|
1
|
Tang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, et alTang H, Zhang W, Cao J, Cao Y, Bi X, Zhao H, Zhang Z, Liu Z, Wan T, Lang R, Sun W, Du S, Yang Y, Lu Y, Zeng D, Wu J, Duan B, Lin D, Li F, Meng Q, Zhou J, Xing B, Tian X, Zhu J, Gao J, Hao C, Wang Z, Duan F, Wang Z, Wang M, Liang B, Chen Y, Xu Y, Li K, Li C, Hu M, Wang Z, Cai S, Ji W, Xia N, Zheng W, Wang H, Li G, Zhu Z, Huang Z, Zhang W, Tao K, Liang J, Zhang K, Dai C, Li J, Qiu Q, Guo Y, Wu L, Ding W, Zhu Z, Gu W, Cao J, Wang Z, Tian L, Ding H, Li G, Zeng Y, Wang K, Yang N, Jin H, Chen Y, Yang Y, Xiu D, Yan M, Wang X, Han Q, Jiao S, Tan G, Wang J, Liu L, Song J, Liao J, Zhao H, Li P, Song T, Wang Z, Yuan J, Hu B, Yuan Y, Zhang M, Sun S, Zhang J, Wang W, Wen T, Yang J, Du X, Peng T, Xia F, Liu Z, Niu W, Liang P, Xu J, Zhao X, Zhu M, Wang H, Kuang M, Shen S, Cui X, Zhou J, Liu R, Sun H, Fan J, Chen X, Zhou J, Cai J, Lu S. Chinese expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition). Biosci Trends 2025; 18:505-524. [PMID: 39721704 DOI: 10.5582/bst.2024.01394] [Show More Authors] [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] [Indexed: 12/28/2024]
Abstract
Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.
Collapse
Affiliation(s)
- Haowen Tang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Junning Cao
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Yinbiao Cao
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Xinyu Bi
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Ze Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhe Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Tao Wan
- Faculty of Hepato-Pancreato-Biliary Surgery, the Eighth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Ren Lang
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Wenbing Sun
- Department of Hepatobiliary Surgery, Beijing ChaoYang Hospital, Capital Medical University, Beijing, China
| | - Shunda Du
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences, Beijing, China
| | - Yongping Yang
- Senior Department of Hepatology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Daobing Zeng
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jushan Wu
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Binwei Duan
- Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Dongdong Lin
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Fei Li
- Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Qinghua Meng
- Department of Medical Oncology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jun Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China
| | - Baocai Xing
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Hepatopancreatobiliary Surgery Department I, Peking University Cancer Hospital & Institute, Beijing, China
| | - Xiaodong Tian
- Department of General Surgery, Peking University First Hospital, Beijing, China
| | - Jiye Zhu
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Jie Gao
- Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China
| | - Chunyi Hao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhiqiang Wang
- Department of Hepatobiliary and Pancreatic Surgery, Qinghai Red Cross Hospital, Qinghai, China
| | - Feng Duan
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhijun Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Maoqiang Wang
- Department of Interventional Radiology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bin Liang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yongwei Chen
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Yinzhe Xu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Kai Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Chengang Li
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Minggen Hu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Zhaohai Wang
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Shouwang Cai
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Wenbin Ji
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Nianxin Xia
- Faculty of Hepato-Pancreato-Biliary Surgery, the Sixth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wenheng Zheng
- Department of Interventional Therapy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Liaoning, China
| | - Hongguang Wang
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Ziman Zhu
- Faculty of Hepato-Pancreato-Biliary Surgery, the Fourth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Wanguang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hosptial, the Fourth Military Medical University, Shanxi, China
| | - Jun Liang
- Department of Medical Oncology, Peking University International Hospital, Beijing, China
| | - Keming Zhang
- Department of Hepatobiliary Surgery, Peking University International Hospital, Beijing, China
| | - Chaoliu Dai
- Department of General Surgery, Shengjing Hospital of China Medical University, Liaoning, China
| | - Jiangtao Li
- Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Qiu Qiu
- Department of Gastroenterology, People's Hospital of Chongqing Hechuan, Chongqing, China
| | - Yuan Guo
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Liqun Wu
- Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Shandong, China
| | - Weibao Ding
- Department of Hepatobiliary Surgery, Weifang People's Hospital, Shandong, China
| | - Zhenyu Zhu
- Hepatobiliary Surgery Center, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Wanqing Gu
- Chinese Journal of Hepatobiliary Surgery, Beijing, China
| | - Jingyu Cao
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Zusen Wang
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Lantian Tian
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Shandong China
| | - Huiguo Ding
- Department of Hepatology and Gastroenterology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Guangming Li
- Department of Liver Transplantation Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Yongyi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, China
| | - Kui Wang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Ning Yang
- Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China
| | - Haosheng Jin
- Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong, China
| | - Yajin Chen
- Department of Hepatobiliopancreatic Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangdong, China
| | - Yinmo Yang
- Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Maolin Yan
