The clonal relation of primary upper urinary tract urothelial carcinoma and paired urothelial carcinoma of the bladder

The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities

Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone

Treatment success for overactive bladder with urinary urge incontinence refractory to oral antimuscarinics: a review of published evidence

<p>Abstract</p> <p>Background</p> <p>Treatment options for overactive bladder (OAB) with urinary urge incontinence (UUI) refractory to oral antimuscarinics include: botulinum toxin type A (BoNTA), sacral neuromodulation (SNM), and augmentation cystoplasty (AC). A standard treatment success metric that can be used in both clinical and economic evaluations of the above interventions has not emerged. Our objective was to conduct a literature review and synthesis of published measures of treatment success for OAB with UUI interventions and to identify a treatment success outcome.</p> <p>Methods</p> <p>We performed a literature review of primary studies that used a definition of treatment success in the OAB with UUI population receiving BoNTA, SNM, or AC. The recommended success outcome was compared to generic and disease-specific health-related quality-of-life (HRQoL) measures using data from a BoNTA treatment study of neurogenic incontinent patients.</p> <p>Results</p> <p>Across all interventions, success outcomes included: complete continence (n = 23, 44%), ≥ 50% improvement in incontinence episodes (n = 16, 31%), and subjective improvement (n = 13, 25%). We recommend the OAB with UUI treatment success outcome of ≥ 50% improvement in incontinence episodes from baseline. Using data from a neurogenic BoNTA treatment study, the average change in the Incontinence Quality of Life questionnaire was 8.8 (95% CI: -4.7, 22.3) higher for those that succeeded (N = 25) versus those that failed (N = 26). The average change in the SF-6D preference score was 0.07 (95% CI: 0.02, 0.12) higher for those that succeeded versus those that failed.</p> <p>Conclusion</p> <p>A treatment success definition that encompasses the many components of underlying OAB with UUI symptoms is currently not practical as a consequence of difficulties in measuring urgency. The treatment success outcome of ≥ 50% improvement in incontinence episodes was associated with a clinically meaningful improvement in disease-specific HRQoL for those with neurogenic OAB with UUI. The recommended success definition is less restrictive than a measure such as complete continence but includes patients who are satisfied with treatment and experience meaningful improvement in symptoms. A standardized measure of treatment success will be useful in clinical and health economic applications.</p

Samen voor God afscheid vieren. Vrijwilligers binnen de uitvaartliturgie.

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'Een vrijwilliger kan meer aandacht geven'. Een model voor vrijwilligers bij uitvaartliturgie.

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Voedsel versus Groen? Overzichtsstudie Bedrijvigheid in de groene ruimte

Achtereenvolgens komen aan bod: 1) verleden en heden (opkomst van nieuwe functies in het landelijk gebied; niet-agrarische bedrijvigheid); 2) analyse van oorzaken (de veranderende rol van de overheid; economische krachten in de toekomst); 3) vooruitblik (schaalvergroting en sanering; verbreding van functies

Voedsel versus Groen? Overzichtsstudie Bedrijvigheid in de groene ruimte

Achtereenvolgens komen aan bod: 1) verleden en heden (opkomst van nieuwe functies in het landelijk gebied; niet-agrarische bedrijvigheid); 2) analyse van oorzaken (de veranderende rol van de overheid; economische krachten in de toekomst); 3) vooruitblik (schaalvergroting en sanering; verbreding van functies

Accelerated ageing protocols for (polymer modified) PA to obtain representative (rheological) properties, mimicking field aged materials

In this work ageing protocols for asphalt and mastics were developed and investigated; i.e representation of the field ageing and their acceleration degree. Here it was aimed to age laboratory prepared specimen analogous to naturally aged materials in the field and compare their material properties. Such simulation of ageing is of importance in order to potentially specify and objectively assess the properties of (novel) binders and asphaltic materials for Porous Aaphalt (PA). Hence, two ageing protocols were developed and investigated; one ageing protocol for asphalt mixtures and one for asphalt mastics. The rheological (DSR) properties of binders from the laboratory aged materials have been evaluated in comparison to binders from field aged specimen