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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Objective: The objective of this study was to report the 12-month oncological outcomes for patients with non-muscle-invasive bladder cancer (NMIBC) within the prospective, international COVIDSurg Cancer study., Patients and Methods: Eligible patients were aged ≥18 years and scheduled for elective surgical management of NMIBC with curative intent (transurethral resection of bladder tumour [TURBT] or bladder biopsy) from 21 January to 14 April 2020. The primary outcome was disease recurrence within 12 months of previous elective TURBT/bladder biopsy. Secondary outcomes included disease progression within 12 months of previous elective TURBT/bladder biopsy, site-declared delay to surgery from diagnosis as a consequence of COVID-19 and deviation in standard care due to COVID-19. Comparisons were made to cohorts from the pre-pandemic era., Results: Bladder cancer accounted for 2.2% ( n  = 446) of patients in the COVIDSurg Cancer study, with data contributed by 27 centres across 12 countries internationally. Within this included cohort, 229 patients had NMIBC and 12-month follow-up data available. On application of National Institute for Health and Care Excellence (NICE) criteria, 47.2% were classified as having high-risk disease. Overall disease recurrence and progression rates were 29.3% and 9.7% at 12 months, respectively. In purely high-risk pre-pandemic cohorts, the International Bladder Cancer Group (IBCG) estimates a recurrence rate of 25% at 12 months, and the European Association of Urology (EAU) NMIBC 2021 scoring model estimates a 12-month progression rate of 3.5%. As a consequence of the COVID-19 pandemic, 10.9% of patients had site-declared delay to TURBT/bladder biopsy; 7.4% did not undergo intravesical therapy or had early discontinuation of this; 9.2% did not undergo early repeat resection for high-risk disease; and 18.3% had a delay to cystoscopic follow-up surveillance., Conclusions: This prospective study indicates that there were widespread deviations in usual care for NMIBC during the pandemic and that 12-month oncological outcomes appear to be impaired compared to published pre-pandemic outcomes., Competing Interests: All authors declare no conflict of interest., (© 2024 The Author(s). BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

An urgent need for societal transformation exists to reduce the environmental impact of humanity, because environmental health affects human health. Health care causes ~5% of global greenhouse gas emissions and other substantial and ongoing environmental harms. Thus, health-care professionals and managers must lead ongoing efforts to improve the environmental performance of health systems. Life-cycle assessment (LCA) is a methodology that enables estimation of environmental impacts of products and processes. It models environmental effects from 'cradle' (raw material extraction) to 'grave' (end of useful life) and conventionally reports a range of different impact categories. LCA is a valuable tool when used appropriately. Maximizing its utility requires rational assumptions alongside careful consideration of system boundaries and data sources. Well-executed LCAs are detailed and transparently reported, enabling findings to be adapted or generalized to different settings. Attention should be given to modelling mitigation solutions in LCAs. This important step can guide health-care systems towards new and innovative solutions that embed progress towards international climate agreements. Many urological conditions are common, recurrent or chronic, requiring resource-intensive management with large associated environmental impacts. LCAs in urology have predominantly focussed on greenhouse gas emissions and have enabled identification of modifiable 'hotspots' including electricity use, travel, single-use items, irrigation, reprocessing and waste incineration. However, the methodological and reporting quality of published urology LCAs generally requires improvement and standardization. Health-care evaluation and commissioning frameworks that value LCA findings alongside clinical outcomes and cost could accelerate sustainable innovations. Rapid implementation strategies for known environmentally sustainable solutions are also needed., (© 2024. Springer Nature Limited.)

