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Lu H, Liang B, Zheng C, Xia X. Comparative analysis of efficacy and safety between D-TACE + HAIC + lenvatinib and D-TACE + lenvatinib in the treatment of unresectable massive hepatocellular carcinoma. BMC Cancer 2024; 24:1422. [PMID: 39558198 PMCID: PMC11575434 DOI: 10.1186/s12885-024-13179-5] [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: 10/12/2023] [Accepted: 11/11/2024] [Indexed: 11/20/2024] Open
Abstract
OBJECTIVE The aim of this study was to investigate the efficacy and safety of the combined treatment regimen of D-TACE, HAIC, and Lenvatinib in patients with massive hepatocellular carcinoma, with the goal of providing a safer and more effective therapeutic strategy for individuals suffering from massive hepatocellular carcinoma. MATERIALS AND METHODS A retrospective analysis was conducted using clinical data from 118 patients with unresectable massive hepatocellular carcinoma who underwent treatment at the Interventional Department of Wuhan Union Hospital between June 2018 and December 2021. Based on the treatment approach, the patients were divided into two groups: the D-TACE + HAIC + Lenvatinib group (N = 54) and the D-TACE + Lenvatinib group (N = 64). The primary study endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups. Additionally, the occurrence of treatment-related adverse events in both groups was considered as a secondary study endpoint. RESULTS Following the treatment, the D-TACE + HAIC + Lenvatinib group exhibited significantly higher ORR and DCR compared to the D-TACE + Lenvatinib group (68.5% vs. 43.8%, 90.7% vs. 73.4%, P < 0.05). Moreover, the D-TACE + HAIC + Lenvatinib group demonstrated longer mPFS and mOS in comparison to the D-TACE + Lenvatinib group (8.6 months vs. 6.6 months, P = 0.005; 19.5 months vs. 14.1 months, P < 0.001). There was no statistically significant difference in the occurrence rate of common treatment-related adverse events between the TACE + HAIC + Lenvatinib group and the D-TACE + Lenvatinib group (P > 0.05). CONCLUSION The combined treatment regimen of D-TACE, HAIC, and Lenvatinib demonstrated superior therapeutic efficacy and safety in managing unresectable massive hepatocellular carcinoma. This combination therapy may serve as a viable option for improving the prognosis of patients with unresectable massive hepatocellular carcinoma.
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
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Lu H, Liang B, Xia X, Zheng C. Predictors and risk factors of bile duct injury after transcatheter arterial chemoembolization for hepatocellular carcinoma. BMC Cancer 2024; 24:1085. [PMID: 39223485 PMCID: PMC11367810 DOI: 10.1186/s12885-024-12864-9] [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: 01/20/2024] [Accepted: 08/27/2024] [Indexed: 09/04/2024] Open
Abstract
PURPOSE Bile duct injury is a serious complication after transcatheter arterial chemoembolization (TACE). If it is not detected early and treated actively, it will not only affect the subsequent tumor-related treatment of hepatocellular carcinoma (HCC) patients, but also may lead to serious consequences such as infection, liver failure and even death. To analyze the risk factors of bile duct injury after TACE in patients with HCC and explore the predictive indicators of bile duct injury after TACE, which is helpful for doctors to detect and intervene early and avoid the occurrence of serious complications. METHOD We retrospectively analyzed the clinical data of 847 patients with primary hepatocellular carcinoma who underwent TACE for the first time in our interventional department. Patients were divided into two groups according to whether bile duct injury occurred after TACE: (1) bile duct injury group, N = 55; (2) no bile duct injury group, N = 792. The basic data, intraoperative conditions and the outcome of bile duct injury were analyzed. The chi-square test was used for comparison of enumeration data. The Mann-Whitney U test was used for comparison of measurement data. Risk factor analysis was performed using binary logistic regression analysis. RESULTS Basic data and intraoperative conditions were compared between the bile duct injury group and the group without bile duct injury: preoperative alkaline phosphatase (ALP) (103.24 ± 32.77U/L vs. 89.17 ± 37.35U/L, P = 0.003); history of hepatobiliary surgery (36.4% vs. 20.8%, P = 0.011); intraoperative lipiodol volume (P = 0.007); combined use of gelatin sponge particles (65.5% vs. 35.0%, P < 0.001); hypovascularity (58.2% vs. 24.5%, P < 0.001); and embolization site (P < 0.001). Comparison of postoperative liver function between bile duct injury group and non-bile duct injury group: postoperative total bilirubin (43.34 ± 25.18umol/L vs. 21.94 ± 9.82umol/L, P < 0.001); postoperative γ-glutamyltransferase(GGT) (188.09 ± 55.62U/L vs. 84.04 ± 36.47U/L, P < 0.001); postoperative ALP(251.51 ± 61.51U/L vs. 99.92 ± 45.98U/L, P < 0.001). CONCLUSION The dosage of lipiodol in TACE, supplementation of gelatin sponge particles, embolization site, and hypovascularity of the tumor are risk factors for biliary duct injury after TACE. After TACE, GGT and ALP increased ≥ 2 times compared with preoperative indicators as predictors of bile duct injury. Bile duct injury occurring after TACE can achieve good outcomes with aggressive management.
