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Lu X, Chen Z, Mi W, Zheng J, Liu Y. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE. Open Med (Wars) 2024; 19:20241060. [PMID: 39534429 PMCID: PMC11554448 DOI: 10.1515/med-2024-1060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 09/07/2024] [Accepted: 09/23/2024] [Indexed: 11/16/2024] Open
Abstract
Purpose This study aimed to investigate the role of microtubule-affinity regulatory protein kinase 1 (MARK1) in hepatocellular carcinoma (HCC) progression, its association with sorafenib sensitivity, and the interplay between MARK1 and POTE Ankyrin domain family member E(POTEE) in HCC cells. Methods Quantitative real-time polymerase chain reaction analysis was used to assess MARK1 and POTEE expression in 60 pairs of HCC tissues and cell lines. The correlation between MARK1 levels, clinicopathological features, and patient prognosis was analyzed. Sorafenib-resistant HCC cell models were developed, followed by MARK1 overexpression to evaluate its impact on cell functions. Luciferase reporter assays and rescue experiments were conducted to elucidate the MARK1-POTEE regulatory mechanism. Results MARK1 exhibited decreased mRNA expression in HCC tissues and cells, correlating with adverse clinicopathological features and poorer patient survival. Luciferase assays confirmed direct binding between MARK1 and POTEE. Sorafenib treatment increased MARK1 protein levels, reduced POTEE, and inhibited cell proliferation. Overexpressing MARK1 suppressed sorafenib-induced proliferation in resistant cells, while co-overexpression of MARK1 and POTEE reversed this effect. Conclusion MARK1 potentially restrains HCC progression and enhances sorafenib resistance by negatively modulating POTEE expression, highlighting its significance as a therapeutic target in HCC treatment.
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Affiliation(s)
- Xin Lu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhiyuan Chen
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Wenting Mi
- Gastroenterology Department, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jianming Zheng
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yubin Liu
- Department of Hepatobiliary Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan Second Road, Yuexiu District, Guangzhou, China
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Feng X, Ma Y, Yang J, Peng P, Zeng X, Shen L, Hu T, Luo Q. Comparison of effects of different anesthesia methods on immune function and liver function of liver cancer patients after operation. Biotechnol Genet Eng Rev 2024; 40:2672-2682. [PMID: 37066843 DOI: 10.1080/02648725.2023.2201521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/06/2023] [Indexed: 04/18/2023]
Abstract
Liver cancer, one of the most common malignant tumors, has seriously threatened people's physical and mental health. The paper was conducted to investigate the functions of two different anesthesia methods on Tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and T lymphocyte subsets in patients undergoing liver cancer resection, and to explore the liver function impact of patients undergoing liver cancer surgery. 80 liver cancer patients were split into propofol intravenous anesthesia group and sevoflurane inhalation anesthesia group. The patient's operation-related indicators and changes in TNF-α, CRP and T lymphocyte subsets before anesthesia, after anesthesia, 1 day after anesthesia, and 3 days after anesthesia were calculated. The levels of TNF-α and CRP in the two groups after operation were clearly higher than those before anesthesia, but there was no obvious difference between the two groups. After operation, the TNF-α of the propofol intravenous anesthesia group was lower than the sevoflurane inhalation anesthesia group. The CD3+, CD4+ and CD4+/CD8+ levels in both groups recovered to the pre-anaesthesia level 3 days after the operation. The levels of ALT, AST, ALB and TBIL returned to normal at d4 in both propofol intravenous anesthesia and sevoflurane inhalation anesthesia groups. Compared with evoflurane inhalation anesthesia for patients with liver cancer, intravenous anesthesia with propofol can reduce the body's inflammatory response to a certain extent, has weak inhibitory effect on T lymphocyte immune function, and a smaller effect on liver function.
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Affiliation(s)
- Xi Feng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Yao Ma
- Department of Anesthesiology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuchang, China
| | - Jun Yang
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Pai Peng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Xiaohua Zeng
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Lei Shen
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Tingting Hu
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
| | - Qin Luo
- Department of Anesthesiology, General Hospital of the Yangtze River Shipping (Wuhan Brain Hospital), Hankou, China
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Li JK, Liu XH, Cui H, Xie XH. Radiofrequency ablation vs. surgical resection for resectable hepatocellular carcinoma: A systematic review and meta-analysis. Mol Clin Oncol 2019; 12:15-22. [PMID: 31814972 PMCID: PMC6888042 DOI: 10.3892/mco.2019.1941] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 08/21/2019] [Indexed: 12/13/2022] Open
Abstract
The treatment of hepatocellular carcinoma (HCC) is a significant challenge. Although radiofrequency ablation (RFA) has emerged as a popular therapeutic option for patients with resectable HCC, whether it can achieve comparable survival outcomes compared with surgical resection (RES) remains unclear. The aim of the present study was to conduct a meta-analysis to assess the survival outcomes of RFA vs. RES in patients with early resectable HCC tumors. A Medline, Embase, and Cochrane Library search was performed for data published between January 2000 and February 2018. A meta-analysis of the efficacy of RFA compared with RES for HCC was subsequently performed, with particular emphasis on overall survival and disease-free survival (DFS) rates. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the random-effects model. In the present study, a total of 13,147 patients with HCC were included; of which, 6,727 were treated with RFA and 6,420 were treated with RES. The overall survival rates (OR1-year, 0.757, 95% CI, 0.578–0.989; OR3-year, 0.530, 95% CI, 0.401–0.700; OR5-year, 0.566, 95% CI, 0.423–0.758) and the DRS rates (OR1-year, 0.569, 95% CI, 0.456–0.711; OR3-year, 0.418, 95% CI, 0.267–0.653; OR5-year, 0.374, 95% CI, 0.231–0.606) of RES were significantly higher than those of RFA. The results indicate that RES is superior to RFA for promoting the survival of selected patients with resectable HCC. However, future randomized controlled trials are required to investigate the specific relevance of these modalities in the treatment of HCC.
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Affiliation(s)
- Jia-Kai Li
- Department of Radiology, Hainan Hospital of PLA General Hospital, Sanya, Hainan 572013, P.R. China
| | - Xiao-Hui Liu
- Department of Medical Psychology, Chinese PLA General Hospital and Medical School PLA, Beijing 100853, P.R. China
| | - Hong Cui
- Department of Medical Psychology, Chinese PLA General Hospital and Medical School PLA, Beijing 100853, P.R. China
| | - Xin-Hui Xie
- Department of Medical Psychology, Anhui Medical University, Hefei, Anhui 230032, P.R. China
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Huang W, Chen Y, Chen L, Zhong J, Johri AM, Zhou J. Multimodality imaging-guided local injection of eccentric magnetic microcapsules with electromagnetically controlled drug release. Cancer Rep (Hoboken) 2019; 2:e1154. [PMID: 32935461 DOI: 10.1002/cnr2.1154] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 11/21/2018] [Accepted: 11/26/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In the past decade, trackable smart drug delivery systems have played important roles in the treatment of many diseases such as cancer because the drug carriers can be visualized through their distinct physical properties. However, it is still difficult to achieve precise drug delivery because such systems usually rely on a single imaging system. AIM This study aimed to present a novel type of multimodality imaging-guided strategy to visualize the drug carriers of eccentric magnetic microcapsule (EMM) designed for potential treatment of hepatocellular carcinoma (HCC). METHOD AND RESULTS The EMMs were prepared by using a three-phase microfluidic device. The as-prepared EMMs embedded with Fe3O4 nanoparticles are magnetic, with high density and acoustic impedance, allowing for visualization by magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound (US) imaging during local injection. The release of drug from these EMMs can be further controlled by an external electromagnetic field (EMF). As a proof of concept, we demonstrated the process of multimodality imaging to guide local injection and the controlled release of doxorubicin (DOX) from the EMMs in a phantom. We showed that the release rate of DOX was directly correlated to the strength of the EMF. In addition, we cocultured green fluorescent protein (GFP)-transfected HeLa cancer cells with the DOX-loaded EMMs and documented their apoptosis by DOX following the release triggered by EMF. CONCLUSION The results suggest that these EMMs serve both as contrast agents that can be visualized by multimodality imaging techniques and as smart drug delivery systems, with great potential for precision medicine.
