New Frontiers in Urethral Reconstruction

Injectables and Alternative Grafts

Alex J. Vanni

Disclosures

Transl Androl Urol. 2015;4(1):84-91. 

In This Article

Injectables

The goal of treating any urethral stricture is to provide a durable, patent urethra with minimal morbidity. While open urethroplasty is the gold standard treatment for anterior urethral strictures, endoscopic management does have a role in highly select patients. Since the outcomes of endoscopic treatment are vastly inferior to urethroplasty, improving our current endoscopic treatments is important, and if successful, has the potential to greatly reduce patient morbidity. There have been a number of different techniques and anti-fibrotic agents used in the hope of blunting wound contraction and scar formation.

The optimal therapeutic intervention is to augment a traditional urethrotomy with an antiproliferative, anti-scar forming agent (Figures 1–3). Steroids (triamcinolone), mitomycin C (MMC), and hyaluronidase are all antifibrotic agents that have the potential to reduce stricture recurrence. Steroids have well known anti-fibrotic and anti-collagen properties. MMC has been shown in both in vitro and animal studies to inhibit fibroblast proliferation, collagen deposition, and scar formation.[1–3] Additionally, MMC has been used in numerous medical specialties for its anti-scar properties. It is used for glaucoma and pterygium excision, nasolacrimal duct obstruction, laryngeal and tracheal stenosis, and vaginal and anal stenosis.[4–12] Hyaluronidase is an antifibrotic agent used in hypertrophic scar, keloid, and pulmonary fibrosis. This agent suppresses wound healing inflammatory mediators, decreases fibroblast proliferation, and decreases collagen and glycosaminoglycan synthesis.[13]

Figure 1.

Ureteral stricture.

Figure 2.

Direct vision internal urethrotomy (DVIU).

Figure 3.

Injection of MMC. MMC, mitomycin C.

The current urologic literature demonstrates few high quality studies investigating the use of antifibrotic injectables for the treatment of anterior urethral strictures. Triamcinolone is the agent that has been studied the most extensively, with original reports going back to the 1960s and 1970s.[14,15] Steroid injection following urethrotomy has been advocated in a number of small studies to be safe and efficacious.[16,17] There has been two small randomized, controlled trials looking at bulbar strictures <1.5 cm treated with urethrotomy with and without triamcinolone.[16,18] With a mean follow-up of 13.7 months (range, 1–25 months), Mazdak et al. found the triamcinolone group had a stricture recurrence rate of 21.7% as compared to 50% in the control arm. In contrast, the study by Tavakkoli et al. did not find a statistically significant difference in the rate of stricture recurrence.[16]

MMC is another antifibrotic agent that has recently been studied. A small randomized, controlled trial of 40 patients with bulbar urethral strictures <1.5 cm was the first study looking at the effects of MMC on urethrotomy. Stricture recurrence was 10% in patients with urethrotomy and MMC versus 50% with urethrotomy alone. However, these results are to be taken with caution, as the follow-up was only 6–24 months and the end point for success poorly defined.[19]

Hyaluronic acid and caroboxymethylcellulose have been proposed to minimize stricture recurrence in one small randomized controlled trial, but no conclusions about the efficacy of this drug can be made as the trial only had a 6 month follow-up.[20]

Lastly, the combination of all three of these drugs has recently been proposed as a means of improving urethrotomy outcomes. In a study of 103 patients with strictures of both the bulbar and penile urethra, the authors performed an urethrotomy and injected a mixture of 40 mg triamcinolone, 2 mg MMC, and 3,000 units of hyaluronic acid into the urethrotomy site.[21] They report a stricture recurrence rate of 19.4% at a median follow-up of 14 months (range, 3–18 months), with no control group.[21]

While all of these studies are an important step in progressing the science and knowledge of endoscopic stricture management, longer follow-up and more rigid outcomes measures will be critical to properly evaluate the role these adjuncts play with regards to traditional treatment. Well-controlled clinical trials with a minimum 2-year follow-up are needed to determine the optimal antifibrotic agent and technical approach for these novel adjuncts to endoscopic management.

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