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
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Lu H, Liang B, Xia X, Zheng C. Efficacy and safety analysis of TACE + Donafenib + Toripalimab versus TACE + Sorafenib in the treatment of unresectable hepatocellular carcinoma: a retrospective study. BMC Cancer 2023; 23:1033. [PMID: 37880661 PMCID: PMC10599044 DOI: 10.1186/s12885-023-11535-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 10/16/2023] [Indexed: 10/27/2023] Open
Abstract
OBJECTIVE To compare the efficacy and safety of TACE combined with Donafenib and Toripalimab versus TACE combined with Sorafenib in the treatment of unresectable hepatocellular carcinoma (HCC), aiming to guide personalized treatment strategies for HCC and improve patient prognosis. MATERIALS AND METHODS A retrospective analysis was conducted on the clinical data of 169 patients with unresectable advanced-stage HCC who underwent treatment at the Interventional Department of Wuhan Union Hospital from January 2020 to December 2022. Based on the patients' treatment strategies, they were divided into two groups: TACE + Donafenib + Toripalimab group (N = 81) and TACE + Sorafenib group (N = 88). The primary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) of the two groups' tumors. The secondary endpoint was the occurrence of treatment-related adverse events in the two groups of patients. RESULTS The TACE + Donafenib + Toripalimab group showed higher ORR and DCR compared to the TACE + Sorafenib group (66.7% vs. 38.6%, 82.6% vs. 68.2%, P < 0.05). The TACE + Donafenib + Toripalimab group also demonstrated longer median progression-free survival (mPFS) (10.9 months vs. 7.0 months, P < 0.001) and median overall survival (mOS) (19.6 months vs. 10.9 months, P < 0.001) compared to the TACE + Sorafenib group. When comparing the two groups, the TACE + Sorafenib group had a higher incidence of grade 3-4 hypertension (14.8% vs. 4.9%, P = 0.041), higher incidence of diarrhea (all grades) (18.2% vs. 7.4%, P = 0.042), and higher incidence of hand-foot syndrome (all grades) (26.1% vs. 12.3%, P = 0.032). CONCLUSION TACE combined with Donafenib and Toripalimab demonstrates superior efficacy and safety in treating unresectable HCC patients. This combination therapy may serve as a feasible option to improve the prognosis of unresectable HCC patients.
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Affiliation(s)
- Haohao Lu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Bin Liang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Xiangwen Xia
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue #1277, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, 430022, China.
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Jiang G, Ling S, Zhan Q, Zhuang L, Xu X. Downstaging treatment for patients with hepatocelluar carcinoma before transplantation. Transplant Rev (Orlando) 2021; 35:100606. [PMID: 33636480 DOI: 10.1016/j.trre.2021.100606] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 12/13/2022]
Abstract
Liver transplantation (LT), one of the radical methods of treating liver cancer, has brought new hope for the treatment of unresectable liver cancer. Currently, patients who meet transplant criteria can achieve a favorable prognosis, but those who exceed transplant criteria tend not to have very satisfactory outcomes. For patients whose tumor burden exceeds the transplant criteria, downstaging treatment is a promising method to reduce tumor burden to within the transplant criteria that may lead to good posttransplant survival. Multiple treatments, such as transcatheter arterial chemoembolization (TACE), transarterial radioembolization (TARE), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA), have been used as downstaging treatments. However, there are still some issues that limit the effectiveness of downstaging treatments, such as the inclusion criteria for downstaging, which the choice of downstaging treatment method, and the endpoint of downstaging, all of which are worthy of further discussion. Based on the published literature, this review discusses these issues.
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Affiliation(s)
- Guangjiang Jiang
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Sunbin Ling
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Qifan Zhan
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
| | - Li Zhuang
- Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University Shulan International Medical College, Hangzhou 310003, China.
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China.
