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Du QW, Xiao F, Zheng L, Chen RD, Dong LN, Liu FY, Cheng ZG, Yu J, Liang P. Importance of the enhanced cooling system for more spherical ablation zones: Numerical simulation, ex vivo and in vivo validation. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2024; 257:108383. [PMID: 39260163 DOI: 10.1016/j.cmpb.2024.108383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 08/20/2024] [Accepted: 08/21/2024] [Indexed: 09/13/2024]
Abstract
INTRODUCTION This study aimed to investigate the efficacy of a small-gauge microwave ablation antenna (MWA) with an enhanced cooling system (ECS) for generating more spherical ablation zones. METHODS A comparison was made between two types of microwave ablation antennas, one with ECS and the other with a conventional cooling system (CCS). The finite element method was used to simulate in vivo ablation. Two types of antennas were used to create MWA zones for 5, 8, 10 min at 50, 60, and 80 W in ex vivo bovine livers (n = 6) and 5 min at 60 W in vivo porcine livers (n = 16). The overtreatment ratio, ablation aspect ratio, carbonization area, and other characteristcs of antennas were measured and compared using numerical simulation and gross pathologic examination. RESULTS In numerical simulation, the ECS antenna demonstrated a lower overtreatment ratio than the CCS antenna (1.38 vs 1.43 at 50 W 5 min, 1.19 vs 1.35 at 50 W 8 min, 1.13 vs 1.32 at 50 W 10 min, 1.28 vs 1.38 at 60 W 5 min, 1.14 vs 1.32 at 60 W 8 min, 1.10 vs 1.30 at 60 W 10 min). The experiments revealed that the ECS antenna generated ablation zones with a more significant aspect ratio (0.92 ± 0.03 vs 0.72 ± 0.01 at 50 W 5 min, 0.95 ± 0.02 vs 0.70 ± 0.01 at 50 W 8 min, 0.96 ± 0.01 vs 0.71 ± 0.04 at 50 W 10 min, 0.96 ± 0.01 vs 0.73 ± 0.02 at 60 W 5 min, 0.94 ± 0.03 vs 0.71 ± 0.03 at 60 W 8 min, 0.96 ± 0.02 vs 0.69 ± 0.04 at 60 W 10 min) and a smaller carbonization area (0.00 ± 0.00 cm2 vs 0.54 ± 0.06 cm2 at 50 W 5 min, 0.13 ± 0.03 cm2 vs 0.61 ± 0.09 cm2 at 50 W 8 min, 0.23 ± 0.05 cm2 vs 0.73 ± 0.05 m2 at 50 W 10 min, 0.00 ± 0.00 cm2 vs 1.59 ± 0.41 cm2 at 60 W 5 min, 0.23 ± 0.22 cm2 vs 2.11 ± 0.63 cm2 at 60 W 8 min, 0.57 ± 0.09 cm2 vs 2.55 ± 0.51 cm2 at 60 W 10 min). Intraoperative ultrasound images revealed a hypoechoic area instead of a hyperechoic area near the antenna. Hematoxylin-eosin staining of the dissected tissue revealed a correlation between the edge of the ablation zone and that of the hypoechoic area. CONCLUSIONS The ECS antenna can produce more spherical ablation zones with less charring and a clearer intraoperative ultrasound image of the ablation area than the CCS antenna.
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Affiliation(s)
- Qiao-Wei Du
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Fan Xiao
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Lin Zheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Ren-Dong Chen
- The Yuquan Campus, Zhejiang University, Hangzhou, Zhejiang, China
| | - Li-Nan Dong
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Fang-Yi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Zhi-Gang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital Fifth Medical Center, Beijing, 100853, China.
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Frackowiak B, Van den Bosch V, Tokoutsi Z, Baragona M, de Greef M, Elevelt A, Isfort P. First validation of a model-based hepatic percutaneous microwave ablation planning on a clinical dataset. Sci Rep 2023; 13:16862. [PMID: 37803064 PMCID: PMC10558472 DOI: 10.1038/s41598-023-42543-x] [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: 04/05/2023] [Accepted: 09/12/2023] [Indexed: 10/08/2023] Open
Abstract
A model-based planning tool, integrated in an imaging system, is envisioned for CT-guided percutaneous microwave ablation. This study aims to evaluate the biophysical model performance, by comparing its prediction retrospectively with the actual ablation ground truth from a clinical dataset in liver. The biophysical model uses a simplified formulation of heat deposition on the applicator and a heat sink related to vasculature to solve the bioheat equation. A performance metric is defined to assess how the planned ablation overlaps the actual ground truth. Results demonstrate superiority of this model prediction compared to manufacturer tabulated data and a significant influence of the vasculature cooling effect. Nevertheless, vasculature shortage due to branches occlusion and applicator misalignment due to registration error between scans affects the thermal prediction. With a more accurate vasculature segmentation, occlusion risk can be estimated, whereas branches can be used as liver landmarks to improve the registration accuracy. Overall, this study emphasizes the benefit of a model-based thermal ablation solution in better planning the ablation procedures. Contrast and registration protocols must be adapted to facilitate its integration into the clinical workflow.
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Affiliation(s)
- Bruno Frackowiak
- Philips Research, Data Science & Digital Twin, 5656 AE, Eindhoven, The Netherlands.
| | - Vincent Van den Bosch
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, 52074, Aachen, Germany
| | - Zoi Tokoutsi
- Philips Research, Data Science & Digital Twin, 5656 AE, Eindhoven, The Netherlands
| | - Marco Baragona
- Philips Research, Data Science & Digital Twin, 5656 AE, Eindhoven, The Netherlands
| | - Martijn de Greef
- Philips Research, Data Science & Digital Twin, 5656 AE, Eindhoven, The Netherlands
| | - Aaldert Elevelt
- Philips Research, Data Science & Digital Twin, 5656 AE, Eindhoven, The Netherlands
| | - Peter Isfort
- Department of Diagnostic and Interventional Radiology, University Hospital RWTH Aachen, 52074, Aachen, Germany
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Zhang Z, Zhang E. Conversion therapy for advanced hepatocellular carcinoma with vascular invasion: a comprehensive review. Front Immunol 2023; 14:1073531. [PMID: 37180144 PMCID: PMC10169581 DOI: 10.3389/fimmu.2023.1073531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 04/12/2023] [Indexed: 05/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high mortality rate worldwide. The percentage of HCC patients with vascular invasion at the time of initial HCC diagnosis is 10%-40%. According to most guidelines, HCC with vascular invasion is classified as advanced stage, and resection is only suggested for a minority of such patients. Recently, advances in systemic and locoregional treatments for such patients have resulted in amazing response rates. Therefore, a "conversion therapy" strategy including systemic and locoregional treatments is proposed to select patients from an initially unresectable state to eventually undergo R0 resection. Recently, many studies have proven that conversion therapy followed by subsequent surgery is achievable in well-selected advanced HCC patients and can provide prolonged long-term outcomes. Based on published research, this review has summarized the clinical experience and evidence of conversion treatment in HCC patients with vascular invasion.
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Affiliation(s)
| | - Erlei Zhang
- Research Laboratory and Hepatic Surgery Center, Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Zhang ZY, Zhang EL, Zhang BX, Chen XP, Zhang W. Treatment for hepatocellular carcinoma with tumor thrombosis in the hepatic vein or inferior vena cava: A comprehensive review. World J Gastrointest Surg 2021; 13:796-805. [PMID: 34512903 PMCID: PMC8394384 DOI: 10.4240/wjgs.v13.i8.796] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 04/12/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate worldwide. The percentage of HCC patients with vascular invasion is high. However, tumor thrombus in the hepatic vein (HVTT) has a lower incidence than tumor thrombus in the portal vein (PVTT). Conventionally, HCC patients with HVTT are treated the same as HCC patients with PVTT and offered sorafenib or other systemic agents. However, according to recent studies, it is evident that HCC with HVTT shows different outcomes when classified into different subgroups. In this review, we discuss the recent progress and changes in treatment of HCC with HVTT.
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Affiliation(s)
- Zun-Yi Zhang
- Research Laboratory and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 434000, Hubei Province, China
| | - Er-Lei Zhang
- Research Laboratory and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 434000, Hubei Province, China
| | - Bi-Xiang Zhang
- Research Laboratory and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 434000, Hubei Province, China
| | - Xiao-Ping Chen
- Research Laboratory and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 434000, Hubei Province, China
| | - Wei Zhang
- Research Laboratory and Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 434000, Hubei Province, China
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Identification of Long Noncoding RNA Biomarkers for Hepatocellular Carcinoma Using Single-Sample Networks. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8579651. [PMID: 33299877 PMCID: PMC7700720 DOI: 10.1155/2020/8579651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 10/19/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023]
Abstract
Objective Many studies have found that long noncoding RNAs (lncRNAs) are differentially expressed in hepatocellular carcinoma (HCC) and closely associated with the occurrence and prognosis of HCC. Since patients with HCC are usually diagnosed in late stages, more effective biomarkers for early diagnosis and prognostic prediction are in urgent need. Methods The RNA-seq data of liver hepatocellular carcinoma (LIHC) were downloaded from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs and mRNAs were obtained using the edgeR package. The single-sample networks of the 371 tumor samples were constructed to identify the candidate lncRNA biomarkers. Univariate Cox regression analysis was performed to further select the potential lncRNA biomarkers. By multivariate Cox regression analysis, a 3-lncRNA-based risk score model was established on the training set. Then, the survival prediction ability of the 3-lncRNA-based risk score model was evaluated on the testing set and the entire set. Function enrichment analyses were performed using Metascape. Results Three lncRNAs (RP11-150O12.3, RP11-187E13.1, and RP13-143G15.4) were identified as the potential lncRNA biomarkers for LIHC. The 3-lncRNA-based risk model had a good survival prediction ability for the patients with LIHC. Multivariate Cox regression analysis proved that the 3-lncRNA-based risk score was an independent predictor for the survival prediction of patients with LIHC. Function enrichment analysis indicated that the three lncRNAs may be associated with LIHC via their involvement in many known cancer-associated biological functions. Conclusion This study could provide novel insights to identify lncRNA biomarkers for LIHC at a molecular network level.
