Patient-reported outcomes after one-stage neourethral reconstruction in transmen with phalloplasty-associated strictures and fistulas.

INTRODUCTION: Urethral strictures and fistulas arising after gender-affirming surgery in transmen require meticulous management strategies. This study evaluates the safety and efficacy of urethral reconstruction and patient satisfaction post-surgery. METHODS: A retrospective analysis examined peri- and postoperative data from transmen undergoing urethral reconstruction for urethral fistula and/or strictures at the distal urethral anastomosis between December 2017 and April 2023. Follow-up involved clinical examinations, uroflowmetry, and voiding cystourethrography. Patient satisfaction and quality of life were assessed using USS PROM and ICIQ-S questionnaires. RESULTS: Among 25 patients, 88% (n = 23) had urethral fistulas, and 48% (n = 12) had urethral strictures. 41% of fistula patients also had strictures, while 75% of stricture patients had concurrent fistulas. Previous surgeries for fistula or stricture repair were noted in 26% of cases. Techniques for stricture included modified flap (50%), buccal oral mucosal grafting (33%), and primary anastomosis (17%). Post-operative urethrogram revealed urethral strictures in 15% (n = 3) and urinary extravasation in an equal number. Postoperative uroflow parameters showed improvement (Qmax 18 ml/s, Qave 7.9 ml, time 37 s, volume 332 ml). Perioperative complications were low (n = 6, 24%), all grade one (Clavien-Dindo). Follow-up revealed that 33% required another surgical intervention. The mean six-item LUTS score was 6.7 (SD 3.9). Mean ICIQ-S overall satisfaction score was 8.6 (SD 1.6) and outcome score was 20 (SD 2.8). DISCUSSION: Our study found a significant recurrence rate of urethral strictures and fistulas post-surgery. Despite this, patient satisfaction remains high and complications are generally low-grade, highlighting the importance of expert surgical intervention.

Mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty: a ventral modification for obliterative strictures.

OBJECTIVES: To present a surgical modification for the repair of bulbar urethral strictures containing short, highly obliterative segments and report on long-term objective and patient-reported outcomes. PATIENTS AND METHODS: We considered patients undergoing bulbar buccal mucosal graft urethroplasty (BMGU) between July 2016 and December 2019. Eligibility criteria for mucomucosal anastomotic non-transecting augmentation (MANTA) urethroplasty were strictures of ≥2 cm with an obliterative segment of ≤1.5 cm. The stricture is approached ventrally to avoid extensive dissection and mobilisation. Dorsally, the scar is superficially excised and the spongiosum is left intact. Dorsal mucomucosal anastomosis is complemented by ventral onlay graft. Perioperative characteristics were prospectively collected including uroflowmetry data and validated patient-reported outcome measures on voiding, erectile, and continence function. We evaluated functional follow-up, incorporating patient-reported (lower urinary tract symptoms [LUTS] score) and functional success. Recurrence was defined as need of re-treatment. RESULTS: Of 641 men treated with anterior BMGU, 54 (8.4%) underwent MANTA urethroplasty. Overall, 26 (48%) and 45 (83%) had a history of dilatation and urethrotomy, respectively, and 14 (26%) were redo cases. Location was bulbar in 38 (70%) and penobulbar in 16 patients (30%), and the mean (SD) graft length was 4.5 (1.4) cm. At a median (interquartile range) follow-up of 41 (27-53) months, the functional success rate was 93%. Whereas the median LUTS score significantly improved from baseline to postoperatively (13 vs 3.5; P < 0.001), there was no change in erectile function (median International Index of Erectile Function - erectile function domain score 27 vs 24) or urinary continence (median International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form sum score 0 vs 0; all P ≥ 0.4). All patients were 'satisfied' (27%) or 'very satisfied' (73%) with the outcome of their operation. CONCLUSION: With excellent long-term objective and patient-reported outcomes, MANTA urethroplasty adds to the armamentarium for long bulbar strictures with a short obliterative segment.

Exploring the Relationship between (De-)Centralized Health Care Delivery, Client-Centeredness, and Health Outcomes-Results of a Retrospective, Single-Center Study of Transgender People Undergoing Vaginoplasty.

