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ObjectiveWe conducted a systematic review and meta-analysis to assess the available literature regarding the surgical and oncologic outcomes of patients undergoing salvage radical cystectomy (SV-RC) for recurrence or failure of bladder sparing therapy (BST) for muscle-invasive bladder cancer (MIBC).MethodsWe searched MEDLINE (PubMed), EMBASE and Google Scholar databases in May 2020. We included all studies of patients with ≥ cT2N0/xM0 bladder cancer that were eligible for all treatment modalities at the time of treatment decision who underwent BST including radiotherapy (RTX). A meta-analysis was conducted to calculate the pooled rate of several variables associated with an increased need for SV-RC. Study quality and risk of bias were assessed using MINORS criteria.Results73 studies comprising 9110 patients were eligible for the meta-analysis. Weighted mean follow-up time was 61.1 months (range 12–144). The pooled rate of non-response to BST and local recurrence after BST, the two primary reasons for SV-RC, was 15.5% and 28.7%, respectively. The pooled rate of SV-RC was 19.2% for studies with a follow-up longer than 5 years. Only three studies provided a thorough report of complication rates after SV-RC. The overall complication rate ranged between 67 and 72% with a 30-day mortality rate of 0–8.8%. The pooled rates of 5 and 10-year disease-free survival after SV-RC were 54.3% and 45.6%, respectively.ConclusionApproximately one-fifth of patients treated with BST with a curative intent eventually require SV-RC. This procedure carries a proportionally high rate of complications and is usually accompanied by an incontinent urinary diversion.

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.

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.

Complete expression loss of S-methyl-5′-thioadenosine phosphorylase ( MTAP ) is caused by homozygous 9p21 deletion and results in a critical vulnerability of cancer cells towards drugs targeting multiple different pathways. MTAP deficiency is common in urothelial cancer, but data on its intratumoral heterogeneity—a potential obstacle for targeted therapies—are lacking. To study the heterogeneity of MTAP expression loss and 9p21 deletions in advanced primary urothelial cancers of the urinary bladder, a tissue microarray (TMA) composed of five different tissue spots from different tissue blocks of 105 pT2-4 urothelial carcinomas was analyzed by immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH). In addition, all tumor containing blocks (1–15, average 6.4) from 41 consecutive pT2-4 carcinomas were analyzed by IHC. Complete absence of MTAP staining (MTAP deficiency) was seen in 34.2% of 385 interpretable TMA samples. All 80 samples with a complete MTAP expression loss and FISH data had a homozygous 9p21 deletion while there were no cases with homozygous deletions within 178 samples with retained MTAP expression (100% FISH/IHC concordance). On a patient level, there was a homogeneous MTAP deficiency in 33%, a heterogeneous MTAP deficiency in 1%, and a retained MTAP expression in 66% of the 98 tumors with at least three interpretable TMA samples. Among 41 consecutive pT2-4 carcinomas from which 1–15 (average 6.4) whole sections were analyzed, MTAP was homogeneously deficient in 34.1%, heterogeneously deficient in 4.9% and homogeneously retained in 61.0%. MTAP deficiency is mostly homogeneous in advanced urothelial carcinoma. MTAP IHC is a near perfect surrogate for the detection of homozygous 9p21 ( MTAP ) deletions. Drugs targeting MTAP deficiency could be highly useful in a relevant subset of invasive urothelial bladder cancers.

ObjectivesTo evaluate objective treatment success and subjective patient-reported outcomes in patients with radiation-induced urethral strictures undergoing single-stage urethroplasty.Patients and methodsMonocentric study of patients who underwent single-stage ventral onlay buccal mucosal graft urethroplasty for a radiation-induced stricture between January 2009 and December 2016. Patients were characterized by descriptive analyses. Kaplan–Meier estimates were employed to plot recurrence-free survival. Recurrence was defined as any subsequent urethral instrumentation (dilation, urethrotomy, urethroplasty). Patient-reported functional outcomes were evaluated using the validated German extension of the Urethral Stricture Surgery Patient-Reported Outcome Measure (USS PROM).ResultsOverall, 47 patients were available for final analyses. Median age was 70 (IQR 65–74). Except for two, all patients had undergone pelvic radiation therapy for prostate cancer. Predominant modality was external beam radiation therapy in 70% of patients. Stricture recurrence rate was 33% at a median follow-up of 44 months (IQR 28–68). In 37 patients with available USS PROM data, mean six-item LUTS score was 7.2 (SD 4.3). Mean ICIQ sum score was 9.8 (SD 5.4). Overall, 53% of patients reported daily leaking and of all, 26% patients underwent subsequent artificial urinary sphincter implantation. Mean IIEF-EF score was 4.4 (SD 7.1), indicating severe erectile dysfunction. In 38 patients with data regarding the generic health status and treatment satisfaction, mean EQ-5D index score and EQ VAS score was 0.91 (SD 0.15) and 65 (SD 21), respectively. Overall, 71% of patients were satisfied with the outcome.ConclusionThe success rate and functional outcome after BMGU for radiation-induced strictures were reasonable. However, compared to existing long-term data on non-irradiated patients, the outcome is impaired and patients should be counseled accordingly.

