Use of TP4303 to identify prostate cancer cells in voided urine samples.

INTRODUCTION: Prostate cancer is the second most common malignancy in men worldwide. Genomic VPAC receptors are expressed on malignant prostate cancer cells and can be targeted and imaged optically by a peptide labeled fluorophore. The objective of our study was to assess the feasibility of detecting cancer of the prostate using a voided urine sample. MATERIALS AND METHODS: Patients ≥ 40 years old, with lower urinary tract symptoms and serum PSA > 4 ng/mL formed the study group. The first 50 mL of voided urine sample was collected and processed. The cells that were shed in the voided urine were fixed and stained with a peptide TP4303 and incubated. The slide was then stained with DAPI which binds with the DNA in the nucleus. All patients underwent a standard 12-core TRUS-guided prostate biopsy. RESULTS: A total of 318 patients were included in the study, of these 158 were histologically confirmed cancers. Voided urine samples were positive for VPAC receptors in 154 (97.46%) of these. The remaining 160 patients had no cancer on the HPR examination and none of these patients were positive for VPAC receptors. CONCLUSIONS: This study validates our belief that patients with prostate cancer shed malignant cells in the urine that can be identified by targeting the VPAC receptors. If these results are further validated by multicentric studies, then this could form the basis for indications for a preliminary prostate biopsy in patients with elevated serum PSA but normal digital examination or in patients needing a repeat biopsy.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART II-Surgical Evaluation and Treatment.

PURPOSE: Surgical therapies for symptomatic bladder outlet obstruction (BOO) due to benign prostatic hyperplasia (BPH) are many, and vary from minimally invasive office based to high-cost operative approaches. This Guideline presents effective evidence-based surgical management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). See accompanying algorithm for a detailed summary of procedures (figure[Figure: see text]). MATERIALS/METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible studies published between January 2007 and September 2020, which includes the initial publication (2018) and amendments (2019, 2020). The Team also reviewed articles identified by Guideline Panel Members. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). RESULTS: Twenty-four guideline statements pertinent to pre-operative and surgical management were developed. Appropriate levels of evidence and supporting text were created to direct urologic providers towards suitable and safe operative interventions for individual patient characteristics. A re-treatment section was created to direct attention to longevity and outcomes with individual approaches to help guide patient counselling and therapeutic decisions. CONCLUSION: Pre-operative and surgical management of BPH requires attention to individual patient characteristics and procedural risk. Clinicians should adhere to recommendations and familiarize themselves with criteria that yields the highest likelihood of surgical success when choosing a particular approach for a particular patient.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia: AUA GUIDELINE PART I-Initial Work-up and Medical Management.

PURPOSE: Benign prostatic hyperplasia (BPH) is a histologic diagnosis describing proliferation of smooth muscle and epithelial cells within the prostatic transition zone. The prevalence and severity of lower urinary tract symptoms (LUTS) in aging men are progressive and impact the health and welfare of society. This revised Guideline provides a useful reference on effective evidence-based management of male LUTS/BPH. See the accompanying algorithm for a summary of the procedures detailed in the Guideline (figures 1 and 2[Figure: see text][Figure: see text]). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, Embase, Cochrane Library, and AHRQ databases to identify eligible English language studies published between January 2008 and April 2019, then updated through December 2020. Search terms included Medical Subject Headings (MeSH) and keywords for pharmacological therapies, drug classes, and terms related to LUTS or BPH. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Nineteen guideline statements pertinent to evaluation, work-up, and medical management were developed. Appropriate levels of evidence and supporting text were created to direct both primary care and urologic providers towards streamlined and suitable practices. CONCLUSIONS: The work up and medical management of BPH requires attention to individual patient characteristics, while also respecting common principles. Clinicians should adhere to recommendations and familiarize themselves with standards of BPH management.

Post-void residual urine ratio: A novel clinical approach to the post-void residual urine in the assessment of males with lower urinary tract symptoms.