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Affiliation(s)
- Wenwei Huang
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China
| | - Yin Chen
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China
| | - Lanxi Chen
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China
| | - Jinshuang Zhong
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China.,Imaging Department, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Amer M Johri
- Department of Medicine, Division of Cardiology, Cardiovascular Imaging Network at Queen's University, Kingston, ON, Canada
| | - Jianhua Zhou
- School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, China
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Hoffmann RT. CT-Guided Tumor Ablation. MEDICAL RADIOLOGY 2017:945-956. [DOI: 10.1007/174_2017_155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Park EK, Kim HJ, Kim CY, Hur YH, Koh YS, Kim JC, Kim HJ, Kim JW, Cho CK. A comparison between surgical resection and radiofrequency ablation in the treatment of hepatocellular carcinoma. Ann Surg Treat Res 2014; 87:72-80. [PMID: 25114886 PMCID: PMC4127905 DOI: 10.4174/astr.2014.87.2.72] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2014] [Revised: 04/30/2014] [Accepted: 05/14/2014] [Indexed: 02/02/2023] Open
Abstract
Purpose The aim of this study was to compare the therapeutic effects of radiofrequency ablation (RFA) and hepatic resection (HR) with regards to procedural morbidity, mortality, overall survival (OS) and disease-free survival (DFS) rates in hepatocellular carcinoma (HCC) patients. Methods Retrospective studies were performed based on the medical records of 129 patients who underwent curative HR, and 57 who patients received RFA for HCC, between 2005 and 2009. The inclusion criteria of HCC were the presence of three or fewer nodules 3 cm or less in diameter or a single nodule of 5 cm or less. Results The 1-, 3- and 5-year OS rates in the HR group were 91.3%, 78.8%, and 64.9%, compared to 94.4%, 74.0%, and 74.0% in the RFA group, with no significant difference between the two groups (P = 0.725). The estimated 1- and 3-year DFS rates were 70.0% and 53.0% in the HR group and 65.2% and 24.7% in the RFA group, respectively. The DFS rates of HR group were significantly higher than RFA group (P = 0.015). Multivariate analysis identified that recurrence (P = 0.036) and portal hypertension (P = 0.036) were associated with OS and that portal hypertension (P = 0.048) and increased serum α-FP (P = 0.008) were the factors significantly associated with DFS. Conclusion HCC within Milan criteria should consider hepatectomy as the primary treatment if the patient's liver function and general conditions are good enough to undergo surgical operation. But in that RFA revealed similar overall survival to HR, RFA can be an alternative therapy for patients who are eligible for surgical resection.
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Affiliation(s)
- Eun Kyu Park
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Hee Joon Kim
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Choong Young Kim
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Young Hoe Hur
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Yang Seok Koh
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Jung Chul Kim
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Hyun Jong Kim
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
| | - Jin Woong Kim
- Department of Radiology, Chonnam National University Medical School, Gwangju, Korea
| | - Chol Kyoon Cho
- Division of Hepatico-Biliary-Pancreatic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea
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Yu X, Zhao H, Liu L, Cao S, Ren B, Zhang N, An X, Yu J, Li H, Ren X. A randomized phase II study of autologous cytokine-induced killer cells in treatment of hepatocellular carcinoma. J Clin Immunol 2013; 34:194-203. [PMID: 24337625 DOI: 10.1007/s10875-013-9976-0] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Accepted: 11/26/2013] [Indexed: 12/13/2022]
Abstract
PURPOSE This prospective study aims to explore the benefit of cytokine-induced killer cell (CIK) treatment in hepatocellular carcinoma patients, which has not yet been thoroughly studied before. METHODS From January 2004 to May 2009, 132 patients who were initially diagnosed with hepatocellular carcinoma of Barcelona Clinic Liver Cancer (BCLC) stage A, B or C, Child-Pugh scores of A or B and without prior treatment were enrolled in the study. Patients were randomly assigned to either arm 1 (n = 66) to receive CIK treatment plus standard treatment, or arm 2 (n = 66) to receive standard treatment only. The primary end point was overall survival (OS) and the secondary endpoint was progression-free survival as evaluated by Kaplan-Meier analyses and treatment hazard ratios with the Cox proportional hazards model. RESULTS The 1-year (OS: 74.2% vs. 50.0%, 95% CI: 63.6-84.8% vs. 37.8-62.2, p = 0.002), 2-year (OS: 53.0% vs. 30.3%, 95% CI: 40.8-65.2% vs. 19.1-41.5%, p = 0.002), 3-year (OS: 42.4% vs. 24.2%, 95% CI: 30.4-54.4% vs. 13.8-34.6%, p = 0.005) and median overall and progression-free survivals of arm 1 patients were significantly higher than those of arm 2. Therefore, in patients who are not suitable for surgery, significant benefit is obtained from CIK treatment. The main adverse effects of CIK included fever, allergy and headache pain. CONCLUSIONS Hepatocellular carcinoma patients who were not suitable for surgery demonstrate prolonged overall and progression-free survival from CIK treatment.
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Affiliation(s)
- Xiaozhou Yu
- Department of Immunology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
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Iezzi R, Cesario V, Siciliani L, Campanale M, De Gaetano AM, Siciliano M, Agnes S, Giuliante F, Grieco A, Pompili M, Rapaccini GL, Gasbarrini A, Bonomo L. Single-step multimodal locoregional treatment for unresectable hepatocellular carcinoma: balloon-occluded percutaneous radiofrequency thermal ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE). LA RADIOLOGIA MEDICA 2013; 118:555-569. [PMID: 23358819 DOI: 10.1007/s11547-012-0914-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2011] [Accepted: 03/20/2012] [Indexed: 02/06/2023]
Abstract
PURPOSE This study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion >3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year. METHODS AND MATERIALS This pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion >3 cm (range, 3.5-6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed. RESULTS No major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5-5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5-1.3cm). CONCLUSIONS TACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.
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Affiliation(s)
- R Iezzi
- Department of Bioimaging and Radiological Sciences, Institute of Radiology, A Gemelli Hospital, Catholic University, L.go A Gemelli 8, 00168 Rome, Italy.
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Li L, Zhang J, Liu X, Li X, Jiao B, Kang T. Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: a meta-analysis. J Gastroenterol Hepatol 2012; 27:51-8. [PMID: 22004366 DOI: 10.1111/j.1440-1746.2011.06947.x] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM To evaluate the evidence comparing radiofrequency ablation (RFA) and surgical resection (RES) on the treatment of hepatocellular carcinoma (HCC) using meta-analytical techniques. METHODS Literature search was undertaken until March 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model. RESULTS These studies included a total of 877 patients: 441 treated with RFA and 436 treated with RES. The overall survival was significantly higher in patients treated with RES than RFA at 1, 3 and 5 years (respectively: OR: 0.50, 95% CI: 0.29-0.86; OR: 0.51, 95% CI: 0.28-0.94; OR: 0.62, 95% CI: 0.45-0.84). In the RES group the 1, 3, and 5 years recurrence-free survival rates were significantly higher than the RFA group (respectively: OR: 0.65, 95% CI: 0.44-0.97; OR: 0.65, 95% CI: 0.47-0.89; OR: 0.52, 95% CI: 0.35-0.77). RFA had a higher rate of local recurrence (OR: 4.08, 95% CI: 2.03-8.20). For tumors ≤ 3 cm RES was better than RFA in the 3-year overall survival rates (OR: 0.38, 95% CI: 0.16-0.89). CONCLUSIONS Surgical resection was superior to RFA in the treatment of HCC. However, the findings have to be carefully interpreted due to the lower level of evidence.
