Docetaxel Inhibits Urethral Stricture Formation, an Initial Study in Rabbit Model

Abstract

IntroductionUrethral stricture, a frequent source of lower urinary tract disorders in men, is still a difficult problem for urologists. Based the anti-restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi-synthetic analogue of paclitaxel, in limiting urethral stricture formation was studied.MethodsForty adult New Zealand male rabbits were involved in this study, which were randomly assigned into 3 groups, namely a high dose docetaxel (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group, with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm-long circumferential electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Drugs were given by urethral irrigation daily and continuous for 28 days. Stricture formation was assessed by retrograde urethrography and videourethroscopy. Urethra pathology was evaluated by hematoxylin and eosin staining and Sirius red staining.ResultsAt the end of this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group, respectively. Urethral diameters in DH, DL and C group were (7.17±1.63) mm, (6.55±0.62) mm, (3.23±1.36) mm, with a normal urethral diameter of (9.08±1.29) mm. Lumen reduction in DH, DL and C group were (36.93±11.58)%, (48.03±7.89)% and (84.66±14.95)%, respectively. Statistically difference could be found between every two groups (p<0.05) both in urethral diameters and in lumen reduction, except for compare of urethral diameters between DH and DL group. Histological examination confirmed mass fibrous tissue and collagen content at the stricture sit in C group, whereas less in docetaxel treated rabbits.ConclusionsDocetaxel could limit urethral stricture formation, which may be due to inhibition of fibrous tissue and collagen expression. Docetaxel may become a new choice in the prevention of urethral stricture formation.

Advances in urethral stricture management

“…Systemic use of other chemotherapeutics such as docetaxel and rapamycin has also been investigated. In a rabbit model, the systemic docetaxel-receiving groups displayed less collagen deposition than did controls 66 . In the rapamycin study, Chong et al .…”

Characterization of urethral fibrosis in a rabbit model: Potential roles of Wnt‐β catenin pathway and epithelial to mesenchymal transition

“…Several animal models have been employed in the past to evaluate urethral injury‐related fibrosis, as well as antifibrotic interventions that limit scarring. Of these, rabbits have been the preferred animal model, and electrocautery has been the most common method to induce injury 14 . Use of this model allows for controlled urethral wall injury at a specific location, as well as monitoring of endogenous repair processes via RUG, providing greater accuracy and validity to preclinical studies.…”

“…Of these, rabbits have been the preferred animal model, and electrocautery has been the most common method to induce injury. 14 Use of this model allows for controlled urethral wall injury at a specific location, as well as monitoring of endogenous repair processes via RUG, providing greater accuracy and validity to preclinical studies. After injury, urethral mucosa is known to regenerate through a series of well-coordinated events.…”

A Comparative Study of Optical Internal Urethrotomy Alone With Optical Internal Urethrotomy Plus Steroid for Anterior Urethral Stricture Disease

“…[8,9] The main pathogenesis of stricture is the fibrosis formation caused by excessive collagen synthesis and changes in the extracellular matrix of the urethral lumen due to the endoscopic instrumentation, trauma and infections. Spongiofibrosis occurs in varying degrees and narrows the urethral lumen so that there are some ideas to treating the fibrosis with antifibrotic agents such as hyaluronidase, mitomycin C, bitoxin A, [19] captopril, [20] docetaxel, [21] somatostatin analogues [22] and steroids. There are many studies that have come with OIU along with injection triamcinolone.…”