Contemporary Management of Bulbar Urethral Strictures

Management Review

ManageMent Review Contemporary Management of Bulbar Urethral Strictures Ross S. Liao, MD, Erica Stern, BS, James E. Wright, MD, Andrew J. Cohen, MD Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD Urethral stricture disease (USD) is a progressive scar-forming disease commonly encountered by urologists and is challenging to manage. USD most frequently occurs in the bulbar urethra. Patients typically present with chronic obstructive voiding symptoms but may develop recurrent urinary tract infections, detrusor failure, or renal disease. The authors review the pathophysiology, diagnostic workup, and evidence-based management of bulbar urethral strictures (BUS). There are multiple surgical options to treat BUS. Endoscopic techniques (eg, dilation and urethrotomy) are suitable for the initial management of short strictures but new evidence-based guidelines recommend against repeated endoscopic treatment. Urethroplasty is the gold standard treatment for BUS of all lengths, with anastomotic techniques appropriate for strictures <2 cm and tissue substitution performed for longer strictures. New techniques, such as non-transecting urethroplasty, lack long-term data but may represent a paradigm shift in the field. Future treatments may utilize tissue-engineered grafts and agents that inhibit inflammation and scar formation. [Rev Urol. 2020;22(4):139–151] © 2021 MedReviews®, LLC KEY WORDS Bulbar urethral stricture • Urethroplasty • Urethrotomy • Urethral dilation • Buccal graft, non-transecting U rethral stricture disease (USD) is a relatively common urologic disease with significant clinical and economic implications. The prevalence of USD is 229 to 627 per 100,000 men (~0.6%) with the highest prevalence seen in men older than 65 years.1 Every year, over 5000 hospital admissions are required for USD.1 In addition, treatment of USD is associated with a high cost burden related to diagnosis, treatment, surveillance, and complications. In 2000, the estimated total cost of treating USD Vol. 22 No. 4 • 2020 • Reviews in Urology • 139 4170020_03_RIU0864_V4_ptg01.indd 139 4/6/21 3:50 PM Management of Bulbar Urethral Strictures continued in the United States was $200 million.1,2 Successful treatment of USD can significantly improve urinary function, sexual health, and overall quality of life. Therefore, an understanding of the diagnostic workup and surgical management of USD is important for the practicing urologist. The most common area of stricture occurrence in the male urethra is the bulbar segment. Etiology The bulbar urethra is the most common site of USD accounting for up to one half of all cases.3 Although some patients report a history of injury, infection, or prior urethral instrumentation, most patients are unable to recall a specific etiology for their strictures.4 This may be due to the lag time between an inciting event and symptomatic presentation.5 As such, the reported distribution of stricture etiologies is variable. A large multi-institutional surgical outcomes group of reconstructive urologists recently reported trends in bulbar stricture etiology over 8 years.5 They found that approximately 63% of BUS were idiopathic or unknown.5 Strictures deemed idiopathic may in fact represent late sequelae of childhood trauma.4 Trauma to the penis or perineum, especially due to straddle injuries, caused approximately 17% of BUS.5 Thirteen percent of BUS were reported to be iatrogenic in origin.5 Iatrogenic strictures stem from ischemic insult during traumatic passage of large instruments during transurethral surgery, clean intermittent catheterization, or prolonged catheterization. Iatrogenic strictures tend to be more complicated to repair than traumatic strictures, frequently requiring extensive operations.3 Finally, about 7% of BUS are inflammatory and caused by sexually transmitted diseases.5 In the past, inflammatory strictures associated with gonorrheal urethritis were the most common etiology, but are now less common due to patient education and the development of effective antibiotics.5 The main cause of inflammatory BUS in developed nations today is lichen sclerosus (LS).6 LS is a chronic inflammatory skin condition commonly involving the anogenital region. LS usually begins with balanitis and inflammation of the glans penis. This progresses to meatal stenosis and/ or stricture of the fossa navicularis. Hypopigmentation of the meatus and glans may be an early sign. The inflammation progresses proximally due to high-pressure voiding and