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Wang C, Luo X, Dong SL, Leng C, Zhang BX, Zhang BH. Small hepatocellular carcinoma suppressed by chemotherapy for synchronous gastric carcinoma after laparoscopy-assisted radical distal gastrectomy: A case report and literature review. Medicine (Baltimore) 2018; 97:e13190. [PMID: 30557968 PMCID: PMC6319982 DOI: 10.1097/md.0000000000013190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2018] [Accepted: 10/17/2018] [Indexed: 11/26/2022] Open
Abstract
RATIONALE Synchronous gastric carcinoma and hepatocellular carcinoma (HCC) is rare. It is hard to distinguish synchronous HCC from metastatic liver cancer in this condition. The treatment and prognosis is quite different for synchronous HCC of gastric carcinoma and liver metastasis of gastric carcinoma. PATIENT CONCERNS A 68-year-old man with a chief complaint of epigastric pain for 1 year, accompanied by reflux and belching. The patient was diagnosed with gastric carcinoma (cT4NxM0) and laparoscopy-assisted radical distal gastrectomy was performed. This was followed by chemotherapy of FOLFOX regimen. However, a liver nodule growth was observed after postoperative systemic treatment. DIAGNOSIS The initial diagnosis was liver metastasis of gastric carcinoma. However after hepatectomy of segment VI and VII as well as thrombectomy of right hepatic vein, histology revealed intermediate to poor differentiated HCC. Hence this case was diagnosed as synchronous gastric carcinoma and HCC. INTERVENTIONS A preventive transcatheter arterial chemoembolization (TACE) was conducted at 4 weeks after hepatectomy. Another FOLFOX regimen was suggested, but was refused by the patient. OUTCOMES The patient survived without tumor recurrence for 9 months after the second surgery. LESSONS Synchronous HCC should be routinely distinguished from gastric carcinoma liver metastasis, especially for patients with hepatitis B virus (HBV) infection. The FOLFOX4 regimen for treating gastric carcinoma liver metastasis may have inhibited the progression of primary HCC in this case. This patient with HCC benefited from liver resection, inspite of hepatic vein tumor thrombosis.
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Affiliation(s)
- Chao Wang
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Luo
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shui-Lin Dong
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chao Leng
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bi-Xiang Zhang
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bin-Hao Zhang
- Hepatic Surgery Center, Department of Surgery, Tongji Hospital of Tongji Medical College
- Division of General Surgery, Sino-French Branch of Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wan LL, Zhang DQ, Zhang JN, Ren LQ. Anti-hepatocarcinoma activity of TT-1, an analog of melittin, combined with interferon-α via promoting the interaction of NKG2D and MICA. J Zhejiang Univ Sci B 2018; 18:522-531. [PMID: 28585428 DOI: 10.1631/jzus.b1600369] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality. Immunotherapy has emerged in clinical treatment, owing to the limitation and severe side effects of chemotherapy. In the immune system, natural killer (NK) cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex (MHC) molecule issues. Hence, treatment which could stimulate NK cells is of great interest. Here, we investigated the efficacy of the combined therapy of TT-1 (a mutant of melittin) and interferon-α (IFN-α) on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo, as well as the mechanism involved. The combination therapy significantly inhibited the growth of HepG-2/Huh7 cells in vivo, but this effect was impaired after depleting NK cells. TT-1 not only up-regulated MHC class I-related chain molecules A (MICA) expression, but also prevented the secretion of soluble MICA (sMICA). Both the mRNA and protein of a disintegrin and metallopeptidase 10 (ADAM 10) in HepG-2/Huh7 cells were decreased after TT-1 treatment. The combined therapy of TT-1 and IFN-α could suppress the growth of HepG-2/Huh7 xenografted tumor effectively via promoting the interaction of NK group 2, member D (NKG2D) and MICA, indicating that TT-1+IFN-α would be a potential approach in treating liver cancer.
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Affiliation(s)
- Lan-Lan Wan
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China.,Department of Anesthesiology, the Second Hospital of Jilin University, Changchun 130041, China
| | - Da-Qi Zhang
- Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Changchun 130033, China
| | - Jin-Nan Zhang
- Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China
| | - Li-Qun Ren
- Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China
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Gaitantzi H, Meyer C, Rakoczy P, Thomas M, Wahl K, Wandrer F, Bantel H, Alborzinia H, Wölfl S, Ehnert S, Nüssler A, Bergheim I, Ciuclan L, Ebert M, Breitkopf-Heinlein K, Dooley S. Ethanol sensitizes hepatocytes for TGF-β-triggered apoptosis. Cell Death Dis 2018; 9:51. [PMID: 29352207 PMCID: PMC5833779 DOI: 10.1038/s41419-017-0071-y] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 09/19/2017] [Accepted: 10/09/2017] [Indexed: 12/14/2022]
Abstract
UNLABELLED Alcohol abuse is a global health problem causing a substantial fraction of chronic liver diseases. Abundant TGF-β-a potent pro-fibrogenic cytokine-leads to disease progression. Our aim was to elucidate the crosstalk of TGF-β and alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol and TGF-β and cell fate was determined. Fluidigm RNA analyses revealed transcriptional effects that regulate survival and apoptosis. Mechanistic insights were derived from enzyme/pathway inhibition experiments and modulation of oxidative stress levels. To substantiate findings, animal model specimens and human liver tissue cultures were investigated. RESULTS On its own, ethanol had no effect on hepatocyte apoptosis, whereas TGF-β increased cell death. Combined treatment led to massive hepatocyte apoptosis, which could also be recapitulated in human HCC liver tissue treated ex vivo. Alcohol boosted the TGF-β pro-apoptotic gene signature. The underlying mechanism of pathway crosstalk involves SMAD and non-SMAD/AKT signaling. Blunting CYP2E1 and ADH activities did not prevent this effect, implying that it was not a consequence of alcohol metabolism. In line with this, the ethanol metabolite acetaldehyde did not mimic the effect and glutathione supplementation did not prevent the super-induction of cell death. In contrast, blocking GSK-3β activity, a downstream mediator of AKT signaling, rescued the strong apoptotic response triggered by ethanol and TGF-β. This study provides novel information on the crosstalk between ethanol and TGF-β. We give evidence that ethanol directly leads to a boost of TGF-β's pro-apoptotic function in hepatocytes, which may have implications for patients with chronic alcoholic liver disease.
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Affiliation(s)
- Haristi Gaitantzi
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Christoph Meyer
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Pia Rakoczy
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
- Miltenyi Biotec GmbH, Friedrich-Ebert-Straße 68, 51429, Bergisch Gladbach, Germany
| | - Maria Thomas
- Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376, Stuttgart, Germany
| | - Kristin Wahl
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Franziska Wandrer
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Heike Bantel
- Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Hamed Alborzinia
- Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
| | - Stefan Wölfl
- Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
| | - Sabrina Ehnert
- Eberhard-Karls University Tübingen, BG Trauma Center, SWI, Schnarrenbergstraße 95, 72076, Tübingen, Germany
| | - Andreas Nüssler
- Eberhard-Karls University Tübingen, BG Trauma Center, SWI, Schnarrenbergstraße 95, 72076, Tübingen, Germany
| | - Ina Bergheim
- University of Vienna, Department of Nutritional Sciences, Molecular Nutritional Science, Althanstr. 14, UZA II, A-1090, Wien, Austria
| | - Loredana Ciuclan
- Roche Products Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, UK
| | - Matthias Ebert
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Katja Breitkopf-Heinlein
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Steven Dooley
- Department of Medicine II, Section Molecular Hepatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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Lin M, Liang S, Wang X, Liang Y, Zhang M, Chen J, Niu L, Xu K. Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer. Oncotarget 2017; 8:81967-81977. [PMID: 29137237 PMCID: PMC5669863 DOI: 10.18632/oncotarget.17804] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Accepted: 04/29/2017] [Indexed: 12/17/2022] Open
Abstract
In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 -15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, P = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, P = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, P < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, P < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer.
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Affiliation(s)
- Mao Lin
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
| | - Shuzhen Liang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China
| | - Xiaohua Wang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China
| | - Yinqing Liang
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China
| | | | - Jibing Chen
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
| | - Lizhi Niu
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China.,Department of Oncology, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China
| | - Kecheng Xu
- Department of Biological Treatment Center, Fuda Cancer Hospital, Jinan University School of Medicine, Guangzhou, China.,Fuda Cancer Institute, Guangzhou, China
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Lyu T, Wang X, Su Z, Shangguan J, Sun C, Figini M, Wang J, Yaghmai V, Larson AC, Zhang Z. Irreversible electroporation in primary and metastatic hepatic malignancies: A review. Medicine (Baltimore) 2017; 96:e6386. [PMID: 28445252 PMCID: PMC5413217 DOI: 10.1097/md.0000000000006386] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Liver cancer makes up a huge percentage of cancer mortality worldwide. Irreversible electroporation (IRE) is a relatively new minimally invasive nonthermal ablation technique for tumors that applies short pulses of high frequency electrical energy to irreversibly destabilize cell membrane to induce tumor cell apoptosis. METHODS This review aims to investigate the studies regarding the use of IRE treatment in liver tumors and metastases to liver. We searched PubMed for all of IRE relevant English language articles published up to September 2016. They included clinical trials, experimental studies, observational studies, and reviews. This review manuscript is nothing with ethics issues and ethical approval is not provided. RESULTS In recent years, increasingly more studies in both preclinical and clinical settings have been conducted to examine the safety and efficacy of this new technique, shedding light on the crucial advantages and disadvantages that IRE possesses. Unlike the current leading thermal ablation techniques, such as radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, IRE requires shorter ablation time without damaging adjacent important vital structures. CONCLUSION Although IRE has successfully claimed its valuable status in the field of hepatic cancer treatment both preclinical and clinical settings. In order to systemically test and establish its safety and efficacy for clinical applications, more studies still need to be conducted.
