OBJECTIVES To investigate the incidence of urinary incontinence and its development over time, to compare the effects of alternative definitions on the incontinence rate and to explore risk factors for incontinence after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. PATIENTS AND METHODS Urinary continence was assessed using a questionnaire administered by a third party in 1144 consecutive patients after undergoing RRP at our department from January 1986 to December 2001. Overall, 985 men (86%) were suitable for evaluation (mean age 64.5 years, mean follow‐up 95.5 months). We compared the effects of three definitions on the actuarial rate of continence: (1) no or occasional pad use; (2) 0 or 1 pads used daily, but for occasional dribbling only; (3) 0–1 pads daily. The time to recovery of continence was defined as the date on which the patient met the continence definitions. The impact of incontinence on health‐related quality of life (HRQoL) was also evaluated. Univariate and multivariate analyses were used to identify predictors of incontinence, using data gathered prospectively. RESULTS At the last follow‐up at 24 months after RRP, 83%, 92.3% and 93.4% of men achieved continence according to definitions 1, 2 and 3, respectively. The difference in time to recovering continence was significant for definition 1 compared to the others (P < 0.001). Most men using 1 pad/day complained of occasional dribbling only (89.3%), considered themselves continent (98%) and their HRQoL was not as seriously affected as those requiring ≥ 2 pads/day. Men continent (by definition 3) at 2 years had an actuarial probability of preserving continence of 72.2% at the last follow‐up. On multivariate analysis the age at surgery (P = 0.009), anastomotic stricture and follow‐up interval (both P < 0.001) were independent prognostic factors. Bilateral neurovascular bundle resection was another independent predictive factor (P = 0.03) in the subset of the last 560 men with available data on surgical technique. The reduction in the incidence of incontinence over time was as high as 86%. CONCLUSIONS Continence improves progressively until 2 years from RRP but some patients can become incontinent later. The criterion of pad use discriminates well between men with a limited reduction in their QoL (no or one pad used) and those with a markedly affected QoL (≥2 pads/day). It could be clinically valid to consider users of 1 pad/day as continent. Age, bilateral neurovascular bundle resection and anastomotic stricture are significant risk factors for incontinence. There was a marked trend for the incidence of incontinence and anastomotic stricture to decrease with time.

The VPS13A gene is associated with the neurodegenerative disorder Chorea Acanthocytosis. It is unknown what the consequences are of impaired function of VPS13A at the subcellular level. We demonstrate that VPS13A is a peripheral membrane protein, associated with mitochondria, the endoplasmic reticulum and lipid droplets. VPS13A is localized at sites where the endoplasmic reticulum and mitochondria are in close contact. VPS13A interacts with the ER residing protein VAP-A via its FFAT domain. Interaction with mitochondria is mediated via its C-terminal domain. In VPS13A-depleted cells, ER-mitochondria contact sites are decreased, mitochondria are fragmented and mitophagy is decreased. VPS13A also localizes to lipid droplets and affects lipid droplet motility. In VPS13A-depleted mammalian cells lipid droplet numbers are increased. Our data, together with recently published data from others, indicate that VPS13A is required for establishing membrane contact sites between various organelles to enable lipid transfer required for mitochondria and lipid droplet related processes.

Study Type – Therapy (RCT) Level of Evidence 1b What's known on the subject? and What does the study add? Peri‐operative pelvic floor muscle training reduces urinary incontinence for men undergoing radical prostatectomy (RP). A preoperative biofeedback session, combined with postoperative pelvic floor muscle training, and assisted sessions on a monthly basis only, is an effective low‐intensity programme to improve recovery of continence in patients undergoing RP. OBJECTIVE To evaluate the efficacy of preoperative biofeedback (BFB) combined with an assisted low‐intensity programme of postoperative perineal physiokinesitherapy in reducing the incidence, duration and severity of urinary incontinence (UI) in patients undergoing radical prostatectomy (RP). PATIENTS AND METHODS A prospective, single‐centre, randomized controlled clinical study was designed. The intervention group received a training session with BFB, supervised oral and written instructions on Kegel exercises and a structured programme of postoperative exercises on the day before open RP. After RP, patients received control visits, including a session of BFB, at monthly intervals only. The control group received, after catheter removal, only oral and written instructions on Kegel exercises to be performed at home. Patients received control visits at 1, 3 and 6 months after catheter removal. At each visit the number of incontinence episodes, the number of pads used and patient‐reported outcome measures (International Consultation on Incontinence Questionnaire on Urinary Incontinence [ICIQ‐UI], [ICIQ]‐Overactive Bladder [OAB], University of California, Los Angeles‐Prostate Cancer Index [UCLA‐PCI], International Prostate Symptom Score‐Quality of Life [IPSS‐QoL]) were assessed in both groups. All patients were followed‐up for a period of at least 6 months after catheter removal. The primary outcome was the recovery of continence, strictly defined as a ICIQ‐UI score of zero. RESULTS Overall, 34 consecutive patients were eligible and 32 were available for the final analysis: 16 patients for each study group. The two groups were homogeneous for all pre‐ and intraoperative features examined. In the intervention group, continence had been achieved by six, eight and 10 patients at 1‐, 3‐ and 6‐month follow‐ups, respectively, vs no patients (P= 0.02), one patient (P= 0.01) and one patient (P= 0.002) in the control group at each follow‐up, respectively. The analysis of the UCLA‐PCI and ICIQ‐OAB scores, the number of incontinence episodes per week and the number of pads per week showed significant differences in favour of patients in the intervention group at 3 and 6 months. Patients in the intervention group reported better IPSS‐QoL scores at all follow‐up times but the difference did not reach statistical significance. CONCLUSIONS Preoperative BFB combined with a postoperative programme of perineal physiokinesitherapy and assisted sessions on a monthly basis only, is a treatment strategy significantly more effective than the standard care in improving reco...

In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion. Among these associations (peaks) we focused our attention on those proximal to the regulatory region of HOTAIR and MALAT1. These transcripts appeared regulated by estrogens and able to control ERs function by interacting with ERα/ERβ as indicated by RNA-ChIP. Further studies performed by ChIRP revealed that in unstimulated condition, HOTAIR and MALAT1 were present on pS2, hTERT and HOTAIR promoters at the ERE/eNOS peaks. Interestingly, upon treatment with17β-estradiol HOTAIR recruitment to chromatin increased significantly while that of MALAT1 was reduced, suggesting an opposite regulation and function for these lncRNAs. Similar results were obtained in cells and in an ex vivo prostate organotypic slice cultures. Overall, our data provide evidence of a crosstalk between lncRNAs, estrogens and estrogen receptors in prostate cancer with important consequences on gene expression regulation.