- Department of Hepatobiliary and Pancreatic Surgery, Fujian Provincial Hospital, Fujian, China
| | - Xiaodong Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Interventional Therapy, Peking UniversityCancer Hospital & Institute, Beijing, China
| | - Quanli Han
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Shunchang Jiao
- Department of Medical Oncology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Guang Tan
- Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Liaoning, China
| | - Jizhou Wang
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery and Organ Transplantation Center, The First Affiliated Hospital of USTC, Division of Life Science andMedicine, University of Science and Technology of China, Anhui, China
| | - Jinghai Song
- Department of General Surgery, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of MedicalSciences, Beijing, China
| | - Jiajie Liao
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Peng Li
- The Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Hainan Medical University, Hainan, China
| | - Tianqiang Song
- Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical ResearchCenter for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory ofDigestive Cancer, Tianjin, China
| | - Zhanbo Wang
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jing Yuan
- Department of Pathology, the First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Bingyang Hu
- Department of General Surgery, Beijing Shijingshan Hospital, Beijing, China
| | - Yufeng Yuan
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Hubei, China
| | - Meng Zhang
- Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Hebei, China
| | - Shuyang Sun
- Department of Gastroenterology, Beijing Chest Hospital, Capital Medical University, Beijing, China
| | - Jialin Zhang
- Department of Radiology, the First Hospital of China Medical University, Liaoning, China
| | - Wentao Wang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Jiayin Yang
- Department of Liver Surgery, West China Hospital, Sichuan University, Sichuan, China
| | - Xilin Du
- Department of General Surgery, Tangdu Hospital, the Fourth Military Medical University, Shanxi, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi, China
| | - Feng Xia
- Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China
| | - Zuojin Liu
- Department of Hepatobiliary Surgery, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Weibo Niu
- Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Ping Liang
- Department of Interventional Ultrasound, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Jianming Xu
- Department of Gastrointestinal Oncology, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Xiao Zhao
- Department of Immunology and National Center for Biomedicine Analysis, the Fifth Medical Center of the Chinese PLA General Hospital, Beijing,China
| | - Min Zhu
- Department of Transplant Surgery, Qilu Hospital of Shandong University, Shandong, China
| | - Huaizhi Wang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing, China
| | - Ming Kuang
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Shunli Shen
- Center of Hepato Pancreato Biliary Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
| | - Xing Cui
- Department of Oncology and Hematology, the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Shandong,China
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Henan,China
| | - Rong Liu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry ofEducation, Shanghai Key Laboratory of Organ Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Zhongshan Hospital,Fudan University, Shanghai, China
| | - Jianqiang Cai
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center of the Chinese PLA General Hospital, Institute of Hepatobiliary Surgery of the Chinese PLA, Beijing, China
| |
Collapse
|
|
2
|
Tabrizian P, Marino R, Chow PK. Liver resection and transplantation in the era of checkpoint inhibitors. JHEP Rep 2024; 6:101181. [PMID: 39741696 PMCID: PMC11686060 DOI: 10.1016/j.jhepr.2024.101181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 06/24/2024] [Accepted: 07/26/2024] [Indexed: 01/03/2025] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape for advanced hepatocellular carcinoma (HCC). The combination of atezolizumab and bevacizumab has demonstrated efficacy, establishing a new standard of care for advanced HCC. Neoadjuvant studies have shown promising results with high response rates, increasing research into ICIs' role. In the peri-operative setting, in addition to adjuvant and neo-adjuvant therapies, strategies for "downstaging" and "bridging" patients to liver transplantation (LT) are being investigated, broadening the eligible candidate pool. Furthermore, therapeutic advances have reshaped conversion strategies for hepatic resection, with emerging evidence indicating a role for adjuvant immunotherapy in patients at high risk of postoperative recurrence. In LT, concerns have arisen over the potential conflict between immunosuppression needs and the immune-enhancing effects of ICIs, with reports of severe rejection. However, liver-specific factors may lessen rejection risks, prompting exploration into the safety of pre-transplant ICI administration. Moreover, ongoing trials must prioritise patient selection and vigilant management protocols. Despite the remarkable progress in immunotherapy, the intricate molecular interactions within the tumour microenvironment and their implications on oncogenic pathways remain incompletely understood. This highlights the need for specialised expertise to effectively integrate immunotherapy into the surgical management of HCC. Key challenges include ensuring safety, optimising oncological outcomes, managing the risk of graft rejection in transplant recipients, and refining patient selection criteria. In this review, we aim to provide a comprehensive overview of the evolving role of immunotherapy in the surgical management of HCC, discussing the rationale for its application in both pre- and post-surgical contexts, leveraging current clinical experience, identifying potential limitations, and envisioning future applications. By integrating existing knowledge and highlighting areas for further investigation, this review seeks to inform clinical practice and guide future research endeavours.
