Predictors of elaborated perineal or a combined abdominoperineal approach during repair for pelvic fracture urethral injury.

PURPOSE: A step-based anastomotic urethroplasty is a standard technique for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). We aim to identify pre-operative factors, including results of conventional radiological imaging, for prediction of elaborated perineal or a combined abdominoperineal procedure. METHODS: Retrospective observational study on 114 consecutive patients undergoing urethroplasty for PFUI between January 2020 and December 2022 was conducted. Surgical procedures were categorized according to the Webster classification into two groups: steps 1-2 (group 1) and steps 3-4 or a combined abdominoperineal repair (group 2). Pre-operative pattern results of RGU/VCUG were categorized regarding the relation between the proximal urethral stump with the pubic symphysis: posterior urethral stump below (pattern 1) or above (pattern 2) the lower margin of the pubic symphysis. Patient demographics were assessed. Univariate and multivariate logistic regression analyses were utilized. RESULTS: Overall, 102 patients were enrolled in the study for data analysis. On the multivariate logistic regression analysis, the presence of erectile dysfunction (OR 4.5; p = 0.014), prior combined treatment (endoscopic and urethroplasty) (OR 6.4; p = 0.018) and RGU/VCUG pattern 2 (OR 66; p < 0.001) significantly increased the likelihood of the need of step 3 or higher. CONCLUSIONS: The need of step 3 or higher during urethroplasty for PFUI can be predicted pre-operatively with conventional imaging (RGU/VCUG). Patients with proximal urethral stump above the lower margin of pubic symphysis were about 66 times more likely to need step 3 or higher during urethroplasty.

Novel single-stage preputial spiral graft for panurethral stricture: a step-by-step description of the technique.

PURPOSE: To report the 12-month results of a novel urethroplasty technique relying on a spiral preputial graft for panurethral stricture disease. MATERIALS AND METHODS: Twenty consecutive patients were treated between May and October 2021 at our center. A spiral preputial mucocutaneous graft is a foreskin-based graft, developed from a 5-cm-wide preputial skin, which is harvested using a helicoidal shape and can reach up to 20 cm in length. Stricture characteristics were assessed through preoperative retrograde and voiding cystourethrogram and maximum uroflowmetry data (Qmax). Complications were collected up to 30 days after surgery and graded using the Clavien-Dindo (C-D) classification. The patients were followed up to 12 months. RESULTS: Preoperative median Qmax was 6.5 ml/s [interquartile range (IQR): 4.0-8.7]. After a median follow-up of 12 months (IQR 12-13), six patients experienced at least one complication. Of them, two patients had grade 2 C-D complications, while only one developed a grade 3a C-D complication. The median postoperative Qmax was 16 ml/s (IQR: 13-18). Only one patient had early urethral stricture recurrence treated with dilatation after catheter removal. At one-year follow-up, no other patients had urethral stricture recurrence with an overall median Qmax of 15.1 ml/s (IQR 13.5-16.4). CONCLUSIONS: Our novel single-stage spiral preputial graft urethroplasty for panurethral stricture treatment appears to be safe and could be used as a valid alternative to two-stage procedures or even to single-stage buccal mucosa graft augmentation.

Management of Pelvic Fracture Urethral Injury: Is Supracrural Urethral Rerouting (Step 4) Becoming Anecdotical or Does It Remain in Force?

Webster described a step-based perineal approach for repairing the posterior urethra in patients with pelvic fracture urethral injury (PFUI). The higher the complexity of the step, the higher the morbidity for the patient and the lower the surgical outcomes. We evaluated the outcomes of anastomotic urethroplasty (especially Step 4 or higher) or substitution urethroplasty in patients with PFUI at our center. Between 2013 to 2021, we retrospectively collected data on patients with PFUI. Surgical procedures were categorized according to the Webster classification and rates of each step were reported. The success rate was defined as Qmax above 10 mL/s and no need for further treatment. In this period, 737 male patients with PFUI were surgically treated. Notably, 18.8%, 17.6%, 46%, 1.8%, and 5.6% of included patients received steps 1, 2, 3, and 4 and the abdominoperineal approach, respectively. In 68 (9.2%) patients, the substitution of urethroplasty with a pedicled preputial tube (PPT) was needed. The success rate was 69.2% in Step 4, 74.4% in the abdominoperineal approach, and 86.4% in PPT; however, recurrence-free survival was not significantly different between groups (p = 0.22). Step 4 perineal anastomotic urethroplasty represents a surgical option in the armamentarium of PFUI treatment. Indications should be carefully reviewed to improve patient selection and avoid surgical failure, stopping at the step which first gives a tension-free anastomosis.

