Intraurethral Catheter: Alternative Management for Urinary Retention in Patients With Benign Prostatic Hypertrophy

A polyurethane intraurethral catheter (IUC) was used in 27 patients with benign prostatic hypertrophy who were unfit for surgery, or were awaiting surgery. All of them had previously had a periurethral catheter inserted. The IUC was inserted with a cystoscope under fluoroscopic control. Spontaneous voiding through the IUC resumed in 25 patients (93%) in the immediate postprocedure period. At the end of 6 months follow-up, the peak flow rates and the residual volumes estimated in 22 patients were satisfactory. Immediate complications included incontinence due to distal displacement in 2 patients and hematuria in one patient; long-term complications included mild encrustation of the IUC in 2 patients and calculus formation on the IUC in 1 patient. None of the patients had clinically significant urinary tract infection. The presence of the IUC did not compromise the subsequent transurethral resection of the prostate gland. We recommend the use of an IUC for up to 6 months in patients with urinary retention who are awaiting surgery or are unfit for surgery as an alternative to an indwelling urethral catheter

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

Characterizing the Syphilis-Causing Treponema pallidum ssp. pallidum Proteome Using Complementary Mass Spectrometry

YesBackground. The spirochete bacterium Treponema pallidum ssp. pallidum is the etiological agent of syphilis, a chronic multistage disease. Little is known about the global T. pallidum proteome, therefore mass spectrometry studies are needed to bring insights into pathogenicity and protein expression profiles during infection. Methodology/Principal Findings. To better understand the T. pallidum proteome profile during infection, we studied T. pallidum ssp. pallidum DAL-1 strain bacteria isolated from rabbits using complementary mass spectrometry techniques, including multidimensional peptide separation and protein identification via matrix-assisted laser desorption ionization-time of flight (MALDI-TOF/TOF) and electrospray ionization (ESI-LTQ-Orbitrap) tandem mass spectrometry. A total of 6033 peptides were detected, corresponding to 557 unique T. pallidum proteins at a high level of confidence, representing 54% of the predicted proteome. A previous gel-based T. pallidum MS proteome study detected 58 of these proteins. One hundred fourteen of the detected proteins were previously annotated as hypothetical or uncharacterized proteins; this is the first account of 106 of these proteins at the protein level. Detected proteins were characterized according to their predicted biological function and localization; half were allocated into a wide range of functional categories. Proteins annotated as potential membrane proteins and proteins with unclear functional annotations were subjected to an additional bioinformatics pipeline analysis to facilitate further characterization. A total of 116 potential membrane proteins were identified, of which 16 have evidence supporting outer membrane localization. We found 8/12 proteins related to the paralogous tpr gene family: TprB, TprC/D, TprE, TprG, TprH, TprI and TprJ. Protein abundance was semi-quantified using label-free spectral counting methods. A low correlation (r = 0.26) was found between previous microarray signal data and protein abundance. Conclusions. This is the most comprehensive description of the global T. pallidum proteome to date. These data provide valuable insights into in vivo T. pallidum protein expression, paving the way for improved understanding of the pathogenicity of this enigmatic organism.This work was supported by the grants from the Flanders Research Foundation, SOFI-B Grant to CRK, http://www.fwo.be/, a Public Health Service Grant from the National Institutes of Health to CEC, (grant # AI-051334), https://www.nih.gov/ and a grant from the Grant Agency of the Czech Republic to DS and MS (P302/12/0574, GP14-29596P), https:// gacr.cz/

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

A 4-Month Whole-Systems Ayurvedic Medicine Nutrition and Lifestyle Intervention Is Feasible and Acceptable for Breast Cancer Survivors: Results of a Single-Arm Pilot Clinical Trial.

