Prognostic impact of variant histology in bladder cancer: Would early and aggressive treatment shift the paradigm?

INTRODUCTION: Bladder cancer (BC) is an increasingly frequent malignancy worldwide. Several variant histologies (VH) have been described in BC with a distinct clinical behavior. OBJECTIVES: This study aims to assess the prognostic impact of VH in BC, comparing its outcomes to pure urothelial carcinoma PUC in both non-muscle invasive (NMIBC) and muscle-invasive (MIBC) settings. METHODS: We included patients with primary BC, comparing those with VH with those with PUC, with an age and sex-matched proportion of 1:3, considering stage at diagnosis, recurrence-free, progression-free, and overall survival (OS). A total of 616 patients were included in the study, (460 UC and 151 VH). RESULTS: After first TURBT, MIBC was present in 99 (64.1%) of patients with VH, and 95 (20.6%) with UC (p<0.001). Concerning NMIBC, we observed higher rates of progression to MIBC amid patients with VH (p=0.009). Nodal involvement (p=0.020) and metastatic disease (p<0.001) were significantly higher within the VH group. A higher OS was observed among patients with NMIBC of PUC (p<0.001). There were no statistically significant differences of metastasis-free survival and OS between VH and UC groups within the MIBC setting. CONCLUSION: We confirmed that VH presents a more aggressive clinical course compared to PUC. An earlier radical treatment within the NMIBC setting could increase the oncological outcomes of the VH patients.

Self-reported urinary incontinence in women is higher with increased age, lower educational level, lower income, number of comorbidities, and impairment of mental health. Results of a large, population-based, national survey in Portugal.

PURPOSE: Urinary incontinence (UI) is a common condition in women. The aim of this study is to analyze women with self-reported UI, focusing on socio-demographic data, health-related conditions and comorbidities, and their impact on healthcare resources. METHODS: We analyzed data from a population-based survey with a representative sample of Portuguese women aged ≥ 18 years (n = 10,465). Women with self-reported symptoms of UI were distributed according to age, education level, and household income. The comparison of comorbidities and use of healthcare resources between the UI and non-UI groups was adjusted for age, education, and body mass index. We computed weighted prevalence and adjusted prevalence ratios with 95% confidence intervals using Poisson regression. RESULTS: Female UI prevalence was 9.9%, increasing with age (6.3% for 18- to 39-year-old, 40.8% for 75- to 85-year-old women). The prevalence decreased with education level (36.8% in women with no education, 4.6% in women with more than 12 years of education) and household income (29.8% in the 2nd quintile of income, 9.9% in the 5th quintile). Women with UI had a higher level of comorbidities, especially cardiovascular, respiratory, and mental health disorders. UI was also associated with higher consumption of healthcare resources. CONCLUSION: UI is highly prevalent among Portuguese women. It increases with age, low education level, and low household income. The use of healthcare resources was higher, possibly related with associated comorbidities. Though obtained in a single European country, these data may be useful to design a comprehensive management of UI in other parts of the western world.

European Association of Urology Guidelines on the Management of Female Non-neurogenic Lower Urinary Tract Symptoms. Part 2: Underactive Bladder, Bladder Outlet Obstruction, and Nocturia.

CONTEXT: Female lower urinary tract symptoms (LUTS) are a common presentation in urological practice. Thus far, only a limited number of female LUTS conditions have been included in the European Association of Urology (EAU) guidelines compendium. The new non-neurogenic female LUTS guidelines expand the remit to include these symptoms and conditions. OBJECTIVE: To summarise the management of underactive bladder (UAB), bladder outlet obstruction (BOO), and nocturia in females. EVIDENCE ACQUISITION: The literature search was updated in September 2021 and evidence synthesis was conducted using modified GRADE approach as outlined for all EAU guidelines. A new systematic review on BOO was carried out by the panel for purposes of this guideline. EVIDENCE SYNTHESIS: The important considerations for informing guideline recommendations are presented, along with a summary of all the guideline recommendations. CONCLUSIONS: Non-neurogenic female LUTS are an important presentation of urological dysfunction. Initial evaluation, diagnosis, and management should be carried out in a structured and logical fashion on the basis of the best available evidence. This guideline serves to present this evidence to practising urologists and other health care providers in an easily accessible and digestible format. PATIENT SUMMARY: This report summarises the main recommendations from the European Association of Urology guideline on symptoms and diseases of the female lower urinary tract (bladder and urethra) not associated with neurological disease. We cover recommendations related to the treatment of underactive bladder, obstruction of the bladder outlet, and nighttime urination.

