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Ke Q, Wang L, Wu W, Huang X, Li L, Liu J, Guo W. Meta-Analysis of Postoperative Adjuvant Hepatic Artery Infusion Chemotherapy Versus Surgical Resection Alone for Hepatocellular Carcinoma. Front Oncol 2021; 11:720079. [PMID: 35004268 PMCID: PMC8727591 DOI: 10.3389/fonc.2021.720079] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 11/30/2021] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND To systematically identify the long-term efficacy of postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC). METHODS PubMed, MedLine, Embase, the Cochrane Library, and Web of Science were searched to collect the eligible studies up to March 31, 2021, that compared the surgical resection (SR) versus SR+HAIC for HCC patients. The endpoints were overall survival (OS) rates and disease-free survival (DFS) rates, and the effect size was determined by hazard ratio (HR) with 95% CI. RESULTS A total of 12 studies (two randomized controlled trials (RCTs) and 10 non-RCTs) including 1,333 patients were eligible for this meta-analysis. The pooled results showed that OS and DFS rates in the SR+HAIC group were both better than those in the SR alone group (HR = 0.56, 95% CI = 0.41-0.77, p < 0.001; HR = 0.66, 95% CI = 0.55-0.78, p < 0.001, respectively). Furthermore, the subgroup analysis showed that patients would benefit from SR+HAIC regardless of chemotherapy regimens and courses (all p < 0.05), and patients with microvascular or macrovascular invasion would also benefit more from SR+HAIC in terms of OS and DFS (all p < 0.05). CONCLUSION Postoperative adjuvant HAIC could improve the long-term prognosis of HCC patients, especially for those with microvascular or macrovascular invasion, regardless of chemotherapy regimens and courses, but it deserves further validation.
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Affiliation(s)
- Qiao Ke
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
- Department of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Lei Wang
- Department of Radiation Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
| | - Weimin Wu
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Xinhui Huang
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Ling Li
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou, China
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Wuhua Guo
- Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
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2
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Liu Y, Wang Y, Guo X, He Y, Zhou J, Lv Q, Huang X, Li X. Comparative Effectiveness of Adjuvant Treatment for Resected Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis. Front Oncol 2021; 11:709278. [PMID: 34540675 PMCID: PMC8445365 DOI: 10.3389/fonc.2021.709278] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/09/2021] [Indexed: 12/24/2022] Open
Abstract
Background It is controversial whether adjuvant treatment could be recommended for hepatocellular carcinoma (HCC) after curative hepatectomy. Thus, we performed a network meta-analysis (NMA) to assess adjuvant treatment’s benefit and determine the optimal adjuvant regimen. Methods We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials comparing adjuvant therapy versus no active treatment after curative hepatectomy among patients with HCC. Pooled data on recurrence and overall survival (OS) were analyzed within pairwise meta-analysis and NMA. Results Twenty-three eligible trials (3,940 patients) reporting eight treatments were included. The direct meta-analysis showed that adjuvant therapy prevented the recurrence (OR = 0.65; 95% CI: 0.55, 0.77; P = 0.177; I2 = 21.7%) and contributed to OS (HR = 0.63; 95% CI: 0.54, 0.73; P = 0.087; I2 = 31.1%) in comparison to the observation. In the NMA, internal radiotherapy (IRT; OR = 0.55; 95% CI: 0.39, 0.77; SUCRA = 87.7%) followed by hepatic artery infusion chemotherapy (HAIC; OR = 0.6; 95% CI: 0.36, 0.97; SUCRA = 77.8%), and HAIC (HR = 0.44; 95% CI: 0.21, 0.87; SUCRA = 82.6%) followed by IRT (HR 0.54; 95% CI:0.36, 0.81; SUCRA = 69.7%) were ranked superior to other treatments in terms of preventing recurrence and providing survival benefit, respectively. Conclusions The addition of adjuvant therapy lowers the risk of recurrence and provide survival benefit after surgical resection for HCC. HAIC and IRT are likely to be the two most effective adjuvant regimens. Systematic Review Registration https://inplasy.com/inplasy-2020-11-0039/.
