A Novel, non-invasive Test Enabling Bladder Cancer Detection in Urine Sediment of Patients Presenting with Haematuria:A Prospective Multicentre Performance Evaluation of ADXBLADDER

Bladder cancer is the sixth most commonly diagnosed cancer in the European Union. Here, we evaluate the performance of a novel, commercially available enzyme-linked immunosorbent assay utilising MCM5 antibodies (ADXBLADDER; Arquer Diagnostics Ltd, Sunderland, UK) for the detection of bladder cancer, in a blinded, prospective study of 856 patients, across seven centres, presenting with haematuria. The results were compared with the patients’ clinical data and final diagnosis as defined by the results of the imaging and cystoscopy, with a prevalence of bladder cancer of 8.6%. ADXBLADDER detected bladder tumours in 54/74 cancers, giving overall sensitivity of 73.0% and an overall negative predictive value (NPV) of 96.4%. Sensitivity and NPV of ADXBLADDER were highest in muscle-invasive bladder cancer, both at 100%, and on analysis of non-pTa (pT1 and above) tumours, the sensitivity for detection was 97% with an NPV of 99.8%. A subset of 173 patients had matching cytology data; of these patients, 18 were positive for bladder cancer. ADXBLADDER detected 16/18 of these cancers, whilst cytology was positive in only four of 18, providing evidence that ADXBLADDER may be a more sensitive test for bladder cancer than standard urine cytology. Patient summary: We conducted a large clinical study of a novel, simple urine test (ADXBLADDER), which measures a protein (MCM5) in urine and can be used to detect bladder cancer in patients. We recruited 856 patients and demonstrated that the new urine test can detect bladder cancer with a high degree of accuracy, performing better than the most commonly used urine test—urine cytology. In conclusion, this novel ADXBLADDER urine test can be used to help detect bladder cancers and it can replace the current, standard urine test. The ADXBLADDER test measures the novel biomarker MCM5. Outperforming cytology, and achieving one of the highest sensitivities and negative predictive values of any urine test for bladder cancer diagnosis, it has the potential to improve the bladder cancer diagnostic pathway.</p

Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

A prospective clinical, cost and environmental analysis of a clinician-led virtual urology clinic

INTRODUCTION: Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism is dependent upon accurate prediction of single-gland disease on the basis of preoperative imaging and biochemistry. The aims of this study were to validate currently available predictive models of single-gland disease in two UK cohorts and to determine if these models can facilitate MIP. MATERIAL AND METHODS: We collected data prospectively from our weekly follow-up virtual clinic over a continuous four-month period between July and September 2017. RESULTS: In total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of our patients were discharged from further follow-up. The majority of our patients (male 57.7%, female 55.5%) were of working age. The satisfaction scores were high, at 90.1%, and there were no reported adverse events as a result of using the virtual clinic. Our calculated cost savings were £18,744, with a predicted 12-month cost saving of £56,232. The creation of additional face-to-face clinic capacity has created an estimated 12-month increase in tariff generation for our unit of £72,072. In total, 4623 travel miles were avoided by patients using the virtual clinic, with an estimated avoided carbon footprint of 0.35-1.45 metric tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided carbon footprint is 1.04-4.04 metric tonnes of CO2e. CONCLUSIONS: Our virtual clinic model has demonstrated a trifecta of positive outcomes, namely, clinical, financial and environmental benefits. The environmental importance and benefits of a virtual clinic should be promoted as a social enterprise value when engaging stakeholders in setting up such a urological service. We propose the adoption of our virtual clinic model in those urological units considering this method of telemedicine

A prospective clinical, cost and environmental analysis of a clinician-led urology virtual clinic

Introduction: A virtual clinic is a form of telemedicine where contact between clinical teams and patients occur without face-to-face consultation. Our study aims to quantify the clinical, financial and environmental benefits of our virtual urology clinic. / Material and methods: We collected data prospectively from our weekly follow-up virtual clinic over a continuous four-month period between July and September 2017. / Results: In total, we reviewed 409 patients. Following virtual clinic consultation, 68.5% of our patients were discharged from further follow-up. The majority of our patients (male 57.7%, female 55.5%) were of working age. The satisfaction scores were high, at 90.1%, and there were no reported adverse events as a result of using the virtual clinic. Our calculated cost savings were £18,744, with a predicted 12-month cost saving of £56,232. The creation of additional face-to-face clinic capacity has created an estimated 12-month increase in tariff generation for our unit of £72,072. In total, 4623 travel miles were avoided by patients using the virtual clinic, with an estimated avoided carbon footprint of 0.35–1.45 metric tonnes of CO2e, depending on mode of transport. Our predicted 12-month avoided carbon footprint is 1.04–4.04 metric tonnes of CO2e. / Conclusions: Our virtual clinic model has demonstrated a trifecta of positive outcomes, namely, clinical, financial and environmental benefits. The environmental importance and benefits of a virtual clinic should be promoted as a social enterprise value when engaging stakeholders in setting up such a urological service. We propose the adoption of our virtual clinic model in those urological units considering this method of telemedicine