intravasation into the glands of Littre.6 This can lead to abscess formation and spongiofibrosis involving long segments of the anterior urethra, including the bulbar urethra.7 A study by Liu and colleagues presented pathologic evidence that LS can be implicated even in isolated BUS.8 Ultimately, strictures due to LS are inherently complex with a high rate of treatment-related morbidity and stricture recurrence.9,10 BUS associated with LS warrant more invasive therapy including single- or multistage urethroplasty with nongenital skin or oral mucosa.9 Moreover, there is an association between LS and development of penile cancer, therefore close surveillance of patients is warranted.11 Ultimately, USD arises from any process that injures urethral epithelium or underlying corpus spongiosum in which healing results in fibrosis. Spongiofibrosis is the deposition of collagen and fibrous tissue deep to the urethral mucosa. The underlying spongiofibrosis associated with urethral strictures can be more extensive than the mucosal involvement and render the effective stricture length longer than what is seen on imaging or endoscopic studies.12,13 Relevant Anatomy and Pathophysiology Urethral Anatomy The male urethra is divided into anterior and posterior segments. The posterior urethra includes the bladder neck, prostatic urethra, and membranous urethra, whereas the anterior urethra includes the bulbar urethra, penile urethra, fossa navicularis, and urethral meatus. The bulbar urethra extends from the suspensory ligament (penoscrotal junction) to the membranous urethra and is the portion of the urethra enclosed by the bulbospongiosus muscle. In the bulbar urethra, the maximum intraluminal diameter is approximately 12 mm (36 Fr). The relative location of the urethra within the spongiosum changes along the divisions of the urethra. In the bulb, the urethra is dorsal within the corpus spongiosum and eccentrically oriented. Thus, the spongiosum is thinnest at the 10 and 2 o’clock position. Bloody Supply The arterial blood supply to the penis and urethra is unique due to its bidirectionality, which has implications for urethroplasty. The vascular supply to the urethra originates from the internal iliac that gives rise to the internal pudendal artery and subsequently, the common penile artery. The common penile artery branches into the dorsal, bulbar, and urethral arteries, the latter two composing the main vascular supply to the anterior urethra. The dorsal artery of the penis anastomoses with the urethral artery in the glans penis and through circumflex arteries along the length of the penis. In anastomotic urethroplasty, the 140 • Vol. 22 No. 4 • 2020 • Reviews in Urology 4170020_03_RIU0864_V4_ptg01.indd 140 4/6/21 3:50 PM Management of Bulbar Urethral Strictures spongiosum is typically transected, which results in transection of the urethral artery and elimination of antegrade blood flow to the distal urethra. However, due to anastomoses of the dorsal and urethral arteries in the glans, perfusion to the distal urethra is preserved in a retrograde fashion. Certain conditions (eg, previous penile surgery, penile trauma, hypospadias) disrupt the vascular connection between the glans and the spongiosum. These patients require thoughtful approaches to reduce the risk of ischemia and necrosis during urethroplasty. Clinical Presentation USD can be asymptomatic for years until voiding symptoms develop.4 BUS, like most anterior urethral strictures, present with chronic obstructive voiding symptoms (eg, weak urinary stream, intermittent flow, post-void dribbling, and incomplete bladder emptying) or, less commonly, acute urinary obstruction. Other presentations include difficult catheterization, urinary spraying, dysuria, recurrent urinary tract infections, and decreased force of ejaculate. Complications of untreated strictures include bladder stones, elevated post-void residual volume, detrusor failure, hydronephrosis, renal failure, urethral fistulas, and periurethral abscesses. Diagnostic Evaluation Patients presenting with chronic obstructive voiding symptoms require workup to assess for other bladder or outlet conditions with similar symptoms such as benign prostatic hyperplasia. A history and physical examination should be performed including penile and perineal palpation (urethral strictures may be palpable) and genital skin examination (for LS and evaluation of tissue for use in reconstruction).14 Voiding symptoms may be assessed using post-void ultrasound, uroflow, and symptom scores. Once stricture is suspected, retrograde urethrography (RUG) is the gold standard imaging test. Voiding cystourethrogram, urethral ultrasound, and cystourethroscopy can also be useful. The location, length, extent of luminal narrowing, depth of scar (spongiofibrosis), and status of the urethra proximal and distal to the stricture should be assessed.7,13 The degree of spongiofibrosis can be estimated based on physical examination, the amount of elasticity noted on urethroscopy, and the appearance of the urethra on contrast studies or ultrasound. Contrast studies can sometimes underestimate stricture length, especially if the patient is not in steep lateral oblique position. In these cases, ultrasound can augment contrast studies and potentially be more accurate in determining the length of the stricture.15 In terms of detecting spongiofibrosis, ultrasound has a sensitivity of 77.3% to 83.3%.16 Defining the proximal extent of the stricture is often challenging.13 Pediatric cystoscopes and rigid ureteroscopes can often pass through narrow caliber areas without dilating the stricture and may be of benefit. “Urethral rest” for 6 to 8 weeks via suprapubic tube, to defunctionalize the urethra and allow the stricture to attain its natural position and length, has been shown to be beneficial for surgical planning.17 This is most applicable to patients with a history of frequent instrumentation, significant hydrodilation of the proximal urethra, or who are performing selfdilation. Biopsy is advisable for suspicious-appearing strictures or patients with history of malignancy. When patients with USD present with acute urinary retention and inability to pass a urethral catheter, most cases are managed with acute urethral dilation.7 However, blind passage of filiforms and dilators without characterization of the stricture can potentially worsen the stricture and complicate further management.18 Instead, suprapubic catheter placement should be considered as initial therapy to allow time for formal evaluation and treatment planning. Preoperatively, the accuracy of diagnostic testing and assessment of stricture and spongiofibrosis can be variable. Thus, the stricture assessment and decision of the surgical approach are often not definitive until the time of operative intervention. Description of Surgical Techniques The appropriate management approach for BUS depends primarily on the length of the stricture as well as stricture etiology, surgeon expertise, availability of tissue for reconstruction, and patient symptoms.13 Not all BUS require intervention. Treatment is indicated in the presence of bothersome voiding symptoms, recurrent urinary tract infections, acute urinary retention, elevated post-void residual volumes, and bladder stones.14,19 One retrospective study of 32 patients found that among those with asymptomatic, wide-caliber, anterior urethral strictures, close to 90% experienced no change or regression of their symptoms after a median follow-up of 23 months.19 On the other hand, symptomatic BUS should be treated as there is a significant risk of complications (eg, urinary retention, infection) if surgical management is delayed.20 Endoscopic Management Endoscopic management can be offered as initial management for Vol. 22 No. 4 • 2020 • Reviews in Urology • 141 4170020_03_RIU0864_V4_ptg01.indd 141 4/6/21 3:50 PM Management of Bulbar Urethral Strictures continued patients with short BUS (<2 cm) confined to the mucosa and without significant spongiofibrosis.14 Repeat endoscopic procedures have extremely high failure rates.21 Indeed, the American Urological Association (AUA) guidelines on urethral stricture disease state, “Urethral strictures that have been previously treated with dilation or [direct visual internal urethrotomy (DVIU)] are unlikely to be successfully treated with another endoscopic procedure with failure rates of >80%. Repeated endoscopic treatment may cause longer strictures and increase the complexity of subsequent urethroplasty.”14,21,22 Thus, patients who fail initial endoscopic management should be referred for open urethroplasty. Dilation or urethrotomy are quite similar in their effectiveness. The goal of urethral dilation is to stretch the stricture scar without tearing it. Tearing the stricture, which often causes bleeding, may increase inflammation and scarring and worsen urethral lumen narrowing. Dilation can be performed in the office or clinic setting and is accomplished using tapered instruments such as sounds, filiforms, and followers, or coaxially over a guidewire. Urethrotomy is transurethral incision of a urethral stricture and can be