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Affiliation(s)
- Le Li
- Department of General Surgery, First Affiliated Hospital, China Medical University, Shenyang, Liaoning Province, China
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Superior long-term outcomes after surgery in child-pugh class a patients with single small hepatocellular carcinoma compared to radiofrequency ablation. Hepatol Int 2010; 5:722-9. [PMID: 21484104 DOI: 10.1007/s12072-010-9237-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2010] [Accepted: 12/09/2010] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS There are insufficient data comparing long-term prognoses after radiofrequency ablation (RFA) and surgery. METHODS We compared the baseline characteristics and survival rates of patients (single, ≤3 cm, and Child-Pugh class A) treated surgically (n = 215) and with RFA (n = 255) from January 2000 to December 2007 at our institution. RESULTS The surgery group was characterized by younger age, higher prevalence of HBsAg, less cirrhosis, and an increased chance of Child-Pugh score of 5 and CLIP score of 1, compared to the RFA group. During the median follow-up period of 42 months (range 1-109), the 3-, 5- and 7-year overall survival rates in the surgery group were 98, 94, and 94%, respectively, which were significantly higher than those in the RFA group (92, 87, and 76%, respectively, P = 0.002). The 3- and 5-year recurrence-free survival rates were 72 and 66%, respectively, in the surgery group, which were significantly higher than those in the RFA group (34 and 24%, respectively, P < 0.001). The superiority of the survival rates in the surgery group persisted in most patients throughout the subgroup analysis, based on the Child-Pugh score and CLIP score. Multivariate analysis showed that age and surgery as a procedure type were the significant predictive factors for both overall survival [HR = 1.04 (CI 1.001-1.08), P = 0.047 for age; HR = 2.97 (CI 1.19-7.45), P = 0.02 for surgery] and recurrence-free survival [HR = 1.02 (CI 1.01-1.04), P = 0.01 for age; HR = 2.44 (CI 1.76-3.37), P < 0.001 for surgery]. CONCLUSIONS The long-term outcome after surgery for Child-Pugh class A and single small HCC is superior to that after RFA.
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Meta-analysis of the therapeutic effect of hepatectomy versus radiofrequency ablation for the treatment of hepatocellular carcinoma. Surg Laparosc Endosc Percutan Tech 2010; 20:130-40. [PMID: 20551807 DOI: 10.1097/sle.0b013e3181d823df] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Surgical resection has been considered to be the best treatment for hepatocellular carcinoma (HCC). However, in recent years, there has been growing interest in the therapy of radiofrequency ablation (RFA). This meta-analysis is to evaluate the therapeutic effect of those 2 therapeutic methods. Outcomes evaluated were death rate, complications, survival rates, recurrence-free survival rates, and recurrence. Primary authors were contacted to retrieve further information if necessary. There is no significant difference in death rates of the treatment of HCC in the groups of hepatectomy and RFA, although the recurrence of HCC may be lower in the hepatectomy group. In the group of RFA, the recurrence rate in the previous site was higher but was lower in the new area, whereas it seems equal in the extrahepatic area. RFA may have comparable results with surgical resection in patients in the therapeutic effect of ablation for the treatment of HCC, if recurrence of HCC after RFA could be timely detected and effectively treated.
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Nanashima A, Tobinaga S, Masuda J, Miyaaki H, Taura N, Takeshita H, Hidaka S, Sawai T, Nakao K, Nagayasu T. Selecting treatment for hepatocellular carcinoma based on the results of hepatic resection and local ablation therapy. J Surg Oncol 2010; 101:481-5. [PMID: 20191611 DOI: 10.1002/jso.21523] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND First-line treatment for <or=3 hepatocellular carcinomas (HCCs) <or=3 cm in size remains controversial. The superiority of survival benefit needs to be clarified between these modalities for such lesions. METHODS We examined post-treatment survival of 144 consecutive HCC patients who underwent hepatectomy and of 56 consecutive HCC patients who underwent thermal ablation therapy limited to the HCC (<or=3 cm, <or=3 lesions). RESULTS Pretreatment liver function was significantly worse and prevalence of Child-Pugh classification B/C was significantly higher in the ablation group compared to the hepatectomy group. Prevalence of tumor recurrence after treatment did not differ significantly between groups, irrespective of solitary or multiple HCC. In solitary HCC, overall survival rates in both groups did not differ significantly. Even in Child-Pugh B patients, survival was not significantly different between hepatectomy and ablation. In HCC with 2-3 lesions <or=3 cm, overall survival was significantly longer with hepatectomy than with ablation and mean survival periods in the hepatectomy and ablation groups were 4.5 and 1.2 years, respectively. CONCLUSION In cases of multiple small HCCs, hepatic resection is recommended over local ablation therapy as the first-line treatment in cases where liver function has been preserved.
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Affiliation(s)
- Atsushi Nanashima
- Division of Surgical Oncology, Nagasaki University Hospital, Nagasaki, Japan.
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Iida T, Shiba H, Misawa T, Ohashi T, Eto Y, Yanaga K. Immunogene therapy against colon cancer metastasis using an adenovirus vector expressing CD40 ligand. Surgery 2010; 148:925-35. [PMID: 20378141 DOI: 10.1016/j.surg.2010.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2008] [Accepted: 02/05/2010] [Indexed: 11/15/2022]
Abstract
BACKGROUND Colon cancer is one of the most common cancers worldwide, and liver metastasis is a poor prognostic factor for all types of digestive cancers, including colon cancer. We studied CD40 ligand (CD40L)-mediated immunogene therapy for metastatic liver cancer in rats. METHODS We studied whether in vitro infection of a rat colon cancer cell line (RCN9) with an adenoviral-vector that expresses the CD40L (AxCAmCD40L) induced CD40L expression. In vivo to confirm the antitumor effect induced by AxCAmCD40L, the tumor cells that had been transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngenic rats (prevention model) or AxCAmCD40L was injected into the tumor tissues of the rats (treatment model). Furthermore, immune cells including NK cells, cytotoxic T cells, and tumor-specific antibodies induced by AxCAmCD40L were examined. RESULTS Immunogene therapy using AxCAmCD40L suppressed the tumor growth strongly or reduced tumor size in the prevention model and treatment model. NK cells, cytotoxic T cells, and tumor-specific antibodies contributed to this antitumor effect in both groups. CONCLUSION These observations suggest that CD40L-mediated immunogene therapy for metastatic colon cancer in the liver and lungs is effective and is mediated by the activation of both the cellular and humoral immune systems.
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Affiliation(s)
- Tomonori Iida
- Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.
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15
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Abstract
PURPOSE Evaluation of a new device designed to achieve large volumes of necrosis in hepatocellular carcinoma (HCC) nodules by application of radiofrequency ablation (RFA). MATERIALS AND METHODS 29 consecutive patients with 31 HCC nodules ≥3 cm in diameter (range 3-7.5 cm; mean diameter 5.5 cm) underwent ultrasound (US) guided percutaneous RFA using an expandable electrode with 7 active arrays and saline injection designed to create tissue ablation in areas of up to 7 cm (Starburst XLi-enhanced RFA device). Treatment was performed in general anesthesia (6 patients) or deep sedation (23 patients). Treatment efficacy was assessed by three-phase contrast-enhanced computed tomography (CT) and bimonthly US follow-up. RESULTS One to three electrode insertions (mean number 1.6) were performed in each patient. CT showed complete necrosis in 23/31 HCC nodules (74%) in 22 patients. Follow-up of these 22 patients ranged from 2 to 15 months (mean time 8.3 months). In 6/22 patients (28%) intrahepatic recurrence occurred within 5-10 months (mean time 8.3 months). Major complications were post-ablation syndrome in 7/29 (24%), peritoneal effusion in 4/29 (14%), pleural effusion in 2/29 (7%) and transient obstructive jaundice in 1/29 (3.4%) patients. One patient died 6 months after treatment because of tumor progression. CONCLUSIONS In the treatment of large HCC nodules, Starburst XLi-enhanced is an effective and safe device.