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Kong JY, Li SM, Fan HY, Zhang L, Zhao HJ, Li SM. Transarterial chemoembolization extends long-term survival in patients with unresectable hepatocellular carcinoma. Medicine (Baltimore) 2018; 97:e11872. [PMID: 30113483 PMCID: PMC6112993 DOI: 10.1097/md.0000000000011872] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The long-term survival benefit of treating unresectable hepatocellular carcinoma (HCC) patients with transarterial chemoembolization (TACE) rather than conservative treatment remains controversial. This retrospective case-control study evaluated the survival of patients with unresectable HCC treated with TACE, relative to that of patients who received best supportive care.From January 2002 to December 2010, 522 of 2386 consecutive patients with unresectable HCC were enrolled. Patients were treated with TACE (n = 347) or best supportive care (non-TACE; n = 175). A survival analysis compared the survival of the 2 groups, as well as only those at Barcelona Clinic Liver Cancer Classification (BCLC)-C and Child-Pugh-B (39 TACE, 61 non-TACE).The median follow-up was 5 months (0.15-106 months).The overall median survival of the TACE group (8.0 months) was significantly longer than that of the non-TACE (2.0 months; P ≤ .01). Of the patients at BCLC-C and Child-Pugh-B, the overall median survivals of the TACE and non-TACE patients were 6.0 and 2.0 months, respectively (P ≤ .01); and the 1, 2, 3, 5, and 8-year overall survival rates were significantly superior in the TACE group (P ≤ .01). For all the patients, the independent predictors of survival were treatment modalities, portal vein tumor thrombosis, alpha-fetoprotein, and BCLC stage. Regarding the TACE patients, contributors to prognosis were portal vein tumor thrombosis, alpha-fetoprotein level, and the number of TACE procedures.TACE for unresectable HCC was associated with longer survival compared with best supportive care, especially for patients at BCLC-C and Child-Pugh-B.
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Affiliation(s)
| | | | - Hai-Yan Fan
- Department of Gastroenterology and Hepatology, Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Lan Zhang
- Department of Gastroenterology and Hepatology, Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Hui-Jin Zhao
- Department of Gastroenterology and Hepatology, Hebei Medical University, Shijiazhuang, Hebei Province, China
| | - Sheng-Mian Li
- Department of Gastroenterology and Hepatology, Hebei Medical University, Shijiazhuang, Hebei Province, China
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Chen CS, Li FK, Guo CY, Xiao JC, Hu HT, Cheng HT, Zheng L, Zong DW, Ma JL, Jiang L, Li HL. Tumor vascularity and lipiodol deposition as early radiological markers for predicting risk of disease progression in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization. Oncotarget 2016; 7:7241-52. [PMID: 26769845 PMCID: PMC4872782 DOI: 10.18632/oncotarget.6892] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Accepted: 12/04/2015] [Indexed: 12/15/2022] Open
Abstract
This study evaluated the factors impacting overall survival (OS) and time to progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). HCC patients were grouped based on tumor vascularity and lipidiol deposition after TACE. Tumor vascularity was classified based on contrast enhancement on arterial phase baseline CT scans. Lipiodol deposition was evaluated using CT scans. The progression-free rate was significantly higher in patients with good blood supply + good lipiodol deposition compared to those with good blood supply + poor lipiodol deposition. In patients with poor lipidiol deposition, risk of death was significantly positively correlated with stage, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Risk of disease progression in these patients was positively correlated with tumor size, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Our data showed that tumor vascularity and lipiodol deposition can be used as early radiological markers to identify patients who do not respond to TACE, and who can be considered earlier for alternative combination treatment strategies. Our data also indicated that poor lipiodol retention may predict a poor TTP and OS despite the blood supply status.
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Affiliation(s)
- Cheng-Shi Chen
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Fang-Kun Li
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Chen-Yang Guo
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Jin-Cheng Xiao
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Hong-Tao Hu
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Hong-Tao Cheng
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Lin Zheng
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Deng-Wei Zong
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Jun-Li Ma
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Li Jiang
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
| | - Hai-Liang Li
- Department of Radiology, Zhengzhou University Affiliated Cancer Hospital, Zhengzhou 450008, China
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7
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Lee JH, Park KM, Lee YJ, Kim JH, Kim SH. A New Chemical Compound, NecroX-7, Acts as a Necrosis Modulator by Inhibiting High-Mobility Group Box 1 Protein Release During Massive Ischemia-Reperfusion Injury. Transplant Proc 2016; 48:3406-3414. [PMID: 27931589 DOI: 10.1016/j.transproceed.2016.09.046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 08/21/2016] [Accepted: 09/14/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND Necrotic cell death is common in a wide variety of pathologic conditions, including ischemia-reperfusion (IR) injury. The aim of this study was to develop an IR injury-induced hepatic necrosis model in dogs by means of selective left hepatic inflow occlusion and to test the efficacy of a new chemical compound, NecroX-7, against the IR injury-induced hepatic damage. METHODS A group of male Beagle dogs received intravenous infusions of either vehicle or different doses of NecroX-7 (1.5, 4.5, or 13 mg/kg) for a 20-minute period before a 90-minute left hepatic inflow occlusion followed by reperfusion. RESULTS The gross morphology in the NecroX-7-treated groups after occlusion appeared to be less congested and less swollen than that in vehicle-treated control group. Circulating alanine transaminase and aspartate transaminase levels in the control group were elevated during the course of IR, and were effectively blocked in the 4.5 and 13 mg/kg NecroX-7-treated groups. The serum levels of high-mobility group box 1 protein showed a peak at 8 hours after occlusion in control group, and this elevation was significantly blunted by 4.5 mg/kg NecroX-7 treatment. Histologic analysis showed a marked ischemia or IR injury-induced hepatocytic degenerations, sinusoidal and portal vein congestions, and inflammatory cell infiltrations in the control group, whereas the treatment groups showed significantly diminished histopathology in a dose-dependent manner. CONCLUSIONS These results demonstrated that NecroX-7 attenuated the hepatocyte lethality caused by hepatic IR injury in a large animal setting. We conclude that NecroX-7 may provide a wide variety of therapeutic options for IR injury in human patients.
