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Lin PT, Teng W, Jeng WJ, Lin CC, Lin CY, Lin SM, Sheen IS. Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment. J Formos Med Assoc 2024; 123:788-795. [PMID: 38310071 DOI: 10.1016/j.jfma.2024.01.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 10/27/2023] [Accepted: 01/29/2024] [Indexed: 02/05/2024] Open
Abstract
BACKGROUND Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. METHODS From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. RESULTS Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). CONCLUSION ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.
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Affiliation(s)
- Po-Ting Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan.
| | - Wei Teng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
| | - I-Shyan Sheen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.
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Zhang X, Zhu X, Zhong J, Zhao Y, Zhang X, Zhang W, Ye F, Yang C, Xue J, Xiong R, Wang J, Shen S, Pan Y, Li D, Song T, Bi X, Sun H, Xiang B, Gu S, Wen T, Lu S, Chen Y, Yin T, Liu L, Kuang M, Xu L, Li D, Cai J. Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: a multicenter retrospective study. Sci Rep 2024; 14:9745. [PMID: 38679630 PMCID: PMC11056363 DOI: 10.1038/s41598-024-60379-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 04/22/2024] [Indexed: 05/01/2024] Open
Abstract
Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.
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Affiliation(s)
- Xiaoshi Zhang
- 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
| | - Xiaodong Zhu
- Department of Liver Surgery and Transplantation, Zhongshan Hospital Affiliated of Fudan University, Shanghai, China
| | - Jianhong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Yang Zhao
- Department of Interventional Therapy, Hunan Cancer Hospital Affiliated of Xiangya School of Medicine, Hunan, China
| | - Xiaoyun Zhang
- Department of Liver Surgery, West China Hospital of Sichuan University, Sichuan, China
| | - Wenwen Zhang
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Feng Ye
- Department of General Surgery, Ruijin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chaoxu Yang
- Department of Medical Oncology, Nanjing Jinling Hospital, Jiangsu, China
| | - Jun Xue
- Cancer Center, Union Hospital Tongji Medical College of Huazhong University of Science and Technology, Shanghai, China
| | - Rui Xiong
- Department of Hepatobiliary and Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Jiabei Wang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Anhui, China
| | - Shunli Shen
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Yangxun Pan
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Dongxiao Li
- Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan, China
| | - Tianqiang Song
- Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 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
| | - Huichuan Sun
- Department of Liver Surgery and Transplantation, Zhongshan Hospital Affiliated of Fudan University, Shanghai, China
| | - Bangde Xiang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Guangxi, China
| | - Shanzhi Gu
- Department of Interventional Therapy, Hunan Cancer Hospital Affiliated of Xiangya School of Medicine, Hunan, China
| | - Tianfu Wen
- Department of Liver Surgery, West China Hospital of Sichuan University, Sichuan, China
| | - Shichun Lu
- Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China
| | - Yongjun Chen
- Department of General Surgery, Ruijin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tao Yin
- Department of Hepatobiliary and Pancreatic Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Anhui, China
| | - Ming Kuang
- Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Li Xu
- Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Sun Yat-Sen University, Guangzhou, China
| | - Deyu Li
- Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan, 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, Panjiayuan, Chaoyang District, in the South, 17th, Beijing, 100021, China.
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Gyoda Y, Ichida H, Kawano F, Takeda Y, Yoshioka R, Imamura H, Mise Y, Fukumura Y, Saiura A. A patient alive without disease 32 months after conversion surgery following lenvatinib treatment for hepatocellular carcinoma with a tumor thrombus originating in the middle hepatic vein and reaching the right atrium via the suprahepatic vena cava: a case report. Clin J Gastroenterol 2024; 17:311-318. [PMID: 38277091 DOI: 10.1007/s12328-023-01909-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 12/12/2023] [Indexed: 01/27/2024]
Abstract
Conversion surgery for initially unresectable hepatocellular carcinoma appears to be increasing in incidence since the advent of new molecular target drugs and immune checkpoint inhibitors; however, reports on long-term outcomes are limited and the prognostic relevance of this treatment strategy remains unclear. Herein, we report the case of a 75-year-old man with hepatocellular carcinoma, 108 mm in diameter, accompanied by a tumor thrombus in the middle hepatic vein that extended to the right atrium via the suprahepatic vena cava. He underwent conversion surgery after preceding lenvatinib treatment and is alive without disease 51 months after the commencement of treatment and 32 months after surgery. Just before conversion surgery, after 19 months of lenvatinib treatment, the main tumor had reduced in size to 72 mm in diameter, the tip of the tumor thrombus had receded back to the suprahepatic vena cava, and the tumor thrombus vascularity was markedly reduced. The operative procedure was an extended left hepatectomy with concomitant middle hepatic vein resection. The tumor thrombus was removed under total vascular exclusion via incision of the root of the middle hepatic vein. Histopathological examination revealed that more than half of the liver tumor and the tumor thrombus were necrotic.
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Affiliation(s)
- Yu Gyoda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hirofumi Ichida
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Fumihiro Kawano
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshinori Takeda
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Ryuji Yoshioka
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Hiroshi Imamura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yoshihiro Mise
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan
| | - Yuki Fukumura
- Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
| | - Akio Saiura
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo, 113-8421, Japan.
