Repeated Transurethral Interventions Increase Elastin Degradation and Stricture Severity.

Abstract

Objective: To investigate the role of elastin in the progression of recurrent urethral strictures induced by repeated transurethral endoscopic interventions, using a preclinical animal model with translational relevance.

Methods: Urethral strictures were induced in middle-aged male New Zealand White rabbits (n = 6) via endoscopic electrocoagulation (50 W, 600 Hz, 10 seconds) at two sites located 4 cm and 5 cm from the urethral meatus. A subset of animals (n = 3) subsequently underwent repeated urethral dilation (UD) using Foley balloon inflation for 10 minutes. Ultrasound-guided imaging was performed at the preinjury and postinjury time points to assess urethral diameter. Urethral tissues collected 45 days postinjury were processed for Verhoeff's Van Gieson (VVG) staining and elastin fragmentation quantification. Human urethral stricture tissues obtained during urethroplasty were also analyzed using VVG staining and immunostaining for collagen I and elastin.

Results: A retrograde urethrogram performed on day 14 post-injury revealed urethral stricture formation at the injury site, with further narrowing observed by day 45. In the electrocoagulation-only group, the urethral cross-sectional area decreased to approximately 5-10 mm² at the injury site (∼30%-50%), whereas in the electrocoagulation plus UD group, a further reduction, reaching approximately 3-8 mm² (∼60%-75%) relative to baseline, was observed. VVG-stained histological sections from the electrocoagulation-only group showed elastic fiber fragmentation, degradation, and irregular distribution, whereas the electrocoagulation plus UD group exhibited more severe elastic fiber fragmentation and a nonuniform distribution. The quantification of elastin fragmentation and elastin% showed higher mean values in the electrocoagulation plus UD group than in the electrocoagulation-only group, although the differences were not statistically significant. VVG staining of human urethral stricture tissues demonstrated extensive degradation of the elastic fiber network, and immunostaining revealed colocalized expression of collagen I and elastin.

Conclusion: This study suggests that elastin degradation is associated with urethral fibrogenesis in recurrent stricture formation following repeated transurethral interventions.