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16
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Takaki H, Yamakado K, Uraki J, Nakatsuka A, Fuke H, Yamamoto N, Shiraki K, Yamada T, Takeda K. Radiofrequency ablation combined with chemoembolization for the treatment of hepatocellular carcinomas larger than 5 cm. J Vasc Interv Radiol 2008; 20:217-24. [PMID: 19097810 DOI: 10.1016/j.jvir.2008.10.019] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2008] [Revised: 10/21/2008] [Accepted: 10/21/2008] [Indexed: 12/11/2022] Open
Abstract
PURPOSE To evaluate survival, recurrence-free survival, technical success, technique effectiveness, and safety of radiofrequency (RF) ablation combined with chemoembolization in patients with hepatocellular carcinomas (HCCs) larger than 5 cm. MATERIALS AND METHODS Patients with Child-Pugh class A or B cirrhosis and three or fewer HCCs with a maximum tumor diameter of 5.1-10 cm were included. Twenty patients with 32 HCCs were included. There were 16 men and four women with mean age of 69 years +/- 7.4 (range, 46-79 years).The maximum mean tumor diameter was 6.2 cm (range, 5.1-9.5 cm). RF ablation was performed under computed tomographic (CT) fluoroscopic guidance 1-2 weeks after chemoembolization. The primary endpoint of this study was survival. RESULTS RF electrodes were placed in the planned sites, and RF ablation was completed with a planned protocol (technical success rate, 100%). Tumor enhancement was eradicated in all patients after 32 RF sessions. The primary and secondary technique effectiveness rates were 40% and 100%, respectively. There were two major complications in the 32 RF sessions (6%)--hepatic abscess and diaphragm perforation. Local tumor progression developed in five of the 20 patients (25%) during the mean follow-up of 30 months. The overall and recurrence-free survival rates were, respectively, 100% and 74% at 1 year, 62% and 28% at 3 years, and 41% and 14% at 5 years. The serum bilirubin level of 1.0 mg/dL (17.1 micromol/L) or less was a significantly better prognostic factor in the univariate analysis. CONCLUSIONS This combination therapy may enhance survival in patients with HCCs larger than 5 cm.
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Affiliation(s)
- Haruyuki Takaki
- Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
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17
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Yamakado K, Nakatsuka A, Takaki H, Yokoi H, Usui M, Sakurai H, Isaji S, Shiraki K, Fuke H, Uemoto S, Takeda K. Early-stage hepatocellular carcinoma: radiofrequency ablation combined with chemoembolization versus hepatectomy. Radiology 2008; 247:260-266. [PMID: 18305190 DOI: 10.1148/radiol.2471070818] [Citation(s) in RCA: 133] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE To retrospectively evaluate the long-term results of radiofrequency (RF) ablation combined with chemoembolization (combination therapy) as compared with hepatectomy for the treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS The study was approved by the institutional review board, and informed consent was waived. Patients with early-stage HCC were included if they underwent either combination therapy or hepatectomy and met the following inclusion criteria: no previous treatment for HCC, three or fewer tumors with a maximum diameter of 3 cm or less each or a single tumor with a maximum diameter of 5 cm or less, Child-Pugh class A liver profile, no vascular invasion, and no extrahepatic metastases. The primary endpoint was overall survival, and the secondary endpoint was recurrence-free survival. RESULTS One hundred four patients (mean age, 66.5 years +/- 8.7 [standard deviation]; 79 men, 25 women) underwent combination therapy, and 62 patients (mean age, 64.5 years +/- 9.6; 51 men, 11 women) underwent hepatectomy. The 1-, 3-, and 5-year overall survival rates following combination therapy (98%, 94%, and 75%, respectively) were similar (P = .87) to those following hepatectomy (97%, 93%, and 81%, respectively). The 1-, 3-, and 5-year recurrence-free survival rates were also comparable (P = .70) for combination therapy (92%, 64%, and 27%, respectively) and hepatectomy (89%, 69%, and 26%, respectively). CONCLUSION RF ablation combined with chemoembolization in patients with early-stage HCC provides overall and disease-free survival rates similar to those achieved by hepatectomy.
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Affiliation(s)
- Koichiro Yamakado
- Department of Radiology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
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18
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Prognostic analysis of pulmonary metastases from hepatocellular carcinoma. Hepatol Int 2008; 2:237-43. [PMID: 19669310 DOI: 10.1007/s12072-008-9052-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2007] [Accepted: 01/23/2008] [Indexed: 02/08/2023]
Abstract
PURPOSE To analyze the prognostic factors for the patients with lung metastases from hepatocellular carcinoma (HCC). METHODS AND MATERIALS One hundred and five patients with lung metastases from HCC were analyzed retrospectively. We analyzed the impact factors, including the gender, age, liver function, serum AFP and gamma-GT level, the status of intrahepatic tumor and pulmonary metastases and treatment for them, the distant metastases beyond the lung, as well as the causes of death. The overall cumulative probability of survival was calculated by the Kaplan-Meier method, and the difference between the groups was compared using the Log-rank test. Univariate and multivariate analyses using the Cox-regression proportional hazard model were performed to evaluate the prognostic parameters for survival. RESULT The survival after the lung metastases was influenced by clinical parameters, such as the status and the treatment for both the intrahepatic tumor and the pulmonary lesions. The causes of death were respiratory failure due to metastatic lesions from HCC in 16 patients (20.0%), liver failure caused by the progressive intrahepatic lesions in 54 (67.5%). The mean and median survival times were 684 and 487 days after HCC diagnosis and 264 and 179 days after lung metastases, respectively. CONCLUSION It was very important to treat the intrahepatic tumor because its worsening was still the major cause of death. The progressive treatment for pulmonary metastases may also be advised for possible prolongation of survival.
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19
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Percutaneous cryoablation of small hepatocellular carcinoma with US guidance and CT monitoring: initial experience. Cardiovasc Intervent Radiol 2008; 31:587-94. [PMID: 18236104 DOI: 10.1007/s00270-008-9293-9] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2007] [Revised: 11/24/2007] [Accepted: 12/28/2007] [Indexed: 12/17/2022]
Abstract
The purpose of this study was to retrospectively determine the safety and effectiveness of percutaneous cryoablation, monitored with computed tomography (CT) and ultrasonographic (US) guidance, for the treatment of hepatocellular carcinoma (HCC). Four patients with small HCCs underwent one percutaneous cryoablation treatment session monitored with CT and US guidance. All patients underwent pretreatment blood chemistry testing and imaging evaluation. We treated lesions with simultaneous insertion of multiple 17-G cryoprobes (two or three) and defined technical success when the extension of a visible iceball was beyond 5 mm from the tumor margin. Intralesional enhancement or tumoral size increase was defined as local progression compared with that on images obtained immediately after ablation. We evaluated complications and follow-up (at 1, 3, and 6 months). All patients survived without short- or long-term complications. Cryoablation was technically successful in all patients at the end of the procedure. During follow-up two patients developed disease recurrence. One patient developed local tumor progression on the margin of the lesion; the other, a new HCC. In the case of local tumor progression a new elevation of alpha-fetoprotein (alphaFP) levels occurred at first follow-up control. In the other case levels of alphaFP remained stable during the first 3 months after the procedure, then demonstrated a progressive increase in alphaFP levels beginning at the fourth month, without tumor evidence during CT control at 3 months. We conclude that percutaneous cryotherapy with US guidance and CT monitoring is a feasible, safe, and effective for treatment of HCC. If local ablative procedures of hepatic lesions are to be performed, percutaneous cryoablation, not laparotomic, should be discussed as an alternative therapeutic measure. Longer follow-up should provide proof of the effectiveness of this technique.
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20
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Duller D, Stiegler P, Schweiger M, Kahn J, Kniepeiss D, Jakoby E, Tscheliessnigg K, Iberer F. Sensitive serum parameters for hepatocellular carcinoma recurrence monitoring after liver transplantation: a case report. Transplant Proc 2007; 39:3281-3. [PMID: 18089371 DOI: 10.1016/j.transproceed.2007.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2007] [Accepted: 04/30/2007] [Indexed: 11/20/2022]
Abstract
Liver cell malignancy can be seen as one of the most common indications for hepatic transplantation, but the recurrence potential of the disease significantly limits its beneficial effects. Hepatic factors influencing the recurrence rate, such as nodule size and criteria wherein transplantations are expedited, are still investigated. Pretransplant intraarterial or percutaneous treatment seem to be predictive for recurrence-free patient survival. Early detection of malignancies via serum parameters as a prognostic factor seems promising. This article reports a special case, where despite an elevated, sensitive, serum marker profile, no HCC recurrence was detected over a 2-year follow-up.
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Affiliation(s)
- D Duller
- Department of Transplantation, Medical University Graz, Gratz, Styria, Austria.