The Getting It Right First Time (GIRFT) programme is a quality improvement initiative covering the National Health Service in England. The programme aims to standardise clinical practices and improve patient and system level outcomes by utilising data-driven insights and clinically-led recommendations. There are GIRFT workstreams for every medical and surgical specialty, including urology. Defining features of the GIRFT methodology are that it is clinically led by experienced clinicians, data-driven, and specialty specific. Each specialty workstream conducts deep-dive visits to every hospital, analysing performance data and engaging with clinicians and management to identify and share improvement priorities. For urology, GIRFT has completed deep-dive visits and published reports outlining priority areas for development. Reports include recommendations pertaining to streamlining care pathways, reducing the acuity of care environments, enhancing emergency services, optimising utilisation of outpatient services, and workforce training and utilisation. The GIRFT academy provides guides for implementing best practices specific to priority areas of care. These include important disease pathways, and GIRFT-advocated innovations such as urology investigation units and urology area networks. GIRFT offers clinical transformation, cost reduction, equity in access to care, and leaner models of care that are often more environmentally sustainable. Evaluation efforts of the programme have focussed on assessing the adoption of GIRFT recommendations, understanding barriers to change, and modelling the climate impact of advocated practices., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background: Magnetic resonance imaging (MRI) of the prostate is a new, more accurate, non-invasive test for prostate cancer diagnosis., Aim: To understand the acceptability of MRI for patients and GPs for prostate cancer diagnosis., Design and Setting: Qualitative study of men who had undergone a prostate MRI for possible prostate cancer, and GPs who had referred at least one man for possible prostate cancer in the previous 12 months in West London and Devon., Method: Semi-structured interviews, conducted in person or via telephone, were audio-recorded and transcribed verbatim. Deductive thematic analysis was undertaken using Sekhon's Theoretical Framework of Acceptability, retrospectively for patients and prospectively for GPs., Results: Twenty-two men (12 from Devon, age range 47-80 years), two patients' partners, and 10 GPs (6 female, age range 36-55 years) were interviewed. Prostate MRI was broadly acceptable for most patient participants, and they reported that it was not a significant undertaking to complete the scan. GPs were more varied in their views on prostate MRI, with a broad spectrum of knowledge and understanding of prostate MRI. Some GPs expressed concerns about additional clinical responsibility and local availability of MRI if direct access to prostate MRI in primary care were to be introduced., Conclusion: Prostate MRI appears to be acceptable to patients. Some differences were found between patients in London and Devon, mainly around burden of testing and opportunity costs. Further exploration of GPs' knowledge and understanding of prostate MRI could inform future initiatives to widen access to diagnostic testing in primary care., (© The Authors.)

Objectives: To describe the contemporary evolution of day-case bladder outflow obstruction (BOO) surgery in England and to profile day-case BOO surgery practices across England in terms of the types of operation performed and their safety profiles., Materials and Methods: This was a retrospective observational analysis of Hospital Episode Statistics and UK Office for National Statistics data. All 111 043 recorded operations across 117 hospital trusts over 66 months, from 1 January 2017 to 30 June 2022, were obtained. Operations were identified as one of: transurethral resection of prostate (TURP); laser ablation or enucleation; vapour therapy; prostatic urethral lift (PUL); or bladder neck incision. Monthly day-case rate trends were plotted across the study period. Descriptive data, day-case rates and 30-day hospital readmissions were analysed for each operation type. Multilevel regression modelling with mixed effects was performed to determine whether day-case surgery was associated with higher 30-day hospital readmissions., Results: Day-case patients were younger, with fewer comorbidities. Time series analysis showed a linear day-case rate increase from 8.3% (January 2017) to 21.0% (June 2022). Day-case rates improved for 92/117 trusts in 2021/2022 compared with 2017. Three of the six trusts with the highest day-case rates performed predominantly day-case TURP, and the other three laser surgery. Nationally, PUL and vapour surgery had the highest day-case rates (80.9% and 38.1%). Most inpatient operations were TURP. Multilevel regression modelling found reduced odds of 30-day readmission after day-case BOO surgery (all operations pooled), no difference for day-case vs inpatient TURP, and reduced odds following day-case LASER operations., Conclusions: The day-case rates for BOO surgery have linearly increased. Minimally invasive surgical technologies are commonly performed as day cases, whereas high day-case rates for TURP and for laser ablation operations are seen in a minority of hospitals. Day-case pathways to treat BOO can be safely developed irrespective of operative modality., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Using devices with microfluidic channels can allow for precise control over liquids flowing through them. Merging flows of immiscible liquids can create emulsions with highly monodispersed microdroplets within a carrier liquid, which are ideal for miniaturised reaction vessels which can be generated with a high throughput of tens of thousands of droplets per second. Control of the size and composition of these droplets is generally performed by controlling the pumping system pushing the liquids into the device; however, this is an indirect manipulation and inadequate if absolute precision is required in the size or composition of the droplets. In this work, we extend the previous development of image-based closed-loop feedback control over microdroplet generation to allow for the control of not only the size of droplets but also the composition by merging two aqueous flows. The feedback allows direct control over the desired parameters of volume and ratio of the two components over a wide range of ratios and outperforms current techniques in terms of monodispersity in volume and composition. This technique is ideal for situations where precise control over droplets is critical, or where a library of droplets of different concentrations but the same volume is required.