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Affiliation(s)
- Ying Liu
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuzhu Wang
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xinkun Guo
- Deparment of Hepatic Oncology, Zhongshan Hospital, Fudan University, Xiamen, China
| | - Yifeng He
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Jian Zhou
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Qianzhou Lv
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xiaowu Huang
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.,Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China
| | - Xiaoyu Li
- Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China
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Li S, Xu J, Zhang H, Hong J, Si Y, Yang T, He Y, Ng DM, Zheng D. The Role of Hepatic Arterial Infusion Chemotherapy in the Treatment of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Chemotherapy 2021; 66:124-133. [PMID: 34515082 DOI: 10.1159/000518257] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/03/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). METHODS The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). RESULTS A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37-0.61) and PFS (HR, 0.52; 95% CI: 0.36-0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27-0.88) and DFS (HR, 0.49; 95% CI: 0.31-0.68). CONCLUSION HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.
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Affiliation(s)
- Shengzhou Li
- Emergency Medical Center, Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| | - Jiaxuan Xu
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Hongya Zhang
- Thyroid and Breast Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| | - Jiaze Hong
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuexiu Si
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tong Yang
- Department of Tumor HIFU Therapy, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Yujing He
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | | | - Dingcheng Zheng
- Department of General Surgery, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
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4
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Zhang W, Zhang B, Chen XP. Adjuvant treatment strategy after curative resection for hepatocellular carcinoma. Front Med 2021; 15:155-169. [PMID: 33754281 DOI: 10.1007/s11684-021-0848-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 02/20/2021] [Indexed: 01/27/2023]
Abstract
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
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Affiliation(s)
- Wei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Bixiang Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Xiao-Ping Chen
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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5
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Moran A, Ramos LF, Picado O, Pendola F, Sleeman D, Dudeja V, Merchant N, Yakoub D. Hepatocellular carcinoma: resection with adjuvant hepatic artery infusion therapy vs resection alone. A systematic review and meta-analysis. J Surg Oncol 2018; 119:455-463. [PMID: 30575028 DOI: 10.1002/jso.25338] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 11/25/2018] [Indexed: 12/14/2022]
Abstract
Hepatocellular carcinoma (HCC) has a recurrence rate of up to 70% in 5 years after resection, detrimentally lowering survival. The role of adjuvant therapy remains controversial; therefore, the aim of this study was to evaluate the disease-free and overall survival of patients with HCC, not candidates for transplantation, undergoing resection and adjuvant hepatic artery infusion therapy vs resection alone. Our meta-analysis showed that adjuvant HAIC improves overall and disease-free survival after resection, especially in tumors ≥7 cm.
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Affiliation(s)
- Alexandra Moran
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Lorena Flor Ramos
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Omar Picado
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Fiorella Pendola
- Department of Medicine, Blake Medical Center, Bradenton, Florida
| | - Danny Sleeman
- Division of General Surgery, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Vikas Dudeja
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Nipun Merchant
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Danny Yakoub
- Division of Surgical Oncology, DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.,Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
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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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7
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Ogawa K, Kamimura K, Watanabe Y, Motai Y, Kumaki D, Seki R, Sakamaki A, Abe S, Kawai H, Suda T, Yamagiwa S, Terai S. Effect of double platinum agents, combination of miriplatin-transarterial oily chemoembolization and cisplatin-hepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases. World J Clin Cases 2017; 5:238-246. [PMID: 28685137 PMCID: PMC5480072 DOI: 10.12998/wjcc.v5.i6.238] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 03/30/2017] [Accepted: 04/18/2017] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers and the third highest cause of cancer-associated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization (TOCE), and hepatic arterial infusion chemotherapy (HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.
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Kamimura K, Suda T, Yokoo T, Kamimura H, Kanefuji T, Tsuchiya A, Takamura M, Kawai H, Waguri N, Yamagiwa S, Terai S. Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial. BMC Cancer 2017; 17:322. [PMID: 28490356 PMCID: PMC5425991 DOI: 10.1186/s12885-017-3320-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 05/03/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy. METHODS Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded. RESULTS The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE). CONCLUSIONS The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).
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Affiliation(s)
- Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Takeshi Suda
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, 949-7302 Niigata Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Tsutomu Kanefuji
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, 949-7302 Niigata Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Nobuo Waguri
- Department of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, 950−1197 Niigata Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510 Niigata Japan
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Kamimura K, Suda T, Yokoo T, Kamimura H, Kanefuji T, Tsuchiya A, Takamura M, Kawai H, Waguri N, Yamagiwa S, Terai S. Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial. BMC Cancer 2017. [PMID: 28490356 DOI: 10.1186/s12885-017-3320-7.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy. METHODS Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded. RESULTS The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE). CONCLUSIONS The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).