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Tai Y, Morita Y, Makino M, Ida S, Muraki R, Kitajima R, Takeda M, Kikuchi H, Hiramatsu Y, Takeuchi H. A Case of Giant Hepatocellular Carcinoma Successfully Treated with Lenvatinib Followed by Parenchymal-Sparing Hepatectomy. THE JAPANESE JOURNAL OF GASTROENTEROLOGICAL SURGERY 2023; 56:547-559. [DOI: 10.5833/jjgs.2022.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Yuta Tai
- Department of Surgery, Shizuoka City Shimizu Hospital
| | | | | | - Shinya Ida
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryuta Muraki
- Department of Surgery, Hamamatsu University School of Medicine
| | - Ryo Kitajima
- Department of Surgery, Hamamatsu University School of Medicine
| | - Makoto Takeda
- Department of Surgery, Hamamatsu University School of Medicine
| | | | - Yoshihiro Hiramatsu
- Department of Surgery, Hamamatsu University School of Medicine
- Department of Perioperative Functioning Care and Support, Hamamatsu University School of Medicine
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine
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Zhu Q, Rao W, Huo J, Li Z, Wang S, Qiu W, Guan G, Xin Y, Fan N, Cai J, Wu L. Real-world systemic sequential therapy with regorafenib for recurrent hepatocellular carcinoma: analysis of 93 cases from a single center. BMC Gastroenterol 2023; 23:28. [PMID: 36726082 PMCID: PMC9890826 DOI: 10.1186/s12876-023-02661-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Accepted: 01/20/2023] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Regorafenib is an oral multikinase inhibitor and became the first second-line systemic treatment for hepatocellular carcinoma (HCC) following the phase III RESORCE trial. This single-center study retrospectively analyzed the clinical data and follow-up results of patients with recurrent HCC treated with regorafenib and discussed the prognostic factors to provide guidance for clinical treatment. METHODS Ninety-three recurrent HCC patients were enrolled in the research and follow up from December 2017 to December 2020. Clinical and pathological data were collected. SPSS software v26.0 was used (Chicago, IL, USA) for statistical analysis. A two-sided P < 0.05 was considered statistically significant. RESULTS The patients included 81 males and 12 females with a median age of 57 years. Eighty-seven patients had hepatitis B virus (HBV) infection. The objective response rate (ORR) was 14.0%, and the disease control rate (DCR) was 62.4%. The median overall survival (mOS) and median time to progression (mTTP) were 15.9 and 5.0 months. Multivariate analysis showed that Child-Pugh classification, the Eastern Cooperative Oncology Group performance status (ECOG PS), the neutrophil-to-lymphocyte ratio (NLR), combined treatment, and the time from first diagnosis of HCC to second-line treatment were independent factors affecting the prognosis of recurrent HCC patients. CONCLUSIONS This real-world study demonstrated similar findings to those of the RESORCE trial. Regorafenib could effectively improve the prognosis of patients after first-line treatment failure. Combination therapy under multidisciplinary treatment (MDT) team guidance could be effective in impeding tumor progression and improving the prognosis of recurrent HCC patients.
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Affiliation(s)
- Qingwei Zhu
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Wei Rao
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Junyu Huo
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Zixiang Li
- grid.412521.10000 0004 1769 1119Department of Interventional Medicine Cancer Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Song Wang
- grid.412521.10000 0004 1769 1119Department of Interventional Medicine Cancer Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Wensheng Qiu
- grid.412521.10000 0004 1769 1119Tumor Hospital, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong People’s Republic of China
| | - Ge Guan
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Yang Xin
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Ning Fan
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Jinzhen Cai
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
| | - Liqun Wu
- grid.412521.10000 0004 1769 1119Liver Disease Center, The Affiliated Hospital of Qingdao University, No.59 Haier Road, Qingdao, 266003 Shandong People’s Republic of China
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Sano S, Asahi Y, Kamiyama T, Kakisaka T, Orimo T, Nagatsu A, Aiyama T, Kazui K, Shomura H, Ueki S, Sakamoto Y, Shirakawa C, Kamachi H, Sugino H, Mitsuhashi T, Taketomi A. Conversion surgery after lenvatinib treatment for multiple lung metastases from hepatocellular carcinoma. Int Cancer Conf J 2023; 12:7-13. [PMID: 36605836 PMCID: PMC9807693 DOI: 10.1007/s13691-022-00567-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 07/13/2022] [Indexed: 01/09/2023] Open
Abstract
Although systemic treatment for hepatocellular carcinoma has advanced after the development of tyrosine kinase inhibitors such as sorafenib and lenvatinib, the effectiveness of a single tyrosine kinase inhibitor in survival extension of unresectable hepatocellular carcinoma is limited to a few months. Therefore, novel treatment options are required for unresectable hepatocellular carcinomas, including those with multiple lung metastases. This case report describes a hepatocellular carcinoma patient with a recurrence of multiple lung metastases, which was successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. A 79-year-old man underwent right hepatectomy for hepatocellular carcinoma, along with removal of the tumor thrombus in the inferior vena cava. Multiple lung metastases were detected 4 months after hepatectomy. Treatment with tyrosine kinase inhibitors, mainly lenvatinib, resulted in complete remission of the lung metastases, except for one lesion in segment 3 of the right lung which gradually enlarged. Twenty-three months after hepatectomy, partial resection of the right lung was performed using video-assisted thoracic surgery for this residual lesion in the right lung. The patient remained disease-free for 11 months after conversion pneumonectomy, without any adjuvant therapies. This is the first case report of multiple lung metastases originating from hepatocellular carcinoma which were successfully treated with conversion pneumonectomy after treatment with tyrosine kinase inhibitors. Conversion pneumonectomy after systemic therapy with tyrosine kinase inhibitors should be considered as a treatment strategy for patients with unresectable multiple lung metastases from hepatocellular carcinomas.