performed in the office setting using a penile block or in the outpatient setting with local, spinal, or general anesthesia. The incision should be performed under direct vision (DVIU) which is preferred over blind incision (historically performed using an Otis urethrotome) and can be performed with a blade, electrocautery wire, or laser. The success rates of urethrotomy are similar to those seen in urethral dilation and depend on the ability of the incision to epithelialize before wound contraction narrows the lumen again.7,18 The diameter of the stricture lumen correlates with urethrotomy outcomes with narrower strictures having worse outcomes.23 Some experts recommend leaving an indwelling Foley catheter after urethrotomy so that the urethra may mold around the catheter as it heals; however, studies show no benefit to long-term catheterization.24 Therefore, the AUA guidelines recommend removal of the catheter within 72 hours postoperatively.14 The method to perform the incision (eg, cold knife, electrocautery, or laser) is a matter of surgeon preference as outcomes are similar.25,26 In regards to incision location, the classic recommendation is to incise at 12 o’clock.26 However, in the bulbar urethra, the spongiosum is thinnest at the 10 to 2 o’clock position and perforation may be a concern at 12 o’clock. Therefore, some experts recommend incising the ventral surface of the urethra between 4 to 8 o’clock.18,25,26 The incision should extend into normal urethra 5 mm proximal and distal to the stricture and should be deep enough to enter healthy tissue without perforating through the outer layer of spongiosum. When extensive spongiofibrosis is present, some urologists prefer to incise deeply into the spongiosum. However, if significant spongiofibrosis is present, endoscopic management will not cure the stricture and open urethroplasty may be required.12 Laser urethrotomy is another potential option to treat BUS, although success rates are similar to other endoscopic approaches.7,25 Types of lasers that have been used include carbon dioxide, argon, KTP, Nd:YAG, holmium:YAG, and excimer lasers. The ideal laser for urethral strictures is one that totally vaporizes tissue, exhibits little peripheral tissue destruction, is unabsorbed by water, and is propagated easily along a fiber.25 With the development of new lasers and increased surgeon experience, future data on laser urethrotomy may yield more promising results. Following endoscopic management, patients can be taught to perform calibration using a soft 14 to 16 Fr catheter that may slow stricture recurrence.27 Calibration is distinct from self-catheterization in that the purpose is not for urine evacuation. There is weak evidence that calibration after urethrotomy may decrease stricture recurrence rates.28-30 Although the optimal regimen is uncertain, performing calibration longer than 4 months is associated with improved outcomes compared with shorter regimens.14,30,31 However, once the calibration is stopped, the stricture will inevitably recur, regardless of length of the regimen.31 In truth, calibration may be simply a proxy outcome metric that allows patients to self-assess the speed of their stricture recurrence. Paradoxically, calibration could lead to iatrogenic urethral injury. Many patients report moderate pain and difficulty with intermittent calibration and often present for urethral reconstruction specifically because they are not satisfied with their quality of life.27 For patients who are not candidates for urethroplasty, endoscopic management followed by calibration can be a palliative solution to allow for continued voiding without diversion, indwelling catheter, or suprapubic tube. Urethral Stents Urethral stents are no longer recommended for management or commercially available due to common and severe stent-related complications (eg, migration, encrustation, hyperplastic tissue reactions, and pain and irritative voiding symptoms).14 Urethral stents are either removable or permanently 142 • Vol. 22 No. 4 • 2020 • Reviews in Urology 4170020_03_RIU0864_V4_ptg01.indd 142 4/6/21 3:50 PM Management of Bulbar Urethral Strictures from referral to a reconstructive urologist. implantable and designed to prevent incorporation of the stent into the urethral wall. For those patients with stents, long-term monitoring with cystoscopy or urethral imaging is recommended as complications can occur at any time after stent placement. Stents do not require prophylactic removal unless significant symptoms develop. Patients experiencing stent complications would likely