Urethral Strictures

9. TISSUE TRANSFER

9.1. Comparison of grafts with flaps

One small RCT (LS excluded) comparing OMG with PSF found no significant difference in urethral patency rate [502]. Penile skin flaps had a higher urogenital morbidity (superficial penile skin necrosis, penile torsion, penile hypoesthesia, and post-void dribbling) and longer operation time compared to OMG. Furthermore, patient dissatisfaction was significantly higher with penile flaps [502]. Another small RCT (LS excluded) comparing penile skin grafts with PSF confirmed these findings with longer operation time and more superficial penile skin necrosis in the group of the flaps, whereas the urethral patency rate was similar between both groups [355]. Several retrospective series also found a comparable urethral patency rate between PSF and grafts [272,274,503,504] (Table 9.1).

Table 9.1: Comparative studies of grafts vs. flaps used in urethroplasty for anterior urethral strictures

BMG = buccal mucosa graft; Excl. = excluded; LIF = longitudinal island flap; LMG = lingual mucosa graft;LS = lichen sclerosus; mo = months; NR = not reported; OMG = oral mucosa graft; PSG = penile skin graft; TIF = transverse island flap; RCT = randomized controlled trial.
* if not reported: recalculated by EAU Urethral Strictures Panel with chi²-statistics.

Due to their robust vascular pedicle, flaps can be used as a tube as well as a patch in a single-stage approach [442]. Castagnetti et al., showed that grafts used as a tube have significantly higher complication rates as compared to onlay grafts (OR: 5.86; 95% CI: 1.5-23.4) [505]. A review by Patterson et al., also reported high (circa 50%) complication and recurrence rates for tubularised grafts [506]. Iqbal et al., have shown an encouraging 87% stricture-free rate in 23 patients who were offered single-stage circumferential skin flap urethroplasty [281]. Therefore, if there is a need to reconstruct a complete urethral segment with a tissuetransfer tube in a one-stage operation, flaps are usually the preferred option. As flaps carry their own vascular supply to the reconstruction site, they do not rely on the local vascularisation of the recipient site. Therefore, they need to be considered in case of poor urethral vascularisation (e.g., after irradiation or dense scarring after previous urethroplasty) [504,507]. In addition, flaps survive well in the presence of active urinary infection [508].

Grafts and flaps should not be considered competitors in urethral surgery. A combination of a flap with a graft is possible for complex, multifocal or penobulbar strictures [504,509,510].

9.2. Comparison of different types of flaps

Different local flaps have been described. Penile skin flaps are generally hairless, although the ventral penile skin can be hair-bearing around the raphe in some ethnic groups/phenotypes. They can be harvested as a transverse preputial skin flap [511], a transverse distal PSF [358,508,512,513] or as a longitudinal island flap [514]. Urethral patency rates vary between 74.2-100% [274,358,508,511-514]. Complications include skin necrosis (0-3.8%), fistula (0-7%), penile deformity (0-7%), post-void dribbling (0-79%) and sacculation (0-16.5%) (see supplementary Table S9.1). As there are no direct comparative series available about these flaps it is not possible to determine which performs better.

Hair-bearing perineal and scrotal flaps have been described as well. Fu et al., demonstrated that PSF had a significantly better urethral patency rate compared to scrotal and perineal skin flaps (respectively 87.7%, 69% and 66.7%) [274]. The hair-bearing perineal and scrotal skin flaps are associated with hairball formation and chronic infection which may cause failure of the repair. A study of Blandy with long-term follow-up, reports 3% revision for calculi and 3% revision for diverticula [515].

An alternative is to epilate the needed scrotal skin prior to tissue transfer [516,517] or to patch an OMG to the underlying dartos tissue of the scrotum after incision of the scrotal skin and use this patch as a flap in a second attempt [442].

9.3. Comparison of different types of grafts

Buccal mucosa is at present the most commonly used graft. A systematic review on anterior urethral strictures reports a urethral patency rates of buccal mucosa of 86.6% with an average follow-up of 31.5 months [518].

Penile skin is another popular graft, especially in uncircumcised men where the foreskin is an abundant source of graft material.

In case of LS, Trivedi et al., demonstrated a significantly higher urethral patency rate when using non-genital mucosal grafts for reconstruction (82.6%) compared to genital skin grafts (4%) [519]; therefore, the use of genital skin in LS cases is not indicated.

In one RCT (Pee’BuSt trial) comparing buccal mucosa with penile skin as a graft for dorsal onlay augmentation urethroplasty for anterior strictures, no significant difference in outcome could be observed [520]. A systematic review and meta-analysis suggests that BMG augmentented urethroplasty, may be superior to penile skin graft urethroplasty. However, there were a lot of confounding factors, and clear conclusions cannot be made [521]. Lengthy skin grafts (up to 20 cm) can be taken from the foreskin in a spiroid fashion which is clearly more difficult with OMG.

