessions using HF spatial-energy-control MWA. Parameters collected were technical success and efficacy, tumor diameter, tumor and ablation volumes, ablation time, output energy, complication rate, 90-day mortality, local tumor progression (LTP), ablative margin size, and ablation zone sphericity. Results were compared with the same parameters retrospectively collected from the last 71 conventional LF-MWA sessions. This group consisted of 56 patients (mean age, 60.3 ± 10.8 years). Statistical comparisons were performed using the Wilcoxon-Mann-Whitney test. RESULTS. Technical success was 98.6% for both technologies; technical efficacy was 97.2% for HF spatial-energy-control MWA and 95.8% for LF-MWA. The 90-day mortality rate was 5.1% (3/59) in the HF spatial-energy-control MWA group and 5.4% (3/56) in the LF-MWA group; for both groups, there were zero intraprocedural deaths. The median ablation time was 8.0 minutes for HF spatial-energy-control MWA and 10.0 minutes for LF-MWA (p < 0.0001). Complications were recorded in 21.1% (15/71) of HF spatial-energy-control MWA sessions and in 31.0% (22/71) of LF-MWA sessions (p = 0.182); of these complications, 4.2% (3/71) were major complications in the HF spatial-energy-control MWA group, and 9.9% (7/71) were major complications in the LF-MWA group. The median deviation from ideal sphericity (1.0) was 0.195 in the HF spatial-energy-control MWA group versus 0.376 in the LF-MWA group (p < 0.0001). Absolute minimal ablative margins per ablation were 7.5 ± 3.6 mm (mean ± SD) in the HF spatial-energy-control MWA group versus 4.2 ± 3.0 mm in the LF-MWA group (p < 0.0001). In the HF spatial-energy-control MWA group, LTP at 12 months was 6.5% (4/62). LTP at 12 months in the LF-MWA group was 12.5% (7/56). Differences in LTP rate (p = 0.137) and time point (p = 0.833) were not significant. CONCLUSION. HF spatial-energy-control MWA technology and conventional LFMWA technology are safe and effective for the treatment of lung malignancies independent of the MWA system used. However, HF spatial-energy-control MWA as an HF and high-energy MWA technique achieves ablation zones that are closer to an ideal sphere and achieves larger ablative margins than LF-MWA (p < 0.0001).
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Yang H, Wang J, Li Z, Yang Y, Yang L, Zhang Y, Shi Y, Cao Y, Zhou J, Wang Z, Chen Q. Risk Factors and Outcomes of Early Relapse After Curative Resection of Intrahepatic Cholangiocarcinoma. Front Oncol 2019; 9:854. [PMID: 31555597 PMCID: PMC6737003 DOI: 10.3389/fonc.2019.00854] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 08/19/2019] [Indexed: 12/24/2022] Open
Abstract
Early relapse after hepatectomy for intrahepatic cholangiocarcinoma (ICC) has a tremendous influence on the long-term survival outcomes of ICC patients. The purpose of our study was to investigate risk factors for early tumor relapse and confirm whether early relapse was correlated with ICC patients' long-term survival outcomes. Three hundred and twenty-two consecutive ICC patients undergoing partial hepatectomy at Liver Surgery Department of Zhongshan Hospital (Fudan University, Shanghai, China) between January 2005 and December 2011 were included in this retrospectively study. The definition of early relapse had been described as tumor relapse within 24 months after hepatectomy in ICC patients. We identified a total of 168 ICC patients with early relapse and 23 ICC patients with late relapse after hepatectomy. From the time of relapse, the long-term survival outcomes were worse among patients who had early vs. late relapse (median OS 16.5 vs. 44.7 months, respectively; P < 0.0001). The overall survival of the early relapse group was lower than that of the late relapse group (P < 0.0001). Multivariate Cox regression analysis indicated that multiple tumors (hazard ratio [HR], 1.951; 95% CI, 1.382-2.755; P < 0.001), lymphonodus metastasis (HR, 1.517; 95% CI, 1.061-2.168; P = 0.022), and higher serum CA19-9 levels (HR, 1.495; 95% CI, 1.095-2.039; P = 0.011) were independent risk factors of early relapse. Moreover, multiple tumors (HR, 1.641; 95% CI, 1.120-2.406; P = 0.011), lymphonodus metastasis (HR, 2.008; 95% CI, 1.367-2.949; P < 0.001), elevated NLR (HR, 1.921; 95% CI, 1.331-2.774; P < 0.001) and higher serum CA19-9 levels (HR, 1.990; 95% CI, 1.409-2.812; P < 0.001) were independent predictors of overall survival for ICC patients with early relapse. Collectively, our findings demonstrated that multiple tumors, lymphonodus metastasis, and higher serum CA19-9 levels were associated with the increased risks of early relapse and worse prognoses of ICC after curative-intent resection.
