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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.
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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
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Hu Z, Yang Z, Wang J, Fu Y, Hu Z, Zhou Z, Chen M, Zhang Y. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. Front Pharmacol 2023; 14:1223632. [PMID: 37799969 PMCID: PMC10549930 DOI: 10.3389/fphar.2023.1223632] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/06/2023] [Indexed: 10/07/2023] Open
Abstract
Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5 years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC.
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Affiliation(s)
- Zili Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhenyun Yang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Jiongliang Wang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yizhen Fu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhiwen Hu
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Zhongguo Zhou
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
| | - Yaojun Zhang
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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Bai J, Huang M, Song B, Luo W, Ding R. The Current Status and Future Prospects for Conversion Therapy in the Treatment of Hepatocellular Carcinoma. Technol Cancer Res Treat 2023; 22:15330338231159718. [PMID: 36855803 PMCID: PMC9983081 DOI: 10.1177/15330338231159718] [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] [Indexed: 03/02/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. In China, most HCC patients are diagnosed with advanced disease and in these cases surgery is challenging. Conversion therapy can be used to change unresectable HCC into resectable disease and is a potential breakthrough treatment strategy. The resection rate for unresectable advanced HCC has recently improved as a growing number of patients have benefited from conversion therapy. While conversion therapy is at an early stage of development, progress in patient selection, optimum treatment methods, and the timing of surgery have the potential to deliver significant benefits. In this article, we review the current evidence and clinical experience of conversion therapy in HCC. General conversion modalities such as systemic treatments (systemic chemotherapy, targeted therapy, or immunotherapy), locoregional therapy (transarterial chemoembolization, hepatic arterial infusion chemotherapy, or selective internal radiation therapy), and combination therapy were summarized. We also discuss the current challenges of conversion therapy and provide identify areas for future research to improve the development of conversion therapy in advanced HCC.
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Affiliation(s)
- Jinfeng Bai
- 531840The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ming Huang
- 531840The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Bohan Song
- 531840The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wei Luo
- 531840The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Rong Ding
- 531840The Third Affiliated Hospital of Kunming Medical University, Kunming, China
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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.
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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
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Sun HC, Zhou J, Wang Z, Liu X, Xie Q, Jia W, Zhao M, Bi X, Li G, Bai X, Ji Y, Xu L, Zhu XD, Bai D, Chen Y, Chen Y, Dai C, Guo R, Guo W, Hao C, Huang T, Huang Z, Li D, Li G, Li T, Li X, Li G, Liang X, Liu J, Liu F, Lu S, Lu Z, Lv W, Mao Y, Shao G, Shi Y, Song T, Tan G, Tang Y, Tao K, Wan C, Wang G, Wang L, Wang S, Wen T, Xing B, Xiang B, Yan S, Yang D, Yin G, Yin T, Yin Z, Yu Z, Zhang B, Zhang J, Zhang S, Zhang T, Zhang Y, Zhang Y, Zhang A, Zhao H, Zhou L, Zhang W, Zhu Z, Qin S, Shen F, Cai X, Teng G, Cai J, Chen M, Li Q, Liu L, Wang W, Liang T, Dong J, Chen X, Wang X, Zheng S, Fan J, Alliance of Liver Cancer Conversion Therapy, Committee of Liver Cancer of the Chinese Anti-Cancer Association. Chinese expert consensus on conversion therapy for hepatocellular carcinoma (2021 edition). Hepatobiliary Surg Nutr 2022; 11:227-252. [PMID: 35464283 PMCID: PMC9023831 DOI: 10.21037/hbsn-21-328] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 11/18/2021] [Indexed: 01/27/2023]
Abstract
Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice. Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.
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Affiliation(s)
- Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zheng Wang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiufeng Liu
- Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China
| | - Qing Xie
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weidong Jia
- Department of Liver Surgery, The First Affiliated Hospital of USTC, Hefei, China
| | - Ming Zhao
- Minimally Invasive Interventional Division, Sun Yat-sen University Cancer Center, Guangzhou, 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
| | - Gong Li
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, Beijing, China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yuan Ji
- Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, China
| | - Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Dousheng Bai
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Yajin Chen
- Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yongjun Chen
- Division of Hepatobiliary Surgery, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chaoliu Dai
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, China
| | - Rongping Guo
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Chunyi Hao
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sarcoma Center, Peking University Cancer Hospital and Institute, Beijing, China
| | - Tao Huang
- Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhiyong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Deyu Li
- Department of Hepato-Biliary Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
| | - Gang Li
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
| | - Tao Li
- Department of general surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Xiangcheng Li
- Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guangming Li
- Center of General Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Xiao Liang
- Department of General Surgery, Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, China
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Fubao Liu
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei, China
| | - Shichun Lu
- Department of Hepatobiliary Surgery, First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Zheng Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College Bengbu, China
| | - Weifu Lv
- Department of Interventional Radiology, The Anhui Provincial Hospital, Hefei, China
| | - Yilei Mao
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, China
| | - Guoliang Shao
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou, China
| | - Yinghong Shi
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
| | - Tianqiang Song
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Guang Tan
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yunqiang Tang
- Department of Hepatic-Biliary Surgery, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
| | - Chidan Wan
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Guangyi Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Lu Wang
- Liver Surgery Department, Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Shunxiang Wang
- Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Tianfu Wen
- Department of Liver Surgery & Liver Transplantation Centre, West China Hospital of Sichuan University, Chengdu, China
| | - Baocai Xing
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
| | - Bangde Xiang
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Sheng Yan
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Dinghua Yang
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Guowen Yin
- Department of Intervention, Cancer Hospital of Jiangsu, Nanjing, China
| | - Tao Yin
- Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, Wuhan, China
| | - Zhenyu Yin
- Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, China
| | - Zhengping Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jialin Zhang
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China
| | - Shuijun Zhang
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ti Zhang
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yamin Zhang
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin, China
| | - Yubao Zhang
- Department of Hepatobiliary Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
| | - Aibin Zhang
- Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ledu Zhou
- Department of Liver Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Wu Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zhenyu Zhu
- Hepatoliliary Surgery Center, 302 Hospital of PLA, Beijing, China
| | - Shukui Qin
- Qinhuai Medical Area, Eastern Theater General Hospital of PLA China, Nanjing, China
| | - Feng Shen
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiujun Cai
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
| | - Gaojun Teng
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 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
| | - Minshan Chen
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiahong Dong
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing, China
| | - Xiaoping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuehao Wang
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
| | - Shusen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Alliance of Liver Cancer Conversion Therapy, Committee of Liver Cancer of the Chinese Anti-Cancer Association
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China
- Department of Infectious Disease, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Liver Surgery, The First Affiliated Hospital of USTC, Hefei, China
- Minimally Invasive Interventional Division, Sun Yat-sen University Cancer Center, Guangzhou, China
- 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
- Department of Radiation Oncology, Beijing Tsinghua Changgung Hospital, Beijing, China
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China
- Department of Liver Surgery, Sun Yat-sen University Cancer Centre, Guangzhou, China
- Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, China
- Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Division of Hepatobiliary Surgery, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
- Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital Affiliated to China Medical University, Shenyang, China
- The Department of Hepatobiliary Oncology of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Sarcoma Center, Peking University Cancer Hospital and Institute, Beijing, China
- Department of Hepatobiliary Surgery, Affiliated Tumour Hospital of Zhengzhou University, Zhengzhou, China
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Hepato-Biliary Pancreatic Surgery, Henan Provincial People’s Hospital, Zhengzhou, China
- Department of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Naval Military Medical University (Second Military Medical University), Shanghai, China
- Department of general surgery, Qilu Hospital, Shandong University, Jinan, China
- Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Center of General Surgery, Beijing YouAn Hospital, Capital Medical University, Beijing, China
- Department of General Surgery, Zhejiang University, School of Medicine, Sir Run Run Shaw Hospital, Hangzhou, China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
- Division of General Surgery, First Affiliated Hospital, Anhui Medical University, Hefei, China
- Department of Hepatobiliary Surgery, First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College Bengbu, China
- Department of Interventional Radiology, The Anhui Provincial Hospital, Hefei, China
- Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC & Chinese Academy of Medical Sciences (CAMS), Beijing, China
- Department of Intervention, Zhejiang Cancer Hospital, Hangzhou, China
- Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China
- Department of Hepatobiliary Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China
- Department of Hepatic-Biliary Surgery, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China
- Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China
- Liver Surgery Department, Shanghai Cancer Center, Fudan University, Shanghai, China
- Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
- Department of Liver Surgery & Liver Transplantation Centre, West China Hospital of Sichuan University, Chengdu, China
- Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China
- Hepatobiliary Surgery Department, Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Key Laboratory for High-Incidence Tumor Prevention and Treatment, Ministry of Education, Guangxi Medical University Cancer Hospital, Nanning, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Unit of Hepatobiliary Surgery, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
- Department of Intervention, Cancer Hospital of Jiangsu, Nanjing, China
- Department of Hepatic & Biliary & Pancreatic Surgery, Hubei Cancer Hospital, Affiliated Hubei Cancer Hospital of Huazhong University of Science and Technology, Wuhan, China
- Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Department of Hepatobiliary Surgery, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin, China
- Department of Hepatobiliary Pancreatic Surgery, Harbin Medical University Cancer Hospital, Harbin, China
- Department of Hepatobiliary Pancreatic Surgery, The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, China
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Department of Liver Surgery, Xiangya Hospital, Central South University, Changsha, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Zhejiang Province, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Hepatoliliary Surgery Center, 302 Hospital of PLA, Beijing, China
- Qinhuai Medical Area, Eastern Theater General Hospital of PLA China, Nanjing, China
- Department of Hepatic Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China
- Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
- 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
- Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- Department of Hepatobiliary Surgery, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Changping, Beijing, China
- Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, China
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6
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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.
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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
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7
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Kim SB. Hepatocellular Carcinoma with Distant Metastasis Cured by 20-Day Sorafenib Treatment. Case Rep Gastroenterol 2021; 15:610-615. [PMID: 34616264 PMCID: PMC8454233 DOI: 10.1159/000514529] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 01/13/2021] [Indexed: 11/29/2022] Open
Abstract
There are only 13 cases of complete remission after sorafenib use in advanced hepatocellular carcinoma (HCC) worldwide. We herein report a rarer case in which the patient was cured after only 20 days of sorafenib use. A 61-year-old male patient was diagnosed with a huge HCC. The mass occupied almost the whole of the right hepatic lobe and a portion of segment 4. We performed extended right hepatectomy for cure. However, 3.5-cm-sized subcarinal lymph node metastasis was detected at 15 months after operation. We prescribed sorafenib 400 mg bid for palliative treatment. The patient had severe fever, pain, and blisters on the hands and feet, so the patient stopped taking it after 20 days. Subcarinal lymph node disappeared on chest computed tomography after 3 months, and there was no evidence of recurrence for a year.
