An Investigation of the Basic Physics of Irrigation in Urology and the Role of Automated Pump Irrigation in Cystoscopy

Objective. To investigate the effects of height, external pressure, and bladder fullness on the flow rate in continuous, non-continuous cystoscopy and the automated irrigation fluid pumping system (AIFPS). Materials. Each experiment had two 2-litre 0.9% saline bags connected to a continuous, non-continuous cystoscope or AIFPS via irrigation tubing. Other equipment included height-adjustable drip poles, uroflowmetry devices, and model bladders. Methods. In Experiment 1, saline bags were elevated to measure the increment in flow rate. In Experiment 2, saline bags were placed under external pressures to evaluate the effect on flow rate. In Experiment 3, flow rate changes in response to variable bladder fullness were measured. Results. Elevating saline bags caused an increase in flow rates, however the increment slowed down beyond a height of 80 cm. Increase in external pressure on saline bags elevated flow rates, but inconsistently. A fuller bladder led to a decrease in flow rates. In all experiments, the AIFPS posted consistent flow rates. Conclusions. Traditional irrigation systems were susceptible to changes in height of irrigation solution, external pressure application, and bladder fullness thus creating inconsistent flow rates. The AIFPS produced consistent flow rates and was not affected by any of the factors investigated in the study

Prospective Study of Antibiotic Prophylaxis for Prostate Biopsy Involving >1100 Men

We aimed to compare infection rates for two 3-day antibiotic prophylaxis regimens for transrectal ultrasound-guided prostate biopsy (TRUSgbp) and demonstrate local microbiological trends. In 2008, 558 men and, in 2009, 625 men had TRUSgpb. Regimen 1 (2008) comprised 400 mg Ofloxacin immediately before biopsy and 200 mg 12-hourly for 3 days. Regimen 2 (2009) comprised Ofloxacin 200 mg 12-hourly for 3 days commencing 24 hours before biopsy. 20/558 (3.6%) men had febrile episodes with regimen 1 and 10/625 (1.6%) men with regimen 2 (P = 0.03). E. coli was the most frequently isolated organism. Overall, 7/13 (54%) of positive urine cultures were quinolone resistant and (5/13) 40% were multidrug resistant. Overall, 5/9 (56%) patients with septicaemia were quinolone resistant. All patients were sensitive to Meropenem. There was 1 (0.2%) death with regimen 1. Commencing Ofloxacin 24 hours before TRUSgpb reduced the incidence of febrile episodes significantly. We observed the emergence of quinolone and multidrug-resistant E. coli. Meropenem should be considered for unresolving sepsis

epiCaPture: a urine DNA methylation test for early detection of aggressive prostate cancer

Purpose Liquid biopsies that noninvasively detect molecular correlates of aggressive prostate cancer (PCa) could be used to triage patients, reducing the burdens of unnecessary invasive prostate biopsy and enabling early detection of high-risk disease. DNA hypermethylation is among the earliest and most frequent aberrations in PCa. We investigated the accuracy of a six-gene DNA methylation panel (Epigenetic Cancer of the Prostate Test in Urine [epiCaPture]) at detecting PCa, high-grade (Gleason score greater than or equal to 8) and high-risk (D'Amico and Cancer of the Prostate Risk Assessment] PCa from urine. Patients and Methods Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicenter prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation-specific polymerase chain reaction in DNA isolated from prebiopsy urine sediments and evaluated by receiver operating characteristic and decision curves (clinical benefit). The epiCaPture score was developed and validated on a two thirds training set to one third test set. Results Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, area under the receiver operating characteristic curve was 0.64, 0.86, and 0.83 for detecting PCa, high-grade PCa, and highrisk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy. Conclusion epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor specificity out-performs that of prostate-specific antigen (greater than 3 ng/mL). Used as an adjunct to prostate-specific antigen, epiCaPture could aid patient stratification to determine need for biopsy

The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial

Background: Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer. Methods: This international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit. Discussion The overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer. Trial registration Clinicaltrials.gov NLM identifier: NCT02453139. Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Prostate cancer progression to androgen independence - do changes in the androgen receptor CAG repeat number play a role?