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Affiliation(s)
- Hua Yang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Jie Wang
- ENT Institute and Otorhinolaryngology Department, Eye & ENT Hospital, Fudan University, Shanghai, China
| | - Zehuan Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yi Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Liuxiao Yang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Yong Zhang
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
| | - Yinghong Shi
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Ya Cao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Cancer Research Institute, Central South University, Ministry of Education, Changsha, China
| | - Jian Zhou
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,State key Laboratory of Genetic Engineering, Fudan University, Shanghai, China
| | - Zheng Wang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Ministry of Education, Shanghai, China
| | - Qing Chen
- Department of General Surgery, Shanghai Public Health Clinical Center, Zhongshan Hospital (South), Fudan University, Shanghai, China
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31
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Kim JM, Kwon CHD, Joh JW, Yoo H, Kim K, Sinn DH, Choi GS, Lee JH. Nomograms in Hepatectomy Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma. J Gastrointest Surg 2019; 23:1559-1567. [PMID: 30671793 DOI: 10.1007/s11605-018-04074-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 11/27/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Several conventional staging systems use tumor count as a variable for tumor classification; however, most conventional staging systems for hepatocellular carcinoma (HCC) are not specifically constructed for surgically treated patients. The aim of this study was to create a prognostic nomogram based on patient' clinical and pathological features for predicting individual patient survival after liver resection as a primary therapy for solitary hepatitis B virus (HBV)-related HCC. METHODS This study included patients who underwent curative liver resection for preoperative treatment-naïve HBV-related HCC between April 2007 and September 2014. All data were collected prospectively. RESULTS A nomogram was generated for HCC recurrence and mortality in 420 hepatectomy patients. HCC recurrence was closely associated with the following factors: increased alkaline phosphatase, low albumin, increased protein induced by vitamin K absence/antagonism-II (PIVKA-II), multiple tumors, tumor hemorrhage, portal vein tumor thrombosis, intrahepatic metastasis, and free resection margin (< 4 cm). Increased alanine transaminase, tumor size ≥ 5 cm, and multiple tumors were predisposing factors for death. Nomograms using those factors had good calibration and discrimination abilities with C-indexes of 0.712 and 0.819, respectively. CONCLUSIONS Our results suggest that prognostic nomograms in hepatectomy patients with HBV-related HCC can more precisely estimate postoperative survival of individual HBV-related HCC patients.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
| | - Heejin Yoo
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Republic of Korea
| | - Kyunga Kim
- Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Republic of Korea
| | - Dong Hyun Sinn
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea
| | - Joon Hyeok Lee
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, Gu WM, Wang H, Chen TH, Zeng YY, Li C, Wu MC, Shen F, Yang T. Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study From China. JAMA Surg 2019; 154:209-217. [PMID: 30422241 PMCID: PMC6439634 DOI: 10.1001/jamasurg.2018.4334] [Citation(s) in RCA: 375] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Accepted: 08/26/2018] [Indexed: 12/15/2022]
Abstract
IMPORTANCE Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. OBJECTIVE To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. DESIGN, SETTING, AND PARTICIPANTS This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. INTERVENTIONS Liver resection for HCC. MAIN OUTCOMES AND MEASURES Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. RESULTS Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. CONCLUSIONS AND RELEVANCE Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.
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Affiliation(s)
- Xin-Fei Xu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Department of Clinical Medicine, Second Military Medical University, Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wan-Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Faculty of Medicine, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu’er People’s Hospital, Yunnan, China
| | - Wei-Min Gu
- The First Department of General Surgery, the Fourth Hospital of Harbin, Heilongjiang, China
| | - Hong Wang
- Department of General Surgery, Liuyang People’s Hospital, Hunan, China
| | - Ting-Hao Chen
- Department of General Surgery, Ziyang First People’s Hospital, Sichuan, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
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Monsky W, Keravnou C, Averkiou M. Contrast-enhanced ultrasound to ultrasound fusion during microwave ablation: feasibility study in a perfused porcine liver model. J Ultrasound 2019; 22:323-335. [PMID: 30811016 DOI: 10.1007/s40477-019-00366-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 02/21/2019] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To obtain a complete response with thermal ablation, the margin and entire tumor volume must be treated. Real-time ultrasound visualization is limited during ablation due to gas production. This study assesses the feasibility of fusing volumetric contrast-enhanced ultrasound (CEUS), obtained immediately prior to microwave ablation, with real-time CEUS during and following ablation in a machine-perfused porcine liver. METHODS Ten, 3-4 cm microwave ablations were performed in five explanted perfused livers. Prior to ablation, microbubbles were injected into the vasculature while an ultrasound sweep across the liver captured a volumetric image during maximum enhancement. This volumetric image was then fused to overlay the real-time ultrasound imaging. Since the perfused livers did not have tumors, a spherical marker circumscribing a target volume was placed on the images. Approximatively, 75% of the total intended circumscribed spherical volume was ablated. Following ablation, a second bolus injection of ultrasound contrast was administered demonstrating continued enhancement of the intentionally non-ablated 25%. A second volumetric image of the post-ablation CEUS was then fused to overlay the real-time ultrasound images for guidance during ablation of the remaining enhancing volume. RESULTS Technical success was achieved in 100% of the cases. The pre- and then the post-ablation CEUS volume was fused with real-time imaging during antenna placement for initial and subsequent ablation. CONCLUSION CEUS-CEUS fusion during thermal ablation is feasible and greatly improves the workflow. The approach may augment the use of dynamic CEUS for guidance, improving antenna placement, and aiding in the identification and ablation of initial and residual enhancing tissue.