Background: Alternative splicing (AS) plays a crucial role in transcriptomic diversity and is a hallmark of cancer that profoundly influences the development and progression of prostate cancer (PCa), a prevalent and potentially life-limiting cancer among men. Accumulating evidence has highlighted the association between AS dysregulation and the onset and progression of PCa. However, a comprehensive and integrative analysis of AS profiles at the event level, utilising data from multiple high-throughput cohorts and evaluating the prognosis of PCa progression, remains lacking and calls for thorough exploration., Results: We identified a differentially expressed retained intron event in ZWINT across three distinct cohorts, encompassing an original array-based dataset profiled by us previously and two RNA sequencing (RNA-seq) datasets. Subsequent in-depth analyses of these RNA-seq datasets revealed  141 altered events, of which 21 demonstrated a significant association with patients' biochemical recurrence-free survival (BCRFS). We formulated an AS event-based prognostic signature, capturing six pivotal events in genes CYP4F12, NFATC4, PIGO, CYP3A5, ALS2CL, and FXYD3. This signature effectively differentiated  high-risk patients diagnosed with PCa, who experienced shorter BCRFS, from their low-risk counterparts. Notably, the signature's predictive power surpassed traditional clinicopathological markers in forecasting 5-year BCRFS, demonstrating robust performance in both internal and external validation sets. Lastly, we constructed a novel nomogram that integrates patients' Gleason scores with pathological tumour stages, demonstrating improved prognostication of BCRFS., Conclusions: Prediction of clinical progression remains elusive in PCa. This research uncovers novel splicing events associated with BCRFS, augmenting existing prognostic tools, thus potentially refining clinical decision-making., (© 2023. The Author(s).)

Introduction: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m 2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both., Methods: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m 2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context., Results: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m 2 ) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m 2 ). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m 2 ), and the proportion of those with stage ≥3 CKD increased from 37% to 51%., Conclusions: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Purpose: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort., Materials and Methods: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival., Results: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage ( P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins ( P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1)., Conclusions: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Droplet microfluidics allows one to address the ever-increasing demand to screen large libraries of biological samples. Absorbance spectroscopy complements the golden standard of fluorescence detection by label free target identification and providing more quantifiable data. However, this is limited by speed and sensitivity. In this paper we increase the speed of sorting by including acoustofluidics, achieving sorting rates of target droplets of 1 kHz. We improved the device design for detection of absorbance using fibre-based interrogation of samples with integrated lenses in the microfluidic PDMS device for focusing and collimation of light. This optical improvement reduces the scattering and refraction artefacts, improving the signal quality and sensitivity. The novel design allows us to overcome limitations based on dielectrophoresis sorting, such as droplet size dependency, material and dielectric properties of samples. Our acoustic activated absorbance sorter removes the need for offset dyes or matching oils and sorts about a magnitude faster than current absorbance sorters.