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Affiliation(s)
- Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Takeshi Suda
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, 949-7302, Niigata, Japan.
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Tsutomu Kanefuji
- Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata Medical and Dental Hospital, 4132 Urasa, Minami-Uonuma, 949-7302, Niigata, Japan
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Nobuo Waguri
- Department of Gastroenterology and Hepatology, Niigata City General Hospital, Niigata, 950-1197, Niigata, Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8510, Niigata, Japan
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10
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Shaohua L, Qiaoxuan W, Peng S, Qing L, Zhongyuan Y, Ming S, Wei W, Rongping G. Surgical Strategy for Hepatocellular Carcinoma Patients with Portal/Hepatic Vein Tumor Thrombosis. PLoS One 2015; 10:e0130021. [PMID: 26076461 PMCID: PMC4468137 DOI: 10.1371/journal.pone.0130021] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Accepted: 05/16/2015] [Indexed: 02/06/2023] Open
Abstract
Background Portal/hepatic vein tumor thrombosis (PVTT/HVTT) in hepatocellular carcinoma (HCC) is a sign of advanced stage disease and is associated with poor prognosis. This study investigated the surgical outcomes of patients with HCC and PVTT/HVTT to determine the most appropriate surgical treatment strategy for these patients. Materials and Methods The study population included 77 HCC patients from January 2004 to June 2009 who underwent hepatectomy in our department and were diagnosed with PVTT/HVTT based on pathological examination. The patients were divided into two groups: in group 1, PVTT/HVTT was located in the hepatic resection area and removed with the tumor en bloc (38 cases); in group 2, PVTT/HVTT was beyond the resection line and removed by suction or thrombectomy (39 cases). Concerning the factor of surgical margins, the patients were further divided into four subgroups: group 1A: patients in group 1 with surgical margins ≤1 cm (28 cases); group 1B: patients in group 1 with surgical margins >1 cm (9 cases); group 2A: patients in group 2 with surgical margins ≤1 cm (28 cases); and group 2B: patients in group 2 with surgical margins >1 cm (9 cases). Results Most of the characteristics of groups 1 and 2 were similar. Patients in group 2 had significantly higher median blood loss (p=0.002) and higher blood transfusion rate (p=0.002) during the operation, which were not considered prognostic factors (p=0.323 and 0.571, respectively). The median overall survival (OS) duration in group 1 was significantly longer than that in group 2 (14.3 vs. 10.4 months, p=0.047). The median OS durations in groups 1A, 1B, 2A, and 2B were 14.3, 42.7, 7.5, and 18.0 months, respectively, which were significantly different(p=0.018). Conclusions When PVTT/HVTT is located in the hepatic resection area and removed with the tumor en bloc, the median OS duration is longer. Based on this finding, widening the surgical margins when technically possible may increase OS.
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Affiliation(s)
- Li Shaohua
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Wang Qiaoxuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Radiation Oncology, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Sun Peng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Anesthesia, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Li Qing
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Ultrasound, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Yang Zhongyuan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- Department of Head and Neck Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Shi Ming
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
| | - Wei Wei
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- * E-mail: (WW); (GR)
| | - Guo Rongping
- Department of Hepatobiliary Surgery, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center of Sun Yat-Sen University, Guangzhou, China
- * E-mail: (WW); (GR)
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Chen J, Yang L, Chen H, Yuan T, Liu M, Chen P. Recombinant adenovirus encoding FAT10 small interfering RNA inhibits HCC growth in vitro and in vivo. Exp Mol Pathol 2014; 96:207-11. [DOI: 10.1016/j.yexmp.2014.01.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 01/03/2014] [Indexed: 02/06/2023]
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12
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Tang QH, Li AJ, Yang GM, Lai ECH, Zhou WP, Jiang ZH, Lau WY, Wu MC. Surgical resection versus conformal radiotherapy combined with TACE for resectable hepatocellular carcinoma with portal vein tumor thrombus: a comparative study. World J Surg 2014; 37:1362-70. [PMID: 23456227 DOI: 10.1007/s00268-013-1969-x] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The aim of this study was to compare the results of surgical resection with three-dimensional conformal radiotherapy (3D-CRT) in the treatment of resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Transarterial chemoembolization (TACE) was given to both groups of patients when possible. METHODS A retrospective study of 371 patients with resectable HCC with PVTT was conducted in two tertiary referral centers. The treatment of choice for these patients in one center was surgical resection. In the other center it was 3D-CRT. In the radiotherapy group (RG, n = 185), patients received 3D-CRT to the tumor and PVTT for a total radiation dose of 30-52 Gy (median 40 Gy). In the surgical group (SG, n = 186), patients underwent surgical resection. TACE was applied after surgery or 3D-CRT and then was repeated every 4-6 weeks if the patient tolerated the treatment. RESULTS The median survival was 12.3 months for RG and 10.0 months for SG. The 1-, 2-, and 3-year overall survivals were 51.6, 28.4, and 19.9 %, respectively, for RG and 40.1, 17.0, and 13.6 %, respectively, for SG (p = 0.029). Stepwise multivariate analysis showed that the extent of PVTT and mode of treatment were independent risk factors of overall survival. The most common cause of death after treatment was liver failure as a consequence of progressive intrahepatic disease. CONCLUSIONS 3D-CRT gave better survival than surgical resection for HCC with PVTT.