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Affiliation(s)
- Wayne Monsky
- Division of Interventional Radiology, Department of Radiology, University of Washington Medical Center, 1959 NE Pacific St., Box 357115, Seattle, WA, USA.
| | - Christina Keravnou
- Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA
| | - Michalakis Averkiou
- Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA
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Solbiati M, Muglia R, Goldberg SN, Ierace T, Rotilio A, Passera KM, Marre I, Solbiati L. A novel software platform for volumetric assessment of ablation completeness. Int J Hyperthermia 2019; 36:337-343. [PMID: 30729818 DOI: 10.1080/02656736.2019.1569267] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/06/2019] [Accepted: 01/09/2019] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To retrospectively evaluate the accuracy of a novel software platform for assessing completeness of percutaneous thermal ablations. MATERIALS & METHODS Ninety hepatocellular carcinomas (HCCs) in 50 patients receiving percutaneous ultrasound-guided microwave ablation (MWA) that resulted in apparent technical success at 24-h post-ablation computed tomography (CT) and with ≥1-year imaging follow-up were randomly selected from a 320 HCC ablation database (2010-2016). Using a novel volumetric registration software, pre-ablation CT volumes of the HCCs without and with the addition of a 5 mm safety margin, and corresponding post-ablation necrosis volumes were segmented, co-registered and overlapped. These were compared to visual side-by-side inspection of axial images. RESULTS At 1-year follow-up, CT showed absence of local tumor progression (LTP) in 69/90 (76.7%) cases and LTP in 21/90 (23.3%). For HCCs classified by the software as "incomplete tumor treatments", LTP developed in 13/17 (76.5%) and all 13 (100%) of these LTPs occurred exactly where residual non-ablated tumor was identified by retrospective software analysis. HCCs classified as "complete ablation with <100% 5 mm ablative margins" had LTP in 8/49 (16.3%), while none of 24 HCCs with "complete ablation including 100% 5 mm ablative margins" had LTP. Differences in LTP between both partially ablated HCCs vs completely ablated HCCs, and ablated HCCs with <100% vs with 100% 5 mm margins were statistically significant (p < .0001 and p = .036, respectively). Thus, 13/21 (61.9%) incomplete tumor treatments could have been detected immediately, were the software available at the time of ablation. CONCLUSIONS A novel software platform for volumetric assessment of ablation completeness may increase the detection of incompletely ablated tumors, thereby holding the potential to avoid subsequent recurrences.
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Affiliation(s)
| | - Riccardo Muglia
- b Department of Biomedical Sciences , Humanitas University , Rozzano , Milan , Italy
| | - S Nahum Goldberg
- c Department of Radiology , Hadassah Hebrew University Medical Centre , Jerusalem , Israel
- d Department of Radiology , Beth Israel Deaconess Medical Center , Boston , MA , USA
| | - Tiziana Ierace
- e Department of Radiology , Humanitas Clinical and Research Center , Rozzano , Milan , Italy
| | | | | | | | - Luigi Solbiati
- b Department of Biomedical Sciences , Humanitas University , Rozzano , Milan , Italy
- e Department of Radiology , Humanitas Clinical and Research Center , Rozzano , Milan , Italy
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Wang X, Deng Q, Feng K, Chen S, Jiang J, Xia F, Ma K, Bie P. Insufficient radiofrequency ablation promotes hepatocellular carcinoma cell progression via autophagy and the CD133 feedback loop. Oncol Rep 2018; 40:241-251. [PMID: 29749472 PMCID: PMC6059746 DOI: 10.3892/or.2018.6403] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 04/19/2018] [Indexed: 12/22/2022] Open
Abstract
Insufficient radiofrequency ablation (iRFA) often leads to residual hepatocellular carcinoma (HCC) progression. However, the mechanism is still poorly understood. In the present study, we demonstrated that LC3B protein expression levels were significantly increased in the residual hepatocellular carcinoma cells after radiofrequency ablation (RFA) treatment in vivo. Moreover, iRFA promoted autophagy, autophagosome formation and autophagic flux in Huh-7 and SMMC7721 cell lines in vitro. In addition, iRFA induced HCC cell viability and invasion. However, blockade of autophagy by the autophagosome inhibitor 3-methyladenine (3-MA) suppressed iRFA-induced cell viability and invasion. Furthermore, we revealed that the expression of liver cancer stem cell marker CD133 was also significantly increased in the residual hepatocellular carcinoma cells after RFA treatment in vivo, and was positively correlated with LC3B protein expression. iRFA also promoted CD133 protein expression in Huh-7 and SMMC7721 cell lines in vitro. CD133 was localized to autophagosomes, and was suppressed by 3-MA or chloroquine (CQ) after iRFA treatment. CD133 downregulation also suppressed iRFA-induced cell viability, invasion and autophagy. Collectively, our results indicated that RFA may promote residual HCC cell progression by autophagy and CD133 feedback loop.
