显微镜辅助下精准切除术在裸鼠非局部晚期结肠癌中的应用

Application of microscopically assisted precision resection in nude mouse model of non-local advanced colon cancer

目的探讨显微镜辅助下结肠区段切除术(MALC)在裸鼠非局部晚期结肠癌(NLACC)模型中的技术可行性和肿瘤学安全性。方法利用已被荧光素酶标记的鼠源性CT-26结直肠癌细胞株建立BALB/c裸鼠NLACC模型。1周后,将NLACC模型随机分成MALC组和假手术组(每组10只),MALC组施行显微镜下结肠区段切除术,而假手术组在显微镜辅助下仅进行开关腹手术(MAOCS)。模型制作后,定期用小动物活体成像系统(IVIS)监测模型体内肿瘤细胞的行为学变化。术后第3周处死所有裸鼠,比较两组模型建模情况和评估手术的近期疗效。结果BALB/c裸鼠NLACC模型制作的成功率为100%(20/20)。两组裸鼠术中无1例死亡。术后MALC组的裸鼠无结肠原位肿瘤的复发,而假手术组结肠原位肿瘤的质量和体积呈进行性增长趋势。除此之外,MALC组在血性腹水(0 vs 40%)、局部侵袭(0 vs 100%)、肠梗阻(0 vs 100%)、淋巴结转移(0 vs 10%)发生率上均明显低于假手术组(P<0.05)。影像学分析提示,MALC组裸鼠体内的肿瘤细胞的生物发光信号即ROI值(region of interest value)显著低于假手术组,差异有统计学意义(P<0.05)。结论MALC模型在技术层面上可行,且其在裸鼠NLACC中的近期肿瘤学行为上安全可靠,但其远期肿瘤学行为仍有待于进一步研究。

Objective To investigate the technical feasibility and the oncological behavior safety of microscope-assisted limited colectomy(MALC)in BALB/c nude mouse model of non-local advanced colon cancer(NLACC).Methods The BALB/c nude mice were injected with mouse-derived CT-26 colorectal cancer cell lines labeled with luciferase into the submucosal layer of colonic wall to induce NLACC models,and then randomly divided into MALC group(n=10)and sham group(n=10).One week later,MALC and the simple microscope-assisted open and close surgery(MAOCS)were implemented in MALC group and sham group,respectively.Three weeks after modeling,the behavioral changes of tumor cells in the models were monitored regularly with the small animal in vivo imag-ing system(IVIS).And then all mice were euthanized to compare the modeling and evaluate the short-term outcomes of surgery between two groups.Results The successful rate of BALB/c nude mouse models of NLACC was 100%(20/20).There was no death in both groups during the operation.After surgery,there was no recurrence of colonic primary tumor in MALC group,but there was a progressive increasing of colonic primary tumor in tumor size including weight and volume in sham group.In addition,the incidences of bloody ascites(0 vs 40%),recurrence or local invasion(0 vs 100%),intestinal obstruction(0 vs 100%)and lymph node metastasis(0 vs 10%)in MALC group were significantly lower than those in sham group(P<0.05).According to imaging analysis,the bioluminescence signal of tumor cells in MALC group,namely,the region of interest(ROI)value,was significantly lower than that in sham group(P<0.05).Conclusion All in all,the MALC is technically feasible,safe and reliable in short-term oncological behavior in nude mice with NLACC,but the long-term outcomes remains to be revealed in the future.