Background: Patient factors associated with urinary tract cancer can be used to risk stratify patients referred with haematuria, prioritising those with a higher risk of cancer for prompt investigation., Objective: To develop a prediction model for urinary tract cancer in patients referred with haematuria., Design, Setting, and Participants: A prospective observational study was conducted in 10 282 patients from 110 hospitals across 26 countries, aged ≥16 yr and referred to secondary care with haematuria. Patients with a known or previous urological malignancy were excluded., Outcome Measurements and Statistical Analysis: The primary outcomes were the presence or absence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC], and renal cancer). Mixed-effect multivariable logistic regression was performed with site and country as random effects and clinically important patient-level candidate predictors, chosen a priori, as fixed effects. Predictors were selected primarily using clinical reasoning, in addition to backward stepwise selection. Calibration and discrimination were calculated, and bootstrap validation was performed to calculate optimism., Results and Limitations: The unadjusted prevalence was 17.2% (n = 1763) for bladder cancer, 1.20% (n = 123) for UTUC, and 1.00% (n = 103) for renal cancer. The final model included predictors of increased risk (visible haematuria, age, smoking history, male sex, and family history) and reduced risk (previous haematuria investigations, urinary tract infection, dysuria/suprapubic pain, anticoagulation, catheter use, and previous pelvic radiotherapy). The area under the receiver operating characteristic curve of the final model was 0.86 (95% confidence interval 0.85-0.87). The model is limited to patients without previous urological malignancy., Conclusions: This cancer prediction model is the first to consider established and novel urinary tract cancer diagnostic markers. It can be used in secondary care for risk stratifying patients and aid the clinician's decision-making process in prioritising patients for investigation., Patient Summary: We have developed a tool that uses a person's characteristics to determine the risk of cancer if that person develops blood in the urine (haematuria). This can be used to help prioritise patients for further investigation., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis)., Methods: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC., Results: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences., Conclusion: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Prostate cancer (PCa) is the second most common male cancer worldwide, but effective biomarkers for the presence or progression risk of disease are currently elusive. In a series of nine matched histologically confirmed PCa and benign samples, we carried out an integrated transcriptome-wide gene expression analysis, including differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), which identified a set of potential gene markers highly associated with tumour status (malignant vs . benign). We then used these genes to establish a minimal progression-free survival (PFS)-associated gene signature (GS) ( PCBP1 , PABPN1 , PTPRF , DANCR , and MYC ) using least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analyses from The Cancer Genome Atlas prostate adenocarcinoma (TCGA-PRAD) dataset. Our signature was able to predict PFS over 1, 3, and 5 years in TCGA-PRAD dataset, with area under the curve (AUC) of 0.64-0.78, and our signature remained as a prognostic factor independent of age, Gleason score, and pathological T and N stages. A nomogram combining the signature and Gleason score demonstrated improved predictive capability for PFS (AUC: 0.71-0.85) and was superior to the Cambridge Prognostic Group (CPG) model alone and some conventionally used clinicopathological factors in predicting PFS. In conclusion, we have identified and validated a novel five-gene signature and established a nomogram that effectively predicted PFS in patients with PCa. Findings may improve current prognosis tools for PFS and contribute to clinical decision-making in PCa treatment., Competing Interests: LH is founder, director and chief scientific officer of SENISCA Ltd. SENISCA’s commercial activities have no bearing on the content of this publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mou, Spencer, Knight, John, McCullagh, McGrath and Harries.)

Purpose: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery., Methods: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery., Results: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation., Conclusion: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK., Patients and Methods: A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery., Results: There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively., Conclusions: There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved., (© 2021 The Authors BJU International © 2021 BJU International.)

Purpose: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer., Materials and Methods: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated., Results: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08)., Conclusions: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

We demonstrate the use of an acoustic device to actively encapsulate single red blood cells into individual droplets in a T-junction. We compare the active encapsulation with the passive encapsulation depending on the number of loaded cells as well as the created droplet volumes. This method overcomes the Poisson limitation statistical loading of cells for the passive encapsulation. In our experiments we reach a single cell encapsulation efficiency of 97.9 ± 2.1% at droplet formation rates exceeding 15 Hz.

Purpose: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC)., Materials and Methods: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age., Results: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype., Conclusions: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age., (© 2021. The Author(s).)