PURPOSE: To assess the correlation between post-void residual urine ratio (PVR-R) and pathological bladder emptying diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: PVR-R and PVR urine were evaluated in 410 males underwent PFS for LUTS. PVR-R was the percentage of PVR to bladder volume (voided volume+PVR). Schafer and International Continence Society (ICS) nomograms, Bladder Contractility Index (BCI) were used to diagnose bladder outlet obstruction (BOO) and detrusor underactivity (DUA). We subdivided the cohort in 4 groups: Group I, BOO+/DUA+; Group II, BOO-/DUA+; Group III, BOO+/DUA-; Group IV, BOO-/DUA- (control group). We subdivided the 4 groups according to PVR-R strata: (1) 0%-20%; (2) 21%-40%; (3) 41%-60%; (4) 61%-80%; (5) 81%-100%. RESULTS: Group I had a greater median PVR-R (50%) with a >40% in 61.4% of the cohort. Median PVR-R was 16.6% in Group II, 24% in Group III, and 0% in the control Group. According to ICS nomograms and BCI, median PVR-R and PVR were significantly higher (p<0.001) in obstructed and underactive males. PVR-R threshold of 20% allowed to recognize males with voiding disorders with high sensibility, specificity, PPV, and NPV. A PVR-R cut-off of 40% identified males with associated BOO and DUA and more severe voiding dysfunction. CONCLUSIONS: A higher PVR-R is related to a more severe pathological bladder emptying, and to the association of BOO and DUA. PVR-R may have a clinical role in first assessment of males with LUTS and severe voiding dysfunction.

Changes in Bacterial Spectrum and Resistance Patterns Over Time in the Urine of Patients with Neurogenic Lower Urinary Tract Dysfunction Due to Spinal Cord Injury.

INTRODUCTION: Urinary tract infections (UTI) are among the most common complications in persons with neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI). As both asymptomatic bacteriuria and UTI are frequently treated with antibiotics, concerns about multidrug resistance arise. Therefore, we analyzed the bacterial spectrum in the urine and the resistance patterns of the strains over time in patients with NLUTD due to SCI. METHODS: In a systematic chart review, we identified all microbiologic urine test results including resistance patterns of persons with SCI in a tertiary referral hospital at 2 time periods (2010-2011 and 2017-2018). We assessed the frequency of the bacterial strains, the resistance patterns of the 5 most frequent bacteria, and the use of antibiotics for in- as well as for outpatients. RESULTS: From 2010 to 2011, 1,308 (outpatients) and 2,479 (inpatients) bacterial strains were detected in the urinalyses performed; these numbers rose to 3,162 and 6,112 during 2017-2018, respectively. The most frequently detected bacteria during both time periods were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae/variicola, Streptococcus viridans, Pseudomonas aeruginosa, and coagulase negative Staphylococci. Fluoroquinolones were the most frequently used antibiotics during both time periods. Despite its frequent use, no relevant increase in resistance against fluoroquinolones was detected. The most prominent increase in resistance appeared in E. coli against amocixillin/clavulanic acid in inpatients (from 26.0 to 38.5%). DISCUSSION AND CONCLUSIONS: Although fluoroquinolones were used frequently, we did not observe an increased resistance against these antibiotics over time in the urine of patients with SCI.

National trends in the use of PSA, urinalysis, and digital rectal exam for evaluation of lower urinary tract symptoms in men.