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Affiliation(s)
- Seok Bae Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea
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8
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Woei‐A‐Jin FSH, Weijl NI, Burgmans MC, Fariña Sarasqueta A, van Wezel JT, Wasser MN, Coenraad MJ, Burggraaf J, Osanto S. Neoadjuvant Treatment with Angiogenesis-Inhibitor Dovitinib Prior to Local Therapy in Hepatocellular Carcinoma: A Phase II Study. Oncologist 2021; 26:854-864. [PMID: 34251745 PMCID: PMC8488766 DOI: 10.1002/onco.13901] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) recurrence rates following locoregional treatment are high. As multireceptor tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFRs) are effective in advanced HCC, we assessed the efficacy and safety of neoadjuvant systemic treatment with dovitinib in early- and intermediate-stage HCC. MATERIALS AND METHODS Twenty-four patients with modified Child-Pugh class A early- and intermediate-stage HCC received neoadjuvant oral dovitinib 500 mg daily (5 days on/2 days off) for 4 weeks, followed by locoregional therapy. Primary endpoints were objective response rates and intratumoral blood flow changes. Secondary endpoints were safety, pharmacodynamical plasma markers of VEGFR-blockade, time to progression (TTP), and overall survival (OS). RESULTS Modified RECIST overall response rate was 48%, including 13% complete remission, and despite dose reduction/interruption in 83% of patients, intratumoral perfusion index decreased significantly. Grade 3-4 adverse events, most frequently (on-target) hypertension (54%), fatigue (25%), and thrombocytopenia (21%), occurred in 88% of patients. Plasma VEGF-A, VEGF-D, and placental growth factor increased significantly, whereas sTie-2 decreased, consistent with VEGFR-blockade. Following neoadjuvant dovitinib, all patients could proceed to their original planned locoregional treatment. No delayed toxicity occurred. Seven patients (three early, four intermediate stage) underwent orthotopic liver transplant after median 11.4 months. Censoring at transplantation, median TTP and OS were 16.8 and 34.8 months respectively; median cancer-specific survival was not reached. CONCLUSION Already after a short 4-week dovitinib treatment period, intratumoral blood flow reduction and modest antitumor responses were observed. Although these results support use of systemic neoadjuvant strategies, the poor tolerability indicates that dovitinib dose adaptations are required in HCC. IMPLICATIONS FOR PRACTICE Orthotopic liver transplantation may cure early and intermediate-stage hepatocellular carcinoma. Considering the expected waiting time >6 months because of donor liver scarcity, there is an unmet need for effective neoadjuvant downsizing strategies. Angiogenesis inhibition by dovitinib does not negatively affect subsequent invasive procedures, is safe to administer immediately before locoregional therapy, and may provide a novel treatment approach to improve patient outcomes if tolerability in patients with hepatocellular carcinoma can be improved by therapeutic drug monitoring and personalized dosing.
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Affiliation(s)
- F.J. Sherida H. Woei‐A‐Jin
- Department of Medical Oncology, Leiden University Medical CenterLeiden,Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical CenterLeiden
| | - Nir I. Weijl
- Department of Medical Oncology, Leiden University Medical CenterLeiden
| | - Mark C. Burgmans
- Department of Radiology, Leiden University Medical CenterLeidenThe Netherlands
| | | | - J. Tom van Wezel
- Department of Pathology, Leiden University Medical CenterLeidenThe Netherlands
| | | | - Minneke J. Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical CenterLeidenThe Netherlands
| | | | - Susanne Osanto
- Department of Medical Oncology, Leiden University Medical CenterLeiden,Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical CenterLeiden
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Zhu XD, Huang C, Shen YH, Ji Y, Ge NL, Qu XD, Chen L, Shi WK, Li ML, Zhu JJ, Tan CJ, Tang ZY, Zhou J, Fan J, Sun HC. Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations. Liver Cancer 2021; 10:320-329. [PMID: 34414120 PMCID: PMC8339461 DOI: 10.1159/000514313] [Citation(s) in RCA: 147] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 01/07/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Combined therapy with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies has shown high tumor response rates for patients with unresectable hepatocellular carcinoma (HCC). However, using this treatment strategy to convert initially unresectable HCC to resectable HCC was not reported. METHODS Consecutive patients with unresectable HCC who received first-line therapy with combined TKI/anti-PD-1 antibodies were analyzed. Tumor response and resectability were evaluated via imaging every 2 months (±2 weeks) using RECIST v1.1. Resectability criteria were (1) R0 resection could be achieved with sufficient remnant liver volume and function; (2) intrahepatic lesions were evaluated as partial responses or stable disease for at least 2 months; (3) no severe or persistent adverse effects occurred; and (4) hepatectomy was not contraindicated. RESULTS Sixty-three consecutive patients were enrolled. Of them, 10 (15.9%) underwent R0 resection in 3.2 months (range: 2.4-8.3 months) after the initiation of combination therapy. At baseline, these 10 patients had a median largest tumor diameter of 9.3 cm, 7 had Barcelona Clinic Liver Cancer stage C (vascular invasion) disease, 2 had stage B, and 1 had stage A. Before surgery, 6 patients were evaluated as a partial response, 3 stable disease, and 1 partial response in the intrahepatic lesion but a new metastatic lesion in the right adrenal gland. Six patients (60%) achieved a pathological complete response. One patient died from immune-related adverse effects 2.4 months after hepatectomy. After a median follow-up of 11.2 months (range: 7.8-15.9 months) for other 9 patients, 8 survived without disease recurrence, and 1 experienced tumor recurrence. CONCLUSIONS Combination of TKI/anti-PD-1 antibodies is a feasible conversion therapy for patients with unresectable HCC to become resectable. This study represents the largest patient cohort on downstaging role of combinational systemic therapy on TKI and PD-1 antibody for HCC.
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Affiliation(s)
- Xiao-Dong Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Cheng Huang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ying-Hao Shen
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ning-Ling Ge
- Department of Hepatic Oncology, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xu-Dong Qu
- Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lingli Chen
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen-Kai Shi
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mei-Ling Li
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jin-Jin Zhu
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chang-Jun Tan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhao-You Tang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jia Fan
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hui-Chuan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China,*Hui-Chuan Sun Department of Liver Surgery and Transplantation Liver Cancer Institute and Zhongshan Hospital, Fudan University No. 180, Fenglin Road, Shanghai 200032 (China)
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10
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Govalan R, Lauzon M, Luu M, Ahn JC, Kosari K, Todo T, Kim IK, Noureddin M, Kuo A, Walid AS, Sundaram V, Lu SC, Roberts LR, Singal AG, Heimbach JK, Agopian VG, Nissen N, Yang JD. Comparison of Surgical Resection and Systemic Treatment for Hepatocellular Carcinoma with Vascular Invasion: National Cancer Database Analysis. Liver Cancer 2021; 10:407-418. [PMID: 34721504 PMCID: PMC8527916 DOI: 10.1159/000515554] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 03/01/2021] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Small studies from outside of the USA suggest excellent outcomes after surgical resection for hepatocellular carcinoma (HCC) with vascular invasion. The study aims to (1) compare overall survival after surgical resection and systemic therapy among patients with HCC and vascular invasion and (2) determine factors associated with receipt of surgical resection in a US population. METHODS HCC patients with AJCC clinical TNM stage 7th T3BN0M0 diagnosed between 2010 and 2017 from the National Cancer Database were analyzed. Cox and logistic regression analyses identified factors associated with overall survival and receipt of surgical resection. RESULTS Of 11,259 patients with T3BN0M0 HCC, 325 (2.9%) and 4,268 (37.9%) received surgical resection and systemic therapy, respectively. In multivariable analysis, surgical resection was associated with improved survival compared to systemic therapy (adjusted hazard ratio: 0.496, 95% confidence interval: 0.426-0.578) with a median survival of 21.4 and 8.1 months, respectively. Superiority of surgical resection was observed in noncirrhotic and cirrhotic subgroups and propensity score matching and inverse probability of treatment weighting adjusted analysis. Asians were more likely to receive surgical resection, whereas Charlson comorbidity ≥3, elevated alpha-fetoprotein, smaller tumor size, care in a community cancer program, and the South or West region were associated with a lower likelihood of surgical resection. CONCLUSION HCC patients with vascular invasion may benefit from surgical resection compared to systemic therapies. Demographic and clinical features of HCC patients and region and type of treating facility were associated with surgical resection versus systemic treatment.
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Affiliation(s)
- Rajalakshmi Govalan
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Marie Lauzon
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Michael Luu
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Joseph C. Ahn
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Kambiz Kosari
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Tsuyoshi Todo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Irene K. Kim
- Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Mazen Noureddin
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Alexander Kuo
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ayoub S. Walid
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vinay Sundaram
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Shelly C. Lu
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Lewis R. Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Amit G. Singal
- Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA,Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Julie K. Heimbach
- Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA,Liver Transplant Program, Mayo Clinic, Rochester, Minnesota, USA
| | - Vatche G. Agopian
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - Nicholas Nissen
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Ju Dong Yang
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA,Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA,Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California, USA,Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, California, USA,*Ju Dong Yang,
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11
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Schipilliti FM, Garajová I, Rovesti G, Balsano R, Piacentini F, Dominici M, Gelsomino F. The Growing Skyline of Advanced Hepatocellular Carcinoma Treatment: A Review. Pharmaceuticals (Basel) 2021; 14:43. [PMID: 33429973 PMCID: PMC7827379 DOI: 10.3390/ph14010043] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/13/2020] [Accepted: 12/30/2020] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the main type of liver cancer. In the majority of cases, HCC is diagnosed at the advanced stage, leading to poor prognosis. In recent years, many efforts have been devoted to investigating potential new and more effective drugs and, indeed, the treatment armamentarium for advanced HCC has broadened tremendously, with targeted- and immune-therapies, and probably the combination of both, playing pivotal roles. Together with new established knowledge, many issues are emerging, with the role of neoadjuvant/adjuvant settings, the definition of the best transitioning time from loco-regional treatments to systemic therapy, the identification of potential predictive biomarkers, and radiomics being just some of the topics that will have to be further explored in the next future. Clearly, the current COVID-19 pandemic has influenced the management of HCC patients and some considerations about this topic will be elucidated.