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Affiliation(s)
- Tianchu Lyu
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Xifu Wang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Zhanliang Su
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Junjie Shangguan
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Chong Sun
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Matteo Figini
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Vahid Yaghmai
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - Andrew C. Larson
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
| | - Zhuoli Zhang
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
- Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA
- Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Tianjin, China
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Yang B, Zan RY, Wang SY, Li XL, Wei ML, Guo WH, You X, Li J, Liao ZY. Radiofrequency ablation versus percutaneous ethanol injection for hepatocellular carcinoma: a meta-analysis of randomized controlled trials. World J Surg Oncol 2015; 13:96. [PMID: 25889181 PMCID: PMC4355988 DOI: 10.1186/s12957-015-0516-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 02/14/2015] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are treatment methods for patients with early-stage hepatocellular carcinoma (HCC) who are not suitable for surgery. Although some reports indicate that RFA is better than PEI, results from previous reviews and analyses are inconsistent. Therefore, this meta-analysis was performed to more thoroughly evaluate the effects of these treatments in patients with HCC. METHODS A literature search was conducted using the Excerpta Medica dataBASE, PubMed, the Cochrane Library, the American Society of Clinical Oncology database, the China National Knowledge Infrastructure database, the Wanfang database, the Chinese Biomedical Literature Database, and the Chongqing VIP database without language limitations. The primary outcome evaluated was overall survival, and secondary outcomes included complete response and local recurrence. Comparisons were made between Asian and European studies. RESULTS Total pooled and subgroup analyses of Asian studies that included selection biases revealed that RFA is superior to PEI with respect to overall survival (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.37 to 0.80; P < 0.01) and complete response (relative risk (RR), 1.10; 95% CI 1.03 to 1.18; P < 0.01). However, no significant difference was observed between RFA and PEI in the European studies. In Asian studies, RFA was associated with a lower local recurrence rate than PEI at 1 year (RR, 0.44; 95% CI 0.20 to 0.95; P < 0.05) and 3 years (RR, 0.35; 95% CI 0.22 to 0.55; P < 0.01). However, local recurrence was significantly lower after only 3 years in European studies (RR, 0.50; 95% CI 0.32 to 0.78; P < 0.05). CONCLUSIONS RFA was only superior to PEI in Asian studies that included selection bias. Thus, there is insufficient evidence to support the idea that RFA is superior to PEI for patients with cirrhotic HCC. Additional large-scale, multicenter, randomized controlled trials that control for selection bias are needed to fully elucidate the optimal treatment method for HCC.
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Affiliation(s)
- Biao Yang
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Rui-yu Zan
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Shi-yu Wang
- Department of Radiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
| | - Xiang-lian Li
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Mao-ling Wei
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Wen-hao Guo
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Xin You
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
| | - Jing Li
- Chinese Evidence-Based Medicine Centre, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, China.
| | - Zheng-yin Liao
- Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, No. 17 Renming Road, Chengdu, 610000, People's Republic of China.
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Alnaggar M, Niu L, Li J, Yao F, Wang Y, Zeng J, Ye J, Chen J, Mu F, Xu K. Cryoprotective therapy for huge hepatocellular carcinoma: a study of 14 patients with a single lesion. Cryobiology 2014; 69:457-61. [PMID: 25445461 DOI: 10.1016/j.cryobiol.2014.10.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Revised: 10/03/2014] [Accepted: 10/07/2014] [Indexed: 02/07/2023]
Abstract
Percutaneous cryoablation is a potential cure for hepatocellular carcinoma (HCC). This study reviewed retrospectively clinical data from 14 patients who underwent cryoablation of huge HCC (long diameter >7 cm). The side effects of cryosurgeries and liver function reverse were recorded and compared everyday. All the patients survived cryosurgery and none died before leaving hospital 2 weeks later. Despite liver-protective treatment before cryosurgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels were increased significantly, but returned to preoperative levels 2 weeks post-cryosurgery. Before cryosurgery, mean total bilirubin (T.BIL) and direct bilirubin (D.BIL) levels were normal; 8-10 days after cryosurgery, they increased more than two-fold, but returned to the preoperative level 2 weeks post-cryosurgery. Serum transaminase and bilirubin levels were compared between hepatitis B positive and negative patients. The hepatitis B negative group's AST level increased significantly 1 day post-cryosurgery (mean, 186 U/L) and decreased to the preoperative level at day 14. In the hepatitis B positive group, means transaminase and bilirubin reached peak values at different days post-cryosurgery. Overall, ALT and AST are valuable indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, close attention to the serum bilirubin level should be paid 8-10 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment caused by cryosurgery of huge HCC.
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Affiliation(s)
- Mohammed Alnaggar
- Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1277 of JieFang Road, Wuhan 430032, China
| | - Lizhi Niu
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Jialiang Li
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Fei Yao
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Yuan Wang
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Jianying Zeng
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Jin Ye
- Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1277 of JieFang Road, Wuhan 430032, China
| | - Jibing Chen
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China.
| | - Feng Mu
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Kecheng Xu
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
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8
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Niu LZ, Li JL, Xu KC. Percutaneous Cryoablation for Liver Cancer. J Clin Transl Hepatol 2014; 2:182-8. [PMID: 26355719 PMCID: PMC4521246 DOI: 10.14218/jcth.2014.00017] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 06/15/2014] [Accepted: 06/27/2014] [Indexed: 12/15/2022] Open
Abstract
Based on the primary tumor site, liver cancer can be divided into two categories: (1) primary liver cancer and (2) metastatic cancer to the liver from a distant primary site. Guided cryoablation via many imaging methods induces iceball formation and tumor necrosisand is an attractive option for treating unresectable hepatocellular carcinoma (HCC) and metastatic liver cancer. There are several advantages to using cryoablation for the treatment of liver cancer: it can be performed percutaneously, intraoperatively, and laparoscopically; iceball formation can be monitored; it has little impact on nearby large blood vessels; and it induces a cryo-immunological response in situ. Clinically, primary research has shown that percutaneous cryoablation of liver cancer is relatively safe and efficient, and it can be combined with other methods, such as radiation therapy, chemotherapy, and immunology, to control disease. Although research is preliminary, cryosurgery is fast becoming an alternative treatment method for HCC or liver tumors. Here, we review the mechanisms of liver tumor cryoablation, cryoablation program selection, clinical efficiency, and complications following treatment.
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Affiliation(s)
- Li-Zhi Niu
- Fuda Cancer Hospital, Jinan University School of Medicine, Tianhe District, Guangzhou, China
- Guangzhou Fuda Cancer Institute, Tianhe District, Guangzhou, China
| | - Jia-Liang Li
- Guangzhou Fuda Cancer Institute, Tianhe District, Guangzhou, China
| | - Ke-Cheng Xu
- Fuda Cancer Hospital, Jinan University School of Medicine, Tianhe District, Guangzhou, China
- Guangzhou Fuda Cancer Institute, Tianhe District, Guangzhou, China
- Correspondence to: Kecheng Xu, No.2 of Tangde West Rd, Tianhe District, Guangzhou, China. Tel: +86-020-38993994-8700, Fax: +86-020-38993994-8700. E-mail:
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9
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Ali AMA, Lizhi N, Jialiang L, Fei Y, Yuan W, Jianying Z, Jin Y, Jibing C, Feng M, Kecheng X. Cryoprotective therapy for hepatocellular carcinoma: study of 51 patients with a single lesion. Cryobiology 2014; 69:61-7. [PMID: 24859156 DOI: 10.1016/j.cryobiol.2014.05.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2014] [Revised: 02/27/2014] [Accepted: 05/08/2014] [Indexed: 02/06/2023]
Abstract
Percutaneous cryoablation is a potentially curative treatment for hepatocellular carcinoma (HCC). After liver cryosurgery, rapid elevations of transaminases and bilirubin are common, but are usually transient and normalize within a few days. This study retrospectively reviewed clinical data from 51 patients who underwent liver cryoablation in our hospital during the past 4.5 years. Sixty-six percutaneous cryoablations were performed in these patients and transaminase and bilirubin levels before and after the procedure were observed. Although most patients received liver-protective treatment before cryosurgery, transaminase levels were double (mean alanine transaminase (ALT) and aspartate transaminase (AST) were 71 U/L and 85 U/L, respectively) the normal ranges in our hospital. One day after cryosurgery, ALT and AST had increased 3.3-fold (peak mean was 241 U/L) and 5-fold (peak mean was 427 U/L), respectively, but were close to the preoperative level 5 days post-cryosurgery. No significant increase of serum bilirubin was observed. Serum transaminase and bilirubin levels were compared between hepatitis B positive and hepatitis B negative patients. Only in the hepatitis B positive group were total bilirubin (74 μmol/L/23 μmol/L=3.2) and direct bilirubin (45 μmol/L/12 μmol/L=3.8) more than 3 times the preoperative level 7-9 days after treatment. Overall, ALT and AST are valuable as indicators of liver function impairment following cryosurgery. In patients with hepatitis B virus, serum bilirubin was 3 times the preoperative level 7-9 days after cryosurgery. Liver-protective treatment may alleviate liver function impairment due to cryosurgery.
