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Abstract Objective There is a shortage of established prognostic biomarkers in bladder cancer. One candidate is tumour protein 63 (p63), a transcription factor of the p53 gene family that is expressed in the normal urothelium. Recently proposed RNA expression‐based molecular classifiers of bladder cancer identified high p63 expression as a component of a basal/squamous subtype linked to poor patient prognosis. Methods In this study, p63 protein expression was analysed by immunohistochemistry on more than 2500 urothelial bladder carcinomas in a tissue microarray format to determine its relationship with clinicopathological parameters of disease progression and patient outcome. Results Nuclear p63 staining was seen in all cells of normal urothelium and at elevated levels in pTaG2 tumours. The rate of p63 positive cases and the staining intensity was lower in pTaG3 tumours (93.2%, p

Abstract Objectives Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low‐grade, 32.0% of 178 pTaG2 high‐grade, and 43.0% of 93 pTaG3 tumours (p 0.25). Conclusion CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2–4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2–4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti‐CEA drugs.

Background: It remains unknown whether there is a causal relationship between intraoperative hypotension and postoperative neurocognitive disorders. We tested the hypothesis that personalised—compared to routine—intraoperative blood pressure management reduces the incidence of postoperative neurocognitive disorders in patients having major noncardiac surgery. Methods: In this single-centre trial, 328 elective major noncardiac surgery patients were randomly allocated to receive personalised blood pressure management (i.e. maintaining intraoperative mean arterial pressure [MAP] above preoperative baseline MAP from automated 24-h blood pressure monitoring) or routine blood pressure management (i.e. maintaining MAP above 65 mm Hg). The primary outcome was the incidence of neurocognitive disorders (composite of delayed neurocognitive recovery and delirium) between postoperative days 3 and 7. Results: The primary outcome, neurocognitive disorders, occurred in 18 of 147 patients (12%) assigned to personalised and 21 of 148 patients (14%) assigned to routine blood pressure management (odds ratio [OR]=0.84, 95% confidence interval [CI]: 0.40–1.75, P=0.622). Delayed neurocognitive recovery occurred in 17 of 146 patients (12%) assigned to personalised and 17 of 145 patients (12%) assigned to routine blood pressure management (OR=0.99, 95% CI: 0.45–2.17, P=0.983). Delirium occurred in 2 of 157 patients (1%) assigned to personalised and 4 of 158 patients (3%) assigned to routine blood pressure management (OR=0.50, 95% CI: 0.04–3.53, P=0.684). Conclusions: Personalised intraoperative blood pressure management maintaining preoperative baseline MAP neither reduced the incidence of the composite primary outcome neurocognitive disorders between postoperative days 3 and 7 nor the incidences of the components of the composite primary outcome—delayed neurocognitive recovery and delirium—compared to routine blood pressure management in patients having major noncardiac surgery. Clinical trial registration: ClinicalTrials.gov (NCT03442907).

Abstract Background A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. Methods To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. Results Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2–4) carcinomas (29.3%; p

Purpose This study investigated the functional outcomes and complication rates of cuff downsizing for the treatment of recurrent or persistent stress urinary incontinence (SUI) in men after the implantation of an artificial urinary sphincter (AUS). Methods Data from our institutional AUS database spanning the period from 2009 to 2020 were retrospectively analyzed. The number of pads per day was determined, a standardized quality of life (QoL) questionnaire and the International Consultation on Incontinence Questionnaire (ICIQ) were administered, and postoperative complications according to the Clavien-Dindo classification were analyzed. Results Out of 477 patients who received AUS implantation during the study period, 25 (5.2%) underwent cuff downsizing (median age, 77 years; interquartile range [IQR], 74–81 years; median follow-up, 4.4 years; IQR, 3–6.9 years). Before downsizing, SUI was very severe (ICIQ score 19–21) or severe (ICQ score 13–18) in 80% of patients, moderate (ICIQ score 6–12) in 12%, and slight (ICIQ score 1–5) in 8%. After downsizing, 52% showed an improvement of >5 out of 21 points. However, 28% still had very severe or severe SUI, 48% had moderate SUI, and 20% had slight SUI. One patient no longer had SUI. In 52% of patients, the use of pads per day was reduced by ≥50%. QoL improved by >2 out of 6 points in 56% of patients. Complications (infections/urethral erosions) requiring device explantation occurred in 36% of patients, with a median time to event of 14.5 months. Conclusions Although cuff downsizing carries a risk of AUS explantation, it can be a valuable treatment option for selected patients with persistent or recurrent SUI after AUS implantation. Over half of patients experienced improvements in symptoms, satisfaction, ICIQ scores, and pad use. It is important to inform patients about the potential risks and benefits of AUS to manage their expectations and assess individual risks.

IntroductionTrophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. MethodsTo evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. ResultsThe staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p

Abstract Objective Administration of targeted therapies provides a promising treatment strategy for urachal adenocarcinoma (UrC) or primary bladder adenocarcinoma (PBAC); however, the selection of appropriate drugs remains difficult. Here, we aimed to establish a routine compatible methodological pipeline for the identification of the most important therapeutic targets and potentially effective drugs for UrC and PBAC. Methods Next‐generation sequencing, using a 161 cancer driver gene panel, was performed on 41 UrC and 13 PBAC samples. Clinically relevant alterations were filtered, and therapeutic interpretation was performed by in silico evaluation of drug‐gene interactions. Results After data processing, 45/54 samples passed the quality control. Sequencing analysis revealed 191 pathogenic mutations in 68 genes. The most frequent gain‐of‐function mutations in UrC were found in KRAS (33%), and MYC (15%), while in PBAC KRAS (25%), MYC (25%), FLT3 (17%) and TERT (17%) were recurrently affected. The most frequently affected pathways were the cell cycle regulation, and the DNA damage control pathway. Actionable mutations with at least one available approved drug were identified in 31/33 (94%) UrC and 8/12 (67%) PBAC patients. Conclusions In this study, we developed a data‐processing pipeline for the detection and therapeutic interpretation of genetic alterations in two rare cancers. Our analyses revealed actionable mutations in a high rate of cases, suggesting that this approach is a potentially feasible strategy for both UrC and PBAC treatments.

Objective The aim of this study was to evaluate the prognostic impact of concomitant prostate cancer (PCa) of the cancer-specific mortality (CSM) in the aging patient’s papulation with bladder cancer (BCa) treated with radical cystoprostatectomy (RCP). Materials and Methods Within the SEER database (2004–2015), 1468 patients were treated with RCP for BCa harboring histopathological PCa findings. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential BCa-CSM differences according to PCa characteristics risk factors predicting CSM Results CRR analysis revealed that only following BCa characteristics, as high pathological tumor stages(Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16-3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45-7.61, p

None.

ObjectivesAn 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 PatientsRetrospective 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

Abstract Background Tumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation of several tissues including squamous epithelium. p63 immunohistochemistry is broadly used for tumor classification but published data on its expression in cancer is conflicting. Methods To comprehensively catalogue p63 expression, tissue microarrays (TMAs) containing 12,620 tissue samples from 115 tumor entities and 76 normal tissue types were analyzed. Results p63 expression was seen in various normal tissues including squamous epithelium and urothelium. At least occasional weak p63 positivity could be detected in 61 (53%) of 115 different tumor types. The frequencies of p63 positivity was highest in squamous cell carcinomas irrespective of their origin (96–100%), thymic tumors (100%), urothelial carcinomas (81–100%), basal type tumors such as basal cell carcinomas (100%), and various salivary gland neoplasias (81–100%). As a rule, p63 was mostly expressed in cancers derived from p63 positive normal tissues and mostly not detectable in tumors derived from p63 negative cancers. However, exceptions from this rule occurred. A positive p63 immunostaining in cancers derived from p63 negative tissues was unrelated to aggressive phenotype in 422 pancreatic cancers, 160 endometrium cancers and 374 ovarian cancers and might be caused by aberrant squamous differentiation or represent stem cell properties. In 355 gastric cancers, aberrant p63 expression occurred in 4% and was linked to lymph node metastasis (p = 0.0208). Loss of p63 in urothelial carcinomas - derived from p63 positive urothelium - was significantly linked to advanced stage, high grade (p

Abstract 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.