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Expression of MMP-2 in residual VX2 liver tumor after transcatheter arterial embolization combined with portal venous embolization in an animal model. J Interv Med 2020; 3:167-173. [PMID: 34805929 PMCID: PMC8562231 DOI: 10.1016/j.jimed.2020.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 07/20/2020] [Accepted: 08/03/2020] [Indexed: 11/21/2022] Open
Abstract
Objective This study aimed to analyze the effects of transcatheter arterial embolization (TAE) combined with portal venous embolization (PVE) on the expression of MMP-2 in residual VX2 liver tumor tissues, liver function and non-embolic lobe regeneration. Methods A total of 72 rabbits were randomly divided into Sham, TAE, PVE and TAE + PVE groups (n = 18/group). The tissue samples from each group were taken at 6 h, 3 days and 7 days after interventional operation, respectively. MMP-2 expression was detected by immunohistochemistry, Real-time PCR, and Western-blotting. The main indicators (such as AST, ATL, and TBIL) of liver function and the volume of non-embolized hepatic lobes were measured in each group after operation. One-way ANOVA and Kruskal-wallis method were used for statistical analysis. Results The expression of MMP-2 mRNA and protein remained the highest in the Sham group, and the expression of MMP-2 mRNA and protein in TAE, PVE and TAE + PVE groups were successively increased, and the expression of MMP-2 in TAE + PVE group was always significantly higher than TAE group. The AST and ALT levels in each group on day 7 after operation showed a significant declination, and all groups have recovered to the preoperative baseline level and TBIL has a slight fluctuation in each group after operation with no statistical difference. On day 7 after operation, the increasing volume of non-embolized liver lobes in TAE + PVE group showed a more significant effect than those in PVE group, but there was no statistical significance (37.62 ± 1.54 ml VS 36.18 ± 1.15 ml, P = 0.881), and its volume was significantly higher than those in the sham group (27.03 ± 1.11 ml). Conclusion TAE + PVE is considered to be an efficient and safe approach for treating rabbit VX2 liver transplantation tumor, but the expression of MMP-2 increased fastest after TAE + PVE, which might promote tumor cell invasion and metastasis.
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Gupta A, Kumar R, Yadav HP, Sharma M, Kamal R, Thaper D, Banik P, Gupta S, Saroha K, Singh S, Kumar Sarin S. Feasibility of 4D CT simulation with synchronized intravenous contrast injection in hepatocellular carcinoma. Rep Pract Oncol Radiother 2020; 25:293-298. [PMID: 32194348 DOI: 10.1016/j.rpor.2019.12.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 12/02/2019] [Indexed: 12/31/2022] Open
Abstract
Background Delivering Stereotactic Body Radiotherapy (SBRT) for Hepatocellular Carcinoma (HCC) is challenging mainly for two reasons: first, motion of the liver occurs in six degrees of freedom and, second, delineation of the tumor is difficult owing to a similar density of HCC to that of the adjoining healthy liver tissue in a non-contrast CT scan. To overcome both these challenges simultaneously, we performed a feasibility study to synchronize intravenous contrast to obtain an arterial and a delayed phase 4D CT. Materials and Methods We included seven HCC patients of planned for SBRT. 4D CT simulation was performed with synchronized intravenous contrast based on the formula TSCAN DELAY = T peak - (L0/Detector Coverage × Cine Duration in Seconds). This was followed by a delayed 4D CT scan. Results We found that, with our protocol, it is feasible to obtain a 4DCT with an arterial and a delayed phase making it comparable to a diagnostic multi-phase CT. The peak HU of the 4D scan and diagnostic CT were similar (mean peak HU 134.2 vs 143.1, p value = 0.58 N.S). Whereas in comparison with a non-contrast CT a significant rise in the peak HU was seen (mean peak 134.2 vs 61.4 p value = .00003). Conclusion A synchronized contrast 4D CT simulation for HCC is safe and feasible. It results in good contrast enhancement comparable to a diagnostic 3D contrast CT scan.
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Affiliation(s)
- Anil Gupta
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Rishabh Kumar
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | | | - Manik Sharma
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Rose Kamal
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Deepak Thaper
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Prabir Banik
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Shipra Gupta
- Radiation Oncology, Institute of Liver and Biliary Sciences, Delhi, India
| | - Kartik Saroha
- Nuclear Medicine, Institute of Liver and Biliary Sciences, Delhi, India
| | - Sandeep Singh
- Nuclear Medicine, Institute of Liver and Biliary Sciences, Delhi, India
| | - Shiv Kumar Sarin
- Hepatology, Institute of Liver and Biliary Sciences, Delhi, India
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Chen G, Zhang J, Sun J, Wei S, Chen J, Ren H, Zhou S. Revisiting Partial Hepatectomy of Large Hepatocellular Carcinoma in Older Patients. Sci Rep 2018; 8:14505. [PMID: 30266965 PMCID: PMC6162215 DOI: 10.1038/s41598-018-32798-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 09/03/2018] [Indexed: 12/18/2022] Open
Abstract
Hepatectomy of large hepatocellular carcinomas (>10 cm) in over 70 year-old patients is presumed futile. We retrospectively reviewed 5970 patients with liver tumors Jan 2010 through Dec 2016 in our institute, of them, 37 older patients with large hepatocellular carcinomas staged I-III and Child-Pugh A liver functions receiving conservative treatments (conservative group, n = 37) and 16 older patients with large hepatocellular carcinomas staged I- III who underwent partial hepatectomy (resection group, n = 16) were included, the risk factors for poor survival were analyzed by univariate and multivariate analyses. Compared with the conservative treatments, Partial hepatectomy achieved better median survival time (25.5 months versus 11 months, log-rank = 0.0001) and better median performance status (1 versus 3, p = 0.023), there was different in Charlson comorbidity index (p = 0.019). For the conservative group, the 3-month, 1, 2, 3-year survival rate was 78.4%, 43.2%, 5.4%, 0%; for the resection group, The 3-month, 1, 2, 3-year survival rate was 100%, 93.7.2%, 56.3%, 12.5%; Multivariate Cox regression analysis showed the Charlson comorbidity index and the performance status associated with poor outcomes of those patients (p = 0.001, 0.018, respectively). Resections of large hepatocellular carcinomas in older patients can be performed safely to prolong life expectancy and improve life quality with or without cancer recurrence.
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Affiliation(s)
- Guoyong Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jiabin Zhang
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China
| | - Jianjun Sun
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Sidong Wei
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Jianbin Chen
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Hui Ren
- Center of Hepatopancreaticobiliary Surgery and liver transplantation, 302 Hospital, Beijing, 100039, China.
| | - Shaotang Zhou
- Section 5 of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China.