benefit Urethroplasty Urethroplasty is the gold standard for repair of BUS of any length. Urethroplasty success in the literature is commonly reported above 85%, but published outcomes involve physicians with significant experience. Indeed, two case series show a clinically significant improvement in outcomes with increasing surgeon experience.32,33 These studies estimate that approximately 70 to 90 urethroplasties are required prior to a clinician reaching their nadir recurrence rate. Urethroplasty can either be performed using primary anastomosis, onlay, inlay, augmentation anastomosis, or tubularized augmentation. A summary of urethroplasty techniques is provided in Table 1. TABLE 1 Recently Reported Outcomes of Urethroplasty (by Type) for Bulbar Urethral Stricturesa Study Anastomotic urethroplasty Number of Stricture Patients Location Stricturefree Ratesb Ekerhult TO et al (2013)34 94 Bulbar urethra 91% Morey AF et al (2014)35 1234 Bulbar urethra Granieri MA et al (2014)36 202 Erickson BA et al (2014)37 Mean/Median Follow-up Complications 41 mo Erectile dysfunction (1%), penile shortening/downward angulation (5%) 93.8% 12-72 mo (across 17 studies) Position-related neuropraxia (3.4%), early UTI (5%), stress urinary incontinence (8%), hematoma (8%), diverticulum (3%), urinoma (3%), stone formation (3%), tissue infection (5%), erectile dysfunction (1%-5%), etc. Bulbar urethra 94.5% 19.2 mo (before 2004), 14.6 mo (after 2004) Not reported 136 Bulbar urethra 90.3% (functional success rate) 13.1 ± 1.2 mo Not reported Sáez-Barranquero F et al (2016)38 107 Majority in bulbar urethra (82.2%) 95.3% 59 mo Not reported Anderson KM et al (2017)39 102 Bulbar urethra 83% 65 mo Not reported Waterloos M et al (2018)40 112 Bulbar urethra 88.4% 118 mo Not reported (Continued) Vol. 22 No. 4 • 2020 • Reviews in Urology • 143 4170020_03_RIU0864_V4_ptg01.indd 143 4/6/21 3:50 PM Management of Bulbar Urethral Strictures continued Study Augmentation anastomotic urethroplasty Number of Stricture Patients Location Stricturefree Ratesb Mean/Median Follow-up Complications Chapman DW et al (2019)41 258 Bulbar urethra 93.8% 74.1 ± 45.4 mo Erectile dysfunction (9.7%), chordee/penile shortening (0.3%), ejaculatory dysfunction (0.9%), genital pain (0.9%), wound-related issues (3.4%), UTI (1.4%), epididymo-orchitis (0.6%), scrotal hematoma (0.9%), urethral bleeding (0.3%), incontinence (0.3%), deep vein thrombosis (0.3%) Furr JR et al (2019)42 139 Bulbar urethra 99.3% 63.3 mo Erectile dysfunction (27%), postvoid dribbling (8.3%), penile tethering with erections (23.4%), decreased glans filling (10.6%), cold glans during erection (5.2%), decreased penile sensation (23.4%) Hussain M et al (2020)43 166 Bulbar urethra 93.3% 43.5 mo Fever (7.3%), penile/ scrotal swelling (3.3%), wound infection (9%), UTI (2.3%), bleeding (1.4%), painful ejaculation (4.3%), post-void dribbling (3.2%), stress incontinence (2.8%), chordee (0.5%) Hoy NY et al (2013)44 163 Bulbar urethra 96.9% 31 mo Postoperative dribbling (41.7%), UTI (3.7%), erectile dysfunction (3.1%), orchalgia (10.4%), donor site morbidity (4.3%) Hofer MD et al (2014)45 72 Bulbomembranous urethra (60.6%), bulbar urethra (39.4%) 69.7% 10 mo New-onset erectile dysfunction (7%), persistent urinary incontinence (8.5%), fistula formation (1.5%) Granieri MA et al (2014)36 103 Bulbar urethra 94.2% (buccal 15.9 mo mucosal graft) Not reported 144 • Vol. 22 No. 4 • 2020 • Reviews in Urology 4170020_03_RIU0864_V4_ptg01.indd 144 4/6/21 3:50 PM Management of Bulbar Urethral Strictures Study Nontransecting anastomotic urethroplasty Onlay urethroplasty Number of Stricture Patients Location Stricturefree Ratesb Mean/Median Follow-up Complications Virasoro R et al (2015)46 65 Bulbar urethra 96.92% 33.1 mo UTI (22.72%), postvoid dribbling (22.72%), oral paresthesias (13.63%), erectile dysfunction (13.63%), wound dehiscence (13.63%), perineal paresthesias (9.09%), persistent perineal pain (4.54%), epididymitis (4.54%), oral pain (4.54%) Chapman DW et al (2017)47 170 Bulbar urethra 92.4% 65.4 mo Not reported Kunz I et al (2018)48 71 Majority in bulbar urethra (83.1%) 90.1% 17 mo Post-void dribble (22.5%), numbness in mouth area (5.6%), recurrent UTI (5.6%), de novo (newonset) erectile dysfunction (4.2%), penile curvature (4.2%), suppurative foreign body granuloma (1.4%), altered sensation in surgical area (1.4%), permanent suprapubic catheter (1.4%) Anderson KM et al (2017)39 50 Bulbar urethra 82% 65 mo Not reported Waterloos M et al (2018)40 88 Bulbar urethra 93.2% 32 mo Not reported Chapman DW et al (2019)41 94 Bulbar