The impact of surgical volume on perioperative safety after urethroplasty: a population-based study.

BACKGROUND: The aim of the study was to assess whether the risk of perioperative complications after urethroplasty was affected by hospital annual surgical volume (ASV). METHODS: In the Nationwide Inpatient Sample, we searched for patients who underwent urethroplasty between 2001 and 2015. Hospitals were categorized into empirically determined tertiles, according to ASV of performed urethroplasties and divided into low (<3) (LVC), intermediate (3-19) (IVC) and high (>20) volume centers (HVC). Multivariable logistic regression (MLR) analyses examined the effect of ASV on perioperative complications and on four specific sub-types of post-operative complications. RESULTS: A weighted estimate of 39 912 patients underwent urethroplasty in the US. 34.9% were operated in HVC, while the rate of performed urethroplasties increased in LVC and decreased in HVC. Overall, 1.1%, 18.8% and 2.1% patients respectively experienced intraoperative, post-operative, and transfusions complications. At MLR, IVC and LVC were associated with higher risk of both intraoperative (IVC: OR 2.65, P=0.0008; LVC: OR 4.98, P<0.0001), post-operative (IVC: OR 1.14, P=0.01; LVC: OR 1.26, P=0.001) and transfusions complications (IVC: OR 1.85, P<0.001; LVC: OR 3.03, P=0.01). LVC was also associated with higher risk of hematuria (OR 3.77), urinary infections (OR 1.60) and sepsis (OR 2.83) complications. CONCLUSIONS: Approximately 65% of patients were operated in IVC and LVC, and patients treated in IVC or LVC had higher risk of developing both intra and post-operative complications. These data provide important indicators for policy makers to categorize institution based on urethroplasty outcomes.

Common Flaps in Genitourinary Reconstruction.

Urethroplasty has evolved over time. The twentieth century saw management of urethral strictures and hypospadias with flaps. Things changed in the late 1990s with reintroduction of grafts. Buccal mucosa grafts gained popularity. There are failed urethroplasties and obliterative strictures, mostly iatrogenic, after urologic endosurgery. Such strictures need vascularized augmentation or substitution with flaps. Reconstructive urologists should be well versed in management of all types of complex cases. This article discusses the commonly used flaps in genitourinary reconstruction. Penile flaps are the commonest. Overall, the winner is the dartos. All penile flaps are based on the excellent vascularity of dartos.

Advanced Squamous Cell Carcinomas of the Pelvic and Perineal Region: A Comprehensive Genomic Profiling Study.