European Association of Urology Guidelines on the Diagnosis and Management of Female Non-neurogenic Lower Urinary Tract Symptoms. Part 1: Diagnostics, Overactive Bladder, Stress Urinary Incontinence, and Mixed Urinary Incontinence.

CONTEXT: Female lower urinary tract symptoms (LUTS) are a common presentation in urological practice. Thus far, only a limited number of female LUTS conditions have been included in the European Association of Urology (EAU) guidelines compendium. The new non-neurogenic female LUTS guideline expands the remit to include these symptoms and conditions. OBJECTIVE: To summarise the diagnostic section of the non-neurogenic female LUTS guideline and the management of female overactive bladder (OAB), stress urinary incontinence (SUI), and mixed urinary incontinence (MUI). EVIDENCE ACQUISITION: New literature searches were carried out in September 2021 and evidence synthesis was conducted using the modified GRADE criteria as outlined for all EAU guidelines. A new systematic review (SR) on OAB was carried out by the panel for the purposes of this guideline. EVIDENCE SYNTHESIS: The important considerations for informing guideline recommendations are presented, along with a summary of all the guideline recommendations. CONCLUSIONS: Non-neurogenic female LUTS are an important cause of urological dysfunction. Initial evaluation, diagnosis, and management should be carried out in a structured and logical fashion based on the best available evidence. This guideline serves to present this evidence to health care providers in an easily accessible and digestible format. PATIENT SUMMARY: This report summarises the main recommendations from the European Association of Urology guideline on symptoms and diseases of the female lower urinary tract (bladder and urethra) not associated with neurological disease. We cover recommendations related to diagnosis of these conditions, as well as the treatment of overactive bladder, stress urinary incontinence, and mixed urinary incontinence.

Benefits and Harms of Conservative, Pharmacological, and Surgical Management Options for Women with Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel.

CONTEXT: While the management of bladder outlet obstruction (BOO) in men has been a topic of several systematic reviews and meta-analyses, no such evidence base exists for female BOO. OBJECTIVE: The aim of this systematic review was to evaluate the benefits and harms of therapeutic interventions for the management of BOO in women. EVIDENCE ACQUISITION: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. The study protocol was registered with PROSPERO (CRD42020183839). A systematic literature search was performed and updated by a research librarian in May 2021. The study population consisted of adult female patients diagnosed with BOO, who underwent treatment. EVIDENCE SYNTHESIS: Out of 6344 records, we identified 33 studies enrolling 1222 participants, of which only six randomized controlled trials (RCTs) were found. One placebo-controlled crossover randomized trial assessed the role of baclofen in 60 female patients with dysfunctional voiding. The trial met its primary endpoint with a significantly greater decrease in the number of voids per day in the baclofen group (-5.53 vs -2.70; p = 0.001). The adverse events were mild and comparable in both groups (25% vs 20%). One placebo-controlled crossover randomized trial assessed the role of sildenafil in 20 women with Fowler's syndrome. There were significant improvements from baseline in maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual (PVR), but with no statistically significant difference when compared with placebo. In a large RCT including 197 female patients with functional BOO, the alpha-blocker alfuzosin significantly improved IPSS, Qmax, and PVR compared with baseline, but the differences were not statistically significant compared with the placebo group. Several small single-arm prospective series reported improvement of BOO-related symptoms and voiding parameters with urethroplasty, sling revision, urethral dilation, vaginal pessary, and pelvic organ prolapse repair. CONCLUSIONS: Evidence to support the use of conservative, pharmacological, and surgical treatments for BOO is scarce. PATIENT SUMMARY: According to the present systematic review of the literature, evidence to support the use of conservative, pharmacological, and surgical treatments for either anatomical or functional bladder outlet obstruction is scarce.

Diagnostic Tests for Female Bladder Outlet Obstruction: A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel.