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Affiliation(s)
- Francesca Matilde Schipilliti
- Oncology Unit, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (G.R.); (F.P.); (M.D.)
| | - Ingrid Garajová
- Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy;
| | - Giulia Rovesti
- Oncology Unit, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (G.R.); (F.P.); (M.D.)
| | - Rita Balsano
- Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43126 Parma, Italy;
| | - Federico Piacentini
- Oncology Unit, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (G.R.); (F.P.); (M.D.)
| | - Massimo Dominici
- Oncology Unit, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (G.R.); (F.P.); (M.D.)
| | - Fabio Gelsomino
- Oncology Unit, University Hospital of Modena and Reggio Emilia, Largo del Pozzo 71, 41125 Modena, Italy; (G.R.); (F.P.); (M.D.)
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12
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Yamaoka K, Kawaoka T, Aikata H, Ando Y, Kosaka Y, Suehiro Y, Fujii Y, Uchikawa S, Morio K, Fujino H, Nakahara T, Murakami E, Yamauchi M, Tsuge M, Hiramatsu A, Imamura M, Takahashi S, Saeki Y, Kuroda S, Kobayashi T, Ohdan H, Miyata Y, Okada M, Chayama K. Complete Response for Advanced Hepatocellular Carcinoma by Conversion Surgery Therapy Following a Good Response of Regorafenib Despite Rapid Progressive Disease with Sorafenib. Intern Med 2021; 60:2047-2053. [PMID: 34193774 PMCID: PMC8313913 DOI: 10.2169/internalmedicine.5870-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
A 68-year-old man with hepatocellular carcinoma (HCC) visited his previous hospital due to abdominal pain and was diagnosed with ruptured HCC. Before visiting our hospital, he underwent HCC treatment at his previous hospital, but his tumors did not improve. Although he started treatment with sorafenib, the tumors rapidly grew. Subsequently, regorafenib was given, and the tumors shrank. After 22 months being treated with regorafenib, HCC reoccurred, with a new lung metastasis and a contrast-enhanced nodule on the peritoneal dissemination appearing. He underwent conversion surgery and survived for 4.5 years after his HCC was diagnosed.
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Affiliation(s)
- Kenji Yamaoka
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Tomokazu Kawaoka
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Hiroshi Aikata
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yuwa Ando
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yumi Kosaka
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yosuke Suehiro
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yasutomo Fujii
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Shinsuke Uchikawa
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Kei Morio
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Hatsue Fujino
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Takashi Nakahara
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Eisuke Murakami
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Masami Yamauchi
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Masataka Tsuge
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Akira Hiramatsu
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Michio Imamura
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Shoichi Takahashi
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yoshihiro Saeki
- Department of Gastroenterological and Transplant Surgery, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Shintaro Kuroda
- Department of Gastroenterological and Transplant Surgery, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Yoshihiro Miyata
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
| | - Kazuaki Chayama
- Department of Gastroenterology and Metabolism, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical and Health Science, Hiroshima University Hospital, Japan
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13
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Ho WJ, Sharma G, Zhu Q, Stein-O'Brien G, Durham J, Anders R, Popovic A, Mo G, Kamel I, Weiss M, Jaffee E, Fertig EJ, Yarchoan M. Integrated immunological analysis of a successful conversion of locally advanced hepatocellular carcinoma to resectability with neoadjuvant therapy. J Immunother Cancer 2020; 8:e000932. [PMID: 33219090 PMCID: PMC7682468 DOI: 10.1136/jitc-2020-000932] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/26/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide with a minority of patients being diagnosed early enough for curative-intent interventions. We report the first use of preoperative cabozantinib plus nivolumab to successfully downstage what presented as unresectable HCC as part of an ongoing phase 1b study. Preoperative treatment with cabozantinib and nivolumab led to >99% reduction in alpha-fetoprotein, -37.3% radiographic reduction by RECIST 1.1 and a near complete pathologic response (80% to 100% necrosis). An integrated immunological analysis was performed on the post-treatment surgical tumor sample and matched pre-treatment and post-treatment peripheral blood samples with high-dimensional imaging and cytometry techniques. Bayesian non-negative matrix factorization (CoGAPS, Coordinated Gene Activity in Pattern Sets) and self-organizing map (FlowSOM) algorithms were used to distinguish changes in functional markers across cellular neighborhoods in the single cell data sets. Brisk immunological infiltration into the tumor microenvironment was observed in non-random, organized cellular neighborhoods. Systemically, combination therapy led to marked promotion of effector cytotoxic T cells and effector memory helper T cells. Natural killer cells also increased with therapy. The patient remains without disease recurrence and with a normal alpha-fetoprotein approximately 2 years from presentation. Our study provides proof-of-concept that borderline resectable or locally advanced HCC warrants consideration of downstaging with effective neoadjuvant systemic therapy for subsequent curative resection.
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Affiliation(s)
- Won Jin Ho
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Gaurav Sharma
- Division of Biostatistics and Bioinformatics, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Qingfeng Zhu
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Genevieve Stein-O'Brien
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jennifer Durham
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Robert Anders
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Aleksandra Popovic
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Guanglan Mo
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Ihab Kamel
- Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Matthew Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Elizabeth Jaffee
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Elana J Fertig
- Division of Biostatistics and Bioinformatics, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Mark Yarchoan
- Department of Oncology, Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
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14
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Hou Z, Zhu K, Yang X, Zhou H, Chen P, Yu G, Zhu X, Cui Y, Song T, Li Q, Li H, Zhang T. Resection of "down-staged" advanced hepatocellular carcinoma after treatment with the VEGFR2 inhibitor apatinib: five cases report. Transl Cancer Res 2020; 9:4999-5007. [PMID: 35117862 PMCID: PMC8799223 DOI: 10.21037/tcr-19-3019] [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: 12/31/2019] [Accepted: 07/03/2020] [Indexed: 11/06/2022]
Abstract
Sorafenib and lenvatinib are currently standard treatments for advanced hepatocellular carcinoma (HCC); however, the therapeutic effect is unsatisfying. Indeed, very few patients with HCC under sorafenib treatment were eligible for surgery in the past ten years. In addition, there is no report of a patient with the opportunity to undergo radical resection after treatment with lenvatinib. Here, we describe five patients with advanced and unresectable HCC that were able to receive curative resection within 1 year of treatment with the tyrosine kinase inhibitor apatinib that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR2). The five patients with advanced and unresectable HCC were treated with apatinib (250 mg po, qd), and all the five patients obtained an objective response to the treatment, allowing for subsequent resection, and the second patient even obtained a pathological complete response. The latest follow-up date was August 20, 2019, and all patients were alive at the latest follow-up. The disease-free survival of the first patient was 13 months. Lung metastasis was found 12 months later after surgery for patient 5. The other three patients have no recurrence. This is the first report of a single drug with promising therapeutic effects in patients with advanced HCC within one year at a single center. Therefore, apatinib may be promising for some patients with locally advanced HCC to undergo radical resection and improve outcomes.
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Affiliation(s)
- Zhenyu Hou
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Keyun Zhu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Xuejiao Yang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Hongyuan Zhou
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ping Chen
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ge Yu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Xiaolin Zhu
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Yunlong Cui
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Tianqiang Song
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Qiang Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Huikai Li
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
| | - Ti Zhang
- Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin, China
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15
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Matsuki R, Kawai K, Suzuki Y, Kogure M, Nakazato T, Naruge D, Okano N, Seki S, Ohmori Y, Kawamura N, Kamma H, Hisamatsu T, Shibahara J, Mori T, Furuse J, Sakamoto Y. Pathological Complete Response in Conversion Hepatectomy Induced by Lenvatinib for Advanced Hepatocellular Carcinoma. Liver Cancer 2020; 9:358-360. [PMID: 32647636 PMCID: PMC7325124 DOI: 10.1159/000506202] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 01/27/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Ryota Matsuki
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
| | - Kirio Kawai
- Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan
| | - Yutaka Suzuki
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
| | - Masaharu Kogure
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
| | - Tetsuya Nakazato
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
| | - Daisuke Naruge
- Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan
| | - Naohiro Okano
- Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan
| | - Satowa Seki
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Yoshihiko Ohmori
- Department of Pathology, Kyorin University Hospital, Mitaka, Japan
| | - Naohiro Kawamura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Hiroshi Kamma
- Department of Pathology, Kyorin University Hospital, Mitaka, Japan
| | - Tadakazu Hisamatsu
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Japan
| | - Junji Shibahara
- Department of Pathology, Kyorin University Hospital, Mitaka, Japan
| | - Toshiyuki Mori
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University Hospital, Mitaka, Japan
| | - Yoshihiro Sakamoto
- Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, Mitaka, Japan,*Yoshihiro Sakamoto, MD, PhD, Department of Hepato-Biliary-Pancreatic Surgery, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan),
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16
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Wu H, Xing H, Liang L, Huang B, Li C, Lau WY, Zhou YH, Gu WM, Wang H, Chen TH, Zhang YM, Zeng YY, Pawlik TM, Wang MD, Wu MC, Shen F, Yang T. Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2019; 45:2360-2368. [PMID: 31543386 DOI: 10.1016/j.ejso.2019.09.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 08/27/2019] [Accepted: 09/11/2019] [Indexed: 01/27/2023]
Abstract
BACKGROUND The Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC. METHODS 1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS Overall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111-1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034-1.358, P = 0.007). CONCLUSIONS Patients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.