Abstract 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.

ObjectivesThe 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 MethodsData 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.ResultsOut 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).ConclusionWe 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.

ObjectivesNumbers 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 Methods108 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.ResultsThe 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.ConclusionThe 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.

Objective To explore feasibility in terms of delivering and evaluating a combination of physiotherapy and psychotherapy for patients with chronic pelvic pain syndrome (CPPS).Design Prospective non-randomised controlled pilot study.Setting Tertiary care facility with a specialised interdisciplinary outpatient clinic for patients with CPPS.Participants A total of 311 patients was approached; 60 participated. 36 patients were included in the intervention group (mean age ±SD 48.6 years±14.8; 52.8% female) and 24 in the control group (mean age ±SD 50.6 years±14.5; 58.3% female). Fourteen participants were lost to follow-up.Interventions Participants were non-randomly allocated to the intervention group with two consecutive treatment modules (physiotherapy and cognitive behavioural therapy) with a duration of 9 weeks each or to the control group (treatment as usual).Main outcome measures Feasibility was operationalised in terms of delivering and evaluating the therapeutic combination. Regarding eligibility as the first aspect of feasibility, willingness to participate, dropout and satisfaction were assessed; for the second aspect, standardised self-report questionnaires measuring health-related quality of life, depression severity and pain were applied.Results Although eligibility and willingness-to-participate rates were low, satisfaction of the participants in the intervention group was high and dropout rates were low. Results indicated a small and non-significant intervention effect in health-related quality of life and significant effects regarding depression severity and pain.Conclusions The combination of physiotherapy and psychotherapy for patients with CPPS seems to be feasible and potentially promising with regard to effect. However, a subsequent fully powered randomised controlled trial is needed.Trial registration number German Clinical Trials Register (DRKS00009976) and ISRCTN (ISRCTN43221600).

Background: Sarcomatoid differentiation/histology of renal cell carcinoma (sRCC) in patients with metastatic renal cell carcinoma (mRCC) is still underresearched in current therapy regimes. We aimed to evaluate the impact of sRCC on outcomes in patients with mRCC treated with tyrosine kinase inhibitors (TKIs).Methods: We collected complete data of 262 consecutive mRCC patients from our institutional database for this retrospective study. All patients were treated with TKIs within a single or multimodal treatment approach. All analyses were adjusted for the presence of sRCC. Descriptive statistics as well as uni- and multivariable outcome metrics, including progression-free (PFS) and overall survival (OS) as endpoints were performed.Results: Overall, 18 patients had sRCC (6.9%). Patients with sRCC had more often clear-cell histology (p = 0.047), a higher T-stage (p = 0.048), and underwent cytoreductive nephrectomy more frequently (p < 0.001). The most common first-line TKIs were Sunitinib (65.6%), Sorafenib (19.5%), and Pazopanib (10.3%), respectively. At a median follow-up of 32 months, patients with sRCC had significantly reduced PFS (p = 0.02) and OS (p = 0.01) compared to patients without sRCC. In multivariable analyses that adjusted for the effects of standard mRCC predictors, the sarcomatoid feature retained its independent association with inferior PFS (HR: 2.39; p = 0.007) and OS (HR: 2.37; p = 0.001). This association remained statistically significant in subgroup analyses of patients with Sunitinib as first-line therapy (PFS p < 0.001; OS: p < 0.001).Conclusion: Despite its rare occurrence, our findings confirm sRCC as a powerful predictor for inferior outcomes in mRCC treated with targeted therapies. This suggests a need for more tailored treatment strategies in patients harboring mRCC with sarcomatoid histology to improve oncological outcomes.

Abstract 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.

