Optimizing decision-making after ventral onlay buccal mucosa graft urethroplasty failure.

OBJECTIVES: To evaluate factors predicting recurrence after treatment and to assess the best rescue option for patients failing buccal mucosa graft (BMG) urethroplasty. MATERIALS AND METHODS: We evaluated the data from 575 patients treated with ventral onlay BMG urethroplasty. Multivariable Cox regression analysis was performed to identify predictors of BMG urethroplasty failure, and their effect on failure risk was estimated using the Kaplan-Meier method and compared using log-rank tests. Then, for those patients who underwent a rescue treatment, namely, direct visual internal urethrotomy (DVIU) vs open urethroplasty, we assessed the probability of success after retreatment using the Kaplan-Meier method and regression tree analyses. RESULTS: On multivariable Cox regression analysis, only stricture length ≥5 cm (hazard ratio 3.46, 95% confidence interval 1.50-7.94; P = 0.003) was a predictor of failure. A total of 103 patients had at least one re-intervention. Notably, 12-month success rates after first rescue DVIU, second rescue DVIU, third rescue DVIU, and fourth rescue DVIU were 66.3%, 62.5%, 37.5% and 25%, respectively. Conversely, for those patients who underwent open urethroplasty retreatment, success rates at 12 months were 83.3%, 79%, 92.3% and 75% after BMG ventral onlay, first rescue DVIU, second rescue DVIU and third rescue DVIU, respectively. These data were confirmed in regression tree analyses. CONCLUSION: Ventral BMG urethroplasty fails in approximately one out of five patients. Despite DVIU as a rescue treatment being a good option, its success rate becomes lower as the number of DVIU treatments performed increases. Conversely, open urethroplasty improves patient outcomes in almost three out of four patients, even in the case of previous failed DVIU treatments for stricture recurrence.

Patient-reported outcomes for typical single cheek harvesting vs atypical lingual, labial or bilateral cheeks harvesting: a single-center analysis of more than 800 patients.

PURPOSE: The optimal harvesting site for oral grafting in patients with urethral strictures remain controversial, with no study investigating morbidity on large scale. We aimed to compare typical single cheek harvesting vs atypical lingual, labial or bilateral cheeks harvesting in terms of complications and patient-reported outcomes. METHODS: Within 827 patients treated at our referral center with oral graft urethroplasty, we compared typical vs atypical harvesting techniques. A self-administered, semiquantitative, non-validated questionnaire assessed early (10 days) and late (4 months) postoperative complications and patient-reported outcomes. A semiquantitative score was calculated according to patient responses, and it was used to assess early (6 questions) and late (13 questions) patient dissatisfaction status. Patients were defined early and/or late dissatisfied when they scored ≥ 7 and ≥ 10 at the early or late questionnaires, respectively. RESULTS: Between 1998 and 2019, our patients predominantly received typical single cheek harvesting (89% vs 11%), with + 1.5% increase rate per year (p < 0.001). Early and late dissatisfied patients were, respectively, 170 (23%) vs 39 (44%) and 59 (8%) vs 16 (18%) in the typical vs atypical groups. Atypical harvesting was associated with higher rates of early (Odds ratio [OR]: 2.34; 95% Confidence interval [CI] 1.44-3.75; p = 0.001) and late (OR: 2.37; 95%CI 1.22-4.42; p = 0.008) postoperative dissatisfaction. CONCLUSIONS: Typical single cheek harvesting was the preferred surgical option at our center and it was associated with negligible early and late rates of complications and patient's dissatisfaction. Conversely, atypical lingual, labial or bilateral cheeks harvesting was associated with higher complications and frequent patient dissatisfaction.

Assessing in-hospital morbidity after urethroplasty using the European Association of Urology Quality Criteria for standardized reporting.

PURPOSE: To conduct a rigorous assessment of in-hospital morbidity after urethroplasty according with the European Association of Urology (EAU) guidelines for complication reporting. METHODS: We retrospectively (2015-2019) identified 469 consecutive patients receiving urethroplasty (e.g. bulbar urethroplasty with grafts, penile urethroplasty with/without grafts/flaps, Johanson, de novo or revision perineostomy, end-to-end anastomosis, meatoplasty and/or meatotomy) at our tertiary care institution. Complications were graded with Clavien-Dindo score and Comprehensive Complication Index (CCI). Complications were classified in: bleeding no gastrointestinal, cardiac, gastrointestinal, genitourinary, infectious, neurological, oral, wound, miscellaneous, and pulmonary. Logistic regression tested for predictors of in-hospital complications and prolonged hospitalization (> 75th percentile). Kaplan-Meier and Cox regression investigated the effect of complications on failure after urethroplasty. RESULTS: Overall, 161 (34.3%) patients experienced at least one complication. Of those, 47 (10%) experienced two or more complications and 59 (12.6%) experienced at least one Clavien-Dindo ≥ II complication. Only two patients had Clavien-Dindo III complications. Infectious was the most frequent complication, and de novo or revision perineostomy was associated with the highest rate of complications. The occurrence of any complications, as well as complication with Clavien-Dindo ≥ II were associated with prolonged hospitalizations, but not with higher rates of post-urethroplasty failure. CONCLUSIONS: Complications after urethroplasty were common events, but rarely with severe sequelae. Infectious were the most common complications and perineostomy was the type of urethroplasty with the highest rate of complications. The application of the EAU recommendations allowed the identifications of a higher number of complications after urethroplasty if compared with previous reports based on unsupervised chart review.