Introduction: Transgender health care interventions (e.g., gender-affirming surgery) support transgender and gender-diverse people to transition to their gender and are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different institutions spread over several locations). In this exploratory study, we investigated the relationship between centralized and decentralized delivery of transgender health care, client-centeredness, and psychosocial outcomes. Methods: A retrospective analysis of 45 clients undergoing vaginoplasty at one medical center was conducted. Mann-Whitney U tests assessed differences regarding five dimensions of client-centeredness and psychosocial outcomes between the health care delivery groups. To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identified predictors that were actually related to the outcomes. Results: All aspects of client-centered care were scored average or high. Decentralized delivery of care was more client-centered in terms of involvement in care/shared decision-making and empowerment. However, participants from decentralized health care delivery settings scored lower on psychosocial health (p = 0.038-0.005). Conclusions: The factor of (de-)centralized health care delivery appears to have a significant impact on the provision of transgender health care and should be investigated by future research.

(De-)centralized health care delivery, surgical outcome, and psychosocial health of transgender and gender-diverse people undergoing vaginoplasty: results of a retrospective, single-center study.

PURPOSE: Previous research on genital gender-affirming surgery lacked to build a framework that took various surrounding factors into account. E.g., transgender health care services are delivered in both centralized (by one interdisciplinary institution) and decentralized settings (by different medical institutions spread over several locations). The present study investigated the effects of different structural and clinical aspects of gender-affirming genital surgery on psychosocial outcomes. METHODS: We surveyed former transgender and gender-diverse people who completed a vaginoplasty between 2014 and 2018. 45 participants were included in the study. We calculated hierarchical linear regression analyses to assess the relationship between psychosocial outcome measures (gender congruence, mental health, quality of life) and different aspects of gender-affirming genital surgery (e.g., setting of service delivery). To address shortcomings regarding the small sample size, we applied a rigorous statistical approach (e.g., Bonferroni correction) to ensure that we only identify predictors that are actually related to the outcomes. RESULTS: A non-responder analysis revealed no systematic bias in the recruitment procedure. Treatment satisfaction was a significant predictor for gender congruence. Moreover, we found the setting of service delivery (centralized, decentralized) to predict psychological health and the physical health dimension of quality of life. The effect sizes of our models were moderate to high, and models explained up to 26% of the total variance with a power up to 0.83. CONCLUSION: The present study is an exploratory attempt into the manifold relationships between treatment-related factors (e.g., aesthetic outcome), the setting of service delivery, and their effects on gender-affirming genital surgery.

Nephrometry and cumulative morbidity after partial nephrectomy: A standardized assessment of complications in the context of PADUA and R.E.N.A.L. scores.

BACKGROUND: Nephrometry scores aid in clinical decision-making, yet evidence is scarce regarding their impact on cumulative morbidity following partial nephrectomy (PN). PATIENTS AND METHODS: Retrospective, monocentric study of 122 patients with suspicious renal masses undergoing open or robot-assisted PN between January 2019 and August 2020. Morbidity assessment followed European Association of Urology guidelines on complication reporting. 30-d complications were extracted using a PN-specific catalog, were graded by the Clavien-Dindo classification (CDC), and Comprehensive Complication Index (CCI®) values were calculated. The impact of nephrometry on cumulative morbidity was evaluated by (1) comparing morbidity estimates between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA)/R.E.N.A.L. complexity groups, (2) by Pearson's correlation between nephrometry scores and CCI®, and (3) by multivariable regression models using any 30-d complication and 30-d CCI® as endpoints. RESULTS: Of 122 patients, 101 (83%) underwent open and 21 (17%) robot-assisted PN. Median PADUA and R.E.N.A.L. scores were 9 (interquartile range, IQR 8-10) and 8 (IQR 6-9), respectively. Of 218 complications in 92 patients (75%), the majority was classified as minor (CDC grade ≤IIIa). Median 30-d CCI® was 8.7 (IQR 0.50-15). There was a small positive correlation between PADUA or R.E.N.A.L. score with CCI® (all P ≤ 0.026), explaining 4.7% and 4.1% of the variation in CCI®, respectively. After adjustment, nephrometry scores were associated with any 30-d complication and the CCI® (all P ≤ 0.011). PADUA and R.E.N.A.L. high complexity tumors were positively associated with both morbidity endpoints compared to low complexity tumors (all P ≤ 0.041). CONCLUSIONS: At a referral center, PN may be safely performed, even if morbidity assessment follows a strict protocol. Nephrometry risk classification does only marginally translate into clinical relevant differences regarding short-term complications. Thus, nephron-sparing surgery should not be withheld from patients with high complexity renal masses.