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Affiliation(s)
- Alnaggar Mohammed Abdulatef Ali
- Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1277 of JieFang Road, Wuhan 430032, China
| | - Niu Lizhi
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Li Jialiang
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Yao Fei
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Wang Yuan
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Zeng Jianying
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Ye Jin
- Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, No. 1277 of JieFang Road, Wuhan 430032, China
| | - Chen Jibing
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China.
| | - Mu Feng
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Xu Kecheng
- Fuda Cancer Hospital, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 Tangdexi Road, Tianhe District, Guangzhou 510665, China
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Niu L, Li J, Zeng J, Zhou L, Wang S, Zhou X, Sheng L, Chen J, Xu K. Comparison of percutaneous cryoablation with microwave ablation in a porcine liver model. Cryobiology 2014; 68:194-9. [PMID: 24485805 DOI: 10.1016/j.cryobiol.2014.01.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 12/19/2013] [Accepted: 01/13/2014] [Indexed: 11/26/2022]
Abstract
We compared imaging and pathological changes between argon-helium cryosurgical (AH) and microwave (MW) ablation in a porcine liver model. Immediately after ablation, computed tomography (CT) imaging showed that the area affected by MW ablation was considerably greater than that affected by AH ablation; moreover, the surface area of necrotic tissue was considerably greater in the AH group, whereas the depth of the necrotic area was similar. Seven days after ablation, the affected area had not changed much in the AH group, but it had significantly increased in the MW group; similarly, the surface and depth of the necrotic areas had not changed much in the AH group, but they had increased significantly in the MW group. The pathological findings showed similar definitive areas for both groups at both time points. The findings indicated that long time after both therapies, complete tissue necrosis can be achieved, but the extent and depth of necrosis differ: necrosis foci after AH ablation could be predicted by ice ball under CT image, and necrosis foci after MW ablation will increase obviously. MW ablation might therefore be suitable for tumors with a larger volume and simple anatomical structures, and AH ablation might be suitable for tumors with complex anatomical structures or those located near important organs. These two methods could therefore be used in combination in clinical settings, but details of the procedure need to be studied.
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Affiliation(s)
- Lizhi Niu
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 of Tangdexi Road, Tianhe District, Guangzhou 510665, China
| | - Jialiang Li
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China
| | - Jianying Zeng
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China
| | - Liang Zhou
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China
| | - Song Wang
- Department of Interventional Ultrasound, Yuquan Hospital, Tsinghua University, No. 5 of Shijingshan Road, Shijingshan District, Beijing 100049, China
| | - Xulong Zhou
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China
| | - Lin Sheng
- Department of Interventional Ultrasound, Yuquan Hospital, Tsinghua University, No. 5 of Shijingshan Road, Shijingshan District, Beijing 100049, China.
| | - Jibing Chen
- Fuda Institute of Cryosurgery for Cancer, No. 2 of Tangdexi Road, Tianhe District, Guangzhou 510665, China.
| | - Kecheng Xu
- Fuda Cancer Hospital, School of Medicine, Jinan University, No. 2 of Tangdexi Road, Tianhe District, Guangzhou, Guangdong 510665, China; Fuda Institute of Cryosurgery for Cancer, No. 2 of Tangdexi Road, Tianhe District, Guangzhou 510665, China
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Niu LZ, Li JL, Zeng JY, Mu F, Liao MT, Yao F, Li L, Liu CY, Chen JB, Zuo JS, Xu KC. Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer. World J Gastroenterol 2013; 19:3473-3480. [PMID: 23801841 PMCID: PMC3683687 DOI: 10.3748/wjg.v19.i22.3473] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2012] [Revised: 03/22/2013] [Accepted: 05/10/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To retrospectively assess the effect of comprehensive cryosurgery (ablation of intra- and extra-hepatic tumors) plus dendritic cell-cytokine-induced killer cell immunotherapy in metastatic hepatocellular cancer.
METHODS: We divided 45 patients into cryo-immunotherapy (21 patients), cryotherapy (n = 12), immunotherapy (n = 5) and untreated (n = 7) groups. Overall survival (OS) after diagnosis of metastatic hepatocellular cancer was assessed after an 8-year follow-up.
RESULTS: Median OS was higher following cryo-immunotherapy (32 mo) or cryotherapy (17.5 mo; P < 0.05) than in the untreated group (3 mo) and was higher in the cryo-immunotherapy group than in the cryotherapy group (P < 0.05). In the cryo-immunotherapy group, median OS was higher after multiple treatments (36.5 mo) than after a single treatment (21 mo; P < 0.05).
CONCLUSION: Cryotherapy and, especially, cryo-immunotherapy significantly increased OS in metastatic hepatocellular cancer patients. Multiple cryo-immunotherapy was associated with a better prognosis than single cryo-immunotherapy.
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12
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Shen A, Zhang H, Tang C, Chen Y, Wang Y, Zhang C, Wu Z. Systematic review of radiofrequency ablation versus percutaneous ethanol injection for small hepatocellular carcinoma up to 3 cm. J Gastroenterol Hepatol 2013; 28:793-800. [PMID: 23432154 DOI: 10.1111/jgh.12162] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/08/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) have been used for patients with hepatocellular carcinomas (HCCs) < 3 cm, but there is controversy which of the two methods is superior. Therefore, we aimed to conduct a systematic review to assess survival, complete tumor necrosis, recurrence and metastasis, major complications, costs, hospital stays, and posttreatment survival quality of RFA versus PEI for treating small HCCs < 3 cm. METHODS We conducted a search for published articles in PubMed, Embase, and the Cochrane Library until March 2012. Only randomized controlled trials (RCTs) and quasi-randomized clinical trials were included. RESULTS Four RCTs with 766 patients were included in this review. We found that RFA is significantly better than PEI with respect to a 3-year overall survival for small HCCs (RFA vs PEI, hazard ratios [HR] = 0.66, 95% confidence interval [CI]: 0.48-0.90, P = 0.009), especially for HCCs > 2 cm (HR = 0.56, 95% CI: 0.31-0.99, P = 0.045). RFA had a lower risk of local recurrence (HR = 0.38, 95% CI: 0.15-0.96, P = 0.040), but no difference is seen for distant intrahepatic recurrence. RFA had higher rates of complete tumor necrosis, but RFA also caused more major complications and was more costly than PEI. Begg's and Egger's tests detected no significant publication bias among the four RCTs. CONCLUSIONS RFA appears superior to PEI with respect to local tumor control and 3-year survival for small HCCs < 3 cm. RFA was more feasible in patients with HCCs > 2 cm or Child-Pugh A liver function.
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Affiliation(s)
- Ai Shen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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13
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Mu F, Niu L, Li H, Liao M, Li L, Liu C, Chen J, Li J, Zuo J, Xu K. Percutaneous comprehensive cryoablation for metastatic hepatocellular cancer. Cryobiology 2012; 66:76-80. [PMID: 23237910 DOI: 10.1016/j.cryobiol.2012.11.008] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Accepted: 11/30/2012] [Indexed: 02/06/2023]
Abstract
Percutaneous ablation is the currently preferred locoregional therapy for non-resectable hepatocellular cancer (HCC). Cryoablation is an attractive option because it forms an ice ball viewable by many imaging methods. This study assessed the therapeutic effect of comprehensive cryoablation (of intra- and extrahepatic tumors) in patients with metastatic HCC. Forty-five patients met the inclusion criteria from January, 2004 to October, 2011. Treatment was performed on 33 patients; 12 patients received no treatment. Procedural safety and overall survival (OS) were assessed according to metastatic stage. The OS of patients who received comprehensive treatment was significantly longer than that of those who received no treatment (median: 26 vs. 3.5months, P<0.001). Large (⩾5cm long diameter) hepatic tumors were treated in advance with transarterial chemoembolization, but the OS of patients in the same metastatic stage was similar (P=0.0677). In the comprehensive cryoablation group, timely treatment (within 2months after diagnosis of metastatic HCC) was associated with a longer OS than when treatment was delayed for 3-7months (median: 38.5 vs. 21months, P=0.0167). Multiple treatments improved the survival of patients who received comprehensive treatment (P=0.0489). In terms of increasing the survival time of metastatic HCC patients, the effect of comprehensive cryosurgery was significant. Timely or multiple treatments had greater therapeutic effects than delayed or single treatment.
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Affiliation(s)
- Feng Mu
- Fuda Hospital, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, No. 91 Judezhong Road, Haizhu District, Guangzhou 510305, China
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14
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Eun HS, Kim MJ, Kim HJ, Ko KH, Moon HS, Lee ES, Kim SH, Lee HY, Lee BS. The retrospective cohort study for survival rate in patients with advanced hepatocellular carcinoma receiving radiotherapy or palliative care. THE KOREAN JOURNAL OF HEPATOLOGY 2012; 17:189-98. [PMID: 22102385 PMCID: PMC3304653 DOI: 10.3350/kjhep.2011.17.3.189] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background/Aims This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC). Methods From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients' Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in survival between the two groups was done to investigate the efficacy of RT. Results Under the analysis in survival, the mean survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein, transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients. In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha fetoprotein was an independent predictors of worse overall survival rate in patients. Conclusions We found that the survival of patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good option for in patients with advanced HCC.
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Affiliation(s)
- Hyuk Soo Eun
- Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
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15
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Liang Y, Yin D, Hou L, Zheng T, Wang J, Meng X, Lu Z, Song X, Pan S, Jiang H, Liu L. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma. PLoS One 2011; 6:e23908. [PMID: 21901145 PMCID: PMC3162018 DOI: 10.1371/journal.pone.0023908] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2010] [Accepted: 07/31/2011] [Indexed: 12/22/2022] Open
Abstract
Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB) pathway and the NF-κB–regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.
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Affiliation(s)
- Yingjian Liang
- Key Laboratory of Hepatosplenic Surgery, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, People's Republic of China
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Belghiti J, Durand F. Criteria for liver transplantation for hepatocellular carcinoma: what is an acceptable outcome? Liver Int 2011; 31 Suppl 1:161-3. [PMID: 21205155 DOI: 10.1111/j.1478-3231.2010.02413.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The incidence of hepato cellular carcinoma (HCC) and the shortage of grafts restrict liver transplantation (LT) in HCC patients with a low risk of recurrence. The risk of recurrence is mainly related to the presence of vascular invasion which increases in parallel with tumour size and number of nodules. A favourable post-transplant outcome has been observed in patients who meet the empirically defined Milan criteria, namely, a single nodule < 5 cm or two or three nodules each < 3 cm in the absence of macroscopic vascular invasion, based on pre-transplant imaging. These criteria were felt to be too restrictive, leading several centers to propose expanded criteria for LT. However, increasing both the size and number of nodules resulted in an increased risk of recurrence. It has not been demonstrated that loco-regional treatment in HCC patients listed for LT (bridging therapies) improve post-transplant survival. More precise predictors of negative prognostic factors including elevated α-feto protein level, poor differentiation and molecular techniques should be considered in order to optimize the use of grafts and achieve zero recurrence.