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21
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Liu HY, Teramoto K, Kawamura K, Oda K, Ishiwata K, Arii S. Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG. ACTA ACUST UNITED AC 2007; 14:276-82. [PMID: 17520203 DOI: 10.1007/s00534-006-1133-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2006] [Accepted: 05/08/2006] [Indexed: 11/28/2022]
Abstract
BACKGROUND/PURPOSE [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is regarded as a unique imaging modality, because the images reflect tumor activity. This characteristic of PET encouraged us to use it to develop a novel method of quantitatively measuring liver metastasis viability. METHODS F344 rats were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor growth and tumor activity were measured by PET. We used a tumor viability index (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor proliferation activity, instead of using the standardized uptake value (SUV) of the tumor tissue. The TVI was compared with the number of tumor nodules and the proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell inoculation. RESULTS [(18)F] FDG uptake by the liver tumors was measured by PET, and the TVI was found to increase as the tumor nodules increased in number and size. The TVI values in the experimental model represented the viability of tumors suppressed by chemotherapy, and the values were significantly correlated with the number of nodules and the PCNA index. CONCLUSIONS The TVI was concluded to be superior to the SUV, the commonly used indicator, for evaluating tumor growth, especially that of multiple, small tumors.
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Affiliation(s)
- Han-Yu Liu
- Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo 113-8549, Japan
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22
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Ishiwata K, Liu HY, Teramoto K, Kawamura K, Oda K, Arii S. Tumor viability evaluation by positron emission tomography with [18F]FDG in the liver metastasis rat model. Ann Nucl Med 2006; 20:463-9. [PMID: 17037278 DOI: 10.1007/bf02987255] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
We prepared a liver metastatic tumor model by injection of rat colon adenocarcinoma cells to Fischer F344 rats through portal vein, and applied positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) ([18F]FDG-PET) to this model. At an early stage of the model, multiple small tumor nodules appeared in the inferior lobes of the livers, and extended later into the superior lobes. To evaluate the tumor growth and tumor viability at the early stage, we proposed a new concept, tumor viability index (TVI), instead of the standardized uptake value (SUV) of the [18F]FDG uptake. The TVI was defined by subtracting the signal based on the normal liver from the total signal in the whole liver including tumor nodules: (whole liver SUV-normal liver SUV) x ml of whole liver region of interest (ROI). For the signal of the whole liver, ROIs were placed on six slices covering the whole liver, and the ROI of normal liver region was located in the superior lobe of the liver. The average TVI values increased with tumor growth and significantly correlated with the numbers of tumor nodules. The new concept may be useful for evaluating the tumor viability non-invasively and quantitatively by [18F]FDG-PET.
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Affiliation(s)
- Kiichi Ishiwata
- Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
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23
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Vogl T, Eichler K, Zangos S, Herzog C, Hammerstingl R, Balzer J, Gholami A. Preliminary experience with transarterial chemoembolization (TACE) in liver metastases of uveal malignant melanoma: local tumor control and survival. J Cancer Res Clin Oncol 2006; 133:177-84. [PMID: 17021903 DOI: 10.1007/s00432-006-0155-z] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2006] [Accepted: 08/30/2006] [Indexed: 10/24/2022]
Abstract
PURPOSE To evaluate results in the palliative treatment of patients with liver metastases of uveal malignant melanoma using transarterial chemoembolization (TACE). MATERIALS AND METHODS Superselective TACE was repeatedly performed in 12 patients with liver metastases of uveal malignant melanoma. Six patients presented with solitary liver metastases (6-12 cm in size) and six patients with oligonodular metastases (n < or = 6). The embolization suspension consisted of a maximum of 10 mg/m(2) Mitomycin C, 10 ml Lipiodol, and an injection of 200-450 mg resorbable microspheres for vascular occlusion. In the follow-up, magnetic resonance imaging was performed in 3-month intervals. RESULTS The TACE procedure was well tolerated in all patients without any relevant side effects. Three patients responded to TACE with a size reduction of more than 50% (partial response), five patients with stable disease, and four patients with progressive disease with an increase in volume of more than 25%. Mean survival following primary tumor treatment was 32.9 months, and after first embolization 19.5 months. Lower survival rates were recorded for the progressive group (16.5 months). CONCLUSION Repeated TACE offers a palliative treatment option in patients with oligonodular liver metastases of uveal malignant melanoma.
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Affiliation(s)
- Thomas Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
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24
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Abstract
Primary hepatocellular carcinoma (HCC) is a significant tumor worldwide and represents the most common primary hepatic neoplasm. Staging criteria are important for appreciation of timely work up of these neoplasms in contradiction with surgical colleagues. This article demonstrates the appearance of HCC on multiphasic, multidetector CT (MDCT) and relates these findings to current staging criteria. The variable appearance on different planes of contrast is critical to appreciate in staging this neoplasm. The hypervascular nature of the primary tumor makes MDCT and three-phase imaging a critical feature in the detection and characterization of this tumor. This is especially critical in the patients who are candidates for surgical resection. Additionally, MDCT has allowed arterial phase imaging to define the vascular supply of the tumor. An accurate representation of the size and number of lesions is critical in not only the initial staging but also the follow-up of hepatocellular carcinoma. The post-treatment features including the appearance post-surgically and after radiofrequency ablation can be well appreciated on MDCT.
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Affiliation(s)
- Paul M Silverman
- Department of Radiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
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25
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Kawakami T, Hoshida Y, Kanai F, Tanaka Y, Tateishi K, Ikenoue T, Obi S, Sato S, Teratani T, Shiina S, Kawabe T, Suzuki T, Hatano N, Taniguchi H, Omata M. Proteomic analysis of sera from hepatocellular carcinoma patients after radiofrequency ablation treatment. Proteomics 2005; 5:4287-4295. [PMID: 16254924 DOI: 10.1002/pmic.200401287] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Comparative proteomic analysis was used to search for characteristic alterations in the sera of hepatocellular carcinoma (HCC) patients who had undergone curative radiofrequency ablation treatment. Serum samples collected from eight patients before and after treatment were subjected to 2-DE. Eighty-eight protein spots differentially expressed with the treatment were selected by clustering analysis, and the proteins were identified by MS based on MALDI-TOF/TOF analysis and public database searches. The statistical analysis suggested that four proteins decreased after treatment (pro-apolipoprotein, alpha2-HS glycoprotein, apolipoprotein A-IV precursor, and PRO1708/PRO2044, which is the carboxy terminal fragment of albumin) and that seven proteins were increased after treatment, including leucine-rich alpha2-glycoprotein and alpha1-antitrypsin. These data facilitate the identification of differentially expressed proteins that are involved in HCC carcinogenesis and provide candidate biomarkers for the development of diagnostic and therapeutic tools.
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Affiliation(s)
- Takayuki Kawakami
- Department of Gastroenterology, Graduate School of Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan
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26
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Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 2005; 242:36-42. [PMID: 15973099 PMCID: PMC1357702 DOI: 10.1097/01.sla.0000167925.90380.fe] [Citation(s) in RCA: 144] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
OBJECTIVE To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy, 2 treatments that have not been evaluated with a prospective study. METHODS A total of 76 patients were randomly assigned to 2 groups based on treatment; all had one or 2 tumors with diameter </=3 cm, with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency. RESULTS Follow-up ranged from 12 to 59 months. Among percutaneous injection patients, 18 had recurrence 1 to 37 months after treatment (true recurrence, 11; original safety margin inadequate, 3; limitation of imaging technology to detect tiny tumors, 4). Three injection therapy patients died of cancer 25, 37, and 57 months after treatment. For the surgical resection group, 15 had recurrence 2 to 54 months after treatment (true recurrence, 12; limitation of imaging, 2; neck metastasis, 1). Five resection patients died of cancer at 11, 20, 23, 26, and 52 months, respectively. By Cox regression model and Kaplan-Meier survival analysis, there is no statistical significance for recurrence and survival between treatment groups. However, tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate, and Child class B liver cirrhosis correlated with shorter survival. CONCLUSIONS Percutaneous ethanol injection therapy appears to be as safe and effective as resection, and both treatments can be considered first-line options for small hepatocellular carcinoma.