Transcroporal Artificial Urinary Sphincter Placement With Closure of Corporal Bodies-A Long-Term Analysis of Functional Outcomes.

Objectives: An artificial urinary sphincter (AUS) is the gold standard for postoperative stress urinary incontinence (SUI). The transcorporal AUS (TC) placement constitutes the main salvage option in high-risk patients suffering from SUI with fragile urethras. The literature analyzing long-term outcomes with respect to explantation rates, continence, and erectile function is scarce. Methods and Patients: Retrospective data collection was performed in 2011. TC was applied according to a standardized protocol. TC was implanted after bulbar urethroplasty or double-cuff (DC) explantation. After TC placement, the tunica albuginea was closed in order to minimize the risk of postoperative bleedings and erectile dysfunction. Activation was performed 6 weeks postoperatively. Further follow-up (FU) was scheduled 6/24 months postoperatively and every 2 years thereafter. Primary/secondary endpoints were explantation/objective, subjective, and social continence rates. Objective or social continence was defined as the use of 0 pads/day or <2 pads/day, respectively. Thereupon, postoperative bleedings and erectile function were analyzed. Results: A total of 39 high-risk patients were available for analysis. The median age was 72 years. In total, 84.6%, 10.3%, and 2.6% had a history of radical prostatectomy, TURP, and radical cystectomy, respectively. In total, 61.5% had a history of radiation therapy of the prostate, 41% had a history of urethral surgery, and 95% had a history of double cuff explantation. The median FU was 27 months. Objective, subjective, and social continence were 54.5%, 69.7%, and 78.8%, respectively. The median pad usage was 1 pad/day [1-2.5]. Only one patient suffered from a postoperative hematoma. In total, 15.4% of the patients were able to have an erection preoperatively, compared to 7.7% after TC placement. The estimated mean explantation-free survival of the TC was 83 months in the Kaplan-Meier analysis. Conclusions: TC AUS implantation constitutes a viable salvage approach in high-risk SUI patients with a mean device survival of almost 7 years and high social continence rates of almost 80%. An intraoperative closure of the tunica albuginea after TC placement allows for very low rates of postoperative hematoma and supports postoperative erectile rigidity.

Reduced CDH16 expression is linked to poor prognosis in clear cell renal cell carcinoma 16.

OBJECTIVE: Cadherin-16 (CDH16) is a member of the cadherin superfamily which is also termed kidney specific cadherin (ksp-cadherin) because of its preferred expression in the normal kidney where it plays a pivotal role in tubulus formation during embryonal development. However, little is known about the prognostic role of CDH16 in renal cell carcinomas. METHODS AND MATERIAL: CDH16 protein was analyzed by immunohistochemistry in more than 1,300 renal cell carcinomas (RCCs) in a tissue microarray format. RESULTS: A CDH16 positivity was found in 81% of 1,115 interpretable tumors. Staining was weak in 34%, moderate in 32% and strong in 15% of tumors. CDH16 positivity was more common in oncocytomas (99% positive) and chromophobe carcinomas (94%) than in papillary (73%) and clear cell RCCs (82%; P < 0.0001). In clear cell RCC, reduced CDH16 staining was significantly linked to high-grade (P < 0.0001), advanced pT stage (P = 0.0452), distant metastasis (P = 0.0003) as well as to shortened recurrence free (P < 0.0001), overall (P = 0.0002), and tumor specific survival (P = 0.0092). In a multivariate analysis including pT, pN, ISUP grade, and M status, CDH16 expression loss was an independent prognostic parameter for overall (P = 0.0016) and tumor specific survival (P = 0.0218) in clear cell RCC. Unequivocal associations with tumor phenotype and prognosis were not seen in papillary RCC. CONCLUSION: Our data demonstrate that reduction of CDH16 expression is a strong and potentially clinically useful independent predictor of poor prognosis in clear cell RCC.

[Contemporary management of pelvic fracture urethral injuries]. / Operative Versorgung von Harnröhrenverletzungen nach pelvinen Traumata.