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Affiliation(s)
- Xiaofei Wang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Qingsong Deng
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Kai Feng
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Shihan Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Jiayun Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Feng Xia
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Kuansheng Ma
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
| | - Ping Bie
- Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
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Zhu K, Huang J, Lai L, Huang W, Cai M, Zhou J, Guo Y, Chen J. Medium or Large Hepatocellular Carcinoma: Sorafenib Combined with Transarterial Chemoembolization and Radiofrequency Ablation. Radiology 2018; 288:300-307. [PMID: 29688153 DOI: 10.1148/radiol.2018172028] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose To determine the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, S-TACE-RFA) in patients with medium or large (range, 3.1-7.0 cm in diameter) hepatocellular carcinoma (HCC). Materials and Methods This retrospective study evaluated the medical records of consecutive patients with medium or large HCC who underwent S-TACE-RFA or combined TACE and RFA (hereafter, TACE-RFA) from January 2010 to December 2014. Sorafenib was started 3-5 days after TACE, and RFA was performed 1-2 weeks after TACE. Treatment complications, recurrence-free survival (RFS), and overall survival (OS) in patients who underwent S-TACE-RFA were compared with those in patients who underwent TACE-RFA. Results Of the 174 patients who underwent S-TACE-RFA or TACE-RFA, 106 who met the eligibility criteria were included in this study. Among them, 40 underwent S-TACE-RFA and 66 underwent TACE-RFA. The patients who underwent S-TACE-RFA had longer RFS (median, 24.0 vs 10.0 months; P = .04) and better OS (median, 63.0 vs 36.0 months, P = .048) than those who underwent TACE-RFA. S-TACE-RFA and α-fetoprotein level were independent prognostic factors for survival in uni- and multivariable analyses. The rate of complications in patients who underwent S-TACE-RFA was similar to that in patients who underwent TACE-RFA (22.5% vs 18.2%, P = .59). Conclusion S-TACE-RFA resulted in longer RFS and better OS than did TACE-RFA in patients with medium or large HCC. © RSNA, 2018 Online supplemental material is available for this article.
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Affiliation(s)
- Kangshun Zhu
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Jingjun Huang
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Lisha Lai
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Wensou Huang
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Mingyue Cai
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Jingwen Zhou
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Yongjian Guo
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
| | - Junwei Chen
- From the Department of Minimally Invasive Interventional Radiology, the Second Affiliated Hospital of Guangzhou Medical University, 250 East Changgang Rd, Guangzhou, Guangdong 510260, China (K.Z., J.H., W.H., M.C., J.Z., Y.G.); Department of Radiology, Guangzhou First Municipal People's Hospital, Guangzhou, China (L.L.); and Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (J.C.)
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Stress-induced phosphoprotein 1 mediates hepatocellular carcinoma metastasis after insufficient radiofrequency ablation. Oncogene 2018; 37:3514-3527. [DOI: 10.1038/s41388-018-0169-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2017] [Revised: 01/20/2018] [Accepted: 01/21/2018] [Indexed: 12/25/2022]
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Kim JM, Yi NJ, Kwon CHD, Lee KW, Suh KS, Joh JW. Early disseminated recurrence after liver resection in solitary hepatocellular carcinoma. Ann Surg Treat Res 2018; 94:129-134. [PMID: 29520346 PMCID: PMC5842084 DOI: 10.4174/astr.2018.94.3.129] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/07/2017] [Accepted: 07/25/2017] [Indexed: 12/14/2022] Open
Abstract
PURPOSE Although few hepatectomy patients develop unexpected early diffuse and multinodular recurrence in the remnant liver, the prognosis in such cases is often dismal. The aim of this study was to evaluate the risk factors of early disseminated multinodular hepatocellular carcinoma (HCC) recurrence within 3 months after liver resection for solitary HCC. METHODS Eighty-four patients who were diagnosed with recurrent HCC within 3 months after hepatectomy for solitary HCC were retrospectively reviewed. Disseminated HCC recurrence was defined as more than 10 tumors in both lobes and total tumor size >10 cm. RESULTS Preoperative α-FP level, incidence of poor tumor grade, and presence of portal vein tumor thrombosis were higher in the patients with disseminated HCC recurrence than in those without disseminated HCC recurrence (P < 0.05). Multivariate analysis showed that α-FP >1,000 ng/dL was a predisposing factor of disseminated HCC recurrence within 3 months after liver resection. The overall survival rate for patients without disseminated HCC recurrence was higher than that for patients with disseminated HCC recurrence (P < 0.001). CONCLUSION Early disseminated multinodular HCC recurrence in hepatectomy patients was associated with preoperative α-FP >1,000 ng/dL. Such patients should be frequently evaluated for the early detection of recurrent HCC for early intervention.
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Affiliation(s)
- Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Division of HBP Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Choon Hyuck David Kwon
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Division of HBP Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Division of HBP Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Jiang H, Luo P, Zhi D, Qi F, Huang X, Lu Z, Ge M, Wang L, Qiu B. <italic>In Vitro</italic> and <italic>In Vivo</italic> Experimental Studies of A Novel MR-Guided Method for Bipolar Radiofrequency Liver Ablation. IEEE ACCESS 2018; 6:21859-21866. [DOI: 10.1109/access.2017.2788858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/11/2024]
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40
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Zhang R, Ma M, Dong G, Yao RR, Li JH, Zheng QD, Dong YY, Ma H, Gao DM, Cui JF, Ren ZG, Chen RX. Increased matrix stiffness promotes tumor progression of residual hepatocellular carcinoma after insufficient heat treatment. Cancer Sci 2017; 108:1778-1786. [PMID: 28699238 PMCID: PMC5581508 DOI: 10.1111/cas.13322] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Revised: 07/02/2017] [Accepted: 07/08/2017] [Indexed: 12/13/2022] Open
Abstract
Aggravated behaviors of hepatocellular carcinoma (HCC) will occur after inadequate thermal ablation. However, its underlying mechanisms are not fully understood. Here, we assessed whether the increased matrix stiffness after thermal ablation could promote the progression of residual HCC. Heat‐treated residual HCC cells were cultured on tailorable 3D gel with different matrix stiffness, simulating the changed physical environment after thermal ablation, and then the mechanical alterations of matrix stiffness on cell phenotypes were explored. Increased stiffness was found to significantly promote the proliferation of the heat‐treated residual HCC cells when the cells were cultured on stiffer versus soft supports, which was associated with stiffness‐dependent regulation of ERK phosphorylation. Heat‐exposed HCC cells cultured on stiffer supports showed enhanced motility. More importantly, vitamin K1 reduced stiffness‐dependent residual HCC cell proliferation by inhibiting ERK phosphorylation and suppressed the in vivo tumor growth, which was further enhanced by combining with sorafenib. Increased matrix stiffness promotes the progression of heat‐treated residual HCC cells, proposing a new mechanism of an altered biomechanical environment after thermal ablation accelerates HCC development. Vitamin K1 plus sorafenib can reverse this protumor effect.
