Historical Background

Oral mucosa has been used in various reconstructive procedures, such as those involving the conjunctiva, larynx, pharynx, trachea, and sulcoplasty. Its application for urethral reconstruction in hypospadias patients traces back to 1941, with a significant gap until the next publication around 50 years later. In 1992, Dessanti et al documented their experience using oral mucosa from the lower lip, employing it as a tube in 3 cases and combining it with bladder mucosa in 5 cases for distal urethral reconstruction to address meatal complications.¹ Concurrently, Bürger et al reported on 6 patients predominantly using buccal mucosa harvested from the inner cheek for tube formation.² Despite the technique’s promise, a notable incidence of complications was observed.

The introduction of Duckett’s onlay island flap technique marked a pivotal moment in adopting oral mucosa for urethral reconstruction. This innovation led to principles transferring to free grafts, notably reducing complications.³ Concurrently, Bracka introduced a 2-stage technique using buccal mucosal grafts for challenging hypospadias cases.⁴ This advancement addressed the scarcity of suitable skin. Subsequently, there has been a surge in publications, expanding indications from hypospadias repair to urethral strictures. Notably, tubes have been phased out in favor of these techniques.

Contemporary Concepts

Harvesting site. Various sites have been used for mucosal graft harvesting, such as the lip, inner cheek, and tongue, with the tongue showing a higher complication rate.^5,6 Based on our experience, we favor lip mucosa harvesting in pediatric patients and for distal urethral reconstruction due to its thinner nature. In adults, inner cheek mucosa is typically used. Closure of the donor site is at the surgeon’s discretion, with comparable outcomes observed for patients.^7,8

Graft placement. Free grafts require optimal coverage with healthy tissue for revascularization. The bulbar urethra benefits from a robust corpus spongiosum, thickest ventrally, favoring ventral graft placement. Conversely, in the penile urethra, with thin ventral corpus spongiosum, dorsal graft placement is preferable. However, published data suggest that the choice of approach—ventral, lateral, dorsal, or a combination—does not significantly affect augmentation (substitution) urethroplasty outcomes.⁹ Prospective evidence from the ongoing multi-institutional DoVe trial (NCT04551417) comparing dorsal onlay vs ventral onlay techniques in isolated bulbar urethral strictures is eagerly anticipated for valuable insights.

Operative techniques. In managing bulbar strictures, many surgeons commonly place the graft dorsally. However, we advocate for the ventral onlay technique,^10,11 as it involves less invasive midline dissection compared to the dorsal approach, which requires extensive mobilization of the urethra and corpus spongiosum. Two primary techniques are used for penile stricture repair: the Barbagli¹² and the Asopa techniques.^13,14 In the Barbagli technique, the urethra and corpus spongiosum are dissected from the corporal bodies, with a dorsal incision made in the urethra. The graft is then fixed either directly to the corporal bodies and subsequently anastomosed to the urethra or first anastomosed to the urethra and then fixed to the corporal bodies. Conversely, the Asopa technique involves a ventral urethrotomy, followed by an additional dorsal incision to prepare a bed for the graft. This technique is also preferred for 1-stage hypospadias repair, as reported by Hayes and Malone,¹⁵ as well as Manzoni and colleagues.¹⁶

Complete obliteration. Transecting the corpus spongiosum increases the risk of penile complications like a floppy glans.¹⁷ To avoid complete transection, techniques like augmented nontransected anastomotic urethroplasty (ANTA) have been developed.¹⁸ In ANTA, the urethra with the corpus spongiosum is dissected from the corporal bodies, and a longitudinal incision is made, akin to classical dorsal inlay procedures. The obliterative segment of the urethra is superficially excised, preserving the corpus spongiosum underneath, followed by a muco-mucosal anastomosis augmented with a dorsal buccal mucosa graft. Alternatively, our team has developed a slightly modified approach termed muco-mucosal anastomotic nontransecting augmentation (MANTA) urethroplasty.¹⁹ In this technique, the urethra is ventrally opened, and the stricture is dorsally excised at the mucosal level while preserving the spongiosum. Subsequently, mucosa is anastomosed and augmented with a ventral buccal mucosa graft. Both ANTA and MANTA techniques have shown excellent success rates, albeit limited to short obliterative segments.^18,19 For longer strictures, Palminteri et al proposed a combination of ventral and dorsal grafting, resembling tube reconstruction.²⁰ However, this approach yielded a lower success rate, notably higher in strictures longer than 4 cm. Consequently, in cases of long obliterative strictures, a 2-stage procedure may be more favorable.