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Affiliation(s)
- Shunji Sano
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Yoh Asahi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Toshiya Kamiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuhiko Kakisaka
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Akihisa Nagatsu
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Takeshi Aiyama
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Keizo Kazui
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hiroki Shomura
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Shinya Ueki
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Yuzuru Sakamoto
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Chisato Shirakawa
- Department of Surgery, JCHO Hokkaido Hospital, 8-3-18, Nakanoshima, Toyohiraku, Sapporo, Hokkaido 062-8618 Japan
| | - Hirofumi Kamachi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
| | - Hirokazu Sugino
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Tomoko Mitsuhashi
- Department of Surgical Pathology, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido 060-8638 Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Hospital, Kita 15, Nishi 7, Kita-ku , Sapporo, Hokkaido 060-8638 Japan
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Tran NH, Muñoz S, Thompson S, Hallemeier CL, Bruix J. Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy. Hepatology 2022; 76:1203-1218. [PMID: 35765265 DOI: 10.1002/hep.32613] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/26/2022] [Accepted: 04/28/2022] [Indexed: 12/08/2022]
Abstract
Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.
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Affiliation(s)
- Nguyen H Tran
- Division of Medical OncologyDepartment of OncologyMayo ClinicRochesterMinnesotaUSA
| | - Sergio Muñoz
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
| | - Scott Thompson
- Division of Vascular and Interventional RadiologyDepartment of RadiologyMayo ClinicRochesterMinnesotaUSA
| | | | - Jordi Bruix
- BCLC GroupLiver UnitHospital Clinic BarcelonaIDIBAPSCIBEREHDUniversity of BarcelonaBarcelonaSpain
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Shindoh J, Kawamura Y, Kobayashi M, Akuta N, Okubo S, Matsumura M, Suzuki Y, Hashimoto M. Prognostic Advantages of Individual Additional Interventions After Lenvatinib Therapy in Patients with Advanced Hepatocellular Carcinoma. J Gastrointest Surg 2022; 26:1637-1646. [PMID: 35715641 DOI: 10.1007/s11605-022-05388-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/14/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND Increasing number of patients with advanced hepatocellular carcinoma (HCC) has recently achieved salvage interventions after introduction of new biologic agents, while there are insufficient data to determine if such additional intervention(s) after treatment with newer biologic agents are truly advantageous for patients with advanced HCC. METHODS The clinical records of 107 consecutive patients who underwent lenvatinib treatment for advanced HCC were extensively reviewed and the prognostic advantages of individual additional treatments after lenvatinib treatment were investigated through a regression analysis considering time-dependent covariates. RESULTS Multivariate analysis revealed that R0 resection or curative-intent radiofrequency ablation (RFA) (hazard ratio [HR], 0.07; 95% CI, 0.01-0.32), transarterial chemoembolization or transarterial infusion therapy (HR, 0.39; 95% CI, 0.19-0.81), and subsequent line of systemic therapy (HR, 0.25; 95% CI, 0.10-0.63) were associated with improved disease-specific survival (DSS), while R2 resection or palliative-intent RFA showed no correlation with DSS. The best response during lenvatinib therapy, nutritional status, plasma des-gamma-carboxyprothrombin level, a baseline CT enhancement pattern, and BCLC stage were also selected as independent predictors for DSS. Among the various treatments performed after lenvatinib therapy, R0 resection also showed clear prognostic advantage in both progression-free survival (HR, 0.30; 95% CI, 0.16-0.58) and time-to-treatment failure (HR, 0.08; 95% CI, 0.02-0.39), suggesting that successful conversion to surgery may prolong survival outcomes through prolonged cancer-free interval in advanced HCC. CONCLUSIONS Additional intervention(s)/treatment(s) after lenvatinib therapy for advanced HCC may have prognostic advantage in strictly selected populations. Successful conversion to curative resection may offer survival benefit with acceptable clinical outcomes.