urethra 97.9% 37.1 ± 20.5 mo Erectile dysfunction (9.7%), chordee/penile shortening (0.3%), ejaculatory dysfunction (0.9%), genital pain (0.9%), wound-related issues (3.4%), UTI (1.4%), epididymo-orchitis (0.6%), scrotal hematoma (0.9%), urethral bleeding (0.3%), incontinence (0.3%), deep vein thrombosis (0.3%) Palminteri E et al (2012)49 216 Bulbar urethra 91.4% 37 mo Fistula (5%), perineal hematoma (0.9%) Haque ME et al (2012)50 108 Bulbar urethra 91.7% 36 mo Periurethral fistula (1.8%), urethral bleeding (0.9%) (Continued) Vol. 22 No. 4 • 2020 • Reviews in Urology • 145 4170020_03_RIU0864_V4_ptg01.indd 145 4/6/21 3:50 PM Management of Bulbar Urethral Strictures continued Study Inlay urethroplasty (Asopa technique) Number of Stricture Patients Location Stricturefree Ratesb Mean/Median Follow-up Complications Ekerhult TO et al (2013)34 75 Bulbar urethra 71% 69 mo Erectile dysfunction (1%) Erickson BA et al (2014)37 77 Bulbar urethra 87% (functional success rate) 13.1 ± 1.2 mo Not reported Pathak HR et al (2017)51 112 Bulbar urethra 81% (overall), Minimum 89% (venfollow-up of 1 tral), 79% y; range, 1-5 y (dorsolateral), 70% (dorsal) Not reported Asopa HS et al (2001)52 12 Anterior urethra 91.7% 26 mo Hematoma (8.3%), temporary fistula (8.3%), worsened chordee (8.3%) Gupta NP et al (2004)53 12 Penobulbar urethra (66.7%), panurethral (33.3%) 91.7% 12 mo Not reported Pisapati VLNM et al (2009)54 45 Majority in bulbar urethra (55.6%) 87% 42 mo Postoperative wound infection (15.6%), urethrocutaneous fistula (11%), difficulty opening mouth (4.4%) Aldaqadossi H et al (2014)55 22 Penile urethra (54.5%), bulbar urethra (36.3%), panurethral (9.2%) 24.2 mo Postvoid dribbling (4.5%) 86.4% UTI, urinary tract infection. aSelected studies are PubMed articles published in the past 10 years (2010-2020) with >50 patients that cited “stricture-free rates” for primarily bulbar strictures (inlay studies [Asopa et al,52 Gupta et al,53 Pisapati et al,54 and Aldaqadossi et al55] included for completeness). bStricture-free was most defined as not requiring further postoperative intervention. Other definitions of stricture-free included patient reporting no symptoms of recurrence, normal follow-up RUG or cystourethroscopy, and/or voiding parameters meeting specified criteria (ie, Qmax >15mL/s, postvoid residual volume <50 mL, flow rate >10 mL/s). Anastomotic Urethroplasty. Anastomotic urethroplasty involves complete excision of the area of fibrosis with spatulation and primary tension-free anastomosis. This technique is best utilized for strictures that are ,2 cm in length but has been successfully used for strictures 2 to 5 cm in length with success rates .90% at 2 years of follow-up.14,56 The closer a stricture is to the membranous urethra, the greater the stricture length that can be repaired by primary anastomosis. The success of anastomotic urethroplasty relies on vigorous mobilization of the corpus spongiosum to completely excise the stricture (Figure 1). Urethroplasty Requiring Tissue Transfer (Substitution Urethroplasty). When the length of stricture prevents total excision and tensionfree anastomosis, tissue transfer is required. Either flaps or grafts can be used. A flap is preferred when the graft bed is diseased and unable to support a graft (eg, radiated or scarred tissue). A graft is preferred 146 • Vol. 22 No. 4 • 2020 • Reviews in Urology 4170020_03_RIU0864_V4_ptg01.indd 146 4/6/21 3:50 PM Management of Bulbar Urethral Strictures Figure 2. Example of a large buccal mucosal graft used for urethroplasty. Figure 1. Typical operative dissection through bulbospongiosus muscle to expose bulbar urethra. when there is limited availability of genital skin (eg, LS or prior hypospadias repair). Penile skin is the most used flap. Graft options include full-thickness skin, bladder epithelium, rectal mucosa, and oral mucosa. Buccal mucosa grafts are the graft tissue of choice (Figure 2). Buccal mucosa is naturally resistant to infection and skin diseases such as LS, generally straightforward to harvest with minimal donor site complications, and adequately available (Figure 3). However, not all patients possess healthy buccal mucosa available for grafting (eg, smokers, tobacco chewers, and others with poor oral hygiene). The buccal mucosa donor site can be left open or closed with some evidence that closure minimally improves Tissue postoperative pain.57 transfer can be used in onlay urethoplasty, inlay urethroplasty, augmentation anastomotic urethroplasty, or tubularized augmentation urethroplasty. Figure 3. Typical operative set-up for