PURPOSE: The purpose of this study was to describe the practices of primary care physicians (PCPs) and urologists in their implementation of the 2010 American Urological Association (AUA) recommendations for the management of benign prostatic hyperplasia (BPH) in a nationally representative sample. METHODS: Data collected from 2008 to 2015 in the National Ambulatory Medical Care Survey (NAMCS) were used. Men aged 45 and older who presented with either a new complaint or exacerbation of lower urinary tract symptoms (LUTS) were included. Primary outcomes were the prevalence and determinants of prostate-specific antigen (PSA) testing, urinalysis (UA), and digital rectal exam (DRE), as all three were included in the AUA guidelines during the time period studied. In logistic regression analyses weighted to reflect national estimates, potential determinants of adherence for each testing modality were examined. RESULTS: Between 2008 and 2015, 878 visits met inclusion criteria, corresponding to 14,399,121 ambulatory visits for new or exacerbated LUTS. Weighted prevalence estimates were 24% for PSA testing (95% CI: 19-29%), 61% for urinalysis (95% CI: 56-66%), and 18% for DRE (95% CI: 15-23%). Age ≥ 75 years was associated with lower prevalence of testing for all three tests, and region was associated with different testing estimates for PSA and UA. Patients referred to urologists were more likely to receive a DRE, although overall rates of DRE decreased per additional year of data. CONCLUSIONS: Adherence to AUA guidelines for evaluation of LUTS in ambulatory visits was low in a nationally representative sample of Americans, particularly for PSA testing and DRE, suggesting substantial discordance between guidelines at the time and practice patterns. Practice patterns also differed by age and region. These discrepancies encourage increased education of providers in the implementation of the guidelines, particularly since they have been updated recently.

Urinary Amine Metabolomics Characterization with Custom 12-Plex Isobaric DiLeu Labeling.

Lower urinary tract symptoms (LUTS) is common in aging males. Disease etiology is largely unknown but likely includes inflammation and age-related changes in steroid hormones. Diagnosis is currently based on subjective symptom scores, and mainstay treatments can be ineffective and bothersome. Biomarker discovery efforts could facilitate objective diagnostic criteria for personalized medicine and new potential druggable pathways. To identify urine metabolite markers specific to hormone-induced bladder outlet obstruction, we applied our custom synthesized multiplex isobaric tags to monitor the development of bladder outlet obstruction across time in an experimental mouse model of LUTS. Mouse urine samples were collected before treatment and after 2, 4, and 8 weeks of steroid hormone treatment and subsequently analyzed by nanoflow ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry. Accurate and high-throughput quantification of amine-containing metabolites was achieved by 12-plex DiLeu isobaric labeling. Metandem, a novel online software tool for large-scale isobaric labeling-based metabolomics, was used for identification and relative quantification of labeled metabolites. A total of 59 amine-containing metabolites were identified and quantified, 9 of which were changed significantly by the hormone treatment. Metabolic pathway analyses showed that three metabolic pathways were potentially disrupted. Among them, the arginine and proline metabolism pathway was significantly dysregulated both in this model and in a prior analysis of LUTS patient samples. Proline and citrulline were significantly changed in both samples and serve as attractive candidate biomarkers. The 12-plex DiLeu isobaric labeling with Metandem data processing presents an accessible and efficient workflow for an amine-containing metabolome study in biological specimens.

Obstructive Sleep Apnea Syndrome as a Potential Cause of Nocturia in Younger Adults.

OBJECTIVES: To investigate the impact of age on the relationship between obstructive sleep apnea syndrome (OSAS), nocturia, and other lower urinary tract symptoms (LUTSs). METHODS: This was a secondary analysis study based on data derived from a previously conducted prospective observational cohort study on OSAS and nocturia. We analyzed 90 subjects who were suspected of having OSAS. Prior to polysomnography, we assessed International Prostate Symptom Score-Quality of Life scores, Overactive Bladder Symptom Scores, and International Consultation on Incontinence Modular Questionnaire-Nocturia Quality of Life scores to evaluate LUTSs. Nocturnal urine volume, night-time frequency, and night-time urine electrolyte content were measured during polysomnography. Patients were divided into groups according to age and OSAS severity determined using apnea-hypopnea index (AHI) scores. Young patients were those aged <65 years and elderly patients, ≥65 years. A multiple linear regression with multiple imputations was performed to examine the association of night-time frequency with demographic, polysomnographic, and clinical characteristics. RESULTS: In young patients, night-time frequency was significantly associated with nocturnal urine volume, AHI score, and total IPSS. However, night-time frequency in elderly subjects was not associated with demographic and polysomnographic characteristics. In order to compare the severity of OSAS, night-time frequency and urinary sodium content significantly increased only in young patients (P = .007 and .004, respectively). CONCLUSION: OSAS is a strong candidate of causative factor for nocturia in younger individuals. When a younger patient complains nocturia without any urological disorders, OSAS should be kept in mind as a potential cause of nocturia.