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Affiliation(s)
- Rui Zhang
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Min Ma
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Gang Dong
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rong-Rong Yao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jing-Huan Li
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qiong-Dan Zheng
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yin-Ying Dong
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hui Ma
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dong-Mei Gao
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jie-Feng Cui
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng-Gang Ren
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Rong-Xin Chen
- Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
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Vogl TJ, Basten LM, Nour-Eldin NEA, Kaltenbach B, Bodelle B, Wichmann JL, Ackermann H, Naguib NNN. Evaluation of microwave ablation of liver malignancy with enabled constant spatial energy control to achieve a predictable spherical ablation zone. Int J Hyperthermia 2017; 34:492-500. [DOI: 10.1080/02656736.2017.1358408] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Affiliation(s)
- Thomas J. Vogl
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
| | - Lajos M. Basten
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
| | - Nour-Eldin A. Nour-Eldin
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine Cairo University, Egypt
| | - Benjamin Kaltenbach
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
| | - Boris Bodelle
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
| | - Julian L. Wichmann
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
| | - Hanns Ackermann
- Department of Biomedical Statistics, Frankfurt-University, Frankfurt am Main, Germany
| | - Nagy N. N. Naguib
- Institute for Diagnostic and Interventional Radiology, Frankfurt-University Hospital, Frankfurt am Main, Germany
- Department of Diagnostic and Interventional Radiology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
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Weiss J, Rempp H, Clasen S, Notohamiprodjo M, Keßler DE, Pereira PL, Blumenstock G, Nikolaou K, Hoffmann R. Diagnostic accuracy of different magnetic resonance imaging sequences for detecting local tumor progression after radiofrequency ablation of hepatic malignancies. Eur J Radiol 2017; 94:85-92. [PMID: 28655432 DOI: 10.1016/j.ejrad.2017.06.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 06/03/2017] [Accepted: 06/12/2017] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To evaluate the diagnostic accuracy of the individual sequences of a clinical routine liver MRI protocol for the detection of local tumour progression after radiofrequency (RF) ablation of hepatic malignancies. MATERIAL AND METHODS A cohort of 93 patients treated for 140 primary and secondary hepatic malignancies with RF ablation was assembled for this retrospective study. The cohort contained 31 cases of local tumour progression, which occurred 8.3±6.2months (range: 4.0-28.2 months) after treatment. All patients underwent clinical routine follow-up MRI at 1.5T including following sequences: unenhanced T1-weighted fast low angle shot (FLASH-2D), T2-weighted turbo-spin-echo sequence, contrast-enhanced (CE) T1-weighted volume-interpolated breath-hold examination (VIBE), diffusion-weighted imaging (DWI). Follow-up was 32.7±22.5months (range: 4.0-138.3 months). Two readers independently evaluated the individual sequences separately for signs of local tumour progression. Diagnostic confidence was rated on a 4-point scale. Inter-reader agreement was assessed with Coheńs kappa. Long-term follow-up and histological specimen served as standard of reference. RESULTS Both readers reached the highest sensitivity for detection of local tumour progression with unenhanced T1-FLASH 2D (88.2% and 94.1%, respectively) and the highest specificity with CE T1-VIBE (96.2% and 97.2%, respectively). Highest inter-reader agreement was reached with T1-FLASH-2D (kappa=0.83). Typical pitfalls for false-positive diagnoses were focal cholestasis and vasculature adjacent to the ablation zone. Diagnostic confidence was highest with CE T1-VIBE for reader 1 and DWI for reader 2. CONCLUSION Unenhanced T1-FLASH-2D is an essential sequence for follow-up imaging after tumour ablation with a high sensitivity for detection of local progression and a high inter-reader agreement.