PurposeOngoing symptoms and impairments in quality of life (QOL) among breast cancer survivors remain a significant problem. We tested the feasibility and acceptability of a manualized Ayurvedic nutrition and lifestyle intervention for breast cancer survivors.MethodsEligible participants had Stage I-III breast cancer, underwent treatment within the past year that included chemotherapy, and were without active disease. The 4-month individualized Ayurvedic intervention included counseling on nutrition, lifestyle, yoga, and marma (like acupressure) during 8 one-on-one visits with an Ayurvedic practitioner. Feasibility and acceptability were the primary outcomes. QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30]) and symptoms-sleep disturbance (General Sleep Disturbance Scale [GSDS]), fatigue (Lee Fatigue Scale [LFS]), depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI-S, STAI-T]), and stress (Perceived Stress Scale [PSS])-were measured prior to, at midpoint, and at the end of the 4-month intervention. Effect sizes (Cohen's d) were calculated along with paired t tests comparing baseline to end of month 4 time points. Mixed effects models were used for repeated measures analyses.ResultsParticipants (n = 32) had a mean age of 48 years (SD = 10). Retention at the end of the intervention was 84%. Among those who completed the intervention (n = 27), adherence was high (99.5% of visits with practitioners attended). Large improvements were seen in QLQ-C30 emotional functioning (d = 0.84, P < 0.001), QLQ-C30 cognitive functioning (d = 0.86, P < 0.001), GSDS (d = -1.23, P < 0.001), and CES-D (d = -1.21, P < 0.001). Moderate improvements were seen in QLQ-C30 global health (d = 0.65, p = 0.003), LFS (d = -0.68, P = 0.002), and PSS (d = -0.75, P < 0.001). No adverse events were observed due to the intervention.ConclusionThis 4-month Ayurvedic whole-systems multimodal nutrition and lifestyle intervention was feasible and acceptable for breast cancer survivors. Promise of clinical benefit was seen in terms of improvements in symptoms and QOL that warrants further investigation

A 4-Month Whole-Systems Ayurvedic Medicine Nutrition and Lifestyle Intervention Is Feasible and Acceptable for Breast Cancer Survivors: Results of a Single-Arm Pilot Clinical Trial.

PurposeOngoing symptoms and impairments in quality of life (QOL) among breast cancer survivors remain a significant problem. We tested the feasibility and acceptability of a manualized Ayurvedic nutrition and lifestyle intervention for breast cancer survivors.MethodsEligible participants had Stage I-III breast cancer, underwent treatment within the past year that included chemotherapy, and were without active disease. The 4-month individualized Ayurvedic intervention included counseling on nutrition, lifestyle, yoga, and marma (like acupressure) during 8 one-on-one visits with an Ayurvedic practitioner. Feasibility and acceptability were the primary outcomes. QOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ C30]) and symptoms-sleep disturbance (General Sleep Disturbance Scale [GSDS]), fatigue (Lee Fatigue Scale [LFS]), depressive symptoms (Center for Epidemiological Studies-Depression Scale [CES-D]), anxiety (Spielberger State-Trait Anxiety Inventory [STAI-S, STAI-T]), and stress (Perceived Stress Scale [PSS])-were measured prior to, at midpoint, and at the end of the 4-month intervention. Effect sizes (Cohen's d) were calculated along with paired t tests comparing baseline to end of month 4 time points. Mixed effects models were used for repeated measures analyses.ResultsParticipants (n = 32) had a mean age of 48 years (SD = 10). Retention at the end of the intervention was 84%. Among those who completed the intervention (n = 27), adherence was high (99.5% of visits with practitioners attended). Large improvements were seen in QLQ-C30 emotional functioning (d = 0.84, P < 0.001), QLQ-C30 cognitive functioning (d = 0.86, P < 0.001), GSDS (d = -1.23, P < 0.001), and CES-D (d = -1.21, P < 0.001). Moderate improvements were seen in QLQ-C30 global health (d = 0.65, p = 0.003), LFS (d = -0.68, P = 0.002), and PSS (d = -0.75, P < 0.001). No adverse events were observed due to the intervention.ConclusionThis 4-month Ayurvedic whole-systems multimodal nutrition and lifestyle intervention was feasible and acceptable for breast cancer survivors. Promise of clinical benefit was seen in terms of improvements in symptoms and QOL that warrants further investigation

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer

Abstract Background Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients’ quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. Methods NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. Discussion NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. Trial registration NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978