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Affiliation(s)
- J H Lee
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea
| | - K M Park
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea.
| | - Y J Lee
- Department of Hepatobiliary and Pancreatic Surgery, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea
| | - J H Kim
- Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea
| | - S H Kim
- LG Life Sciences, Daejeon, Korea
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She WH, Cheung TT. Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation. Transl Gastroenterol Hepatol 2016; 1:34. [PMID: 28138601 DOI: 10.21037/tgh.2016.03.04] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 01/04/2016] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common primary malignancy worldwide especially in the patients with the background of chronic liver disease. Liver transplantation (LT) is the only curative treatment effective for both malignancy as well as the cirrhosis and portal hypertension. Unfortunately, living donor is not always possible and the deceased graft is scarce. Neoadjuvant therapies, therefore, have been developed as a downstaging treatment to try to downstage the tumor within the transplant criteria, or as a bridging therapy to control the tumor growth in patients while waiting in the transplant list. This paper reviewed the common modalities used as bridging and downstaging therapies for patients suffering from HCC before undergoing LT.
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Affiliation(s)
- Wong Hoi She
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - Tan To Cheung
- Division of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Department of Surgery, the University of Hong Kong, Queen Mary Hospital, Hong Kong
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Firouznia K, Ghanaati H, Alavian SM, Azadeh P, Nasiri Toosi M, Haj Mirzaian A, Najafi S, Shakiba M, Jalali AH. Transcatheter arterial chemoembolization therapy for patients with unresectable hepatocellular carcinoma. HEPATITIS MONTHLY 2014; 14:e25792. [PMID: 25737732 PMCID: PMC4329238 DOI: 10.5812/hepatmon.25792] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 12/17/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Although transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC), its actual efficacy and prognostic usefulness have not been clarified in past studies. OBJECTIVES The aim of the study is to investigate the efficacy, complications, and prognostic factors of the TACE in unresectable HCC patients. PATIENTS AND METHODS Thirty-two patients with unresectable HCC were treated with TACE. The procedure was performed with a combination of Lipiodol, doxorubicin, and cytomycin followed by gelatin-sponge particles embolization. CT-scan imaging and liver function tests (AST, ALT, ALP, BIL, and PT) were performed before and after the TACE. All patients were followed-up for 6-months. RESULTS Of all patients, 1 and 11 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, CR+PR, 44%). Data have shown that tumor size, number of lesions and number of involved segments are significantly reduced after the TACE performance (P < 0.05). No significant clinical adverse effect was observed in patients after the intervention. Also, liver function tests including AST, ALT, ALP, BIL, and PT did not significantly differ before and after the intervention (P > 0.05). The 6-month cumulative survival rates of the 32 patients were 78.1 %, respectively. Univariate analysis showed that survival correlated significantly with the following factors: tumor size; ≥ 8 cm versus < 8 cm (P < 0.010), serum ALP level; < 300 versus ≥ 300 (P < 0.043), and number of liver involved segments; < 2 versus ≥ 2 (P < 0.020). CONCLUSIONS We showed that in treatment of patients with unresectable hepatocellular carcinoma, TACE significantly improved the disease and the overall survival rate. Also, we introduce the tumor size, serum ALP level, and number of liver involved segments as prognostic factors of the procedure. Finally, TACE can be recommended as the initial treatment for unresectable HCC patients.
