Histological and Biochemical Evaluation of Urethral Scar following Three Different Hypospadias Repairs: An Experimental Study in Rabbits
03 June 2017
04 July 2017
24 August 2017 (eFirst)
Introduction Several urethroplasties have been employed in the surgical treatment of hypospadias. Neourethral strictures are among the most common postoperative complications that often require reoperation.
Materials and Methods We created a hypospadias model in New Zealand white male rabbits through a hypospadias-like defect and acute repair. A total of 24 animals were randomly allocated into three groups: tubularized incised-plate urethroplasty (TIPU) group (8), perimeatal-based flap urethroplasty (Mathieu) group (8), onlay island flap urethroplasty (onlay) group (8), and corresponding surgical procedures were immediately performed to reconstruct neourethra. The rabbits were killed postoperatively at 5 days, 2 weeks, 6 weeks, and 3 months, respectively. The penile tissue was harvested for histological and biochemical investigations to evaluate the expressions of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMactin) in all groups.
Results All rabbits were operated on uneventfully. The amount of collagen content was increased in the Mathieu and onlay groups than in the TIPU group (p < 0.05). Biochemical analysis showed that the expression of TGF-β1 in the TIPU group was decreased compared with the two other groups at 2 or 6 weeks postoperatively (p < 0.01). The expression pattern regarding α-SMactin was similar at 6 weeks or 3 months postoperatively (p < 0.01).
Conclusion The neourethra repaired by TIPU was practically resumed to normal anatomy and scarring was less apparent than the two other groups. Therefore, TIPU is considered as a relatively rational approach for hypospadias repair. The activity of fibroblasts has been increased in the long term, which may be the pathogenesis of neourethral stricture following hypospadias repair.
This study was financially supported by the National Natural Science Foundation of China (grant number 81370782).
- 1 Borer JG, Retik AB. Hyposadias. In: Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders; 2007: 3703-3710
- 2 Lee OT, Durbin-Johnson B, Kurzrock EA. Predictors of secondary surgery after hypospadias repair: a population based analysis of 5,000 patients. J Urol 2013; 190 (01) 251-255
- 3 Castagnetti M, El-Ghoneimi A. Surgical management of primary severe hypospadias in children: systematic 20-year review. J Urol 2010; 184 (04) 1469-1474
- 4 Fenner A. Pediatrics: 20 years of hypospadias repair—yet still no consensus. Nat Rev Urol 2010; 7 (12) 647
- 5 Springer A, Krois W, Horcher E. Trends in hypospadias surgery: results of a worldwide survey. Eur Urol 2011; 60 (06) 1184-1189
- 6 Snodgrass W. Tubularized, incised plate urethroplasty for distal hypospadias. J Urol 1994; 151 (02) 464-465
- 7 Snodgrass WT, Bush N, Cost N. Tubularized incised plate hypospadias repair for distal hypospadias. J Pediatr Urol 2010; 6 (04) 408-413
- 8 Ververidis M, Dickson AP, Gough DC. An objective assessment of the results of hypospadias surgery. BJU Int 2005; 96 (01) 135-139
- 9 Snodgrass WT, Lorenzo A. Tubularized incised-plate urethroplasty for proximal hypospadias. BJU Int 2002; 89 (01) 90-93
- 10 Jesus LE, Schanaider A, Kirwan T. , et al. Reduced flow after tubularized incised plate urethroplasty--increased fibrogenesis, elastin fiber loss or neither?. J Urol 2014; 191 (06) 1856-1862
- 11 Leslie B, Jesus LE, El-Hout Y. , et al. Comparative histological and functional controlled analysis of tubularized incised plate urethroplasty with and without dorsal inlay graft: a preliminary experimental study in rabbits. J Urol 2011; 186 (4, Suppl): 1631-1637
- 12 Lalla M, Riis C, Jørgensen CS, Danielsen CC, Jørgensen TM. A biomechanical, histological and biochemical study in an experimental rabbit hypospadias repair model using scanning acoustic microscopy. J Pediatr Urol 2011; 7 (04) 404-411
- 13 Abidu-Figueiredo M, Ribeiro IC, Chagas MA, Cardoso LE, Costa WS, Sampaio FJ. The penis in diabetes: structural analysis of connective tissue and smooth muscle alterations in a rabbit model. BJU Int 2011; 108 (03) 400-404
- 14 Erol A, Baskin LS, Li YW, Liu WH. Anatomical studies of the urethral plate: why preservation of the urethral plate is important in hypospadias repair. BJU Int 2000; 85 (06) 728-734
- 15 Hsiao KC, Baez-Trinidad L, Lendvay T. , et al. Direct vision internal urethrotomy for the treatment of pediatric urethral strictures: analysis of 50 patients. J Urol 2003; 170 (03) 952-955
- 16 Bleustein CB, Esposito MP, Soslow RA, Felsen D, Poppas DP. Mechanism of healing following the Snodgrass repair. J Urol 2001; 165 (01) 277-279
- 17 Taneli F, Ulman C, Genc A, Yilmaz O, Taneli C. Biochemical analysis of urethral collagen content after tubularized incised plate urethroplasty: an experimental study in rabbits. Urol Res 2004; 32 (03) 219-222
- 18 Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. J Int Med Res 2009; 37 (05) 1528-1542
- 19 Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF. Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 1987; 237 (4820): 1333-1336
- 20 Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002; 3 (05) 349-363
- 21 Wang XJ, Han G, Owens P, Siddiqui Y, Li AG. Role of TGF beta-mediated inflammation in cutaneous wound healing. J Investig Dermatol Symp Proc 2006; 11 (01) 112-117
- 22 Baskin L, Howard PS, Macarak E. Effect of mechanical forces on extracellular matrix synthesis by bovine urethral fibroblasts in vitro. J Urol 1993; 150 (2 Pt 2): 637-641