Current status of urology surgical training in Europe: an ESRU-ESU-ESUT collaborative study.

PURPOSE: To determine the current status of surgical training amongst European Urology Residents, including their satisfaction with training and their confidence in performing procedures. METHODS: A 23-item survey was distributed to the 15th European Urology Residents Education Programme (EUREP) 2017 participants. An analysis of demographics, workload, training resources, surgical exposure, surgical caseload, satisfaction and confidence in performing each procedure was performed. RESULTS: A total of 152/350 participants completed the survey (response rate 43%), of which 14% think they perform enough surgeries during their training, and 83% would like to continue training with a fellowship. Confidence in performing procedures without supervision and satisfaction with training was associated with higher surgical caseloads. Confidence in all laparoscopic/robotic procedures (except for laparoscopic/robotic partial nephrectomy) was associated with laparoscopic and robotics training, participation in practical courses and having training resources in hospitals. Satisfaction with surgical training was statistically associated with working ≤  50 h per week, laparoscopic training and having laparoscopic training boxes. CONCLUSIONS: Surgical exposure of European Urology residents for major/minimally invasive procedures, confidence in performing these procedures, and overall satisfaction with training is low. A higher volume of cases, as well as resources for training are associated with higher individual confidence and satisfaction with training.

Differential tissue expression of extracellular vesicle-derived proteins in prostate cancer.

BACKGROUND: Proteomic profiling of extracellular vesicles (EVs) from prostate cancer (PCa) and normal prostate cell lines, led to the identification of new candidate PCa markers. These proteins included the nuclear exportin proteins XPO1 (also known as CRM1), the EV-associated PDCD6IP (also known as ALIX), and the previously published fatty acid synthase FASN. In this study, we investigated differences in expression of XPO1 and PDCD6IP on well-characterized prostate cancer cohorts using mass spectrometry and tissue microarray (TMA) immunohistochemistry to determine their diagnostic and prognostic value. METHODS: Protein fractions from 67 tissue samples (n = 33 normal adjacent prostate [NAP] and n = 34 PCa) were analyzed by mass spectrometry (nano-LC-MS-MS). Label-free quantification of EVs was performed to identify differentially expressed proteins between PCa and NAP. Prognostic evaluation of the candidate markers was performed with a TMA, containing 481 radical prostatectomy samples. Samples were stained for the candidate markers and correlated with patient information and clinicopathological outcome. RESULTS: XPO1 was higher expressed in PCa compared to NAP in the MS data analysis (P > 0.0001). PDCD6IP was not significantly higher expressed (P = 0.0501). High cytoplasmic XPO1 staining in the TMA immunohistochemistry, correlated in a multivariable model with high Gleason scores (P = 0.002) and PCa-related death (P = 0.009). CONCLUSION: High expression of cytoplasmic XPO1 shows correlation with prostate cancer and has added clinical value in tissue samples. Furthermore, as an extracellular vesicles-associated protein, it might be a novel relevant liquid biomarker.

Tissue proteomics outlines AGR2 AND LOX5 as markers for biochemical recurrence of prostate cancer.

Although many patients are cured from prostate cancer (PCa) by surgery only, there are still patients who will experience rising prostate-specific antigen (PSA) levels after surgery, a condition known as biochemical recurrence (BCR). Novel protein prognostic markers in PCa tissue might enable finding better treatment for those patients experiencing BCR with a high chance of metastasis. In this study, we aimed to identify altered proteins in prostate cancer tissue, and to evaluate their potential role as prognostic markers. We used two proteomics strategies to analyse 34 prostate tumours (PCa) and 33 normal adjacent prostate (NAP) tissues. An independent cohort of 481 samples was used to evaluate the expression of three proteins: AGR2, FASN and LOX5 as prognostic markers of the disease. Tissue microarray immunohistochemical staining indicated that a low percentage of positive tumour cells for AGR2 (HR (95% CI) = 0.61 (0.43-0.93)), and a low percentage of positive tumour cells for LOX5 expression (HR (95% CI) = 2.53 (1.23-5.22)) are predictors of BCR after RP. In contrast, FASN expression had no prognostic value for PCa.

Immuno-based detection of extracellular vesicles in urine as diagnostic marker for prostate cancer.

Extracellular vesicles (including the subclass exosomes) secreted by cells contain specific proteins and RNA that could be of interest in determining new markers. Isolation/characterization of PCa-derived exosomes from bodily fluids enables us to discover new markers for this disease. Unfortunately, isolation with current techniques (ultracentrifugation) is labor intensive and other techniques are still under development. The goal of our study was to develop a highly sensitive time-resolved fluorescence immunoassay (TR-FIA) for capture/detection of PCa-derived exosomes. In our assay, biotinylated capture antibodies against human CD9 or CD63 were incubated on streptavidin-coated wells. After application of exosomes, Europium-labeled detection antibodies (CD9 or CD63) were added. Cell medium from 37 cell lines was taken to validate this TR-FIA. Urine was collected (after digital rectal exam) from patients with PCa (n = 67), men without PCa (n = 76). As a control, urine was collected from men after radical prostatectomy (n = 13), women (n = 16) and patients with prostate cancer without digital rectal exam (n = 16). Signal intensities were corrected for urinary PSA and creatinine. This TR-FIA can measure purified exosomes with high sensitivity and minimal background signals. Exosomes can be measured in medium from 37 cell lines and in urine. DRE resulted in a pronounced increase in CD63 signals. After DRE and correction for urinary PSA, CD9 and CD63 were significantly higher in men with PCa. This TR-FIA enabled us to measure exosomes with high sensitivity directly from urine and cell medium. This TR-FIA forms the basis for testing different antibodies directed against exosome membrane markers to generate disease-specific detection assays.