Collapse
Affiliation(s)
- Parissa Tabrizian
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Rebecca Marino
- Liver Transplant and Hepatobiliary Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, USA
| | - Pierce K.H. Chow
- Department of Hepato-pancreato-Biliary and Transplant Surgery, National Cancer Center Singapore and Singapore General Hospital, Singapore
- Surgery Academic-Clinical Program, Duke-NUS Medical School Singapore, Singapore
| |
Collapse
|
|
3
|
Kocjan J, Rydel M, Adamek M. Hepatocellular Carcinoma (HCC) Metastasis to the Diaphragm Muscle: A Systematic Review and Meta-Analysis of Case Reports. Cancers (Basel) 2024; 16:3076. [PMID: 39272934 PMCID: PMC11394088 DOI: 10.3390/cancers16173076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 08/24/2024] [Accepted: 08/31/2024] [Indexed: 09/15/2024] Open
Abstract
The purpose of this study was to conduct a systematic review and meta-analysis of case reports presenting HCC spread to the diaphragm muscle and to determine possible risk factors for this condition. An extensive literature search was performed using the following electronic databases: MEDLINE, CINAHL, ScienceDirect, Google Scholar, and DOAJ. A total of 18 articles describing 27 hepatocellular carcinoma patients were included in this review. The presence of HCC cells in the superior liver segment is strongly associated with metastases to the diaphragm. Among the two types of diaphragm involvement by HCC cells, diaphragm infiltration occurs much more frequently than diaphragm adhesion. However, an HCC nodule in the 8th liver segment and a higher number of liver segments involved by HCC cells predispose patients to diaphragm adhesion. Hepatitis B is a risk factor for diaphragm metastases in recurrent HCC. The tumor diameter is not associated with HCC spread to the diaphragm muscle. We did not find specific symptoms reported by patients that could indicate HCC metastasis to the diaphragm muscle. The presence of hepatitis B and the localization of HCC cells in superior liver segments, especially in the 8th liver segment, should be take into consideration in the diagnostic process.
Collapse
Affiliation(s)
- Janusz Kocjan
- Diaphragm Concept Academy, Private Clinic Centre Specializing in Treating of Diaphragm Disorders, 32-300 Olkusz, Poland
| | - Mateusz Rydel
- Department of Thoracic Surgery, Faculty of Medicine with Dentistry Division, Medical University of Silesia, 40-055 Katowice, Poland
| | - Mariusz Adamek
- Department of Thoracic Surgery, Faculty of Medicine with Dentistry Division, Medical University of Silesia, 40-055 Katowice, Poland
- Faculty of Health Sciences with Institute of Maritime and Tropical Medicine, Department of Radiology, Medical University of Gdansk, 80-210 Gdansk, Poland
| |
Collapse
|
|
4
|
Lin PT, Teng W, Jeng WJ, Lin CC, Lin CY, Lin SM, Sheen IS. Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment. J Formos Med Assoc 2024; 123:788-795. [PMID: 38310071 DOI: 10.1016/j.jfma.2024.01.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 10/27/2023] [Accepted: 01/29/2024] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. METHODS From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. RESULTS Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). CONCLUSION ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.
Collapse
Affiliation(s)
- Po-Ting Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan.
| | - Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| |
Collapse
|
|
5
|
Gyoda Y, Ichida H, Kawano F, Takeda Y, Yoshioka R, Imamura H, Mise Y, Fukumura Y, Saiura A. A patient alive without disease 32 months after conversion surgery following lenvatinib treatment for hepatocellular carcinoma with a tumor thrombus originating in the middle hepatic vein and reaching the right atrium via the suprahepatic vena cava: a case report. Clin J Gastroenterol 2024; 17:311-318. [PMID: 38277091 DOI: 10.1007/s12328-023-01909-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/12/2023] [Indexed: 01/27/2024]
Abstract
Conversion surgery for initially unresectable hepatocellular carcinoma appears to be increasing in incidence since the advent of new molecular target drugs and immune checkpoint inhibitors; however, reports on long-term outcomes are limited and the prognostic relevance of this treatment strategy remains unclear. Herein, we report the case of a 75-year-old man with hepatocellular carcinoma, 108 mm in diameter, accompanied by a tumor thrombus in the middle hepatic vein that extended to the right atrium via the suprahepatic vena cava. He underwent conversion surgery after preceding lenvatinib treatment and is alive without disease 51 months after the commencement of treatment and 32 months after surgery. Just before conversion surgery, after 19 months of lenvatinib treatment, the main tumor had reduced in size to 72 mm in diameter, the tip of the tumor thrombus had receded back to the suprahepatic vena cava, and the tumor thrombus vascularity was markedly reduced. The operative procedure was an extended left hepatectomy with concomitant middle hepatic vein resection. The tumor thrombus was removed under total vascular exclusion via incision of the root of the middle hepatic vein. Histopathological examination revealed that more than half of the liver tumor and the tumor thrombus were necrotic.