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Affiliation(s)
- Jakob Weiss
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany.
| | - Hansjoerg Rempp
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
| | - Stephan Clasen
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
| | - Mike Notohamiprodjo
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
| | - David-Emanuel Keßler
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
| | - Philippe L Pereira
- Department of Radiology, Minimally Invasive Therapies and Nuclearmedicine, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany
| | - Gunnar Blumenstock
- Department of Clinical Epidemiology and Applied Biometry, Eberhard-Karls-University, Silcherstrasse 5, 72076 Tuebingen, Germany
| | - Konstantin Nikolaou
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
| | - Rüdiger Hoffmann
- Department of Diagnostic and Interventional Radiology, Eberhard Karls University Tuebingen, Germany
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Kang TW, Lim HK, Cha DI. Aggressive tumor recurrence after radiofrequency ablation for hepatocellular carcinoma. Clin Mol Hepatol 2017; 23:95-101. [PMID: 28349677 PMCID: PMC5381839 DOI: 10.3350/cmh.2017.0006] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Image-guided radiofrequency ablation (RFA) is an evolving and growing treatment option for patients with hepatocellular carcinoma (HCC) and hepatic metastasis. RFA offers significant advantages as it is less invasive than surgery and carries a low risk of major complications. However, serious complications, including aggressive tumor recurrence, may be observed during follow-up, and recently, mechanical or thermal damage during RFA has been proposed to be one of the causes of this kind of recurrence. Although the exact mechanism of this still remains unclear, physicians should be familiar with the imaging features of aggressive tumor recurrence after RFA for HCC and its risk factors. In addition, in order to prevent or minimize this newly recognized tumor recurrence, a modified RFA technique, combined RFA treatments with transarterial chemoembolization, and cryoablation can be used as alternative treatments. Ultimately, combining an understanding of this potential complication of RFA with an understanding of the possible risk factors for aggressive tumor recurrence and choosing alternative treatments are crucial to optimize clinical outcomes in each patient with HCC.
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Affiliation(s)
- Tae Wook Kang
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyo Keun Lim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Ik Cha
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Zhang Q, Kong J, Dong S, Xu W, Sun W. Metformin exhibits the anti-proliferation and anti-invasion effects in hepatocellular carcinoma cells after insufficient radiofrequency ablation. Cancer Cell Int 2017; 17:48. [PMID: 28450808 PMCID: PMC5404300 DOI: 10.1186/s12935-017-0418-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Accepted: 04/18/2017] [Indexed: 02/06/2023] Open
Abstract
Background The mechanisms and prevention of progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA) has been preliminarily investigated, therefore, new strategy needs to be investigated to prevent the process. Whether metformin could be used to inhibit the growth of HCC after insufficient RFA and further prevent the progression of residual HCC remains unclearly. Methods MTT assay, colony formation assay and transwell assay were used to observe the cell viability, migration and invasion. Western blot and immunohistochemistry methods were used to observe the expression of proteins. Xenograft model was used to evaluate the growth of HCC cells in vivo. Results Metformin inhibited the enhanced proliferation, migration and invasion of HepG2 and SMMC7721 cells after insufficient RFA (named as HepG2-H and SMMC7721-H). Metformin deregulated the expression of p-Akt in HepG2 and SMMC7721 cells after insufficient RFA through AMPK/PTEN pathway. HepG2-H cells also exhibited larger tumor size in vivo. Higher expression of Ki-67 and CD31 and lower expression of E-cadherin were observed in HepG2-H tumors. Metformin blocked the enhanced growth of HepG2 cells in vivo after insufficient RFA. Metformin had no apparent toxicity on nude mice. Conclusions Metfromin inhibited the growth of HCC cells after insufficient RFA, and may be used to prevent the progression of HCC after RFA. Electronic supplementary material The online version of this article (doi:10.1186/s12935-017-0418-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qingyun Zhang
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100043 China.,Department of General Surgery, Affiliated Hospital of Chengde Medical University, Hebei, 067000 China
| | - Jian Kong
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100043 China
| | - Shuying Dong
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100043 China
| | - Wenlei Xu
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100043 China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing, 100043 China
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Tong Y, Yang H, Xu X, Ruan J, Liang M, Wu J, Luo B. Effect of a hypoxic microenvironment after radiofrequency ablation on residual hepatocellular cell migration and invasion. Cancer Sci 2017; 108:753-762. [PMID: 28182306 PMCID: PMC5406608 DOI: 10.1111/cas.13191] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2016] [Revised: 01/27/2017] [Accepted: 02/04/2017] [Indexed: 12/26/2022] Open
Abstract
Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem-like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)-1α signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelial-mesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1α signaling might be effective strategies for patients who experience insufficient RFA therapy.
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Affiliation(s)
- Yuyang Tong
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China.,Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Haiyun Yang
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaolin Xu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China.,Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jingliang Ruan
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Ming Liang
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Jiayi Wu
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Baoming Luo
- Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
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Liao M, Zhong X, Zhang J, Liu Y, Zhu Z, Wu H, Zeng Y, Huang J. Radiofrequency ablation using a 10-mm target margin for small hepatocellular carcinoma in patients with liver cirrhosis: A prospective randomized trial. J Surg Oncol 2017; 115:971-979. [PMID: 28334430 DOI: 10.1002/jso.24607] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/17/2017] [Indexed: 02/05/2023]
Abstract
BACKGROUND AND OBJECTIVES To compare 3-year clinical outcomes of radiofrequency ablation (RFA) targeting 5- or 10-mm margins for small hepatocellular carcinomas (HCCs) in cirrhotic patients. METHODS In total, 96 cirrhotic patients with a small solitary HCC (diameter ≤3 cm) were included in this prospective trial (ChiCTRTRC-10000954). Patients were stratified by Child-Pugh class and randomly allocated into groups targeting either wide margins (≥10 mm, WM) or narrow margins (≥5 mm but <10 mm, NM). RFA was performed under real-time monitoring, and ablative margins were evaluated by pre- and post-operative three-dimensional registration on CT. RESULTS The mean follow-up time was 38.3 ± 4.8 months, 83.3% (40/48) of patients succeeded in obtaining a 10-mm margin in WM group. Based on intention-to-treat analysis, the 3-year incidences of local tumor progression (LTP) (14.9% vs 30.2%), intrahepatic recurrence (IHR) (15.0% vs 32.7%), and recurrence-free survival (RFS) (31.7 ± 12.1 vs 24.0 ± 11.7 months) for WM group were significantly improved compared to NM group. Several prognostic factors were identified from univariate and multivariate analyses. Additionally, cirrhosis-stratified subgroup analyses demonstrated significant survival benefits of WM in patients with Child-Pugh class B cirrhosis. CONCLUSIONS RFA treatment targeting 10-mm margin may reduce the risk of tumor recurrence in cirrhotic patients with a single small HCC.