Alpha-blockers as medical expulsive therapy for ureteral stones.

BACKGROUND: Urinary stone disease is one of the most common reasons for patients visiting a urology practice, affecting about 5% to 10% of the population. Annual costs for stone disease have rapidly increased over the years and most patients with ureteral colic or other symptoms seek medical care. Stone size and location are important predictors of stone passage. In most cases medical expulsive therapy is an appropriate treatment modality and most studies have been performed with alpha-blockers. Alpha-blockers tend to decrease intra-ureteral pressure and increase fluid passage which might increase stone passage. Faster stone expulsion will decrease the rate of complications, the need for invasive interventions and eventually decrease healthcare costs. A study on the effect of alpha-blockers as medical expulsive therapy in ureteral stones is therefore warranted. OBJECTIVES: This review aimed to answer the following question: does medical treatment with alpha-blockers compared to other pharmacotherapy or placebo impact on stone clearance rate, in adult patients presenting with symptoms of ureteral stones less than 10 mm confirmed by imaging? Other clinically relevant outcomes such as stone expulsion time, hospitalisation, pain scores, analgesic use and adverse effects have also been explored. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 9 July 2012 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), comparing alpha-blockers with other pharmacotherapy or placebo on ureteral stone passage in adult patients were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Reporting bias was investigated using funnel plots. Subgroup analysis was used to explore possible sources of heterogeneity. Sensitivity analysis was performed removing studies of poor methodological quality. MAIN RESULTS: Thirty-two studies (5864 participants) were included. The stone-free rates were significantly higher in the alpha-blocker group (RR 1.48, 95% CI 1.33 to 1.64) when compared to standard therapy. Stone expulsion time was 2.91 days shorter with the use of alpha-blockers (MD -2.91, 95% CI -4.00 to -1.81). Use of alpha-blockers reduced the number of pain episodes (MD -0.48, 95% CI -0.94 to -0.01), the need for analgesic medication (diclofenac) (MD -38.17 mg, 95% CI -74.93 to -1.41) and hospitalisation (RR 0.35, 95% CI 0.13 to 0.97). Patients using alpha-blockers were more likely to experience adverse effects when compared to standard therapy (RR 2.74, 95% CI 1.38 to 5.45) or placebo (RR 2.73, 95% CI 1.50 to 4.96). Most adverse effects were mild of origin and did not lead to cessation of therapy, and several studies reported no adverse events in either the treatment or control group.In 7/32 studies patients and doctors were both blinded. In the other studies blinding was not described in the methods or no blinding had taken place. Two studies described incomplete data and only one study showed a relatively high number of patients who withdrew from the study. These factors limited the methodological strength of the evidence found. AUTHORS' CONCLUSIONS: The use of alpha-blockers in patients with ureteral stones results in a higher stone-free rate and a shorter time to stone expulsion. Alpha-blockers should therefore be offered as part of medical expulsive therapy as one of the primary treatment modalities.

Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer.

BACKGROUND: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, the complexity of body fluids often hampers biomarker discovery. An attractive alternative approach is the isolation of small vesicles, i.e. exosomes, ∼100 nm, which contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific biomarker discovery. MATERIALS AND METHODS: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. After tryptic digestion, proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode. Accurate Mass and Time (AMT) tag approach was employed for peptide identification and quantitation. Candidate biomarkers were validated by Western blotting and Immunohistochemistry. RESULTS: Proteomic characterization resulted in the identification of 248, 233, 169, and 216 proteins by at least 2 peptides in exosomes from PNT2C2, RWPE-1, PC346C, and VCaP, respectively. Statistical analyses revealed 52 proteins differently abundant between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. CONCLUSIONS: Identification of exosomal proteins using high performance LC-FTMS resulted in the discovery of PDCD6IP, FASN, XPO1 and ENO1 as new candidate biomarkers for prostate cancer.

Exosomes as biomarker treasure chests for prostate cancer.