Safety, Tolerability, Pharmacokinetics, and Food Effects on TAC-302 in Healthy Participants: Randomized, Double-Blind, Placebo-Controlled, Single-Dose and Multiple-Dose Studies.

TAC-302 stimulates neurite outgrowth activity and is expected to restore urinary function in patients with lower urinary tract dysfunction. We conducted 2 phase 1, randomized, placebo-controlled studies to confirm the safety and pharmacokinetics (PK) of TAC-302 in healthy adult Japanese male volunteers. In the first-in-human single-dose study (n = 60), TAC-302 was administered at doses from 100 to 1200 mg after an overnight fast. The effects of a meal on the PK of TAC-302 400 mg were also examined. A multiple-dose study (n = 36) evaluated the effects of meal fat content on the PK of single doses of TAC-302 (100, 200, or 400 mg) and multiple doses of TAC-302 administered for 5 days (100, 200, and 400 mg twice daily). TAC-302 showed linear PK up to doses of 1200 mg in the fasting state, and across the dose range of 100-400 mg in the fed state. No accumulation of TAC-302 was observed. Food, particularly with high fat content, increased TAC-302 plasma concentrations. No differences were observed in the adverse event incidence between the TAC-302 and placebo groups in either study. TAC-302 showed a wide safety margin.

A Novel Proteomics Approach to Identify Serum and Urinary Biomarkers and Pathways that Associate with Lower Urinary Tract Symptoms in Men and Women: Pilot Results of the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) Study.

OBJECTIVES: To assess the feasibility of a novel proteomics approach to identify biomarkers associated with lower urinary tract symptoms (LUTS) within serum and urine, because many clinical factors contribute to LUTS in men and women. These factors confound clinicians' abilities to reliably evaluate and treat LUTS. Previous studies identified candidate LUTS biomarkers, but none are clinically utilized. METHODS: Eighteen male and 18 female symptoms of lower urinary tract dysfunction research network (LURN) observational cohort study participants with LUTS (measured on the LUTS Tool questionnaire) were randomly selected. Twelve male and 12 female controls with minimal or no LUTS were recruited and matched for clinico-demographic characteristics. The SomaScan Assay (SomaLogic) was used to measure the abundance of 1305 proteins contained within urine and serum. Statistical analyses were performed to evaluate reproducibility of assays, compare protein abundances, and estimate effect size. RESULTS: SomaScan assay results were more reproducible in serum than in urine. Within serum, there were many more differentially abundant proteins between cases and controls in males than in females. An enrichment/pathway analysis of the affected proteins in male and female subjects demonstrated that the enriched Gene Ontology processes were related to prostate morphogenesis in men and growth and inflammation in women. CONCLUSION: The pilot study results support that the etiology and pathophysiologic mechanisms underlying LUTS may be sex-specific. While further studies involving larger numbers of subjects are warranted, our results support the feasibility of a novel proteomic approach to identify biomarkers for diagnostic classification of LUTS.

The Impact of Chronic Pelvic Ischemia on LUTS and Urinary Levels of Neuroinflammatory, Inflammatory, and Oxidative Stress Markers in Elderly Men: A Case-control Study.