a buccal mucosa graft harvest. Vol. 22 No. 4 • 2020 • Reviews in Urology • 147 4170020_03_RIU0864_V4_ptg01.indd 147 4/6/21 3:51 PM Management of Bulbar Urethral Strictures continued Onlay Urethroplasty. In onlay urethroplasty, the stricture is incised but not excised, dorsally, ventrally, or laterally, and the graft is sutured onto the defect to widen the stricture lumen. Although the ideal method continues to be controversial,58 success rates between dorsal, ventral, and lateral onlay repairs seem to be similar. Ventral onlay repairs technically require less urethral dissection and mobilization but are thought to be limited to the proximal and middle bulbar urethra due to the presence of thicker corpus spongiosum and adequate blood supply to support the graft.58 Dorsal onlay repairs, also known as the Barbagli technique, have the theoretical advantage of the corpora cavernosa as a suitable graft bed while also impeding diverticulum formation.59 Onlay and inlay urethroplasties are commonly used for excessively long strictures in which excision is unfeasible.52,60 Inlay Urethroplasty. Dorsal inlay urethroplasty involves a ventral midline urethral incision to expose the stricture followed by a dorsal midline urethral incision to the level of the tunica.52 Further dissection of the margins of the incised dorsal urethra exposes an elliptical-shaped space in which an inlay graft can then be placed and secured with interrupted sutures. The primary advantage of the inlay technique is the creation of a grafting space without lifting the urethral plate that preserves the circumflex and perforating vessels to the spongiosum. The main disadvantage of this technique is the decreased width of the graft that can be achieved compared with the onlay technique.61 Some groups have reported high success rates combining a dorsal-inlay graft and ventral-onlay graft in a two-sided, double-graft urethroplasty.62,63 Augmentation Anastomotic Urethroplasty. Augmentation anastomotic urethroplasty involves complete stricture excision followed by augmentation with a ventral or dorsal onlay. The roof or floor of the urethra is anastomosed, and a ventral or dorsal onlay, respectively, is used to repair the urethral side opposite to the anastomosis.60 Augmentation anastomotic urethroplasty is preferred over tubularized augmentation urethroplasty due to higher success rates.56,60 Tubularized Augmentation Urethroplasty. Tubularized augmentation urethroplasty involves complete stricture excision and repair of the entire circumference of the urethra with a tubularized tissue transfer and should be performed as a staged procedure.13 The AUA guidelines on urethral stricture disease state, “[Tubularized graft urethroplasty], when attempted in a single stage, has a high risk of restenosis and should be avoided.14 When no alternative exists, a tubularized flap can be performed with results that are inferior to onlay flaps.”14,64,65 Non-transecting Anastomotic Urethroplasty. Recent evidence suggests a higher risk of sexual dysfunction with bulbar urethroplasty than previously reported.66 A prospective study of 50 patients showed that anterior urethroplasty caused erectile dysfunction in approximately 40% of patients, although recovery was seen in most by 6 months.66 This was attributed to transection of the corpus spongiosum during urethral mobilization. Observations in the operating room also suggest that the bulk of the spongiosum on transection is healthy and can actively bleed.67 To address these concerns, a new non-transecting urethroplasty technique has been developed.67 This technique involves removing only the scarred mucosa and leaving the sponge intact in order to maintain antegrade and retrograde blood flow for improved healing and preservation of erectile function. Although preliminary results are promising, long-term follow-up is needed to compare this technique with anastomotic urethroplasty. Palliative Alternatives and Perineal Urethrostomy. In patients who are unfit or unwilling to undergo urethroplasty, repeat endoscopic procedures or intermittent selfcatheterization may be considered. Urinary diversion, using suprapubic catheter, permanent urinary diversion, or perineal urethrostomy, is also an option for these patients. Perineal urethrostomy is especially useful for elderly patients or those with complex strictures, medical comorbidities, extensive LS, and numerous failed urethroplasties.68 Quality of life is reportedly high for patients who elect perineal urethrostomy although surgical revision may be necessary to maintain patency.69 