The correlation between erectile function and adiponectin levels in men with late-onset hypogonadism.

Aim: This study investigated the relationship between erectile dysfunction (ED) and adiponectin levels in hypogonadal men.Methods: In this study, 218 patients with hypogonadism (mean age: 65.1 ± 8.3 years) were enrolled. All patients underwent physical examinations, with measurement of body mass index, body fat ratio, and waist circumference. The erectile function was assessed using the sexual health inventory for men (SHIM) scoring system. Blood biochemical profiles such as free testosterone, fasting blood glucose, and lipid profile including adiponectin levels were measured. All patients were divided into two groups based on their SHIM score: normal to moderate ED (SHIM score ≥ 12) and severe ED (SHIM score < 12), and the factors associated with severe ED were determined. Patients with severe ED were divided into two groups based on adiponectin levels (cutoff value of 7.0 µg/mL), and their basic characteristics were compared between these two groups.Results: The severe ED group was older and had higher adiponectin levels. In patients with severe ED, various metabolic parameters were significantly worse in the low adiponectin groups than in the non-low adiponectin group.Conclusions: The risk of developing cardiovascular diseases is extremely high in hypogonadal men with severe ED who had lower serum adiponectin levels.

Low free testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors.

Aim: We investigated whether low plasma free testosterone (FT) levels could predict cardiovascular events (CVE) in Japanese men with coronary risk factors.Methods: Male patients with classical coronary risk factors who had undergone serum FT testing were enrolled. New incidences of CVE were retrospectively investigated among all eligible participants based on their medical records.Results: Overall, 466 male outpatients with coronary risk factors without a previous history of CVE were identified. Throughout the follow-up period (median = 92 months), 126 CVE occurred. The Kaplan-Meier survival analysis according to the tertiles of plasma FT levels revealed that patients with the lowest FT tertile (<6.5 pg/mL) had a higher likelihood of developing CVE than those with the highest tertile (>9.3 pg/mL) (p<.01). Multivariate analysis showed that increased frequency of CVE was observed with lower FT tertiles, independent of other coronary risk factors, with hazard ratios of 0.617 (95% CI, 0.389-0.976; p=.030) and 0.524 (95% CI, 0.309-0.887; p=.016) for the second and highest tertile relative to the lowest FT tertile, respectively.Conclusion: Among Japanese men with coronary risk factors, a lower FT level was a predictor for the development of cardiovascular diseases independent of other coronary risk factors and age.

The five-year effects of testosterone replacement therapy on lipid profile and glucose tolerance among hypogonadal men in Japan: a case control study.

Objective: This study investigated the efficacy of 5-year testosterone replacement therapy (TRT) on lipid profile and glucose tolerance in Japanese hypogonadal men.Methods: Fourteen patients, who received continuous TRT for 5 years, and 22 controls with 5-year observations were enrolled. The patients in the TRT group had received intramuscular injections of testosterone enanthate (250 mg) every month for 5 years. We collected the following data: blood pressure, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), total cholesterol, triglyceride (TG), high density lipoprotein-Chol values, and prostate specific antigen (PSA) level at baseline, 1-, 3-, and 5-years from initial intervention. These data were compared between the two groups.Results: There were no statistically significant differences in any other baseline characteristic, excluding SBP, between the two groups. FBS was significantly improved at 3- and 5-year visits in the TRT group compared to the control group. Furthermore, the HbA1c level and TG value demonstrated a significant decrease at 1-, 3-, and 5-years in the TRT group. However, no significant difference in changes to PSA levels from baseline in both groups was observed.Conclusions: Five-year TRT could improve FBS, HbA1c, and TG levels among Japanese hypogonadal men with no significant increase in PSA.

Sleep disturbance as a clinical sign for severe hypogonadism: efficacy of testosterone replacement therapy on sleep disturbance among hypogonadal men without obstructive sleep apnea.