Delayed blood transfusion is associated with mortality following radical cystectomy

Objectives: To examine the temporal association between blood transfusion and 90-day mortality in patients with bladder cancer treated with radical cystectomy. / Methods: This represents a retrospective cohort study of patients treated with radical cystectomy within the Premier Hospital network between 2003 and 2015. Patients outcomes were stratified those who received early blood transfusion (day of surgery) vs delayed blood transfusion (postoperative day ≥1) during the index admission. Primary end point was 90-day mortality following surgery. / Results: The median age of 12,056 patients identified was 70 years. A total of 7,201 (59.7%) patients received blood transfusion. Within 90 days following surgery, 57 (2.2%), 162 (5.9%) and 123 (6.7%) patients in the early, delayed and both early and delayed transfused patients died respectively. Following multivariate logistic regression to account for patient (age and Charlson Comorbidity Index [CCI]) and hospital (surgeon volume, surgical approach and academic status) factors, delayed blood transfusion was independently associated with 90-day mortality (Odds ratio [OR], 2.64; 95% Confidence Interval [CI], 1.98–3.53; p < 0.001). A sensitivity analysis defining early blood transfusion as <2 days postoperatively, increased 90-day mortality persisted in patients receiving delayed transfusion (OR, 2.20; 95% CI, 1.63-3.00; p < 0.001). Older patients (≥77 years) with the highest CCI (≥2) had a 7% absolute increase in the predicted probability of 90-day mortality if they were transfused late compared to patients transfused early. / Conclusion: Patient undergoing cystectomy may benefit from expedited transfusion to prevent subsequent clinical deterioration which may lead to patient mortality. Future work is needed to elucidate the optimal timing of blood transfusion

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

UK Multicenter Prospective Evaluation of the Leibovich Score in Localized Renal Cell Carcinoma: Performance has Altered Over Time

\ua9 2019 The AuthorsObjective: To examine changes in outcome by the Leibovich score using contemporary and historic cohorts of patients presenting with renal cell carcinoma (RCC) Patients and Methods: Prospective observational multicenter cohort study, recruiting patients with suspected newly diagnosed RCC. A historical cohort of patients was examined for comparison. Metastasis-free survival (MFS) formed the primary outcome measure. Model discrimination and calibration were evaluated using Cox proportional hazard regression and the Kaplan-Meier method. Overall performance of the Leibovich model was assessed by estimating explained variation. Results: Seven hundred and six patients were recruited between 2011 and 2014 and RCC confirmed in 608 (86%) patients. Application of the Leibovich score to patients with localized clear cell RCC in this contemporary cohort demonstrated good model discrimination (c-index = 0.77) but suboptimal calibration, with improved MFS for intermediate- and high-risk patients (5-year MFS 85% and 50%, respectively) compared to the original Leibovich cohort (74% and 31%) and a historic (1998-2006) UK cohort (76% and 37%). The proportion of variation in outcome explained by the model is low and has declined over time (28% historic vs 22% contemporary UK cohort). Conclusion: Prognostic models are widely employed in patients with localized RCC to guide surveillance intensity and clinical trial selection. However, the majority of the variation in outcome remains unexplained by the Leibovich model and, over time, MFS rates among intermediate- and high-risk classified patients have altered. These findings are likely to have implications for all such models used in this setting

Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer

Objectives: To describe the frequency and nature of symptoms in patients presenting with suspected renal cell carcinoma (RCC) and examine their reliability in achieving early diagnosis. Design: Multicentre prospective observational cohort study. Setting and participants: Eleven UK centres recruiting patients presenting with suspected newly diagnosed RCC. Symptoms reported by patients were recorded and reviewed. Comprehensive clinico-pathological and outcome data were also collected. Outcomes: Type and frequency of reported symptoms, incidental diagnosis rate, metastasis-free survival and cancer-specific survival. Results: Of 706 patients recruited between 2011 and 2014, 608 patients with a confirmed RCC formed the primary study population. The majority (60%) of patients were diagnosed incidentally. 87% of patients with stage Ia and 36% with stage III or IV disease presented incidentally. Visible haematuria was reported in 23% of patients and was commonly associated with advanced disease (49% had stage III or IV disease). Symptomatic presentation was associated with poorer outcomes, likely reflecting the presence of higher stage disease. Symptom patterns among the 54 patients subsequently found to have a benign renal mass were similar to those with a confirmed RCC. Conclusions: Raising public awareness of RCC-related symptoms as a strategy to improve early detection rates is limited by the fact that related symptoms are relatively uncommon and often associated with advanced disease. Greater attention must be paid to the feasibility of screening strategies and the identification of circulating diagnostic biomarkers