BACKGROUND: Advanced pelvic squamous cell carcinoma (pSCC) is a broad category of cancers affecting different pelvic organs and usually featuring unfavorable clinical outcomes. Thus, we aimed to assess genomic differences among pSCC cases and learn whether pSCC could potentially benefit from targeted therapies and/or immunotherapy. MATERIALS AND METHODS: A total of 1917 advanced pSCCs, including penile (penSCC), male urethral (murthSCC), male anal (manSCC), female urethral (furthSCC), vulvar (vulSCC), cervical (crvSCC), female anal (fanSCC), and vaginal (vagSCC), underwent comprehensive genomic profiling (CGP). We used hybrid capture-based CGP to evaluate recurrent genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 95 loci. Programmed cell-death-ligand-1 (PD-L1) expression was determined by immunohistochemistry (IHC; Dako 22C3). RESULTS: PIK3CA was the most frequently identified potentially "actionable" GA (22%-43%), followed by mTOR pathway [PTEN (0%-18%), FBXW7 (7%-29%)], and cell-cycle GAs. DNA-damage response (DDR) GAs and receptor-tyrosine kinase (RTK) targeted options were uncommon. NOTCH1 GAs were present in >15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was >15% in manSCC, fanSCC, crvSCC, and vagSCC. PD-L1 high expression was >18% in all pSCC except urthSCC, manSCC, and vagSCC. HPV-16/18 detection was highest in manSCC, fanSCC, and crvSCC. CONCLUSION: Despite similar histology, pSCCs can differ in GAs and HPV status. Overall, PIK3CA is the most frequent potentially "targetable" GA followed by mTOR and cell cycle pathway. RTK and DDR GAs are rare in pSCC. Immunotherapy could be considered for pSCC management based on TMB and PD-L1 expression.

Which Are the Commonest Sites and Characteristics of Post-Transurethral Prostate Surgery Strictures in a High-Volume Reconstructive Center?

Background: Urethral stricture is a well-known complication after transurethral prostate surgery (TPS) and it is usually considered an easy-to-treat condition. We aimed to examine characteristics of post-TPS urethral stricture cases that were referred for urethroplasty at our tertiary center. Methods: We identified 201 patients with TPS-induced stricture treated with urethroplasty at our institution from 2017 to 2021. First, stricture length and location were evaluated during preoperative assessment. Second, multiple sets of multivariable logistic regression (MLR) analyses were run to assess whether clinical variables were associated with the location of the stricture. Results: Median stricture length was 5 cm (4-7). One hundred forty-one (70.1%) patients received previous no-invasive treatments (dilatation and/or direct visual internal urethrotomy). Proximal bulbar urethra was the commonest site for stricture, whereas panurethral stricture (≥10 cm) was diagnosed in 41 (20.4%) patients. Lichen sclerosus was more common in patients with penile stricture location, compared with patients with other involved segments (26% vs 19%, p = 0.03), and it was the only predictor of penile and midbulbar urethra location at MLR. Surgical approaches were augmented urethroplasty in 94% of patients, especially for patients with previous treatment including urethroplasty (95.8% vs 82.5% for naive, p = 0.004). Dorsal onlay was the preferred approach for bulbar (53.4%) and penile urethra (90.7%), whereas ventral onlay (38.2%) and double face augmentation (20.6%) were the preferred approaches in membranous strictures. Conclusions: Most patients who were referred for TPS-induced stricture attempted previous noninvasive managements. Referred TPS-induced urethral strictures were long and frequently involving multiple segments of urethra. Augmentation urethroplasty was our preferred surgical approach because of the characteristics and complexity of these strictures. The presence of lichen may increase the risk of post-TPS stricture in a specific segment of urethra, namely the penile and midbulbar urethra.

Mucosal-sparing augmented non-transected anastomotic (MsANTA) urethroplasty: a step forward in ANTA urethroplasty.

The surgical advancement of urethral reconstruction is a rapidly moving field. In the last decade, the technique for bulbar urethroplasty has evolved towards less invasive approaches with minimal transection and more tissue sparing in order to increase the patency rate. In this study, we provide a step forward in the augmented non-transected anastomotic (ANTA) urethroplasty proposed in 2012, with a true mucosa-sparing modification of the technique. In detail, the bulbar urethral lumen is approached with either a ventral or dorsal urethrotomy. Differently from previous techniques, the native urethral mucosa is neither transected nor resected but is reconstructed with a direct mucosa-to-mucosa anastomosis. This allows a complete sparing of communicant vessels that come from the corpus spongiosum to the urethral mucosa. The technique aims to preserve the native vascularity of the urethral mucosa by enlarging the native urethral plate with a direct anastomosis at the level of the stricture, and without the need for resection. In our hands the technique was easy and reproducible, and it carried promising results in the preliminary cohort where it was applied.

Long-term outcomes from a multi-institutional experience with prefabricated composite gracilis-buccal mucosal flap for reconstruction of devastated urethras.