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Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
- Okinaka Memorial Institute for Medical Disease, Tokyo, Japan.
| | | | | | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Satoshi Okubo
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Masaru Matsumura
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | | | - Masaji Hashimoto
- Hepatobiliary-Pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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9
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Hidaka Y, Tomita M, Desaki R, Hamanoue M, Takao S, Kirishima M, Ohtsuka T. Conversion surgery for hepatocellular carcinoma with portal vein tumor thrombus after successful atezolizumab plus bevacizumab therapy: a case report. World J Surg Oncol 2022; 20:228. [PMID: 35831894 PMCID: PMC9277871 DOI: 10.1186/s12957-022-02691-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 06/30/2022] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND The treatment of hepatocellular carcinoma (HCC) requires diverse and multidisciplinary approaches. In recent years, new agents with good antitumor effects have emerged for systemic chemotherapy, and conversion surgery (CS) after systemic chemotherapy is expected to be an effective treatment strategy for unresectable HCC. We herein report a case of unresectable HCC with portal vein tumor thrombus (PVTT) in which atezolizumab plus bevacizumab therapy induced PVTT regression, followed by CS with R0 resection. CASE PRESENTATION The patient was a 79-year-old man with S2/S3 HCC who was referred to our department due to tumor re-growth and PVTT after two rounds of transcatheter arterial chemoembolization. The PVTT extended from the left portal vein to the main trunk, and it was determined that the resection of the left portal vein would be difficult to perform with R0 status. Based on the diagnosis of unresectable HCC, treatment with atezolizumab plus bevacizumab was initiated. After two courses of treatment, contrast-enhanced computed tomography showed that the PVTT had regressed to the peripheral side of the left portal vein, and R0 resection became possible. The patient developed grade 3 skin lesions as an immune-related adverse event, and it was determined that the continuation of chemotherapy would be difficult. Four weeks after the second course of atezolizumab plus bevacizumab administration, left lobectomy was performed. Intraoperative ultrasonography was used to confirm the location of the tumor thrombus in the left portal vein during the resection, and a sufficient surgical margin was obtained. The histopathological findings showed that primary tumor and PVTT were mostly necrotic with residues of viable tumor cells observed in some areas. The liver background was determined as A1/F4 (new Inuyama classification). The resection margins were negative, and R0 resection was confirmed. There were no postoperative complications. No recurrence was observed as of five months after surgery. CONCLUSIONS CS with atezolizumab plus bevacizumab therapy has potential utility for the treatment of unresectable HCC with PVTT.
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Affiliation(s)
- Yoshifumi Hidaka
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan.
| | - Miyo Tomita
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Ryosuke Desaki
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Masahiro Hamanoue
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Sonshin Takao
- Department of Surgery, Tanegashima Medical Center, 7463 Nishinoomote, Nishinoomote, Kagoshima, 891-3198, Japan
| | - Mari Kirishima
- Department of Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
| | - Takao Ohtsuka
- Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan
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10
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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: 4] [Impact Index Per Article: 1.3] [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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11
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Shindoh J. Multidisciplinary Approach to the Treatment of Advanced Hepatocellular Carcinoma in the Era of New Biologic Agents. J NIPPON MED SCH 2022; 89:145-153. [PMID: 34840212 DOI: 10.1272/jnms.jnms.2022_89-223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
With recent advances in systemic therapy, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are expected to benefit from surgery. However, given the complex background of the disease and frequent presence of underlying liver injury, treatment of advanced HCC is complex and the treatment principle applied to colorectal liver metastases, for which conversion surgery has been actively performed, is often not applicable to patients with HCC. To maximize the survival outcomes of patients with HCC, optimization of each step of treatment through a multidisciplinary approach is inevitable. As initial treatment, systematic removal of tumor-bearing portal territory is associated with improved survival in patients with solitary HCC, and radiofrequency ablation is also effective for small, oligo HCCs. Although the high incidence of recurrence even after curative-intent treatment is a major concern in HCC, aggressive treatment for recurrence is important, because a prolonged cancer-free interval is associated with improved overall survival. For patients with advanced disease, recently introduced molecular-targeted agents may be effective for successful conversion to surgery in initially unresectable cases, although the overall response rate of HCC to systemic therapies remains unsatisfactory as compared to that of colorectal liver metastases. This report revisits the theoretical bases for management of HCC and discusses current strategies for maximizing survival of patients with advanced HCC.
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Affiliation(s)
- Junichi Shindoh
- Hepatobiliary-pancreatic Surgery Division, Department of Gastroenterological Surgery, Toranomon Hospital
- Okinaka Memorial Institute for Medical Disease
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12
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Kaneko S, Tsuchiya K, Yasui Y, Tanaka Y, Inada K, Ishido S, Kirino S, Yamashita K, Hayakawa Y, Nobusawa T, Matsumoto H, Kakegawa T, Higuchi M, Takaura K, Tanaka S, Maeyashiki C, Tamaki N, Takahashi Y, Nakanishi H, Irie T, Ariizumi S, Kurosaki M, Izumi N. Conversion surgery for hepatocellular carcinoma after tyrosine kinase inhibitor treatment. JGH Open 2022; 6:301-308. [PMID: 35601130 PMCID: PMC9120872 DOI: 10.1002/jgh3.12735] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/25/2022] [Accepted: 03/14/2022] [Indexed: 12/20/2022]
Abstract
Background and Aim Conversion surgery (CS), which aims to cure after systematic therapy, is only scarcely reported in the field of hepatocellular carcinoma (HCC). However, advancements in systemic therapy for HCC are expected to increase the candidates eligible for CS because of the higher response rate. The aim of this study was to clarify the characteristics of patients who underwent CS after tyrosine kinase inhibitor (TKI) therapy. Methods In all, 364 patients who were treated with first-line sorafenib (SOR; n = 292) and lenvatinib (LEN; n = 72) from July 2009 to October 2020 were retrospectively enrolled. The endpoint of this analysis was overall survival (OS), and factors associated with CS are revealed. Results Six patients underwent CS after TKI therapy, and of these four (1.4%) and two (2.7%) patients received SOR and LEN, respectively. At baseline, patients who underwent CS were significantly younger (median 52 [range, 46-83] years of age, P = 0.019), and their etiology included viral hepatitis, especially hepatitis B virus (HBV) (P = 0.049). Improvements or maintenance of preoperative modified albumin-bilirubin grade from baseline were observed in five (83.3%) patients, and partial radiologic response was observed in four (66.7%) patients. The median OS and 3-year survival rate of patients treated with CS were "not reached" and 80.0%, respectively. Conclusion The patients who underwent CS after TKI therapy for HCC experienced long survival, were relatively young, and exhibited radiologic response to TKIs, and their liver function was either maintained or improved. Therefore, CS may lead to a better prognosis in patients with advanced HCC.