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Affiliation(s)
- Kavous Firouznia
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Hossein Ghanaati
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
- Corresponding Author: Hossein Ghanaati, Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran. Tel: +98-2166581516, Fax: +98-2166581578, E-mail:
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
| | - Payam Azadeh
- Department of Radiation Oncology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Mohsen Nasiri Toosi
- Internal Medicine Department, Imam-Khomeini Hospital, Tehran University of Medical Sciences (TUMS), Tehran, IR Iran
| | - Arya Haj Mirzaian
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Safa Najafi
- Tehran University of Medical Sciences, Tehran, IR Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
| | - Amir Hossein Jalali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, IR Iran
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Chok KSH, Cheung TT, Lo RCL, Chu FSK, Tsang SHY, Chan ACY, Sharr WW, Fung JYY, Dai WC, Chan SC, Fan ST, Lo CM. Pilot study of high-intensity focused ultrasound ablation as a bridging therapy for hepatocellular carcinoma patients wait-listed for liver transplantation. Liver Transpl 2014; 20:912-921. [PMID: 24753206 DOI: 10.1002/lt.23892] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2013] [Accepted: 04/09/2014] [Indexed: 12/18/2022]
Abstract
The objective of this study was to investigate the outcomes of high-intensity focused ultrasound (HIFU) ablation as a bridging therapy for patients with hepatocellular carcinoma (HCC) who had been wait-listed for deceased donor liver transplantation (DDLT). Adult patients with unresectable and unablatable HCCs within the University of California San Francisco criteria who had been wait-listed for DDLT were screened for their suitability for HIFU ablation as a bridging therapy if they were not suitable for transarterial chemoembolization (TACE). Treatment outcomes for patients receiving HIFU ablation, TACE, and best medical treatment (BMT) were compared. Fifty-one patients were included in the analysis. Before the introduction of HIFU ablation, only 39.2% of the patients had received bridging therapy (TACE only, n = 20). With HIFU ablation in use, the rate increased dramatically to 80.4% (TACE + HIFU, n = 41). The overall dropout rate was 51% (n = 26). Patients in the BMT group had a significantly higher dropout rate (P = 0.03) and significantly poorer liver function as reflected by higher Model for End-Stage Liver Disease scores and higher Child-Pugh grading. Clinically relevant ascites was found in 5 patients in the HIFU group and 2 patients in the BMT group, but none was found in the TACE group (P = 0.01 and P = 0.03, respectively). The TACE and HIFU groups had comparable percentages of tumor necrosis in excised livers (P = 0.35), and both were significantly higher than that in the BMT group (P = 0.01 and P = 0.02, respectively). In conclusion, HIFU ablation was safe even for HCC patients with Child-Pugh C disease. Its adoption increased the percentage of patients receiving bridging therapy from 39.2% to 80.4%. A randomized controlled trial for further validation of its efficacy is warranted.
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Affiliation(s)
- Kenneth S H Chok
- Department of Surgery, University of Hong Kong, Hong Kong SAR, China
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Kawashita Y, Deb NJ, Garg MK, Kabarriti R, Fan Z, Alfieri AA, Roy-Chowdhury J, Guha C. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model. Radiat Res 2014; 182:201-10. [PMID: 24992166 DOI: 10.1667/rr13617.1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and natural killer cells. The addition of Adeno-CD40L further improved the median survival of animals to 80 ± 15 days and this effect was abolished only when using anti-CD8 antibodies. Chromium-51 (51Cr) release assay showed cytotoxic T lymphocyte (CTL) activation, suggesting efficient dendritic cell (DC) activation with CTL activation after the treatment. Furthermore, when surviving mice were rechallenged with BNL-ETK cells on the foot pad, RT + HSV-TK/GCV + Flt3L + CD40L-treated mice developed a small tumor on day 56 but the tumor eventually disappeared after 105 days. Mice treated with RT + HSV-TK/GCV + Flt3L showed a slowed tumor growth curve compared with untreated mice. Therefore, combination therapy using Flt3L to induce DC proliferation and CD40L to enhance DC maturation holds great promise for immunomodulation of radiation therapy to enhance HCC tumor control and prevent progression of disease in patients with diffuse HCC.
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Affiliation(s)
- Yujo Kawashita
- a Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York; and
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Kawashita Y, Deb NJ, Garg M, Kabarriti R, Alfieri A, Takahashi M, Roy-Chowdhury J, Guha C. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 1. Flt3 ligand gene transfer increases antitumor effects of a radio-inducible suicide gene therapy in an ectopic tumor model. Radiat Res 2014; 182:191-200. [PMID: 24972258 DOI: 10.1667/rr13594.1] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Hepatocellular carcinoma (HCC) often presents as a diffuse or multifocal tumor making it difficult to control by surgery or radiation. Radio-inducible herpes simplex virus thymidine kinase (HSV-TK) gene therapy has been shown to enhance local tumor control after radiation therapy (RT), while limiting the expression of the transgene in the irradiated tumor tissues. To prevent liver tumor recurrence and control systemic disease while limiting the potential bystander toxicity of HSV-TK therapy, we proposed to stimulate endogenous dendritic cell (DC) proliferation with systemic adenovirus Flt3 ligand (Adeno-Flt3L) gene therapy, followed by primary tumor radiation therapy combined with a radio-inducible HSV-TK gene therapy. We hypothesized that adenovirus-expressing Flt3L gene therapy will stimulate DC proliferation, allowing the upregulated DCs to locally harness tumor antigens released from HSV-TK/RT-treated HCC cells, thereby converting irradiated tumors to an autologous in situ tumor vaccine in mice with primary liver tumors. To test this hypothesis, an expression vector of HSV-TK was constructed under the control of a radio-inducible promoter early-growth response (Egr-TK) and a recombinant adenovirus-expressing human Flt3L was constructed. The Adeno-Flt3L [10(9) plaque forming units (pfu)] was administered intravenously on days 1 and 8 after radiation therapy. The murine hepatoma cell line (BNL1ME) was stably transfected by Egr-TK or Egr-Null (encoding no therapeutic gene). Palpable tumors in BALB/c mice were treated with a localized dose of 25 Gy of radiation followed by ganciclovir (GCV, 100 mg/kg, 14 days). Four treatment cohorts were compared: Egr-Null/GCV + RT + Adeno-LacZ; Egr-Null/GCV + RT + Adeno-Flt3L; Egr-TK/GCV + RT + Adeno-LacZ; and Egr-TK/GCV + RT + Adeno-Flt3L. There was no primary tumor regression in the Egr-Null tumors after radiation therapy alone. In contrast, Egr-TK tumors had nearly complete tumor regression for 3 weeks after radiation therapy (P < 0.01), however, long-term follow-up demonstrated primary tumor recurrence and death secondary to pulmonary metastasis. Flt3L expression was confirmed by serum bioassay (mean = 88 ng/mL) in these animals and Western blotting of tissue culture medium in Adeno-Flt3L-infected BaF/huFlt3L cells. Radiation therapy with Adeno-Flt3L gene therapy effectively retarded primary tumor growth when compared to radiation therapy alone. The trimodality therapy (Egr-TK/GCV + RT + Adeno-Flt3L) was the most efficacious with 40% complete tumor regression (>100 days) and <20% pulmonary metastases, indicating the development of sustained antitumor immune response. These studies provide a rationale for triple modality therapies with radiation-inducible HSV-TK gene therapy and Adeno-Flt3L when used in combination with primary tumor radiation therapy for improved local and systemic control of HCC.
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Affiliation(s)
- Yujo Kawashita
- a Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
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13
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Dekervel J, van Malenstein H, Vandecaveye V, Nevens F, van Pelt J, Heye S, Laleman W, Van Steenbergen W, Vaninbroukx J, Verslype C, Maleux G. Transcatheter arterial chemoembolization with doxorubicin-eluting superabsorbent polymer microspheres in the treatment of hepatocellular carcinoma: midterm follow-up. J Vasc Interv Radiol 2013; 25:248-55.e1. [PMID: 24295569 DOI: 10.1016/j.jvir.2013.10.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 10/11/2013] [Accepted: 10/12/2013] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To investigate prospectively the safety, tolerability, and efficacy of transarterial chemoembolization using superabsorbent polymer (SAP) microspheres loaded with doxorubicin for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS During the years 2006-2011, 64 patients underwent 144 transarterial chemoembolization with SAP microspheres procedures. Most of the patients were staged as Barcelona Clinic Liver Cancer class B (65%). The most frequent underlying liver diseases were hepatitis C (35%) and alcoholic liver disease (28%) resulting in Child-Pugh A (73.4%) or Child-Pugh B (17%) liver cirrhosis. Tumor response was assessed using modified Response Evaluation Criteria in Solid Tumors with magnetic resonance (MR) imaging performed 4-6 weeks after each procedure. RESULTS Serious adverse events (n = 9) were ischemic or infectious in nature. Transarterial chemoembolization with SAP microspheres resulted in objective response rates of 67.5%, 44.5%, and 25% after first, second, and third sessions. There were 16 patients (25%) who underwent orthotopic liver transplantation after transarterial chemoembolization with SAP microspheres, of whom 2 experienced recurrent disease. During a median follow-up time of 14 months (range, 2-55 mo), 26 patients (40.5%) died. Median overall and transplant-free survivals were 20.5 months (95% confidence interval, 13.2-27.7) and 18 months (95% confidence interval, 14.2-21.8), respectively. CONCLUSIONS Transarterial chemoembolization with SAP microspheres has an excellent safety profile in cirrhotic patients, even in the presence of advanced liver disease (Child-Pugh B) or advanced stages of HCC. This treatment produced meaningful tumor response rates as assessed by MR imaging.
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Affiliation(s)
- Jeroen Dekervel
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Hannah van Malenstein
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | | | - Frederik Nevens
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Jos van Pelt
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Sam Heye
- Department of Radiology, University Hospitals Leuven, Herestraat 49
| | - Wim Laleman
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Werner Van Steenbergen
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | | | - Chris Verslype
- Department of Hepatology, University Hospitals Leuven, Herestraat 49; Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium
| | - Geert Maleux
- Department of Radiology, University Hospitals Leuven, Herestraat 49.