OBJECTIVE: To investigate lower urinary tract symptoms (LUTS) and urinary levels of neuroinflammatory, inflammatory, and oxidative stress markers in elderly men with chronic pelvic ischemia (CPI) caused by significant aortoiliac disease. MATERIALS AND METHODS: Thirteen men aged over 60 years, with aorta, unilateral or bilateral common/internal iliac artery occlusion documented by computed tomography angiography or angiography, were enrolled from the vascular surgery department. Twelve sex- and age-matched controls without significant aortoiliac disease were used for comparison. Exclusion criteria included neurogenic bladder dysfunction, bladder or prostate cancer, prostatic surgery, pelvic radiotherapy, or chronic treatment for LUTS. Participants underwent urological examination, including assessment of International Prostate Symptom Score (IPSS), uroflowmetry, postvoid residual (PVR), and prostate volume. Urine samples were collected, and levels of neuroinflammatory (nerve growth factor, NGF), inflammatory (cytokines), and oxidative stress markers (8-hydroxy-2'-deoxyguanosine) were determined by enzyme-linked immunosorbent assay. RESULTS: Groups were similar for age, PVR, prostate volume, and most cardiovascular risk factors. IPSS was higher in patients with CPI (11 ± 3 vs 8 ± 2, P = .02), with a significant mean difference between groups of three points. Urinary NGF was significantly higher in men with CPI (3.7 ± 0.8 vs 2.9 ± 0.7, P = .02), but no differences were found in inflammatory and oxidative biomarkers among groups. CONCLUSION: Severe CPI in elderly men is associated with a significant increase in LUTS and bladder neurogenic inflammation, as suggested by the increase of NGF release in urine, sensitizing bladder afferents. These findings confirm the relevance of ischemia in bladder function and appear to validate animal models of bilateral iliac artery occlusion.

Development of novel and non-invasive diagnostic markers for lower urinary tract symptoms using urothelial cells in voided urine.

OBJECTIVES: We evaluated the association between lower urinary tract symptoms (LUTS) and the expression of connexin (Cx) and transient receptor potential (TRP) channel on urothelial cells non-invasively collected from voided urine in humans. METHODS: A total of 55 patients (36 males and 19 females, median age: 71 years old), who were followed up at University of Yamanashi Hospital, were enrolled in the present study. Urothelial cells were collected from voided urine of patients, and the mRNA expression of each subtype of Cxs and TRP channels was measured using quantitive real-time reverse transcription polymerase chain reaction. We then analyzed the correlation between the expression of Cxs and TRP channels and symptom scores in International Prostate Symptom Scoreand Overactive Bladder Symptom Score, in addition to Interstitial Cystitis Symptom Index (ICSI) from only interstitial cystitis (IC) patients. RESULTS: Non-adjusted statistical procedure using Spearman's rank-correlation showed that there were significant correlations between the following expressions and symptom scores; (positive correlations) Cx26 versus urgency score, Cx40 versus nocturia, TRPM2 versus intermittency, TRPV1 versus urge incontinence, (negative correlation) Cx40 versus intermittency, TRPM7 versus pollakisuria. However, a multiple comparison adjustment using Bonferroni correction showed that only Cx40 had a trend of correlation with nocturia in ICSI. CONCLUSIONS: The expressions of Cxs and TRP channels on urothelial cells in voided urine could be related to LUTS. Further analysis of urothelial cells in voided urine has the potential to reveal the mechanism of the LUTS and develop new markers with non-invasive methods.

Lower urinary tract symptoms that predict microscopic pyuria.