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Affiliation(s)
- Shun Kaneko
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kaoru Tsuchiya
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yutaka Yasui
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuki Tanaka
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kento Inada
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Shun Ishido
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Sakura Kirino
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Koji Yamashita
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuka Hayakawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Tsubasa Nobusawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Hiroaki Matsumoto
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Tatsuya Kakegawa
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Mayu Higuchi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Kenta Takaura
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Shohei Tanaka
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Chiaki Maeyashiki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Nobuharu Tamaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Yuka Takahashi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Hiroyuki Nakanishi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Takumi Irie
- Department of SurgeryMusashino Red Cross HospitalTokyoJapan
| | - Shun‐Ichi Ariizumi
- Department of Surgery, Institute of GastroenterologyTokyo Women's Medical UniversityTokyoJapan
| | - Masayuki Kurosaki
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
| | - Namiki Izumi
- Department of Gastroenterology and HepatologyMusashino Red Cross HospitalTokyoJapan
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13
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Endo Y, Shimazu M, Sakuragawa T, Uchi Y, Edanami M, Sunamura K, Ozawa S, Chiba N, Kawachi S. Successful treatment with laparoscopic surgery and sequential multikinase inhibitor therapy for hepatocellular carcinoma: A case report. World J Gastrointest Surg 2022; 14:260-267. [PMID: 35432767 PMCID: PMC8984515 DOI: 10.4240/wjgs.v14.i3.260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/08/2022] [Accepted: 03/17/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with massive portal vein tumor thrombosis (PVTT) and distant metastasis is considered unresectable. However, due to recent developments in systemic chemotherapy, successful cases of conversion therapy for unresectable diseases have been reported. Herein, we report a successful multidisciplinary approach for treatment of multi-visceral recurrence with sequential multikinase inhibitor and laparoscopic surgery.
CASE SUMMARY A 63-year-old woman with chronic hepatitis B virus infection was diagnosed with HCC. Subsequently, she underwent two rounds of laparoscopic partial hepatectomy, laparoscopic left adrenalectomy, and transcatheter arterial chemoembolization plus sorafenib for recurrence. Four years after initial hepatectomy, she presented with a 43-mm mass in the spleen and tumor thrombus involving the main portal vein trunk with ascites. Her liver function was Child-Pugh B (8), and protein induced by vitamin K absence or antagonist II (PIVKA II) levels were elevated up to 46.291 mAU/mL. Since initial treatment with regorafenib for three months was unsuccessful, the patient was administered lenvatinib. Ten months post-treatment, there was no contrast enhancement of PVTT or splenic metastasis. Chemotherapy was discontinued due to severe diarrhea. Afterward, splenic metastasis became viable, and PIVKA II increased. Therefore, hand-assisted laparoscopic splenectomy was performed. She experienced no clinical recurrence 14 mo after resection.
CONCLUSION Conversion surgery after successful multikinase inhibitor treatment might be considered an effective treatment option for advanced HCC.