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Affiliation(s)
- Qing-he Tang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China
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Adjuvant hepatic arterial infusion chemotherapy after hepatic resection of hepatocellular carcinoma with macroscopic vascular invasion. World J Surg 2013; 37:1034-42. [PMID: 23435678 DOI: 10.1007/s00268-013-1957-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND The prognosis of hepatocellular carcinoma (HCC) with macroscopic vascular invasion is extremely poor even after hepatic resection. We aimed to clarify the efficacy of adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with vascular invasion. METHODS A total of 73 HCC patients with macroscopic vascular invasion were divided into two groups: 38 with hepatectomy with HAI (HAI group) and 35 with hepatectomy alone (non-HAI group). From 1997 to 2007, HAI was performed via an implanted injection port. The treatment comprised three courses of weekly infusion of HAI, which comprised cisplatin (10 mg daily on days 1-5) followed by 5-fluorouracil (5-FU; 250 mg daily on days 1-5) infusion. From 2007, cisplatin (60 mg/m(2)), 5-FU (600 mg/m(2)), and a mixture of mitomycin C (3 mg/m(2)) and degradable starch microspheres were administered for two courses. RESULTS Overall, 92 % of patients completed adjuvant HAI. In the HAI and non-HAI groups, the 5-year disease-free survival (DFS) rates were 33.1 % and 11.8 %, respectively (p = 0.029), and the 5-year overall survival (OS) rates were 46.7 % and 32.7 %, respectively (p = 0.318). Among the patients with Vp3/4 or Vv3 (n = 32) in the HAI group, the 3-year DFS and OS rates were 33.7 % and 56.8 %, respectively (p = 0.049). Those in the non-HAI group were 8.3 % and 12.0 %, respectively (p = 0.023). Cox proportional multivariate analysis for DFS revealed that HAI was an independent favorable prognostic factor in all 73 patients (hazard ratio 0.536; p = 0.029). CONCLUSIONS Adjuvant HAI for HCC patients with vascular invasion might reduce the risk of recurrence.
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Kamimura K, Suda T, Tamura Y, Takamura M, Yokoo T, Igarashi M, Kawai H, Yamagiwa S, Nomoto M, Aoyagi Y. Phase I study of miriplatin combined with transarterial chemotherapy using CDDP powder in patients with hepatocellular carcinoma. BMC Gastroenterol 2012; 12:127. [PMID: 22994941 PMCID: PMC3482551 DOI: 10.1186/1471-230x-12-127] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2012] [Accepted: 09/17/2012] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND There is no standard therapeutic procedure for the hepatocellular carcinoma (HCC) in patients with poor hepatic reserve function. With the approval of newly developed chemotherapeutic agent of miriplatin, we have firstly conducted the phase I study of CDDP powder (DDP-H) and miriplatin combination therapy and reported its safety and efficacy for treating unresectable HCC in such cases. To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for the combination of transarterial oily chemoembolization (TOCE) and transarterial chemotherapy (TAC) using miriplatin and DDP-H for treating unresectable hepatocellular carcinoma (HCC). METHODS Transarterial chemotherapy using DDP-H was performed through the proper hepatic artery targeting the HCC nodules by increasing the dose of DDP-H (35-65 mg/m(2)) followed by targeting the HCC nodules by transarterial oily chemoembolization with miriplatin. RESULTS A total of nine patients were enrolled in this study and no DLT was observed with any dose of DDP-H in all cases in whom 80 mg (median, 18-120) miriplatin was administered. An anti-tumour efficacy rating for partial response was obtained in one patient, while a total of four patients (among eight evaluated) showed stable disease response, leading to 62.5% of disease control rate. The pharmacokinetic results showed no further increase in plasma platinum concentration following miriplatin administration. CONCLUSION Our results suggest that a combination of DDP-H and miriplatin can be safely administered up to their respective MTD for treating HCC. TRIAL REGISTRATION This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003541).