CONTEXT: Female bladder outlet obstruction (fBOO) is a relatively uncommon condition compared with its male counterpart. Several criteria have been proposed to define fBOO, but the comparative diagnostic accuracy of these remains uncertain. OBJECTIVE: To identify and compare different tests to diagnose fBOO through a systematic review process. EVIDENCE ACQUISITION: A systematic review of the literature was performed according to the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. The EMBASE/MEDLINE/Cochrane databases were searched up to August 4, 2020. Studies on women ≥18 yr of age with suspected bladder outlet obstruction (BOO) involving diagnostic tests were included. Pressure-flow studies or fluoroscopy was used as the reference standard where possible. Two reviewers independently screened all articles, searched reference lists of retrieved articles, and performed data extraction. The risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). EVIDENCE SYNTHESIS: Overall, 28 nonrandomised studies involving 10 248 patients were included in the qualitative analysis. There was significant heterogeneity regarding the characteristics of women included in BOO cohorts (ie, mixed cohorts including both anatomical and functional BOO). Pressure-flow studies ± fluoroscopy was evaluated in 25 studies. Transperineal Doppler ultrasound was used to evaluate bladder neck dynamics in two studies. One study tested the efficacy of transvaginal ultrasound. The urodynamic definition of fBOO also varied amongst studies with different parameters and thresholds used, which precluded a meta-analysis. Three studies derived nomograms using the maximum flow rate (Qmax) and voiding detrusor pressure at Qmax. The sensitivity, specificity, and overall accuracy ranges were 54.6-92.5%, 64.6-93.9%, and 64.1-92.2%, respectively. CONCLUSIONS: The available evidence on diagnostic tests for fBOO is limited and heterogeneous. Pressure-flow studies ± fluoroscopy remains the current standard for diagnosing fBOO. PATIENT SUMMARY: Evidence on tests used to diagnose female bladder outlet obstruction was reviewed. The most common test used was pressure-flow studies ± fluoroscopy, which remains the current standard for diagnosing bladder outlet obstruction in women. TAKE HOME MESSAGE: The available evidence on diagnostic tests for female bladder outlet obstruction is limited and heterogeneous. The most common test used was video-urodynamics, which remains the current standard for diagnosing bladder outlet obstruction in women.

Can serum endoglin be used to improve the diagnostic performance in prostate cancer?

PURPOSE: New biomarkers may contribute to avoid unnecessary biopsies resulting from the suboptimal performance of prostate-specific antigen (PSA) testing. This study aimed to assess serum endoglin as a prostate cancer (PCa) diagnostic tool among biopsy candidates. METHODS: A total of 262 consecutive patients referred for prostate biopsy based on abnormal digital rectal examination and/or elevated total PSA (tPSA) who had serum endoglin assessed by solid-phase enzyme-linked immunosorbent assay were selected. Receiver operating characteristic curves were used to compare the predictive accuracy of different combinations of biomarkers to distinguish between PCa and benign prostatic conditions, and to identify cut-offs that maximize the ability of endoglin to rule out patients for biopsy (highest sensitivities). RESULTS: Serum endoglin levels were higher in patients with PCa (median: 7.86 vs. 5.88 pg/mL, P < 0.001). Among patients with baseline tPSA ≤ 10 ng/mL the area under the curve was 0.69 for endoglin. Approximately one-quarter of the patients had serum endoglin < 4.92 ng/mL (sensitivity: 90.3%; specificity: 32.8%), and the probability of PCa varied from 37.7% before testing to 15.2% among those with low endoglin levels [negative predictive value (NPV) = 84.8%]. When restricting the analyses to patients with free/total PSA ratio > 0.25, the probability of cancer was less than 5% among those with serum endoglin < 6.04 ng/mL (sensitivity: 93.8%; specificity: 56.1%), corresponding to a NPV of 95.8%; this could allow sparing approximately 40% of patients from biopsy. CONCLUSIONS: Serum endoglin may be useful in clinical practice to distinguish between PCa and non-cancer patients among prostatic biopsy candidates.

Kidney transplantation from donation after circulatory death using abdominal normothermic oxygenated circulation: are the outcomes equivalent?

