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Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.

Objectives The objective of this study is to report the pilot phase of the Targeted Prostate Health Check programme that aims to identify men in the Surrey and Sussex region who have prostate cancer and who failed to be detected during the Covid era. Subjects and methods Men aged 50 to 70, or 45 to 70 if Black or with a family history of prostate cancer, were identified from participating general practitioner (GP) records. Short message service (SMS) texts invited men to visit www.talkprostate.co.uk for information on prostate cancer and give consent to prostate‐specific antigen (PSA) checks coordinated by a third‐party virtual healthcare provider. Elevated age‐related PSA levels, or levels below age‐related thresholds but at 3 ng/mL or more, triggered referral to a rapid access urology clinic. GPs were informed of the results. Results From 1842 text messages inviting 1549 people, 544 men consented to a PSA check. From 500 phlebotomy appointments, 485 (30% of invited men) took the PSA test of whom 68 (14%) were referred with an elevated PSA. After clinical review with multiparametric magnetic resonance imaging (mp‐MRI), 22 patients underwent transperineal biopsies, and prostate cancer was detected in 18 men of whom 17 (95%) had clinically significant cancer. Conclusion Our Targeted Prostate Cancer Health Check system identifies men at risk without burdening primary care. Awareness on prostate cancer risk was raised in 1549 invited men, half of whom were further educated via the registration website. One third of invited men were checked in whom clinically significant prostate cancer was found in 3.5%.

Ion channels are important for many cellular functions and disease states including cystic fibrosis and multidrug resistance. Previous work in the Dunning rat model of prostate cancer has suggested a relationship between voltage-activated Na+ channels (VASCs) and the invasive phenotype in vitro. The objectives of this study were to 1) evaluate the expression of VASCs in the LNCaP and PC-3 human prostate cancer cell lines by Western blotting, flow cytometry, and whole-cell patch clamping, 2) determine their role in invasion in vitro using modified Boyden chambers with and without a specific blocker of VASCs (tetrodotoxin). A 260-kd protein representing VASCs was found only in the PC-3 cell line, and these were shown to be membrane expressed on flow cytometry. Patch clamping studies indicated that functional VASCs were present in 10% of PC-3 cells and blocking these by tetrodotoxin (600 nmol/L) reduced their invasiveness by 31% (P = 0.02) without affecting the invasiveness of the LNCaP cells. These results indicate that the reduction of invasion is a direct result of VASC blockade and not a nonspecific action of the drug. This is the first report of VASCs in a human prostatic cell line. VASCs are present in PC-3 but not LNCaP cells as determined by both protein and functional studies. Tetrodotoxin reduced the invasiveness of PC-3 but not LNCaP cells, and these data suggest that ion channels may play an important functional role in tumor invasion.

ObjectiveTo evaluate predictive factors of urinary incontinence (UI) after holmium laser enucleation of the prostate (HoLEP).MethodsPatients (n = 2346) were included in a retrospective multicentric study from April 2012 to November 2017. Patients’ characteristics (age, BMI, percentage with diabetes), preoperative data (IPSS score, whole gland volume, urinary drainage), operative data (enucleation time, enucleation efficiency, tissue enucleated weight, total delivered energy) and postoperative data were recorded. Absence of UI was defined as no pads at 3 and 6 months. Surgeon experience was stratified in three categories: beginners (< 21 cases), intermediate (21–40 cases) and experienced (> 40 cases). Multivariate logistic regression analysis was performed.ResultsUI was observed in 14.5% of patients (340/2346) at 3 months (95%CI 13–16%) and in 4.2% (98/2346) at 6 months (95%CI 3–5%). On multivariate analysis at 3 months, increasing age (OR per SD = 1.3 [1.14–1.48]), elevated BMI (OR per SD = 1.23 [1.09–1.38]), preoperative urinary drainage (OR = 0.62 [0.45–0.85]), increasing enucleated tissue weight (OR per SD = 1.29 [1.16–1.45]) and experienced surgeon with at least 40 cases (OR = 0.56 [0.42–0.75]) were significantly associated with UI. At 6 months, increasing age (OR per SD = 1.25 [1.01–1.53]), elevated BMI (OR per SD = 1.25 [1.03–1.5]), increasing whole gland volume (OR per one SD log = 1.24 [1.01–1.53]) and diabetes disorder (OR = 1.7 [1.03–2.78]) were significantly associated with UI.ConclusionUI after HoLEP was observed in 14.5% of patients at 3 months and 4.2% at 6 months, with stress UI in half of the cases. Surgeon experience with at least 40 cases was the main predictive factor of 3 months UI after HoLEP and diabetes disorder of persistent UI at 6 months.

MATERIAL AND METHODS In this prospective study carried out in 2010 at a district general hospital registered with the Trust Research and Audit Department (Number P1080), we assessed two hundred female patients referred by primary care practitioners to the female urology clinic with urinary incontinence. Patients with recurrent urinary tract infections, recently failed incontinence surgery, suspected urinary fistulas, spinal cord injury, genitourinary malformations, pelvic malignancy and previous abdominopelvic radiotherapy were excluded. In the present study, symptoms of leakage of urine during physical activity (3IQ question 3, part a) identified less than half the women with UDSUI (sensitivity 43%), but a positive answer increased the probability significantly of UDSUI being present (predictive value 87%, positive likelihood ratio 5.4) This is in keeping with the findings of Bergman et al. wherein the correlation of detailed urinary symptoms 64-item questionnaire and urodynamics findings for SUI was 80% [13]. The 3IQ questionnaire showed low performance in diagnosing urodynamically demonstrated MUI. [...]we would suggest that a complete history, thorough clinical evaluation and in selected cases urodynamic testing are still essential in the accurate diagnosis and appropriate management of female urinary incontinence.