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Affiliation(s)
- Yutaka Endo
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motohide Shimazu
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | | | - Yusuke Uchi
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Motonori Edanami
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Ken Sunamura
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Soji Ozawa
- Department of Surgery, Tama Kyuryo Hospital, Tokyo 1940297, Japan
| | - Naokazu Chiba
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
| | - Shigeyuki Kawachi
- Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Tokyo 1930998, Japan
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14
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Naganuma A, Suzuki Y, Hoshino T, Yasuoka H, Tamura Y, Naruse H, Tanaka H, Hirai K, Sakamoto I, Ogawa T, Hatanaka T, Kakizaki S. A case of conversion hepatectomy for huge ruptured hepatocellular carcinoma after transarterial embolization and lenvatinib therapy. Clin J Gastroenterol 2021; 15:177-184. [PMID: 34811701 DOI: 10.1007/s12328-021-01558-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 11/10/2021] [Indexed: 12/09/2022]
Abstract
We herein report a successfully treated case of huge ruptured hepatocellular carcinoma (HCC) by conversion hepatectomy after transarterial embolization (TAE) and lenvatinib therapy. A 33-year-old male patient with right hypochondralgia and liver tumor was referred to our hospital. He had a history of surgery for heart malformation. The tumor at the right lobe was 15 cm in diameter with bloody ascites. Right atrial thrombus 4.5 cm in diameter and marked cardiac dilatation were observed. TAE with ethanol suspended in lipiodol and gelatin sponge achieved hemostasis of the ruptured HCC. Although viable HCC remained after TAE, surgical treatment was abandoned because of abdominal wall invasion and his heart function. Lenvatinib and rivaroxaban were then initiated for HCC and atrial thrombus, respectively. Lenvatinib treatment resulted in a reduction in tumor marker levels and the tumor size. First, we planned conversion hepatectomy after 5 months of lenvatinib. However, recurrence of atrial thrombus prompted us to put off the surgery, and lenvatinib was re-administered. After improvement of atrial thrombus, we finally performed conversion hepatectomy 10 months after starting lenvatinib administration. The tumor was completely removed by combined resection of the diaphragm, and the patient has been doing well without any signs of recurrence.
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Affiliation(s)
- Atsushi Naganuma
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuhei Suzuki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takashi Hoshino
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hidetoshi Yasuoka
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Yuki Tamura
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroaki Naruse
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Hiroshi Tanaka
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Keitaro Hirai
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Ichiro Sakamoto
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Tetsushi Ogawa
- Department of Surgery, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan
| | - Takeshi Hatanaka
- Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, 564-1 Kamishindenmachi, Maebashi, Gunma, 371-0821, Japan
| | - Satoru Kakizaki
- Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan. .,Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, 36 Takamatsu-cho, Takasaki, Gunma, 370-0829, Japan.
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15
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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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16
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Endo K, Kuroda H, Abe T, Sato H, Kooka Y, Oikawa T, Sato A, Nishiya M, Sugai T, Takikawa Y. Two hepatectomy cases for initially unresectable hepatocellular carcinoma after achieving a radiological complete response to sequential therapy with lenvatinib and transcatheter arterial chemoembolization. Hepatol Res 2021; 51:1082-1086. [PMID: 33982336 DOI: 10.1111/hepr.13665] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/16/2021] [Accepted: 05/08/2021] [Indexed: 11/29/2022]
Abstract
We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.
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Affiliation(s)
- Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Hidekatsu Kuroda
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Tamami Abe
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Hiroki Sato
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Youhei Kooka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Takayoshi Oikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
| | - Ayaka Sato
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Masao Nishiya
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Tamotsu Sugai
- Department of Molecular Diagnostic Pathology, Iwate Medical University, Yahaba, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University School of Medicine, Yahaba, Japan
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17
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Yamamura K, Beppu T. Conversion surgery for hepatocellular carcinoma after multidisciplinary treatment including lenvatinib. Hepatol Res 2021; 51:1029-1030. [PMID: 34596312 DOI: 10.1111/hepr.13691] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Kensuke Yamamura
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
| | - Toru Beppu
- Department of Surgery, Yamaga City Medical Center, Kumamoto, Japan
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18
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Yang X, Xu H, Zuo B, Yang X, Bian J, Long J, Wang D, Zhang J, Ning C, Wang Y, Xun Z, Wang Y, Lu X, Mao Y, Sang X, Zhao H. Downstaging and resection of hepatocellular carcinoma in patients with extrahepatic metastases after stereotactic therapy. Hepatobiliary Surg Nutr 2021; 10:434-442. [PMID: 34430522 PMCID: PMC8350994 DOI: 10.21037/hbsn-21-188] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 06/18/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND A combination of tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies with local regional therapy has elicited yield substantial clinical benefits in patients who have hepatocellular carcinoma (HCC) with extrahepatic metastases. Using this treatment strategy to convert HCC patients with extrahepatic metastases from unresectable to resectable has not yet been reported. METHODS Consecutive hepatocellular carcinoma patients with extrahepatic metastases who received first-line therapy with a combination of TKIs and anti-PD-1 antibodies and at least one local regional therapy were analysed. RESULTS Nine patients with localized disease who received first-line systemic therapy were enrolled. At baseline, all of them had oligometastatic disease, namely, Barcelona Clinic Liver Cancer stage C (or Chinese Liver Cancer stage IIIB). The most common treatment administered was lenvatinib plus anti-PD-1 antibody and transarterial chemoembolization, and the median time span from systemic therapy to surgery was 3.2 (IQR, 2.8-6.2) months. Three patients achieved a pathological complete response. Six patients underwent laparoscopic surgery, and the other 3 patients underwent open surgery. After a median follow-up of 10.2 (IQR, 8.6-20.0) months, 7 patients survived without disease recurrence, and 2 experienced tumour recurrence. All patients had any-grade AEs, and 55.6% of the patients experienced grade 3 AEs. Fatigue was the most common AE, followed by elevated aminotransferase levels and hypertension. CONCLUSIONS Stereotactic therapy is a feasible conversion therapy for HCC patients with extrahepatic metastases to become resectable. This is the first study to analyse therapeutic outcomes of patients receiving these therapies for HCC with extrahepatic metastases.
