Diethylnitrosamine-induced Rat Orthotopic Liver Cancer Model And Its Application For Transarterial Chemoembolization

Objective:To establish a rat model of orthotopic liver cancer induced by oral diethylnitrosamine(DEN),and to evaluate the biological characteristics of the animal liver cancer model and its application in transarterial chemoembolization(TACE).Materials and Methods:Healthy and male Sprague Dawley(SD)rats(average weight 160g-180g)were randomly divided into model group(n=40),TACE treatment group(n=20).Each group was given DEN with a concentration of 0.01% twice a week.In model group,at the beginning of the 6th week of induction,liver MRI was performed regularly every week to observe the formation of tumor.When the longest transverse dimension of tumor reached 0.2cm on imaging,the induction of DEN was stopped,and 5 animals were randomly sacrificed.The tumor and liver samples were examined by macroscopic pathology,HE and Masson examination to observe the pathological changes of tumor and adjacent liver tissues.When the results of MRI examination showed that the nodules of liver tumor reached 0.5cm,5 animals were randomly sacrificed to observe the pathological changes of tumor and adjacent liver tissues.After the tumor formation was confirmed by MRI,the liver MRI examination was continued every week and the lung CT examination was continued every two weeks to record the tumor growth laws,metastasis and the animal survival time.In TACE application group,after the longest transverse dimension of tumor reaching 0.5cm by imaging examination,transcatheter arterial angiography and TACE treatment were performed by retrograde intubation through gastroduodenal artery,and the angiographic characteristics,success rate of TACE operation,mortality and tumor necrosis of rat liver cancer were determined.Half of the experimental animals were sacrificed 3 days and 7 days after TACE operation,and the tumor necrosis was detected by macroscopic pathology and HE test.Results:Severe cirrhosis and autochthonous HCCs were characterized in a cohort of rats composed of all rats identically treated with DEN by oral administration.In model group,when the diameter of tumor nodule was 0.2cm,the median induction weeks was 8 weeks(7,10).The results of macroscopic pathology showed that the volume of the liver increased,and the surface of the gray white small nodules.The results of HE examination showed that liver cells were edema,inflammatory cells infiltrated,and some false lobules formed,which were confirmed as hepatocellular carcinoma.Masson staining showed that collagen fibers were deeply stained.When the diameter of tumor nodule was 0.5cm,the median induction weeks was 11 weeks(10,12).The volume of the specimen was reduced and a large number of nodules appeared on the surface of the liver.HE staining showed that typical false lobules were formed and normal fibrous septa were destroyed.Masson staining showed that collagen fibers increased significantly and liver fibrosis was further aggravated.Extrahepatic organs and lymph metastasis were observed in some rats.Median survival time of tumor-bearing rats was 13 weeks after induction(8,20).In TACE treatment group,DSA confirmed that the lesion in this cancer model was hypervascular.Four rats died during the induction period,the success rate of TACE operation on the experimental rats was 68.8%(11/16),and the operation-related mortality was 18.8%(3/16).The results of HE staining showed that the necrosis rate was 48.16%±2.65 three days after operation and 50.36%±2.92 seven days after operation.Conclusions:This model better imitates the tumor characteristics and inflammatory background of human HCC,and TACE could be performed by retrograde transgastroduodenal artery intubation,which is an ideal animal model for interventional transcatheter intra-arterial therapy.