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Affiliation(s)
- Mingheng Liao
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaofei Zhong
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Jingyi Zhang
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Yangyang Liu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Zexin Zhu
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Wu
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
| | - Yong Zeng
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
| | - Jiwei Huang
- Department of Liver Surgery, Liver Transplantation Division, West China Hospital, Sichuan University, Chengdu, China
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Li K, Su Z, Xu E, Huang Q, Zeng Q, Zheng R. Evaluation of the ablation margin of hepatocellular carcinoma using CEUS-CT/MR image fusion in a phantom model and in patients. BMC Cancer 2017; 17:61. [PMID: 28103837 PMCID: PMC5244580 DOI: 10.1186/s12885-017-3061-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 01/12/2017] [Indexed: 02/06/2023] Open
Abstract
Background To assess the accuracy of contrast-enhanced ultrasound (CEUS)-CT/MR image fusion in evaluating the radiofrequency ablative margin (AM) of hepatocellular carcinoma (HCC) based on a custom-made phantom model and in HCC patients. Methods Twenty-four phantoms were randomly divided into a complete ablation group (n = 6) and an incomplete ablation group (n = 18). After radiofrequency ablation (RFA), the AM was evaluated using ultrasound (US)-CT image fusion, and the results were compared with the AM results that were directly measured in a gross specimen. CEUS-CT/MR image fusion and CT-CT / MR-MR image fusion were used to evaluate the AM in 37 tumors from 33 HCC patients who underwent RFA. Results The sensitivity, specificity, and accuracy of US-CT image fusion for evaluating AM in the phantom model were 93.8, 85.7 and 91.3%, respectively. The maximal thicknesses of the residual AM were 3.5 ± 2.0 mm and 3.2 ± 2.0 mm in the US-CT image fusion and gross specimen, respectively. No significant difference was observed between the US-CT image fusion and direct measurements of the AM of HCC. In the clinical study, the success rate of the AM evaluation was 100% for both CEUS-CT/MR and CT-CT/MR-MR, and the duration was 8.5 ± 2.8 min (range: 4–12 min) and 13.5 ± 4.5 min (range: 8–16 min) for CEUS-CT/MR and CT-CT/MR-MR, respectively. The sensitivity, specificity, and accuracy of CEUS-CT/MR imaging for evaluating the AM were 100.0, 80.0, and 90.0%, respectively. Conclusions A phantom model composed of carrageenan gel and additives was suitable for the evaluation of HCC AM. CEUS-CT/MR image fusion can be used to evaluate HCC AM with high accuracy.
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Affiliation(s)
- Kai Li
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China
| | - Zhongzhen Su
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China
| | - Erjiao Xu
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China
| | - Qiannan Huang
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China
| | - Qingjing Zeng
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China
| | - Rongqin Zheng
- Department of Ultrasound, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, Guangdong Province, People's Republic of China.
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Cho JY, Choi MS, Lee GS, Sohn W, Ahn J, Sinn DH, Gwak GY, Paik YH, Lee JH, Koh KC, Paik SW. Clinical significance and predictive factors of early massive recurrence after radiofrequency ablation in patients with a single small hepatocellular carcinoma. Clin Mol Hepatol 2016; 22:477-486. [PMID: 28081587 PMCID: PMC5266342 DOI: 10.3350/cmh.2016.0048] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Revised: 10/04/2016] [Accepted: 10/28/2016] [Indexed: 12/21/2022] Open
Abstract
Background/Aims Radiofrequency ablation (RFA) is one of the most frequently applied curative treatments in patients with a single small hepatocellular carcinoma (HCC). However, the clinical significance of and risk factors for early massive recurrence after RFA—a dreadful event limiting further curative treatment—have not been fully evaluated. Methods In total, 438 patients with a single HCC of size ≤3 cm who underwent percutaneous RFA as an initial treatment between 2006 and 2009 were included. Baseline patient characteristics, overall survival, predictive factors, and recurrence after RFA were evaluated. In addition, the incidence, impact on survival, and predictive factors of early massive recurrence, and initial recurrence beyond the Milan criteria within 2 years were also investigated. Results During the median follow-up of 68.4 months, recurrent HCC was confirmed in 302 (68.9%) patients, with early massive recurrence in 27 patients (6.2%). The 1-, 3-, and 5-year overall survival rates were 95.4%, 84.7%, and 81.8%, respectively, in patients with no recurrence, 99.6%, 86.4%, and 70.1% in patients with recurrence within the Milan criteria or late recurrence, and 92.6%, 46.5%, and 0.05% in patients with early massive recurrence. Multivariable analysis identified older age, Child-Pugh score B or C, and early massive recurrence as predictive of poor overall survival. A tumor size of ≥2 cm and tumor location adjacent to the colon were independent risk factors predictive of early massive recurrence. Conclusion Early massive recurrence is independently predictive of poor overall survival after RFA in patients with a single small HCC. Tumors sized ≥2 cm and located adjacent to the colon appear to be independent risk factors for early massive recurrence.