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Ghanaati H, Alavian SM, Jafarian A, Ebrahimi Daryani N, Nassiri-Toosi M, Jalali AH, Shakiba M. Imaging and Imaging-Guided Interventions in the Diagnosis and Management of Hepatocellular Carcinoma (HCC)-Review of Evidence. IRANIAN JOURNAL OF RADIOLOGY 2012; 9:167-77. [PMID: 23407596 PMCID: PMC3569547 DOI: 10.5812/iranjradiol.8242] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2012] [Revised: 10/24/2012] [Accepted: 10/27/2012] [Indexed: 12/12/2022]
Abstract
The imaging of hepatocellular carcinoma (HCC) is challenging and plays a crucial role in the diagnosis and staging of the disease. A variety of imaging modalities, such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine are currently used in evaluating patients with HCC. Although the best option for the treatment of these cases is hepatic resection or transplantation, only 20% of HCCs are surgically treatable. In those patients who are not eligible for surgical treatment, interventional therapies such as transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radio-frequency ablation (RFA), percutaneous microwave coagulation therapy (PMC), laser ablation or cryoablation, and acetic acid injection are indicated. In this paper, we aimed to review the evidence regarding imaging modalities and therapeutic interventions of HCC.
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Affiliation(s)
- Hossein Ghanaati
- Department of Radiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
- Corresponding author: Hossein Ghanaati, Medical Imaging Center, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. Tel.: +98-2166581516, Fax: +98-2166581578, E-mail:
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Jafarian
- Hepatobilliary and Liver Transplantation Division, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Department of Gastroenterology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Nassiri-Toosi
- Department of Gastroenterology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Jalali
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
| | - Madjid Shakiba
- Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Tehran, Iran
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15
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Xia JZ, Xie FL, Ran LF, Xie XP, Fan YM, Wu F. High-intensity focused ultrasound tumor ablation activates autologous tumor-specific cytotoxic T lymphocytes. ULTRASOUND IN MEDICINE & BIOLOGY 2012; 38:1363-1371. [PMID: 22633269 DOI: 10.1016/j.ultrasmedbio.2012.03.009] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2010] [Revised: 03/07/2012] [Accepted: 03/10/2012] [Indexed: 06/01/2023]
Abstract
Previous studies have shown that high-intensity focused ultrasound (HIFU) ablation can enhance host antitumor immune response, though the mechanism is still unknown. In the present study, we investigated whether HIFU ablation could activate tumor-specific T lymphocytes and then induce antitumor cellular immunity. We studied 70 C57BL/6J mice bearing the H(22) tumor; they were randomly divided into a HIFU group and a sham-HIFU group. Of the mice, 35 in the HIFU group underwent HIFU ablation of the H(22) hepatic tumor, and the remaining 35 received a sham-HIFU procedure. In addition, 35 female, naïve syngeneic C57BL/6J mice were used as controls. All mice were sacrificed 14 days after HIFU, and the spleens were harvested. The function of T lymphocytes was determined. As a valuable tool for detecting and characterizing peptide-specific cells, the frequency of MHC class I tetramer/CD8-positive cells was quantified, which could help to determine the response and number of T lymphocytes. The therapeutic effect of the HIFU-activated lymphocytes on tumor-bearing mice was investigated after adoptive transfer of the lymphocytes. The results showed that compared to sham-HIFU and control groups, HIFU ablation significantly increased the cytotoxicity of cytotoxic T lymphocytes (p < 0.05), with a significant increase of IFN-γ and TNF-α secretion (p < 0.001). The frequency of the MHC class I tetramer/CD8-positive cells was significantly higher in the HIFU group (p < 0.05). A stronger inhibition of tumor progression and higher survival rates were observed to be significant after adoptive immunotherapy in the HIFU group as compared to the sham-HIFU and control groups (p < 0.01). It is concluded that HIFU ablation could activate tumor-specific T lymphocytes, thus inducing antitumor cellular immune responses in tumor-bearing mice.
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Affiliation(s)
- Ji-Zhu Xia
- Institute of Ultrasonic Engineering in Medicine, Chongqing Medical University, Chongqing, China
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16
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Kim DY, Ryu HJ, Choi JY, Park JY, Lee DY, Kim BK, Kim SU, Ahn SH, Chon CY, Han KH. Radiological response predicts survival following transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma. Aliment Pharmacol Ther 2012; 35:1343-1350. [PMID: 22486716 DOI: 10.1111/j.1365-2036.2012.05089.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2012] [Revised: 02/24/2012] [Accepted: 03/15/2012] [Indexed: 12/24/2022]
Abstract
BACKGROUND It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular carcinoma (HCC). AIM To reveal the clinical relevance of compact lipiodolisation after TACE. METHODS We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not. RESULTS Of the 490 patients, 409 (83.5%) were in Child-Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5-10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1-, 3- and 5-year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child-Pugh class, alpha-fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival. CONCLUSIONS Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.
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Affiliation(s)
- D Y Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Liver, gastrointestinal, and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial. AJR Am J Roentgenol 2011; 197:W562-70. [PMID: 21940527 DOI: 10.2214/ajr.10.4379] [Citation(s) in RCA: 144] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC). SUBJECTS AND METHODS Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography. RESULTS The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018). CONCLUSION PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.