Surgical treatment of bulbar urethral strictures: tips and tricks.

The surgical treatment of bulbar urethral strictures is still one of the most challenging reconstructive surgery problems. Bulbar urethral strictures are usually categorized as traumatic and non-traumatic strictures depending on the aetiology. The traumatic strictures are caused by trauma and they determine disruption of the urethra with obliteration of the urethral lumen, ending with fibrotic gaps between the urethral ends. Differently, the non-traumatic urethral strictures are mainly caused by catheterization, instrumentation, and infection, or they can also be idiopathic. They are usually asso-ciated with spongiofibrosis of the segment of the urethra that has been involved. Worldwide, two different surgical approaches are currently adopted for bulbar urethral repair: transecting techniques with end-to-end anastomosis and non-transecting techniques followed by grafting. Traumatic obliterated strictures require transection of the urethra allowing complete removal of the fibrotic tissue that involves the urethral ends. Conversely, non-traumatic, non-obliterated urethral strictures require augmentation of the urethral plate using oral mucosa grafts. Nowadays, it is still difficult to choose the correct surgical management for non-obliterated bulbar stricture repair. Indeed, different surgical techniques have been proposed (pedicled flap vs free graft, dorsal vs ventral placement of the graft, non-transecting technique using or non-using free graft, etc.) but none emerged as the best solution since all techniques have showed similar success and complication rates. Consequently, the final choice is still based on surgeon's preferences and patient's characteristics. Within the current manuscript, we like to present some of our tips and tricks that we developed along our prolonged surgical experience on the treatment of bulbar urethral strictures. These might be of interest for surgeons that approach this complex surgery. Moreover, our suggestions want to be useful regardless the type of chosen technique being adaptable for different scenario.

Treatments of 1242 bulbar urethral strictures: multivariable statistical analysis of results.

PURPOSE: We investigated the success rate of different surgical techniques for bulbar stricture repair. METHODS: Retrospective study of patients with bulbar urethral strictures treated using different techniques. The primary outcome of the study was to evaluate the overall results of treatment (success vs. failure); the secondary outcome was to evaluate the outcome according to any surgical technique. Cysto-urethrography was performed 1 month following surgery. Patients underwent clinical evaluation, uroflowmetry and residual urine measurement every 6 months for 2 years after surgery and later once on year. When patient showed obstructive symptoms, Qmax < 12 ml/s, the urethrography was repeated. Patients who underwent further treatment for recurrent stricture were classified as failures. A bivariable and multivariable statistical analysis was performed. RESULTS: Overall, 1242 patients were included in the study with mean age 40 years (range 12-84). Median stricture length was 4 cm (range 1-8). The median follow-up was 103 months (range 12-362). Over 1242 patients, 916 (73.8%) were success and 326 (26.2%) failures. Fourteen different surgical techniques showed a success rate ranging from 87.5 to 14.3%. The multivariable analysis showed that stricture length was an independent predictor factors for failure: p < 0.0001 CI 1146-1509. End-end anastomosis and oral mucosa graft urethroplasty are independent predictor factor of success after internal urethrotomy failure. CONCLUSIONS: Our results showed that treatment of bulbar urethral stricture is satisfactory on 73.8% of patients, but with a wide range of success rate (from 14.3 to 87.5%) using different techniques. Oral mucosa is greatly superior to the skin as substitute material.

Risk calculator for prediction of treatment-related urethroplasty failure in patients with penile urethral strictures.