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Affiliation(s)
- Ju-Yeon Cho
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Medicine, Chosun University School of Medicine, Gwangju, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Gil Sun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Sohn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Hepatology, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jemma Ahn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong-Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Hoffmann R, Rempp H, Keßler DE, Weiß J, Pereira PL, Nikolaou K, Clasen S. MR-guided microwave ablation in hepatic tumours: initial results in clinical routine. Eur Radiol 2016; 27:1467-1476. [PMID: 27553935 DOI: 10.1007/s00330-016-4517-x] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Revised: 05/11/2016] [Accepted: 07/19/2016] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Evaluation of the technical success, patient safety and technical effectiveness of magnetic resonance (MR)-guided microwave ablation of hepatic malignancies. METHODS Institutional review board approval and informed patient consent were obtained. Fifteen patients (59.8 years ± 9.5) with 18 hepatic malignancies (7 hepatocellular carcinomas, 11 metastases) underwent MR-guided microwave ablation using a 1.5-T MR system. Mean tumour size was 15.4 mm ± 7.7 (7-37 mm). Technical success and ablation zone diameters were assessed by post-ablative MR imaging. Technique effectiveness was assessed after 1 month. Complications were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). Mean follow-up was 5.8 months ± 2.6 (1-10 months). RESULTS Technical success and technique effectiveness were achieved in all lesions. Lesions were treated using 2.5 ± 1.2 applicator positions. Mean energy and ablation duration per tumour were 37.6 kJ ± 21.7 (9-87 kJ) and 24.7 min ± 11.1 (7-49 min), respectively. Coagulation zone short- and long-axis diameters were 31.5 mm ± 10.5 (16-65 mm) and 52.7 mm ± 15.4 (27-94 mm), respectively. Two CTCAE-2-complications occurred (pneumothorax, pleural effusion). Seven patients developed new tumour manifestations in the untreated liver. Local tumour progression was not observed. CONCLUSIONS Microwave ablation is feasible under near real-time MR guidance and provides effective treatment of hepatic malignancies in one session. KEY POINTS • Planning, applicator placement and therapy monitoring are possible without using contrast enhancement • Energy transmission from the generator to the scanner room is safely possible • MR-guided microwave ablation provides effective treatment of hepatic malignancies in one session • Therapy monitoring is possible without applicator retraction from the ablation site.
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Affiliation(s)
- Rüdiger Hoffmann
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany.
| | - Hansjörg Rempp
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - David-Emanuel Keßler
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Jakob Weiß
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Philippe L Pereira
- Department of Radiology, Minimally Invasive Therapies and Nuclear Medicine, SLK-Kliniken Heilbronn GmbH, Am Gesundbrunnen 20-26, 74078, Heilbronn, Germany
| | - Konstantin Nikolaou
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
| | - Stephan Clasen
- Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University, Hoppe-Seyler-Strasse 3, 72076, Tübingen, Germany
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Tang H, Tang Y, Hong J, Chen T, Mai C, Jiang P. A measure to assess the ablative margin using 3D-CT image fusion after radiofrequency ablation of hepatocellular carcinoma. HPB (Oxford) 2015; 17:318-25. [PMID: 25346478 PMCID: PMC4368395 DOI: 10.1111/hpb.12352] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Accepted: 09/12/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To examine the feasibility of three-dimensional computed tomography (3D-CT) image fusion in facilitating assessment of the ablative margin (AM) after radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS This study involved 75 patients with solitary HCC who underwent RFA. The AM was evaluated using 3D-CT image fusion. All cases were categorized into two groups based on the extent of the AM: in Group A, sufficient AM was obtained, which was greater than or equal to 5 mm; in Group B, the lesion was also ablated successfully, but a 5 mm AM was not obtained. RESULTS 3D-CT Image Fusion was performed on 36 and 39 patients in Group A and Group B, respectively. The 1, 3, 5 year RFS was 87.6%, 63.2%, 50.6% for Group A, and 77.2%, 51.5%, 35.6% for Group B, respectively (P = 0.042); the corresponding OS was 94.3%, 73.8%, 64.6%, and 86.2%, 60.5%, 47.6%, respectively (P = 0.046). Multivariate analysis showed that the AM (P = 0.048, HR = 2.15, 95% CI 1.01-4.60) and Pre-NLR were independent prognostic factors for PFS. CONCLUSIONS 3D-CT image fusion is a feasible and useful method to evaluate the AM after RFA of HCC.
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Affiliation(s)
- Hui Tang
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China
| | - Yunqiang Tang
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China,Correspondence, Yunqiang Tang, Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical University, 78 Hengzhigang Road, Guangzhou 510095, Guangdong, China. Tel.: + 86 2066673655. Fax: + 86 2083489984. E-mail:
| | - Jian Hong
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China
| | - Tiejun Chen
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China
| | - Cong Mai
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China
| | - Peng Jiang
- Department of Hepatobiliary Oncology, Cancer Center of Guangzhou Medical UniversityGuangzhou, China
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