There are limited studies evaluating the 3 Incontinence Questionnaire (3IQ) against urodynamics based diagnosis as a reference standard. The 3IQ has been proposed to be useful to evaluate women at the level of primary care. The aim of this study was to determine correlation between 3IQ and video-urodynamics (VUDS) in diagnosing types of urinary incontinence. Prospective data was collected on 200 consecutive female patients referred by primary care physicians for urinary incontinence. The mean age was 55 years (range 15-83 years). The patients were evaluated using the 3IQ and video-urodynamics. The 3IQ-based diagnosis of type of female urinary incontinence was compared to VUDS-based results. Sensitivity, specificity, positive likelihood ratios and positive predictive values were calculated. On 3IQ based self-evaluation, 28% of patients were classified as having stress urinary incontinence, 20% with urge incontinence and 40% with mixed incontinence. On video-urodynamics, urodynamic stress urinary incontinence (UDSUI) was detected in 56% of patients, detrusor overactivity (DO) in 15% and mixed urinary incontinence (MUI) in 19%. The 3IQ had a sensitivity and specificity respectively of 43% and 92% for UDSUI, 57% and 86% for DO and 58% and 64% for MUI. The corresponding positive likelihood ratios (CI, 95%) were 5.4 (CI 2.6 to 11.3) for stress urinary incontinence, 4.0 (CI 2.5 to 6.5) for DO and 1.62 (1.2 to 2.3) for MUI. The respective positive predictive values were 87% (CI 75% to 95%), 42% (CI 26% to 58%) and 28% (18% to 39%). In our study population, stress urinary incontinence was reasonably well predicted by the 3IQ, but the questionnaire under-performed in the diagnoses of detrusor overactivity and mixed urinaryincontinence.

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatments for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.

TRUS-guided needle biopsy of the prostate is the standard technique in the diagnosis of prostate cancer. However the practice is highly variable across the United Kingdom. We survey the standard approaches to TRUS biopsy of prostate, highlighting the nationwide diversity of practice and training. One hundred and eighty questionnaires were sent out to specialist registrars, investigating the number of prostate biopsy cores taken, the use of prophylactic antibiotics, rectal preparation and local analgesia in TRUS biopsy of the prostate. One hundred and fourteen trainees (63%) returned the questionnaires. Twenty-three percent reported sextant biopsy as standard, 36% taking eight-core and 26% taking 10 or more cores. There is no standard regime for antibiotic prophylaxis. Eighteen percent also reported rectal preparation as routine. Thirty-eight percent of the patients receive local anaesthesia prior to the biopsy. Overall, 42% of the TRUS biopsies are carried out by urologists, 29% by radiologists and 21% by both. Six percents have nurse practitioners' involvement. Fifty-six percent of trainees are involve in the TRUS biopsy, 68% do not think they received enough training to carry out the procedure. TRUS-guided needle biopsy of the prostate is the standard technique in the diagnosis of prostate cancer. Our survey highlights nationwide diversity in practice in the UK with respect of the number of cores taken, antibiotic prophylaxis and local anaesthesia utilisation. This raised the issue of standardising the practice. More urologists are also actively taking part in this procedure, making the structured training increasingly important.

We prospectively evaluate the safety, morbidity and characteristics of complications for transrectal ultrasound guided needle biopsy of prostate carried out solely by urologists in a single unit. This will help to counsel patient prior to the biopsy. One hundred consecutive patients were recruited to complete questionnaires prospectively, 2 weeks and 3 months after TRUS and prostate biopsy. Haematospermia, haematuria and rectal bleeding characteristics were evaluated. Pain, analgesia requirement, infection and urinary retention rates were also assessed. Ninety-two patients (92%) returned questionnaires 2 weeks and 63 patients (63%) three months after the biopsy. At 2 weeks questionnaire, 58 patients (63%) experienced haematuria and 9 patients (10%) for more than 1 week. Eighty-five percent of the 58 patients who had haematuria described it as mild and intermittent. Twenty-three (25%) patients experienced a rectal bleed and none for more than four days. Only 1 patient experienced clots with the rectal bleeding. Twelve (13%) patients had difficulty passing urine but the symptoms resolved by day four. Acute urinary retention did not occur. Thirty-five (38%) patients had some degree of discomfort and only one patient had pain for more than three days. Twenty-five (27%) patients took analgesia between 1 and 8 days (Mean 3 days). Two patients had a urinary tract infection despite prophylactic antibiotics. At three months, 4 patients (6%) had experienced secondary haematuria 3 weeks after the biopsy. Two patients experienced more rectal bleeding 2 weeks after the biopsy and 1 patient had residual discomfort 2 weeks after the procedure. Thirteen patients (21%) had haematospermia between day 6 and 56 (Mean 21 days). Transrectal ultrasound guided biopsy of the prostate is generally well tolerated with minor pain and morbidity in our urologist-led service. Our data will assist counselling of patients prior to the procedure.