Transcatheter Arterial Chemoembolization Combined With Recombinant Human Endostatin Via Intravenous Injection For The Treatment Of Hepatocellular Carcinoma: An Experimental Study

ObjectiveTo investigate the safety and efficacy of the treatment of rabbit VX2 hepatic carcinoma with the combination of transcatheter arterial chemoembolization and recombinant human endostatin via intravenous injection.Materials and Methods1. Establishment of animal modelVX2 carcinoma fragments were inoculated in the liver of New Zealand white rabbits by ultrasound-guided percutaneous puncture. PET/CT was performed on the 20th day after inoculation, the rabbits bearing single intrahepatic lesion, 1cm-2cm in diameter, without extra-hepatic metastasis were selected as subjects. US were performed on the same day, the maximum tumor diameter and smallest tumor diameter were measured to calculate the volume before treatment.2. Experimental groupingThere were 3 groups in our experiment, TACE alone group (G1), combined therapy group (G2), and control group (G3). G1: TACE was performed on the 21st day after inoculation; saline via intravenous injection was followed for 7 days. G2: TACE was performed on the 21st day after inoculation; recombinant human endostatin via intravenous injection was followed for 7 days. G3: Hepatic angiography was performed on the 21st day after inoculation, saline via intravenous injection was followed for 7 days. Each group included 20 animals. 3. Outcome measures①Blood routine and liver function: the blood and liver function tests were performed on the 21st day and 28th day after inoculation to analyze the WBC and ALT changes.②Tumor growth: tumor volume was measured on the 20th day (V1) and the 28th day (V2) after inoculation respectively, the V2/V1 of each group was analyzed.③Tumor metastasis rate: PET/CT was performed on the 28th day after inoculation, the rabbits bearing metastasis lesions were detected, and the metastasis rats of each group was analyzed.④Tumor microvessel density: all the animals were sacrificed for immunohistochemical examination (anti-CD34 staining) on the 28th day after inoculation, MVD was calculated by the measure recommend by Weidner and his coworker.Results1. Survival of animalsAt the begging of experiment, 20 animals were included in each group , however, only few survived to the 28th day after inoculation: G1=14,G2=15,G3=18.2. Blood and liver functionChanges of WBC before and after treatment were not statistically significant in each group. ALT of TACE alone group (G1) and combined therapy group (G2) after treatment was higher then that of before(P <0.01). The difference of pre-treatment ALT in each group was not statistically significant, and that of post-treatment in each group was statistically significant(F=7.068, P=0.002), among which ALT of TACE alone group (G1) and combination therapy group (G2) was higher than that of control group (G3), however, the difference between G1 and G2 was not statistically significant.3. Tumor growthAverage V2/V1 in each group were: G1=1.216±0.304 , G2=1.211±0.314 ,G3=4.723±1.562. The difference of average V2/V1 in each group was statistically significant (F=68.312 P=0.000), among which average V2/V1 of TACE alone group (G1) and combination therapy group (G2) was lower than that of control group (G3), however, the difference between G1 and G2 was not statistically significant. 3. Tumor metastasisAccording to the PET/CT examination on 28th day after inoculation, metastasis rate in each group were: G1=78.57%(11/14), G2=33.33%(5/15), G3=77.78%(14/18). The difference in each group was statistically significant (χ2=8.877,P=0.012), among which the metastasis rate of combination therapy group (G2) was lower then that of TACE alone group (G1) (P=0.014) and control group (G3) (P=0.010), however the difference between G1 and G2 was not statistically significant. The most common involved organs were liver (26 cases), lymph nodes (21 cases), lung (10 cases), bone (3 cases).4. Tumor angiogenesisMVD (anti-CD34 stain, 200×field of vision) in each group were: G1=75.2±11.0, G2=21.7±10.1, G3=61.3±12.3. The differences between each group was statistically significant (F = 89.874 P = 0.000).ConclusionThe combination of TACE and recombinant human endostatin via intravenous injection for the treatment of rabbit VX2 hepatic carcinoma, cause no more serious liver dysfunction then TACE alone, didn't induce superior suppression on tumor growth then TACE alone, however, it could suppress angiogenesis, and cause superior suppression on tumor metastasis then TACE alone.