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Affiliation(s)
- Kenya Kamimura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Suda
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yasushi Tamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Takeshi Yokoo
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Masato Igarashi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Minoru Nomoto
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
| | - Yutaka Aoyagi
- Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
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Chen JS, Wang Q, Chen XL, Huang XH, Liang LJ, Lei J, Huang JQ, Li DM, Cheng ZX. Clinicopathologic characteristics and surgical outcomes of hepatocellular carcinoma with portal vein tumor thrombosis. J Surg Res 2011; 175:243-50. [PMID: 21601221 DOI: 10.1016/j.jss.2011.03.072] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Revised: 02/20/2011] [Accepted: 03/28/2011] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) has a high predilection for portal vein invasion. Furthermore, the treatment of HCC with portal vein tumor thrombosis (PVTT) is controversial. The objective of this study was to investigate clinicopathologic characteristics and surgical outcomes of HCC patients with PVTT. METHODS The clinicopathologic data and surgical outcomes of 88 patients HCC with PVTT and 211 patients without PVTT who underwent surgery were retrospectively reviewed. The risk factors and the prognosis of HCC patients with PVTT were determined. RESULTS Cirrhosis, serum alkaline phosphatase (ALP) > 100 IU/L, tumor size > 8 cm, incomplete tumor capsule, and adjacent organ invasion were risk factors for PVTT in HCC on multivariate analysis. Furthermore, HCC patients with PVTT received more major hepatectomies, had more intraoperative blood loss and greater blood transfusion requirements, and higher incidence of postoperative mortality compared with HCC patients without PVTT. The median overall survival of HCC patients with PVTT after surgery was 9 mo, with the 1-, 2-, and 3-y overall survival rates of 31.1%, 18.3%, and 15.2 %, respectively. AFP level, adjacent organ invasion, and PVTT location predicted overall survival of HCC patients with PVTT. CONCLUSIONS High serum ALP level, cirrhosis, large tumor, incomplete tumor capsule and adjacent organ invasion are predictors of PVTT in HCC. Surgery is a valid therapy for selected HCC patients with PVTT.
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Affiliation(s)
- Jing-Song Chen
- Department of General Surgery, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China
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Ueda S, Shirabe K, Morita K, Umeda K, Kayashima H, Uchiyama H, Soejima Y, Taketomi A, Maehara Y. Evaluation of ERCC1 Expression for Cisplatin Sensitivity in Human Hepatocellular Carcinoma. Ann Surg Oncol 2010; 18:1204-11. [DOI: 10.1245/s10434-010-1414-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Indexed: 12/24/2022]
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Shi J, Lai ECH, Li N, Guo WX, Xue J, Lau WY, Wu MC, Cheng SQ. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus. Ann Surg Oncol 2010; 17:2073-80. [PMID: 20131013 DOI: 10.1245/s10434-010-0940-4] [Citation(s) in RCA: 216] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND The role of liver resection in patients with hepatocellular carcinoma (HCC) accompanying with portal vein tumor thrombus (PVTT) remains controversial. This article aimed to evaluate the significance of different location and extent of PVTT on surgical outcomes after liver resection for HCC. MATERIALS AND METHODS A retrospective study was carried out on patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with PVTT in a single tertiary center from January 2001 to December 2003. According to the extent, PVTT was divided into 4 types (I-segmental/sectoral branches of portal vein, II-left and/or right portal vein, III-main portal vein trunk, and IV-superior mesenteric vein). RESULTS A total of 406 patients with HCC and PVTT who underwent partial hepatectomy were studied. The complication rate and hospital mortality rate were 32.8 and 0.2%, respectively. After a median follow-up of 6.4 months, 128 patients (31.5%) died. The 1- and 3-year overall survival rates were 34.4 and 13.0%, respectively. The 1- and 3-year disease-free survival rates were 13.3 and 4.7%, respectively. Patients with PVTT located in the segmental, sectoral, or right and/or left portal veins (types I and II) showed significantly better survival than those with PVTT extended to the main trunk of the portal vein or the superior mesenteric vein (types III and IV). CONCLUSIONS Liver resection is justified in selected patients with PVTT located in the segmental or sectoral branches of the portal vein. However, surgical resection for PVTT involving the portal bifurcation or the main trunk is still controversial.
