Cytotoxicity Assessment of a New Design for a Biodegradable Ureteral Mitomycin Drug-Eluting Stent in Urothelial Carcinoma Cell Culture.

Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.

Assessment of a Coated Mitomycin-Releasing Biodegradable Ureteral Stent as an Adjuvant Therapy in Upper Urothelial Carcinoma: A Comparative In Vitro Study.

A major limitation of the treatment of low-grade upper tract urothelial carcinoma is the difficulty of intracavitary instillation of adjuvant therapy. Therefore, the aim of this in vitro study was to develop and to assess a new design of biodegradable ureteral stent coated with a silk fibroin matrix for the controlled release of mitomycin C as a chemotherapeutic drug. For this purpose, we assessed the coating of a biodegradable ureteral stent, BraidStent®, with silk fibroin and subsequently loaded the polymeric matrix with two formulations of mitomycin to evaluate its degradation rate, the concentration of mitomycin released, and changes in the pH and the weight of the stent. Our results confirm that the silk fibroin matrix is able to coat the biodegradable stent and release mitomycin for between 6 and 12 h in the urinary environment. There was a significant delay in the degradation rate of silk fibroin and mitomycin-coated stents compared to bare biodegradable stents, from 6-7 weeks to 13-14 weeks. The present study has shown the feasibility of using mitomycin C-loaded silk fibroin for the coating of biodegradable urinary stents. The addition of mitomycin C to the coating of silk fibroin biodegradable stents could be an attractive approach for intracavitary instillation in the upper urinary tract.

Assessment of the Grades of Vesicoureteral Reflux in Stented Ureters: An Experimental Study.

INTRODUCTION: The aim of this experimental study is to assess, in a porcine model, the onset and grades of vesicoureteral reflux associated with ureteral stents. METHODS: Twenty-four female porcine models were used. A 4.7-Fr ureteral stent was placed in all right ureters and kept in place for 6 weeks. Follow-ups were performed on weeks 1, 3, 6, and 12. Ultrasonography, cystoscopy, and fluoroscopy were used to analyze grade of hydronephrosis, presence and grade of vesicoureteral reflux, bacteriuria, and macroscopic changes of the ureteral orifices. Vesicoureteral reflux was classified using a modification of the International Reflux Study Committee grades. RESULTS: 91.7% animals present vesicoureteral reflux, 89.5% grade IA, 3.5% grade IB, and 7% grade II. There is a significant increase in reflux during follow-ups at 3 and 6 weeks, whereas 6 weeks after removal, 26.3% of the ureters still present vesicoureteral reflux. Hydronephrosis and macroscopic changes of the ureteral orifice increase significantly with stenting, but there is no significant association between them and vesicoureteral reflux; the relationship between bacteriuria and the presence of vesicoureteral reflux is not significant either. CONCLUSION: Vesicoureteral reflux caused by ureteral stents in an animal model is mostly low grade and mainly affects the distal ureter.

Experimental Assessment of New Generation of Ureteral Stents: Biodegradable and Antireflux Properties.

Objective: The aim was to assess a new biodegradable and antireflux intraureteral stent (BraidStent®) design in a swine model after ureteral laparoscopic operation. Materials and Methods: A total of 24 female pigs underwent initial endoscopic, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Afterward, unilateral ureteropelvic junction obstruction was performed by laparoscopic approach. Six weeks later, the animals underwent laparoscopic Anderson-Hynes pyeloplasty, and were randomly assigned to Group-I, in which a double-pigtail ureteral stent was inserted for 6 weeks, or Group-II, in which a BraidStent®, a biodegradable intraureteral stent design, was placed. Follow-up assessments were performed at 3 and 6 weeks and 5 months. Results: In terms of therapeutic success, complete resolution was observed in 91.6% of Group-I animals and 88.8% in Group-II. No evidence of vesicoureteral reflux (VUR) was observed in Group-II animals and statistical significance in VUR and ureteral orifice damage were observed between groups. BraidStent® degradation occurred in a controlled manner between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6% and 83.3% in Group-II at 3 and 6 weeks of follow-up, respectively. In Group-II, the positive bacteriuria rate was 41.6% and the migration rate 25%. Pathological assessment showed a significant improvement in ureteral healing in Group-II vs Group-I. Conclusions: The results of this comparative study in a porcine model indicate that the intraureteral BraidStent performed similarly to conventional ureteral stents. It avoids complete ureteral length intubation, the adverse effects associated with conventional ureteral stents, and maintains a high level of distal ureteral peristalsis. Moreover, the BraidStent® exhibited a predictable and controlled degradation rate and did not cause any obstructive fragments. However, further studies are needed to improve the anchoring system and reduce the risk of bacterial colonization.

Antireflux ureteral stent proof of concept assessment after minimally invasive treatment of obstructive uropathy in animal model.

OBJECTIVES: To assess the efficacy of a new anti-reflux intraureteral stent design in a swine model after minimally invasive treatment of ureteral stricture to reduce ureteral stent morbidity, previous to manufacture this design in a biodegradable fashion. METHODS: Twenty-eight female pigs were included. The study began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment. Afterwards, obstructive uropathy model in right ureter was created. Obstruction was confirmed 6 weeks later and animals were randomly distributed into 2 groups. Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the aforementioned diagnostic methods and pathological study. RESULTS: None of the study animals showed any vesicoureteral reflux signs or ureteral orifice injury. There were no urinomas or ureteric fistulas. The dislodgement rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral peristalsis below the stent, and 100% at the final follow-up. After pathological assessment, no differences were shown at UPJ and healing in the incised area was correct in both groups. CONCLUSIONS: The new stent design avoids vesicoureteral reflux and bladder trigone irritation, consequently might reduce morbidity associated with double pigtail ureteral stents. This study also shows that it is only necessary temporary scaffolding the incised ureteral segment and not the entire length of the ureter after minimally invasive surgery. It is also necessary to manufacture this design in a biodegradable material, thus avoiding its removal.