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Affiliation(s)
- Xiaobo Yang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Haifeng Xu
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Bangyou Zuo
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Xu Yang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Jin Bian
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Junyu Long
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Dongxu Wang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Junwei Zhang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Cong Ning
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yanyu Wang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Ziyu Xun
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yunchao Wang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Xin Lu
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Yilei Mao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Xinting Sang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
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Luo YC, Lu HL, Song WL, Xuan FF. Multidisciplinary treatment of advanced hepatocellular carcinoma with severe arterioportal shunt: a case report. J Int Med Res 2021; 49:3000605211024840. [PMID: 34250825 PMCID: PMC8278469 DOI: 10.1177/03000605211024840] [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: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality globally. In addition, most patients present in advanced stages with limited curative treatment options. Therefore, multidisciplinary treatment is often warranted. Here, we report a patient with HCC and severe arterioportal shunt (APS) who was treated with a multidisciplinary approach comprising interventional radiology procedures, apatinib and camrelizumab. After treatment, the intrahepatic mass was stable, and a notable decrease in the number and size of lung lesions was observed. The patient achieved a long-term survival of more than 2 years. These data suggest that multidisciplinary treatments may be effective in the treatment of advanced HCC with severe APS.
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Affiliation(s)
- Yao-Chang Luo
- Department of Interventional Radiology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China
| | - Hai-Lin Lu
- Department of Interventional Radiology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China
| | - Wen-Ling Song
- Department of Interventional Radiology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China
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20
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Takahashi K, Kim J, Takahashi A, Hashimoto S, Doi M, Furuya K, Hashimoto R, Owada Y, Ogawa K, Ohara Y, Akashi Y, Hisakura K, Enomoto T, Shimomura O, Noguchi M, Oda T. Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: A case report. World J Hepatol 2021; 13:384-392. [PMID: 33815680 PMCID: PMC8006080 DOI: 10.4254/wjh.v13.i3.384] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 01/31/2021] [Accepted: 03/10/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) accompanied by portal vein tumour thrombus (PVTT) presents an aggressive disease course, worsening liver function reserve, and a high recurrence rate. Clinical practice guidelines recommend systemic therapy as the first-line option for HCC with portal invasion. However, to achieve longer survival in these patients, the treatment strategy should be concluded with removal of the tumour by locoregional therapy. We experienced a case of initially unresectable HCC with main PVTT converted to radical hepatectomy after lenvatinib treatment. CASE SUMMARY A 59-year-old male with chronic hepatitis C infection visited our clinic as a regular post-surgery follow-up. Contrast-enhanced abdominal computed tomography revealed a liver mass diffusely located at the lateral segment with a massive PVTT extending from the umbilical portion to the main and contralateral third-order portal branches. With the diagnosis of unresectable HCC with Vp4 (main trunk/contralateral branch) PVTT, lenvatinib was started at 12 mg/d. The computed tomography taken 3 mo after starting lenvatinib showed regression of the PVTT, which had retreated to the contralateral first-order portal branch. He tolerated the full dose without major adverse effects. With cessation of lenvatinib for 7 d, radical left lobectomy and PVTT thrombectomy were conducted. The patient's postoperative course was uneventful. Microscopically, the primary lesion showed fibrotic changes, with moderately to poorly differentiated tumour cells surrounded by granulation tissues in some areas. The majority of the PVTT showed necrosis. He was alive without recurrence for 8 mo. CONCLUSION This is the first case of HCC with Vp4 PVTT in which radical conversion hepatectomy was succeeded after lenvatinib treatment.
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Affiliation(s)
- Kazuhiro Takahashi
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan.
| | - Jaejeong Kim
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Amane Takahashi
- Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama 3620806, Saitama, Japan
| | - Shinji Hashimoto
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Manami Doi
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Kinji Furuya
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Ryosuke Hashimoto
- Department of Diagnostic Pathology, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Yohei Owada
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Koichi Ogawa
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Yusuke Ohara
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Yoshimasa Akashi
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Katsuji Hisakura
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Tsuyoshi Enomoto
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Osamu Shimomura
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Masayuki Noguchi
- Department of Diagnostic Pathology, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
| | - Tatsuya Oda
- Department of Gastrointestinal and Hepatobiliary Pancreatic Surgery, University of Tsukuba, Tsukuba 3058575, Ibaraki, Japan
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21
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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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22
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Yokoo H, Takahashi H, Hagiwara M, Iwata H, Imai K, Saito Y, Matsuno N, Furukawa H. Successful hepatic resection for recurrent hepatocellular carcinoma after lenvatinib treatment: A case report. World J Hepatol 2020; 12:1349-1357. [PMID: 33442460 PMCID: PMC7772741 DOI: 10.4254/wjh.v12.i12.1349] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/29/2020] [Accepted: 10/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lenvatinib has been shown to be noninferior to sorafenib regarding prognosis and recurrence rate in patients with unresectable hepatocellular carcinoma (HCC) who have not received prior systemic chemotherapy. In patients treated with lenvatinib, 40% of cases achieved sufficient tumor reduction to make potential surgery possible. However, the outcomes of such surgery are unknown. We report a successful case of hepatic resection for recurrent HCC after lenvatinib treatment. CASE SUMMARY A 69-year-old man underwent right anterior sectionectomy for HCC in segment 8 of the liver. Ten months later, he was found to have an intrahepatic HCC recurrence that grew rapidly to 10 cm in diameter with sternal bone metastases. After confirming partial response to lenvatinib administration for 2 mo, a second hepatectomy was performed. Pathological examination showed that 80% of the tumor was necrotic. The patient did not develop any adverse effects under lenvatinib treatment. He was discharged at 25 d after surgery. Radiation therapy for bone metastases continued to be given under lenvatinib, and the patient has remained alive for 1 year after the second hepatectomy. CONCLUSION The prognosis of patients with recurrent HCC may be improved by liver resection combined with prior lenvatinib therapy.