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Affiliation(s)
- Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Lei Liang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Bin Huang
- Department of Radiology, 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
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China; Medicine, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - 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
| | - Yao-Ming Zhang
- 2(nd) Department of Hepatobiliary Surgery, Meizhou People's Hospital of Sun Yat-sen University, Meizhou, China
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fujian, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, United States
| | - Ming-Da Wang
- 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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17
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Akateh C, Black SM, Conteh L, Miller ED, Noonan A, Elliott E, Pawlik TM, Tsung A, Cloyd JM. Neoadjuvant and adjuvant treatment strategies for hepatocellular carcinoma. World J Gastroenterol 2019; 25:3704-3721. [PMID: 31391767 PMCID: PMC6676544 DOI: 10.3748/wjg.v25.i28.3704] [Citation(s) in RCA: 109] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 06/13/2019] [Accepted: 06/22/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide and a major cause of cancer-related mortality for which liver resection is an important curative-intent treatment option. However, many patients present with advanced disease and with underlying chronic liver disease and/or cirrhosis, limiting the proportion of patients who are surgical candidates. In addition, the development of recurrent or de novo cancers following surgical resection is common. These issues have led investigators to evaluate the benefit of neoadjuvant and adjuvant treatment strategies aimed at improving resectability rates and decreasing recurrence rates. While high-level evidence to guide treatment decision making is lacking, recent advances in locoregional and systemic therapies, including antiviral treatment and immunotherapy, raise the prospect of novel approaches that may improve the outcomes of patients with HCC. In this review, we evaluate the evidence for various neoadjuvant and adjuvant therapies and discuss opportunities for future clinical and translational research.
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Affiliation(s)
- Clifford Akateh
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Sylvester M Black
- Division of Transplant Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Lanla Conteh
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric D Miller
- Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Anne Noonan
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Eric Elliott
- Division of Diagnostic Radiology, Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Allan Tsung
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, United States
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18
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Zhu J, Yin T, Xu Y, Lu XJ. Therapeutics for advanced hepatocellular carcinoma: Recent advances, current dilemma, and future directions. J Cell Physiol 2019; 234:12122-12132. [PMID: 30644100 DOI: 10.1002/jcp.28048] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Accepted: 11/30/2018] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a serious threat to people's health worldwide. The prognosis of advanced HCC is dim if left untreated. In the clinic, the treatment options for advanced HCC include surgery, radiotherapy, transcatheter arterial chemoembolization, and so forth. In recent years, molecular targeted therapy and immunotherapy have also made great progress, bringing new hope to patients with advanced HCC. In this study, therapeutic advances, current dilemma, and future directions of advanced HCC are reviewed, which might serve as a summary for clinicians and may stimulate future research.
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Affiliation(s)
- Jing Zhu
- Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, The Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
| | - Tailang Yin
- Reproductive Medicine Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
| | - Yong Xu
- Department of Nephrology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China
| | - Xiao-Jie Lu
- Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, The Sparkfire Scientific Research Group of Nanjing Medical University, Nanjing, China
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19
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Kim DH, Cho E, Cho SB, Choi SK, Kim S, Yu J, Koh YI, Sim DW, Jun CH. Complete response of hepatocellular carcinoma with right atrium and pulmonary metastases treated by combined treatments (a possible treatment effect of natural killer cell): A case report and literature review. Medicine (Baltimore) 2018; 97:e12866. [PMID: 30334999 PMCID: PMC6211840 DOI: 10.1097/md.0000000000012866] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/25/2018] [Indexed: 01/14/2023] Open
Abstract
RATIONALE Hepatocellular carcinomas (HCCs) with metastases to the right atrium (RA) and lungs are rare, with a poor prognosis. Furthermore, the treatment outcomes in patients with advanced HCCs remain unsatisfactory. PATIENT CONCERNS A 46-year-old man presented to our hospital for dyspnea on exertion and abdominal pain. DIAGNOSES HCC and extra-hepatic metastases to the lung and RA. INTERVENTIONS Multidisciplinary treatment including radiotherapy (RT), transarterial chemoembolization (TACE), and sorafenib. During a follow-up evaluation computed tomography, he experienced a radio-contrast-induced anaphylaxis. After the event, treatment such as RT, TACE, and sorafenib were continued. OUTCOMES His tumor burden decreased, finally leading to a complete response as per the modified Response Evaluation Criteria in Solid Tumors. The patient is still alive, 30 months after the episode. Subsequent blood tests showed increased natural killer (NK) cell activity, which was significantly higher than that seen in other age-matched HCC patients with an identical stage of the tumor, receiving sorafenib. This suggests that the increase in NK cells induced by anaphylaxis influenced the tumor burden. LESSONS We report here a rare case of long-term survival of an HCC patient with multiple metastases treated with multidisciplinary modalities, in which high NK cell activity was observed after a radio-contrast-induced anaphylactic reaction during follow-up investigations.
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Affiliation(s)
| | | | | | | | | | - Jieun Yu
- Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Hospital and Medical School, Gwangju, South Korea
| | - Young-Il Koh
- Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Hospital and Medical School, Gwangju, South Korea
| | - Da Woon Sim
- Division of Allergy, Asthma, and Clinical Immunology, Department of Internal Medicine, Chonnam National University Hospital and Medical School, Gwangju, South Korea
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20
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Wang JC, Xia AL, Xu Y, Lu XJ. Comprehensive treatments for hepatocellular carcinoma with portal vein tumor thrombosis. J Cell Physiol 2018; 234:1062-1070. [PMID: 30256409 DOI: 10.1002/jcp.27324] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2017] [Accepted: 08/03/2018] [Indexed: 12/31/2022]
Abstract
Portal vein tumor thrombosis (PVTT) is one of the most common complications in hepatocellular carcinoma (HCC). HCC with PVTT usually indicates poor prognosis, which has a number of characteristics including a rapidly progressive disease course, worse liver function, complications connected with portal hypertension, and poorer tolerance to treatment. The exact mechanisms of PVTT remain unknown, even though some concerned signal transduction or molecular pathways have been identified. In western countries, sorafenib is the only recommended therapeutic strategy regardless of PVTT types. However, multiple treatment options including transhepatic arterial chemoembolization, hepatectomy, radiotherapy, and sorafenib available in the clinic. In this review, we enumerate and discuss therapeutics against patients with HCC having PVTT available in the clinic and put forward directions for future research.
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Affiliation(s)
- Jin-Cheng Wang
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - An-Liang Xia
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yong Xu
- Department of Nephrology, Huai'an Second People' Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Xiao-Jie Lu
- Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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21
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Zhang YF, Shang H, Zeng XL, Ji H, Li YM, Lu HW. Postoperative adjuvant chemo (embolization) therapy for hepatocellular carcinoma with portal vein tumor thrombosis. Onco Targets Ther 2018; 11:5407-5417. [PMID: 30214246 PMCID: PMC6128276 DOI: 10.2147/ott.s171612] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Background The present meta-analysis was aimed to evaluate the effects of postoperative adjuvant chemotherapy/transarterial chemoembolization (TACE) on the survival/disease-free survival (DFS) rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Methods The relevant trials were collected using a database search of MEDLINE, Embase, Cochrane Library, Web of Science, ScienceDirect, the China Journal Full-text Database, and the National Institute of Health Clinical Trials Database. The 1-, 3-, and 5-year survival/DFS rates were considered to be the primary end points. A sensitivity analysis was conducted by reanalyzing the data using different statistical approaches. Results Eight studies met the inclusion criteria. When compared with surgery alone, the pooled OR showed that the postoperative adjuvant therapy significantly increased the 1-, 3-, and 5-year survival rates for HCC patients with PVTT (the pooled OR and 95% CI of the 1-, 3-, and 5-year survival rates, respectively, were as follows: 2.72, 1.98-3.74; 1.62, 1.13-2.33; 1.99, 1.20-3.29). In addition, when compared with surgery alone, subgroup analysis showed that the postoperative chemotherapy improved the 1-, 3-, and 5-year survival rates of HCC patients with PVTT. Conclusion Compared with surgery alone, postoperative adjuvant chemotherapy can improve the 1-, 3- and 5-year survival rates of HCC patients with PVTT. However, postoperative TACE can only increase the 1-year survival rate. However, due to the limitations of this meta-analysis, additional relevant trials are required to confirm these findings.
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Affiliation(s)
- Ya-Fei Zhang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hao Shang
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Xian-Ling Zeng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Hong Ji
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Yi-Ming Li
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
| | - Hong-Wei Lu
- Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China,
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22
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Liu K, McCaughan GW. How to select the appropriate "neoadjuvant therapy" for hepatocellular carcinoma. Expert Opin Pharmacother 2018; 19:1167-1170. [PMID: 30011239 DOI: 10.1080/14656566.2018.1498843] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Ken Liu
- a AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,b Liver Injury and Cancer Program , The Centenary Institute , Sydney , NSW , Australia.,c Sydney Medical School , The University of Sydney , Sydney , NSW , Australia
| | - Geoffrey W McCaughan
- a AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,b Liver Injury and Cancer Program , The Centenary Institute , Sydney , NSW , Australia.,c Sydney Medical School , The University of Sydney , Sydney , NSW , Australia
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23
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Takeyama H, Beppu T, Higashi T, Kaida T, Arima K, Taki K, Imai K, Nitta H, Hayashi H, Nakagawa S, Okabe H, Hashimoto D, Chikamoto A, Ishiko T, Tanaka M, Sasaki Y, Baba H. Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma. Surg Today 2017; 48:431-438. [PMID: 29110089 DOI: 10.1007/s00595-017-1603-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Accepted: 10/18/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.
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Affiliation(s)
- Hideaki Takeyama
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Toru Beppu
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takaaki Higashi
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takayoshi Kaida
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Kota Arima
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Katsunobu Taki
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Katsunori Imai
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hidetoshi Nitta
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hiromitsu Hayashi
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Shigeki Nakagawa
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hirohisa Okabe
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Daisuke Hashimoto
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Akira Chikamoto
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Takatoshi Ishiko
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Motohiko Tanaka
- Department of Gastroenterology and Hepatology, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Yutaka Sasaki
- Department of Gastroenterology and Hepatology, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Kumamoto University Graduate School of Life Sciences, 1-1-1 Honjo, Chuo-Ku, Kumamoto, 860-8556, Japan.