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Affiliation(s)
- Guan-Tarn Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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27
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Huang GT, Lee PH, Tsang YM, Lai MY, Yang PM, Hu RH, Chen PJ, Kao JH, Sheu JC, Lee CZ, Chen DS. Percutaneous ethanol injection versus surgical resection for the treatment of small hepatocellular carcinoma: a prospective study. Ann Surg 2005. [PMID: 15973099 DOI: 10.1016/s0021-7697(05)80947-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
OBJECTIVE To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy, 2 treatments that have not been evaluated with a prospective study. METHODS A total of 76 patients were randomly assigned to 2 groups based on treatment; all had one or 2 tumors with diameter </=3 cm, with hepatitis without cirrhosis or Child class A or B cirrhosis without evident ascites or bleeding tendency. RESULTS Follow-up ranged from 12 to 59 months. Among percutaneous injection patients, 18 had recurrence 1 to 37 months after treatment (true recurrence, 11; original safety margin inadequate, 3; limitation of imaging technology to detect tiny tumors, 4). Three injection therapy patients died of cancer 25, 37, and 57 months after treatment. For the surgical resection group, 15 had recurrence 2 to 54 months after treatment (true recurrence, 12; limitation of imaging, 2; neck metastasis, 1). Five resection patients died of cancer at 11, 20, 23, 26, and 52 months, respectively. By Cox regression model and Kaplan-Meier survival analysis, there is no statistical significance for recurrence and survival between treatment groups. However, tumor size larger than 2 cm and alpha-fetoprotein over 200 ng/mL correlated with higher recurrence rate, and Child class B liver cirrhosis correlated with shorter survival. CONCLUSIONS Percutaneous ethanol injection therapy appears to be as safe and effective as resection, and both treatments can be considered first-line options for small hepatocellular carcinoma.
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Affiliation(s)
- Guan-Tarn Huang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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28
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Jansen MC, van Hillegersberg R, Chamuleau RAFM, van Delden OM, Gouma DJ, van Gulik TM. Outcome of regional and local ablative therapies for hepatocellular carcinoma: a collective review. Eur J Surg Oncol 2005; 31:331-47. [PMID: 15837037 DOI: 10.1016/j.ejso.2004.10.011] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2004] [Revised: 09/14/2004] [Accepted: 10/01/2004] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Transcatheter arterial (chemo) embolization (TACE), cryoablation (CA) and percutaneous ethanol injection (PEI) were the first regional and local ablative techniques that came into use for irresectable HCC. Radiofrequency ablation (RFA) and interstitial laser coagulation (ILC) followed and have now evolved rapidly. It would not be ethical to compare resection with ablation in patients well enough to undergo major surgery. Therefore, hepatic resection and hepatic transplantation remain the only curative treatment options for HCC. METHODS On the basis of a Medline literature search and the authors' experiences, the principles, current status and prospects of TACE and local ablative techniques in HCC are reviewed. RESULTS Complete tumour necrosis can be achieved in 60-100% of patients treated with PEI (70-100%), cryoablation (60-85%), RFA (80-90%) or ILC (70-97%). After TACE significant tumour response is achieved in 17-61.9% but complete tumour response is rare (0-4.8%) as viable tumour cells remain after TACE. Five-year survival rates are available for TACE (1-8%), PEI (0-70%) and cryoablation (40%). Only PEI and RFA were compared in one RCT. RFA was associated with fewer treatment sessions and a higher complete necrosis rate. Furthermore, all techniques are associated with low morbidity and mortality, but cryoablation seems to be associated with a higher morbidity rate. CONCLUSION TACE has shown to be a valuable therapy with survival benefits in strictly selected patients with unresectable HCC. RFA and PEI are now considered as the local ablative techniques of choice for the treatment of, preferably small, HCC. When tumours are located close to bile ducts or large vessels, PEI remains a valuable therapy. Completeness of ablation can be more easily monitored during cryoablation and another advantage of cryoablation is the possibility of edge freezing. The results of ILC are comparable to RFA with only few side effects and high tumour response rates.
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Affiliation(s)
- M C Jansen
- Department of Surgery, Academic Medical Center, Meibergdreef 9, P.O. Box 22660, 1105 AZ Amsterdam, The Netherlands
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29
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Hong SN, Lee SY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC, Rhee JC, Choi D, Lim HK, Lee KW, Joh JW. Comparing the outcomes of radiofrequency ablation and surgery in patients with a single small hepatocellular carcinoma and well-preserved hepatic function. J Clin Gastroenterol 2005; 39:247-52. [PMID: 15718869 DOI: 10.1097/01.mcg.0000152746.72149.31] [Citation(s) in RCA: 179] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
GOALS To compare the efficacy of radiofrequency ablation (RFA) and surgical resection in a group of patients with a Child-Pugh score of 5 and a single HCC less than 4 cm in diameter. BACKGROUND Radiofrequency ablation (RFA) has become a popular method for treatment of hepatocellular carcinoma (HCC) and has been applied as an alternative primary therapy to surgical resection. STUDY We compared outcomes for 148 patients treated with RFA (n = 55) and those treated surgically (n = 93). RESULTS The rate of local recurrence among patients in the RFA group was significantly higher than in the surgery group (P = 0.005), while the incidence of remote recurrence was similar between the two groups (P = 0.30). The cumulative 1- and 3-year overall survival rates (P = 0.24) and the cumulative 1- and 3-year recurrence-free survival rates (P = 0.54) were not significantly different between the two groups. CONCLUSIONS Despite a higher rate of local recurrence, RFA was found to be as effective as surgical resection for the treatment of single small HCC in patients with well-preserved liver function, in terms of the incidence of remote recurrence and the patients' likelihood of achieving overall and/or recurrence-free survival.
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Affiliation(s)
- Sung Noh Hong
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea
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30
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Abstract
PURPOSE Most men 50 to 80 years old will have development of some degree of benign prostatic hyperplasia (BPH). Many who experience lower urinary tract symptoms (LUTS) will be treated medically. However, significant numbers will have more severe and progressive disease requiring surgery. Transurethral resection of the prostate is the current gold standard of treatment for BPH. Minimally invasive therapies for symptomatic BPH emerge and fade continuously. However, intraprostatic injection for BPH has been used for more than 100 years and may be on the verge of a rebirth. The goal of this review is to familiarize the reader with the origins and history of intraprostatic injection, and its evolution using transperineal, transrectal and transurethral routes with multiple injectants. Initially used to treat urinary retention in men with BPH, its primary indication is now for LUTS. MATERIALS AND METHODS We performed a structured MEDLINE review of the literature on intraprostatic injections from 1966 to 2003, augmented with relevant articles from select journals and documents dating to 1832. RESULTS In patients with BPH transperineal and transurethral injections have the most systematic evaluation. Most injectants will cause localized prostatic necrosis and gland volume reduction with varying degrees of LUTS relief. Anhydrous ethanol is the most widely studied injectable to date. There are advantages and disadvantages associated with each route of injection. CONCLUSIONS Examined for more than a century, the potential for using injectables for prostatic tissue ablation remains significant. More systematic laboratory research and clinical trials, currently ongoing, need to be completed.
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Affiliation(s)
- Mark K Plante
- Division of Urology, Department of Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405, USA.
