| ObjectiveTo analyze the effectiveness and safety on rabbit VX2 hepatoma by transhepatic arterial chemoembolization(TACE) combined with intrahepatic artery infusion of pHGF.Materials and Methods1. VX2 carcinoma animal model was established under the ultrasonographic(US) guidance. After 2 weeks PET/CT was performed, the rabbits bearing single intrahepatic lesion, with 1cm-2cm hepatic tumor in diameter were selected as subjects. 2. The rabbit VX2 hepatoma models were randomly divided into 3 groups with 10 in each group. Group A was treated with TACE only(TACE meant administration of lipiodol 0.2ml/kg+DDP 1mg/kg). Group B was treated with TACE combined with intrahepatic artery infusion of pHGF. Group C was treated with physiological saline via hepatic artery. 3. Outcome measures:①The general conditions after TACE.②The HGF and ALT were performed before the procedure and on the3th day,the 7th day and the 28th day after procedure respectively to analyze the ATL and HGF variations.③Tumor volume was measured before the procedure and the 28th day after procedure respectively to analyze the tumor volume variations.④PET/CT was performed on the 28th day after procedure to analyze the metastasis rate of each group.⑤The microvessel density(MVD)value of the tumors was also measured on the 28th day after procedure respectively.Results1. The quality of life after TACE After the procedure, the majority of experimental animals in all groups decreased their appetite apparently. Most of them were in depression and drowsiness and moved litter, especially group A with the most obvious. Two animals in group A and group B, three animals in group C were dead within 7 days after procedure. On the 28th day after procedure, the weight loss apparently in group A. Compared with the group B and group C, the differences were statistically significant(p<0.05).2. Tumor growthOn the 28th day after procedure, the tumor growth and tumor growth rate in each group were as follows: Group A=3.42±0.45cm3,316.77±82.44%, Group B=4.92±0.38cm3,551.36±121.92%, Group C=8.11±0.52cm3,818.70±231.27%. The differences between each group were statistically significant (p<0.05).3. Tumor metastasisAccording to the PET/CT examination on 28th day after procedure, the most common site of metastasis were liver (22 cases), lymph nodes (19 cases), lung (14 cases). The metastatic rate in each group was as follows: Group A=70%(7/10),Group B =80%(8/10),Group C =100%(10/10). The difference between each group was not statistically significant(p>0.05).4. Serum HGFVariations of serum HGF before procedure had no statistically significant in each group(p>0.05). Variations of serum HGF before and after procedure had no statistically significant in group C. There was a peak of serum HGF concentrations on the 3th day after procedure,and declined on the 7th day and then returned to normal level on the 28th day in group A and group B. The serum HGF on the 3th day after procedure was as follows: A=2.02±0.11ng/ml, B=4.63±0.75ng/ml. On the 7th day after procedure, serum HGF was as follows: A=1.87±0.10ng/ml, B=2.61±0.50ng/ml. On the 3th day and the 7th day after procedure, the differences between each group were statistically significant(p<0.05). Serum HGF on the 28th day after procedure was as follows: A=1.57±0.12ng/ml, B=1.56±0.08ng/ml. The difference had no statistically significant in each group(p>0.05). 5. Liver functionVariations of ALT level before procedure had no statistically significant in each group(p>0.05). On the 3th day,the 7th day and the 28th day after the procedure, the ALT level elevated apparently and then gradually decreased in group A and group B.ALT level on the 3th day after procedure was as follows: A=133.85±3.80μ/L, B=84.29±4.10μ/L. On the 7th day after procedure, ALT level was as follows: A=80.31±2.40μ/L, B=56.57±3.06μ/L. ALT level on the 28th day after procedure was as follows: A=51.74±3.74μ/L, B=39.57±2.31μ/L. ALT level elevated continuously after procedure in group C. On the 3th day, the 7th day and the 28th day, the differences between each group were statistically significant(p<0.05).6. Tumor angiogenesisOn the 28th day after procedure, the most exuberant tissue in the periphery of the tumor was selected to paraffin embed. MVD (anti-CD34 stain,×200 field of vision) in each group: Group A=75.97±11.46,GroupB=85.34±4.90,GroupC=63.88±10.04. The difference between each group was statistically significant (F = 13.533 P = 0.000).Conclusion1. Non-tumor liver cells regeneration may be a main factor leading to high level of serum HGF after TACE. 2. The combination of TACE and intrahepatic artery infusion of pHGF for the treatment of rabbit VX2 hepatic carcinoma can improve the quality of life and lighten the liver dysfunction after TACE.3. The combination of TACE and intrahepatic artery infusion of pHGF promotes more angiogenesis and the tumor growth than TACE alone, while it causes no more serious tumor metastasis than TACE alone.
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