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24
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Higaki T, Yamazaki S, Moriguchi M, Nakayama H, Kurokawa T, Takayama T. Indication for surgical resection in patients with hepatocellular carcinoma with major vascular invasion. Biosci Trends 2017; 11:581-587. [PMID: 29021421 DOI: 10.5582/bst.2017.01210] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Major portal vein invasion (MVI) by hepatocellular carcinoma (HCC) carries an extremely poor prognosis. Our aim was to clarify the indications of hepatic resection in the presence of MVI by HCC. Between 2001 and 2015, 1,306 patients undergoing primary treatment for HCC were analyzed (866 hepatic resections and 440 transarterial therapies). Significant prognostic factors were identified by retrospectively analyzing tumor status, liver function and treatment. Overall survival was compared in terms of the degree of vascular invasion and treatment. The 5-year survival rates according to the degree of vascular invasion (Vp) were Vp0: 51.9%, Vp1: 33.0%, Vp2: 16.7%, Vp3: 21.8%, and Vp4: 0%, respectively. Overall survival (OS) did not differ significantly between patients with Vp3 and Vp4 MVI (p = 0.153). Median survival following hepatic resection of Vp3 cases was significantly better than that for Vp4 cases (1,913 vs. 258 days, p = 0.014), while OS following transarterial therapy was not significantly different (164 vs. 254 days in Vp3 vs. Vp4, p = 0.137). Multivariate analysis revealed hepatic resection (Odds: 2.335 [95%CI: 1.236-4.718], p = 0.008) and multiple tumors (1.698 [1.029-2.826], p = 0.038) as independent predictors of survival. Hepatic resection in HCC patients with MVI should be indicate in patients with Vp3 invasion.
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Affiliation(s)
- Tokio Higaki
- Department of Digestive Surgery, Nihon University School of Medicine
| | - Shintaro Yamazaki
- Department of Digestive Surgery, Nihon University School of Medicine
| | | | - Hisashi Nakayama
- Department of Digestive Surgery, Nihon University School of Medicine
| | - Tomoharu Kurokawa
- Department of Digestive Surgery, Nihon University School of Medicine
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25
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Kim TS, Kim JH, Kim BH, Lee YS, Yoo YJ, Kang SH, Suh SJ, Jung YK, Seo YS, Yim HJ, Yeon JE, Byun KS. Complete response of advanced hepatocellular carcinoma to sorafenib: another case and a comprehensive review. Clin Mol Hepatol 2017. [PMID: 28633200 PMCID: PMC5760007 DOI: 10.3350/cmh.2016.0070] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
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Affiliation(s)
- Tae Suk Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Gangwon, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Kangwon National University School of Medicine, Gangwon, Korea
| | - Baek Hui Kim
- Department of Pathology, Korea University College of Medicine, Seoul, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yang Jae Yoo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang-June Suh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jong Eun Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kwan Soo Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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26
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Ziogas IA, Tsoulfas G. Evolving role of Sorafenib in the management of hepatocellular carcinoma. World J Clin Oncol 2017; 8:203-213. [PMID: 28638790 PMCID: PMC5465010 DOI: 10.5306/wjco.v8.i3.203] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/03/2017] [Accepted: 04/23/2017] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide and comes third in cancer-related mortality. Although there is a broad spectrum of treatment options to choose from, only a few patients are eligible candidates to receive a curative therapy according to their stage of disease, and thus palliative treatment is implemented in the majority of the patients suffering from liver cancer. Sorafenib, a multikinase inhibitor, is the only currently approved agent for systemic therapy in patients with advanced stage HCC and early stage liver disease. It has been shown to improve the overall survival, but with various side effects, while its cost is not negligible. Sorafenib has been in the market for a decade and has set the stage for personalized targeted therapy. Its role during this time has ranged from monotherapy to neoadjuvant and adjuvant treatment with surgical resection, liver transplantation and chemoembolization or even in combination with other chemotherapeutic agents. In this review our aim is to highlight in depth the current position of Sorafenib in the armamentarium against HCC and how that has evolved over time in its use either as a single agent or in combination with other therapies.
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27
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Calistri L, Cordopatri C, Nardi C, Gianni E, Marra F, Colagrande S. Sudden cardiac death in a patient with advanced hepatocellular carcinoma with good response to sorafenib treatment: A case report with literature analysis. Mol Clin Oncol 2017; 6:389-396. [PMID: 28451419 PMCID: PMC5403270 DOI: 10.3892/mco.2017.1132] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 10/19/2016] [Indexed: 12/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the principal primary liver tumor, representing the third largest cause of cancer-associated death worldwide. The actual reference standard systemic treatment for advanced HCC is represented by sorafenib, a multi-targeted orally active small-molecule tyrosine kinase inhibitor. Sorafenib has exhibited a good general safety profile in multiple clinical trials. However, adverse drug-associated events are common, occasionally severe, and special attention should be paid to cardiovascular adverse events, particularly in patients with risk factors or known heart disease. In the present study, the case of a patient with no known cardiovascular risk factors affected by highly enhancing advanced HCC in cirrhotic liver, who died during successful sorafenib monotherapy, is reported.
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Affiliation(s)
- Linda Calistri
- Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, University of Florence-Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
| | - Cesare Cordopatri
- Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, University of Florence-Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
| | - Cosimo Nardi
- Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, University of Florence-Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
| | - Elena Gianni
- Department of Experimental and Clinical Medicine, University of Florence, I-50134 Florence, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, I-50134 Florence, Italy
| | - Stefano Colagrande
- Department of Experimental and Clinical Biomedical Sciences, Radiodiagnostic Unit n. 2, University of Florence-Azienda Ospedaliero-Universitaria Careggi, I-50134 Florence, Italy
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28
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Nakano N, Kawaoka T, Aikata H, Honda F, Nakamura Y, Morio K, Hatooka M, Fukuhara T, Kobayashi T, Hiramatsu A, Imamura M, Kawakami Y, Takahashi S, Chayama K. Complete response to short-term sorafenib treatment alone for hepatocellular carcinoma with bone, lymph node, and peritoneum metastases. Hepatol Res 2016; 46:1402-1408. [PMID: 26988002 DOI: 10.1111/hepr.12698] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 03/03/2016] [Accepted: 03/08/2016] [Indexed: 02/08/2023]
Abstract
We report a 60-year-old male patient who developed extrahepatic metastases in bone, peritoneum, and lymph nodes (confirmed by computed tomography and positron emission tomography-computed tomography) after hepatectomy for hepatocellular carcinoma. He was treated with sorafenib (800 mg/day) but developed grade 3 hand-foot syndrome. He continued to be treated with sorafenib but at a lower dose (400 mg/week). The response to sorafenib therapy was graded as complete response at 6 months by the Response Evaluation Criteria in Solid Tumors. Sorafenib was continued for 8 months and the patient remained in complete response for 11 months. Further reporting of similar cases should help design treatment strategies and evaluate predictors of the response to sorafenib therapy.
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Affiliation(s)
- Norihito Nakano
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Tomokazu Kawaoka
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Aikata
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Fumi Honda
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Yuki Nakamura
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Kei Morio
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Masahiro Hatooka
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Takayuki Fukuhara
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Tomoki Kobayashi
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Akira Hiramatsu
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Michio Imamura
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Yoshiiku Kawakami
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Shoichi Takahashi
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Medicine and Molecular Science, Division of Frontier Medical Science, and, Hiroshima University, Hiroshima, Japan
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29
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Takano M, Kokudo T, Miyazaki Y, Kageyama Y, Takahashi A, Amikura K, Sakamoto H. Complete response with sorafenib and transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma. World J Gastroenterol 2016; 22:9445-9450. [PMID: 27895433 PMCID: PMC5107709 DOI: 10.3748/wjg.v22.i42.9445] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Revised: 08/11/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
Patients with advanced hepatocellular carcinoma (HCC) showing portal vein tumor thrombosis (PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization (TACE) showing complete histological response. Two months after induction with sorafenib, a significant decrease in serum alpha-fetoprotein level was observed and computed tomography imaging showed a significant decrease in tumor size. Because of remaining PVTT, TACE and curative resection were performed. The combination of sorafenib and TACE may be an effective treatment for HCC patients with PVTT.
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30
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Recurrence-free survival of a hepatocellular carcinoma patient with tumor thrombosis of the inferior vena cava after treatment with sorafenib and hepatic resection. Int Surg 2016; 100:908-14. [PMID: 26011214 DOI: 10.9738/intsurg-d-14-00133.1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Sorafenib (Nexabar, Bayer, Berlin, Germany), one of multikinase inhibitors, can infrequently downstage advanced hepatocellular carcinoma (HCC). There are some reports that sorafenib in combination with other modalities, such as transcatheter arterial chemoembolization (TACE) or radiation therapy, could represent a bridge to surgery. We have observed a progressive HCC case with hepatic vein tumor thrombosis proceeding to the inferior vena cava (IVC-HVTT) convert to a state of feasible curative resection after a multidisciplinary treatment which included sorafenib. The patient underwent a successful resection in consequence of this therapy. A 45-year-old male with Hepatitis B Virus-associated chronic hepatitis was diagnosed as HCC with IVC-HVTT. To obtain oncological curative resection, we performed TACE, radiation therapy followed by administration of sorafenib (800 mg per day, total 72 g). The tumor including IVC-HVTT remarkably shrank, therefore, an extended posterior sectionectomy and total removal of the IVC-HVTT was successfully performed. The operation time was 736 minutes and the amount of intraoperative hemorrhage was 805 mL. No postoperative complication occurred. Adjuvant therapy with sorafenib was started four weeks after the operation and continued for 6 months (800 mg per day, total 144 g). The patient is alive without recurrence for about 4 years from the initial therapy. Multidisciplinary therapy including sorafenib, TACE, radiation, and hepatic resection may be an effective strategy to treat HCC patients with IVC-HVTT.
