JX-594和紫杉醇双层覆膜支架治疗兔食管鳞癌实验研究

JX-594 and paclitaxel bilayer covered stent for esophageal squamous cell carcinoma: an experimental study in rabbits

目的评价负载重组牛痘病毒JX-594和紫杉醇的覆膜金属支架对兔食管鳞癌模型的治疗作用。方法通过手术将VX2肿瘤组织块种植于新西兰大白兔食管黏膜下层,成功构建VX2兔食管鳞癌模型。食管DSA造影检查确认食管狭窄>2/3管腔直径,作为支架置入适应证。将兔模型随机分为覆膜的紫杉醇负载金属食管支架(PEMS)组和双层覆膜的紫杉醇和JX-594共载金属食管支架(PJEMS)组,每组6只。DSA透视下支架输送器将支架置入食管狭窄病变部位。支架置入后2周处死实验兔,分析PEMS和PJEMS治疗兔食管鳞癌的安全性和有效性。结果支架置入术中两组各有1只兔窒息死亡,术后2周内无死亡,均未发生出血、穿孔及支架移位等并发症。两组各有5只荷瘤兔数据纳入统计学分析,结果显示PJEMS组平均肿瘤体积为(1.286±0.463)cm3,明显小于PEMS组(5.014±2.082)cm3(P<0.05);PEMS组中3只实验兔出现远处转移,其中1只为肺部弥漫性转移,PJEMS组仅1只出现远处转移;PEMS组、PJEMS组兔体质量丢失分别为(0.334±0.084)kg、(0.162±0.177)kg,差异无统计学意义(P>0.05)。结论JX-594可增强紫杉醇对局部食管鳞癌生长的抑制作用,更好地辅助食管支架治疗食管恶性狭窄,也许可为晚期食管鳞癌临床治疗提供新的研究方向。

Objective To evaluate the therapeutic effect of bilayer covered metal stent loaded with recombinant vaccinia virus JX-594 and paclitaxel in treating esophageal squamous cell carcinoma(ESCC) in experimental rabbits. Methods The rabbit models of VX2 ESCC were successfully established by surgically implanting VX2 tumor tissue block into the esophageal submucosa of New Zealand white rabbits. Esophageal stenosis exceeding 2/3 lumen diameter confirmed by DSA esophagography was defined as the indication of stent implantation. The rabbit models were randomly divided into paclitaxel-loaded esophageal metal stent(PEMS) group and paclitaxel and JX-594 co-loaded esophageal metal stent(PJEMS) group, with 6 rabbits in each group. Under DSA fluoroscopic guidance and with the help of stent conveyor, the stent was placed into the stenotic site of the esophagus. All the experimental rabbits were sacrificed 2 weeks after stent implantation. The safety and efficacy of PEMS and PJEMS for the treatment of ESCC in experimental rabbits were analyzed. Results During stent implantation one rabbit in each group died of asphyxia. Within 2 weeks after stent implantation, neither death nor complications such as bleeding, perforation or stent displacement occurred in both groups. The experimental data of 5 experimental rabbits in each group were finally included in the statistical analysis. The mean tumour volume in the PJEMS group was(1.286±0.463) cm3, which was significantly smaller than(5.014±2.082) cm3 in the PEMS group(P<0.05). In the PEMS group 3 rabbits developed distant metastases, one of which presented as diffuse pulmonary metastasis, while in the PJEMS group only one rabbit developed distant metastases. The average loss of body mass in the PEMS group and the PJEMS group was(0.334±0.084) kg and(0.162±0.177) kg respectively, the difference between the two groups was not statistically significance(P>0.05). Conclusion JX-594 can enhance the inhibition effect of paclitaxel on the local growth of ESCC, which can effectively assist esophageal stent to alleviate malignant esophageal stricture.This therapeutic method may provide a new research direction for the clinical treatment of advanced ESCC.(J Intervent Radiol, 2021, 30: 475-479)