PURPOSE: To design a dedicated risk calculator for patients with penile urethra stricture who are scheduled to urethroplasty that might be used to counsel patients according to their pre-operative risk of failure. METHODS: Patients treated with penile urethroplasty at our center (1994-2018) were included in the study. Patients received 1-stage or staged penile urethroplasty. Patients with failed hypospadias repair, lichen sclerosus or incomplete clinical records were excluded. Treatment failure was defined as any required postoperative instrumentation, including dilation. Univariable Cox regression identified predictors of post-operative treatment failure and Kaplan-Meier analysis plotted the failure-free survival rates according to such predictors. Multivariable Cox regression-based risk calculator was generated to predict the risk of treatment failure at 10 years after surgery. RESULTS: 261 patients met the inclusion criteria. Median follow-up was 113 months. Out of 216 patients, 201 (77%) were classified as success and 60 (23%) failures. Former smoker (hazard ratio [HR] 2.12, p = 0.025), instrumentation-derived stricture (HR 2.55, p = 0.006), and use of grafts (HR 1.83, p = 0.037) were predictors of treatment failure. Model-derived probabilities showed that the 10-year risk of treatment failure varied from 5.8 to 41.1% according to patient's characteristics. CONCLUSIONS: Long-term prognosis in patients who underwent penile urethroplasty is uncertain. To date, our risk-calculator represents the first tool that might help physicians to predict the risk of treatment failure at 10 years. According to our model, such risk is largely influenced by the etiology of the stricture, the use of graft, and patient's smoking habits.

Focus on Internal Urethrotomy as Primary Treatment for Untreated Bulbar Urethral Strictures: Results from a Multivariable Analysis.

BACKGROUND: The use of internal urethrotomy for treatment of urethral stricture remains a controversial topic in urology. OBJECTIVE: To investigate outcomes and predictors of failure for internal urethrotomy as primary treatment for untreated bulbar urethral strictures. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of patients who underwent internal urethrotomy. Patients with bulbar urethral stricture who did not receive any previous treatment were included. Patients with traumatic, penile or posterior urethral strictures, lichen sclerosus, failed hypospadias repair, or stricture length >4cm were excluded. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was treatment failure. Kaplan-Meyer plots were used to depict treatment failure-free survival. Univariate and multivariable Cox regression analyses were used to test the association between predictors (age, body mass index, diabetes, history of smoking, etiology, stenosis type and length, preoperative maximum flow [pQmax]) and treatment failure. RESULTS AND LIMITATIONS: Overall, 136 patients were included. The median stricture length was 2cm. Median follow-up was 55 mo. At 5-yr follow-up the failure-free survival rate was 57%. On univariate analysis, diabetes, nonidiopathic etiology, stricture length of 3-4cm, and pQmax were significantly associated with treatment failure. These predictors were included in a multivariable analysis, in which pQmax was the only significant predictor of treatment failure. CONCLUSIONS: Failure of internal urethrotomy for untreated bulbar urethral strictures greatly depends on pQmax flow at uroflowmetry. Patients with pQmax >8ml/s have a high probability of success, while patients with pQmax <5ml/s have a low probability of success. PATIENT SUMMARY: The use of internal urethrotomy in patients with an untreated bulbar urethral stricture should only be considered in selected cases.

Memokath Stent Failure in Recurrent Bulbar Urethral Strictures: Results From an Investigative Pilot Stage 2A Study.

OBJECTIVE: To evaluate the efficacy of the Memokath stent in managing recurrent bulbar urethral strictures. MATERIALS AND METHODS: This is an investigative pilot stage 2A study in patients with a recurrent bulbar urethral stricture who underwent a Memokath stent implant from January 2014 to January 2016 in a single high-volume center for urethral reconstruction. The Memokath stent (Pnn Medical A/S, Kvistgaard, Denmark) was manufactured from nitinol, a biocompatible alloy of nickel and titanium, which was endoscopically placed. It had a 24-Fr outside diameter and was preloaded on a disposable delivery device. When correctly positioned, the stent was anchored by a warm water (55°C) instillation, which expanded the proximal end of the stent from 24 to 42 Fr .The stent was provided in lengths of 3-7 cm in 1-cm increments. RESULTS: Sixteen patients were included in the study. The median follow-up was 16 months. In 7 patients (43.7%), the stent was removed within 1 year. The main adverse events were pain, encrustations, stones, and recurrent strictures. Four patients (25%) were considered a success and 12 (75%) were failures. Study limitations include the small sample. CONCLUSION: The Memokath stent was deemed to be not clinically helpful and had significant side effects, and therefore should not be considered a treatment option for men with bulbar urethral strictures.

History and evolution of the use of oral mucosa for urethral reconstruction.