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Affiliation(s)
- Jie Shi
- Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China
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Zhang XB, Wang JH, Yan ZP, Qian S, Du SS, Zeng ZC. Hepatocellular carcinoma with main portal vein tumor thrombus: treatment with 3-dimensional conformal radiotherapy after portal vein stenting and transarterial chemoembolization. Cancer 2009; 115:1245-52. [PMID: 19156918 DOI: 10.1002/cncr.24139] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (MPVTT) is often associated with poor prognosis. We retrospectively assessed the effectiveness of percutaneous transhepatic portal vein stenting and transarterial chemoembolization (PTPVS-TACE) combined with or without 3-dimensional conformal radiotherapy (3-DCRT) for HCC with MPVTT. METHODS Forty-five patients with HCC complicated by MPVTT were treated with PTPVS-TACE. Among them, 16 patients (group A) received 3-DCRT with 30-60Gy as daily 2Gy fractions. The remaining 29 patients (group B) received no radiotherapy. The tumor responses, complications, stent patency rates, and cumulative survival rates were evaluated, and the Kaplan-Meier method and log-rank test were used for survival analysis. RESULTS No severe complications were associated with PTPVS-TACE and 3-DCRT. The objective response rate (CR and PR) was 35.6%. The 60-, 180-, and 360-day cumulative stent patency rates were 93.3%, 62.2%, and 34.6% in group A, and 58.6%, 21.7%, and 10.8% in group B, respectively, showing significant difference between the 2 groups (P<.01). The mean patency time was 475.20+/-136.97 and 199.58+/-61.40 days, respectively. The 60-, 180-, and 360-day cumulative survival rates were 93.8%, 81.3%, and 32.5%, respectively, for group A, 86.2%, 13.8%, and 6.9%, respectively, for group B. Significant statistical differences were detected between the 2 groups (P<.01). CONCLUSIONS These findings suggest that sequential therapy by PTPVS-TACE-3-DCRT is possibly an effective treatment modality for HCC complicated by main portal vein tumor thrombus.
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Affiliation(s)
- Xue-Bin Zhang
- Department of Radiology, Zhong Shan Hospital, Fudan University, Fenglin Road, Shanghai, China
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Masuda T, Beppu T, Ishiko T, Horino K, Baba Y, Mizumoto T, Hayashi H, Okabe H, Horlad H, Doi K, Okabe K, Takamori H, Hirota M, Iyama KI, Baba H. Intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy. ACTA ACUST UNITED AC 2008; 15:589-95. [PMID: 18987928 DOI: 10.1007/s00534-007-1288-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2007] [Accepted: 11/02/2007] [Indexed: 02/07/2023]
Abstract
BACKGROUND/PURPOSE We aimed to clarify the histological features of and risk factors for intrahepatic dissemination after local ablation therapy (LAT) for hepatocellular carcinoma (HCC). METHODS Between April 1992 and December 2005, 192 HCC patients underwent hepatic resection at our department, among whom were 17 patients who had local recurrences after LAT. Eight of these 17 patients had intrahepatic dissemination. The clinical and histological characteristics of these 8 surgically treated patients with intrahepatic dissemination were investigated. RESULTS Histologically, numerous intrahepatic metastases were observed, mainly in the same section as the treated tumor, together with main or sectional portal vein tumor thrombi. Before the ablation therapy, the average tumor diameter was 2.1 cm, and 62.5% of the tumors were adjacent to the main or sectional portal vein. In terms of therapeutic factors, 25% of the patients had a prior needle biopsy and 62.5% had insufficient safety margins. CONCLUSIONS LAT for HCCs (even those less than 3 cm in diameter) adjacent less than 5 mm to the main or sectional portal vein possibly promotes intrahepatic dissemination.
