| Objective To explore the pharmacokinetics and significance of implant chemotherapy via para-colon approach. To evaluate the effect of a neoadjuvant chemotherapy with 5-fluorouracil sustained release for implant(5-FU SRI)injected in rectal submucosal in the patients with rectal cancer. The effect of this treatment was judged by cellular degeneration,necrosis degree,apoptotic index,oncogene expression, the positive rate of proliferating expression.Methods Twenty five adult hybrid dogs were divided into two groups, 20 in chemotherapy group and 5 in control. Two hundred milligram 5-FU SRI were imbedded at one point in para-sigmoid colon via abdomen operation. A pipe was inserted into portal vein for collecting blood samples. At different time points, tissue samples in different distance from the imbed point and different lymphoid node and blood samples from periphery and portal vein were collected to be taken for drug concentration measurement in HPLC method. Tissue samples around mesentery and anastomose were collected in deferent period and were checked for anastomose heal in pathology. The patient with rectal cancer did the operation after 5-FU SRI seven days, observe the degeneration and necrosis of the implant point. The Bcl-2, Bax and caspase gene expression of carcinoma cells were examined by immunohistochemical method and apoptosis with TUNEL.Results 1)The drug concentration of local tissue and different lymphoid node decreased gradually at distance increase. The drug concentration of portal vein,tissue and lymphoid node also decreased at time prolong. At 15 day point, drug concentration of tissue away from imbed point 15 cm (0.101±0.015μg/g),mesentery lymphoid node(0.204±0.059μg/g) and portal vein (0.102μg/ml) were all more than treatment concentration(0.1μg/ml). 2)The colonic anastomose tissues only occurred inflammatory reaction in early stage, and no necrosis and cellular degeneration presented in pathology. The anastomose tissues healed completely at tenth day post-operation. 3)After treatment with 5-FU SRI, in 15 patients,the expression of bcl-2 diminished,while the bax and caspase were remarkly increased. The apoptotic index of experiment group was significantly increased. There was significant different as compared with the control(p<0.05).Conclusion The chemotherapy of implant delayed release drug via para-colon approach may maintain lasting and effective and higher concentration in tissue,lymphoid node and portal vein. It had no effect on anastomose heal. This results indicate that 5-FU may induce apoptosis of rectal carcinoma cell line and the possible mechanism of apoptosis induction is through upregulation of bax and caspase expression and the change of bax to bcl-2 ratio. |