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Qin J, Yang L, Sheng X, Sa Z, Huang T, Li Q, Gao K, Chen Q, Ma J, Shen H. Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo. Oncol Lett 2018; 15:6137-6146. [PMID: 29731843 PMCID: PMC5920962 DOI: 10.3892/ol.2018.8168] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Accepted: 10/12/2017] [Indexed: 12/29/2022] Open
Abstract
In vitro and in vivo studies have demonstrated that brucine is able to inhibit the proliferation of liver cancer cells and growth of animal tumors, and may be a promising anticancer drug. However, high toxicity, poor water solubility, short half-life, narrow therapeutic window, and similar therapeutic and toxic doses limit its clinical application in the treatment of malignant tumors. In our previous study, brucine immuno-nanoparticles were successfully prepared and added to the culture medium of liver cancer SMMC-7721 cells, and the results indicated that the brucine immuno-nanoparticles were able to target the cell membrane of liver cancer SMMC-7721 cells and significantly inhibit the proliferation, adhesion, invasion and metastasis of SMMC-7721 cells. The aim of the present study was to investigate the antitumor effect of brucine immuno-nanoparticles in vivo by establishing an in situ transplanted liver cancer in nude mice. The results indicated that in vivo application of the brucine immuno-nanoparticles resulted in temporary liver and kidney damage, and significantly reduced the α-fetoprotein (AFP) secretion of tumor cells (Bru-NP-MAb vs. the other groups; P<0.05). The brucine concentration of tumor tissues in the brucine immuno-nanoparticles group was significantly increased compared with that of the brucine nanoparticles group (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). The brucine immuno-nanoparticles were able to inhibit tumor growth and cluster of differentiation 34 expression and angiogenesis of tumor tissues, and induce the apoptosis of tumor cells (Bru-NP-MAb vs. Bru-NP group or brucine group; P<0.05). In conclusion, as a novel type of targeted drug, brucine nanoparticles combined with anti-AFP monoclonal antibodies was more effective compared with brucine nanoparticles or brucine alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis in vivo. Therefore, the brucine immuno-nanoparticle is a promising targeted drug for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Jianmin Qin
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China.,Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Lin Yang
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Xia Sheng
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Zhongqiu Sa
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China.,Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Tao Huang
- Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China
| | - Qi Li
- Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Kepan Gao
- National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, P.R. China
| | - Qinghua Chen
- National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, P.R. China
| | - Jingwei Ma
- Department of Physical Chemistry, Shanghai Normal University, Shanghai 200234, P.R. China
| | - Hebai Shen
- Department of Physical Chemistry, Shanghai Normal University, Shanghai 200234, P.R. China
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Huang BS, Tsang NM, Lin SM, Lin DY, Lien JM, Lin CC, Chen WT, Chen WY, Hong JH. High-dose hypofractionated X-ray radiotherapy for hepatocellular carcinoma: Tumor responses and toxicities. Oncol Lett 2013; 6:1514-1520. [PMID: 24179551 PMCID: PMC3813808 DOI: 10.3892/ol.2013.1582] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2013] [Accepted: 08/22/2013] [Indexed: 02/07/2023] Open
Abstract
Hypofractionated radiotherapy (RT) has been employed to treat hepatocellular carcinoma (HCC). The present study aimed to report the treatment effects, the dose-response associations and the factors that are associated with radiation-induced liver disease (RILD) in a high-dose hypofractionated RT procedure. A total of 40 patients with non-metastatic HCC who underwent RT for local control of irradiated tumors were studied. The treatment technique was that of three-dimensional conformal or intensity-modulated radiation therapy, with a fraction size of 3 Gy and a total dose of 40–66 Gy in 14–23 fractions. The biologically-effective dose (BED) was 52.0–85.8 Gy10 (median, 74.1 Gy10). Tumor regression was observed in 28 patients (70.0%) with a complete response, partial response, stable disease and progressive disease status in 11 (27.5%), 17 (42.5%), five (12.5%) and seven patients (17.5%), respectively. The one-, two- and five-year overall survival (OS) and in-field control (IFC) rates were 60, 40 and 21% and 73, 62 and 56%, respectively. A positive correlation also emerged between the radiation dose and the IFC (P=0.035). Eight of the 40 patients (20%) developed non-classic RILD. A higher Cancer of the Liver Italian Program score was associated with a higher probability of non-classic RILD (P=0.02). The tumor response and IFC rate of HCC following irradiation were significantly dose-dependent. High-dose hypofractionated X-ray RT is a feasible and effective treatment for HCC in patients with good liver function and for those who meet the criteria for a curative attempt.
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Affiliation(s)
- Bing-Shen Huang
- Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan ; Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan, Taiwan
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Zhang X, Zhou X, Chen R, Zhang H. Radiosensitization by inhibiting complex I activity in human hepatoma HepG2 cells to X-ray radiation. JOURNAL OF RADIATION RESEARCH 2012; 53:257-263. [PMID: 22510598 DOI: 10.1269/jrr.11124] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/31/2023]
Abstract
The purpose of this study is to investigate the influence of mitochondrial respiratory chain complex I inhibition on the radiosensitivity of HepG2 cells. The complex I inhibitor rotenone was used to inhibit complex I activity on HepG2 cells before X-ray irradiation. The cytotoxicity of rotenone was analyzed by MTT assay at various doses. Rotenone induced dissipation of mitochondrial membrane potential and increase of intracellular ROS production were observed. Intracellular ATP production level was determined using luciferin-luciferase assay kit. We further analyzed cell survival and cell cycle distribution of a combined treatment which HepG2 cells underwent 0.5 µM rotenone pretreatment firstly and irradiated with different doses of X-ray radiation afterwards. Our results suggest rotenone pretreatment prior to X-ray irradiation could induce a sensitizing effect on HepG2 cells by enhancing X-ray radiation induced proliferation inhibition and cell apoptosis.
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Affiliation(s)
- Xin Zhang
- Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
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Gervais DA, Goldberg SN, Brown DB, Soulen MC, Millward SF, Rajan DK. Society of Interventional Radiology position statement on percutaneous radiofrequency ablation for the treatment of liver tumors. J Vasc Interv Radiol 2009; 20:S342-7. [PMID: 19560023 DOI: 10.1016/j.jvir.2009.04.029] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Revised: 09/05/2008] [Accepted: 09/05/2008] [Indexed: 02/08/2023] Open
Abstract
Focal tumor ablation--whether applied percutanously, laparoscopically, or by means of open surgery--is an effective therapy for selected liver tumors. The choice of liver ablation as well as the choice between percutaneous and surgical approaches is dependent on tumor factors, patient factors, and other viable treatment options. Currently, the largest cumulative reported experience is with radiofrequency (RF) ablation of hepatocellular carcinoma and colorectal metastases. This document is a position statement of the Interventional Oncology Task Force and the Standards Division of the Society of Interventional Radiology regarding the use of percutaneous RF ablation for the treatment of liver tumors.
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Affiliation(s)
- Debra A Gervais
- Department of Radiology, Division of Abdominal Imaging and Intervention, Massachusetts General Hospital, White 270, 55 Fruit St, Boston, MA 02114, USA.
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Rhim H. Review of Asian experience of thermal ablation techniques and clinical practice. Int J Hyperthermia 2009; 20:699-712. [PMID: 15675666 DOI: 10.1080/0265673042000196487] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
The field of image-guided tumour ablation has gained great attention from Asian physicians because it represents a safe and effective technique for many commonly seen tumours in this population, showing minimal morbidity and excellent local control rates. Based on the current survey data from Asian physicians who are currently performing image-guided tumour ablation, thermal ablation has been mainly performed for patients with unresectable liver tumours. Radiofrequency ablation has replaced many other local ablation techniques such as microwave or ethanol ablation in treating small focal hepatic tumours for the last 5 years. Surgery and transcatheter arterial chemoembolization also have a unique role as curative and palliative treatment options for patients with more extensive tumour burden. Although radiofrequency ablation represents a paradigm shift in local therapy, more sophisticated strategies to enhance the therapeutic efficacy are necessary and more randomized and controlled investigations to estimate its clinical benefit are warranted.
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Affiliation(s)
- H Rhim
- Department of Diagnostic Radiology, Hanyang University Hospital, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-792, Korea.
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14
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Berry DP, Garcea G, Vanderzon P, Slimani E, Chong C, Dennison AR, Maddern GJ. Augmenting the Ablative Effect of Liver Electrolysis: Using Two Electrodes and the Pringle Maneuver. J INVEST SURG 2009; 17:105-12. [PMID: 15204717 DOI: 10.1080/08941930490422546] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Several methods of liver tumor ablation have been investigated, and these include the novel technique of electrolysis. Electrolysis is slower than other forms of ablative therapy. This study determined methods of increasing the ablative effect of electrolysis. Domestic white pigs were divided. One group received electrolysis using two electrode catheters, and in the other group a concurrent intermittent Pringle maneuver was performed to induce intermittent ischemia. The effect of two electrode catheters versus a single electrode catheter was compared, and the effect of the Pringle maneuver versus no Pringle was examined with two electrode catheters. The livers were harvested, and the volume of each lesion was calculated. There was a linear relationship between the volume of hepatic necrosis and the electrolytic dose in (p <.005) in both the single-electrode-catheter and two-electrode-catheter groups. Comparison between the single- and multiple-electrode groups showed a highly significant difference in the dose response (p <.0000002) when more than one electrode was used. Use of the Pringle maneuver during electrolysis produced larger volumes of hepatic necrosis over all doses when using two electrode catheters. Rates of necrosis were 3.8 cm(3)/100 C for a single electrode catheter, 5.46 cm(3)/100 C for two electrode catheters without Pringle, and 6.17 cm(3)/100 C for electrolysis with two electrode catheters coupled with intermittent Pringle maneuver. Thus, electrolysis was both reliable and predictable in producing hepatic necrosis in a dose-dependent manner. The time delay in achieving tumor ablation via electrolysis can be overcome by using two electrodes combined with the Pringle maneuver to increase the volume of the lesion produced.
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Affiliation(s)
- D P Berry
- Hepatobiliary Unit, Leicester General Hospital, Leicester, United Kingdom
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15
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Gervais DA, Goldberg SN, Brown DB, Soulen MC, Millward SF, Rajan DK. Society of Interventional Radiology position statement on percutaneous radiofrequency ablation for the treatment of liver tumors. J Vasc Interv Radiol 2008; 20:3-8. [PMID: 18948025 DOI: 10.1016/j.jvir.2008.09.007] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2008] [Revised: 09/05/2008] [Accepted: 09/05/2008] [Indexed: 01/21/2023] Open
Abstract
Focal tumor ablation--whether applied percutanously, laparoscopically, or by means of open surgery-is an effective therapy for selected liver tumors. The choice of liver ablation as well as the choice between percutaneous and surgical approaches is dependent on tumor factors, patient factors, and other viable treatment options. Currently, the largest cumulative reported experience is with radiofrequency (RF) ablation of hepatocellular carcinoma and colorectal metastases. This document is a position statement of the Interventional Oncology Task Force and the Standards Division of the Society of Interventional Radiology regarding the use of percutaneous RF ablation for the treatment of liver tumors.
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Affiliation(s)
- Debra A Gervais
- Department of Radiology, Division of Abdominal Imaging and Intervention, Massachusetts General Hospital, Boston, MA 02114, USA.
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16
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Misirli Y, Oztürk E, Kurşaklioğlu H, Denkbaş EB. Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization. J Microencapsul 2008; 22:167-78. [PMID: 16019902 DOI: 10.1080/02652040400026368] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl(2) was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and approximately 100-400 microm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50-280%. CaCl(2) concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in approximately 30 min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1 h) values.