We report here the history and evolution of the use of oral mucosa in reconstructive urethral surgery since it was first used for urethroplasty in 1894. Since that time, many authors have contributed to develop, improve and popularize the use of oral mucosa as a substitute material. Paediatric urologists should be considered pioneers on the use of oral mucosa as they used it to repair primary and failed hypospadias. The use of oral mucosa to repair penile and bulbar urethral strictures was described, for the first time, in 1993. Important evolutions in the technique for harvesting oral mucosa from the cheek were reported in 1996. Today, oral mucosa is considered the gold standard material for any type of anterior urethroplasty in a one- or two-stage repair due to its biological and structural characteristics that make it a highly versatile that is adaptable to any environment required by the reconstructive urethral surgery. As the future approaches, tissue engineering techniques will provide patients with new materials originating from the oral epithelial mucosal cells, which are cultured and expanded into a scaffold. However, the path to reach this ambitious objective is still long and many difficulties must be overcome along the way.

Comparative Assessment of Cultures from Oral and Urethral Stem Cells for Urethral Regeneration.

Urethral reconstruction has received much attention in recent years, due to pathologies such as recurrence of urethral strictures after treatments. Various surgical techniques have been developed to obtain the best risk-benefit ratio, such as autologous grafts taken from the oral cavity. Tissue engineering and stem cells, growing in a tissue from a small biopsies, can further improve surgery, reducing invasiveness and morbidity. To determine whether urethra or other epithelia can be equally useful for urethra engineering, a comparison of clonogenic ability, proliferative potential and stem cell markers should be obtained. In this study, 19 biopsies from urethra, and 21 from oral mucosa were obtained from patients, during reconstructive surgery. Urethral and oral tissues were removed from the same donor, to develop primary cultures and cell characterization. The long term regenerative properties of both tissues were investigated in vitro by life span, clonal analysis and markers of different clonal types. Results revealed the same high proliferative potential for urethra and oral mucosa cultures, but maintenance of specific markers. Karyotype and growth factor dependence confirmed the normal phenotype of cultured cells. Clonal analysis of the proliferative compartment highlighted a very different proportion of stem and transient amplifying cells, characterised by dissimilar cell size profile and marker expression. In conclusion, both tissues can be cultured and preserve their stem cells in vitro. Few differences appeared in oral mucosa vs urethra, suggesting that they can be equally useful for tissue engineering of the urethral tract.

Surgical treatment of bulbar urethral strictures: tips and tricks

ABSTRACT The surgical treatment of bulbar urethral strictures is still one of the most challenging reconstructive-surgery problems. Bulbar urethral strictures are usually categorized as traumatic and non-traumatic strictures depending on the aetiology. The traumatic strictures are caused by trauma and they determine disruption of the urethra with obliteration of the urethral lumen, ending with fibrotic gaps between the urethral ends. Differently, the non-traumatic urethral strictures are mainly caused by catheterization, instrumentation, and infection, or they can also be idiopathic. They are usually associated with spongiofibrosis of the segment of the urethra that has been involved. Worldwide, two different surgical approaches are currently adopted for bulbar urethral repair: transecting techniques with end-to-end anastomosis and non-transecting techniques followed by grafting. Traumatic obliterated strictures require transection of the urethra allowing complete removal of the fibrotic tissue that involves the urethral ends. Conversely, non-traumatic, non-obliterated urethral strictures require augmentation of the urethral plate using oral mucosa grafts. Nowadays, it is still difficult to choose the correct surgical management for non-obliterated bulbar stricture repair. Indeed, different surgical techniques have been proposed (pedicled flap vs free graft, dorsal vs ventral placement of the graft, non-transecting technique using or non-using free graft, etc.) but none emerged as the best solution since all techniques have showed similar success and complication rates. Consequently, the final choice is still based on surgeon's preferences and patient's characteristics. Within the current manuscript, we like to present some of our tips and tricks that we developed along our prolonged surgical experience on the treatment of bulbar urethral strictures. These might be of interest for surgeons that approach this complex surgery. Moreover, our suggestions want to be useful regardless the type of chosen technique being adaptable for different scenario.

Lichen sclerosus of the male genitalia and urethral stricture diseases.

INTRODUCTION: The true incidence of urethral involvement in patients with genital lichen sclerosus (LS) is unknown. We review the epidemiology and discuss the pathogenesis of LS and urethral stricture diseases. MATERIALS AND METHODS: During the period 1991-2002, of 925 patients who underwent urethroplasty for anterior urethral stricture, 130 patients (14%) received the diagnosis of LS. In all patients with LS the histology was re-examined to confirm the clinical diagnosis. Retrograde and voiding urethrography was used to establish urethral involvement in the disease. RESULTS: In 106 patients (82%) the histology provided the classical features of LS, and 24 patients (18%) showed some histological variations. In 49 patients (37%) the LS involved the pendolous urethra (meatus-navicularis-penile), and in 53 cases (41%) a panurethral stricture was evident. CONCLUSIONS: LS urethral involvement appears to be a much more common and extensive disease than previously reported, and requires particular care in its early diagnosis.