Innovative Approaches for Complex Penile Urethral Strictures

Jordan Siegel; Timothy J. Tausch; Jay Simhan; Allen F. Morey


Transl Androl Urol. 2014;3(2):179-185. 

In This Article

Alternative Graft Material

Graft material in adequate supply can be a limiting factor in long complex urethral strictures. This is especially true with lichen sclerosis or hypospadias failure where usable penile skin is scarce. When buccal mucosa has been previously harvested or is not of sufficient supply, lingual graft tissue can be utilized, with excellent results.[50] Oral mucosa can also be obtained from labial grafts, with good outcomes demonstrated in pediatric patients, generally in repair of hypospadias defects.[51] Similar outcomes have been shown in adults as well, with no significant difference in postoperative quality of life due to graft site complications.[52]

Additionally, buccal mucosa and lingual grafts can be hard to procure in a patient with prior graft harvesting or in cases where the patient has concomitant oral disease. Regenerative medicine offers the possibility of production of patient-specific grafts, negating the necessity of graft harvesting.[53]

Tissue-engineered grafts are generally divided into cellular and acellular subtypes. Acellular grafts are usually from cadaveric or animal sources and treated to make the matrix cell-free. Alternatively, cellular grafts are made by culturing a particular cell type, generally obtained via biopsy, and then populating biologic scaffolding to produce a histologically similar construct of the native tissue.

Acellular grafts have been used in the treatment of urethral stricture disease with varying success. Palminteri reported his use of porcine small intestinal mucosa as a graft material in bulbar urethroplasties of 25 men.[54] At 71 months follow-up, 24% of patients failed as they required additional interventions. In particular, those with strictures >4 cm experienced a higher failure rate.

With regard to cellular tissue-engineered buccal mucosal grafts, Bhargava and colleagues attempted urethroplasty in five patients using a graft derived from an acellular human dermal matrix seeded with human oral fibroblasts and keratinocytes.[55] Initial graft take was observed in all patients, however, at 33.6 months follow up, two patients required partial or full removal of the graft due to fibrosis and hyperproliferation. The other three patients had patent urethras but only after additional instrumentation to correct strictures that developed from graft contraction. It is noteworthy that all patients in this study had strictures caused by lichen sclerosis, potentially causing poorer outcomes.

Various techniques have also been employed in the production of tissue-engineered urothelial grafts for the treatment of urethral stricture disease.[56,57] In particular, Raya-Rivera and colleagues were able to create autologous urethras on a biologic scaffold, populated with bladder epithelial and muscle cells taken from bladder biopsies.[58] These neourethras were then used in the repair of five boys with traumatic posterior urethral injuries. Biopsies of the reconstructed urethras showed similar histologic characteristics to native urethras. Additionally cystoscopy at 72 months demonstrated patency in all five boys. While these results are encouraging, there are clear limitations. Further investigation of these tissue-engineered grafts needs to take place with defined stricture characteristics (etiology, size, location), larger patient numbers, and direct comparison to traditional graft tissues.