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Zangos S, Mack MG, Balzer J, Engelmann K, Straub R, Eichler K, Herzog C, Lehnert T, Söllner O, Heller M, Thalhammer A, Vogl TJ. Neoadjuvant Transarterial Chemoembolization (TACE) before Percutaneous MR-guided Laser-induced Thermotherapy (LITT): Results in Large-sized Primary and Secondary Liver Tumors. ACTA ACUST UNITED AC 2004. [DOI: 10.1078/1615-1615-00130] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Vogl TJ, Mack MG, Balzer JO, Engelmann K, Straub R, Eichler K, Woitaschek D, Zangos S. Liver metastases: neoadjuvant downsizing with transarterial chemoembolization before laser-induced thermotherapy. Radiology 2003; 229:457-64. [PMID: 14500854 DOI: 10.1148/radiol.2292021329] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
PURPOSE To evaluate a treatment protocol with repeated transarterial chemoembolization (TACE) before laser-induced thermotherapy (LITT) in patients with unresectable liver metastases that are too large for LITT alone. MATERIALS AND METHODS One hundred sixty-two patients who had unresectable liver metastases, with the largest lesion as large as 80 mm in diameter, and no more than four lesions were treated with repeated TACE between March 1999 and December 2001. TACE was performed with a maximum of 10 mg/m2 mitomycin for chemotherapy and a maximum of 15 mL/m2 of iodized oil and microspheres for vessel occlusion. Tumor volume before and during treatment was measured at magnetic resonance (MR) imaging. If the diameter of the tumor decreased to less than 50 mm, the patients were treated with MR imaging-guided LITT 4-6 weeks following embolization. RESULTS Eighty-two patients (62 with metastases from colorectal cancer, 14 with metastases from breast cancer, and six with metastases from other primary tumors) responded to TACE, with a mean reduction in tumor size of 35% +/- 14 (SD), and were treated with LITT. Each patient underwent two to seven TACE treatments (mean, 4.3) prior to LITT. In 47 patients, no reduction in tumor size was achieved, which led to further follow-up. In 33 patients, disease progression was found, with either an increasing size of the lesions (n = 18) or newly developing metastases (n = 15), and these results led to further TACE treatments or change to systemic chemotherapy. Median survival of patients who responded to this combined treatment was 26.2 months; in patients treated with only TACE, median survival was 12.8 months (range, 0.3-29.4 months). CONCLUSION With repeated TACE, reduction in size of primary unresectable hepatic metastases is achieved in 50.6% of cases and allows local ablative treatments such as MR imaging-guided LITT.
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Affiliation(s)
- Thomas J Vogl
- Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
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Giorgio A, Tarantino L, de Stefano G, Scala V, Liorre G, Scarano F, Perrotta A, Farella N, Aloisio V, Mariniello N, Coppola C, Francica G, Ferraioli G. Percutaneous sonographically guided saline-enhanced radiofrequency ablation of hepatocellular carcinoma. AJR Am J Roentgenol 2003; 181:479-484. [PMID: 12876030 DOI: 10.2214/ajr.181.2.1810479] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE The purpose of our study was to analyze the efficacy, side effects, and short-term complications of saline-enhanced percutaneous radiofrequency ablation performed under sonographic guidance in a series of cirrhotic patients with hepatocellular carcinoma. SUBJECTS AND METHODS. Between September 2000 and June 2002, 84 patients (55 men and 29 women) with cirrhosis who ranged in age from 48 to 74 years (mean age, 64 years) and who had 95 hepatocellular carcinomas (seven patients had two tumors and two patients had three tumors) were treated with high frequency-induced thermotherapy. The diameters of the tumors ranged from 1.5 to 8.5 cm (mean, 3.6 cm). The efficacy of radiofrequency ablation was evaluated with triphasic contrast-enhanced CT performed 4 weeks after the procedure. RESULTS Posttreatment CT showed complete necrosis in 73 (77%) of 95 hepatocellular carcinomas in 62 patients. Complete necrosis based on tumor size was seen in 40 (95%) of 42 tumors with diameters equal to or smaller than 3 cm, 32 (71%) of 45 tumors with diameters between 3.1 and 5.0 cm, and one (12%) of eight tumors with diameters larger than 5.0 cm. Twenty-two hepatocellular carcinomas showed incomplete necrosis. None of the patients experienced major complications. Four patients were lost to follow-up. The length of the follow-up period ranged from 4 to 22 months (mean, 10 months). One patient died 8 months after the radiofrequency ablation treatment. All the remaining patients are still alive. During the follow-up period, eight (10%) of 80 patients showed a local recurrence on sonography and CT. CONCLUSION Our experience suggests that percutaneous radiofrequency ablation of hepatocellular carcinoma with high frequency-induced thermotherapy is safe and effective in the treatment of hepatocellular carcinomas equal to or smaller than 3 cm, fairly effective for hepatocellular carcinomas between 3 and 5 cm, and ineffective for tumors larger than 5 cm.
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Affiliation(s)
- Antonio Giorgio
- Interventional Ultrasound Service, D. Cotugno Hospital, Viale Colli Aminei 491, Naples 80131, Italy
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Gaiani S, Celli N, Cecilioni L, Piscaglia F, Bolondi L. Review article: percutaneous treatment of hepatocellular carcinoma. Aliment Pharmacol Ther 2003; 17 Suppl 2:103-10. [PMID: 12786621 DOI: 10.1046/j.1365-2036.17.s2.21.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In early stage hepatocellular carcinoma (HCC), liver transplantation, surgical resection and percutaneous techniques are classified as radical treatments, and may be offered to about 25% of all patients with HCC evaluated in referral centres. The restricted inclusion criteria for surgical resection and the shortage of liver donors for transplantation have stimulated an increasing demand for minimally invasive treatments able to achieve effective and reproducible percutaneous tumour ablation, with less associated morbidity and lower cost than other interventions. Among percutaneous techniques, ethanol injection has proven to be highly effective in single HCC up to 3 cm, with a rate of complete response of 80%, being well tolerated and with a limited risk of minor complication. In larger and/or multinodular HCC the efficacy is reduced to 50% of complete response in nodules between 3 and 5 cm, and to lower rate in larger tumours. Alternative options to ethanol injection have been recently proposed, including radiofrequency, microwave and laser thermal ablation, aimed to extend the necrotic area thus improving the rate of complete response. To date, radiofrequency is the most used technique, with a reported rate of complete response of 90-98% in nodules smaller than 3 cm, and with the advantage of fewer sessions, otherwise counteracted by a higher rate of side-effects. Microwave and laser are promising technologies, but only few clinical data are available. Randomized controlled trials are needed in order to assess treatment response, long-term survival, rate of complication and cost-efficacy of newer technologies in comparison to ethanol injection.
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Affiliation(s)
- S Gaiani
- Dipartimento di Medicina Interna e Gastroenterologia, Università di Bologna, Italy.
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von Euler H, Olsson JM, Hultenby K, Thörne A, Lagerstedt AS. Animal models for treatment of unresectable liver tumours: a histopathologic and ultra-structural study of cellular toxic changes after electrochemical treatment in rat and dog liver. Bioelectrochemistry 2003; 59:89-98. [PMID: 12699824 DOI: 10.1016/s1567-5394(03)00006-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
INTRODUCTION Electrochemical treatment (EChT) has been taken under serious consideration as being one of several techniques for local treatment of malignancies. The advantage of EChT is the minimal invasive approach and the absence of serious side effects. Macroscopic, histopathological and ultra-structural findings in liver following a four-electrode configuration (dog) and a two-electrode EChT design (dog and rat) were studied. MATERIALS AND METHODS 30 female Sprague-Dawley rats and four female beagle dogs were studied with EChT using Platinum:Iridium electrodes and the delivered dose was 5, 10 or 90 C (As). After EChT, the animals were euthanized. RESULTS The distribution of the lesions was predictable, irrespective of dose and electrode configuration. Destruction volumes were found to fit into a logarithmic curve (dose-response). Histopathological examination confirmed a spherical (rat) and cylindrical/ellipsoidal (dog) lesion. The type of necrosis differed due to electrode polarity. Ultra-structural analysis showed distinct features of cell damage depending on the distance from the electrode. Histopathological and ultra-structural examination demonstrated that the liver tissue close to the border of the lesion displayed a normal morphology. CONCLUSIONS The in vivo dose-planning model is reliable, even in species with larger tissue mass such as dogs. A multi-electrode EChT-design could obtain predictable lesions. The cellular toxicity following EChT is clearly identified and varies with the distance from the electrode and polarity. The distinct border between the lesion and normal tissue suggests that EChT in a clinical setting for the treatment of liver tumours can give a reliable destruction margin.
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Affiliation(s)
- Henrik von Euler
- Department of Small Animal Clinical Sciences, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences (SLU), Uppsala, Sweden.