INTRODUCTION AND HYPOTHESIS: Urinary dipsticks and culture analyses of a mid-stream urine specimen (MSU) at 105 cfu ml-1 of a known urinary pathogen are considered the gold standard investigations for diagnosing urinary tract infection (UTI). However, the reliability of these tests has been much criticised and they may mislead. It is now widely accepted that pyuria (≥1 WBC µl-1) detected by microscopy of a fresh unspun, unstained specimen of urine is the best biological indicator of UTI available. We aimed to scrutinise the greater potential of symptoms analysis in detecting pyuria and UTI. METHODS: Lower urinary tract symptom (LUTS) descriptions were collected from patients with chronic lower urinary tract symptoms referred to a tertiary referral unit. The symptoms informed a 39-question inventory, grouped into storage, voiding, stress incontinence and pain symptoms. All questions sought a binary yes or no response. A bespoke software package was developed to collect the data. The study was powered to a sample of at least 1,990 patients, with sufficient power to analyse 39 symptoms in a linear model with an effect size of Cohen's f2 = 0.02, type 1 error probability = 0.05; and power (1-ß); 95% where ß is the probability of type 2 error). The inventory was administered to 2,050 female patients between August 2004 and November 2011. The data were collated and the following properties assessed: internal consistency, test-retest reliability, inter-observer reliability, internal responsiveness, external responsiveness, construct validity analysis and a comparison with the International Consultation on Incontinence Modular Questionnaire for female lower urinary tract symptoms (ICIQ-FLUTS). The dependent variable used as a surrogate marker of UTI was microscopic pyuria. An MSU sample was sent for routine culture. RESULTS: The symptoms proved reliable predictors of microscopic pyuria. In particular, voiding symptoms correlated well with microscopic pyuria (χ2 = 88, df = 1, p < 0.001). The symptom inventory has significant psychometric characteristics as below: test-retest reliability: Cronbach's alpha was 0.981; inter-observer reliability, Cronbach's alpha was 0.995, internal responsiveness F = 221, p < 0.001, external responsiveness F = 359, df = 5, p < 0.001. The correlation coefficients for the domains of the ICIQ-FLUTS were around R = 0.5, p < 0.001. CONCLUSION: This symptoms score performed well on the standard, psychometric validation. The score changed in response to treatment and in a direction appropriate to the changes in microscopic pyuria. It correlated with measures of quality of life. It would seem to make a good candidate for monitoring treatment progress in ordinary clinical practice.

Association of increased urine brain derived neurotrophic factor with lower urinary tract symptoms in men with benign prostatic hyperplasia.

Urinary brain-derived neurotrophic factor (BDNF), an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia (BPH). We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms (LUTS) in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score (IPSS) was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity (DO) in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine (Cr) levels. Seventy-six BPH patients were divided into moderate LUTS group (n=51, 720) according to the IPSS. Of the 76 BPH patients, DO was present in 34 (44.7%) according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS (8.29±3.635, P<0.0001) and severe LUTS (11.8±6.44, P<0.0001) than normal controls (1.71±0.555). Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS (11.8±6.44 vs. 8.29±3.635, P=0.000). The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker for the diagnosis of DO in BPH patients.

Diagnosis of trichomoniasis in men by urine cytology.

BACKGROUND: Trichomonas vaginalis is a rare finding in urine cytology specimens, especially those from men; only 2 case reports have been described in the literature. The authors of the current report sought to determine the incidence and clinical significance of this finding in urine cytology in males. METHODS: The authors' cytopathology archives were queried for urine cytology specimens that contained Trichomonas over a 30-year period. Clinical information from men with Trichomonas-positive urines was reviewed retrospectively. Slides were reviewed, and the morphologic characteristics of the organisms were recorded. RESULTS: Trichomonas was detected in 73 of 60,000 urine cytology specimens (0.1%). The patients included 45 women and 28 men. Men with Trichomonas in their urine ranged in age from 28 to 87 years (mean age, 67 years; median, 71 years). Trichomonas organisms were round to oval, with eccentric nuclei and cytoplasmic granules. Acute inflammation was observed in 6 of 7 cases. Clinical history was available in 13 of 28 men. Lower urinary tract symptoms were reported in 10 of 13 men, most commonly hematuria; and urethral strictures were identified by cystoscopy in 3 of 13 men. Clinical follow-up was available for 10 of 13 patients; of these, 8 (80%) had received treatment with metronidazole based on urine cytology results. CONCLUSIONS: This study is the largest series of Trichomonas infection in men diagnosed by urine cytology in the literature. Most men had no prior diagnosis of trichomoniasis and received specific antibiotic therapy based on their urine cytology results. Urine cytology may represent the initial diagnostic test for Trichomonas in men, and accurate cytologic diagnosis may prevent undesired adverse outcomes for them and their partners. Cancer Cytopathol 2017;125:55-59. © 2016 American Cancer Society.

