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Lethal hepatic injury by combined treatment of radiation plus chemotherapy in rats with thioacetamide-induced liver cirrhosis

Authors
 Jinsil Seong  ;  Kwang Hyub Han  ;  Kyung Sik Kim  ;  Woong Sub Keum  ;  Sung Hee Kim  ;  Sun Hye Nam  ;  Young Nyun Park 
Citation
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, Vol.57(1) : 282-288, 2003 
Journal Title
 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 
ISSN
 0360-3016 
Issue Date
2003
MeSH
Animals ; Combined Modality Therapy/adverse effects ; Combined Modality Therapy/methods ; Fluorouracil/adverse effects* ; Fluorouracil/therapeutic use* ; Liver/drug effects ; Liver/injuries ; Liver/pathology ; Liver/radiation effects ; Liver Cirrhosis, Experimental/chemically induced ; Liver Cirrhosis, Experimental/diagnosis ; Liver Cirrhosis, Experimental/drug therapy* ; Liver Cirrhosis, Experimental/radiotherapy* ; Liver Failure/etiology* ; Liver Failure/mortality ; Liver Failure/pathology ; Male ; Radiotherapy/adverse effects* ; Rats ; Survival Rate ; Thioacetamide ; Treatment Outcome
Keywords
Thioacetamide ; Liver cirrhosis ; Radiation ; Chemotherapy
Abstract
PURPOSE: To assess lethal hepatic injury by combined treatment of radiation (RT) plus chemotherapy in a rat model with thioacetamide (TAA)-induced liver cirrhosis. METHODS AND MATERIALS: Male Wistar rats were treated with 0.3 g/L TAA in drinking water. The development of liver cirrhosis was histologically confirmed, and the degree of liver function impairment was assessed by indocyanine green retention test (ICG R15). The established cirrhotic rats were given one of the following treatments: partial liver radiotherapy (25 Gy on about one-third of the whole liver), 5-fluorouracil (5-FU) chemotherapy (50 mg/kg), and combined treatment of partial RT plus 5-FU. The treated rats were closely followed until either death or 30 weeks after the treatment, and the postmortem liver sampling was examined for lethal hepatic injury by the treatments. RESULTS: The rats developed overt liver cirrhosis after 30 weeks of TAA treatment. At that time, the mean ICG R15 level in the TAA-treated rats (TAA-rats) was 14.1% +/- 0.7% compared to 4.6% +/- 0.7% in the control (p < 0.05). The 30-week survival rates in the control and TAA-rats were 100% (5/5) and 75% (6/8), respectively, after partial liver RT (p = 0.72). In the 5-FU chemotherapy group, the survival in TAA-rats was only one-half of that in the controls (100% vs. 50%, p = 0.06). Poor survival in TAA-rats was shown also in the combined group of partial RT plus 5-FU (87.5% vs. 16.7%, p = 0.06). The rats that died before the last observation time showed advanced cirrhosis with areas of lobular collapse, in contrast to the moderate cirrhotic features in those that survived. CONCLUSION: In a rat cirrhosis model with mildly impaired liver function, combined treatment of partial RT plus 5-FU resulted in significantly high incidence of lethal liver injury. The results in this study show that a combined treatment of RT plus chemotherapy in cirrhotic patients should be applied with extreme caution.
Full Text
http://www.sciencedirect.com/science/article/pii/S0360301603005406
DOI
10.1016/S0360-3016(03)00540-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/113556
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