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Affiliation(s)
- Y Misirli
- Hacettepe University, Beytepe, Ankara, Turkey
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17
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Huang W, Qu ZQ, Li XD, He P, Ding N, Zhang SL, Wu M. The effect of transcatheter arterial chemoembolization on CYP1A2 activity in patients with hepatocellular carcinoma. J Clin Pharm Ther 2008; 33:489-93. [DOI: 10.1111/j.1365-2710.2008.00937.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ren J, Jia J, Zhang H, Zhang L, Ma B, Jiang H, Di L, Song G, Yu J. Dendritic cells pulsed with alpha-fetoprotein and mutant P53 fused gene induce bi-targeted cytotoxic T lymphocyte response against hepatic carcinoma. Cancer Sci 2008; 99:1420-6. [PMID: 18422751 PMCID: PMC11158406 DOI: 10.1111/j.1349-7006.2008.00820.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2007] [Revised: 03/04/2008] [Accepted: 03/11/2008] [Indexed: 11/27/2022] Open
Abstract
Dendritic cell (DC)-based immunotherapy is rapidly emerging as a promising treatment in cancer therapy. We had previously shown that DC pulsed with either defined mRNA of tumor antigen (Ag) such as alpha-fetoprotein (AFP), or total RNA of hepatocellular carcinoma (HCC) could elicit Ag-specific cytotoxic T lymphocyte (CTL) response. Therefore, we suggested a novel DC-based therapeutic method, in which DCs derived from CD34(+) cells enriched peripheral blood mononuclear cells were pulsed with liposome-coated AFP and mutant P53 (mtP53) fused gene pEGFP-C3/AFP-mtP53 to induce bi-targeted specific CTL responses against HCC. Three different genotype HCC cell lines, HepG2 (human histocompatibility leukocyte antigens (HLA) A2 positive, AFP expressing positive, P53 expressing negative), SMMC7721 (HLA A2 positive, neither AFP nor P53 expressing positive), and HMCC97 (HLA A2 positive, both AFP and P53 expressing positive) were selected as targets for CTL responses. An important finding was that DCs pulsed with the liposome-coated fused gene could evoke more intensive bi-targeted Ag-specific CTL responses against HMCC97 than DCs pulsed with either AFP or P53 single gene (P < 0.05). This experimental therapeutic model provides a new promising cytotherapeutic approach, in that DCs pulsed with the fused gene of different Ags might induce more extensive multitargeted antitumor immunity.
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Affiliation(s)
- Jun Ren
- Department of Medical Oncology, Peking University School of Oncology/Beijing Cancer Hospital, No. 52 Fucheng Rd, Beijing, China 100036.
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19
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Addario L, Di Costanzo GG, Tritto G, Cavaglià E, Angrisani B, Ascione A. Fatal ischemic acute pancreatitis complicating trans-catheter arterial embolization of small hepatocellular carcinoma: do the risks outweigh the benefits? J Hepatol 2008; 49:149-52. [PMID: 18486260 DOI: 10.1016/j.jhep.2008.02.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2007] [Revised: 02/10/2008] [Accepted: 02/13/2008] [Indexed: 12/04/2022]
Abstract
Hepatocellular carcinoma (HCC) is an accepted indication for liver transplantation (LT). Pre-LT adjuvant ablation treatments to prevent tumour progression and drop out from the waiting list have been increasingly adopted at most transplant centers. Trans-catheter arterial chemo-embolization (TACE) is frequently used, but the procedure can be difficult and severe complications may arise. Among them, acute ischemic pancreatitis occasionally occurs and may clinically mimic a post-embolization syndrome. Fatal outcomes of this complication have been reported exceptionally but never in patients awaiting LT. The present case raises concern about the widespread application of TACE and highlights the need for a critical evaluation of the risks and benefits to patients with monofocal small HCC who are scheduled for LT. Superselective embolization of the tumour-feeding artery and systematic monitoring of serum pancreatic enzymes after this radiological procedure are recommended.
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Affiliation(s)
- Luigi Addario
- Hepatology Unit, Department of Gastroenterology, Cardarelli Hospital, Napoli, Italy
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20
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Kanhere HA, Leopardi LN, Fischer L, Kitchener MI, Maddern GJ. TREATMENT OF UNRESECTABLE HEPATOCELLULAR CARCINOMA WITH RADIOLABELLED LIPIODOL. ANZ J Surg 2008; 78:371-6. [DOI: 10.1111/j.1445-2197.2008.04480.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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21
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Hsu WC, Chan SC, Ting LL, Chung NN, Wang PM, Ying KS, Shin JS, Chao CJ, Lin GD. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma. Jpn J Clin Oncol 2006; 36:93-9. [PMID: 16517834 DOI: 10.1093/jjco/hyi242] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. METHODS Between 1999 and 2003, 121 patients (mean age, 54.4 +/- 12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52 +/- 408.50 cm(3) (range, 26.89-2284.82 cm(3)). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. RESULTS Treatment responses were observed in 61% of the patients. Liver cirrhosis (P = 0.001) and tumor size (P = 0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P = 0.003), Karnofsky performance status (P = 0.007), tumor size (P < 0.001), portal vein tumor thrombosis (P < 0.001) and alpha-fetoprotein level (P = 0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P = 0.039) and alpha-fetoprotein level (P = 0.006) were shown to be factors affecting survival. CONCLUSIONS Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma.
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Affiliation(s)
- Wei-Chung Hsu
- Department of Radiation Oncology, Cheng-Ching General Hospital, Taichung, Taiwan
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22
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Clark HP, Carson WF, Kavanagh PV, Ho CPH, Shen P, Zagoria RJ. Staging and current treatment of hepatocellular carcinoma. Radiographics 2006; 25 Suppl 1:S3-23. [PMID: 16227495 DOI: 10.1148/rg.25si055507] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Early-stage hepatocellular carcinoma (HCC) is typically clinically silent, and HCC is often advanced at first manifestation. Without treatment, the 5-year survival rate is less than 5%. The selected treatment depends on the presence of comorbidity; tumor size, location, and morphology; and the presence of metastatic disease. Complete surgical resection followed by hepatic transplantation offers the best long-term survival, but few patients are eligible for this therapy. All other therapies are palliative. Radiofrequency ablation is the preferred method for managing unresectable small HCCs that are few in number. More widespread disease is treated with percutaneous therapies such as chemoembolization and selective internal radiation therapy. Systemic administration of biologic and chemotherapeutic agents is minimally successful in slowing the growth of HCC and typically is used to control symptoms in patients with overwhelming disease. A multidisciplinary approach that includes surgery, systemic therapy, and radiation therapy and that is based on the cooperation of radiation oncologists, interventional and diagnostic radiologists, hepatologists, and pathologists may offer the best chance of a cure or at least a longer and more normal life. To participate effectively in this effort, radiologists must be familiar with staging and treatment options for HCC and with the factors that affect the choice of management method.
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Affiliation(s)
- Hollins P Clark
- Department of Radiology, Wake Forest University School of Medicine, Meads Hall, 2nd Floor, Medical Center Blvd, Winston-Salem, NC 27157-1088, USA.
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23
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Zeng ZC, Tang ZY, Fan J, Qin LX, Ye SL, Zhou J, Sun HC, Wang BL, Wang JH. Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients. Int J Radiat Oncol Biol Phys 2005; 63:1067-76. [PMID: 15913915 DOI: 10.1016/j.ijrobp.2005.03.058] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2005] [Revised: 03/23/2005] [Accepted: 03/24/2005] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To evaluate the role of radiotherapy (RT) for hepatocellular carcinoma (HCC) patients with abdominal lymph node (LN) metastasis at our institution in the past 7 years. METHODS AND MATERIALS We identified 125 patients with HCC metastasis to regional LNs treated with or without external beam RT (EBRT) between 1998 and 2004. Clinical characteristics collected included alpha-fetoprotein status, gamma-glutamyltransferase, status of intrahepatic tumors (size and number), previous therapy for intrahepatic tumors, metastatic LN status (location, number, and size), tumor thrombi, and Child-Pugh classification. Of the 125 patients, 62 received local limited EBRT and were classified as the EBRT group. They received locoregional LN irradiation. The tumor dose ranged from 40 to 60 Gy in daily 2.0-Gy fractions, 5 times weekly. Another 63 patients, who did not receive EBRT, were selected from hospitalized patients in the same period and were classified as the non-EBRT group. The parameters studied included survival rates and tumor response to EBRT both as demonstrated by clinical symptoms and as seen on CT. The Kaplan-Meier method was used to evaluate the survival rates, and the Cox regression model was used to identify predictors of outcome. RESULTS After EBRT, partial responses and complete responses were observed in 37.1% and 59.7% of patients, respectively. The median survival was 9.4 months (95% confidence interval 5.8-13.0) for the EBRT group and 3.3 months (95% confidence interval, 2.7-3.9) for the non-EBRT group (p < 0.001). Multivariate analysis showed that multiple intrahepatic primary tumors, occurrence of tumor thrombi, no therapy for intrahepatic tumors, and greater Child-Pugh classification were related to a poorer prognosis in all patients. In the EBRT group, the survival periods decreased as the distance of LN involvement from the liver increased (following the natural flow of lymph) and was also associated with the intrahepatic primary tumor size. The incidence of death resulting from LN-related complications was lower in the EBRT group. CONCLUSION Lymph node metastasis from HCC is sensitive to EBRT. EBRT with 25 fractions of 2 Gy is an effective palliative treatment for patients with LN metastases from HCC presenting with good performance status and may prolong overall survival.