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Affiliation(s)
- Jacques Belghiti
- Department of Hepato-Pancreato-Biliary and Transplantation Surgery, Beaujon Hospital, Assistance Publique Hôpitaux de Paris, Clichy, France.
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Giuliani ME, Knox J, Dawson LA. Malignant Intracardiac Thrombus from Hepatocellular Carcinoma Treated with External Beam Radiation Therapy. J Palliat Med 2010; 13:1293-5. [DOI: 10.1089/jpm.2010.0040] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
- Meredith E. Giuliani
- Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
| | - Jennifer Knox
- Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, Ontario, Canada
| | - Laura A. Dawson
- Department of Radiation Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
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Transcatheter arterial chemoembolization for advanced hepatocellular carcinoma with inferior vena cava and right atrial tumors. Cardiovasc Intervent Radiol 2008; 31:735-44. [PMID: 18427894 DOI: 10.1007/s00270-008-9342-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2007] [Revised: 03/09/2008] [Accepted: 03/17/2008] [Indexed: 01/14/2023]
Abstract
Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 microm, N = 9; and (B) 47-180 microm, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/8 [corrected] patients) for group A and 72.2% [corrected] for group B (13/18 [corrected] patients) (p < 0.01). [corrected] No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 microm) are superior to large ones (>180 microm).
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Shan YS, Hsieh YH, Lin PW. Telomerase Activity in Tumor and Remnant Liver as Predictor of Recurrence and Survival in Hepatocellular Carcinoma after Resection. World J Surg 2007; 31:1121-8. [PMID: 17429564 DOI: 10.1007/s00268-006-0783-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Results after curative liver resection in hepatocellular carcinoma are unsatisfactory with regard to high postoperative intrahepatic recurrence and liver failure. This study evaluates telomerase activity in liver with and without tumor as a predictor of recurrence and survival. MATERIALS AND METHODS Liver tissue with and without tumor from 53 hepatocellular carcinoma patients receiving curative resection during the period of 1998-2000 was used for detecting telomerase activity by PCR-ELISA. Clinicopathological data were compared to identify predictors of recurrence and survival. RESULTS Telomerase activity was detected in 98% of liver tissue with tumor and 70% liver tissue without. Telomerase activity in cancerous liver correlated significantly with HCV infection (P = 0.012) and cirrhotic change in liver parenchyma (P = 0.006). Telomerase activity in non-cancerous liver correlated with high serum AFP level (P = 0.002). The telomerase activity of liver tissue with and without tumor is significant higher in patients with recurrence than in those without recurrence, 413.7 +/- 100.5 versus 110.8 +/- 32.7, P = 0.006, and 34.7 +/- 14.2 versus 4.2 +/- 1.4, P = 0.039. Recurrence could be predicted by abnormally high tumor telomerase activity (P = 0.026) or by advanced TNM stage (P = 0.001). TNM stage or high serum ALT level could predict multinodular intrahepatic recurrence (P = 0.028 and P = 0.030). High serum AFP combined with high telomerase activity in liver without tumor had a significant ability to predict poor survival (OR: 11.19, CI: 1.95-64.12, P = 0.007). CONCLUSION Tumor telomerase is an independent predictor of recurrence. Simultaneous high remnant liver telomerase and high serum AFP is a strong negative predictor of survival.
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Affiliation(s)
- Yan-Shen Shan
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, 70428, Tainan, Taiwan ROC
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20
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Zhou ZH, Liu LM, Chen WW, Men ZQ, Lin JH, Chen Z, Zhang XJ, Jiang GL. Combined therapy of transcatheter arterial chemoembolisation and three-dimensional conformal radiotherapy for hepatocellular carcinoma. Br J Radiol 2006; 80:194-201. [PMID: 17038412 DOI: 10.1259/bjr/33521596] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
To evaluate the toxicity and efficacy of combined therapy of three-dimensional conformal radiotherapy (3DCRT) and transcatheter arterial chemoembolisation (TACE) for hepatocellular carcinoma (HCC). 50 HCC patients treated by combined TACE and 3DCRT were selected from a patient database. Sequence of treatments was that TACE was performed first, followed by 3DCRT with an interval of about 4 weeks between. TACE was administered by 5-Fu 500-600 mg m(-2), cis-platinum 30-40 mg m(-2), epi-adriamycin 40-60 mg m(-2) mixed with iodized oil and Gelfoam embolisation. A median of two courses of TACE was given. 3DCRT was delivered by 4-6 coplanar or non-coplanar fields. The mean tumour dose was 43.0+/-6.3 Gy by conventional fractionation (2 Gy per fraction, five fractions a week), and mean dose to normal liver, 19.1+/-6.3 Gy. Acute hepatic toxicities were notable in five patients (10%) with Common Toxicity Criteria (CTC) grade 1 in two cases and grade 3 in three patients, but all recovered eventually. Two patients developed radiation-induced liver disease (RILD) and died soon after the onset of RILD. Four patients had Radiation Therapy Oncology Group (RTOG) grade 1 acute gastrointestinal complication and one patient had acute gastrointestinal bleeding. Five patients experienced RTOG Grade 1 leukopenia and Grade 2 in five cases. Nine patients achieved have partial response, and 37 patients were in stable disease. Four patients were observed to have progressive disease. The overall survival rates at 1 year, 2 years and 3 years were 60%, 38% and 28%, respectively, with a median survival period of 17 months. Irradiation dose, T-stage and hepatic cirrhosis were identified as independent predictors for overall survival by Cox proportional regression analysis. The 1 year, 2 years and 3 years local progression-free rates were 74%, 57% and 38%, and the 1 year, 2 years and 3 years distant metastasis rates were 15%, 21% and 40%, respectively. The combined modality of TACE and 3DCRT was tolerable for the majority of HCC patients, resulted in good outcome and warrants for further prospective trial.
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Affiliation(s)
- Z-H Zhou
- Department of Integrative Chinese and Western Medicine, Fudan University Cancer Hospital, Shanghai 200032, China
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21
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Dudeck O, Bogusiewicz K, Pinkernelle J, Gaffke G, Pech M, Wieners G, Bruhn H, Jordan A, Ricke J. Local Arterial Infusion of Superparamagnetic Iron Oxide Particles in Hepatocellular Carcinoma. Invest Radiol 2006; 41:527-35. [PMID: 16763472 DOI: 10.1097/01.rli.0000209601.15533.5a] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES We sought to prove feasibility of selective arterial infusion of superparamagnetic iron oxide (SPIO) particles in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS We studied 13 patients with HCC who underwent modified transarterial chemoembolization (TACE). Six patients received concurrent infusion of Ferucarbotran (Resovist, Schering, Berlin, Germany) in tumor-feeding arteries, and another 6 received MFL AS (MagForce, Nanotechnologies, Berlin, Germany). The iron content of both dispersions was 3.92 mg. One patient served as a control. All patients underwent magnetic resonance imaging (MRI) as baseline and immediate follow-up investigation. RESULTS Selective arterial infusion of both SPIO particles resulted in significant intratumoral signal intensity decrease on T1-weighted sequences (P < 0.0001), which was greater after MagForce infusion compared with Resovist (P = 0.002). Only minimal amounts of dispersed particles were found in adjacent normal liver parenchyma. No change in intratumoral signal intensity was noted when ferromagnetic particles were omitted. CONCLUSIONS Modified TACE with selective arterial infusion of SPIO particles can be used for precise tumor targeting in patients with HCC, for which MagForce appeared superior to Resovist.
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Affiliation(s)
- Oliver Dudeck
- Department of Radiology, Rudolf Virchow, Berlin, Germany.
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22
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Lambert B, Van de Wiele C. Treatment of hepatocellular carcinoma by means of radiopharmaceuticals. Eur J Nucl Med Mol Imaging 2005; 32:980-9. [PMID: 16032439 DOI: 10.1007/s00259-005-1859-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Several techniques have been developed for radionuclide therapy of hepatocellular carcinoma (HCC). Medical literature databases (Pubmed, Medline) were screened for available literature and articles were critically analysed as to their scientific relevance. In a palliative setting, intra-arterial administration of 131I-Lipiodol yields responses in 17-92% of patients. According to a randomised study, 131I-Lipiodol was far better tolerated than classic chemo-embolisation. The additive value of a single 131I-Lipiodol administration following partial liver resection for HCC was evaluated and evidence is available that adjuvant radionuclide treatment reduces the recurrence rate. Data concerning the role of 131I-Lipiodol in bridging patient to liver transplantation are scarce but suggest a potential benefit in terms of reducing the drop-out rate while patients are listed for transplantation. 188Re- and 90Y-labelled conjugates are emerging and initial clinical data are promising. Treatment of HCC with 90Y-labelled microspheres is likely as efficacious as treatment with radiolabelled Lipiodol but pretreatment 99mTc-MAA scintigraphy is required in order to exclude patients with significant lung shunting. Several antibodies targeting antigens expressed on HCC have been radiolabelled, almost exclusively with 131I, and evaluated in a preclinical or clinical setting. The use of radiolabelled Lipiodol and microspheres allows for selective targeting of HCC with limited toxicity. Prospective, randomised controlled trials demonstrating that both treatment modalities may provide a survival benefit in a palliative setting are mandatory. In addition, future research should focus on the complementary role of radionuclide treatment in patients at risk for recurrent disease following partial liver resection or while awaiting liver transplantation.