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Szklaruk J, Silverman PM, Charnsangavej C. Imaging in the diagnosis, staging, treatment, and surveillance of hepatocellular carcinoma. AJR Am J Roentgenol 2003; 180:441-54. [PMID: 12540450 DOI: 10.2214/ajr.180.2.1800441] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Janio Szklaruk
- Division of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 57, Houston, TX 77030-4009, USA
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Abstract
Minimally invasive therapies are gaining increasing attention as an alternative to standard surgical therapies in the treatment of primary hepatocellular carcinoma. These include therapies administered transcatheterally (arterial embolization, intraarterial chemoinfusion, and combination chemoembolization) and percutaneously (chemical ablation with ethanol or acetic acid, and thermal ablation with radiofrequency, microwave, or laser energies). Benefits over surgical resection include the anticipated reduction in morbidity and mortality, low cost, suitability for real time image guidance, the ability to perform ablative procedures on outpatients, and the potential application in a wider spectrum of patients, including nonsurgical candidates. This review examines reported clinical success, potential complications, current limitations, and future directions of development of chemoembolization, ethanol and acetic acid instillation, and radiofrequency, microwave, and laser thermal ablation.
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Affiliation(s)
- S Nahum Goldberg
- Minimally Invasive Tumor Therapy Laboratory, Department of Radiology, Beth Israel Deaconess medical Center, Harvard Medical School, Boston Massachusetts 02215, USA.
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Ahrar K, Madoff DC, Gupta S, Wallace MJ, Price RE, Wright KC. Development of a large animal model for lung tumors. J Vasc Interv Radiol 2002; 13:923-8. [PMID: 12354827 DOI: 10.1016/s1051-0443(07)61776-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Minimally invasive locoregional therapies for human liver tumors have been developed in recent years, and similar treatment options may be successful in the management of human lung cancer. Our goal was to develop a lung tumor model in a large animal to simulate human lung cancer for preclinical assessment of novel therapeutic options. MATERIALS AND METHODS Fresh canine transmissible venereal tumor (cTVT) fragments were inoculated into the lungs of 10 dogs by intraarterial (n = 2) or percutaneous (n = 8) methods. Cyclosporin was administered to produce immunosuppression in nine of the dogs. Tumor growth was monitored at regular intervals (every 1-2 weeks) by computed tomography. All animals were killed between 6 and 10 weeks after inoculation; complete necropsy examinations were performed and appropriate tissues were removed for gross and histopathologic evaluation. RESULTS Administration of tumor fragments into the right apical pulmonary artery resulted in the development of more than 20 well-defined scattered pulmonary nodules in the affected lung segment. Nodules grew to a maximum diameter of 12 mm in 10 weeks. Percutaneous inoculation of tumor fragments resulted in more predictable growth of solitary tumors (range, 7-35 mm in diameter) in the transplantation bed. No tumor growth was observed in the dog that did not receive cyclosporin. CONCLUSIONS Percutaneous inoculation and intraarterial transplantation of cTVT fragments in the canine lung result in predictable patterns of tumor growth resembling the solitary pulmonary nodules and metastatic disease found in humans. In addition, cyclosporin administration may be necessary to promote growth of viable tumor.
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Affiliation(s)
- Kamran Ahrar
- University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 325, Houston, Texas 77030, USA.
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Abstract
Radiofrequency thermal ablation is receiving increasing attention as an alternative to standard surgical therapies for the treatment of liver neoplasms. Benefits over surgical resection include the anticipated reduction in morbidity and mortality, low cost, suitability for real time image guidance, the ability to perform ablative procedures on outpatients, and the potential application in a wider spectrum of patients, including nonsurgical candidates. This review examines reported clinical results of this new therapeutic technique, potential complications, current limitations, thermal ablation mechanisms, as well as technical features and diagnostic modalities used in the procedure.
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Affiliation(s)
- Giuseppe D'Ippolito
- Minimally Invasive Therapies Laboratory, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Liu LX, Zhang WH, Jiang HC, Zhu AL, Wu LF, Qi SY, Piao DX. Arterial chemotherapy of 5-fluorouracil and mitomycin C in the treatment of liver metastases of colorectal cancer. World J Gastroenterol 2002; 8:663-7. [PMID: 12174375 PMCID: PMC4656317 DOI: 10.3748/wjg.v8.i4.663] [Citation(s) in RCA: 17] [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: Regional chemotherapy using hepatic artery catheters is a good method of treating patients with colorectal cancer liver metastases. We investigated the survival of patients with liver metastases from colorectal cancer using 5-fluorouracil (5-FU) and mitomycin C Cthrough implantable hepatic arterial infusion port.
METHODS: Seventy-five patients with inoperable liver metastases from colorectal cancer were included between March, 1992 and November, 2001. We placed implantable hepatic arterial catheter (HAC) port by laparotomy.5-FU, 1000 mg/m2/d continuous infusion for five days every four weeks, was delivered in the hepatic arterial catheter through the port. Mitomycin C, 30 mg/m2/d infusion in the first day every cycle through the port. Response to the treatment was evaluated by serial determinations of plasma CEA and imaging techniques consisting of computerized tomography and sonography of liver.
RESULTS: Sixty-eight were performed hepatic artery chemotherapy and fifty-six were followed up among seventy-five HAC patients. Twenty-six patients (46.4%) have responded and 4 complete remission were achieved. Eight patients (14.3%) had stable liver metastases. Twenty-two patients (39.3%) were progressed with increased tumor size and number. Twenty-nine patients (51.8%) had a decreased serum CEA level, while 10 patients (17.9%) were stable and 17 patients (30.4%) had an increased serum CEA level. There were no operative death in this series. Complications, which occurred in 18 patients (32.1%), were as followed: hepatic artery thrombosis in 11, Upper gastric and intestinal bleeding in 3, liver abscess in 1, pocket infection in 1, cholangitis in 1, and hepatic artery pseudo-aneurysm in one patient.
CONCLUSION: Combined infusion of 5-FU and mitomycin C by hepatic artery catheter port is an effective treatment for liver metastases from colorectal cancer. The high response and lower complication rates prove the adjuvant treatment of colorectal cancer with this treatment.
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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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Ahmed M, Lobo SM, Weinstein J, Kruskal JB, Gazelle GS, Halpern EF, Afzal SK, Lenkinski RE, Goldberg SN. Improved coagulation with saline solution pretreatment during radiofrequency tumor ablation in a canine model. J Vasc Interv Radiol 2002; 13:717-24. [PMID: 12119331 DOI: 10.1016/s1051-0443(07)61850-8] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS Significantly greater RF heating (73 degrees C +/- 11 degrees C at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47 degrees C +/- 5 degrees C observed when 18% or no NaCl was injected (P <.02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P <.01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice.
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Affiliation(s)
- Muneeb Ahmed
- Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA
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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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Abstract
Intraoperative magnetic resonance imaging (iMRI) is a new development in medicine that bridges the specialties of surgery and radiology. Deficiencies in the visualization of anatomical architecture and the perception of tumour boundaries in conventional open surgery have led to the integration of imaging within surgery. The superior soft tissue and multiplanar imaging features of magnetic resonance (MR) make this imaging modality superior to that of alternatives. The unique properties of MR to detect heat change and perfusion, and diffusion characteristics of tissue enhance the usefulness of this medium. Concurrent developments in computer aided image guidance and thermoablative technology, herald the era of minimally invasive tumour ablation. Applications have been developed for areas such as neurosurgery, general surgery, gynaecology and urology.
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Affiliation(s)
- Laurence Gluch
- Magnetic Resonance Therapy Unit, Brigham and Womens' Hospital, Boston, Massachusetts, USA.
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Abstract
The liver is one of the most common sites for cancer metastases that result in significant morbidity and mortality. Although surgical resection is associated with improvements in local control and survival, only a minority of patients are candidates for this approach. Radiofrequency ablation (RFA) is an important alternative/complementary tool in the treatment of metastatic disease to the liver and can lead to palliation as well as increased survival in selected patients. RFA has been shown to be safer and better tolerated than other ablative techniques and has been associated with a low rate of local recurrence when performed properly. RFA also has shown some promise in combination with surgical resection and other therapies. Patients who undergo RFA still suffer from progressive metastatic disease, reinforcing the premise that local therapies have little impact on the natural history of aggressive cancers. Trials combining RFA with surgical resection and regional and systemic chemotherapy are ongoing and it is the hope that RFA combined with multimodality adjuvant therapy will reduce the development of both local disease and progressive metastatic disease, leading to improved overall survival.
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Affiliation(s)
- Alexander A Parikh
- Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA
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