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Affiliation(s)
- Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
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24
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Su YW, Huang YW, Chen SH, Tzen CY. Quantitative analysis of plasma HBV DNA for early evaluation of the response to transcatheter arterial embolization for HBV-related hepatocellular carcinoma. World J Gastroenterol 2005; 11:6193-6. [PMID: 16273649 PMCID: PMC4436639 DOI: 10.3748/wjg.v11.i39.6193] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assesse changes in plasma HBV DNA after TAE in HBV-related HCC and correlate the levels with the pattern of lipiodol accumulation on CT.
METHODS: Between April and June 2001, 14 patients with HBV-associated HCC who underwent TAE for inoperable or recurrent tumor were studied. Levels of plasma HBV DNA were measured by real-time quantitative PCR daily for five consecutive days after TAE. More than twofold elevation of circulating HBV DNA was considered as a definite elevation. Abdominal CT was performed 1-2 mo after TAE for the measurement of lipiodol retention.
RESULTS: Circulating HBV DNA in 10 out of 13 patients was elevated after TAE, except for one patient whose plasma HBV DNA was undetectable before and after TAE. In group I patients (n = 6), the HBV DNA elevation persisted for more than 2 d, while in group II (n = 7), the HBV DNA elevation only appeared for 1 d or did not reach a definite elevation. There were no significant differences in age or tumor size between the two groups. Patients in group I had significantly better lipiodol retention (79.31±28.79%) on subsequent abdominal CT than group II (18.43±10.61%) (P = 0.02).
CONCLUSION: Patients with durable HBV DNA elevation for more than 2 d correlated with good lipiodol retention measured 1 mo later, while others associated with poor lipiodol retention. Thus, circulating HBV DNA may be an early indicator of the success or failure of TAE.
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Affiliation(s)
- Ying-Wen Su
- Department of Pathology, Mackay Memorial Hospital, 45 Minsheng Road, Tamshui, Taipei, Taiwan, China
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25
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Li Y, Si JM, Zhang J, Du J, Wang F, Jia B. Somatostatin receptor subtype 2-mediated scintigraphy and localization using 99mTc-HYNIC-Tyr 3-octreotide in human hepatocellular carcinoma-bearing nude mice. World J Gastroenterol 2005; 11:3953-7. [PMID: 15991301 PMCID: PMC4504904 DOI: 10.3748/wjg.v11.i25.3953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the uptake of 99mTc-HYNIC-Tyr3-octreotide (99mTc-HYNIC-TOC) in human hepatocellular carcinoma (HCC), which can provide the localizable diagnosis in hepatic carcinoma.
METHODS: The expression of somatostatin receptor 2 (SSTR2) messenger RNA (mRNA) in human HCC cell line HepG2 was examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Uptake of 99mTc-HYNIC-TOC was evaluated in the human HCC implanted into BALB/c nude mice. ANMIS2000 nuclear medicine analysis system was used to calculate the ratio of 99mTc uptake between tumor tissue and vital organs.
RESULTS: We demonstrated the expression of SSTR2 mRNA in human HCC cell line HepG2 by RT-PCR. The size of the RT-PCR products was 364 bp detected by sequence analysis of the human SSTR2 mRNA. Scintigraphy proved that 99mTc-HYNIC-TOC was uptaken in the tumor tissue, liver and kidney of the tumor-bearing mice.
CONCLUSION: Based on expression of the SSTR2 mRNA in human HCC, 99mTc-HYNIC-TOC can markedly bind with and be uptaken by human HCC tissues as compared with normal liver tissue. The significant retention of radionuclide in kidney and bladder is probably related to non-specific peptide uptake in the tubulus cells of kidney and possibly due to excretion by kidney. Our results show that localizable diagnosis and targeting radiotherapy with radionuclide-labeled somatostatin analog for HCC are of great value to be further studied.
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Affiliation(s)
- Yong Li
- Gastrointestinal Laboratory of Clinical Medical Institute of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
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Rand T, Loewe C, Schoder M, Schmook MT, Peck-Radosavljevic M, Kettenbach J, Wolf F, Schneider B, Lammer J. Arterial Embolization of Unresectable Hepatocellular Carcinoma with Use of Microspheres, Lipiodol, and Cyanoacrylate. Cardiovasc Intervent Radiol 2005; 28:313-8. [PMID: 15886943 DOI: 10.1007/s00270-004-0153-y] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
We performed a retrospective analysis of 46 patients with histologically confirmed hepatocellular carcinoma (HCC) who were treated with transarterial embolization (TAE) of the hepatic arteries. To induce permanent embolization, microspheres (Embosphere; 100 to 700 micron) and a mixture of ethiodized oil (Lipiodol Ultrafluide) with cyanoacrylate (Glubran) was injected. A total of 106 TAE procedures were performed. Cumulative survival rates were calculated. No patient died during embolization or within the first 24 hours. Severe procedure-related complications were observed in 2 patients. At the time of analysis, 38 of 46 patients were alive. The 180-, 360-, 520-, and 700-day cumulative survival rates for the total study population were 80.6%, 70.7%, 70.7%, and 47.1%, respectively, with a median survival of 666 days. TAE with the use of microspheres and Lipiodol and cyanoacrylate for unresectable HCC is a feasible treatment modality. Bland embolization with the use of microspheres can be used in patients for whom chemoembolization is not desired.
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Affiliation(s)
- Thomas Rand
- Department of Angiography and Interventional Radiology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
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Abstract
Hepatocellular carcinoma is one of the most common malignancies worldwide. The general management of hepatocellular carcinoma begins with an accurate diagnosis. With advances in imaging studies, noninvasive diagnosis has become an accepted standard of care for hepatocellular carcinoma, though pathologic examination is still required in selected cases. Following diagnosis, accurate staging is the next most important step in selecting the most appropriate treatment modality. Patients with localised tumor and compensated liver disease should be considered for partial hepatectomy, and patients with poor hepatic function but early tumor stage are candidates for liver transplantation. Patients who do not qualify for either of these curative treatments may be evaluated for palliative therapy, of which transarterial chemoembolisation is most widely used. This review will discuss the role of biopsy, the pros and cons of noninvasive and pathologic tissue diagnosis as well as the general approach to choose the most appropriate treatment for patients with hepatocellular carcinoma.
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Affiliation(s)
- Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, 750 Welch Road, Suite 210, Palo Alto, CA 94304-1509, USA
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28
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Zhao L, Mou DC, Leng XS, Peng JR, Wang WX, Huang L, Li S, Zhu JY. Expression of cancer-testis antigens in hepatocellular carcinoma. World J Gastroenterol 2004; 10:2034-8. [PMID: 15237429 PMCID: PMC4572328 DOI: 10.3748/wjg.v10.i14.2034] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To investigate the expression of cancer-testis (CT) antigens MAGE-1, SSX-1 ,CTp11 and HCA587 genes in hepatocellular carcinoma (HCC) and the possibility of applying these antigens as targets for specific immunotherapy for HCC.
METHODS: Expression levels of MAGE-1, SSX-1, CTp11 and HCA587 mRNA were detected with reverse transcription polymerase chain reaction (RT-PCR) in HCC tissues and corresponding adjacent non-cancerous tissues from 105 HCC patients, 40 samples of cirrhosis and normal liver tissues. Genes of five samples with positive PCR results were sequenced.
RESULTS: Of 105 HCC tissues, MAGE1, SSX-1 ,CTp11 and HCA587 mRNA expressions were detectable in 75.2% (79/105), 72.4% (76/105), 62.9% (66/105) and 56.2% (59/105) of HCC samples, respectively. About 93.3% (98/105), 72.4% (76/105), 48.6% (51/105) and 37.1% (39/105) of HCC tissues positively expressed at least one, two, three, and four members of CT antigens, respectively. Conversely, only SSX-1 could be detectable in 2.9% (3/105) of the corresponding adjacent non-HCC tissues in which no metastatic lesion was found. Of the latter 3 patients, biopsy samples far from tumor were obtained in 2 patients and RT-PCR indicated no expression of SSX-1 mRNA in these two samples. In addition, none of 40 samples of cirrhotic and normal liver tissues expressed CT antigen gene mRNA. DNA sequences confirmed that the RT-PCR products were true target cDNA. No relationship was found between expression of CT antigens and clinico pathological indicators such as age, gender, tumor size, degree of tumor differentiation, serum α-fetoprotein level and infection of hepatitis B virus or hepatitis C virus (P > 0.05).
CONCLUSION: CT antigens genes (MAGE-1, SSX-1, CTp11 and HCA587) are expressed with high percentage and specificity in HCC and their products are promising targets for antigen-specific immunotherapy of HCC. High frequent co-expression of multiple members of CT antigens in HCC provides possibility of polyvalent vaccinations for HCC.