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Affiliation(s)
- Bieke Lambert
- Nuclear Medicine Division, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium
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Selective and enhanced transgene expression in hepatocellular carcinoma cells by asialofetuin-labelled liposomes and AFP promoter. J Drug Deliv Sci Technol 2005. [DOI: 10.1016/s1773-2247(05)50031-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Abstract
Hepatocellular carcinoma (HCC) is the most important primary hepatic cancer, being a common cancer type worldwide. Many aetiological factors have been related with HCC development, such as cirrhosis, hepatitis viruses and alcohol. Chronic infection with hepatitis B (HBV) and C viruses (HCV) often results in cirrhosis and enhances the probability of developing HCC. The underlying mechanisms that lead to malignant transformation of infected cells, however, remain unclear. HBV is a DNA virus that integrates into the host genome, and this integration is believed, in part, to be carcinogenic. Besides, the virus encodes a 17 kDa protein, HBx, which is known to be a causative agent in the formation of HCC. On the contrary, HCV is a RNA virus that does not integrate into the host genome but likely induces HCC through host protein interactions or via the inflammatory response to the virus. Products encoded in the HCV genome interfere with and disturb intracellular signal transduction. Some HCV proteins, such as the core protein, NS3 and NS5A, have seen to have a regulatory effect on cellular promoters, to interact with a number of cellular proteins, and to be involved in programmed-cell death modulation under certain conditions. The identification of these proteins functions in HCC development and the subsequent development of strategies to inhibit protein-protein interactions may be the first step towards reducing the chronicity and/or of the carcinogenicity of these two viruses.
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Affiliation(s)
- M Anzola
- Departamento de Z, y Dinámica Celular, Facultad de Farmacia, Universidad del País Vasco, Vitoria, Spain.
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Yoon SM, Kim JH, Choi EK, Ahn SD, Lee SW, Yi BY, Chung YW, Lee YS, Seo DJ. Radioresponse of hepatocellular carcinoma-treatment of lymph node metastasis. Cancer Res Treat 2004; 36:79-84. [PMID: 20396570 DOI: 10.4143/crt.2004.36.1.79] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2003] [Accepted: 02/19/2004] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To analyze the radioresponse of hepatocellular carcinomas (HCC), using accurate measurements of the tumor size in extrahepatic lymph node metastasis, and to obtain information for the future treatment of primary intrahepatic lesions. MATERIALS AND METHODS Fifty-one extrahepatic lymph node metastases from primary HCCs, which could be treated by external radiotherapy alone, were included in this study. The radiation dose ranged from 30 to 51 Gy with fraction sizes of 2.0 approximately 3.0 Gy. Responses were determined by measuring the areas on CT scans 0, 1 and 3 months after the completion of radiotherapy. The median follow-up period of the surviving patients was 10 months. RESULTS The overall response rate was 76%, and the important factors were; total dose of radiation, time dose fractionation (TDF) value and the biologically effective dose (BED). A dose of 45 Gy or higher showed an objective response rate of 93%, and if the TDF value was higher than 90, a similar result was observed. In about half (47%) of the patients the maximum response was observed at 3 months or later. The response duration was observable in 14 patients surviving 12 months or longer. Regrowth of irradiated lesions were observed in 4 (66.7%) patients among those who received less than 45 Gy, and in 4 (50%) among those who were treated with 45 Gy or more. There was a statistically significant difference in the survivals between the responders and non-responders (p=0.008). Gastrointestinal bleeding or ulceration was observed in 8 patients, including 3 with NCI common toxicity criteria grade III or higher. CONCLUSION Radiotherapy was an effective palliative modality for extrahepatic metastasis in HCCs. A radiation dose of 45 Gy or higher (or a TDF value >or=90), was required for a major response.
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Affiliation(s)
- Sang Min Yoon
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Inoue K, Takayama T, Higaki T, Watanabe Y, Makuuchi M. Clinical significance of early hepatocellular carcinoma. Liver Transpl 2004; 10:S16-9. [PMID: 14762833 DOI: 10.1002/lt.20049] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Early hepatocellular carcinoma (HCC) is defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable by surgery. We studied 70 patients who had a single HCC smaller than 2 cm in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up. Based on our typing system, the tumors were assigned as early HCC (n=15), overt HCC (n=52), and non-HCC tumor (n=3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P=.01). After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P=.01; P=.001, respectively): the 5-year rates of overall survival were 93% and 54% and those of recurrence-free survival were 47% and 16%, respectively. The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% confidence interval, 0.15-0.65; P=.002) and death (0.26; 0.09-0.73; P=.01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure.
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Affiliation(s)
- Kazuto Inoue
- Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan
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Martinho JMDSG, Moraes HPD, Oliveira MED, Moreira LFP, Silva ACD, Pereira LDS, Maia F. Modelo de indução de necrose focal hepática: estudo experimental em ratos. Acta Cir Bras 2004. [DOI: 10.1590/s0102-86502004000100008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
OBJETIVO: Investigar a área de necrose focal induzida pela injeção intra-hepática de quatro diferentes substâncias no fígado de ratos. MÉTODOS: Foram utilizados 25 ratos Wistar, com peso variando entre 200 a 250 g, distribuidos em 5 grupos, que receberam 0,1cc das seguintes substâncias: Grupo I (Gr. I) - soro fisiológico a 0,9% (controle). Grupo II (Gr. II) - glicose hipertônica a 50%. Grupo III (Gr. III) - NaCl a 20%. Grupo IV (Gr. IV) - formol a 10%. Grupo V (Gr. V) - etanol. Os animais foram submetidos a laparotomia para que a punção fosse realizada no lobo hepático médio sob visão direta. Todos os animais foram sacrificados após 24 horas da injeção.. Os fígados foram avaliados histologicamente, com o intuito de mensurar a área do tecido necrótico. RESULTADOS: Nos cinco grupos estudados observou-se: Gr. I - 2829mm² (controle); Gr. II - 3805mm² (glicose hipertônica); Gr. III - 3930mm² (NaCl); Gr. IV - 4532mm² (formol) e Gr. V - 6432mm² (etanol). A análise estatística destes valores foi feita pelo método das comparações múltiplas. CONCLUSÃO: 1. O soro fisiológico foi à substância que causou a menor área de necrose (P< 0,05). 2. O NaCl a 20% e a glicose hipertônica a 50% produzem efeitos semelhantes (P > 0,05). 3. O formol a 10% produziu necrose mais extensa que a glicose hipertônica a 50% (P < 0,05) e que o NaCl a 20%, porém não apresentou diferença estatisticamente significativa com esta última (P > 0,05). 4. O etanol foi à substância que, comparada com as outras, mais necrose produziu (P < 0,05).
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Seong J, Park HC, Han KH, Chon CY. Clinical results and prognostic factors in radiotherapy for unresectable hepatocellular carcinoma: a retrospective study of 158 patients. Int J Radiat Oncol Biol Phys 2003; 55:329-36. [PMID: 12527045 DOI: 10.1016/s0360-3016(02)03929-9] [Citation(s) in RCA: 146] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE To analyze the treatment results and prognostic factors affecting survival in patients with unresectable hepatocellular carcinoma treated with local radiotherapy (RT). METHODS AND MATERIALS Between 1992 and 2000, 158 patients with unresectable hepatocellular carcinoma received local RT. Sixty-seven patients had an advanced UICC Stage III lesion and 91 patients had Stage IVA. The mean tumor size was 9.0 +/- 3.0 cm, and liver cirrhosis was present in 142 patients. Local RT was combined with transarterial chemoembolization as primary treatment (107 patients) or as salvage after failure of repeated transarterial chemoembolization (51 patients). The mean radiation dose was 48.2 +/- 7.9 Gy in daily 1.8-Gy fractions. RESULTS The mean follow-up was 21.6 months after diagnosis and 14.6 months after RT. The response rate was 67.1%. The overall survival rate at 2 and 5 years was 30.5% and 9%, respectively, from the time of diagnosis (median survival time 16 months) and 19.9% and 4.7%, respectively, after RT (median survival time 10 months). On univariate analysis, tumor size (p = 0.047), the presence of portal vein thrombosis (p = 0.007), and RT dose (p = 0.001) were significant factors for survival. However, on multivariate analysis, RT dose was the only significant factor (p = 0.01). CONCLUSION Local RT achieved substantial tumor regression and survival. The radiation dose was found to be a significant prognostic factor in the RT of hepatocellular carcinoma. Additional efforts for dose escalation are warranted to improve the treatment results in parallel with better protecting the nontumorous liver.
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Affiliation(s)
- Jinsil Seong
- Department of Radiation Oncology, Brain Korea 21 Project for Medical Science, Yonsei University Medical College, Seoul, South Korea.
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Fukuda S, Okuda K, Imamura M, Imamura I, Eriguchi N, Aoyagi S. Surgical resection combined with chemotherapy for advanced hepatocellular carcinoma with tumor thrombus: report of 19 cases. Surgery 2002; 131:300-10. [PMID: 11894035 DOI: 10.1067/msy.2002.120668] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Prognosis of hepatocellular carcinoma (HCC) with tumor thrombus in the main portal vein (MPV), inferior vena cava (IVC), or extrahepatic bile duct (EBD) treated by conventional therapies has been considered poor. This study aimed to evaluate the efficacy of hepatic arterial infusion chemotherapy after surgical resection as an adjuvant therapy or as a treatment for intrahepatic recurrence of HCC with tumor thrombus in MPV, IVC, or EBD. METHODS Nineteen patients with HCC and tumor thrombus in the MPV, IVC, or EBD who underwent hepatectomy with thrombectomy were reviewed retrospectively. RESULTS The overall 3-year survival rate was 48.5%. Two patients with postoperative residual tumor thrombus died within 6 months owing to rapid progression of the residual tumor thrombus. Five patients survived more than 5 years after their operations. Tumors disappeared completely in 3 patients after hepatic arterial infusion chemotherapy with a combination of cisplatinum and 5-fluorouracil, and the longest survival period was 17 years and 11 months in a patient with EBD thrombus. CONCLUSIONS If hepatic reserve is satisfactory, an aggressive surgical approach combined with chemotherapy seems to be of benefit for patients having HCC with tumor thrombus in the MPV, IVC, or EBD.