Two-stage procedures. Two-stage procedures are commonly recommended for lengthy strictures characterized by severe spongiofibrosis, panurethral involvement, and complex conditions. A long-standing debate revolves around the optimal timing for graft placement—during the initial or subsequent stage—a question addressed by the ongoing MAGIC I trial, currently recruiting participants (NCT04965025). Notably, placing buccal mucosa grafts during the first stage carries a risk of graft shrinkage, potentially up to 30%, due to exposure to air. Consequently, it is often preferable to provide coverage with local, nonhair-bearing skin during the first stage. However, in cases of penobulbar or bulbar strictures where local skin with hair follicles is available or in hypospadias patients with deficient skin, using oral grafts during the first stage becomes necessary.

Outcomes

Numerous publications have explored oral mucosa urethroplasty outcomes, mainly through single-center retrospective analyses, often with small sample sizes and lacking long-term follow-up. However, literature reviews and meta-analyses are scarce. The review by Markiewicz et al covering hypospadias, epispadias, and strictures found onlay techniques superior to tube procedures, with multistaged repairs showing superiority in hypospadias cases but not in strictures.²¹ Lumen et al compared oral mucosa with penile skin grafts, favoring oral grafts despite shorter follow-up periods and stricture lengths.²² Jasionowska et al noted best outcomes for bulbar strictures with 1-stage repairs and hypospadias-related strictures with 2-stage repairs in redo procedures.²³ Furthermore, in a systematic review conducted by Sharma et al, including 1406 patients from 16 studies, oral mucosa was favored over penile skin grafts.²⁴ In a very important recent meta-analysis by Benson et al on augmentation urethroplasty, long-term results were analyzed in 954 patients from 10 studies with a minimal follow-up of 100 months.²⁵ The study revealed a recurrence-free survival rate of only 45% at 15 years, indicating worse-than-anticipated outcomes. Taking the same line, we recently initiated a long-term follow-up study at our institution, focusing on patients who underwent anterior urethroplasty from 2010 to 2013. While mature follow-up is pending, we conducted an interim analysis in March 2024. Out of 506 patients who underwent anterior urethroplasty during this period, 174 censored patients were considered lost to follow-up due to a follow-up duration of less than 4 months. After further excluding 51 patients who underwent urethroplasty techniques other than 1-stage augmentation, 281 men underwent buccal mucosal graft urethroplasty with a median graft length of 4 cm (IQR 3-5). The median follow-up in censored patients was 126 months. Stricture recurrence was defined as urethroscopic or urethrographic evidence of recurrence or any stricture-related reintervention. Statistical analyses were performed using Stata (StataCorp 2023. Stata Statistical Software: Release 18. College Station, Texas: StataCorp LLC). Kaplan-Meier analysis revealed recurrence-free survival rates of 66% at 5 years and 59% at 10 years (Figure). This finding is highly intriguing as it supports questioning the historical belief of long-term success rates of well over 80% for anterior augmentation urethroplasty, which originates from short- to midterm follow-up series of up to 5 years. Things indeed appear different, even at a high-volume reconstructive referral center, when considering an extensive “super-long-term” follow-up. This raises multiple questions for further research, focusing on delving into more detailed intricacies such as etiology, stricture characteristics, and the operative technique performed.

Tissue Engineering

A 2017 meta-analysis reviewed 80 preclinical and 23 clinical studies on tissue engineering for urethral repair, with only 4 clinical studies involving cell use.²⁶ While cells significantly reduced side effects in preclinical studies, no difference was seen clinically. Consequently, the authors could not definitively determine tissue engineering’s urethral repair efficacy. Nonetheless, outcomes were comparable to current options, suggesting tissue engineering’s potential for urethral repair. Nevertheless, per the updated AUA stricture guidelines, surgeons are advised against using allografts, xenografts, or synthetic materials for substitution urethroplasty, except under experimental protocols.²⁷

Conclusions

Buccal mucosa for urethral reconstruction has indeed demonstrated its effectiveness over time, yet several caveats remain:

• While buccal mucosa is widely utilized, it may not represent the ultimate solution sought in urethral reconstruction.
• It has established itself as a standard component in our armamentarium for urethral reconstruction.
• Buccal mucosa is the material of choice for urethral stricture repair and for reconstructing failed hypospadias cases with insufficient local skin.
• Despite numerous publications documenting its utility, concerns persist regarding the quality of outcomes. The absence of prospective randomized studies makes drawing definitive conclusions challenging.
• Long-term data are imperative, as emerging evidence suggests a potential decline in the success rates of oral mucosa grafts over time.

Conflict of Interest Disclosures: The Authors have no conflicts of interest to disclose.