Collapse
Affiliation(s)
- Yu Gyoda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Fumihiro Kawano
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
| |
Collapse
|
|
6
|
Tai Y, Morita Y, Makino M, Ida S, Muraki R, Kitajima R, Takeda M, Kikuchi H, Hiramatsu Y, Takeuchi H. A Case of Giant Hepatocellular Carcinoma Successfully Treated with Lenvatinib Followed by Parenchymal-Sparing Hepatectomy. THE JAPANESE JOURNAL OF GASTROENTEROLOGICAL SURGERY 2023; 56:547-559. [DOI: 10.5833/jjgs.2022.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Yuta Tai
- Department of Surgery, Shizuoka City Shimizu Hospital
| | | | | | - Shinya Ida
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryuta Muraki
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryo Kitajima
- Department of Surgery, Hamamatsu University School of Medicine
| | - Makoto Takeda
- Department of Surgery, Hamamatsu University School of Medicine
| | | | - Yoshihiro Hiramatsu
- Department of Surgery, Hamamatsu University School of Medicine
- Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine
| |
Collapse
|
|
7
|
Zhu Q, Rao W, Huo J, Li Z, Wang S, Qiu W, Guan G, Xin Y, Fan N, Cai J, Wu L. Real-world systemic sequential therapy with regorafenib for recurrent hepatocellular carcinoma: analysis of 93 cases from a single center. BMC Gastroenterol 2023; 23:28. [PMID: 36726082 PMCID: PMC9890826 DOI: 10.1186/s12876-023-02661-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 01/20/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Regorafenib is an oral multikinase inhibitor and became the first second-line systemic treatment for hepatocellular carcinoma (HCC) following the phase III RESORCE trial. This single-center study retrospectively analyzed the clinical data and follow-up results of patients with recurrent HCC treated with regorafenib and discussed the prognostic factors to provide guidance for clinical treatment. METHODS Ninety-three recurrent HCC patients were enrolled in the research and follow up from December 2017 to December 2020. Clinical and pathological data were collected. SPSS software v26.0 was used (Chicago, IL, USA) for statistical analysis. A two-sided P < 0.05 was considered statistically significant. RESULTS The patients included 81 males and 12 females with a median age of 57 years. Eighty-seven patients had hepatitis B virus (HBV) infection. The objective response rate (ORR) was 14.0%, and the disease control rate (DCR) was 62.4%. The median overall survival (mOS) and median time to progression (mTTP) were 15.9 and 5.0 months. Multivariate analysis showed that Child-Pugh classification, the Eastern Cooperative Oncology Group performance status (ECOG PS), the neutrophil-to-lymphocyte ratio (NLR), combined treatment, and the time from first diagnosis of HCC to second-line treatment were independent factors affecting the prognosis of recurrent HCC patients. CONCLUSIONS This real-world study demonstrated similar findings to those of the RESORCE trial. Regorafenib could effectively improve the prognosis of patients after first-line treatment failure. Combination therapy under multidisciplinary treatment (MDT) team guidance could be effective in impeding tumor progression and improving the prognosis of recurrent HCC patients.
Collapse
Affiliation(s)
- Qingwei Zhu
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Wei Rao
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Junyu Huo
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Zixiang Li
- grid.412521.10000 0004 1769 1119Department of Interventional Medicine Cancer Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Song Wang
- grid.412521.10000 0004 1769 1119Department of Interventional Medicine Cancer Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Wensheng Qiu
- grid.412521.10000 0004 1769 1119Tumor Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Ge Guan
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Yang Xin
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Ning Fan
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Jinzhen Cai
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Liqun Wu
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| |
Collapse
|
|
8
|
Sano S, Asahi Y, Kamiyama T, Kakisaka T, Orimo T, Nagatsu A, Aiyama T, Kazui K, Shomura H, Ueki S, Sakamoto Y, Shirakawa C, Kamachi H, Sugino H, Mitsuhashi T, Taketomi A. Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma. Int Cancer Conf J 2023; 12:7-13. [PMID: 36605836 PMCID: PMC9807693 DOI: 10.1007/s13691-022-00567-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/13/2022] [Indexed: 01/09/2023] Open
Abstract
Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
Collapse
Affiliation(s)
- Shunji Sano
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Keizo Kazui
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hiroki Shomura
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Shinya Ueki
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Yuzuru Sakamoto
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Chisato Shirakawa
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Hirokazu Sugino
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| |
Collapse
|
|
9
|
Kato H, Asano Y, Ito M, Arakawa S, Shimura M, Koike D, Ochi T, Yasuoka H, Kawai T, Higashiguchi T, Tani H, Kunimura Y, Kondo Y, Nagata H, Sato H, Horiguchi A. A case of Vp4 hepatocellular carcinoma with tumor thrombosis extending into the confluence of the splenic/portal vein achieved a good prognosis with emergent hepatectomy and postoperative adjuvant therapy with lenvatinib. World J Surg Oncol 2022; 20:278. [PMID: 36057621 PMCID: PMC9440518 DOI: 10.1186/s12957-022-02740-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 08/24/2022] [Indexed: 11/16/2022] Open
Abstract
In this report, we describe a case of highly advanced hepatocellular carcinoma with tumor thrombosis extending into the main portal vein of the pancreas that was successfully treated with adjuvant lenvatinib after right hepatic resection with thrombectomy. A 70-year-old woman was referred from the clinic because of elevated hepatobiliary enzymes. The patient was positive for the hepatitis B virus antigen at our hospital. The tumor markers were highly elevated with alpha-fetoprotein (14.5 U/mL) and protein induced by vitamin K absence (PIVKAII) (1545 ng/mL), suggesting hepatocellular carcinoma. Dynamic abdominal computed tomography showed an early enhanced tumor approximately 6 cm in size and portal vein tumor thrombosis filling the main portal vein, but not extending into the splenic or superior mesenteric vein (SMV). On magnetic resonance imaging 1 week after CT, portal vein tumor thrombosis had extended to the confluence of the splenic vein with the SMV, indicating rapid tumor growth. Thus, we performed emergent right hepatectomy with tumor thrombectomy. Postoperatively, we treated the patient with lenvatinib for a tumor reduction surgery. Fortunately, the patient was alive 2 years postoperatively without recurrence. This case report suggests that a favorable outcome may be achieved with multidisciplinary treatment including resection and postoperative treatment with lenvatinib.