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Affiliation(s)
- Shuichi Fukuda
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
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30
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31
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Gotsman I, Alper R, Klein A, Rabbani E, Engelhardt D, Ilan Y. Inducing oral immune regulation of hepatitis B virus envelope proteins suppresses the growth of hepatocellular carcinoma in mice. Cancer 2002; 94:406-14. [PMID: 11900226 DOI: 10.1002/cncr.10237] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) expresses hepatitis B surface antigen (HBsAg) on its cell surface, and this may serve as a tumor-associated antigen. It was shown previously that adoptive transfer of immunity against HBsAg facilitates the suppression of experimental human HCC-expressing HBsAg in athymic mice. The authors recently showed that it was possible to augment the anti-HBV immune response through induction of oral immune regulation for HBV-associated antigens. The objective of this study was to evaluate the effect of oral immune regulation for HBV antigens on the growth of HBsAg-expressing HCC. METHODS Recipient athymic Balb/c mice were irradiated sublethally and injected with 10(7) human hepatoma cells followed by the adoptive transfer of 2 x 10(6) splenocytes from donor mice. Four groups of donor Balb/c mice were studied: Two groups were immune modulated through oral administration of HBV antigens (HBsAg, PreS1, and Pre S2) or bovine serum albumin (BSA). Two control groups were immunized for HBsAg and fed HBV antigens or BSA. Recipient mice were followed for tumor volume and serum alpha-fetoprotein (aFP) levels. The humoral immune response was determined by measuring serum HBs antibodies. HBV specific T-cell immune modulation was assessed in vitro by HBV specific T-cell proliferation and interferon gamma (IFNgamma) ELISPOT assays as well as cytokine expression by reverse transcriptase-polymerse chain reaction assays. RESULTS The adoptive transfer of orally immune modulated HBV splenocytes induced complete tumor suppression in recipient mice compared with control mice transplanted with nonimmune modulated cells (BSA), which showed significant tumor growth (serum aFP levels were 3.5 ng/mL and 2320.0 ng/mL, respectively). Control mice transplanted with anti-HBs immunized cells (with or without oral immune modulation) manifested similar tumor suppression (3.5 ng/mL and 0.5 ng/mL, respectively). Immunoregulation for HBV antigens augmented the HBV specific T-cell immune response, as manifested by an increase in HBV specific T-cell proliferation and IFNgamma ELISPOT assays in mice orally immune regulated with HBV proteins compared with naïve mice. Tumor suppression was mediated through increased IFNgamma production in immune regulated and immunized mice. CONCLUSIONS The induction of oral immune regulation for HBV antigens modulated the antitumor immune response, thus suppressing the growth of HCC in mice. This effect was mediated by the enhancement of anti-HBV specific T-cell immunity.
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MESH Headings
- Administration, Oral
- Adoptive Transfer
- Animals
- Antigens, Neoplasm/immunology
- Antigens, Neoplasm/metabolism
- Body Weight
- Carcinoma, Hepatocellular/immunology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/prevention & control
- Cytokines/metabolism
- Female
- Hepatitis B Antibodies/blood
- Hepatitis B Surface Antigens/immunology
- Hepatitis B virus/immunology
- Humans
- Immune Tolerance
- Interferon-gamma/metabolism
- Liver Neoplasms, Experimental/immunology
- Liver Neoplasms, Experimental/pathology
- Liver Neoplasms, Experimental/prevention & control
- Mice
- Mice, Inbred BALB C
- Mice, Transgenic
- Neoplasm Transplantation
- Recombinant Proteins/immunology
- Reverse Transcriptase Polymerase Chain Reaction
- Spleen/immunology
- T-Lymphocytes/immunology
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Affiliation(s)
- Israel Gotsman
- Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
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Ko S, Kanehiro H, Hisanaga M, Nagao M, Ikeda N, Nakajima Y. Liver fibrosis increases the risk of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma. Br J Surg 2002; 89:57-62. [PMID: 11851664 DOI: 10.1046/j.0007-1323.2001.01969.x] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) commonly develops in patients with chronic hepatitis. Intrahepatic recurrence after hepatectomy often includes nodules of new tumour in the liver remnant. The aim of this study was to examine hepatitis-related factors that might predict this type of recurrence. METHODS The influence of various hepatitis-related factors on intrahepatic recurrence of HCC was studied by multivariate analysis in 138 patients who underwent curative resection and were followed for more than 2 years. RESULTS The Cox proportional hazard model showed that histological evidence of fibrosis of the underlying liver was the most significant predictive factor for intrahepatic recurrence (P = 0.001). Serum albumin level was also significantly associated with recurrence (P = 0.038). The relative risks of histological fibrosis and low serum albumin levels were 8.9 and 1.7 respectively. Among tumour-related factors, only tumour size was significantly associated with recurrence (P = 0.017). Major hepatectomy was also an independent risk factor for intrahepatic recurrence (P = 0.004). CONCLUSION Histological evidence of fibrosis and low serum albumin levels are useful predictors of intrahepatic recurrence after hepatectomy, presumably owing to metachronous multifocal tumour in the liver remnant.
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Affiliation(s)
- S Ko
- First Department of Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
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Abstract
Primary hepatocellular cancer is a disease with a poor prognosis for which there is little consensus on treatment and a paucity of comparative trials. The coexistence of cancer with cirrhosis complicates treatment, and also confers a high risk for the development of further tumours. Surgery, either by hepatic resection or orthotopic liver transplantation, is only a feasible option in a minority of patients. This article surveys the non-surgical approaches to the treatment of hepatocellular cancers-local ablation techniques, arterial embolization with and without chemotherapy, conventional chemotherapy and hormonal modulation, and targeted and external irradiation.
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Affiliation(s)
- A M Alsowmely
- Centre for Hepatology, Royal Free and University College Medical School, London, UK
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35
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Suehiro T, Terashi T, Shiotani S, Soejima Y, Sugimachi K. Liver transplantation for hepatocellular carcinoma. Surgery 2002; 131:S190-4. [PMID: 11821809 DOI: 10.1067/msy.2002.119575] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The surgical management for hepatocellular carcinoma (HCC) is multiplicity. In Japan, liver resection has generally been considered to be the only curative treatment for HCC. The resectability of a tumor in cirrhotic patients, however, is limited by the diminished functional reserve of the cirrhotic liver and the attendant risk for intraoperative bleeding and postoperative liver failure. In cirrhotic patients, liver transplantation has been considered as the indication for HCC in many countries except Japan. Although the survival rate of patients with HCC who received liver transplants was poor in the early period, it later moved to the same level as for patients with other liver diseases. In 1993, living donor adult liver transplantation was started in Japan and it became an additional option for the treatment of HCC. A shortage of liver donors means that new methods of liver procurement must be explored. Domino liver transplantation using the livers of patients with familial amyloid polyneuropathy was also another option for advanced HCC. For the prevention of a recurrence of HCC, pre-, intra-, and postoperative chemotherapy have been performed after both liver resection and liver transplantation. We should also try to minimize intraoperative dissemination by surgical manipulation. Recently, potential gene therapies for HCC have been studied. Electroporation-mediated IL-12 gene therapy for HCC was found to be effective for both mIL-12-transferred HCC and for distant HCC. For patients with HCC accompanied by liver cirrhosis, liver transplantation remains the ultimate curative therapy. Immunologic and oncologic approaches to HCC can help prevent tumor recurrence and also help us to obtain better results after liver transplantation.
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Affiliation(s)
- Taketoshi Suehiro
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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Moroz P, Jones SK, Winter J, Gray BN. Targeting liver tumors with hyperthermia: ferromagnetic embolization in a rabbit liver tumor model. J Surg Oncol 2001; 78:22-9; discussion 30-1. [PMID: 11519064 DOI: 10.1002/jso.1118] [Citation(s) in RCA: 64] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
BACKGROUND AND OBJECTIVES Ferromagnetic embolization hyperthermia (FEH) consists of arterially embolizing liver tumors with ferromagnetic particles, and then applying an external alternating magnetic field to generate hysteretic heating within the embolized particles. The objective of this study was to assess the ability of FEH to selectively target liver tumors with hyperthermia. METHODS Twenty rabbits containing hepatic VX2 carcinomas were arterially infused with ferromagnetic particles suspended in lipiodol, and then exposed to an external alternating magnetic field. Temperatures in the tumor, normal hepatic parenchyma (NHP), and rectum were recorded. Tumour and NHP were chemically analyzed for iron content, which was then correlated with the observed heating rates. RESULTS The mean tumor-to-NHP iron concentration ratio was 5.3:1 (P < 0.001, N = 20). The mean tumor heating rates were 3.0-11.5 times greater than those in the NHP (P < 0.001, N = 20). After 5 min of heating, the greatest increase in mean tumor temperature was 11.0 degrees C and the greatest increase in mean NHP temperature was 1.3 degrees C. There was a positive relationship between tumor iron concentration and heating rate (correlation coefficient = 0.82, P < 0.001, N = 20). A tumor iron concentration of 2-3 mg/g resulted in tumor heating rates of 0.5-1.0 degrees C/min. CONCLUSIONS Hepatic arterial infusion of lipiodol containing ferromagnetic particles can result in excellent targeting of liver tumors with hyperthermia on the subsequent application of an external alternating magnetic field. The promising results of this study warrant further investigation of FEH as a potential treatment for advanced liver cancer.
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Affiliation(s)
- P Moroz
- Centre for Applied Cancer Studies, The University of Western Australia, Nedlands, Perth, Western Australia, Australia.
