MP60-20 DEVELOPMENT OF A LARGE ANIMAL URETHRAL STRICTURE MODEL IN CANINES

Abstract

INTRODUCTION AND OBJECTIVE: Male urethral stricture disease (USD) is a relatively common condition that can lead to significant voiding symptoms requiring multiple endoscopic and open procedures. Existing pre-clinical models of USD are limited to small animals. We sought to develop a large animal urethral model in canines for testing and validating future diagnostic and therapeutic innovations. METHODS: 3 canines (Marshall Bioresourcers, 25-30 Kgs, 9-12 months old) underwent scrotal urethrostomy for urethral access and urine diversion. Following a 3-4 week recovery period, a pre-intervention retrograde urethrogram (RUG) was performed. Circumferential thermocoagulation of the defunctionalized distal urethral segment was performed using pediatric resectoscope (Karl Storz, Tuttlingen, Germany) for 30-45 sec in intermittent bursts at 25-30 W power setting, until visible blanching with minimal tissue reaction was observed. Further cystoscopic, radiographic and perfusion (Moor laser Doppler Flowmetry; LDF) monitoring was performed at 2 & 8 week intervals before subsequent euthanasia and tissue harvest. Histologic examination was performed using H&E, Hart’s and Gomori’s trichrome stains. RESULTS: Comparative analysis between pre & post RUG indicated an average 50% reduction in urethral caliber which was confirmed via cystoscopic evaluations. Histologically, the urethral lumen was markedly narrowed, and the corpora spongiosa was largely replaced by proliferating fibroblasts and mature collagen. CONCLUSIONS: We describe the first successful urethral stricture disease model in an anatomically-comparable and physiologically-similar large animal. This pre-clinical model will facilitate development of novel technical and surgical therapy options for USD.Source of Funding: Johns Hopkins Tech Ventures (JHTV) Thalheimer Translational Research Fund