Collapse
Affiliation(s)
- Hiroyuki Kato
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan.
| | - Yukio Asano
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Masahiro Ito
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Satoshi Arakawa
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Masahiro Shimura
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Daisuke Koike
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Takayuki Ochi
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Hironobu Yasuoka
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Toki Kawai
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Takahiko Higashiguchi
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Hiroki Tani
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Yoshiki Kunimura
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Yuka Kondo
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Hidetoshi Nagata
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Harunobu Sato
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| | - Akihiko Horiguchi
- Department of Gastroenterological Surgery, Fujita Health University School of Medicine, Bantane Hospital, 3-6-10 Otobashi Nakagawa Ward Nagoya, Nagoya, Aichi, 454-8509, Japan
| |
Collapse
|
|
10
|
Clinical effectiveness of surgical treatment after lenvatinib administration for hepatocellular carcinoma. Int J Clin Oncol 2022; 27:1725-1732. [PMID: 35962255 DOI: 10.1007/s10147-022-02229-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 07/31/2022] [Indexed: 11/05/2022]
Abstract
BACKGROUND There is little evidence concerning survival after surgery in patients with hepatocellular carcinoma who have received lenvatinib treatment. The aim of this study was to evaluate whether post-lenvatinib surgical treatment in patients with hepatocellular carcinoma improves overall survival. METHODS The cohort of this retrospective study comprised 55 patients with hepatocellular carcinoma who had undergone lenvatinib treatment. We classified them into two groups according to post-lenvatinib surgical treatment status and compared clinicopathologic factors and prognosis between the two groups with the aim of identifying predictors of overall survival. RESULTS The median duration of lenvatinib administration was 5.8 months (range, 0.4-24.0 months). Twelve of the 55 patients underwent surgery after receiving lenvatinib. There was no significant difference in assessed clinicopathological factors between patients who did and did not undergo surgery after being treated with lenvatinib. Multivariate analysis revealed that older age was associated with a significantly worse overall survival (hazard ratio: 2.332; 95% confidence interval 1.062-5.168; P = 0.0369) and that surgery after treatment with lenvatinib achieved better overall survival than other forms of treatment (hazard ratio: 0.121; 95% confidence interval 0.016-0.901; P = 0.0393). CONCLUSIONS Surgical treatment after lenvatinib administration may be a useful therapeutic option for select patients with hepatocellular carcinoma.
Collapse
|
|
11
|
Shindoh J, Kawamura Y, Kobayashi M, Akuta N, Okubo S, Matsumura M, Suzuki Y, Hashimoto M. Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma. J Gastrointest Surg 2022; 26:1637-1646. [PMID: 35715641 DOI: 10.1007/s11605-022-05388-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/14/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Increasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC. METHODS The clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates. RESULTS Multivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01-0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19-0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10-0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16-0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02-0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC. CONCLUSIONS Additional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.
Collapse
Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | | | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Okubo
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masaru Matsumura
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | | | - Masaji Hashimoto
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| |
Collapse
|
|
12
|
Arita J, Ichida A, Nagata R, Mihara Y, Kawaguchi Y, Ishizawa T, Akamatsu N, Kaneko J, Hasegawa K. Conversion surgery after preoperative therapy for advanced hepatocellular carcinoma in the era of molecular targeted therapy and immune checkpoint inhibitors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:732-740. [PMID: 35306748 DOI: 10.1002/jhbp.1135] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 01/06/2022] [Accepted: 01/24/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Optimal strategies for advanced hepatocellular carcinoma (HCC) tumors, such as those with vascular tumor thrombus and those with extrahepatic metastases are unclear. METHODS A literature review was conducted focusing on conversion surgery for HCC after molecular targeted therapy and therapy using immune checkpoint inhibitors. RESULTS Upfront surgical resection of advanced HCC tumors has been challenged at some institutions because of lack of promising therapeutic options. Preoperative transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and radiotherapy in patients with unresectable HCC were developed to improve long-term outcome, but the results were not promising. Nonetheless, the recent advent of molecular targeted therapies and immune check-point inhibitors, enabling frequent tumor responses, has accelerated the use of conversion surgery after these therapies in patients with initially unresectable HCC. Increasing numbers of conversion surgeries after lenvatinib therapy has been reported, and the first prospective clinical trial assessing conversion surgery after lenvatinib therapy in initially unresectable HCC has been commenced. Furthermore, the superiority of combination therapy using atezolizumab and bevacizumab over sorafenib, a conventional first-line drug for unresectable HCC, in terms of overall survival and tumor response has been demonstrated, and the use of this regimen alongside conversion surgery is expected in addition to lenvatinib. CONCLUSION The literature demonstrated the feasibility of conversion surgery after systemic therapy. Further clinical investigation of surgery after systemic therapy for advanced HCC may be undertaken by clearly distinguishing the tumor status as technically unresectable or oncologically unresectable but technically resectable.