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Affiliation(s)
- Li Zhao
- Center of Hepatobiliary Surgery, People's Hospital, Peking University, 11 XiZhimen Nandajie, West District, Beijing 100044, China
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Yoon SM, Kim JH, Choi EK, Ahn SD, Lee SW, Yi BY, Chung YW, Lee YS, Seo DJ. Radioresponse of hepatocellular carcinoma-treatment of lymph node metastasis. Cancer Res Treat 2004; 36:79-84. [PMID: 20396570 DOI: 10.4143/crt.2004.36.1.79] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2003] [Accepted: 02/19/2004] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To analyze the radioresponse of hepatocellular carcinomas (HCC), using accurate measurements of the tumor size in extrahepatic lymph node metastasis, and to obtain information for the future treatment of primary intrahepatic lesions. MATERIALS AND METHODS Fifty-one extrahepatic lymph node metastases from primary HCCs, which could be treated by external radiotherapy alone, were included in this study. The radiation dose ranged from 30 to 51 Gy with fraction sizes of 2.0 approximately 3.0 Gy. Responses were determined by measuring the areas on CT scans 0, 1 and 3 months after the completion of radiotherapy. The median follow-up period of the surviving patients was 10 months. RESULTS The overall response rate was 76%, and the important factors were; total dose of radiation, time dose fractionation (TDF) value and the biologically effective dose (BED). A dose of 45 Gy or higher showed an objective response rate of 93%, and if the TDF value was higher than 90, a similar result was observed. In about half (47%) of the patients the maximum response was observed at 3 months or later. The response duration was observable in 14 patients surviving 12 months or longer. Regrowth of irradiated lesions were observed in 4 (66.7%) patients among those who received less than 45 Gy, and in 4 (50%) among those who were treated with 45 Gy or more. There was a statistically significant difference in the survivals between the responders and non-responders (p=0.008). Gastrointestinal bleeding or ulceration was observed in 8 patients, including 3 with NCI common toxicity criteria grade III or higher. CONCLUSION Radiotherapy was an effective palliative modality for extrahepatic metastasis in HCCs. A radiation dose of 45 Gy or higher (or a TDF value >or=90), was required for a major response.
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Affiliation(s)
- Sang Min Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Hsieh CB, Chang HM, Chen TW, Chen CJ, Chan DC, Yu JC, Liu YC, Chang TM, Shen KL. Comparison of transcatheter arterial chemoembolization, laparoscopic radiofrequency ablation, and conservative treatment for decompensated cirrhotic patients with hepatocellular carcinoma. World J Gastroenterol 2004; 10:505-8. [PMID: 14966906 PMCID: PMC4716969 DOI: 10.3748/wjg.v10.i4.505] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: To compare the therapeutic effect of transcatheter arterial chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and conservative treatment for the therapy of decompensated liver cirrhosis patients with hepatocellular carcinomas (HCC).
METHODS: Between October 2000 and July 2003, one hundred patients with histologically proven primary HCC and clinical decompensated liver cirrhosis (Child classification B or C) were included in this study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE group), and forty received conservative treatment (control group). We compared the survival, recurrence, and complication rates in these three groups, making adjustment using the tumor metastastic node staging system.
RESULTS: The major complication rate in the TACE group (9/20) was significantly higher than that in the LRFA group (7/40). For patients with TMN stage II HCC, the survival rate of the LRFA group was better than that of the TACE and control groups (P = 0.003) but the recurrence rates befween the LRFA and TACE groups did not differ.
CONCLUSION: The LRFA group of patients had better clinical outcomes in terms of survival and complication rates in comparison with the TACE group or conservative treatment in patients with decompensated liver cirrhosis, especially in TMN patients with stage II HCC. LRFA is thus an appropriate alternative treatment for poor liver function among patients with HCC.
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Affiliation(s)
- Chung-Bao Hsieh
- Division of General Surgery, Department of Surgery, National Defense Medical Center, Tri-Service General Hospital, 325 Sec 2 Cheng-Kung Road, Taipei, Taiwan, China.
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Deng XD, Shen YZ, Huang M, Yan Y, Sun Q. Contrast-enhanced Doppler Ultrasound for Guiding Percutaneous Microwave Ablation of Hepatocellular Carcinoma: A Report of 32 Cases. J Med Ultrasound 2004. [DOI: 10.1016/s0929-6441(09)60068-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Meza-Junco J, Montaño-Loza A, Candelaria M. Modalidades de tratamiento para pacientes con carcinoma hepatocelular: una serie retrospectiva de una sola institución en México. GASTROENTEROLOGIA Y HEPATOLOGIA 2004; 27:11-7. [PMID: 14718103 DOI: 10.1016/s0210-5705(03)70438-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND To date, curative treatment options for hepatocellular carcinoma (HCC) include orthotopic liver transplantation or surgical resection. Most patients are detected with nonresectable or transplantable HCC due to disease extension or comorbid factors, and are therefore candidates for palliative treatments only. Few follow-up data are available in patients with HCC in Latin America. We therefore reviewed the experience of HCC treatment in a single institution over a 10-year period. PATIENTS AND METHOD A total of 135 patients attending the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a national referral center in Mexico, from January 1991 to December 2000 were included. In all patients etiology, stage, and diagnostic and therapeutic measures were documented. Survival time was calculated as a function of staging and therapy. RESULTS Of 135 patients, 77 (57%) were men and 58 (43%) were women. The mean age at diagnosis was 59.17 years (range: 16-87 years). Cirrhosis was diagnosed in 89 patients (64.4%). The median overall survival for all patients with HCC was 7.9 months. Treatment included surgical resection (n=22), hepatic artery chemoembolization (n=10), percutaneous ethanol injection (n=6), systemic chemotherapy (n=5), tamoxifen (n=11), and thalidomide (n=1). Eighty patients received support measures. The median survival in the group of patients who underwent surgical resection (37.89 months) was significantly higher than that in the groups of patients who did not undergo resection. CONCLUSIONS Patients with HCC who received no treatment had a median survival of 1.7 months. Hepatic resection offers the best chance of cure in patients with HCC. The strong association between HCC and cirrhotic liver disease makes surgical resection difficult in patients with low hepatic reserve.
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Affiliation(s)
- J Meza-Junco
- Departamento de Hemato-Oncología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF, México.
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Martinho JMDSG, Moraes HPD, Oliveira MED, Moreira LFP, Silva ACD, Pereira LDS, Maia F. Modelo de indução de necrose focal hepática: estudo experimental em ratos. Acta Cir Bras 2004. [DOI: 10.1590/s0102-86502004000100008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVO: Investigar a área de necrose focal induzida pela injeção intra-hepática de quatro diferentes substâncias no fígado de ratos. MÉTODOS: Foram utilizados 25 ratos Wistar, com peso variando entre 200 a 250 g, distribuidos em 5 grupos, que receberam 0,1cc das seguintes substâncias: Grupo I (Gr. I) - soro fisiológico a 0,9% (controle). Grupo II (Gr. II) - glicose hipertônica a 50%. Grupo III (Gr. III) - NaCl a 20%. Grupo IV (Gr. IV) - formol a 10%. Grupo V (Gr. V) - etanol. Os animais foram submetidos a laparotomia para que a punção fosse realizada no lobo hepático médio sob visão direta. Todos os animais foram sacrificados após 24 horas da injeção.. Os fígados foram avaliados histologicamente, com o intuito de mensurar a área do tecido necrótico. RESULTADOS: Nos cinco grupos estudados observou-se: Gr. I - 2829mm² (controle); Gr. II - 3805mm² (glicose hipertônica); Gr. III - 3930mm² (NaCl); Gr. IV - 4532mm² (formol) e Gr. V - 6432mm² (etanol). A análise estatística destes valores foi feita pelo método das comparações múltiplas. CONCLUSÃO: 1. O soro fisiológico foi à substância que causou a menor área de necrose (P< 0,05). 2. O NaCl a 20% e a glicose hipertônica a 50% produzem efeitos semelhantes (P > 0,05). 3. O formol a 10% produziu necrose mais extensa que a glicose hipertônica a 50% (P < 0,05) e que o NaCl a 20%, porém não apresentou diferença estatisticamente significativa com esta última (P > 0,05). 4. O etanol foi à substância que, comparada com as outras, mais necrose produziu (P < 0,05).
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Garcea G, Lloyd TD, Aylott C, Maddern G, Berry DP. The emergent role of focal liver ablation techniques in the treatment of primary and secondary liver tumours. Eur J Cancer 2003; 39:2150-64. [PMID: 14522372 DOI: 10.1016/s0959-8049(03)00553-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Only 20% of patients with primary or secondary liver tumours are suitable for resection because of extrahepatic disease or the anatomical distribution of their disease. These patients could be treated by ablation of the tumour, thus preserving functioning liver. This study presents a detailed review of established and experimental ablation procedures. The relative merits of each technique will be discussed and clinical data regarding the efficacy of the techniques evaluated. A literature search from 1966 to 2003 was undertaken using Medline, Pubmed and Web of Science databases. Keywords were Hepatocellular carcinoma, liver metastases, percutaneous ethanol injection, cryotherapy, microwave coagulation therapy, radiofrequency ablation, interstitial laser photocoagulation, focused high-intensity ultrasound, hot saline injection, electrolysis and acetic acid injection. Ablative techniques offer a promising therapeutic modality to treat unresectable tumours. Large-scale randomised controlled trials are required before widespread acceptance of these techniques can occur.
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Affiliation(s)
- G Garcea
- Department of Hepatobiliary Surgery, The Leicester General Hospital, Gwendolen Road, Leicester LE2 7LX, UK.
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Abstract
BACKGROUND Primary hepatocellular carcinoma (HCC) and metastases from colorectal cancer are the most common malignant liver tumours. Surgical resection is the optimum treatment in suitable patients. Interstitial laser thermotherapy (ILT) is gaining acceptance for the treatment of irresectable liver tumours and as a potential alternative to surgery. An understanding of the principles of therapy and review of clinical outcomes may allow better use of this technology. METHOD An electronic search using the Medline database was performed for studies on the treatment of hepatic malignancy published between January 1983 and February 2003. RESULTS Current information on the efficacy of ILT is based on prospective studies. ILT appears to be a safe and minimally invasive technique that consistently achieves tumour destruction. The extent of destruction depends on the fibre design, delivery system, tumour size and tumour biology. Real-time magnetic resonance imaging provides the most accurate assessment of laser-induced tumour necrosis. In selected patients with HCC and colorectal cancer liver metastases, ILT achieves complete tumour necrosis, provides long-term local control, and improves survival, compared with the natural history of the disease. In addition, ILT has survival benefits for patients with other tumour types, especially those with isolated liver metastases from a breast cancer primary. CONCLUSION ILT improves overall survival in specific patients with liver tumours. Advances in laser technology and refinements in technique, and a better understanding of the processes involved in laser-induced tissue injury, may allow ILT to replace surgery as the procedure of choice in selected patients with liver malignancies.