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31
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Kokudo T, Hasegawa K, Matsuyama Y, Takayama T, Izumi N, Kadoya M, Kudo M, Ku Y, Sakamoto M, Nakashima O, Kaneko S, Kokudo N. Survival benefit of liver resection for hepatocellular carcinoma associated with portal vein invasion. J Hepatol 2016; 65:938-943. [PMID: 27266618 DOI: 10.1016/j.jhep.2016.05.044] [Citation(s) in RCA: 361] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 05/20/2016] [Accepted: 05/30/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS The presence of portal vein tumor thrombosis (PVTT) in patients with hepatocellular carcinoma (HCC) is regarded as indicating an advanced stage, and liver resection (LR) is not recommended. The aim of this study was to evaluate the survival benefit of LR for HCC patients with PVTT through the analysis of the data from a Japanese nationwide survey. METHODS We analyzed data for 6474 HCC patients with PVTT registered between 2000 and 2007. Of these patients, 2093 patients who underwent LR and 4381 patients who received other treatments were compared. The propensity scores were calculated and we successfully matched 1058 patients (66.1% of the LR group). RESULTS In the Child-Pugh A patients, the median survival time (MST) in the LR group was 1.77years longer than that in the non-LR group (2.87years vs. 1.10years; p<0.001) and 0.88years longer than that in the non-LR group (2.45years vs. 1.57years; p<0.001) in a propensity score-matched cohort. A subgroup analysis revealed that LR provides a survival benefit regardless of age, etiology of HCC, tumor marker elevation, and tumor number. The survival benefit was not statistically significant only in patients with PVTT invading the main trunk or contralateral branch. In the LR group, the postoperative 90-day mortality rate was 3.7% (68 patients). CONCLUSIONS As long as the PVTT is limited to the first-order branch, LR is associated with a longer survival outcome than non-surgical treatment. LAY SUMMARY The presence of portal vein tumor thrombosis in patients with hepatocellular carcinoma is regarded as indicating an advanced stage, and liver resection is not recommended. We performed a multicenter, nationwide study to assess the survival benefit of liver resection in hepatocellular carcinoma patients with portal vein tumor thrombosis using propensity score-based matching. As long as the portal vein tumor thrombosis is limited to the first-order branch, liver resection is associated with a longer survival outcome than non-surgical treatment.
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Affiliation(s)
- Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan; Division of Gastroenterological Surgery, Saitama Cancer Center, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan
| | - Yutaka Matsuyama
- Department of Biostatistics, School of Public Health, The University of Tokyo, Japan
| | - Tadatoshi Takayama
- Department of Digestive Surgery, Nihon University School of Medicine, Japan
| | - Namiki Izumi
- Department of Gastroenterology, Musashino Red Cross Hospital, Japan
| | - Masumi Kadoya
- Department of Radiology, Shinshu University School of Medicine, Japan
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Japan
| | - Yonson Ku
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Japan
| | - Michiie Sakamoto
- Department of Pathology, Keio University School of Medicine, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Japan
| | - Shuichi Kaneko
- Department of Gastroenterology, Kanazawa University Hospital, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
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Zhang Q, Yang J, Wang J. Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer. Oncol Lett 2016; 12:4767-4772. [PMID: 28101223 DOI: 10.3892/ol.2016.5291] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2014] [Accepted: 02/24/2016] [Indexed: 12/21/2022] Open
Abstract
Liver cancer is one of the leading causes of cancer-associated mortality worldwide. Due to changes in lifestyle and daily exposure to various chemicals, which may lead to chemical intoxication, liver cancer has become a prominent disease in humans. Chemical-induced carcinogenesis in experimental animals has become a reliable model for the investigation of liver cancer-associated biological alterations that may mimic human hepatic cancer. Liver cancer in BALB/c mice was induced by administering diethylnitrosamine (DN) in drinking water for 6 weeks. Luteolin (LUT) is a flavone that is found in the leaves of the majority of spice-associated plants. In the present study, 20 µg/kg of body weight LUT was administered intraperitoneally every alternate day to treat the DN-induced liver cancer in mice. LUT improved the host system by modifying the levels of α-fetoprotein, enzymatic antioxidants, such as superoxide dismutase and catalase, marker enzymes, such as AST and ALT, and lipid peroxides in the plasma or liver tissue. LUT also reduced the levels of glutathione and the inflammatory cytokines interleukin-2 and interferon-γ in the plasma or liver tissue. These findings augmented the treatment against liver cancer and supported the effective anticancer activity of LUT against DN-induced liver carcinogenesis in mice.
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Affiliation(s)
- Qiang Zhang
- Department of General Surgery, Xiangyang Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Jie Yang
- Department of General Surgery, Xiangyang Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
| | - Jun Wang
- Department of General Surgery, Xiangyang Hospital, Affiliated Hospital of Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China
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Yamasaki A, Umeno N, Harada S, Tanaka K, Kato M, Kotoh K. Deteriorated portal flow may cause liver failure in patients with hepatocellular carcinoma being treated with sorafenib. J Gastrointest Oncol 2016; 7:E36-40. [PMID: 27284486 DOI: 10.21037/jgo.2015.10.07] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We encountered two patients with hepatocellular carcinoma (HCC) who showed rapid progression of liver failure during sorafenib treatment. One had portal vein tumor thrombus (PVTT) and the other developed portal vein thrombosis (PVT) during the treatment, and both of them experienced the elevation of serum lactate dehydrogenase (LDH) concentration during the administration of sorafenib. Their clinical courses indicate that the liver failure might have been caused by sorafenib-induced liver hypoxia, being amplified in the circumstances with reduced portal flow. To our best knowledge, all the reported patients who achieved complete remission (CR) during sorafenib monotherapy had a condition that could decrease portal blood flow. We hypothesized that pathogenesis of disease may be similar in HCC patients who achieve CR and those who experience liver failure while on sorafenib. Sorafenib treatment of patients with HCC and deteriorated portal flow may be a double-edged sword.
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Affiliation(s)
- Akihiro Yamasaki
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Narihiro Umeno
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shigeru Harada
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kosuke Tanaka
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazuhiro Kotoh
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Lorenzin D, Pravisani R, Leo CA, Bugiantella W, Soardo G, Carnelutti A, Umberto B, Risaliti A. Complete Remission of Unresectable Hepatocellular Carcinoma After Combined Sorafenib and Adjuvant Yttrium-90 Radioembolization. Cancer Biother Radiopharm 2016; 31:65-9. [DOI: 10.1089/cbr.2015.1905] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Dario Lorenzin
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Riccardo Pravisani
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Cosimo Alex Leo
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Walter Bugiantella
- General Surgery, AUSL Umbria 2, Italy
- School of Biotechnologies, University of Perugia, Italy
| | - Giorgio Soardo
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Alessia Carnelutti
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Baccarani Umberto
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
| | - Andrea Risaliti
- General Surgery and Transplantation Unit, University Hospital “S. Maria della Misericordia,” Udine, Italy
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Park JG. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy. Clin Mol Hepatol 2015; 21:287-94. [PMID: 26527250 PMCID: PMC4612290 DOI: 10.3350/cmh.2015.21.3.287] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2015] [Revised: 08/21/2015] [Accepted: 08/28/2015] [Indexed: 12/20/2022] Open
Abstract
Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate.
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Affiliation(s)
- Jung Gil Park
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, CHA Gumi Medical Center, CHA University, Gumi, Korea
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Azmi AN, Chan WK, Goh KL. Sustained complete remission of advanced hepatocellular carcinoma with sorafenib therapy. J Dig Dis 2015; 16:537-40. [PMID: 26147446 DOI: 10.1111/1751-2980.12270] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Ahmad Najib Azmi
- Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Kuala Lumpur, Malaysia.,Gastroenterology and Hepatology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Wah-Kheong Chan
- Gastroenterology and Hepatology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khean-Lee Goh
- Gastroenterology and Hepatology Unit, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Kitajima T, Hatano E, Mitsunori Y, Taura K, Fujimoto Y, Mizumoto M, Okajima H, Kaido T, Minamiguchi S, Uemoto S. Complete pathological response induced by sorafenib for advanced hepatocellular carcinoma with multiple lung metastases and venous tumor thrombosis allowing for curative resection. Clin J Gastroenterol 2015; 8:300-5. [PMID: 26249525 DOI: 10.1007/s12328-015-0594-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 07/18/2015] [Indexed: 12/16/2022]
Abstract
We report the first case of initially unresectable advanced hepatocellular carcinoma (HCC) with portal vein and hepatic venous tumor thrombosis and multiple lung metastases that allowed for curative hepatectomy after multidisciplinary treatment including sorafenib. A 54-year-old male presented with a large HCC in the right liver with tumor thrombosis of the left portal vein and middle hepatic vein (MHV) as well as multiple lung metastases. His serum alpha-fetoprotein level was elevated at 52,347 ng/mL and palliative treatment with sorafenib was initiated. One month later, a significant reduction in the serum AFP level, decrease in the tumor size with recanalization of the portal vein and the absence of lung metastases were noted. Three months after the start of sorafenib treatment, external-beam radiotherapy was performed to treat enlargement of the area of MHV thrombosis, and the thrombosis regressed. Five months after the initiation of sorafenib treatment, central bisegmentectomy associated with removal of the tumor thrombus in the inferior vena cava was performed. A microscopic examination revealed complete necrosis of the tumor. Sorafenib treatment may be a bridge to curative resection in selected patients with initially unresectable advanced HCC, even in cases involving multiple extrahepatic metastases.
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Affiliation(s)
- Toshihiro Kitajima
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yusuke Mitsunori
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Kojiro Taura
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Yasuhiro Fujimoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Masaki Mizumoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Hideaki Okajima
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | - Toshimi Kaido
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
| | | | - Shinji Uemoto
- Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan
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Zhang ZM, Lai ECH, Zhang C, Yu HW, Liu Z, Wan BJ, Liu LM, Tian ZH, Deng H, Sun QH, Chen XP. The strategies for treating primary hepatocellular carcinoma with portal vein tumor thrombus. Int J Surg 2015; 20:8-16. [PMID: 26026424 DOI: 10.1016/j.ijsu.2015.05.009] [Citation(s) in RCA: 128] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Revised: 04/26/2015] [Accepted: 05/06/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE To further improve the effectiveness and prognosis of primary hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), the current status of treatment for HCC with PVTT was reviewed. METHODS A Medline search was undertaken to identify articles using the keywords "HCC", "PVTT" and "therapy". Additional papers were identified by a manual search of the references from the key articles. RESULTS PVTT, as a common complication of HCC, was divided into type I ∼ IV. The therapeutic approach is mainly composed of five types: surgical resection, regional interventional therapy, radiotherapy, combination therapy, targeted therapy. All of these therapeutic approaches were separately evaluated in detail. CONCLUSIONS For those resectable tumors, the better choice for treatment of HCC with PVTT should be hepatectomy and removal of PVTT. For those unresectable tumors, TACE (especially the super-selective TACE) has been the preferred palliative treatment, the other regional interventional therapy and/or radiotherapy could improve the therapeutic effects. The multidisciplinary treatments may further improve the quality of life and prolong the survival period for the HCC patients associated with PVTT.