Collapse
Affiliation(s)
- Junichi Arita
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Akihiko Ichida
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Rihito Nagata
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yuichiro Mihara
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yoshikuni Kawaguchi
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Takeaki Ishizawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Junichi Kaneko
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary and Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| |
Collapse
|
|
13
|
Shindoh J. Multidisciplinary Approach to the Treatment of Advanced Hepatocellular Carcinoma in the Era of New Biologic Agents. J NIPPON MED SCH 2022; 89:145-153. [PMID: 34840212 DOI: 10.1272/jnms.jnms.2022_89-223] [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] [Indexed: 11/19/2022]
Abstract
With recent advances in systemic therapy, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are expected to benefit from surgery. However, given the complex background of the disease and frequent presence of underlying liver injury, treatment of advanced HCC is complex and the treatment principle applied to colorectal liver metastases, for which conversion surgery has been actively performed, is often not applicable to patients with HCC. To maximize the survival outcomes of patients with HCC, optimization of each step of treatment through a multidisciplinary approach is inevitable. As initial treatment, systematic removal of tumor-bearing portal territory is associated with improved survival in patients with solitary HCC, and radiofrequency ablation is also effective for small, oligo HCCs. Although the high incidence of recurrence even after curative-intent treatment is a major concern in HCC, aggressive treatment for recurrence is important, because a prolonged cancer-free interval is associated with improved overall survival. For patients with advanced disease, recently introduced molecular-targeted agents may be effective for successful conversion to surgery in initially unresectable cases, although the overall response rate of HCC to systemic therapies remains unsatisfactory as compared to that of colorectal liver metastases. This report revisits the theoretical bases for management of HCC and discusses current strategies for maximizing survival of patients with advanced HCC.
Collapse
Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital
- Okinaka Memorial Institute for Medical Disease
| |
Collapse
|
|
14
|
Kaneko S, Tsuchiya K, Yasui Y, Tanaka Y, Inada K, Ishido S, Kirino S, Yamashita K, Hayakawa Y, Nobusawa T, Matsumoto H, Kakegawa T, Higuchi M, Takaura K, Tanaka S, Maeyashiki C, Tamaki N, Takahashi Y, Nakanishi H, Irie T, Ariizumi S, Kurosaki M, Izumi N. Conversion surgery for hepatocellular carcinoma after tyrosine kinase inhibitor treatment. JGH Open 2022; 6:301-308. [PMID: 35601130 PMCID: PMC9120872 DOI: 10.1002/jgh3.12735] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/25/2022] [Accepted: 03/14/2022] [Indexed: 12/20/2022]
Abstract
Background and Aim Conversion surgery (CS), which aims to cure after systematic therapy, is only scarcely reported in the field of hepatocellular carcinoma (HCC). However, advancements in systemic therapy for HCC are expected to increase the candidates eligible for CS because of the higher response rate. The aim of this study was to clarify the characteristics of patients who underwent CS after tyrosine kinase inhibitor (TKI) therapy. Methods In all, 364 patients who were treated with first-line sorafenib (SOR; n = 292) and lenvatinib (LEN; n = 72) from July 2009 to October 2020 were retrospectively enrolled. The endpoint of this analysis was overall survival (OS), and factors associated with CS are revealed. Results Six patients underwent CS after TKI therapy, and of these four (1.4%) and two (2.7%) patients received SOR and LEN, respectively. At baseline, patients who underwent CS were significantly younger (median 52 [range, 46-83] years of age, P = 0.019), and their etiology included viral hepatitis, especially hepatitis B virus (HBV) (P = 0.049). Improvements or maintenance of preoperative modified albumin-bilirubin grade from baseline were observed in five (83.3%) patients, and partial radiologic response was observed in four (66.7%) patients. The median OS and 3-year survival rate of patients treated with CS were "not reached" and 80.0%, respectively. Conclusion The patients who underwent CS after TKI therapy for HCC experienced long survival, were relatively young, and exhibited radiologic response to TKIs, and their liver function was either maintained or improved. Therefore, CS may lead to a better prognosis in patients with advanced HCC.
Collapse
Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yutaka Yasui
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuki Tanaka
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kento Inada
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Shun Ishido
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Sakura Kirino
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Koji Yamashita
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuka Hayakawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Tsubasa Nobusawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Hiroaki Matsumoto
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Tatsuya Kakegawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Mayu Higuchi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kenta Takaura
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Shohei Tanaka
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuka Takahashi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Takumi Irie
- Department of SurgeryMusashino Red Cross HospitalTokyoJapan
| | - Shun‐Ichi Ariizumi
- Department of Surgery, Institute of GastroenterologyTokyo Women's Medical UniversityTokyoJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| |
Collapse
|
|
15
|
Endo Y, Shimazu M, Sakuragawa T, Uchi Y, Edanami M, Sunamura K, Ozawa S, Chiba N, Kawachi S. Successful treatment with laparoscopic surgery and sequential multikinase inhibitor therapy for hepatocellular carcinoma: A case report. World J Gastrointest Surg 2022; 14:260-267. [PMID: 35432767 PMCID: PMC8984515 DOI: 10.4240/wjgs.v14.i3.260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/08/2022] [Accepted: 03/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with massive portal vein tumor thrombosis (PVTT) and distant metastasis is considered unresectable. However, due to recent developments in systemic chemotherapy, successful cases of conversion therapy for unresectable diseases have been reported. Herein, we report a successful multidisciplinary approach for treatment of multi-visceral recurrence with sequential multikinase inhibitor and laparoscopic surgery.
CASE SUMMARY A 63-year-old woman with chronic hepatitis B virus infection was diagnosed with HCC. Subsequently, she underwent two rounds of laparoscopic partial hepatectomy, laparoscopic left adrenalectomy, and transcatheter arterial chemoembolization plus sorafenib for recurrence. Four years after initial hepatectomy, she presented with a 43-mm mass in the spleen and tumor thrombus involving the main portal vein trunk with ascites. Her liver function was Child-Pugh B (8), and protein induced by vitamin K absence or antagonist II (PIVKA II) levels were elevated up to 46.291 mAU/mL. Since initial treatment with regorafenib for three months was unsuccessful, the patient was administered lenvatinib. Ten months post-treatment, there was no contrast enhancement of PVTT or splenic metastasis. Chemotherapy was discontinued due to severe diarrhea. Afterward, splenic metastasis became viable, and PIVKA II increased. Therefore, hand-assisted laparoscopic splenectomy was performed. She experienced no clinical recurrence 14 mo after resection.