CONTEXT: Although progress has been made with regard to types of markers (protein, DNA, RNA, and metabolites) and implementation of improved technologies (mass spectrometry, arrays, and deep sequencing), the discovery of novel biomarkers for prostate cancer (PCa) in complex fluids, such as serum and urine, remains a challenge. Meanwhile, recent studies have reported that many cancer-derived proteins and RNAs are secreted through small vesicles known as exosomes. OBJECTIVE: This narrative review describes recent progress in exosome research, focusing on the potential role of exosomes as novel biomarkers for PCa. The purpose of this review is to acquaint clinicians and researchers in the field of urology with the potential role of exosomes as biomarker treasure chests and with their clinical value. EVIDENCE ACQUISITION: Medline and Embase entries between 1966 and September 2010 were searched using the keywords exosomes, microvesicles, prostasomes, biomarkers, prostate cancer, and urology. Leading publications and articles constructively contributing to exosome research were selected for this review. EVIDENCE SYNTHESIS: Exosomes are small vesicles (50-100 nm) secreted by almost all tissues; they represent their tissue origin. Purification of prostate- and PCa-derived exosomes will allow us to profile exosomes, providing a promising source of protein and RNA biomarkers for PCa. This profiling will contribute to the discovery of novel markers for the early diagnosis and reliable prognosis of PCa. CONCLUSIONS: Although the initial results are promising, further investigations are required to assess the clinical value of these exosomes in PCa.

Steroid injection in addition to macular laser grid photocoagulation in diabetic macular oedema: a systematic review.

OBJECTIVES: This study aimed to evaluate the evidence for the effects of steroid injection in addition to macular laser grid (MLG) photocoagulation versus those of MLG photocoagulation alone on visual acuity (VA) in patients with diabetic macular oedema (DMO). METHODS: An extensive literature search in Medline (PubMed), Experta Medica (EMBASE) and the Cochrane Library (CENTRAL) using synonyms for MLG photocoagulation, steroid injection and DMO found 181 articles. Of the articles that met selection criteria, three studies in which patients receiving MLG photocoagulation were randomized to additional pretreatment with steroids provided the best available evidence. In addition to VA, central foveal thickness (CFT) was measured at baseline and at 6 months in all three studies. RESULTS: Two studies, with total populations of 73 and 42 eyes, respectively, reported no additional effect of steroid injection on VA. One study, with a total of 41 eyes, reported a beneficial effect of pretreatment with steroids on VA of -0.21 ETDRS logMAR units. All three studies reported larger reductions in CFT in eyes pretreated with steroids, the smallest of which was 64 microm. CONCLUSIONS: Although there is a greater reduction in CFT in eyes pretreated with steroids, this does not consistently result in higher VA. The literature search does not provide sufficiently strong evidence to recommend steroid injection before MLG photocoagulation in DMO.

alpha-Blockers to assist stone clearance after extracorporeal shock wave lithotripsy: a meta-analysis.

OBJECTIVE: To review the evidence for the use of alpha-blockers after extracorporeal shock wave lithotripsy (ESWL) in enhancing the effectiveness of renal and ureteric stone clearance. METHODS: We searched MEDLINE, Embase and the Cochrane Library up to January 2009. All randomized controlled trials in which alpha-blockers were evaluated after ESWL were eligible for the analysis. Outcome measures assessed were clearance rate (primary) and expulsion time (secondary). Two authors independently assessed study quality and extracted data. All data were analysed using RevMan 5. RESULTS: Of the 29 identified papers, seven trials with a total of 484 patients met the predefined criteria. These studies evaluated the effectiveness of the alpha-blocker tamsulosin, and studied clearance rate as the primary outcome. There was large heterogeneity between trials, but their methodological quality was adequate. The pooled absolute risk difference of clearance rate was 16% (95% confidence interval 5-27%) in favour of the tamsulosin group, i.e. an average of six patients have to be treated with tamsulosin after ESWL to achieve clearance in one. Subgroup analysis for the six studies that used a dose of 0.4 mg tamsulosin showed a pooled risk difference of 19 (10-29)%. The expulsion time was analysed in three studies and the pooled mean difference was 8 (-3-20) days in favour of the tamsulosin group. Pain and analgesic usage was reported to be lower with tamsulosin. Adverse effects of tamsulosin, mainly dizziness, were reported in eight patients (3%). CONCLUSIONS: Treatment with tamsulosin after ESWL appears to be effective in assisting stone clearance in patients with renal and ureteric calculi. To make a definite clinical recommendation to use tamsulosin after ESWL for renal and ureteric calculi, a high quality confirmatory trial is warranted.

[Urological symptoms due to rectus sheath haematoma]. / Urologische symptomen bij het rectusschedehematoom.

Two men presented at the Accident & Emergency Department with lower urinary tract symptoms. The first patient was a 76-year-old male with reddish urine and lower abdominal pain. A CT-scan revealed a tumorous mass related to the bladder. The second patient was a 61-year-old male with dysuria and lower abdominal pain. In both patients the complaints were due to a rectus sheath haematoma. Rectus sheath haematoma is a rare condition caused by damage of the epigastric vessels or a rupture of the rectus abdominis muscle. Voiding problems can arise when the haematoma extends into the prevesical (Retzius) space that is anatomically related to the rectus sheath. A haematoma of the rectus sheath is difficult to diagnose. Current insights show that conservative treatment is generally sufficient.