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Affiliation(s)
- Zong-ming Zhang
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Eric C H Lai
- Department of Surgery, Pamela Youde Nethersole Eastern Hospital, Chaiwan, Hong Kong, China
| | - Chong Zhang
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Hong-wei Yu
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Zhuo Liu
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Bo-jiang Wan
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Li-min Liu
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Zu-hao Tian
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Hai Deng
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Qiu-hong Sun
- Department of General Surgery, Beijing Electric Power Hospital, Capital Medical University, Beijing, China
| | - Xiao-ping Chen
- Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
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Allard MA, Sebagh M, Ruiz A, Guettier C, Paule B, Vibert E, Cunha AS, Cherqui D, Samuel D, Bismuth H, Castaing D, Adam R. Does pathological response after transarterial chemoembolization for hepatocellular carcinoma in cirrhotic patients with cirrhosis predict outcome after liver resection or transplantation? J Hepatol 2015; 63:83-92. [PMID: 25646884 DOI: 10.1016/j.jhep.2015.01.023] [Citation(s) in RCA: 100] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 12/17/2014] [Accepted: 01/21/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS To investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC), and to identify predictors of complete pathologic response (CPR). METHODS Between 1990 and 2010, 373 consecutive cirrhotic patients with HCC were treated by TACE followed by either liver resection (LR:184 patients) or liver transplantation (LT:189 patients). The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. CPR was defined as the absence of any viable tumor area in all the present nodules. RESULTS A total of 59 (32%) and 37 (20%) patients had CPR after LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR compared to those without, after LR (58% vs. 34%; p=0.0006) and tends to be higher after LT (84% vs. 65%; p=0.09). The 5-year recurrence-free survival (RFS) rates were significantly higher in both groups (24% vs. 13% after LR; p=0.008 and 94% vs. 73% after LT, p=0.007). A cut-off value of >90% necrosis emerged as an impacting factor on patient survival after LR or LT. On multivariate analysis stratified on the type of procedure (LR or LT), PR >90% remained an independent factor of better OS and RFS. Independent factors associated with CPR were: a maximal tumor size <30 mm (RR 2.17 [1.27-3.74]), a single tumor (RR 6.08 [3.29-12.07]), and an preoperative AFP<100 ng/ml (see results section) (RR 3.99 [1.63-11.98]). The probability to achieve a CPR ranged from 2% in the absence of any factors to 48% in the presence of all factors. CONCLUSION In cirrhotic patients with HCC, a complete or nearly complete PR improves long-term survival after LR and LT independently of other pathological factors. This underlines the importance of neoadjuvant treatment to obtain a significant decrease of active tumor load.
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Affiliation(s)
- Marc-Antoine Allard
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S776 Inserm, Villejuif, France
| | - Mylène Sebagh
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; Departement of Pathology, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - Aldrick Ruiz
- University Medical Center Utrecht, Utrecht, The Netherlands
| | - Catherine Guettier
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; Departement of Pathology, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - Bernard Paule
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France
| | - Eric Vibert
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - Antonio Sa Cunha
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S776 Inserm, Villejuif, France
| | - Daniel Cherqui
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - Didier Samuel
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - Henri Bismuth
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France
| | - Denis Castaing
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S785 Inserm, Villejuif, France
| | - René Adam
- Centre Hépato-biliaire, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris, Univ Paris-Sud, Villejuif, France; UMR-S776 Inserm, Villejuif, France.
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Qi X, Guo X. Sorafenib for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis: a systematic review of comparative studies. PRZEGLAD GASTROENTEROLOGICZNY 2015; 10:142-147. [PMID: 26516379 PMCID: PMC4607698 DOI: 10.5114/pg.2015.52470] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 03/15/2015] [Accepted: 04/10/2015] [Indexed: 02/07/2023]
Abstract
Sorafenib is the first-line treatment of choice for advanced hepatocellular carcinoma (HCC). However, the benefits of sorafenib in HCC patients with portal vein tumour thrombosis (PVTT) remain uncertain. Until now, a total of eight comparative studies have been identified for this systematic review. Four retrospective studies showed that hepatic arterial infusion chemotherapy, hepatic resection, and three-dimensional conformal radiotherapy might be superior to sorafenib in improving the overall survival. Two ongoing randomised controlled trials (RCTs) will compare the outcomes of transarterial chemoembolisation or radioembolisation with those of sorafenib for the treatment of HCC with PVTT. In addition, two completed RCTs found that additional use of cryotherapy or radiofrequency ablation could prolong the survival of patients receiving sorafenib. In conclusion, the clinical efficacy of sorafenib in HCC patients with PVTT has been widely challenged by other interventions. However, further well-designed RCTs are necessary to confirm the findings of retrospective analyses. Cryotherapy or radiofrequency ablation may be considered as an adjunctive therapy in such patients, if sorafenib is prescribed.
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Affiliation(s)
- Xingshun Qi
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
| | - Xiaozhong Guo
- Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, China
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Park JG, Park SY, Lee HW. Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy. World J Gastroenterol 2015; 21:2568-2572. [PMID: 25741170 PMCID: PMC4342939 DOI: 10.3748/wjg.v21.i8.2568] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Revised: 10/18/2014] [Accepted: 11/11/2014] [Indexed: 02/07/2023] Open
Abstract
Sorafenib, a potent multikinase inhibitor, lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma (HCC). Though sorafenib has proven its efficacy in advanced stage HCC, there are limited reports on the role of sorafenib allowing for curative treatment by down-staging. We herein report a case of advanced HCC with vascular invasion, which showed treatment response by sorafenib therapy as to allow for radiofrequency ablation as curative treatment. The patient was followed-up for 6 mo without recurrence with continued sorafenib therapy.
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Liu D, Liu A, Peng J, Hu Y, Feng X. Case analysis of complete remission of advanced hepatocellular carcinoma achieved with sorafenib. Eur J Med Res 2015; 20:12. [PMID: 25649133 PMCID: PMC4323035 DOI: 10.1186/s40001-015-0085-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 11/13/2014] [Indexed: 12/31/2022] Open
Abstract
Background To evaluate the feasibility and security of complete remission (CR) of advanced hepatocellular carcinoma (HCC) achieved with sorafenib treatment, and investigate the previously described predictive factors in CR. Methods The case of a patient who achieved CR of advanced HCC with sorafenib treatment was analyzed. The case analysis was performed by a literature review of relevant reports retrieved from the PubMed database. Results A 58-year-old male patient achieved CR of advanced HCC after 23 weeks of oral treatment with sorafenib alone for 41 months and maintained CR for more than 35 months. Eleven reports worldwide have documented a total of twelve patients who achieved CR of advanced HCC, including six with nonsurgical oral sorafenib treatment, four with surgical resection in the descent stage following oral sorafenib treatment and two with oral sorafenib treatment for postoperative metastasis. Conclusions For unresectable advanced HCC, sorafenib can significantly improve progression-free survival and overall survival, achieving CR in some cases. In addition, surgical resection of advanced HCC in the descent stage is possible following oral sorafenib treatment. For patients with postoperative distant metastasis of HCC, sorafenib treatment also provides clinical benefits and can even achieve CR. Besides, long-term sorafenib administration is safe, and patients should continually receive sorafenib to avoid recurrence after complete remission of cancer. Furthermore, early HFSR, rapid decline of AFP levels and rapid tumor shrinking observed by imaging are known parameters describing sorafenib’s effects. Finally, it is important to assess the gene locus of sorafenib sensitivity in HCC patients in future research.
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Affiliation(s)
- Daizhong Liu
- Department of Surgery, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan Province, China.
| | - Aixiang Liu
- Department of Surgery, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan Province, China.
| | - Junping Peng
- Department of Surgery, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan Province, China.
| | - Yong Hu
- Department of Surgery, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan Province, China.
| | - Xielin Feng
- Department of Surgery, Sichuan Cancer Hospital, Chengdu, 610041, Sichuan Province, China.
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Shiba S, Okusaka T, Ikeda M, Saito H, Ichida T. Characteristics of 18 patients with hepatocellular carcinoma who obtained a complete response after treatment with sorafenib. Hepatol Res 2014; 44:1268-76. [PMID: 24405694 DOI: 10.1111/hepr.12297] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2013] [Revised: 11/29/2013] [Accepted: 12/27/2013] [Indexed: 12/17/2022]
Abstract
AIM Sorafenib, a multi-targeted tyrosine kinase inhibitor, is a first-line systemic treatment for advanced hepatocellular carcinoma (HCC). However, possible predictors of the efficacy of sorafenib treatment in HCC patients remain unclear. METHODS We conducted a nationwide survey to examine the situation of patients with HCC treated with sorafenib who obtained a complete response (CR) according to the modified response evaluation criteria in solid tumors (mRECIST). The investigation was intended to collect clinical information regarding CR patients and to compare this data with an interim report examining all-patient surveillance for sorafenib use in Japan, which was released in May 2012. RESULTS Among the 3047 patients who were treated at institutions belonging to the Liver Cancer Study Group of Japan, 18 patients (0.6%) obtained a CR. Significant factors in the CR group were a female sex, a low bodyweight (<59 kg), an early clinical stage and a small initial dose of sorafenib (P < 0.05). Furthermore, specific adverse events (palmar-plantar erythrodysesthesia syndrome, hypertension, diarrhea, alopecia, fatigue, nausea and anorexia) were frequently observed in the CR group (P < 0.05). CONCLUSION This study identified the characteristics of CR patients during sorafenib treatment. The evaluation of patients receiving sorafenib, including the investigation of biomarkers, warrants further exploration in future clinical studies to identify a population in which sorafenib treatment is remarkably effective.
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Affiliation(s)
- Satoshi Shiba
- Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan
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Huan HB, Lau WY, Xia F, Ma KS, Bie P. Complete response to sorafenib in a patient with recurrent hepatocellular carcinoma. World J Gastroenterol 2014; 20:14505-14509. [PMID: 25339839 PMCID: PMC4202381 DOI: 10.3748/wjg.v20.i39.14505] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Revised: 05/12/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Partial hepatectomy is still the treatment of choice aiming at a cure for patients with hepatocellular carcinoma (HCC), provided that the patient can tolerate the treatment. For patients with multiple recurrent HCC after partial hepatectomy which cannot be treated by re-hepatectomy or local ablative therapy, the prognosis is extremely poor. Sorafenib is a molecular-targeted agent which has been demonstrated in two global phase III randomized controlled trials to show survival benefit for advanced HCC. Here, we present a 56-year-old patient with HCC who showed complete clinical response after sorafenib was used for tumor recurrence which developed 3 mo after partial hepatectomy. There was no evidence of progression of disease for 60 mo till now after continuous treatment with sorafenib.