Posterior urethral injuries in men usually result from polytrauma with pelvic fractures and severe associated injuries. If left untreated, posterior urethral injury can lead to severe complications and even death, so precise diagnosis should be made when urethral injury is suspected. The cardinal symptom of urethral injury is blood leakage from the meatus. Retrograde urethrography is the diagnostic tool of choice. In the case of complete urethral avulsion, the formation of a urethral stricture due to pronounced scarring fibrosis is inevitable. In principle, various therapeutic approaches are available. Often, urinary diversion by means of a transurethral or suprapubic catheter is performed first. However, there is also the possibility of direct endoscopic or open urethral realignment with subsequent temporary catheterization. Immediate surgical reconstruction is useful only in exceptional cases of simultaneous bladder neck or rectal injury. In cases of complete urethral avulsion, secondary transperineal bulboprostatic reanastomosis at the interval after three months of suprapubic continuous drainage with excellent success rate is the gold standard and can be supplemented with ancillary maneuvers if necessary to ensure a tension-free anastomosis.

Penile Flap Inversion Vaginoplasty in Transgender Women: Contemporary Morbidity and Learning-Curve Analysis From a High-Volume Reconstructive Center.

Objectives: Numbers of PIV are rising. The aim of this study is to analyze the surgical learning-curve (LC) on the grounds of perioperative complications. Patients and Methods: 108 PIVs, performed by a single surgeon between 2015 and 2018 have been analyzed. Learning-curve analysis was based on three factors: operating time, vaginal depth and complications. Results: The median FU was 6.3 months. Median age at surgery was 36 years, median time of hormone treatment was 36 months. The median CI was 0.3 and the median BMI was 25 kg/cm3. Median CCI® was 8.08. 40.7% of the patients developed short-term complications, more than half of which were Clavien I. Overall only 1.9% had Clavien IIIb complications. There were no Clavien IV or V complications. 17.6% of patients had wound infections, 13% wound dehiscence, 9.3% introitus strictures, 13.9% suffered from atrophy of the neovagina, i.e. loss of depth or width, and 8.3% from meatus urethrae strictures. Duration of hormonal therapy, BMI and CI had no impact on surgical outcome. Age had a significant impact on CCI®, as younger patients had a higher risk for complications. Use of scrotal skin and surgeries performed had a significant influence. LC analysis via CUSUM analysis showed that after 32 surgeries, the PIV is performed safely. Conclusion: The PIV is a safe GAS-technique, associated with minor complications leading to low rates of revision surgery. Younger age, the use of scrotal skin and surgeon's experience has significant impact on complications. Duration of hormonal therapy, circumcision and BMI has no impact on complications.

Urethral Stricture Formation Following Cuff Erosion of AMS Artificial Urinary Sphincter Devices: Implication for a Less Invasive Explantation Approach.

OBJECTIVES: The objective of this study is to describe a standardized less invasive approach in patients with artificial urinary sphincter (AUS) explantation due to cuff erosion and analyze success and urethral stricture rates out of a prospective database. Evidence regarding complication management is sparse with heterogenous results revealing high risk of urethral stricture formation despite simultaneous urethroplasty in case of AUS explantation. PATIENTS AND METHODS: Data of all patients undergoing AUS implantation due to stress urinary incontinence (SUI) in our tertiary center were prospectively collected from 2009 to 2015. In case of cuff erosion, AUS explantation was carried out in an institutional standardized strategy without urethroplasty, urethral preparation or mobilization nor urethrorrhaphy. Transurethral and suprapubic catheters were inserted for 3 weeks followed by radiography of the urethra. Further follow-up (FU) consisted of pad test, uroflowmetry, postvoiding residual urine (PVR), and radiography. Primary endpoint was urethral stricture rate. RESULTS: Out of 235 patients after AUS implantation, 24 (10.2%) experienced cuff erosion with consecutive explantation and were available for analysis. Within a median FU of 18.7 months after AUS explantation, 2 patients (8.3%) developed a urethral stricture. The remaining 22 patients showed a median Qmax of 17 ml/s without suspicion of urethral stricture. Median time to reimplantation was 4 months (IQR 3-4). CONCLUSION: We observed a considerably low stricture formation and could not prove an indication for primary urethroplasty nor delay in salvage SUI treatment possibilities. Therefore, the presented standardized less invasive explantation strategy with consequent urinary diversion seems to be safe and effective and might be recommended in case of AUS cuff erosion.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

European Association of Urology Guidelines on Urethral Stricture Disease (Part 2): Diagnosis, Perioperative Management, and Follow-up in Males.