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Seong J, Kim SH, Suh CO. Enhancement of tumor radioresponse by combined chemotherapy in murine hepatocarcinoma. J Gastroenterol Hepatol 2001; 16:883-9. [PMID: 11555102 DOI: 10.1046/j.1440-1746.2001.02533.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS Recent studies have shown that local radiotherapy can be an effective component of the treatment for hepatocellular carcinoma. To further improve therapeutic efficacy, use of drugs that can beneficially interact with radiation has been suggested. The purpose of this study was to identify drugs that can enhance radioresponse of murine hepatocarcinoma. METHODS C3H/HeJ mice bearing 8 mm tumors of murine hepatocarcinoma, HCa-I, were treated with 25 Gy radiation and one of the following drugs: 5-Fu, 150 mg/kg; adriamycin, 8 mg/kg; cisplatin, 6 mg/kg; paclitaxel, 40 mg/kg; and gemcitabine, 50 mg/kg. Tumor response to the treatment was determined by the use of a tumor growth delay assay and by an enhancement factor. The apoptotic level was assessed in tissue sections. The expression of regulating molecules was analyzed by using western blotting for p53, Bcl-2, Bax, Bcl-XL, Bcl-XS, and p21(WAF1/CIP1). RESULTS Among the drugs tested, only gemcitabine enhanced the antitumor effect of radiation, with an enhancement factor of 1.6. The induction of apoptosis by a combination of gemcitabine and radiation was shown as only an additive level. In the analysis of radiation-induced expression of regulating molecules, the most significant change by combining gemcitabine with radiation was the activation of p21(WAF1/CIP1). CONCLUSION Gemcitabine is the first to show an enhancement of radioresponse of murine hepatocarcinoma when combined with radiation. The key element of enhancement is thought to be p21(WAF1/CIP1).
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Affiliation(s)
- J Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Medical College, Seoul, Korea.
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Gotsman I, Ilan Y. Downregulation of a tumor promotion immune response via induction of oral tolerance towards tumor-associated-antigens: can we 'eat the tumor'? Med Hypotheses 2001; 56:487-92. [PMID: 11339853 DOI: 10.1054/mehy.2000.1196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The mechanism by which hepatocellular carcinoma (HCC) develops and the role of the hepatitis B virus (HBV) in inducing tumors, are not yet well understood. Patients persistently infected with HBV tend to have a defective immune response against the virus, which fails to clear the virus and also induces liver injury. This defective response may also have an inducible effect on the virus and on cells that express HBV antigens, as well as play a role in the growth of neoplasm. It is possible that one of the mechanisms of tumor growth is related to a deviant immune response towards viral or tumor associated antigens. We describe two responses against the tumor. A 'good' response that would suppress the tumor and a 'bad' response that would promote it and theorize that the net balance between 'bad' and 'good' responses of the immune system towards a cancerous cell and/or antigen will predict whether a tumor grows or is suppressed. Oral tolerance involves the induction of immunological hyporesponsiveness towards specific antigens. It was shown that oral tolerance induces antigen-specific immune suppression towards tumor-associated-antigens by feeding of HBV or other tumor proteins. We hypothesize that induction of immune tolerance towards tumor-associated antigens will suppress the immune response towards these antigens, thus reducing the 'bad' response. The proposed new treatment strategy would redirect the focus from augmenting anti-tumor immune responses to inducing host tolerance towards the tumor.
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Affiliation(s)
- I Gotsman
- Liver Unit Division of Medicine, Hadassah University Hospital, Jerusalem, Israel
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Prudhomme M, Rouy S, Tang J, Landgrebe J, Delacrétaz G, Godlewski G. Biliary structures lead to tumour recurrences after laser-induced interstitial thermotherapy. Lasers Surg Med 2000; 24:269-75. [PMID: 10327045 DOI: 10.1002/(sici)1096-9101(1999)24:4<269::aid-lsm4>3.0.co;2-i] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVE Thermal diffusion during laser-induced interstitial thermotherapy (LITT) has not yet been fully investigated in heterogeneous tissue architecture such as liver. LITT was performed on rabbit liver tumours to analyse the role of biliary structures in thermal diffusion. STUDY DESIGN/MATERIALS AND METHODS Twenty-four VX2 tumours were grafted onto 12 rabbit livers. The animals were randomly separated into two groups when tumour size reached 8 mm. Thermotherapy was performed by delivering the 830-nm output of a diode laser to the centre of the tumour with a 300-,microm fibre. Irradiation conditions were 1.5 W over 900 sec. On day 7 or 14, the tumours were removed and stained with haematoxylin-eosin and picrosirius red F3BA (PR). Thermal damage was evaluated by PR and electron microscopic examinations. RESULTS Among the treated tumours, recurrences were found both at the periphery (one on day 7, seven on day 14) and within the treated area (two on day 7, two on day 14). All recurrences were located in the vicinity of the biliary structures, which are frequently spared from thermal injury. CONCLUSION Biliary ducts lead to a heat sink, thereby facilitating tumour recurrences.
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Affiliation(s)
- M Prudhomme
- Laboratoire d'Anatomie Expérimentale, Faculté de Médecine Montpellier-Nîmes, Université Montpellier I, Nîmes, France
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Caturelli E, Siena DA, Fusilli S, Villani MR, Schiavone G, Nardella M, Balzano S, Florio F. Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: evaluation of damage to nontumorous liver tissue-long-term prospective study. Radiology 2000; 215:123-8. [PMID: 10751477 DOI: 10.1148/radiology.215.1.r00ap21123] [Citation(s) in RCA: 71] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
PURPOSE To evaluate damage to cirrhotic liver tissue after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS TACE was performed in 111 patients with HCC that involved less than 30% of the liver. Baseline liver function was evaluated with Child-Pugh scores and other indicators. Eighty-two patients had Child-Pugh class A disease, 27 had class B disease, and two had class C disease. All patients underwent chemotherapy followed by gelatin sponge particle embolization in the proper ("complete" embolization; n = 69) or right or left main ("partial" embolization; n = 42) hepatic artery. Liver function was assessed 4 months later, and 95 patients underwent a second TACE (complete embolization in 57, partial in 38). Liver function was again assessed 4 months later in 60 patients. RESULTS No patient died. Child-Pugh scores increased in all patients from a mean 5.96 to 6.28 (not significant) and 6.51 (P =. 05) after first and second TACEs, respectively. In patients with class A disease, scores increased from a mean 5.37 to 5.73 (P =.01) and 5.89 (P =.001) after first and second TACEs, respectively; in patients with class B disease, scores changed from a mean of 7.48 to 7.67 and 7.30 after first and second TACEs, respectively (not significant). CONCLUSION TACE does not induce significant long-term worsening of liver function in patients with class A or B cirrhosis.
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Affiliation(s)
- E Caturelli
- Division of Gastroenterology, Ospedale "Casa Sollievo della Sofferenza" IRCC, Foggia, Italy
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41
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Khan KN, Yamasaki M, Yamasaki K, Inoue O, Yatsuhashi H, Koga M, Yano M. Proposed abdominal sonographic staging to predict severity of liver diseases: analysis with peritoneoscopy and histology. Dig Dis Sci 2000; 45:554-64. [PMID: 10749333 DOI: 10.1023/a:1005491018415] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Abdominal sonography is a routinely used noninvasive modality for screening and treatment of liver diseases. We attempted to establish a morphological sonographic staging to predict the severity of liver diseases with their consequent analysis with morphological staging of peritoneoscopy and histology. In all, 136 patients were enrolled for the final confirmation of disease state by peritoneoscopy and histology preceded by abdominal sonography. All patients were categorized from stage 0 to stage 5, depending on a proposed criterion of sonographic features based on surface pattern of liver and the appearance of internal echogenic bands relating to the irregularity of the liver texture. A digitized computer quantitation of histogram-based standard deviation (SD) values from different stages of sonographic images was analyzed, and their values were justified by correlation with the definite appearance of an internal echogenic band. The association of different sonographic stages with disease progression was also demonstrated by their relation with peritoneoscopy and histology. In all patients, the different sonographic staging results were significantly correlated with hepatic surface features of peritoneoscopic staging (r = 0.939, P < 0.0001) graded from stage 0 to stage 5 and were also correlated with biopsy-proven staging of fibrosis (r = 0.739, P < 0.0001). The greater SD values of histogram-based echo levels, as analyzed from digitized sonographic images of 90 patients, were associated with the appearance of internal echogenic bands (P < 0.0001). Furthermore, the corresponding SDS were significantly correlated with the qualitative staging of sonographic features (r = 0.781, P < 0.0001), peritoneoscopy (r = 0.786, P < 0.0001) and histology (r = 0.779, P < 0.0001). We concluded that our proposed sonographic staging is well correlated with peritoneoscopic and histological staging of liver diseases, with only a small discrepancy, and can be used clinically to demonstrate the ongoing severity of liver diseases.
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Affiliation(s)
- K N Khan
- Institute for Clinical Research, Nagasaki Chuo National Hospital, Omura City, Japan
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42
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Maurer CA, Renzulli P, Baer HU, Mettler D, Uhlschmid G, Neuenschwander P, Suter UW, Triller J, Zimmermann A. Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein. J Hepatol 2000; 32:261-8. [PMID: 10707866 DOI: 10.1016/s0168-8278(00)80071-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIM In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.
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Affiliation(s)
- C A Maurer
- Clinic for Visceral and Transplantation Surgery, University of Bern, Switzerland
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Lim JH, Jang HJ, Kim EY, Park CK, Joh JW, Kim YI. Early recurring hepatocellular carcinoma after partial hepatic resection: preoperative CT findings. Korean J Radiol 2000; 1:38-42. [PMID: 11752927 PMCID: PMC2718136 DOI: 10.3348/kjr.2000.1.1.38] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE The purpose of this study was to determine the utility of preoperative CT in predicting early recurrence of hepatocellular carcinoma after partial hepatic resection. MATERIALS AND METHODS Preoperative three-phase helical CT scans in 53 patients with hepatocellular carcinoma were retrospectively reviewed by two radiologists. In 27 patients (group I), HCC had recurred within six months, while 26 (group II) had remained disease free for at least two years. In each group, preoperative CT findings were evaluated in each group for the tumor size and number, the presence or absence of capsule, distinctness of tumor margin, perinodular extension, and the presence or absence of portal vein thrombosis. RESULTS In group I, a tumor capsule of tumor was seen in five of 27 patients (19%), and in group II, in 16 of 26 (62%) (p =.001). The tumor margin was distinct in eight patients (30%) in group I and in 20 (77%) in group II (p =.001). Multiple tumors, perinodular extension, and portal vein thrombosis were more frequently seen in group I but the differences were not statistically significant (p >.05). Tumor size was similar in each group (p >.05). CONCLUSION Preoperative CT findings that may help predict the early recurrence of hepatocellular carcinoma after surgical resection are an absence of capsule of tumors and an indistinct margin. Reference to these findings during preoperative CT can guide clinicians in their choice of treatment.