PURPOSE: Patients with devastated bulbar urethras have limited surgical options to restore normal upright voiding. We investigated the long-term feasibility of using two independently vascularized urethral hemi-plates lined with buccal mucosal graft (BMG) to treat these patients. METHODS: A multi-institutional retrospective review was conducted for patients that underwent this staged repair. In stage-1, the affected urethra is dissected and removed or prepared for a dorsal inlay augmentation. Two BMG segments are harvested; one graft is quilted on corpora cavernosa and urethra, creating an augmented perineal urethrostomy, and the other is quilted on the exposed distal gracilis muscle. Stage-2 utilizes the gracilis-BMG composite to recreate ventral bulbar urethra. The primary outcome measure was stricture recurrence. Secondary outcome measures included patient-reported outcome measures (PROMs). RESULTS: Five patients with mean age of 50 years (45-56) underwent staged repairs at two institutions between 7/2014 and 4/2016. All patients presented with suprapubic tubes and underwent at least one prior failed repair (1-9). Mean stricture length was 7.2 cm (5-9). Mean time between stage-1 and stage-2 repairs was 6.2 weeks (1-10). At a mean follow-up of 61 months (39-87), there were no recurrences. The mean uroflow was 20 cc/s (9-42) with a mean PVR of 59 cc (0-157). Four patients completed post-operative surveys; all reported at least a moderate improvement in their condition on Global Response Assessment (GRA), and a mean IPSS of 7.3 (0-26). CONCLUSIONS: Our bi-institutional case series demonstrates that this technique is a feasible option for devastated urethras with long-term durability.

Dorsal approach for double-face bulbar urethroplasty: ventral inlay plus dorsal onlay using Kulkarni one-side dissection.

BACKGROUND: Non-traumatic obliterative bulbar urethral stricture with residual urethral lumen below 3 Fr is a challenging surgical scenario for reconstructive surgeons, because either anastomotic or single augmentation urethroplasty is not an option. OBJECTIVES: To describe our double-face buccal mucosa graft (BMG) urethroplasty with dorsal onlay and ventral inlay relying on the vessels and nerve-sparing technique of Kulkarni's one-side dissection. METHODS: We retrospectively reviewed a prospectively maintained database of patients with non-traumatic obliterative bulbar urethral strictures who underwent double-face bulbar urethroplasty with one-side dissection and dorsal onlay plus ventral inlay BMG. Patient demographics, clinical data, and follow-up were analyzed. RESULTS: A total of 59 patients underwent double-face urethroplasty with dorsal approach. The median age was 37 years (IQR 27-49) and the median stricture length was 5 cm (IQR 3.75-6). No patients had immediate post-operative complications. The overall success rate was 88% with a median follow-up of 30.9 months (IQR 16.9-44.2). Two patients were treated with DVIU, and two patients with open urethral surgery. One patient developed erectile dysfunction after surgery. Age, etiology, stenosis length and previous treatment were not factors related to surgical failure. CONCLUSION: Our preliminary albeit encouraging results showed that this approach was feasible in all patients and with negligible perioperative complications. Success rate was 88%. We did not find any factors related to surgical failure. Our dorsal double-face augmented urethroplasty may be a valid alternative to the Palminteri's ventral double-face urethroplasty, especially in those patients with mid-distal bulbar or peno-bulbar urethral strictures.

Bladder-sparing combination treatments for muscle-invasive bladder cancer: A plea for standardized assessment and definition of clinical trials endpoints.

