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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.

The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

Background To evaluate outcome of buccal mucosa graft urethroplasty (BMGU) for the treatment of urethral stricture disease, including a detailed analysis of success, morbidity and quality of life (QoL). Methods Between 12/05/2008 and 07/21/2010, 187 patients with urethral stricture disease, who were treated with BMGU at our University Medical Center, received a standardized questionnaire, evaluating postoperative success, morbidity and QoL. The primary endpoint was the success, i.e., stricture recurrence-free survival plus patients’ satisfaction with surgery. Secondary endpoints included erectile function, voiding symptoms, pain and health-related QoL, which were assessed with a modified Urethral Stricture Surgery Patient Reported Outcome Measure (USS PROM), including the Erectile Function domain of the International Index of Erectile Function (IIEF-EF), Incontinence Questionnaire Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS) and EuroQol-5 dimensions (EQ-5D). Results In total, 83 patients (51.9%) completed the questionnaire. Bulbar, penile and panurethral strictures were found in 69 patients (83.1%), 13 patients (15.7%) and one patient (1.2%), respectively. The median length of the stricture was 5 cm (range: 1–16). At a median follow-up of 46 months (range: 36–54), 65 patients (78.3%) had no stricture recurrence and were satisfied with BMGU. Median scores for ICIQ-MLUTS, IIEF-EF and EQ-5D visual analogue scale were 6, 22 and 80, respectively. Based on USS PROM, postoperative improvement of QoL and satisfaction with BMGU was found in 67 patients (80.7%) and 68 patients (81.9%), respectively. Conclusions In patients with urethral stricture disease, BMGU offers excellent success, morbidity and QoL.

Purpose To validate a German language version of the patient-reported outcome measurement (PROM) following urethral stricture surgery (USS) in a cohort of men undergoing one-stage buccal mucosa graft urethroplasty (BMGU) for urethral stricture. Furthermore, to explore the responsiveness of erectile function (EF) and urinary incontinence (UI) constructs in the context of this intervention. Methods The USS-PROM captures voiding symptoms (ICIQ-MLUTS) and health-related quality of life (HRQoL) (EQ-5D). To evaluate EF and UI, the IIEF-5 and ICIQ-UI SF were included. Between March 2012 and April 2013, all patients undergoing BMGU at our institution were prospectively enrolled in this study. Psychometric assessment included internal consistency, test–retest reliability, criterion validity and responsiveness. Results Ninety-three men completed the USS-PROM before and 3 months after surgery, with 40 (43 %) also completing the USS-PROM 6 months after surgery to assess reliability. Internal consistency: for the ICIQ-MLUTS, Cronbach’s α was 0.83. The test–retest intraclass correlation coefficient was 0.94. There was a negative correlation between change in ICIQ-MLUTS total score and change in Q max ( r  = −0.40). All values exceeded our predefined thresholds. Significant improvements of voiding symptoms and HRQoL demonstrate responsiveness to change (all p values <0.001). While ICIQ-UI scores did not change ( p  > 0.05), IIEF-5 scores improved significantly ( p  = 0.048). Conclusions The German language USS-PROM shows similar psychometric properties to the English language version. This instrument can be improved by assessing EF by the use of IIEF-5. Further studies with larger patient cohorts are needed to evaluate the significance of measuring UI in urethroplasty patients.

A number of techniques have been described for managing anterior urethral strictures in men. In this review, we aimed to summarize contemporary considerations regarding the holistic management of such strictures. The efficacy of reported outcomes is compared to provide evidence-based treatment recommendations. For anterior urethral strictures, durable long-term success rates of >90% may be achieved if the procedure is performed in capable hands at a high-volume referral center, even in recurrent strictures after previous open reconstruction. A one-stage urethroplasty is preferable to avoid a protracted treatment course with multiple interventions after dilation and direct vision internal urethrotomy. Staged urethroplasties are useful in complex anterior strictures providing durable success rates. In addition, perineal urethrostomy represents a valid last resort option with sufficient objective and subjective results. A follow-up evaluation should incorporate objective assessments such as radiographic and functional diagnostics as well as subjective, validated, and disease-specific patient-reported outcome measurement tools to allow for a better comparability and to improve individual risk prediction.

Background Deletions of 17p13 recurrently occur in renal cell carcinoma (RCC) but their prognostic role seems to be uncertain. Methods To determine prevalence, relationship with tumor phenotype, and patient prognosis, a tissue microarray containing samples from 1809 RCCs was evaluated using dual labeling fluorescence in situ hybridization (FISH) with 17p13 and chromosome 17 centromere probes. Results A 17p13 deletion was found in 72 of 1429 interpretable tumors. The frequency of 17p13 deletions varied greatly between RCC subtypes and was highest in chromophobe RCC (24/72; 33.3%). 17p13 deletions were also found in 35 (3.7%) of 946 clear cell RCC, 9 (4.3%) of 208 papillary RCC, 1 of 121 oncocytomas (0.8%), as well as in several rare cases of comprising 1 of 7 Xp11.2 translocation cancers, 1 of 3 collecting duct carcinomas, and 1 of 20 not otherwise specified (NOS) carcinomas. In clear cell carcinomas, 17p13 deletions revealed a strong and consistent association with higher Fuhrman, ISUP, and Thoenes grade ( p < 0.0001 each), and linked to advanced tumor stage ( p = 0.0168), large tumor diameter ( p = 0.0004), distant metastases ( p = 0.0077), cancer-specific survival ( p = 0.0391), and recurrence-free survival ( p = 0.0072). In multivariate analysis, 17p13 deletions showed in clear cell RCC a dependent prognostic role for established clinical-pathological parameters. Conclusion 17p13 deletions have a dual role in RCC. They are associated with disease progression in clear cell RCC and possibly other subtypes and they are linked to the development of chromophobe RCC—a subtype with a particularly favorable prognosis.

