化疗栓塞对膀胱肿瘤新生血管生成及血管内皮细胞生长因子表达的影响

Influence of chemoembolization on neovascularization and vascular endothelial growth factor expression in bladder cancer

目的 探讨膀胱动脉化疗栓塞对膀胱肿瘤新生血管生成及血管内皮细胞生长因子（VEGF）表达的影响。方法 膀胱癌患者30例。临床分期Tis 1例、Ta 2例、T1 6例、T2 11例、T3 9例、T4 1例。病理分级G1 9例、G2 13例、G3 8例。采用丝裂霉素20mg或羟喜树碱10mg联合顺铂60mg经膀胱动脉灌注及明胶海绵栓塞。化疗栓塞前后膀胱镜下取肿瘤组织，免疫组织化学SP法测定VEGF表达及微血管密度（MVD），并进行病理观察及随访。结果 化疗栓塞前后肿瘤VEGF阳性表达率分别为73．33％（22例）及43.33％（13例）；MVD分别为69．81±3．38及56．35±3．26，差异均有统计学意义（P〈0．05）。病理观察栓塞前后瘤体直径分别为（2。17±0．88）及（1．58±0．87）cm，差异有统计学意义（P〈O．05）。化疗栓塞后肿瘤组织明显坏死、退变。30例随访12～36个月，平均24.6个月，5例复发（G1T1、G2T1、G2T3、G3T3、G3T4各1例，单纯移行细胞癌4例、混合癌1例），复发时间为栓塞后6个月1例，6～12个月2例，24～36个月2例。复发组栓塞前后VEGF阳性分别为5例（均为强阳性）及4例（阳性3例、强阳性1例），差异无统计学意义（P〉0．05），但强阳性表达差异有统计学意义（P〈0．05）；MVD值分别为87．35±2．96、72．37±4．11，差异有统计学意义（P〈0．05）。未复发组栓塞后MVD值为53.15±3.50，与复发组比较差异有统计学意义（P〈0.05）。结论 化疗栓塞能降低膀胱癌组织VEGF表达，减少MVD计数，提示化疗栓塞可影响膀胱癌的分化程度，使肿瘤降级降期，减少术后转移，降低复发率，提高生存率。

Objective To study the influence of transcatheter bladder arterial chemoembolization on neovascularization and vascular endothelial growth factor （VEGF） expression in bladder cancer treatment. Methods Thirty bladder cancer patients （Tis=l, Ta=2, T1=6, T3=11, T3=9, T4= 1 ; G1 =9, G2 = 13, G3 =8） were treated with transcatheter arterial chemotherapy with Mitomycin （20 mg） or Hydroxycamptothecin （10 mg） adding cisplatin （60 mg） and embolization with gelatine sponge particle gelform 1 week before surgery. Before and after the chemoembolization, the expression of VEGF and microvessel density （MVD） count in cancer tissue were examined by SP immunohistochemical staining. Tumor samples after chemoembolization were taken and sent for pathological examination. The over all survival rates were recorded and analyzed as well. Results Before and after the chemoembolization, positive rates of VEGF expression in bladder cancer tissue were 73. 3% and 43.3%, respectively and MVD were 69.8±3.4 and 56.4±3.3, respectively. There were significant differences between the parameters before and after the treatment （P〈0.05）. After the intervention, tumor diameter decreased from 2.2±0.9 cm to 1.6±0.9 cm （P〈0.05） and tumor tissues were in severe necrosis and degeneration. During the follow up of 24.6 months （ranging from 12 to 36 months）, there were 5 recurrent cases （G1 T1 = 1, G2 T1=1, G2 T3=1, G3 T3 = 1, G3 T4 = 1, primary transitional cell carcinoma-4, admixture carcinoma= 1）. In the recurrent group, VEGF expression were positive in 5 cases （100% strong positive） and 4 cases （80%, 3 positive, 1 strong positive） （P〉0.05） before and after the chemoembolization. However, it had significant difference in strong positive ex pression （P〈0.05）; MVD were 87.4±3.0 and 72. 4±4. 1 （P〈0.05） before and after the treatment. The MVD in no recurrent group was 53.2±3.5 after chemoembolization, and it had statistical significance comparing with the recurrent group （P〈0.05）. Conclusions The chemoembolization can decrease the expression of tumor VEGF and MVD. Thus, it can adjust bladder cancer malignancy, downgrade and downstage the tumors and decrease the risk of postoperative metastasis. For the long-term, this treatment ;viii improve the survival rate and reduce recurrence rate.