[A Study of the Efficacy of the Additional Administration of Tadalafil in Japanese Men with α1-Blocker-Resistant LUTS/BPH].

Alpha 1-blockers are widely used at present for lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). However, some patients experience little improvement of symptoms, and it is difficult to provide additional treatment. We have additionally administered tadalafil to patients with inadequate symptom improvement, despite treatment with alpha-1 blockers. The subjects were 57 patients with a diagnosis of LUTS/BPH who showed a poor response to treatment with alpha-1 blockers for 1 month or more (international prostate symptom score [IPSS] ≥8 and/or quality of life [QOL] index ≥3). Tadalafil 5 mg was administered on consecutive days to patients orally receiving alpha-1 blockers. We determined IPSS, the QOL index, overactive bladder symptom scores (OABSS), maximum urine flow, residual urine volume, and the sexual health inventory for men (SHIM) before, and 4, 8, and 12 weeks after administration, and then evaluated improvement effects. IPSS, the QOL index, OABSS, and SHIM showed significant improvement (P ＜0.05) at 4 weeks after the start of treatment and onward. IPSS and the QOL index showed greater improvement effects at 8 and 12 weeks. Residual urinary volume was significantly improved only at 8 weeks. However, the maximum urine flow showed no improvement at any time point. Our results demonstrated the additional administration of tadalafil to patients with LUTS showing poor responses to alpha-1 blockers to improve LUTS/BPH symptoms as well as sexual function.

Solifenacin and Tamsulosin Combination Therapy Decreases Urine Nerve Growth Factor/Creatinine Levels in Men.

OBJECTIVE: To evaluate urinary nerve growth factor (NGF)/creatinine (Cr) levels from men with symptomatic lower urinary tract symptoms (LUTS) and measure the effect of combination therapy with solifenacin and tamsulosin. MATERIALS AND METHODS: From January 2012 to February 2014, all male patients referred for evaluation and management of LUTS were screened for enrollment. In all subjects, urinary NGF and Cr levels were measured and normalized to the urinary Cr concentrations (NGF/Cr). Uroflow, postvoid residual, and symptom questionnaires were measured at baseline, 4 weeks, 8 weeks, and 12 weeks after starting combination therapy with solifenacin 5 mg and tamsulosin 0.4 mg. The primary endpoint was urinary NGF and NGF/Cr change from baseline compared with week 12. RESULTS: Ten patients were recruited into the study. Peak urine flow at baseline 20.3 ± 2.5 ml/s and postvoid residual 45.3 ± 13.6 ml did not significantly change with 3 months of combination treatment 14.9 ± 1.8 ml/s and 58.5 ± 23.9 ml. However, urine NGF/Cr (pg/mg) levels were significantly reduced following treatment with levels of 39.7 ± 6.6 at baseline to 17.9 ± 5.1 at 3 months (P value <.05). The decrease in urine NGF/Cr levels correlated with significant decreases in patient reported outcomes. CONCLUSION: Male patients with LUTS had decreased urinary NGF/Cr levels after treatment with combination solifenacin and tamsulosin in this novel pilot study. This corresponded with improvement in patient reported outcomes.

Decreased urinary glycosaminoglycan excretion following alfuzosin treatment on ureteral stent-related symptoms: a prospective, randomized, placebo-controlled study.