Introduction and Objectives: Knowledge about the significance of sarcopenia (muscle loss) in prostate cancer (PCa) patients is limited. The aim of this study was to determine the influence of skeletal muscle index (SMI) on early functional and pathological outcome in patients undergoing radical prostatectomy (RP).Materials and Methods: One hundred randomly chosen patients who received RP between November 2016 and April 2017 at Martini-Klinik (Hamburg, Germany) were retrospectively assessed. SMI (skeletal muscle mass cross-sectional area at L3/m2) was measured by preoperative staging computed tomography scans at L3 level. Cox regression analysis was applied to determine the impact of SMI on post-operative outcome. Follow-up was 12 months. Continence was defined as no more than one safety pad per day.Results: Mean age of the cohort was 63.6 years. Mean SMI was 54.06 cm2/m2 (range, 40.65–74.58 cm2/m2). Of the patients, 41.4% had pT2, 28.7% had pT3a, and 29.9% had pT3b or pT4 PCa. SMI revealed to be without significant correlation on tumor stage. Follow-up data of 55 patients were available for early functional outcome analysis. SMI showed no significant influence on erectile function in multivariable Cox regression analysis. In multivariable Cox regression analysis, SMI turned out to have no influence on continence rates 6 weeks after surgery.Conclusion: The present study shows that patients undergoing RP have a wide range of SMI. Unlike in other urological malignancies, there was no significant impact of SMI on early functional outcome and pathological outcome. A larger cohort is needed to confirm these results.

Background: Since January 2018 performance of urethroplasties is done on regular basis at the University Hospital Frankfurt (UKF). We aimed to implement and transfer an institutional standardized perioperative algorithm for urethral surgery (established at the University Hospital Hamburg-Eppendorf—UKE) using a validated Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) in patients undergoing urethroplasty at UKF.Materials and Methods: We retrospectively analyzed all patients who underwent urethroplasty for urethral stricture disease between January 2018 and January 2020 at UKF. All patients were offered to revisit for clinical follow-up (FU) and completion of USS-PROM. Primary end point was stricture recurrence-free survival (RFS). Secondary endpoints were functional outcomes, quality of life (QoL), and patient satisfaction.Results: In total, 50 patients underwent urethroplasty and 74 and 24% had a history of previous urethrotomy or urethroplasty, respectively. A buccal mucosal graft urethroplasty was performed in 86% (n = 43). After patient's exclusion due to lost of FU, FU

Vesico-urethral anastomotic stenosis is a well-known sequela after radical prostatectomy for prostate cancer and has significant impact on quality of life. This review aims to summarize contemporary therapeutical approaches and to give an overview of the available evidence regarding endoscopic interventions and open reconstruction. Initial treatment may include dilation, incision or transurethral resection. In treatment-refractory stenoses, open reconstruction via an abdominal (retropubic), transperineal or combined abdominoperineal approach is a viable option with high success rates. All of the open surgical procedures are generally accompanied by a high risk of developing de novo incontinence and patients may need further interventions. In such cases, subsequent artificial urinary sphincter implantation is the most common treatment option with the best available evidence.

Introduction: To evaluate the impact of reconstructive strategies and post-operative management on short- and long-term surgical outcome and complications of classical bladder exstrophy (CBE) patients' comprehensive data of the multicenter German-wide Network for Congenital Uro-Rectal malformations (CURE-Net) were analyzed.Methods: Descriptive analyses were performed between 34 prospectively collected CBE patients born since 2009, median 3 months old [interquartile range (IQR), 2–4 months], and 113 cross-sectional patients, median 12 years old (IQR, 6–21 years).Results: The majority of included individuals were males (67%). Sixty-eight percent of the prospectively observed and 53% of the cross-sectional patients were reconstructed using a staged approach (p = 0.17). Although prospectively observed patients were operated on at a younger age, the post-operative management did not significantly change in the years before and after 2009. Solely, in prospectively observed patients, peridural catheters were used significantly more often (p = 0.017). Blood transfusions were significantly more frequent in males (p = 0.002). Only half of all CBE individuals underwent inguinal hernia repair. Cross-sectional patients after single-stage reconstructions showed more direct post-operative complications such as upper urinary tract dilatations (p = 0.0021) or urinary tract infections (p = 0.023), but not more frequent renal function impairment compared to patients after the staged approach (p = 0.42). Continence outcomes were not significantly different between the concepts (p = 0.51). Self-reported continence data showed that the majority of the included CBE patients was intermittent or continuous incontinent. Furthermore, subsequent consecutive augmentations and catheterizable stomata did not significantly differ between the two operative approaches. Urinary diversions were only reported after the staged concept.Conclusions: In this German multicenter study, a trend toward the staged concept was observed. While single-stage approaches tended to have initially more complications such as renal dilatation or urinary tract infections, additional surgery such as augmentations and stomata appeared to be similar after staged and single-stage reconstructions in the long term.

