Comparison and combination of mutation and methylation-based urine tests for bladder cancer detection.

Background And Aims: Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection.

Image directed redesign of bladder cancer treatment pathways: the BladderPath RCT.

Background: Transurethral resection of bladder tumour has been the mainstay of bladder cancer staging for > 60 years. Staging inaccuracies are commonplace, leading to delayed treatment of muscle-invasive bladder cancer. Multiparametric magnetic resonance imaging offers rapid, accurate and non-invasive staging of muscle-invasive bladder cancer, potentially reducing delays to radical treatment.

Long-term Monitoring of Oxygen Consumption Rates in Highly Differentiated and Polarized Retinal Pigment Epithelial Cultures.

Mitochondrial metabolism is critical for the normal function of the retinal pigment epithelium (RPE), a monolayer of cells in the retina important for photoreceptor survival. RPE mitochondrial dysfunction is a hallmark of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the developed world, and proliferative vitreoretinopathy (PVR), a blinding complication of retinal detachments. RPE degenerative conditions have been well-modeled by RPE culture systems that are highly differentiated and polarized to mimic in vivo RPE.

Low-grade Urothelial Carcinoma Recurs at a Tempo that Naturally Accelerates Over Time.

Objective: To investigate the cadence of recurrence in patients with low grade intermediate-risk non-muscle invasive bladder cancer (LG IR-NMIBC) based on clinical determinants. We aim to describe patterns in rates of recurrence to better inform surveillance regimens for this chronic, burdensome, and costly disease.

Methods: Using baseline and follow-up data from participants in the West Midlands' (United Kingdom, UK) Bladder Cancer Prognosis Programme (BCPP), we assessed overall recurrence rate and recurrence-free intervals throughout the follow-up period for IR-NMIBC participants.

Improved Disease-Free Survival With Adjuvant Chemotherapy After Nephroureterectomy for Upper Tract Urothelial Cancer: Final Results of the POUT Trial.

JCO POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node-positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature.

Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.

Purpose: Retinal pigment epithelium (RPE) oxidative metabolism is critical for normal retinal function and is often studied in cell culture systems. Here, we show that conventional culture media volumes dramatically impact O2 availability, limiting oxidative metabolism. We suggest optimal conditions to ensure cultured RPE is in a normoxic environment permissive to oxidative metabolism.

Selenium and Vitamin E for Prevention of Non-Muscle-Invasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial.

Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer.

Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC.

Design, Setting, And Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK.

The sex gap in bladder cancer survival - a missing link in bladder cancer care?

The differences in bladder cancer outcomes between the sexes has again been highlighted. Uncommon among cancers, bladder cancer outcomes are notably worse for women than for men. Furthermore, bladder cancer is three to four times more common among men than among women.

BMaps: A Web Application for Fragment-Based Drug Design and Compound Binding Evaluation.

Fragment-based drug design uses data about where, and how strongly, small chemical fragments bind to proteins, to assemble new drug molecules. Over the past decade, we have been successfully using fragment data, derived from thermodynamically rigorous Monte Carlo fragment-protein binding simulations, in dozens of preclinical drug programs. However, this approach has not been available to the broader research community because of the cost and complexity of doing simulations and using design tools.

Elevated levels of MMP12 sourced from macrophages are associated with poor prognosis in urothelial bladder cancer.

Background: Urothelial bladder cancer is most frequently diagnosed at the non-muscle-invasive stage (NMIBC). However, recurrences and interventions for intermediate and high-risk NMIBC patients impact the quality of life. Biomarkers for patient stratification could help to avoid unnecessary interventions whilst indicating aggressive measures when required.

An Association Study of Germline Variants in Bladder Cancer-Related Genes with the Prognosis of Non-Muscle Invasive Bladder Cancer.

Background: Various germline genetic variants are associated with the prognosis of non-muscle invasive bladder cancer (NMIBC). Germline variants in genes frequently somatically mutated in bladder cancer have not been studied thoroughly in relation to risk of recurrence or progression in NMIBC.

Objective: To identify germline DNA variants in bladder carcinogenesis-related genes associated with recurrence or progression in NMIBC.

Medium depth influences O availability and metabolism in cultured RPE cells.

Purpose: RPE oxidative metabolism is critical for normal retinal function and is often studied in cell culture systems. Here, we show that conventional culture media volumes dramatically impact O availability, limiting oxidative metabolism. We suggest optimal conditions to ensure cultured RPE is in a normoxic environment permissive to oxidative metabolism.

The influence of match exposure on injury risk in elite men's rugby union.

Objectives: To investigate the influence of previous season match exposure on injury incidence and burden in elite men's rugby union.

Design: A three-season (2016-17 to 2018-19) retrospective cohort design was used to collect and analyse injury and exposure data across English Premiership rugby union teams.

Methods: Generalised linear mixed-effects models were used to model the influence of match exposure (all match involvements, match involvements of ≥20 mins, and full-game equivalents) upon match and training injury incidence and burden in the following season.

Novel intravesical therapeutics in the treatment of non-muscle invasive bladder cancer: Horizon scanning.