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Affiliation(s)
- J H Lim
- Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Yip D, Findlay M, Boyer M, Tattersall MH. Hepatocellular carcinoma in central Sydney:a 10-year review of patients seen in a medical oncology department. World J Gastroenterol 1999; 5:483-487. [PMID: 11819496 PMCID: PMC4688790 DOI: 10.3748/wjg.v5.i6.483] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/1998] [Revised: 09/11/1998] [Accepted: 04/02/1999] [Indexed: 02/06/2023] Open
Abstract
AIM:To report a single Australian oncology unit's experience with the management of patients with hepatocellular carcinoma (HCC), in the context of a literature review of the current management issues.METHODS:Retrospective case record review of 76 patients with diagnosis of HCC referred to the unit between 1984 and 1995.RESULTS:Sixty three patients had adequate records for analysis. Thirty six (56%) were migrants with half from Southeast Asia. Twenty-four patients had a documented viral aetiology.Nine (14%) of 51 patients with pathological confirmation of HCC had normal alpha fetoprotein levels. Median survival of the 20 patients managed palliatively was 5 weeks compared to 16 weeks for the cohort overall. Surgery in 16 patients rendered all initially disease free with a median survival of 88 weeks. Chemoembolisation induced tumor responses in 5 of the 11 patients so treated. Systemic chemotherapy and tamoxifen treatment caused tumor response in two of 12 and one of 25 respectively.CONCLUSION:Prolonged survival of patients with HCC depends on early detection of small tumors suitable for surgical resection. Other active treatments are palliative in intent and have limited success.In addition to tumor response and survival duration, the toxicities of therapies and the overall quality of life of patients need to be considered as important outcomes. Viral hepatitis prevention and screening of individuals at risk are strategies that are important for HCC management in communities where the disease is endemic.
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Khan KN, Nakata K, Nakao K, Kato Y, Eguchi K. Use of FDP and F1P aldolase to detect tumorous and nontumorous tissue damage by ethanol injection of hepatocellular carcinoma. Dig Dis Sci 1999; 44:1610-8. [PMID: 10492142 DOI: 10.1023/a:1026623312806] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
Changes in serum levels of tumor-specific fructose 1,6-diphosphate (FDP) aldolase and nontumor-specific fructose 1-phosphate (F1P) aldolase activities were analyzed in patients with hepatocellular carcinoma (HCC) to detect the damage of tumorous and nontumorous hepatic cells after percutaneous ethanol injection (PEI). Initial PEI was performed in 20 patients containing 22 HCC nodules with a diameter of < or = 4 cm. Changes in serum hepatic enzyme activities were measured before and after repeated PEI. FDP and F1P aldolase levels were measured by substrate-specific enzymatic methods. Pre- and posttreatment alpha-fetoprotein (AFP) levels were determined by radioimmunoassay. The consequent changes in the total nontumorous liver volumes after PEI were also analyzed by follow-up CT scans. Serum levels of FDP aldolase released by ethanol injection were progressively increased (P < 0.0001) until the third PEI and thereafter decreased. In contrast, serum levels of F1P aldolase were continuously elevated even after the third PEI (P < 0.0001). Serum levels of transaminases were also elevated after repeated PEI (P < 0.0001). The FDP/FIP aldolase ratio decreased significantly with increased volume (>20 ml) of injected ethanol (P = 0.01) caused by nontumorous liver damage. The elevation of FDP aldolase was markedly associated with a decrease in serum levels of AFP (P < 0.001), indicating adequate tumor necrosis. The progression of the total nontumor liver atrophy depended on the volume of injected ethanol and correlated significantly with F1P aldolase levels after PEI (P < 0.01) but not with FDP aldolase. These results demonstrated that caution is needed to avoid nontumorous liver damage caused by the large volume of ethanol injection in treating HCC. Measurement of FDP and F1P aldolase activities in serum after PEI is clinically useful to detect the degree of tumorous and nontumorous tissue damage by ethanol.
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Affiliation(s)
- K N Khan
- First Department of Internal Medicine, Nagasaki University School of Medicine, Japan
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Chevret S, Trinchet JC, Mathieu D, Rached AA, Beaugrand M, Chastang C. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire. J Hepatol 1999; 31:133-41. [PMID: 10424293 DOI: 10.1016/s0168-8278(99)80173-1] [Citation(s) in RCA: 360] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND/AIMS In patients with hepatocellular carcinoma, prediction of survival is difficult. The aim of this prospective study was to provide a simple classification for predicting survival of patients with hepatocellular carcinoma, based on a multivariable Cox model. METHODS Seven hundred and sixty-one patients who presented with hepatocellular carcinoma from 24 Western medical centers were enrolled over a 30-month period. Patients were randomly assigned to either a training sample (n=506, with 418 deaths) from which a classification system was established, or a test sample (n=255, with 200 deaths) for validating its prognostic significance. RESULTS Five prognostic factors were selected at the 0.0001 level: Karnofsky index <80% (relative risk of death=2.2, 95% confidence interval: 1.7-2.7), serum bilirubin >50 micromol/l (relative risk=2.1, 95% confidence interval: 1.7-2.6), serum alkaline phosphatase at least twice the upper limit of normal range (relative risk=1.6, 95% confidence interval: 1.3-2.0), serum alpha-fetoprotein >35 microg/l (relative risk=1.7, 95% confidence interval: 1.4-2.1), and ultrasonographic portal obstruction (relative risk=1.3, 95% confidence interval: 1.1-1.7). Three risk groups with different 1-year survival rates (72%, 34%, 7%) were derived, and independently validated in the test sample (79%, 31%, 4%). CONCLUSION This classification could be useful in the assessment of prognosis from homogeneous groups of patients with respect to their expected outcome.
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Affiliation(s)
- S Chevret
- Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, Paris, France.
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Ahmadi T, Okumura T, Onaya H, Akine Y, Itai Y. Preservation of hypervascularity in hepatocellular carcinoma after effective proton-beam radiotherapy--CT observation. Clin Radiol 1999; 54:253-6. [PMID: 10210346 DOI: 10.1016/s0009-9260(99)91161-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
AIM The aim of this study was to describe persistence of hypervascularity in proton treated hepatocellular carcinoma at serial follow-up computed tomography (CT). METHODS Four patients with unresectable solitary hypervascular hepatocellular carcinoma underwent 55-82 Gy proton-beam irradiation for a period of 15-47 days. Follow-up CT including plain, enhanced and dynamic imaging was performed for a period of 9-36 months. RESULTS Good preservation of arterial blood supply while gradual decrease in tumour size was clearly depicted by dynamic CT. CONCLUSION We believe that preservation of hypervascularity as judged by enhancement at CT and magnetic resonance imaging, does not necessarily mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.
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Affiliation(s)
- T Ahmadi
- Department of Radiology, Institute of Clinical Medicine, University of Tsukuba, Japan
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Seong J, Keum KC, Han KH, Lee DY, Lee JT, Chon CY, Moon YM, Suh CO, Kim GE. Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma. Int J Radiat Oncol Biol Phys 1999; 43:393-7. [PMID: 10030267 DOI: 10.1016/s0360-3016(98)00415-5] [Citation(s) in RCA: 107] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.
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Affiliation(s)
- J Seong
- Department of Radiation Oncology, Yonsei University Medical College, Seoul, Korea
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Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S. Early hepatocellular carcinoma as an entity with a high rate of surgical cure. Hepatology 1998; 28:1241-6. [PMID: 9794907 DOI: 10.1002/hep.510280511] [Citation(s) in RCA: 285] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Early hepatocellular carcinoma (HCC) has been defined as a well-differentiated cancer containing Glisson's triad, but it remains unknown whether this lesion is curable. We prospectively studied 70 patients (enrolled from 1,172 referrals between 1982 and 1991) who had a diagnosis of a single HCC 2 cm or less in diameter (Stage T1) and who underwent curative hepatectomy and long-term follow-up (range, 0.2 to 14.3 years). Patients were eligible for surgery if they had a tumor that met the diagnostic criteria for HCC and were in Child-Pugh class A (n = 59) or B (n = 11) status. Among the 70 patients, there was 1 operative death. Based on our typing system, the tumors were assigned as early HCC (n = 15), overt HCC (n = 52), and non-HCC tumor (n = 3). The rate of microscopic regional spread was lower in early HCCs than in overt HCCs (7% vs. 42%; P = .01). The early HCC group had a longer time to recurrence than did the overt HCC group (3.9 vs. 1.7 years; P < .001) and had no local recurrence. After a median follow-up of 6.3 years, both overall survival and recurrence-free survival in the early HCC group were significantly better than those in the overt HCC group (P = .01; P = .001). In these two groups, the 5-year rates of overall survival were 93% and 54% (P = .01), and those of recurrence-free survival were 47% and 16% (P = .05), respectively; a significant survival benefit persisted over a decade (57% vs. 21%; P = .05). The early HCC group was at a lower risk of recurrence (relative risk, 0.31; 95% CI, 0.15 to 0.65; P = .002) and death (relative risk, 0.26; 95% CI, 0.09 to 0.73; P = .01) than was the overt HCC group. Early HCC is a distinct clinical entity with a high rate of surgical cure, thereby justifying its definition. It can be a lesion that corresponds to "Stage 0" cancer in other organs.
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Affiliation(s)
- T Takayama
- Department of Surgery, University of Tokyo, Japan
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