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Affiliation(s)
- M Nikfarjam
- Department of Surgery, University of Melbourne, Austin Hospital, LTB 8, Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia
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Xu HX, Yin XY, Lu MD, Liu GJ, Xu ZF. Estimation of liver tumor volume using a three-dimensional ultrasound volumetric system. ULTRASOUND IN MEDICINE & BIOLOGY 2003; 29:839-846. [PMID: 12837499 DOI: 10.1016/s0301-5629(02)00775-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The usefulness of a new three-dimensional ultrasound (3DUS) volumetric system developed recently was validated in volume measurement of liver tumor in the present study. The system was used to estimate the volumes of 22 regular phantoms, 25 irregular phantoms and 37 liver tumors from 33 patients. The results showed that the consumed time of measurement with the system ranged from 1 to 15 min, depending on different rotation angles. The measured volumes at different rotation angles all significantly correlated with the true volumes and there were no significant differences among measured volumes at different angles. The measurement error of 3DUS was 0.3% +/- 3.3% in regular phantoms, -0.4% +/- 3.7% in irregular phantoms and 0.9% +/- 11.3% in liver tumors, respectively, as compared with -5.3 +/- 9.4%, 13.6 +/- 28.0% and 15.3 +/- 37.3% for two-dimensional ultrasound, respectively (all p < 0.05). The volume estimation with 3DUS also had significant intraobserver and interobserver reproducibility both in vitro and in vivo. It can be concluded that the new system that we used can greatly reduce the consumed time and manual labor for volume measurement with high accuracy and reproducibility. 3DUS volumetry using the new system is more acceptable and valuable in clinical practice and is expected to be useful for evaluation of the efficacy of tumor therapy in situ in patients with hepatic tumors.
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Affiliation(s)
- Hui-Xiong Xu
- Department of Medical Ultrasonics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China
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Iwashita Y, Tahara K, Goto S, Sasaki A, Kai S, Seike M, Chen CL, Kawano K, Kitano S. A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol Immunother 2003; 52:155-61. [PMID: 12649744 PMCID: PMC11032976 DOI: 10.1007/s00262-002-0360-9] [Citation(s) in RCA: 90] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2002] [Accepted: 10/23/2002] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS To evaluate the safety and feasibility of immunotherapy based on autologous dendritic cells (DC) for patients with unresectable primary liver cancer (PLC). METHODS A total of ten patients were enrolled and immunized with DCs. Autologous DCs were generated ex vivo in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Cells were then pulsed with tumor lysate (TL), tumor necrosis factor-alpha (TNF-alpha) and keyhole limpet hemocyanin (KLH). Non-adherent cells were collected on day 9 and cells were administered into the inguinal lymph node. Each patient received 1-10 x 10(6) cells four times at weekly intervals. RESULTS Immunization was well tolerated in all patients without significant toxicity. DC vaccination induced delayed-type hypersensitivity (DTH) against KLH in seven out of ten patients. In one patient, one of the two liver tumors (tumor in segment 7, 13 mm in diameter) decreased in size to 7 mm and showed necrotic change on computed tomography examination after eight immunizations. In two patients, serum levels of tumor markers decreased after vaccination. CONCLUSION The present clinical trial suggested that immunization by TL-pulsed DCs is feasible in patients with unresectable PLC without any toxicity. Further improvement in the clinical results of immunotherapy might be expected by modifying the therapeutic protocol.
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Affiliation(s)
- Yukio Iwashita
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Kouichirou Tahara
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Shigeru Goto
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Atsushi Sasaki
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Seiichiro Kai
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Masataka Seike
- />Department of Medicine I, Oita Medical University, Oita, Japan
| | - Chao-Long Chen
- />Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan R.O.C
| | - Katsunori Kawano
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
| | - Seigo Kitano
- />Department of Surgery I, Oita Medical University, Hasama-machi, 879-5593 Oita, Japan
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Abstract
BACKGROUND Most patients with liver tumours are not suitable for surgery but interstitial ablative techniques may control disease progression and improve survival rates. METHODS A review was undertaken using Medline of all reported studies of cryoablation, radiofrequency ablation, microwave ablation, interstitial laser photocoagulation, high-intensity focused ultrasound and ethanol ablation of primary liver tumours and hepatic metastases. RESULTS Although there are no randomized clinical trials, cryoablation, thermal ablation and ethanol ablation have all been shown to be associated with improved palliation in patients with primary and secondary liver cancer. The techniques can be undertaken safely with minimal morbidity and mortality. CONCLUSION Although surgical resection remains the first line of treatment for selected patients with primary and secondary liver malignancies, interstitial ablative techniques are promising therapies for patients not suitable for hepatic resection or as an adjunct to liver surgery.
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Affiliation(s)
- C Erce
- Department of Clinical and Surgical Sciences (Surgery), University of Edinburgh, Edinburgh, UK
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39
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Abstract
The liver is the commonest site of distant metastasis of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver involved during the course of their diseases. Surgery is the only therapy that offers the possibility of cure for patients with hepatic metastatic diseases. Five-year survival rates after resection of all detectable liver metastases can be up to 40%. Unfortunately, only 25% of patients with colorectal liver metastases are candidates for liver resection, while the others are not amenable to surgical resection. Regional therapies such as radiofrequency ablation and cryotherapy may be offered to patients with isolated unresectable metastases but no extrahepatic diseases. Hepatic artery catheter chemotherapy and chemoembolization and portal vein embolization are often used for the patients with extensive liver metastases but without extrahepatic diseases, which are not suitable for regional ablation. For the patients with metastatic colorectal cancer beyond the liver, systemic chemotherapy is a more appropriate choice. Immunotherapy is also a good option when other therapies are used in combination to enhance the efficacy. Selective internal radiation therapy is a new radiation method which can be used in patients given other routine therapies without effects.
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Affiliation(s)
- Lian-Xin Liu
- Department of Surgery, First Clinical College, Harbin Medical University, No. 23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, China.
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Ahrar K, Gupta S. Hepatic artery embolization for hepatocellular carcinoma: technique, patient selection, and outcomes. Surg Oncol Clin N Am 2003; 12:105-26. [PMID: 12735133 DOI: 10.1016/s1055-3207(02)00089-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Most patients with HCC do not qualify for surgical interventions. In carefully selected patients, TACE may improve survival, reduce the rate of tumor growth, and decrease the incidence of portal vein occlusion. Since the introduction of TACE in the 1980s, the technical aspects of the procedure have significantly improved. Sophisticated angiographic equipment and techniques have made superselective arterial catheterization possible for more focused drug delivery. The use of ethiodized oil allows for more effective targeting of HCC and provides dual embolization of the hepatic artery and the portal venules supplying the tumor. Many important technical questions about TACE remain unanswered at this time: there are no reliable, standardized patient selection criteria, ideal cytotoxic agents have not yet been identified, the optimal dose of ethiodized oil has not been confirmed, and the optimal frequency and timing of repeat treatment sessions remain unknown. One major limitation of TACE--the need for repeated treatments, which can result in deterioration of liver function--may be avoided by use of a combination of interventional therapies. The combination of limited TACE with PEI or RFA may lead to improved survival and decreased risk of liver failure. More recently, two excellent randomized clinical trials have demonstrated significant survival benefit for patients treated with TACE when compared with those treated symptomatically.
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Affiliation(s)
- Kamran Ahrar
- Section of Vascular and Interventional Radiology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 325, Houston, TX 77030, USA.
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Li X, Zheng CS, Feng GS, Zhuo CK, Zhao JG, Liu X. An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features. World J Gastroenterol 2002; 8:1035-9. [PMID: 12439920 PMCID: PMC4656375 DOI: 10.3748/wjg.v8.i6.1035] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish an ideal implantable rat liver tumor model for interventional therapy study and examine its angiographic signs and MRI, CT features before and after embolization.
METHODS: Forty male Wistar rats were implanted with Walker-256 tumor in the left lateral lobe of liver. Digital subtraction angiography (DSA) and transarterial chemoembolization were performed on day 14 after implantation. Native computer tomography (CT, n = 8) and native magnetic resonance (MR, n = 40) were performed between the day 8 and day 21 after implantation. The radiological morphological characteristics were correlated with histological findings.
RESULTS: Successful implantation was achieved in all forty rats, which was confirmed by CT and MRI. MR allowed tumor visualization from day 8 while CT from day 11 after implantation. The tumors were hypodensity on CT, hypointense on MR T1-weighted and hyperintense on T2-weighted. The model closely resembled human hepatocarcinoma in growth pattern and the lesions were rich in vasculature on angiography and got its filling mainly from the hepatic artery. Before therapy, tumor size was 211.9 ± 48.7 mm3. No ascites, satellite liver nodules or lung metastasis were found. One week after therapy, tumor size was 963.6 ± 214.8 mm3 in the control group and 356.5 ± 78.4 mm3 in TACE group. Ascites (4/40), satellite liver nodules (7/40) or lung metastasis (3/40) could be seen on day 21.