Introduction: Non-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous disease; many patients develop recurrent or progress to muscle-invasive disease. Intravesical drug therapy is a pillar in the current management of NMIBC; notwithstanding, Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) have numerous limitations including international supply issues, and local and systemic toxicity. Here we review novel intravesical therapeutic options and drug delivery devices with potential for clinical use in the treatment of NMIBC.

Combined exome and transcriptome sequencing of non-muscle-invasive bladder cancer: associations between genomic changes, expression subtypes, and clinical outcomes.

Background: Three-quarters of bladder cancer patients present with early-stage disease (non-muscle-invasive bladder cancer, NMIBC, UICC TNM stages Ta, T1 and Tis); however, most next-generation sequencing studies to date have concentrated on later-stage disease (muscle-invasive BC, stages T2+). We used exome and transcriptome sequencing to comprehensively characterise NMIBCs of all grades and stages to identify prognostic genes and pathways that could facilitate treatment decisions. Tumour grading is based upon microscopy and cellular appearances (grade 1 BCs are less aggressive, and grade 3 BCs are most aggressive), and we chose to also focus on the most clinically complex NMIBC subgroup, those patients with grade 3 pathological stage T1 (G3 pT1) disease.

STAG2 Protein Expression in Non-muscle-invasive Bladder Cancer: Associations with Sex, Genomic and Transcriptomic Changes, and Clinical Outcomes.

Background: Mutations in cause complete loss of STAG2 protein in approximately one-third of non-muscle-invasive bladder cancers (NMIBCs). STAG2 protein expression is easily determined via immunohistochemistry (IHC) and published data suggest that loss of STAG2 expression is a good prognostic indicator in NMIBC.

Objective: To confirm the relationship between protein expression and clinical outcomes and tumour characteristics in NMIBC.

Highly Sensitive and Specific Detection of Bladder Cancer via Targeted Ultra-deep Sequencing of Urinary DNA.

Background: There is an unmet need for an accurate, validated, noninvasive test for diagnosing and monitoring bladder cancer (BC). Detection of BC-associated mutations in urinary DNA via targeted deep sequencing could meet this need.

Objective: To test the ability of mutational analysis of urinary DNA to noninvasively detect BC within the context of haematuria investigations and non-muscle-invasive BC (NMIBC) surveillance.

Scoping review: bladder cancer in Nigeria - what are the gaps in clinical care and research?

Objectives: There are currently no national guidelines regarding bladder cancer treatment and clinical care pathways in Nigeria. The aim of this scoping review was to identify any gaps in the knowledge of epidemiology, clinical care and translational research in order to aid the development of a defined clinical care pathway and guide future research.

Methods: A scoping review was conducted by searching Medline, Ovid Gateway, The Cochrane library and Open Grey literature using predefined search terms from date of inception to June 2020.

The Role of Diagnostic Imaging in Macular Telangiectasia Type 2.

While uncommon with subtle findings, macular telangiectasia type 2 can be diagnosed with careful retinal examination and selective use of diagnostic imaging.

Evidence or Prejudice? Critical Re-Analysis of Randomized Controlled Trials Comparing Overall Survival After Cisplatin Versus Carboplatin-Based Regimens in Advanced Urothelial Carcinoma.

Introduction: For many years EAU guidelines have recommended the use of cisplatin-based regimens over carboplatin for treatment of advanced urothelial cell carcinoma (UCC) in eligible patients. The claim of an overall survival (OS) benefit is based on (a meta-analysis of) 2 RCTs totalling 190 patients, of which one study has methodological flaws. These studies warrant secondary analysis to substantiate the evidence for an OS benefit of cisplatin- versus carboplatin-based regimens.

Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer.

Introduction And Objectives: Bladder cancer is primarily a disease of older age and little is known about the differences between patients diagnosed with bladder cancer at a younger versus older age. Our objectives were to compare bladder cancer specific survival in patients aged <50 versus those aged 50-70 at time of diagnosis.

Materials And Methods: The Swedish bladder cancer database provided data on patient demographics, clinical characteristics and treatments for this observational study.

Immunotherapy for non-muscle-invasive bladder cancer: from the origins of BCG to novel therapies.

Supplies of intravesical Bacillus Calmette-Guérin (BCG), the first-line treatment for most intermediate- and high-risk non-muscle-invasive bladder cancers (NMIBC), have proven unreliable over the past decade. This review considers the evolution of BCG immunotherapy for NMIBC: from the discovery of the antitumour side effects of tuberculosis and subsequently the BCG vaccine, to recent advances in novel immunotherapeutic agents. We summarize the evidence for alternative options to standard intravesical BCG therapy regimens and describe the potential for immune response manipulating drugs in the treatment of NMIBC.

The Sirenic Links between Diabetes, Obesity, and Bladder Cancer.

There is considerable evidence of a positive association between the incidence of type 2 diabetes mellitus (T2DM) and obesity with bladder cancer (BCa), with the link between T2DM and obesity having already been established. There also appear to be potential associations between Pleckstrin homology domain containing S1 ( and the Insulin-like Growth Factor (IGF) axis. Seven literature searches were carried out to investigate the backgrounds of these potential links.