Defining Treatment Success and Postoperative Follow-up Traditionally, successful treatment for BUS has been defined as lack of need for a secondary procedure. This definition is easily defined and quantified but assumes that patients return to the center that performed their urethroplasty for follow-up. It also fails to account for asymptomatic recurrences that can account for up to 35% of recurrent strictures.70 Some experts suggest amending the definition of success to include both anatomic and functional outcomes. Such a definition would include, for example, 148 • Vol. 22 No. 4 • 2020 • Reviews in Urology 4170020_03_RIU0864_V4_ptg01.indd 148 4/6/21 3:51 PM Management of Bulbar Urethral Strictures the ability to pass a flexible cystocope through a stricture without manipulation and patient-reported outcome measures (PROMs). Many groups have developed follow-up algorithms for urethroplasty patients that account for both anatomic and functional outcomes using noninvasive uroflow tests, PROMs, and cystoscopy when indicated.70 One algorithm employs a patient-reported questionnaire, uroflow, and cystoscopy at 3 to 6 months postoperatively followed by another questionnaire and uroflow at 12 to 15 months, and then annually thereafter.71 After the 3-month visit, cystoscopy is only used if there is a change in flow or symptoms. Increased attention during follow-up should be given to erectile function, post-void dribbling, and stream dynamics such as spray as these are commonly reported postoperative complications. Cost and patient burden are also factors affecting surveillance. Future Directions There are several exciting areas of research in reconstructive urology that involve tissue engineering and urethral scar modulation. Human buccal mucosa, bladder washings, and acellular matrices have all been used to synthesize large sheets of urothelium-like grafting material for urethral reconstruction.72,73 A small series of 12 patients with bulbar urethral strictures showed that tissueengineered oral mucosa used for urethroplasty had a stricture-free success rate of 91.6% at 10 months median follow-up.74 Urethral scar modulation is an active area of research that aims to facilitate urethral wound healing and prevent inflammation and scarring following urethral surgery. Amniotic membrane contains growth factors and cytokines that have been used in animal models of urethroplasty to decrease scarring and improve healing.75 An injectable form, Amniofix® (dehydrated human amnion/chorion membrane [dHACM] allograft; MiMedx, Marietta, GA), has been used to decrease inflammation and promote healing following urethral dilation in humans.75 Other scarmodulating agents that have been used include colchicine, mitomycin C, tacrolimus, and paclitaxel.76,77 These compounds have been shown to inhibit inflammation and proliferation of fibroblasts to reduce stricture recurrence. Randomized trials, such as the ROBUST III trial (paclitaxel-coated inflatable balloon for urethral dilation) are already underway to examine the use of scar-modulating agents in combination with endoscopic therapies. These areas of exciting new research suggest that the future of reconstructive urology is a bright one, and patients with urethral strictures will continue to have access to the latest and most effective treatments. Conclusions USD most commonly occurs in the bulbar urethra. The etiology of BUS is typically idiopathic although attempts to understand the etiology and pathophysiology are ongoing. There are multiple surgical options to manage BUS, including endoscopic and open surgical approaches; however, the most durable stricture-free success is found after urethroplasty. The authors thank the patients who provided consent for use of intraoperative photos. MAin POinTS • Bulbar urethral strictures may be caused by trauma to the perineum, iatrogenic injury, or infection, but commonly have unknown etiology. • Patients most often present with chronic obstructive voiding symptoms. • The gold standard for diagnosis is retrograde urethrography; however, definitive stricture assessment may not be complete until the time of operative intervention. • Endoscopic management is an initial strategy for managing short bulbar strictures, but guidelines suggest against repeated use given failure rates of >80% with repeated endoscopic treatment. • Urethroplasty is the gold standard for the repair of bulbar urethral strictures of any length. Surgical techniques vary by stricture location, complexity, and physician preference. 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