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45
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Lee HS, Choi GH, Choi JS, Kim KS, Han KH, Seong J, Ahn SH, Kim DY, Park JY, Kim SU, Kim BK. Surgical resection after down-staging of locally advanced hepatocellular carcinoma by localized concurrent chemoradiotherapy. Ann Surg Oncol 2014; 21:3646-3653. [PMID: 24916746 DOI: 10.1245/s10434-014-3652-3] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Indexed: 09/25/2023]
Abstract
BACKGROUND This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection. METHODS DFS and OS were investigated using clinicopathologic variables. Functional residual liver volume (FRLV) was assessed before CCRT and again before surgery in patients with major hepatectomy. Tumor marker response was defined as elevated tumor marker levels at diagnosis but levels below cutoff values before surgery (α-fetoprotein < 20 ng/mL, protein induced by vitamin K absence or antagonist-II < 40 mAU/mL). RESULTS Of 243 patients who received CCRT followed by HAIC between 2005 and 2011, 41 (16.9 %) underwent curative resection. Tumor down-staging was demonstrated in 32 (78 %) of the resected patients. FRLV significantly increased from 47.5 to 69.9 % before surgery in patients who underwent major hepatectomy. In addition, the OS of the curative resection group was significantly higher than the OS of the CCRT followed by HAIC alone group (49.6 vs. 9.8 % at 5-year survival; p < 0.001). By multivariate analysis, the poor prognostic factors for DFS after curative resection were tumor marker non-response and the presence of a satellite nodule; however, tumor marker non-response was the only independent poor prognostic factor of OS. CONCLUSIONS CCRT followed by HAIC increased resectability by down-staging tumors and increasing FRLV. Curative resection may provide good long-term survival in tumor marker responders who undergo CCRT followed by HAIC.
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Affiliation(s)
- Hyung Soon Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
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Kokudo T, Hasegawa K, Yamamoto S, Shindoh J, Takemura N, Aoki T, Sakamoto Y, Makuuchi M, Sugawara Y, Kokudo N. Surgical treatment of hepatocellular carcinoma associated with hepatic vein tumor thrombosis. J Hepatol 2014; 61:583-588. [PMID: 24798618 DOI: 10.1016/j.jhep.2014.04.032] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 03/27/2014] [Accepted: 04/21/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Presence of hepatic vein tumor thrombosis (HVTT) in patients with hepatocellular carcinoma (HCC) is regarded as signaling an extremely poor prognosis. However, little is known about the prognostic impact of surgical treatment for HVTT. METHODS Our database of surgical resection for HCC between October 1994 and December 2011 in a tertiary care Japanese hospital was retrospectively analysed. We statistically compared the patient characteristics and surgical outcomes in HCC patients with tumor thrombosis in a peripheral hepatic vein, including microscopic invasion (pHVTT), tumor thrombosis in a major hepatic vein (mHVTT), and tumor thrombosis of the inferior vena cava (IVCTT). Among 1525 hepatic resections, 153 cases of pHVTT, 21 cases of mHVTT, and 13 cases of IVCTT were identified. RESULTS The median survival time (MST) in the pHVTT and mHVTT groups was 5.27 and 3.95 years, respectively (p=0.77), and the median time to recurrence (TTR) was 1.06 and 0.41 years, respectively (p=0.74). On the other hand, the MST and TTR in the patient group with IVCTT were 1.39 years and 0.25 year respectively; furthermore, the MST of Child-Pugh class B patients was significantly worse (2.39 vs. 0.44 years, p=0.0001). Multivariate analyses revealed IVCTT (risk ratio [RR] 2.54, p=0.024) and R 1/2 resection (RR 2.08, p=0.017) as risk factors for the overall survival. CONCLUSIONS Hepatic resection provided acceptable outcomes in HCC patients with mHVTT or pHVTT when R0 resection was feasible. Resection of HCC may be attempted even in patients with IVCTT, in the presence of good liver function.
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Affiliation(s)
- Takashi Kokudo
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Satoshi Yamamoto
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Junichi Shindoh
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuyuki Takemura
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Taku Aoki
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Sakamoto
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masatoshi Makuuchi
- Division of Hepato-Biliary-Pancreatic Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yasuhiko Sugawara
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norihiro Kokudo
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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Kee KM, Hung CH, Wang JH, Lu SN. Serial changes of clinical parameters in a patient with advanced hepatocellular carcinoma with portal vein thrombosis achieving complete response after treatment with sorafenib. Onco Targets Ther 2014; 7:829-34. [PMID: 24920924 PMCID: PMC4043808 DOI: 10.2147/ott.s61740] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The prognosis is usually poor in advanced hepatocellular carcinoma (HCC). Sorafenib is approved for Child-Pugh class A patients with unresectable and advanced HCC. We report here a rare case of a patient with advanced HCC with right portal vein thrombosis (PVT) who achieved a complete response after treatment with sorafenib. This 74-year-old man was a case of non-hepatitis B and C virus-related cirrhosis. Multiphase liver computed tomography showed an 8 cm tumor with early enhance, early wash out, and right PVT at segment 8 of the right lobe. A liver tumor biopsy confirmed the diagnosis of poorly differentiated HCC. Blood tests showed Child-Pugh class A cirrhosis and an alpha-fetoprotein level of 33,058 ng/mL. Sorafenib was initiated at 800 mg/day but was eventually reduced to 400 mg every other day because of a grade 3 hand-foot skin reaction. The alpha fetoprotein (AFP) level decreased rapidly with a linear trend after treatment. After log transformation, the calculated half-life of AFP was 6.84 days. There was no more tumor arterial enhancement, and tumor size was decreased to 3.7 cm on day 42. PVT shrank gradually and localized to the right anterior branch at month 9. There was no recurrence of tumor at the end of follow-up in month 19. Typical serial changes of clinical parameters were demonstrated in this patient.
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Affiliation(s)
- Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan ; Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Andersen KJ, Knudsen AR, Kannerup AS, Nyengaard JR, Hamilton-Dutoit S, Ladekarl M, Mortensen FV. Postoperative but not preoperative treatment with sorafenib inhibits liver regeneration in rats. J Surg Res 2014; 191:331-8. [PMID: 24834802 DOI: 10.1016/j.jss.2014.04.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 03/08/2014] [Accepted: 04/09/2014] [Indexed: 11/19/2022]
Abstract
BACKGROUND Sorafenib, a multikinase inhibitor, has been shown to halt the growth of hepatocellular carcinoma. The aim of the present study was to investigate the effect of Sorafenib on liver regeneration in healthy rats. METHODS In two substudies we examined the effect of pre- or post-operative treatment with Sorafenib (15 mg/kg/d). Wistar rats (n = 120) received either Sorafenib (S) or placebo (P). After 70% partial hepatectomy, the rats were euthanized on postoperative days 2, 4, or 8. Body weight and liver weight were recorded and regeneration rate (RR) calculated. Hepatocyte proliferation was estimated by immunohistochemistry for Ki-67 antigen using unbiased stereological methods. RESULTS Eleven animals (9%) died after surgery. In the preoperative substudy, lower body weight gains during the gavage period in the S group were found. No difference between groups S and P regarding liver weight gain, liver RRs, and hepatocyte proliferation on postoperative days 2 and 4 were found. In the postoperative substudy, significantly lower values of liver weight gain, liver RRs, and hepatocyte proliferation were found in the S group. CONCLUSIONS In our rat model, Sorafenib did not increase posthepatectomy mortality. Postoperative treatment significantly impaired liver regeneration. Preoperative treatment impaired body weight during the gavage period, but was without effect on liver regeneration.
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Affiliation(s)
| | | | - Anne-Sofie Kannerup
- Department of Surgical Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Jens Randel Nyengaard
- Stereology & Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark
| | | | - Morten Ladekarl
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
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Poullenot F, Bioulac-Sage P, Laumonier H, Saric J, Carteret T, Blanc JF. Hepatocellular carcinoma treated by sorafenib with complete radiological response according to mRECIST criteria: could we stop the treatment? About four cases. Acta Oncol 2014; 53:420-3. [PMID: 23713857 DOI: 10.3109/0284186x.2013.795286] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Florian Poullenot
- Department of Gastroenterology and Hepatology, Saint-André Hospital, University Hospital of Bordeaux and Victor Segalen University , Bordeaux , France
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Ross SB, Luberice K, Kurian TJ, Paul H, Rosemurgy AS. Defining the learning curve of laparoendoscopic single-site Heller myotomy. Am Surg 2013; 11:171. [PMID: 23914915 PMCID: PMC3735470 DOI: 10.1186/1477-7819-11-171] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 07/27/2013] [Indexed: 12/17/2022]
Abstract
Initial outcomes suggest laparoendoscopic single-site (LESS) Heller myotomy with anterior fundoplication provides safe, efficacious, and cosmetically superior outcomes relative to conventional laparoscopy. This study was undertaken to define the learning curve of LESS Heller myotomy with anterior fundoplication. One hundred patients underwent LESS Heller myotomy with anterior fundoplication. Symptom frequency and severity were scored using a Likert scale (0 = never/not bothersome to 10 = always/very bothersome). Symptom resolution, additional trocars, and complications were compared among patient quartiles. Median data are presented. Preoperative frequency/severity scores were: dysphagia = 10/8 and regurgitation = 8/7. Additional trocars were placed in 12 patients (10%), of whom all were in the first two quartiles. Esophagotomy/gastrotomy occurred in three patients. Postoperative complications occurred in 9 per cent. No conversions to "open" operations occurred. Length of stay was 1 day. Postoperative frequency/severity scores were: dysphagia = 2/0 and regurgitation = 0/0; scores were less than before myotomy (P < 0.001). There were no apparent scars, except where additional trocars were placed. LESS Heller myotomy with anterior fundoplication well palliates symptoms of achalasia with no apparent scar. Placement of additional trocars only occurred early in the experience. For surgeons proficient with the conventional laparoscopic approach, the learning curve of LESS Heller myotomy with anterior fundoplication is short and safe, because proficiency is quickly attained.
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Affiliation(s)
- Sharona B Ross
- HPB & Foregut Advanced Laparoscopic & Robotic Surgery, Florida Hospital Tampa, Tampa, Florida 33613, USA
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