Radical cystectomy is the standard of care for muscle invasive bladder cancer, although it represents a surgical procedure with high complication and mortality burden. Thus, more and more emphasis has been placed in favor of alternative treatments especially for patients who are unfit for or aim to avoid radical cystectomy. In this context, preclinical studies highlighted that chemoradiation therapy (CRT) may have immunomodulatory properties on tumor microenvironment with a consequent increase in immune biomarkers. Thus, following the encouraging results reached by immune checkpoint inhibitors (ICIs) in both metastatic and localized disease, CRT and ICIs combination treatment gained momentum as bladder-sparing option and several clinical trials were recently launched both as concurrent and sequential treatments. A narrative review of the literature was performed to summarize the rationale and clinical outcomes of trials testing CRT and ICIs combination. Promising results were recently released mainly from phase II trials reporting clinal complete response rates from 48% to 83%. Moreover, combination treatment, both as concurrent and sequential schedules, appeared to be quite tolerable. However, interpretation of preliminary findings is made difficult due to the heterogeneity of clinical endpoints among trials, patient population included and different measurement of response to treatment. Novel bladder-sparing strategies are finally gaining momentum in bladder cancer treatment. Despite preliminary findings are encouraging, harmonization of terminology and definition of clinical endpoints among trials will be mandatory to correctly assess the potential role of CRT and immunotherapy combination as bladder-sparing solution in routine clinical practice.

Graft Plus Fasciocutaneous Penile Flap for Nearly or Completely Obliterated Long Bulbar and Penobulbar Strictures.

BACKGROUND: Graft plus flap urethroplasty is gaining momentum in patients with nearly or completely obliterated urethral strictures, in whom staged procedures or perineal urethrostomy is the only possible alternative. However, graft plus flap urethroplasty is mainly adopted for strictures involving the penile urethra. OBJECTIVE: To report our experience on graft plus flap urethroplasty for bulbar and penobulbar reconstruction. DESIGN SETTING AND PARTICIPANTS: Between January 2014 and June 2020, patients with nearly or completely obliterated long (>4 cm) bulbar or penobulbar strictures, who required graft plus flap urethroplasty, were considered for this study. SURGICAL PROCEDURE: The bulbar and the penile urethra were accessed through a perineal incision and penile invagination when required. Grafts were harvested from cheek, lingual, or preputial skin and quilted over the corpora to reconstruct the dorsal plate of the neourethra. The fasciocutaneous penile flap recreated the ventral plate of the neourethra. The corpus spongiosum was flapped over the neourethra to prevent the formation of diverticula. MEASUREMENTS: Any need for instrumentation after surgery was defined as the primary failure. Obstructive symptoms or maximum flow rate (Qmax) below 10 ml/s, with or without a need for instrumentation, was defined as a secondary failure. RESULTS AND LIMITATIONS: We identified 15 patients who met the inclusion criteria. The median stricture length was 7 cm (interquartile range [IQR] 5-8 cm). The inner cheek was the preferred site for graft harvesting (53.3%). No perioperative complication of Clavien-Dindo grade ≥III were recorded in the first 30 postoperative days. The median Qmax at catheter removal was 23 ml/min (IQR 21.5-26 ml/min). The median follow-up was 25 mo (IQR 10-30 mo). The primary success rate was 86.7% (13/15) and the secondary success rate was 73.3% (11/15). Post-traumatic strictures represent a contraindication for this technique. CONCLUSIONS: In referral centers, graft plus flap urethroplasty represents a feasible option for patients with nearly or completely obliterated long (>4 cm) strictures. Our study demonstrated that this option is also feasible for strictures involving mainly the bulbar urethra. PATIENT SUMMARY: Perineal urethrostomy should be considered as the last option in patients with a nearly or completely obliterated bulbar urethral stricture. Nowadays, graft plus fasciocutaneous penile flap augmentation enriched our armamentarium of bulbar urethra reconstruction.

A global approach to improving penile cancer care.

Rare tumours such as penile carcinoma have been largely neglected by the urology scientific community in favour of more common - and, therefore, more easily fundable - diseases. Nevertheless, penile cancer represents a rising burden for health-care systems around the world, because a lack of widespread expertise, ineffective centralization of care and absence of research funds have hampered our ability to improve the global care of these patients. Moreover, a dichotomy has arisen in the field of penile cancer, further impeding care: the countries that are mainly supporting research on this topic through the development of epidemiological studies and design of clinical trials are not the countries that have the highest prevalence of the disease. This situation means that randomized controlled trials in developed countries often do not meet the minimum accrual and are intended to close before reaching their end points, whereas trials are almost completely absent in those areas with the highest disease prevalence and probability of successful recruitment, such as Africa, South America and South Asia. The scientific and organizational inaction that arises owing to this mismatch translates into a burdensome cost for our patients. A global effort to gather experts and pull together scientific data from around the world may be the best way to boost clinical research, to change clinical practice and, ultimately, to improve care for patients and their families.