PURPOSE: To increase the pool of kidneys available for transplantation, a renewed interest in donation after circulatory death (DCD) has emerged. This study aims to determine the outcomes of kidney transplantation from DCD after abdominal normothermic oxygenated circulation (ANOR) support. METHODS: From January 2016 to December 2018, 58 kidneys were implanted from uncontrolled DCD after ANOR support. We performed an observational prospective study, assessing graft function and cumulative incidence of surgical complications. A descriptive analysis was conducted. Potential determinants of the outcomes were evaluated, including donor and receptor gender and age, and warm and cold ischemia times. Regression coefficients (ß) and odds ratio (OR) were calculated with 95% confidence intervals. A p-value < 0.05 was considered statistically significant. Statistical analysis was accomplished using Stata 11.0 software. RESULTS: The median follow-up time was 31.2 months. Delayed graft function (DGF) was evident in 80%, with a mean Cr one month after transplantation of 1.81 mg/dL and 1.33 mg/dL after one year. Primary non-function (PNF) occurred in 5.2% of cases. Male donors were associated with a lower DGF (OR = 0.21, p < 0.05), and a higher donor age was a predictor of poorer graft function at one year (ß = - 0.88, p < 0.05). Surgical complications occurred in 31% patients, predominantly vascular. Warm ischemia time superior to 60 min correlated with a higher risk of surgical complications (OR = 11.33, p < 0.05). CONCLUSION: Kidney transplantation from DCD is a valuable option, allowing an improvement in the balance between patients waiting for a transplant and the available kidneys.

Mini-Slings: Do They Stand the Test of Time? A 10-Year Cohort.

INTRODUCTION: It is known that failures after midurethral slings increase with the follow-up time. Nevertheless, data concerning mini-slings are sparse. To clarify this statement, we analyze a mini-sling cohort with a median follow-up of 10 years. Although the brand used, MiniArc®, is no longer available, an identical device, Solyx™, can still be used, which makes the analysis of the cohort clinically relevant. MATERIAL AND METHODS: A total of 172 women with predominant stress urinary incontinence (SUI) were consecutively treated with the mini-sling MiniArc® from 2006 until 2013. They were reevaluated in 2018. The primary outcome, treatment success, was defined as no self-reported SUI symptoms and no reintervention. Secondary outcomes included the response to patient-reported outcomes. Adverse events were assessed. RESULTS: After a median follow-up time of 113 months, 115 (66.9%) women were available for reevaluation. Forty-four (38.3%) women self-reported SUI. Seventeen women had been reoperated, 14 (12.2%) due to the reappearance of SUI and 3 due to complications. Altogether, MiniArc® had an overall success rate of 47.0% at 10 years. Among those not reoperated, 63.3% stated that they were much better or very much better in Patient Global Impression of Improvement (PGI-I) and 71.4% affirmed that their continence problem was normal or mild in Patient Global Impression of Severity (PGI-S). Almost 85% would repeat the surgery. Reoperation due to complications was rare (2.6%). De novo urgency appeared in 30.6% of the patients and it was managed with anticholinergic drugs with favorable outcomes. DISCUSSION/CONCLUSION: This report adds evidence to the long-term outcomes of mini-slings, confirming that they can cure or improve SUI and give patients high satisfaction rates, at the expense of low morbidity.

Renal Cell Carcinoma with Venous Thrombus: Should Surgery Be Offered When Metastasis Is Present at Diagnosis?

INTRODUCTION: Renal cell carcinoma (RCC) reveals a tendency towards venous invasion in its advanced stages, making clinical management challenging. Survival may be improved following surgery, but is less clear if it applies to patients with metastatic disease at diagnosis. MATERIALS AND METHODS: Review of clinical files of patients submitted to surgery for RCC at our institution. RESULTS: Twenty-one patients underwent radical nephrectomy and thrombectomy from 2000 to 2017, with a median follow-up of 25 months. Eighteen (85.7%) men and 3 (14.3%) women, with median age of 63 at the time of diagnosis, were included. The thrombus was in the renal vein in 10 (47.6%) patients and had extension to inferior vena cava (IVC) in 11 (52.4%). The level of involvement in IVC was grade II in 4 (19%) cases, grade III in 4 (19%) cases and grade IV in 3 (14.4%) cases. Surgery was successful in all but 1 patient. Ten patients died during the follow-up (47.6%), resulting in a 5-year overall survival of 34.8%. When considering the metastatic population at diagnosis, the overall survival at 5 years was 45.7%. CONCLUSION: Radical nephrectomy with removal of the venous thrombus remains the preferential treatment for patients with RCC with venous thrombus, even if they have metastatic disease at diagnosis.