The objectives of the study were to evaluate changes in ureteral stent-related symptoms and urinary glycosaminoglycan (GAG) excretion after alfuzosin treatment, and to further investigate the relationship between stent-related symptoms and loss of urinary GAGs. Seventy consecutive patients scheduled for unilateral retrograde ureteroscopy with stent placement were recruited. Patients were randomly assigned to treatment with alfuzosin 10 mg/day or placebo for 3 weeks starting on the third postoperative day. The ureteral stent was removed when treatment stopped. International Prostate Symptom Score (IPSS), visual analog scale (VAS) score, and urinary GAG excretion were determined before treatment at 1, 2, and 3 weeks after treatment, and at 3 weeks after stent removal. Fifty-nine patients completed the study. IPSS, VAS score, and urinary GAG excretion were significantly lower in the alfuzosin group, compared with the placebo group, at 1, 2, and 3 weeks after treatment (P < 0.01). In both groups, IPSS, VAS score, and urinary GAG excretion were significantly lower at 3 weeks after stent removal compared with those before stent removal. No significant differences in IPSS, VAS score, or urinary GAG excretion were observed between the two groups at baseline and 3 weeks after stent removal (P > 0.05). Positive correlations were found between urinary GAG excretion (R(2) = 0.65, P < 0.001) and IPSS and between urinary GAG excretion and VAS score (R(2) = 0.33, P < 0.001). Stent placement contributes to loss of urinary GAGs. However, alfuzosin effectively reduces such loss and improves ureteral stent-related symptoms. Loss of urinary GAGs plays a role in these symptoms.

Evaluación clínica del paciente con síntomas del tracto urinario inferior / Clinical evaluation of the patient with lower urinary tract symptoms

Lower urinary tract symptoms are divided into three groups, storage, voiding and post micturition symptoms. Their level of agreement with urodynamic investigation is poor. Clinicalhistory should be complemented by the application of validated symptom questionnaires and the recording of urinary events. Here we refer to: a) the International Consultation onIncontinence Questionnaire, Short Form (ICIQ-SF), b) the Urogenital Distress Inventory - Short Form (UDI-6) and Incontinence Impact Questionnaire – Short Form (IIQ-7), c) the urinary incontinence Severity Index and d) the American Urological Association Symptom Index. The recordings of urinary events can be done in three main forms: a) micturition time chart, b)frequency volume chart, and c) bladder diary. The International Consultation on Incontinence Questionnaire bladder diary (ICIQ bladder diary) is the only one validated. Physical exam should include abdominal and genital examination, covering pelvic organ prolapse quantification in women, prostate evaluation in men, pelvic floor muscle function evaluation in both genders, and a neurologic examination focused on evaluation of the sacral nerves. It is useful to supplementthe physical examination with the evaluation of the mobility of the bladder neck and proximal urethra through the Q-tip test, and with the quantification of urine leakage through the pad test.

Custom 4-Plex DiLeu Isobaric Labels Enable Relative Quantification of Urinary Proteins in Men with Lower Urinary Tract Symptoms (LUTS).

The relative quantification of proteins using liquid chromatography mass spectrometry (LC-MS) has allowed researchers to compile lists of potential disease markers. These complex quantitative workflows often include isobaric labeling of enzymatically-produced peptides to analyze their relative abundances across multiple samples in a single LC-MS run. Recent efforts by our lab have provided scientists with cost-effective alternatives to expensive commercial labels. Although the quantitative performance of these dimethyl leucine (DiLeu) labels has been reported using known ratios of complex protein and peptide standards, their potential in large-scale proteomics studies using a clinically relevant system has never been investigated. Our work rectifies this oversight by implementing 4-plex DiLeu to quantify proteins in the urine of aging human males who suffer from lower urinary tract symptoms (LUTS). Protein abundances in 25 LUTS and 15 control patients were compared, revealing that of the 836 proteins quantified, 50 were found to be differentially expressed (>20% change) and statistically significant (p-value <0.05). Gene ontology (GO) analysis of the differentiated proteins showed that many were involved in inflammatory responses and implicated in fibrosis. While confirmation of individual protein abundance changes would be required to verify protein expression, this study represents the first report using the custom isobaric label, 4-plex DiLeu, to quantify protein abundances in a clinically relevant system.