CONCLUSION Conversion surgery after successful multikinase inhibitor treatment might be considered an effective treatment option for advanced HCC.
Collapse
Affiliation(s)
- Yutaka Endo
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motohide Shimazu
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | | | - Yusuke Uchi
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motonori Edanami
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Ken Sunamura
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Soji Ozawa
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Naokazu Chiba
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
| | - Shigeyuki Kawachi
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
| |
Collapse
|
|
16
|
Naganuma A, Suzuki Y, Hoshino T, Yasuoka H, Tamura Y, Naruse H, Tanaka H, Hirai K, Sakamoto I, Ogawa T, Hatanaka T, Kakizaki S. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2022; 15:177-184. [PMID: 34811701 DOI: 10.1007/s12328-021-01558-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/10/2021] [Indexed: 12/09/2022]
Abstract
We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.
Collapse
Affiliation(s)
- Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuhei Suzuki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hidetoshi Yasuoka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuki Tamura
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroaki Naruse
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroshi Tanaka
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Keitaro Hirai
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Ichiro Sakamoto
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Tetsushi Ogawa
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, 564-1 Kamishindenmachi, Maebashi, Gunma, 371-0821, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
- Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
| |
Collapse
|
|
17
|
Shindoh J, Kawamura Y, Kobayashi Y, Kobayashi M, Akuta N, Okubo S, Suzuki Y, Hashimoto M. Prognostic Impact of Surgical Intervention After Lenvatinib Treatment for Advanced Hepatocellular Carcinoma. Ann Surg Oncol 2021; 28:7663-7672. [PMID: 33904001 DOI: 10.1245/s10434-021-09974-0] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 03/22/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND With the introduction of new molecular-targeted agents, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are benefiting from salvage interventions; however, the actual rate of conversion surgery and its prognostic advantages remain unclear. METHODS The clinical outcomes of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were reviewed and the efficacy of additional therapy, including surgery, was investigated. RESULTS Of the 107 patients who were initially unsuitable for curative-intent therapy or transarterial chemoembolization (TACE), 54 (50.5%) received further therapy after lenvatinib treatment (surgery [n = 16] and TACE or other treatments [n = 38]). Of the 16 patients who received surgical intervention, R0 resection was achieved in 9 (8.4%) patients. Survival analysis confirmed that successful conversion to R0 resection was associated with a longer time to treatment failure (hazard ratio [HR] 0.04, 95% confidence interval [CI] 0.01-0.29; p = 0.002) and better disease-specific survival (HR 0.04, 95% CI 0.01-0.30; p = 0.002) compared with no additional treatment, while additional treatment other than surgery or R2 resection was associated with only a marginal or no prognostic advantage. Multivariate analysis confirmed that a decrease in plasma des-gamma-carboxyprothrombin levels compared with baseline levels (odds ratio 22.22, 95% CI 3.42-144.29; p = 0.001) was significantly correlated with successful R0 resection after lenvatinib treatment, irrespective of the tumor response as assessed by imaging analysis. CONCLUSIONS In selected patients with advanced HCC, conversion surgery after lenvatinib treatment may offer significant survival benefit as long as R0 resection is achieved.
Collapse
Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | | | - Yuta Kobayashi
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Okubo
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| | | | - Masaji Hashimoto
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo, Japan
| |
Collapse
|
|
18
|
Asahi Y, Kamiyama T, Kakisaka T, Orimo T, Shimada S, Nagatsu A, Aiyama T, Sakamoto Y, Kamachi H, Taketomi A. Outcomes of reduction hepatectomy combined with postoperative multidisciplinary therapy for advanced hepatocellular carcinoma. World J Gastrointest Surg 2021; 13:1245-1257. [PMID: 34754392 PMCID: PMC8554724 DOI: 10.4240/wjgs.v13.i10.1245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/21/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The prognosis of advanced hepatocellular carcinoma (HCC) that is not indicated for curative hepatectomy remains poor, despite advances in the treatment of HCC, including the development of tyrosine kinase inhibitors (TKIs). The outcomes of reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy, including those of recently treated cases, should be investigated.
AIM To examine the outcomes of combination treatment with reduction hepatectomy and multidisciplinary postoperative treatment for advanced HCC that is not indicated for curative hepatectomy.
METHODS Thirty cases of advanced HCC that were not indicated for curative hepatectomy, in which reduction hepatectomy was performed between 2000 and 2018 at the Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, were divided into postoperative complete remission (POCR) (+) and POCR (-) groups, depending on whether POCR of all evaluable lesions was achieved through postoperative treatment. The cases in the POCR (-) group were subdivided into POCR (-) TKI (+) and POCR (-) TKI (-) groups, depending on whether TKIs were administered postoperatively.