Magnetic resonance imaging procedure for pelvic fracture urethral injuries and recto urethral fistulas: A simplified protocol.

OBJECTIVE: The urethral gap in pelvic fracture urethral injury (PFUI) is traditionally assessed using voiding cystourethrogram (VCUG) and retrograde urethrogram (RGU). Magnetic resonance imaging (MRI) is performed in complex cases. We assessed the refined "Joshi" MRI protocol to evaluate complex urethral defects after PFUI. MATERIAL AND METHODS: A prospective study was conducted at our center from January 2018 to January 2020, involving patients aged >18 years with PFUI, suitable for MRI, and those who gave consent to perform standard RGU, VCUG, and MRI using standard and "Joshi" protocol. Forty men were included in the study. Distance between urethral/prostatic stumps was measured. Image quality was scored by four radiologists and four urologists. The surgical approach and type of PFUI repair were noted. We also established the need for inferior pubectomy by assessing the position of the posterior urethra (membranous) in relation to a horizontal line drawn from the lower edge of the pubic bone anteriorly to the rectum posteriorly in a sagittal image. RESULTS: The mean age was 30 years (SD, 5.25; range, 21-43), and the time from injury to imaging was 4 months (3-10 months); 40% of the men underwent crural separation, 57.5%, inferior pubectomy, and 2.5%, crural rerouting. There was a difference of 0.3 to 1.1 cm in the urethral gap measurements between MR images using the standard versus "Joshi" technique. MRI identified complex injuries such as rectourethral fistula, the need for inferior pubectomy, and the orientation of the posterior urethra. Urologists' and radiologists' satisfaction scores for the MR images were satisfactory to excellent. If the posterior urethra was over the defined mark, there was a 100% likelihood of inferior pubectomy (23/40 patients). CONCLUSION: MR image acquisition using the "Joshi" protocol provided high-quality anatomical information in PFUI cases to assist with surgical planning.

A prospective, multi-center, open-label, single-arm phase 2b study of autologous adult live cultured buccal epithelial cells (AALBEC) in the treatment of bulbar urethral stricture.

PURPOSE: To evaluate the safety and efficacy of autologous adult live cultured buccal epithelial cells (AALBEC) in treatment and management of bulbar urethral stricture in men. METHODS: This was a prospective, multi-center, open-label, single-arm phase 2b study. A total of 18 male patients with bulbar urethral stricture of at least 1 - 4 cm in length were enrolled in the study. All 16 patients had AALBEC implanted and were included in the safety set. Change in total American Urology Association (AUA) symptom score, urinary flow rates assessed by uroflowmetry and a requirement for surgery after 24 weeks from baseline were determined in patients. Data of treatment efficacy were analyzed. RESULTS: The AUA score at baseline was 21 (3.9) that showed a statistically significant reduction starting from week 2 [8 (4.4), p = 0.0001] which sustained until week 24 [2 (1.2), p = 0.0005]. Overall mean total AUA symptom score was reduced by 90.5% after the treatment. Significant reductions from baseline at week-24 were also observed in voiding time (92.5 (47.3) vs. 51.9 (17.4) s, p = 0.0046) and flow time [86.9 (48.2) vs. 47.9 (19.6) s, p = 0.0052]. All patients showed absence of any significant adverse events. CONCLUSION: Significant improvement was seen in the AUA symptom score and uroflowmetry parameters and no patients required surgery during 24 weeks post-treatment. It can be concluded that AALBEC is a safe and effective treatment for bulbar urethral stricture of 1 - 4 cm length to improve the quality of life and the physiological function of urethra.