Experimental study on metastasis and correlation of metastasis with angiogenesis of hepatic tumor in rabbits after transcatheter arterial chemoembolization using As₂O₃ and lipiodol

Objective: To investigate the effect of transcatheter arterial chemoembolization (TACE) using As₂O₃ and Lipiodol on the growth and metastasis of the implanted hepatic tumor in rabbits and the correlation of metastasis with angiogenesis of the residual tumor. Methods: Forty-eight New Zealand white rabbits were randomly divided into four groups and VX₂ carcinoma was implanted in the left lobes of the livers. Two weeks later, a catheter was inserted into the hepatic artery and infusion was performed via the hepatic artery using physiological saline (group A), Lipiodol (group B), ADM-Lipiodol (group C), and As₂O₃-Lipiodol (group D), respectively. One week after the treatment, the value of microvessel density (MVD) of tumors (samples got by biopsy) was examined by immunohistochemistry. Three weeks after the treatment, the volume and necrotic area of the implanted tumor were measured. The metastases in the liver, lungs and other organs were recorded. Results: One week after the treatment, the value of MVD of the tumors was (21.8 ± 5.3), (23.4 ± 3.9), (22.4 ± 4.5), and (14.3 ± 3.4) /400 power LM (F11.246, P=0.000). Three weeks after the treatment, the mean volume of the implanted tumor was (35.5 ± 7.1), (21.2 ± 8.3), (20.7 ± 9.1), and (11.8 ± 3.7) cm³ (F=21.203, P=0.0000) in groups A, B, C and D, respectively. There was significant difference between group D and group B (q 4.398, P<0.05), and between group D and group C (q=4.178, P<0.05). Meanwhile there was significant difference between group B, C, D versus group A (q=6.723, 6.940, 11.119, P<0.05). There was no statistical difference for necrosis area of the tumors (F=1.284, P=0.292). The number of lung metastatic nodes in group D was less than that in other groups (H=14.983, P=0.002), and the diameter of lung metastatic nodes in group D was also smaller than that in other groups (F=4.580, P=0.007). The score of celiac lymph node metastasis grading in As₂O₃-Lipiodol treatment group was less than that in other groups (H=9.148, P=0.027). There was a positive correlation between the number and size of metastasis in lungs and the value of MVD in the tumor area (P<0.05), and also between the celiac lymph node metastasis and the value of MVD in the tumor area (P<0.05). Conclusion: TACE using As₂O₃ and Lipiodol can inhibit the growth of tumor and decrease tumor metastasis in lungs and celiac lymph node, and the inhibition of the neovascularization may be an important mechanism for inhibiting tumor growth and metastasis. (authors)