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.

ObjectivesTo analyze functional outcomes and complication rates of artificial urinary sphincter (AUS) implantation in patients who had undergone buccal mucosa graft urethroplasty (BMGU) beforehand.Patients and methodsThis prospectively maintained single-center database comprises data from 236 patients from 2009 to 2015 who underwent AUS implantation. A total of 17 patients after BMGU were available for analysis. Primary endpoints consisted of continence and complication rates. Continence was defined as no use of safety pads, social continence as < 2 pads per day. Stricture recurrence was defined as a decrease in uroflowmetry, a maximum flow rate < 10 ml/s or residual urine volume (> 100 ml). Kaplan–Meier analysis determined explantation-free survival.ResultsMedian follow-up was 24 months (interquartile range [IQR] 6–31 months). Indication for AUS implantation was severe urinary incontinence with a history of radical prostatectomy (RRP) in 8 (47.1%), trauma in 1 (5.9%) and TUR-P in 8 (47.1%) patients. Pelvic irradiation was reported in 13 (76.5%) cases. The median length of buccal mucosa graft for urethroplasty was 4 cm (3–5 cm). A double cuff was implanted in 14 patients (82.4%), 3 patients received a single cuff. Complete and social continence was achieved in 76.5% and 100% of the patients, respectively. There was no significant difference in complications and explantation-free survival (log-rank, p = 0.191) between patients who had undergone BMGU before AUS compared to patients with no history of BMGU.ConclusionsAccording to the prospective follow-up data in a homogenous cohort, AUS implantation seems to be a viable, safe and effective therapeutic strategy for incontinence treatment despite previous BMGU.

PurposeTo critically report outcomes from a contemporary series of patients undergoing single-stage Asopa dorsal inlay urethroplasty for penile stricture.MethodsFirst, we retrospectively evaluated patients who underwent Asopa urethroplasty for penile stricture between 2009 and 2016 at our department. Clinical and surgical characteristics were compared across treatment groups (proximal penile, mid-penile, distal penile). Recurrence-free survival was plotted using Kaplan–Meier curves. Treatment satisfaction was assessed using a validated outcome measurement tool. Second, a literature review was performed through Medline to summarize the available evidence on Asopa urethroplasty and put our own results into context.ResultsOf 125 patients, 38 (30%), 74 (59%), and 13 (10%) had distal penile, mid-penile, and proximal penile stricture, respectively. Patients with distal strictures were younger and graft length was shorter compared to other groups (P ≤ 0.009). The majority of strictures were iatrogenic (38%), followed by hypospadias related (24%), congenital (17%), traumatic (10%), inflammatory (9%), and post-infectious strictures (2.4%). At a median follow-up of 36 months, overall success rate was 70%. In sensitivity analyses, success rates were only marginally improved to 71% after exclusion of hypospadias- and lichen sclerosus-associated strictures. Patients with mid-penile strictures were significantly more satisfied compared to other groups. Overall, 272 patients from 9 studies in the literature review underwent Asopa urethroplasty and success rates ranged from 73 to 100%.ConclusionsSuccess rates of Asopa urethroplasty in penile strictures are lower than previously reported. This is most likely due to both complex stricture etiology and surgical history and last resort single-stage surgery in many cases. Pre-operative counseling must consider high recurrence risk and staged urethroplasty should be discussed in selective cases to optimize patient satisfaction.

Objectives To re-evaluate safety and efficacy of transperineal reanastomosis (TPRA) as a viable therapeutic option in highly recurrent anastomotic strictures (AS) after radical retropubic prostatectomy (RRP). Methods Retrospective analysis by standardized questionnaire inquiring for recurrence of stricture, stress urinary incontinence (SUI), sexual function, satisfaction, and changes in quality of life (QoL) was performed in all patients undergoing TPRA. Validated questionnaires (ICIQ-UI, EQ-5D, and IPSS) were included. Results Median follow-up was 45.0 months. The average number of prior operations was 4.69. Success rate was 87% (20/23). Three recurrences were successfully treated via endoscopic means. All patients had urinary incontinence pre-op and post-op. Implantation of an artificial urinary sphincter (AUS) has been performed successfully in 73.9% (17/23). Rate of complications was low (8.7%; 2/23, Clavien–Dindo Grade II + III). EQ-5D-VAS showed a good general state of health (73.5/100). An improvement in QoL was noted in 63.6% (14/22) and patient satisfaction was high (72.7%; 16/22). Conclusions This extended follow-up confirms the initial results for TPRA as an excellent treatment option for highly recurrent AS after RRP. Postoperative SUI as a consequence of transsphincteric urethral mobilization can be satisfactorily treated by the implantation of AUS. In case of AS recalcitrant to endoscopic treatment, the described procedure—even though technically challenging—represents a valuable treatment option.