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Wang SH, Chen LM, Yang WK, Lee JD. Increased extrinsic apoptotic pathway activity in patients with hepatocellular carcinoma following transarterial embolization. World J Gastroenterol 2011; 17:4675-81. [PMID: 22180709 PMCID: PMC3233673 DOI: 10.3748/wjg.v17.i42.4675] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2011] [Revised: 06/10/2011] [Accepted: 06/17/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the apoptosis pathway in residual viable hepatocellular carcinoma (HCC) tissues following transarterial embolization (TAE).
METHODS: Ten patients with HCC who received surgical resection after TAE were enrolled in the study group, and 24 patients with HCC who received surgical resection only served as the control group. In the study group, we measured the changes in tumor size and α fetoprotein (AFP) levels after TAE. All tissue samples were taken from the residual tumors. The expression of various apoptotic proteins was evaluated via immunoblotting procedures. The results were analyzed using a Student’s t test.
RESULTS: Tumor size and the AFP level decreased by 46.2% and 55.3% after TAE, respectively. There was no significant difference detected for the Bcl-2/Bax ratio or the cleaved caspase-9 expression levels in either group. However, extrinsic apoptopic pathway-related expression of Fas and cleaved caspase-8 expression were significantly higher in the study group than in the control group (P < 0.05). In addition, cleaved caspase-3 expression in the study group was higher (1.62-fold) than in control group (P < 0.05).
CONCLUSION: TAE is an effective palliative therapy that decreases tumor size and AFP levels via an increase in extrinsic apoptosis pathway in patients with unresectable HCC.
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Higgins LJ, Hwang GL, Rosenberg J, Katzenberg RH, Kothary N, Sze DY, Hofmann LV. In Vitro Design and Characterization of the Nonviral Gene Delivery Vector Iopamidol, Protamine, Ethiodized Oil Reagent. J Vasc Interv Radiol 2011; 22:1457-1463.e2. [DOI: 10.1016/j.jvir.2011.06.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2011] [Revised: 06/29/2011] [Accepted: 06/30/2011] [Indexed: 11/15/2022] Open
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20
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Heinzow HS, Meister T, Nass D, Köhler M, Spieker T, Wolters H, Domschke W, Domagk D. Outcome of supraselective transarterial chemoembolization in patients with hepatocellular carcinoma. Scand J Gastroenterol 2011; 46:201-10. [PMID: 20969491 DOI: 10.3109/00365521.2010.525256] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic patients with a median survival of only 8-10 months if untreated. Supraselective transarterial chemoembolization (STACE) is supposed to be a well-established method for treating HCC patients. In the present study, we evaluated the effect of STACE on post-transplant survival in patients with HCC. MATERIAL AND METHODS The charts of 53 HCC patients were retrospectively analyzed. Twenty-seven patients had STACE as a bridging therapy while 26 patients were scheduled for liver transplantation (LTX) without prior STACE therapy. A total of 53% of the patients who underwent LTX preoperatively fulfilled the Milan criteria, while 70.6% fulfilled the expanded University of California, San Francisco (UCSF) transplant criteria. Primary endpoint was the post-transplant survival. Statistical analysis included Kaplan-Meier-method, log rank, and chi square tests. RESULTS Between the LTX groups (STACE vs. non-STACE), there was no significant difference in terms of age, Child classification, Okuda stage, co-morbidities, underlying disease, and post-transplant survival (p > 0.05). Independent of prior STACE, however, disease-free survival after LTX was highly significantly prolonged if LTX was performed within 3 months after initial diagnosis of HCC (p < 0.01) or if patients met the expanded transplant UCSF criteria (p = 0.02). Post-transplant survival did not depend on tumor size. CONCLUSIONS We conclude that STACE performed prior to LTX does not secure any post-transplant survival benefit, while early LTX, i.e. within 3 months after HCC diagnosis, does improve survival regardless of whether STACE was performed or not. Additionally, fulfillment of the expanded transplant UCSF criteria leads to a prolonged post-transplant survival.
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Chen HY, Wang Y, Li Q. Advances in research of microspheres containing Chinese medicine for interventional cancer therapy. Shijie Huaren Xiaohua Zazhi 2010; 18:2350-2354. [DOI: 10.11569/wcjd.v18.i22.2350] [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] [Indexed: 02/06/2023] Open
Abstract
Drug-loaded microspheres represent a newly developed particulate drug delivery system that possesses the characteristics of controlled release and targeting delivery. The use of microsphere agents in Chinese medicine can make up for the deficiency of traditional preparations, improve bioavailability, and decrease use dosage and non-target toxicity, so it have controlled release and targeting characteristics. Therefore, the research on microsphere agents has become a hot topic in the development of new delivery system for Chinese medicine. In this paper, we will review the biological characteristics of microsphere agents and discuss the recent advances and problems encountered in the research of microsphere agents.
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