Adjustable Transobturator Male System after Failed Surgical Devices for Male Stress Urinary Incontinence: A Feasibility Study.

OBJECTIVES: Feasibility study to evaluate the efficacy and safety of Adjustable Transobturator Male System (ATOMS) after failed surgical devices for male stress urinary incontinence (SUI). MATERIALS AND METHODS: Thirty patients were implanted with ATOMS after they were implanted with surgical device/s previously. SUI severity was evaluated as dryness (0-1 pad/day), mild (2 pads/day), moderate (3-5 pads/day), or severe (≥6 pads/day). Change in pad-test and pad-count after adjustment, operative parameters, patient satisfaction, and number and grade of complications were investigated. RESULTS: Previous failed treatment methods were artificial urinary sphincter (AUS; n = 19), Advance (n = 10), and Virtue (n = 1). Six cases had multiple previous treatments. Preoperative SUI was mild 6 (20%), moderate 11 (36.7%), and severe 13 (43.3%). Median pad-test decreased from 435 mL baseline to 10 mL after adjustment and pad-count from 4 to 0. Dry-rate was 76.7 and 83.3% declared satisfied. Postoperative SUI distribution was mild in 3 (10%) and moderate in 4 (13.3%). No patient had urinary retention after catheter removal. Complications presented in 4 (13.3%; 3 grade-I, 1 grade-II). After a median of 24 months follow-up, no system experienced infection or urethral erosion and 1 (3.3%) was removed for inefficacy. CONCLUSION: Based on short-term efficacy and patient satisfaction, ATOMS can be a realistic alternative for male SUI after other failed systems, including AUS. The absence of urethral erosion and limited infective problems makes this alternative attractive for cases with previous failed treatments.

Treatment of male stress urinary incontinence with the adjustable transobturator male system: Outcomes of a multi-center Iberian study.

AIM: To evaluate effectiveness and safety of the adjustable transobturator male system (ATOMS) for male stress urinary incontinence (SUI). MATERIAL AND METHODS: A retrospective multicenter study was conducted in nine Iberian institutions using a board-approved database for 215 patients intervened between 2012 and 2017, with no case excluded. Continence status, patient satisfaction, number, and grade of complications (Clavien-Dindo) and factors affecting dry rate at adjustment were evaluated. Multivariate analysis defined the population at best success rate. Incontinence recurrence due to device failure and/or explant was evaluated and Kaplan-Meier curve for durability performed. RESULTS: Adjustment was achieved at a mean 1.4 ± 1.9 fillings. Dry-rate after adjustment was 80.5% (96.2% mild and 75.3% moderate-severe), 121 (56.3%) used no pads, and 52 (24.2%) a security pad with urine loss under 10 mL. Mean basal daily pad-test and pad-count decreased from 484 ± 372.3 mL and 3.9 ± 2 pads to 63.5 ± 201.2 mL and 0.9 ± 1.5pads (both P < 0.0001). Satisfaction rate was 85.1% (94.3% mild and 82.1% moderate-severe). Factors associated to dryness were: lesser severity of SUI (P < .0001), absence of radiotherapy (P = 0.0002) and device generation (P = 0.05). Multivariate analysis revealed absence of radiation (OR = 3.12; 1.36-7.19), mild (OR = 19.61; 3.95-100), and moderate (OR = 2.48; 1.1-5.59) SUI were independent predictors. Complications presented in 33(15.35%); 66.7% grade 1, 9.1% grade 2, and 24.2% grade 3. At 24.3 ± 15 mo mean follow-up device was explanted in seven (3.25%) and SUI worsened after adjustment in nine (4.2%). Dry-rate at follow-up was 73% and durability of device in dry patients at adjustment was 89.8% (82.9-94) at 2-years. CONCLUSIONS: This study confirms ATOMS device is safe and achieves high treatment efficacy and patient satisfaction in a multicenter setting. Significantly better results are achieved in less severe and non-irradiated cases. Durability of the device is reassuring in the short-term.