CONTEXT: Urethral stricture management guidelines are an important tool for guiding evidence-based clinical practice. OBJECTIVE: To present a summary of the 2021 European Association of Urology (EAU) guidelines on diagnosis, classification, perioperative management, and follow-up of male urethral stricture disease. EVIDENCE ACQUISITION: The panel performed a literature review on the topics covering a time frame between 2008 and 2018, and using predefined inclusion and exclusion criteria for the literature. Key papers beyond this time period could be included if panel consensus was reached. A strength rating for each recommendation was added based on a review of the available literature after panel discussion. EVIDENCE SYNTHESIS: Routine diagnostic evaluation encompasses history, patient-reported outcome measures, examination, uroflowmetry, postvoid residual measurement, endoscopy, and urethrography. Ancillary techniques that provide a three-dimensional assessment and may demonstrate associated abnormalities include sonourethrography and magnetic resonance urethrogram, although these are not utilised routinely. The classification of strictures should include stricture location and calibre. Urethral rest after urethral manipulations is advised prior to offering urethroplasty. An assessment for urinary extravasation after urethroplasty is beneficial before catheter removal. The optimal time of catheterisation after urethrotomy is <72 h, but is unclear following urethroplasty and depends on various factors. Patients undergoing urethroplasty should be followed up for at least 1 yr. Objective and subjective outcomes should be assessed after urethral surgeries, including patient satisfaction and sexual function. CONCLUSIONS: Accurate diagnosis and categorisation is important in determining management. Adequate perioperative care and follow-up is essential for achieving successful outcomes. The EAU guidelines provide relevant evidence-based recommendations to optimise patient work-up and follow-up. PATIENT SUMMARY: Urethral strictures have to be assessed adequately before planning treatment. Before surgery, urethral rest and infection prevention are advised. After urethral surgery, x-ray dye tests are advised before removing catheters to ensure that healing has occurred. Routine follow-up is required, including patient-reported outcomes. These guidelines aim to guide doctors in the diagnosis, care, and follow-up of patients with urethral stricture.

European Association of Urology Guidelines on Urethral Stricture Disease (Part 1): Management of Male Urethral Stricture Disease.

OBJECTIVE: To present a summary of the 2021 version of the European Association of Urology (EAU) guidelines on management of male urethral stricture disease. EVIDENCE ACQUISITION: The panel performed a literature review on these topics covering a time frame between 2008 and 2018, and used predefined inclusion and exclusion criteria for the literature to be selected. Key papers beyond this time period could be included as per panel consensus. A strength rating for each recommendation was added based on a review of the available literature and after panel discussion. EVIDENCE SYNTHESIS: Management of male urethral strictures has extensively been described in literature. Nevertheless, few well-designed studies providing high level of evidence are available. In well-resourced countries, iatrogenic injury to the urethra is one of the most common causes of strictures. Asymptomatic strictures do not always need active treatment. Endoluminal treatments can be used for short, nonobliterative strictures at the bulbar and posterior urethra as first-line treatment. Repetitive endoluminal treatments are not curative. Urethroplasty encompasses a multitude of techniques, and adaptation of the technique to the local conditions of the stricture is crucial to obtain durable patency rates. CONCLUSIONS: Management of male urethral strictures is complex, and a multitude of techniques are available. Selection of the appropriate technique is crucial, and these guidelines provide relevant recommendations. PATIENT SUMMARY: Injury to the urethra by medical interventions is one of the most common reasons of male urethral stricture disease in well-resourced countries. Although different techniques are available to manage urethral strictures, not every technique is appropriate for every type of stricture. These guidelines, developed based on an extensive literature review, aim to guide physicians in the selection of the appropriate technique(s) to treat a specific type of urethral stricture.

Free Graft Augmentation Urethroplasty for Bulbar Urethral Strictures: Which Technique Is Best? A Systematic Review.

