PD31-05 REPEATED TRANSURETHRAL INTERVENTIONS INCREASE ELASTIN DEGRADATION AND STRICTURE SEVERITY

Abstract

You have accessJournal of UrologyCME1 May 2022PD31-05 REPEATED TRANSURETHRAL INTERVENTIONS INCREASE ELASTIN DEGRADATION AND STRICTURE SEVERITY Michael Witthaus, Jathin Bandari, Thomas Will Fuller, Valmik Bhargava, Jill Buckley, and Mahadevan Rajasekaran Michael WitthausMichael Witthaus More articles by this author , Jathin BandariJathin Bandari More articles by this author , Thomas Will FullerThomas Will Fuller More articles by this author , Valmik BhargavaValmik Bhargava More articles by this author , Jill BuckleyJill Buckley More articles by this author , and Mahadevan RajasekaranMahadevan Rajasekaran More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002582.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Repeated transurethral interventions can cause or exacerbate urethral stricture disease by increasing tissue damage. A clear understanding of molecular mechanisms involved in increased fibrogenesis would enable development of optimal strategies to minimize progression or prevent stricture recurrence. Recently elastin, an extracellular matrix protein has been implicated in heart, liver and kidney fibrosis. We hypothesize repeated transurethral mechanical stretch accelerates elastin degradation and increases stricture severity. METHODS: Electrocautery was used to induce strictures in middle aged rabbits (12 months; n=6; Fig A). Rabbits (n=3) that showed evidence of stricture development at 14 days post-injury were further subjected to urethral wall stretch using a Foley catheter (balloon inflated to 14 mm diameter for 10 minutes, once a week for 4 weeks; Fig B). Animals were then allowed to recover and subjected to retrograde urethrogram (RUG) to confirm stricture progression and sacrificed at 45 days post-injury. Urethral tissues were harvested and subjected to immunostaining (Verhoeff–Van Gieson; VVG) for elastin. Results were then validated in human urethral scar tissues (n=3) obtained from patients undergoing urethroplasty. RESULTS: RUG findings are summarized in the Fig C. The RUGs performed showed a significant increase in stricture severity after balloon dilation (Fig C -bottom panel). The methodology utilized in the animal model was confirmed fluoroscopically to be replicable. VVG showed strong labeling for elastin (Fig E-F; black stain; yellow arrows) in rabbit and human (Fig G) scar tissues relative to controls (Fig D). CONCLUSIONS: Our findings confirm that this approach is a viable model to study transurethral intervention induced fibrogenesis. It further supports our hypothesis that urethral wall stretch worsens stricture severity due to elastin degradation. This may be an initiating factor in tissue remodeling after injury. Targeting elastin using an elastase may be a potential pharmacological intervention to treat or prevent stricture recurrence after transurethral interventions. Source of Funding: UCSD Academic Senate © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e542 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Witthaus More articles by this author Jathin Bandari More articles by this author Thomas Will Fuller More articles by this author Valmik Bhargava More articles by this author Jill Buckley More articles by this author Mahadevan Rajasekaran More articles by this author Expand All Advertisement PDF DownloadLoading ...