PurposeTo determine whether salvage artificial urinary sphincter (AUS) implantation after prior incontinence surgery achieves outcomes comparable to primary AUS implantation.MethodsWe retrospectively evaluated data of patients undergoing AUS implantation from 2009 to 2014. Functional outcome was objectified by 1-h stress pad test, uroflowmetry, post-void residual urine measurement, clinical examination, and chart review. Complications were categorized according to Clavien–Dindo classification system. Kaplan–Meier analysis determined explantation-free survival.ResultsA total of 235 patients were included of whom 165 (70.2%) underwent primary AUS. In 70 patients, salvage incontinence surgery was performed, with 24 (10.2%) patients undergoing AUS reimplantation after prior AUS surgery (repeat AUS) and 46 (19.6%) patients undergoing AUS surgery after any other type of incontinence surgery (secondary AUS). There were no significant differences in rates of continence among primary AUS and repeat AUS patients. Patients undergoing secondary AUS had significantly better continence rates than primary and repeat AUS patients. Three-year explantation-free survival rates after AUS insertion were 82.3% (primary AUS), 78.6% (repeat AUS) and 81.5% (secondary AUS). There were no differences in complication rates among the groups.ConclusionAUS is a safe option in the treatment of severe incontinence even after prior AUS or any other prior incontinence surgery and can still achieve satisfactory outcomes as salvage treatment.

PurposeTo prospectively investigate early and consecutive changes of lower urinary tract symptoms (LUTS), specifically storage symptoms after holmium laser enucleation of the prostate (HoLEP).MethodsPatients referred for HoLEP completed the International Prostatic Symptom Score (IPSS) the day before, at discharge, and 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, and 52 weeks after HoLEP. Total IPSS was stratified into mild (score 0–7), moderate (8–19), and severe (20–35) LUTS. Storage symptoms were sub-stratified into storage “negative” and “positive”. IPSS changes served as the main postoperative outcome. Mixed linear models identified risk factors affecting postoperative recovery of LUTS.ResultsBetween December 2010 and 2012, 144 consecutive HoLEP patients were prospectively included in the study. Preoperatively 57.6% of the cohort reported severe storage symptoms (mean total IPSS: 22.6 ± 5.0). Total IPSS decreased significantly immediately after surgery (p < 0.001). Patients with severe LUTS, storage-positive sub-score, and high maximum urinary flow rate were affected by a rebound of mainly storage symptoms 6–8 weeks after HoLEP and prolonged recovery from LUTS. Of these, about 7.4% presented persisting urge complaints. Finally, 12 weeks following HoLEP, the vast majority of patients were symptom-free. Limitations of this study include missing urodynamic workup and a comparative patient cohort.ConclusionImmediately after HoLEP, patients experience a significant decrease of LUTS. Continuous symptom recovery seems to be hampered in patients with severe and storage-positive baseline symptoms. (De-novo) storage symptoms slightly affect postoperative recovery. Quality of life is restored to a stable and significantly improved status 3 months after surgery.

Background Loss of chromosome Y (LOY) has recently been proposed to be associated with cancer aggressiveness, altered T-cell function, and poor prognosis in bladder carcinomas. Methods Chromosome Y was analyzed using fluorescence in-situ hybridization on a tissue microarray containing 2,071 urothelial carcinomas of the urinary bladder from male patients, including 487 patients who had undergone cystectomy for muscle-invasive disease and for whom follow-up data were available. Data on tumor microenvironment were obtained from a previous study. Results LOY was found in 26.0% of 1,704 analyzable cancers. In non-invasive cancers, LOY frequency was comparable in pTa G2 (22.8%) and pTa G3 (24.1%, p  = 0.8036) carcinomas and slightly increased from pTa to pT2 - 4 carcinomas (23.1% for pTa and 27.2% for pT2 - 4) but these differences were not significant ( p = 0.0794). In muscle-invasive cancers, LOY frequency slightly increased from pT2 (25.5%) to pT4 cancers (33.0%), but this association was not significant ( p = 0.1814). Among pT2 - 4 cancers, LOY was associated with venous invasion ( p = 0.0010) but unrelated to pT, pN, and L-status, as well as to overall, recurrence-free, and cancer-specific survival. Muscle-invasive urothelial carcinomas with and without LOY did not show significant differences in the number of CD8 positive lymphocytes, fraction of CD8 positive intraepithelial lymphocytes, number of macrophages and dendritic cells, and fraction of T helper and T regulatory cells. Conclusion The lack of a clear association of LOY with histopathological parameters of cancer aggressiveness, patient prognosis, and parameters describing the tumor microenvironment strongly argues against the driving role of LOY in bladder cancer progression and cancer-associated immune reactions.