CONTEXT: Four techniques for graft placement in one-stage bulbar urethroplasty have been reported: dorsal onlay (DO), ventral onlay (VO), dorsolateral onlay (DLO), and dorsal inlay (DI). There is currently no systematic review in the literature comparing these techniques. OBJECTIVE: To assess if stricture recurrence and secondary outcomes vary between the four techniques and to assess if one technique is superior to any other. EVIDENCE ACQUISITION: The EMBASE, MEDLINE, and Cochrane Systematic Reviews-Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED) databases and ClinicalTrials.gov were searched for publications in English from 1996 onwards. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), observational studies (cohort, case-control/comparative, single-arm), and case series with ≥20 adult male participants were included. EVIDENCE SYNTHESIS: A total of 41 studies were included involving 3683 patients from one RCT, four NRCSs, and 36 case series. Owing to the overall low quality of the evidence, a narrative synthesis was performed. CONCLUSIONS: No single technique appears to be superior to another for bulbar free graft urethroplasty. Both DO and VO are suitable for bulbar augmentation urethroplasty, with a ≤20% recurrence rate over medium-term follow-up. No recommendations can be made regarding DI or DLO techniques owing to the paucity of evidence. Secondary outcomes including sexual function, and complications are infrequently reported. Recurrence rates deteriorate in the long term for both DO and VO procedures. PATIENT SUMMARY: We reviewed the evidence for four different skin-graft techniques used to repair narrowing of a section of the urethra (bulbar urethra, under the scrotum and perineum) in men. Two of the techniques seem to give consistent results, with recurrence rates lower than 20%. Recurrence rates increase over time, so patients should continue to monitor their symptoms. There is poorer reporting of other outcomes such as sexual function, urinary symptoms, and complications, and it is possible that these occur more frequently than the current data suggest.

Tumor cell PD-L1 expression is a strong predictor of unfavorable prognosis in immune checkpoint therapy-naive clear cell renal cell cancer.

BACKGROUND: PD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome. METHODS: We analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8+ cytotoxic cells. RESULT: At a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (p < 0.0001), Fuhrman (p < 0.0001), Thoenes grade (p < 0.0001), distant metastasis (p = 0.0042), short recurrence-free (p < 0.0001), and overall survival (p = 0.0002). Intratumoral CD8+ lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8+ cells (p < 0.0001), high ISUP (p < 0.0001), Fuhrman (p = 0.0027), and Thoenes grade (p < 0.0001), and poor tumor-specific survival (p = 0.0280). CONCLUSIONS: These data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.

Exploring the intersection of functional recurrence, patient-reported sexual function, and treatment satisfaction after anterior buccal mucosal graft urethroplasty.

PURPOSE: To evaluate the interplay of stricture recurrence, sexual function, and treatment satisfaction after substitution urethroplasty. METHODS: Observational study of men undergoing 1-stage buccal mucosal graft urethroplasty for anterior urethral stricture between 2009 and 2016. Patients were dichotomized by self-reported treatment satisfaction. Sexual function was assessed by validated and non-validated patient-reported outcome measures. Functional recurrence was defined as symptomatic need of re-intervention. Bivariate analyses, Kaplan-Meier estimates, qualitative and quantitative analyses by uni- and multivariable regression were employed to evaluate the interplay of sexual function, functional recurrence, and treatment satisfaction. RESULTS: Of 534 men with bulbar (82%), penobulbar (11%), and penile strictures (7.3%), 451 (84%) were satisfied with the surgery. There were no differences in stricture location, previous treatment, graft length, or surgical technique between satisfied and unsatisfied patients (all p ≥ 0.2). Recurrence-free survival was 85% at a median follow-up of 33 mo and decreased significantly with each Likert item towards increasing dissatisfaction (p < 0.001). Dissatisfied patients more often reported postoperative loss of rigidity, tumescence, reduced ejaculatory volume, ejaculatory pain, and reduced penile length (all p ≤ 0.042). In 83 dissatisfied men, functional recurrence (28%) and oral morbidity (20%) were the main drivers of dissatisfaction in qualitative analysis. Multivariable analyses revealed functional recurrence and impaired postoperative ejaculatory function as independent predictors of treatment dissatisfaction (all p ≤ 0.029) after adjusting for confounders. CONCLUSION: We found an association of both functional success and sexual function with patient-reported treatment satisfaction after substitution urethroplasty. Such findings validate the clinical significance of defining the symptomatic need for re-intervention as an endpoint and underline the importance of further research evaluating sexual function before and after open urethral reconstruction.