CONCLUSION: Walker-256 tumor rat model is suitable for the interventional experiment. CT and MRI are helpful in animal optioning and evaluating experimental results.
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Affiliation(s)
- Xin Li
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Province, China.
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Lee HS, Kim KM, Yoon JH, Lee TR, Suh KS, Lee KU, Chung JW, Park JH, Kim CY. Therapeutic efficacy of transcatheter arterial chemoembolization as compared with hepatic resection in hepatocellular carcinoma patients with compensated liver function in a hepatitis B virus-endemic area: a prospective cohort study. J Clin Oncol 2002; 20:4459-65. [PMID: 12431969 DOI: 10.1200/jco.2002.02.013] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
PURPOSE Identifying a special subgroup of hepatocellular carcinoma (HCC) patients who may benefit from transcatheter arterial chemoembolization (TACE) when compared with the standard treatment of hepatic resection (HR) warrants research in Asian countries. PATIENTS AND METHODS From January 1993 to December 1994, 182 patients with operable HCC (Child-Pugh class A and International Union Against Cancer [UICC] stage T1-3N0M0) were enrolled. After initial TACE and lipiodol computed tomography, 91 received HR and 91, who refused the operation, received repeated sessions of TACE. After stratification according to the tumor stage (UICC and Cancer of the Liver Italian Program [CLIP]) and lipiodol retention pattern, the survival rates of the two treatment groups were compared. The median follow-up period was 83 months. RESULTS As of December 31, 2000, 48 patients who underwent HR and 68 patients who underwent TACE had died. In a subgroup analysis according to tumor stage, the HR group survival rate was significantly higher than the TACE group in both UICC T1-2N0M0 (P =.0058) and CLIP 0 (P =.0027) subgroups. However, there was no significant difference in either UICC T3N0M0 (P =.7512) or CLIP 1-2 (P =.5366) subgroups. Even in patients with UICC T1-2N0M0 HCC, when lipiodol was compactly retained, the survival rate of the HR group was comparable to that of the TACE group (P =.0596). CONCLUSION TACE proved to be as effective as HR in the subpopulations with UICC T3N0M0 or CLIP 1-2 HCC and adequate liver function, and even with UICC T1-2N0M0 HCC when lipiodol was compactly retained in the tumor. In such cases, the choice of treatment modality between TACE and HR may be left to the patient's preference.
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Affiliation(s)
- Hyo-Suk Lee
- Department of Internal Medicine, Liver Research Institute, Seoul National University Hospital, Chongno-gu, Korea.
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Abstract
Liver transplantation is an established treatment modality for patients with hepatocellular carcinoma (HCC), creating a potential for disease-free, long-term survival. In Asia, due to a severe shortage of donors, resection remains the treatment of choice for patients with HCC and good liver functional reserve. The use of marginal donors, split liver grafts and grafts from living donors are potential solutions that are best performed in experienced liver transplant centres to ensure an optimal outcome. Ethical issues relating to living donor liver transplantation have yet to be fully addressed. The roles of therapies to limit tumour progression during the waiting period, such as transarterial chemoembolization, need to be further investigated in the setting of a prospective trial and their benefits better defined.
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Affiliation(s)
- Kenneth S W Mak
- Liver Transplant Unit, National University Hospital, Singapore.
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Molmenti EP, Klintmalm GB. Liver transplantation in association with hepatocellular carcinoma: an update of the International Tumor Registry. Liver Transpl 2002; 8:736-48. [PMID: 12200772 DOI: 10.1053/jlts.2002.34879] [Citation(s) in RCA: 103] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is an epithelial tumor derived from hepatocytes that accounts for more than 80% of all primary hepatic tumors. The severity of the underlying disease is almost always the key factor in deciding whether to consider liver resection or transplantation as its treatment. Data in our registry corresponding to almost 800 patients from transplant centers throughout the world showed that patient survival after liver transplantation was significantly affected by histologic grade, tumor size >5 cm, and the presence of positive nodes. Recurrence-free survival showed a correlation with tumor size >5 cm, positive nodes, bilobar spread, and vascular invasion. At the present time, 59% of patients in our registry are alive, 84% of whom are free of tumor. Of those who died, half did so without evidence of tumor.
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Affiliation(s)
- Ernesto P Molmenti
- Baylor University Medical Center, Transplantation Services, Dallas, TX 75246, USA
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45
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Abstract
In this article, the author reviews the recent advances in the surgical management of hepatocellular carcinoma (HCC). Partial hepatic resection or, in some instances, liver transplantation provides the best chance for cure. Risk of perioperative mortality after partial hepatectomy is less than 5% in most experienced centers. Careful preoperative assessment of hepatic function is important to reduce the risk of postoperative liver failure after liver resection. Long-term outcomes after resection are comparable to those with liver transplantation, with reported 5-year survival rates of 25%-50%. Although limited controlled comparative studies exist, surgical and nonsurgical local ablative therapies, including ethanol and radiofrequency ablation, may result in survival benefit.
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Affiliation(s)
- Michael A Choti
- Department of Surgery, Johns Hopkins University School of Medicine, 1830 Monument Street, Baltimore, MD 21025, USA.
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46
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Abstract
Primary and secondary malignant liver cancers are some of most common malignant tumors in the world. Chemotherapy and radiotherapy are not very effective against them. Surgical resection has been considered the only potentially curtive option, but the majority of patients are not candidates for resection because of tumor size, location near major intrahepatic blood vessels and bile ducts, precluding a margin-negative resection, cirrhotic, hepatitis virus infection or multifocial. Radiofrequence ablation (RFA), which is a new evolving effective and minimally invasive technique, can produce coagulative necrosis of malignant tumors. RFA should be used percutaneously, laparscopically, or during the open laparotomy under the guidance of ultrasound, CT scan and MRI. RFA has lots of advantages superior to other local therapies including lower complications, reduced costs and hospital stays, and the possibility of repeated treatment. In general, RFA is a safe, effective treatment for unresectable malignant liver tumors less than 7.0 cm in diameter. We review the principle, mechanism, procedures and experience with RFA for treating malignant liver tumors.
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Affiliation(s)
- Lian-Xin Liu
- Department of Surgery, the First Clinical College, Harbin Medical University, No.23 Youzheng Street, Nangang District, Harbin 150001, Heilongjiang Province, China.
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Rose DM, Chapman WC. Chemoembolization and interstitial therapies for hepatocellular carcinoma. Cancer Treat Res 2002; 109:101-16. [PMID: 11775431 DOI: 10.1007/978-1-4757-3371-6_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2023]
Affiliation(s)
- D M Rose
- John Wayne Cancer Institute, Santa Monica, CA, USA
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Ishikura S, Ogino T, Furuse J, Satake M, Baba S, Kawashima M, Nihei K, Ito Y, Maru Y, Ikeda H. Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus. Am J Clin Oncol 2002; 25:189-93. [PMID: 11943901 DOI: 10.1097/00000421-200204000-00019] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% CI 28-72%). The 1-year overall survival rate was 25% (95% CI 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT. The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.
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Affiliation(s)
- Satoshi Ishikura
- Radiation Oncology Division, National Cancer Center Hospital East, Kashiwa, Japan
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Benson AB, Mitchell E, Abramson N, Klencke B, Ritch P, Burnhan JP, McGuirt C, Bonny T, Levin J, Hohneker J. Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular carcinoma. Ann Oncol 2002; 13:576-81. [PMID: 12056708 DOI: 10.1093/annonc/mdf079] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Conventional systemic chemotherapy currently available for patients with inoperable hepatocellular carcinoma is ineffective. The purpose of this study was to evaluate the safety and efficacy of eniluracil/5-fluorouracil (5-FU) in the treatment of patients with this highly refractory disease. PATIENTS AND METHODS This multicenter, open-label study evaluated a 28-day oral regimen of 5-FU (1 mg/m2 twice daily) plus the dihydropyrimidine dehydrogenase inhibitor, eniluracil (10 mg/m2 twice daily), in patients with chemotherapy-naive or anthracycline-refractory inoperable hepatocellular carcinoma. RESULTS A total of 36 patients enrolled into the study. No patient showed a confirmed partial or complete tumor response, although nine patients (25%) had a best response of stable disease. The median duration of progression-free survival was 9.6 weeks [95% confidence interval (CI) 9.1-10.6 weeks], and the median duration of overall survival was 32.7 weeks (95% CI 17.4-71.6 weeks). Eniluracil/5-FU was well tolerated. Diarrhea, the most frequent treatment-related non-hematological toxicity, occurred in 11 patients (31%). Hematological toxicities were infrequent and usually mild. CONCLUSIONS Eniluracil/5-FU as a 28-day oral outpatient regimen is well tolerated by patients with inoperable hepatocellular carcinoma, although minimal activity was observed when given as monotherapy at the dose used in this study.
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Affiliation(s)
- A B Benson
- Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA.
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Figueras J, Ramos E, Ibáñez L, Valls C, Serrano T, Rafecas A, Casanovas T, Fabregat J, Xiol X, Torras J, Baliellas C, Jaurrieta E, Casais L. [Surgical treatment of hepatocellular carcinoma. Long term results]. Med Clin (Barc) 2002; 118:410-4. [PMID: 11943103 DOI: 10.1016/s0025-7753(02)72404-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies. MATERIAL AND METHOD Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics. RESULTS Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98). CONCLUSIONS After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.
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Affiliation(s)
- Juan Figueras
- Servicio de Cirugía General, Ciudad Sanitaria y Universitaria de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.
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