The main disadvantage of BMG harvesting is the oral morbidity and because of this morbidity, lingual mucosa has been proposed as alternative. A SR and meta-analysis of comparative studies comparing LMG with BMG (four prospective, two retrospective studies) showed no significant differences in urethral patency rate and overall long-term complication rate [522-524]. These studies revealed that LMG was associated with more difficulties in eating/drinking, speaking, tongue protrusion and dysgeusia [522,523]. In 13.8-20%, speaking problems remained after six months [522,523]. A retrospective study of Xu et al., reported difficulties in tongue movements, numbness over the donor site and speaking difficulties in 6.2%, 4.9% and 2.5% of patients, respectively after twelve months [301]. On the other hand, BMG harvesting provoked more oral tightness which was present in up to 24% of patients after six months [522,523]. Chauhan et al., showed that immediate and early donor site complications were more common in the BMG group, except for bleeding being more common in the LMG group. Numbness (61%), difficulty in chewing (54%), swelling (48%) and articulation (40%) were the most common problems during the first week. Late donor site complications were rare [525]. Pal et al., describes more short-term complications (difficulty in tongue movement and slurring of speech) in the LMG group, compared to the BMG group. Long-term complications (after three months) at the donor site (persistent pain, perioral numbness, tightness of mouth, salivary disturbance, scarring of the cheeks) were only seen in the BMG group [526]. For long strictures, buccal mucosa can be combined with lingual mucosa [301].

The use of lower lip mucosa was described, especially when smaller grafts are needed, and has similar qualities to lingual mucosa. However, a narrative review based on the experience from retrospective series showed that these grafts have a higher post-operative donor site morbidity and can lead to permanent sequelae (persistent discomfort, neurosensory deficits, salivary flow changes and important aesthetic changes) at the donor site, which have not been described with lingual mucosa [527].

Beyond the oral mucosa and penile skin graft, a multitude of other autologous grafts have been described. These include: postauricular skin [510,528], abdominal skin [360], split-thickness mesh graft from the thigh [341], inguinal skin [300] and colonic mucosa [529] (Table 9.2). Manoj et al., only used the postauricular skin when both genital skin and oral mucosa were not usable [528]. Marchal et al., used postauricular skin in addition to oral mucosa to reconstruct lengthy strictures [510]. Meeks et al., reported the use of abdominal skin graft mainly in patients with lengthy strictures where OMG harvesting would be insufficient, in case of prior OMG urethroplasty or if OMG was refused by the patient [360]. Pfalzgraf et al., reported a comparable urethral patency rate for split-thickness mesh graft and BMG (respectively 84 and 83%), but more penile deviation (9% vs. 0%) and lower satisfaction (83.3% vs. 96.7%) with split-thickness mesh graft [341]. Xu et al., used colonic mucosa for lengthy (> 10 cm) strictures. Urethral patency rate was 85.7% but graft harvest requires an abdominal procedure, and 1/35 (2.9%) patient developed a colonic-abdominal fistula [529]. Due to the limited experience with grafts other than oral mucosa and penile skin, they should only be considered if oral mucosa and penile skin are not available, indicated, or desired.

Table 9.2: Outcome of case series of other autologous grafts

N = number of patients; NR = not reported.

9.4. Tissue engineered grafts

9.4.1. Cell-free tissue engineered grafts

These grafts are derived from cadaveric or animal sources (e.g., porcine small intestine submucosa [SIS], acellular bladder matrix, acellular dermal matrix), are completely cell-free and serve as a scaffold for host cell ingrowth [530]. The main advantage suggested for their use is the off-shelf availability [530].

A small RCT (n=30) comparing acellular bladder matrix with BMG reported a urethral patency rate of respectively 66.6% and 100%. The poorer results of acellular bladder matrix were the most apparent in cases of an unhealthy urethral bed [531].

Several small retrospective case series using mainly porcine small intestinal submucosa, demonstrate varying patency rates from 20-110%. The patient groups were heterogenious in terms of aetiology, previous treatment, urethral location and definition of success rate. An overview can be found in Table 9.3. Most papers report a poorer outcome in case of extensive spongiofibrosis, poor vascular graft bed, previous treatments and longer strictures [531-535] (Table 9.3).

Table 9.3: Outcome of retrospective case series using cell-free tissue engineered grafts

9.4.2. Autologous tissue engineered oral mucosa graftss

These grafts contain a matrix seeded with autologous oral mucosa cells. Production requires a small oral mucosa biopsy (at 0.5 cm²) and the graft is further manufactured in the lab. The main advantage suggested is the reduction of oral donor site morbidity whereas the main disadvantages are costs and the strict time frame between manufacturing and implantation of the graft [530].

The clinical use of autologous tissue-engineered OMG was evaluated in a prospective, multicentre study including 99 patients [536]. Estimated twelve- and 24-months urethral patency rate was 67.3 and 58.2%, respectively. Oral adverse events were minimal. No comparative studies with acellular grafts or native OMGs are available nor are there any data about the cost-effectiveness [530].

9.5. Management of oral cavity after buccal mucosa harvesting

The post-operative morbidity of closure vs. non-closure of the buccal mucosa harvesting site has been evaluated by a number of prospective RCTs.

The results are summarised in Table 9.4. Based on these findings, no clear recommendation can be provided as to whether or not to close the harvesting site and the decision can be left to the treating physician.

Oral rinsing with chamomile [537] or chlorhexidine [523,538] solution has been suggested in the first post-operative days without any evidence that this reduces pain or other oral complications.

Table 9.4: Effect of non-closure compared to closure on oral morbidity after buccal mucosa harvesting

↓ = less morbidity with non-closure; ↑ = more morbidity with non-closure; = = no significant difference; NR = not reported.