THESIS 8359Prostate cancer is the commonest non-cutaneous male malignancy and is the second commonest cause of cancer-related deaths in many Western countries. Approximately half of all men diagnosed with prostate cancer will have incurable advanced disease. Most of these men are treated with and initially respond to androgen-ablative therapy. However, the duration of response is variable, and most patients will eventually progress to androgen-independent disease. The mechanisms that drive prostate cancer progression are not clear, although the androgen receptor appears to play a key role. The androgen receptor gene contains polymorphic CAG and GGC trinucleotide repeats. CAG repeat length has been inversely correlated with prostate cancer risk and androgen receptor transcriptional activity. This study aimed to examine the role of the CAG repeat in prostate cancer progression to androgen-independence. This study firstly examined the CAG repeat number in a range of tumorogenic and non-tumorogenic prostate cell lines. In particular, the study compared the CAG repeat number of the androgen-dependent LNCaP cell line with that of the androgen-independent sub-line of LNCaP, the LNCaP-HOF cell line

Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance

The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells

Characteristics of gram-negative urinary tract infections caused by extended spectrum beta lactamases: pivmecillinam as a treatment option within South Dublin, Ireland

Abstract Background The prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin. Methods A prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents. Results Sixty-nine percent of patients (N = 66) with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %), and nursing homes (24 %). The vast majority of ESBL isolates were E. coli (80 %). The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC) of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively. Conclusions This is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms

A multilingual evaluation of current health information on the Internet for the treatments of benign prostatic hyperplasia

To compare the quality of current Internet information on benign prostatic hyperplasia (BPH) and its surgical and medical managements across four Western languages and a comparative analysis of website sponsors. BPH Internet information quality is particularly relevant in an era of expanding, minimally invasive and surgical therapies. However, no comprehensive analysis exists. Methods: World Health Organization Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.google.com), 9,000 websites were assessed using keywords related to BPH and its medical and surgical treatment in English, French, German, and Spanish. The first 150 websites in each language had HON principles measured whilst a further analysis of site sponsorship was undertaken. Results: Very few BPH websites had greater than ten per cent HON accredited with significant differences (P<0.001) based on terms used for BPH, its medical and surgical management. Tertiles (thirds) of the first 150 websites returned differences in accredited websites (P<0.0001). English language had most accredited websites. Odds ratios for different terms returning accredited websites also were significantly different across terms (P<0.001). Websites were largely commercially sponsored. Conclusions: A lack of validation of most BPH sites should be appreciated with discrepancies in quality and number of websites across diseases, languages and also between medical and alternate terms. Physicians should participate in and encourage the development of informative, ethical and reliable health websites on the Internet and direct patients to them

Perceptions of Higher Specialist Trainees and Fellows of the Proposed Sláintecare Consultant Contract and Implications for Workforce Planning in Ireland

To explore the perceptions of higher specialist trainees and fellows in Ireland with respect to the Irish Department of Health’s recent proposal to implement a drafted, non-negotiated, consultant contract under a new model for healthcare, termed the Sláintecare plan. A customized survey, incorporating multiple-choice and Likert-scale questions and a free-text option, was disseminated to doctors enrolled in Irish higher specialist training (HST) programmes and pre-consultant HST graduates (fellows). Responses were compiled and analysed. There were a total of 1109 respondents across all specialities. Trainees were particularly concerned regarding the Sláintecare contract’s potential impact on their abilities to engage in patient advocacy and provide optimal patient care in the future, the maintenance of specialist skillsets, their ownership of intellectual property and a stable location of the practice.  Of respondents, 93.7% (1003/1070) indicated that they would consider working abroad rather than accept the proposed contract. This study highlights the perceptions and concerns of the higher specialist trainees and fellows of Ireland. A large proportion may emigrate rather than accept the Sláintecare proposals.  Concerns exist surrounding the ability to advocate for patients, to provide patient care, the proposed working conditions and perceived potential to deskill under this contract’s terms