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Affiliation(s)
- Hideki Yokoo
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan.
| | - Hiroyuki Takahashi
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Masahiro Hagiwara
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Hiroyoshi Iwata
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Koji Imai
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Yoshinori Saito
- Department of Gastroenterology, Asahikawa-Kosei General Hospital, Asahikawa 078-8211, Hokkaido, Japan
| | - Naoto Matsuno
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
| | - Hiroyuki Furukawa
- Division of Hepato-Biliary-Pancreatic Surgery and Transplant Surgery, Department of Surgery, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan
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23
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Huge hepatocellular carcinoma with extrahepatic collateral arteries successfully treated by multidisciplinary treatment including laparoscopic devascularization: a case report. Clin J Gastroenterol 2020; 14:251-257. [PMID: 33180262 DOI: 10.1007/s12328-020-01286-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 10/25/2020] [Indexed: 02/07/2023]
Abstract
Multidisciplinary treatment is recommended for the management of patients with advanced hepatocellular carcinoma (HCC). Some operative decollateralization of extrahepatic feeding arteries with laparotomy have been introduced for HCC. We herein newly develop laparoscopic devascularization (LDEV) to continue transarterial chemoembolization (TACE) for HCC with extrahepatic collateral arteries. A 74-year-old man with multiple huge HCC (4 tumors, 18 cm in diameter) and poor liver function (non-alcoholic steatohepatitis, Child-Pugh score 7) was treated with 6 times of chemoembolization in combination with LDEV, 3 times of ablation therapies, and lenvatinib therapy. His tumor markers were triple positive (AFP, 12,906.5 ng/ml; PIVKA-II, 491,743 mAU/ml; AFP-L3, 91.8%) before treatments; however, they all returned to normal limits. Complete response was achieved according to the modified RECIST criteria. Unfortunately, he died 6 months after the final treatment with no recurrence of HCC due to the postoperative complication of primary lung cancer. LDEV is a useful tool to continue effective TACE, and multidisciplinary treatment including chemoembolization and LDEV can cure advanced HCC patients with extrahepatic collaterals and impaired liver function.
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Liu Z, Fu Z, Li G, Lin D. Downstaging of Recurrent Advanced Hepatocellular Carcinoma After Lenvatinib Treatment: Opportunities or Pitfalls? A Case Report. Onco Targets Ther 2020; 13:10267-10273. [PMID: 33116607 PMCID: PMC7568629 DOI: 10.2147/ott.s261521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 08/18/2020] [Indexed: 12/24/2022] Open
Abstract
Background The majority of patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage that excludes them from potentially curative surgical treatment. Lenvatinib is associated with a high objective response rate (ORR) (40.6%) in advanced HCC, indicating the potential for tumor downstaging and conversion to surgical intervention. We report the case of a patient with recurrent, advanced HCC who achieved a partial response and downstaging following third-line treatment with lenvatinib but missed the opportunity for conversion hepatectomy. Case Presentation A male Chinese patient aged 42 years presented with an obstructive liver lesion, revealed by CT imaging to be a single tumor in segments V and VIII of the liver, without macrovascular invasion. The patient had chronic hepatitis B infection, Barcelona Clinic Liver Cancer (BCLC) Stage A, normal liver function (Child-Pugh Score 5 and Grade A) and AFP level 4.45 ng/mL. The patient underwent a successful hepatectomy but experienced recurrence 14 months later. The recurrent tumor was detected at an early stage and the patient underwent successful radiofrequency ablation and transarterial chemoembolization. After a further 11 months, the patient experienced a second relapse characterized by multiple disseminated metastases in the left and right lobes of the liver and possible macrovascular invasion, equal to BCLC Stage B/C. The patient received lenvatinib and achieved a partial response with complete disappearance of a number of lesions, recovering to BCLC Stage A and becoming eligible for liver transplantation. However, the patient refused surgery and after 4 months experienced progressive disease. Conclusion Our case suggests that radical treatment, such as conversion hepatectomy or liver transplantation, should be undertaken quickly following downstaging and within the expected PFS time associated with lenvatinib. However, further studies are required to provide additional evidence for this treatment strategy.
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Affiliation(s)
- Zhaobo Liu
- Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People's Republic of China
| | - Zhi Fu
- Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People's Republic of China
| | - Guangming Li
- Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People's Republic of China
| | - Dongdong Lin
- Department of General Surgery, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People's Republic of China
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