Continence and Complication Rates of Artificial Urinary Sphincter Devices (AMS 800) for Parkinson and Stroke Patients with Incontinence after Prostate Surgery: Retrospective Analysis of a Prospective Database.

OBJECTIVES: The artificial urinary sphincter (AUS) is the gold standard treatment for severe stress urinary incontinence (SUI). According to the literature, patients suffering from Parkinson's disease (PD) or stroke (ST) show adverse continence outcomes after prostate surgery and, therefore, constitute a challenging cohort for continence surgery. However, little is known with respect to the results of AUS surgery in these patients. A retrospective analysis of our institutional, prospectively maintained AUS database aims to address this aspect with a focus on surgical and functional outcomes. METHODS AND PATIENTS: All data of patients with an AUS implantation were prospectively collected in our database since 2009. The AUS was implanted according to a standardized protocol and activated at 6 weeks postoperatively at our institution. Further follow-up (FU) consisted of pad-test, uroflowmetry, residual urine, and radiography as well as a standardized questionnaire including the Incontinence Quality of Life questionnaire (I-Quol) and International Consultation on Incontinence questionnaire (ICIQ-SF) and is scheduled at 6 and 24 months and every 2 years thereafter. Patients received a preoperative urodynamic evaluation (UD). Patients with normal voiding and storage function were considered for AUS implantation. All patients performed a preoperative test for manual dexterity. Patients with a history of ST or PD were grouped and compared to nonneurological patients. Primary/secondary endpoints of the study were complications/continence. RESULTS: 234 patients were available for analysis. The median FU was 24 months (interquartile range 7-36). Twenty-four patients (10%) had a neurological history (PD and ST). Neurological patients showed significantly worse outcomes regarding continence (objective/subjective/social continence; p = 0.04/p = 0.02/p = 0.1). Significant differences concerning explantation rates were not observed (p = 1). Kaplan-Meier analysis showed no significant difference regarding explantation-free survival (log-rank p = 0.53). CONCLUSION: AUS implantation shows significantly worse continence rates for neurological patients, despite the fact that all patients showed normal UD results and sufficient manual dexterity. Although neurological patients showed worse outcomes for continence, AUS implantation seems to be a safe and viable treatment for patients with a history of neurological disease.

High level of EZH2 expression is linked to high density of CD8-positive T-lymphocytes and an aggressive phenotype in renal cell carcinoma.

PURPOSE: Enhancer of zeste homolog 2 (EZH2), the catalytic part of the Polycomb repressive complex 2 (PRC2), has a prognostic role in renal cell carcinoma (RCC) and was recently shown to modulate the immune response by reducing tumor cell immunogenicity. METHODS: To investigate whether the prognostic role of EZH2 might be driven by a modified immune environment, more than 1800 RCCs were analyzed in a tissue microarray for EZH2 expression and CD8 positive lymphocytes were quantitated by automated digital imaging. RESULTS: EZH2 positivity was found in 75.2% of 1603 interpretable tumors. In clear cell RCC, high EZH2 expression was significantly linked to high ISUP, Furmann, and Thoenes grade (p < 0.0001 each), advanced stage (p < 0.0001), nodal (p = 0.0190) and distant metastasis (p < 0.0001) as well as shortened overall (p < 0.0027) and recurrence free survival (p < 0.0001). The density of CD8+ cells varied from 0 to 5048 cells/mm2 (Median 120 cells/mm2). A high CD8+ count was significantly associated with high ISUP, Fuhrmann, and Thoenes grade (p < 0.0001 each), advanced tumor stage (p = 0.0041), distant metastasis (p = 0.0026) as well as reduced overall survival (p = 0.0373) and recurrence free survival (p = 0.0450). The density of CD8+ cells continuously increased with raising EZH2 levels (p < 0.0001). CONCLUSION: Our data support a striking prognostic role of both EZH2 expression and the density of CD8+ cells in RCC. The tight relationship of EZH2 expression and CD8+ cell counts in RCC is consistent with models suggesting that EZH2 overexpression can be caused by high lymphocyte content in certain tumor types. Such a mechanism could explain the unique finding of high lymphocyte counts driving poor prognosis in RCC patients.