RESULTS The 5-year overall survival rate and mean survival time (MST) after reduction hepatectomy were 15.7% and 28.40 mo, respectively, for all cases; 37.5% and 56.55 mo, respectively, in the POCR (+) group; and 6.3% and 14.84 mo, respectively, in the POCR (-) group (P = 0.0041). Tumor size, major vascular invasion, and the number of tumors in the remnant liver after the reduction hepatectomy were also found to be related to survival outcomes. The number of tumors in the remnant liver was the only factor that differed significantly between the POCR (+) and POCR (-) groups, and POCR was achieved significantly more frequently when ≤ 3 tumors remained in the remnant liver (P = 0.0025). The MST was 33.52 mo in the POCR (-) TKI (+) group, which was superior to the MST of 10.74 mo seen in the POCR (-) TKI (-) group (P = 0.0473).
CONCLUSION Reduction hepatectomy combined with multidisciplinary postoperative treatment for unresectable advanced HCC that was not indicated for curative hepatectomy was effective when POCR was achieved via multidisciplinary postoperative therapy. To achieve POCR, reduction hepatectomy should aim to ensure that ≤ 3 tumors remain in the remnant liver. Even in cases in which POCR is not achieved, combined treatment with reduction hepatectomy and multidisciplinary therapy can improve survival outcomes when TKIs are administered.
Collapse
Affiliation(s)
- Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Shingo Shimada
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Yuzuru Sakamoto
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Hokkaido, Japan
| |
Collapse
|
|
19
|
Endo K, Kuroda H, Abe T, Sato H, Kooka Y, Oikawa T, Sato A, Nishiya M, Sugai T, Takikawa Y. Two hepatectomy cases for initially unresectable hepatocellular carcinoma after achieving a radiological complete response to sequential therapy with lenvatinib and transcatheter arterial chemoembolization. Hepatol Res 2021; 51:1082-1086. [PMID: 33982336 DOI: 10.1111/hepr.13665] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/16/2021] [Accepted: 05/08/2021] [Indexed: 11/29/2022]
Abstract
We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.
Collapse
Affiliation(s)
- Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Tamami Abe
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Hiroki Sato
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Youhei Kooka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Takayoshi Oikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Ayaka Sato
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Masao Nishiya
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Tamotsu Sugai
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| |
Collapse
|
|
20
|
Yamamura K, Beppu T. Conversion surgery for hepatocellular carcinoma after multidisciplinary treatment including lenvatinib. Hepatol Res 2021; 51:1029-1030. [PMID: 34596312 DOI: 10.1111/hepr.13691] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Kensuke Yamamura
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| |
Collapse
|
|
21
|
Retrospective evaluation of the effect of Ninjin'yoeito in hepatocellular carcinoma patients treated with lenvatinib. Surg Today 2021; 52:441-448. [PMID: 34417867 DOI: 10.1007/s00595-021-02358-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 06/15/2021] [Indexed: 02/08/2023]
Abstract
PURPOSES Lenvatinib (LEN) is a molecular-target drug, used for unresectable hepatocellular carcinoma (HCC). It is associated with adverse events (AEs), including hypertension, proteinuria, fatigue, and anorexia, which may force dose reduction or discontinuation. Ninjin'yoeito (NYT) is a Chinese-Japanese herbal compound that can effectively treat fatigue and anorexia, and which has been used for chronic liver diseases. NYT reduces AEs and improves the liver function in patients treated with sorafenib but its effect on LEN is unclear. METHODS The present study included 46 patients (male, n = 32; female, n = 14) who received LEN for HCC at our hospital. Their median age was 70 years (range 36-88 years), and their median body weight was 61.5 kg (range 38.4-97.0 kg). Patients were divided into two groups, depending on whether they received NYT medication. Their AEs and liver function were examined one month after starting LEN. RESULTS The NYT group suffered less fatigue (63.6% vs. 11.4%, P = 0.0014) and showed elevated aspartate aminotransferase levels (45.5% vs. 14.3%, P = 0.0433) in comparison to the non-NYT group. The non-NYT group also showed a significantly exacerbated albumin-bilirubin (ALBI) grade (P = 0.0342) and ALBI score (average change: + 0.232, P = 0.0001) at 1 month in comparison to baseline. CONCLUSION NYT apparently suppressed LEN-induced fatigue and helped maintain liver function in patients with HCC.
Collapse
|
|
22
|
Colón Rodríguez A, Velasco Sánchez E, Rodríguez-Bachiller L, Díaz-Zorita B, López Baena JÁ, Álvarez Luque A, Rincón Rodríguez D, Matilla Peña AM. Neoadjuvant combined strategy to surgery based on chemoembolization and lenvatinib in hepatocellular carcinoma. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:490-491. [PMID: 34400190 DOI: 10.1016/j.gastrohep.2021.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/19/2021] [Accepted: 07/26/2021] [Indexed: 11/25/2022]
Affiliation(s)
- Arturo Colón Rodríguez
- Sección Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón, Madrid, España.
| | - Enrique Velasco Sánchez
- Sección Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Luis Rodríguez-Bachiller
- Sección Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Benjamín Díaz-Zorita
- Sección Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - José Ángel López Baena
- Sección Cirugía Hepatobiliopancreática y Trasplante Hepático, Servicio de Cirugía General, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Arturo Álvarez Luque
- Sección de Radiología Intervencionista, Servicio de Radiología, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Diego Rincón Rodríguez
- Sección de Hepatología. Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| | - Ana María Matilla Peña
- Sección de Hepatología. Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Madrid, España
| |
Collapse
|