结直肠癌术前肝动脉联合区域动脉灌注化疗对肿瘤增殖凋亡的影响

摘要

Objective To investigate the tumor proliferation and apoptosis changes after preoperative hepatic and regional arterial infusion chemotherapy (PHRAIC) after radical colorectal cancer resection. Methods Five hundred and nine patients with stage Ⅱ or stage Ⅲ colorectal cancer from June 2001 to Jane 2007 were randomly assigned to PHRAIC group ( n = 256) or control group ( n = 253, surgery alone). Tumor proliferation and apoptosis index were evaluated in tumor tissues of the control and PHRAIC group (pre and after intervention). The survival rates were also recorded in the two groups. Results There was no significant differences in sex, age, tumor location, tumor size, tumor stage, tumor differentiation and follow-up time for the two groups (P > 0. 05 ). There was no significant differences in all the evaluation factors between the control group and PHRAIC group before intervention (P > 0. 05 ). Before and after intervention for PHRAIC group : stage 3 necrosis rate were 3.1% and 22. 7%, stage 4 necrosis rate were 0 and 13. 5% (P < 0. 05) ; lable index of Ki67 were 48. 6 + 17. 1 and 38.4 ± 13.3 ( P < 0. 05 ) ; expression rate of Bax, bel-2 and survivin were 48.0% vs 77.0%, 75.0% vs 43.0%, 52. 0% vs 31.6% ,respectively( P < 0. 05) ; apoptosis rate were 4. 3% ± 2. 2% and 16. 7% ± 6. 4% ( P < 0. 05). In the PHRAIC group, 42. 1% ± 11.2% of the cells in the tumor tissue were in S phase before intervention and the rate fell to 21.8% ± 10. 7% after intervention(P < 0. 05) ; and G0-G1 phase rate of the group pre and post intervention were 35.1%±12. 1% and 57. 1% ± 18. 1% (P <0. 05). All the patients were followed-up for a mean time of 42 ± 14 months. For patients with stage Ⅲ tumor in PHRAIC group and control group, the 5-year liver metastasis rate were 18. 9% and 27. 3% (P = 0. 033), recurrence and metastasis rate were 26. 3% and 38.0 (P =0. 024), overall survival rate were 81.0% and 60. 4% (P =0. 011 ) ,median survival time were 45 and 40 months(P =0. 02) ; no significant differences of aforementioned factors was found in patients with stage Ⅱ tumors between the two groups. Conclusion The schedule of preoperative hepatic and regional arterial infusion chemotherapy before surgery can restrain proliferation, promote apoptesis and reduce liver metastasis and improve survival rate in stage Ⅲ colorectal cancer.%目的 探讨结直肠癌术前肝动脉联合区域动脉灌注化疗(PHRAIC)对肿瘤增殖凋亡的影响. 方法 将2001年6月至2007年6月收治的509例Ⅱ期和Ⅲ期结直肠癌患者随机分成PHRAIC组(n=256)和对照组(n=253),评价两组术前和术后组织标本的坏死程度、Ki67、P16、Bax、bel-2、survivin、凋亡率和细胞周期. 结果 两组一般临床资料无统计学差异.PHRAIC组术前标本的各项评价与对照组相比差异无统计学意义(P>0.05).PHRAIC组介入前后标本坏死程度3级者分别为3.1%和22.7%,4级者分别为0和13.5%(P<0.05);Ki67标记指数介入前后分别为48.6±17.1和38.4±13.3(P<0.05);BAX、bel-2和sttrvivin过表达率分别为48.0%和77.0%、75.0%和43.0%、52.0%和31.6%(P<0.05);凋亡率分别为4.3%±2.2%和16.7%±6.4%(P<0.05);PHRAIC组介入后病理标本S期比例为21.8%±10.7%,低于介入前的42.1%±11.2%(P<0.05);G0-G1的比例为57.1%±18.1%,高于介入前的35.1%±12.1%(P<0.05).所有患者均获得随访,平均随访(42±14)个月.PHRAIC组和对照组Ⅲ期患者术后5年肝转移率分别为18.9%和27.3%,转移复发率分别为26.3%和38.0%,总生存率分别为81.0%和60.4%,中位生存期分别为45和40个月,差异均有统计学意义(P<0.05);两组Ⅱ期患者间上述指标间无明显差异. 结论 术前肝动脉联合区域动脉灌注化疗可抑制肿瘤细胞的增殖,促进凋亡,降低Ⅲ期结直肠癌患者术后肝转移的发生率,延长生存期.