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Affiliation(s)
- Toshiro Masuda
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan
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Hepatocellular carcinoma invading the main portal vein: treatment with transcatheter arterial chemoembolization and portal vein stenting. Cardiovasc Intervent Radiol 2008; 32:52-61. [PMID: 18931871 DOI: 10.1007/s00270-008-9454-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2008] [Revised: 08/28/2008] [Accepted: 09/19/2008] [Indexed: 12/20/2022]
Abstract
To retrospectively analyze the therapeutic results of percutaneous transhepatic portal vein stenting (PTPVS) and transcatheter arterial chemoembolization (TACE) treatment in 58 patients with hepatocellular carcinoma (HCC) invading the main portal vein (MPV). A total of 58 procedures of PTPVS were performed, immediately after which TACE was undertaken to control HCC. The clinical effects, complications, digital subtraction angiographic appearance, stent patency rates, cumulative survival rates, and predictive factors for survival were evaluated. The Kaplan-Meyer method and the log rank test were used for survival analysis. Multivariable analysis was also conducted by the Cox proportional hazard model. No patient died during stent placement or within the first 24 h. No severe procedure-related complications were observed. After stent placement, the mean +/- standard deviation portal venous pressure levels decreased from 41.43 +/- 8.56 cmH(2)O to 37.19 +/- 7.89 cmH(2)O (p < 0.01). At the time of analysis, 9 of the 58 patients survived. The 60-, 180-, 360-, and 720-day cumulative patency rates were 98.1%, 71.0%, 52.6%, and 42.1%, respectively, with a mean patency time of 552.9 +/- 88.2 days and a median patency time of 639.00 +/- 310.00 (95% confidence interval [95% CI], 31.40-1246.60) days. The 60-, 180-, 360-, and 720-day cumulative survival rates for the total study population were 74.1%, 27.1%, 17.2%, and 13.8%, respectively, with a median survival time of 113 +/- 27.29 (95% CI, 59.51-166.49) days. In the univariate analysis, the following six variables were significantly associated with the prognosis: (1) HCC type; (2) Child-Pugh grade; (3) MPV stenosis/occlusion; (4) arteriovenous shunt; (5) iodized oil deposition; and (6) number of TACE procedure. In addition, having diffuse-type HCC and Child-Pugh grade B disease were each independent factors associated with decreased survival time in the multivariate analysis. PTPVS-TACE is feasible and may be useful to control HCC invading the MPV.
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Liang LJ, Hu WJ, Yin XY, Zhou Q, Peng BG, Li DM, Lu MD. Adjuvant intraportal venous chemotherapy for patients with hepatocellular carcinoma and portal vein tumor thrombi following hepatectomy plus portal thrombectomy. World J Surg 2008; 32:627-31. [PMID: 18228094 DOI: 10.1007/s00268-007-9364-0] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the clinical value of adjuvant chemobiotherapy via portal vein for patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT) following hepatectomy plus thrombectomy. METHODS Eighty-six HCC patients with tumor thrombi in the portal trunk and/or the first-order branch were divided into groups A (n = 33) and B (n = 53). Patients in group A were treated with hepatectomy plus portal thrombectomy in combination with postoperative adjuvant chemobiotherapy administered via portal vein. The chemobiotherapy regimen consisted of 5-FU, adriamycin, cisplatin, and IFNalpha. Patients in Group B were subjected to hepatectomy plus thrombectomy alone. Survival rates of the two groups were compared and prognostic factors were identified using Cox proportional hazards model. RESULTS Group A had a significantly longer median tumor-free survival time and median survival time compared with group B, i.e., 5.1 vs. 2.5 months (p = 0.017) and 11.5 vs. 6.2 months (p = 0.007), respectively. One-, two-, and three-year tumor-free survival rates were remarkably higher in group A than in group B, i.e., 18.4% vs. 8.4%, 13.8% vs. 4.2%, and 9.2% vs. 4.2%, respectively. One-, two-, and three-year survival rates were markedly greater in group A than in group B, i.e., 46.8% vs. 23.4%, 14.4% vs. 5.8%, and 9.6% vs. 5.8%, respectively. Multivariate analysis using the Cox proportional hazards model revealed that adjuvant chemobiotherapy, pathologic grading, and tumor size were independent prognostic factors for survival time (p = 0.000, 0.001, and 0.013, respectively), and chemobiotherapy and pathologic grading were independent prognostic factors for tumor-free survival time (p = 0.002 and 0.003, respectively). CONCLUSIONS Surgical resection combined with adjuvant chemobiotherapy via portal vein is an effective and safe treatment modality for hepatocellular carcinoma with major portal vein thrombus.
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Affiliation(s)
- Li-Jian Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
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