动物模型评估一种新设计的涂层丝裂霉素释放可生物降解输尿管支架,作为上尿路移行细胞癌辅助治疗的腔内注入方式。
Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma.
发表日期:2023 Apr
作者:
Federico Soria, Julia E Delacruz, Salvador D Aznar-Cervantes, Javier Aranda, Luna Martínez-Pla, Marcos Cepeda, Alberto Pérez-Lanzac, Gonzalo Bueno, Francisco M Sánchez-Margallo
来源:
Minerva Urology and Nephrology
摘要:
上尿路尿路癌治疗中的主要局限是,由于现有腔内注入技术的缺点,辅助治疗的使用受到限制。目的是评估一种用桑蚕丝纤维蛋白包覆的可生物降解输尿管支架,用于丝裂霉素的释放,即BraidStent-SF-MMC。共有14头单肾雌猪进行了初步尿液分析、血液化学、肾超声和造影检查。之后,反行放入BraidStent-SF-MMC来评估从0-48小时的丝裂霉素尿液浓度。随访每周一次,直到完全分解,以评估尿路、支架并发症中的宏观和微观变化。药物释放支架在前12小时释放丝裂霉素。主要并发症是在第一至第三周,28.5%和7.1%的动物释放了阻塞性输尿管包覆碎片,与尿pH <7.0有关,导致支架包覆不稳定。另一种并发症是第四至第六周间尿路狭窄 (21%)。支架完全降解需6-7周。没有支架相关的全身毒性反应。成功率为67.5%,并发症率为25.7%。我们首次展示了一种可生物降解的防癌药物释放支架BraidStent-SF-MMC,在动物模型中提供了对丝裂霉素的可控和良好耐受的上尿路释放。来自丝素衣包膜的丝裂霉素释放可能是上尿路尿路癌辅助化疗注入的一个有说服力的方法。
A major limitation in the treatment of upper urinary tract urothelial carcinoma is the limited use of adjuvant therapy due to the drawbacks of current techniques for intracavitary instillation. The aim was to assess, in a large animal model, a biodegradable ureteral stent coated with silk fibroin for mitomycin release, i.e. BraidStent-SF-MMC.A total of 14 female pigs with a solitary kidney underwent initial urinalysis, blood chemistry, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Later, the BraidStent-SF-MMC was placed retrogradely to assess the mitomycin urine concentration from 0-48 hours. Follow-up was performed weekly until complete stent degradation to assess the macroscopic and microscopic changes in the urinary tract, stent complications.The drug eluting stent released mitomycin for the first 12 h. The main complication was the release of obstructive ureteral coating fragments during the first to third week in 28.5 and 7.1% of animals, respectively, related to urinary pH<7.0, which destabilized the stent coating. Another complication was ureteral strictures between the fourth and sixth week in 21%. The stents were completely degraded by 6-7 weeks. There were no stent-related systemic toxic effects. The success rate was 67.5% and the complication rate was 25.7%.For the first time, we have shown that a biodegradable anti-cancer drug eluting stent, BraidStent-SF-MMC, provides controlled and well-tolerated release of mitomycin into the upper urinary tract in an animal model. Mitomycin release from a silk fibroin coating could be a compelling approach for adjuvant chemotherapy instillation in upper tract urothelial carcinoma management.