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.

Iatrogenic ureteral injuries and strictures are relatively common complication of pelvic surgery and radiation treatment. Left untreated they are associated with severe short- and long-term complications such as urinoma, septic state, renal failure, and loss of a renal unit. Treatment depends on timing of diagnosis, as well as extent of injury, and ranges from simple endoscopic management to complex surgical reconstruction under usage of pedicled grafts. While recent advances in ureteral tissue engineering are promising the topic is still underreported. Historically a domain of open surgery, laparoscopic and robotic-assisted approaches have proven their feasibility in small case series, and are increasingly being utilized as means of reconstructive surgery. This review aims to give an outline of incidence and treatment of ureteral injuries and strictures in light of the latest advances. Keywords: Iatrogenic, Outcomes, Reconstructive surgical procedures, Surgical technique, Surgical management, Trauma, Ureter, Ureteral strictures

(1) Background: The intravesical instillation of interleukin-2 (IL-2) has been shown to be very well tolerated and promising in patients with bladder malignancies. This study aims to confirm the use of a new IL-2 containing immunotherapy candidate as safe for intravesical application. IL-2, produced in mammalian cells, is glycosylated, because of its unique solubility and stability optimized for intravesical use. (2) Materials and Methods: Urothelial cells and fibroblasts were generated out of porcine bladder and cultured until they reached second passage. Afterwards, they were cultivated in renal epithelial medium (REM) and Dulbecco’s modified Eagles medium (DMEM) with the IL-2 candidate (IMS-Research) and three more types of human interleukin-2 immunotherapy products (IMS-Pure, Natural IL-2, Aldesleukin) in four different concentrations (100, 250, 500, 1000 IU/mL). Cell proliferation was analyzed by water soluble tetrazolium (WST) proliferation assay after 0, 3, and 6 days for single cell culture and co-culture. (3) Results: Proliferation assays showed that all IL-2 products induced very similar cultivation results and none of the IL-2 variants had a negative impact on the proliferation of urothelial cells and fibroblast in either concentration. (4) Conclusion: Human recombinant glycosylated IL-2 as well as human non-glycosylated IL-2 have no negative influence on the tissue cell proliferation of porcine urothelial cells and fibroblasts in vitro and represent a promising and innovative potential intravesical therapy candidate for patients in high need.

Pediatric anterior urethral strictures are rare and recommendations regarding treatment strategies derive from small monocentric case series. In 2014, a collaborative effort of the Société Internationale d'Urologie and the International Consultation on Urological Diseases drafted the first systematic and evidence-based guideline for diagnosis and treatment of urethral strictures in children. Against this backdrop, we performed an updated literature review to provide a comprehensive summary of the available evidence and contemporary outcomes with a focus on comparative effectiveness of endoscopic treatment (dilation or urethrotomy) vs. open surgical reconstruction. Overall, 22 articles reporting on children with anterior urethral strictures were included into the review. Most strictures were iatrogenic (48%) and traumatic (34%), whereas congenital (13%), inflammatory (4%), or postinfectious strictures (1%) were rather rare. The cumulative success rate of endoscopic treatment and urethroplasty was 46% (range: 21–75; N = 334) and 84% (range: 25–100; N = 347), respectively. After stratifying patients according to urethroplasty technique, success rates were 82% (range: 25–100; N = 206) for excision and primary anastomosis, 94% (range: 75–100; N = 40) for graft augmentation, 97% (range: 87–100; N = 30) for flap urethroplasty, and 70% (one study; N = 20) for pull-through urethroplasty. In conclusion, endoscopic approaches are rather ineffective in the long-term and open surgical reconstruction via urethroplasty should be preferred to avoid multiple, repetitive interventions. Future research may involve multi-institutional, collaborative, and prospective studies, incorporating well-defined outcome criteria and assessing objective surgical endpoints as well as patient-reported functional outcomes.

ObjectivesThe objective of this study was to compare the recurrence rate and de novo incontinence after endoscopic treatment of vesicourethral stenosis (VUS) after radical prostatectomy (RP) and for bladder neck stenosis (BNS) after transurethral resection of the prostate (TURP).MethodsRetrospective analysis of patients treated endoscopically for VUS after RP or for BNS after TURP at three German tertiary care centers between March 2009 and June 2016. Investigated endpoints were recurrence rate and de novo incontinence. Chi-squared tests and t-tests were used to model the differences between groups.ResultsA total of 147 patients underwent endoscopic therapy for VUS (59.2%) or BNS (40.8%). Mean age was 68.3 years (range 44–86), mean follow-up 27.1 months (1–98). Mean time to recurrence after initial therapy was 23.9 months (1–156), mean time to recurrence after prior endoscopic therapy for VUS or BNS was 12.0 months (1–159). Patients treated for VUS underwent significantly more often radiotherapy prior to endoscopic treatment (33.3 vs. 13.3%; p = 0.006) and the recurrence rate was significantly higher (59.8 vs. 41.7%; p = 0.031). The overall success rate of TUR for VUS was 40.2%, success rate of TUR for BNS was 58.3%. TUR for BNS is significantly more successful (p = 0.031). The mean number of TUR for BNS vs. TUR for VUS in successful cases was 1.5 vs. 1.8, which was not significantly different. The rate of de novo incontinence was significantly higher in patients treated for VUS (13.8 vs. 1.7%; p = 0.011). After excluding those patients with radiotherapy prior to endoscopic treatment, the recurrence rate did not differ significantly between both groups (60.3% for VUS vs. 44.2% for BNS; p = 0.091), whereas the rate of de novo incontinence (13.8 for VUS vs. 0% for BNS; p = 0.005) stayed significantly higher in patients treated for VUS.ConclusionMost patients with BNS are successfully treated endoscopically. In patients with VUS, the success rate is lower. Both stenoses differ with respect to de novo incontinence. Patients must be counseled regarding the increased risk of de novo incontinence after endoscopic treatment of VUS, independent of prior radiotherapy. Longer follow-up is warranted to address long-term outcomes.

Purpose This study evaluates the effectiveness of artificial urinary sphincter (AUS) implantation following transperineal reanastomosis in men with vesicourethral anastomotic stenosis (VUAS) and stress urinary incontinence (SUI) after radical prostatectomy (RP), focusing on long-term explantation rates and urinary continence.Methods Patients treated between 2009 and 2020 were retrospectively analyzed. Those undergoing AUS implantation post-transperineal reanastomosis for recurrent VUAS, excluding cases with prior pelvic irradiation and overactive bladder, were included. Primary outcomes were AUS explantation rates and patient-reported continence. Median follow-up was calculated using reverse Kaplan-Meier estimates, and explantation-free survival illustrated via Kaplan-Meier analyses.Results At final follow-up, 19 patients were included at a median follow-up of 79 months. Explantation occurred in 16% (N = 3) of cases, with a median time to explantation of 107 months. No urethral erosion was observed. Explantation-free survival at 2, 5, and 10 years was 100%, 87%, and 73%, respectively. The median number of pads/day decreased significantly postoperatively, with 78% (N = 14) reporting subjective continence and 89% (N = 16) achieving social continence.Conclusion AUS implantation following transperineal reanastomosis for VUAS post-RP offers favorable long-term outcomes, with low explantation rates and no erosion, making it a viable management strategy.