OBJECTIVE: The present subanalysis of the EARTH study investigates the effects of one year testosterone replacement therapy (TRT) on sleep disturbance among hypogonadal men without obstructive sleep apnea. METHODS: Sleep disturbance was defined as three or more points in question 4 of the aging males symptoms (AMS) questionnaire. All participants completed the AMS scale, International Prostatic Symptoms Score (IPSS), Sexual Health Inventory for Men (SHIM) and Short Form 36 (SF-36) health survey at baseline and after 12 months. Sexual symptoms were also evaluated based on three AMS subscores (Q15, 16 and 17). RESULTS: We identified 100 patients with sleep disturbance, of whom 48 (24 each in the TRT and control groups) were ultimately included for analysis. All SF-36 categories , AMS scale, IPSS and SHIM score subdomains were significantly worse in patients with sleep disturbance than in those without disturbance. Statistically significant differences in sleep disturbance, erectile symptoms, sexual desire and some domains of the SF-36 were observed between the TRT and control groups after 12 months. CONCLUSION: Sleep disturbance may be one of the clinical signs for severe hypogonadism. Moreover, TRT improved sleep conditions, sexual function and quality of life among hypogonadal men with sleep disturbance.

NCCN Asia Consensus Statement prostate cancer.

The National Comprehensive Cancer Network, an NPO organization comprised of university hospitals and cancer centers in the US. The publication of clinical practice guidelines on the treatment, diagnosis, prevention and screening is one of important activities. Background factors of prostate cancer patients, such as the prevalence, age at the diagnosis and mortality are markedly different between Western countries and Asia. Thus, various factors should be taken into consideration at the treatment choice for individual patients. Experts from Asian countries were published as the Asia Consensus Statement. In this review, we explain important points of the Asia Consensus Statement such as differences in the epidemiological backgrounds of patients, differences in treatment options and differences in medical insurance systems.

Association of TUSC1 and DPF3 gene polymorphisms with male infertility.

PURPOSE: Recently, genome-wide association studies of a Hutterite population in the USA revealed that five single nucleotide polymorphisms (SNPs) with a significant association with sperm quality and/or function in ethnically diverse men from Chicago were significantly correlated with family size. Of these, three SNPs (rs7867029, rs7174015, and rs12870438) were found to be significantly associated with the risk of azoospermia and/or oligozoospermia in a Japanese population. In this study, we investigated whether the rs10966811 (located in an intergenic region between the TUSC1 and IZUMO3 genes) and rs10129954 (located in the DPF3 gene) SNPs, previously related to family size, are associated with male infertility. In addition, we performed association analysis between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility. METHODS: We genotyped 145 patients with infertility (including 83 patients with azoospermia and 62 with oligozoospermia) and 713 fertile controls by PCR-RFLP technique for polymorphism. Because rs10966811 has no restriction sites, the SNP rs12376894 with strong linkage disequilibrium was selected as an alternative to rs10966811. RESULTS: There was a statistically significant association between rs12376894 proxy SNP of rs10966811 and oligozoospermia. Also, a statistically significant association between rs10129954 and azoospermia, and oligozoospermia was observed. When we assessed the relationship between rs12348 in TUSC1 and rs2772579 in IZUMO3 and male infertility traits, we found that rs12348 in TUSC1 was significantly associated with azoospermia and oligozoospermia, but rs2772579 in IZUMO3 was not associated with male infertility. CONCLUSION: We found that the polymorphisms in TUSC1 and DPF3 displayed strong associations with male infertility.

Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.

Through genome-wide association analysis and an independent replication study using a total of 1131 bladder cancer cases and 12 558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P-value of 4.03 × 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. SNP rs8041357, which is in complete linkage disequilibrium (r(2) = 1) with rs11543198, was also associated with bladder cancer risk in Europeans (P = 0.045 for an additive and P = 0.025 for a recessive model), despite much lower minor allele frequency in Europeans (3.7%) compared with the Japanese (22.2%). Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative candidate gene. We also confirmed the association of previously reported loci, namely SLC14A1, APOBEC3A, PSCA and MYC, with bladder cancer. Our finding implies the crucial roles of genetic variations on the chemically associated development of bladder cancer.

Enzalutamide versus abiraterone as a first-line endocrine therapy for castration-resistant prostate cancer (ENABLE study for PCa): a study protocol for a multicenter randomized phase III trial.

BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC. METHODS/DESIGN: The present study is a phase III, investigator-initiated, multicenter, head-to-head, randomized controlled trial investigating enzalutamide vs. abiraterone as a first-line treatment for CRPC patients. Patients will be randomly assigned to an enzalutamide or an abiraterone treatment group. The primary endpoint is the time to prostate-specific antigen progression. The target sample size is set at 100 patients per group (total, 200 patients). The study duration is 5 years, and the duration for recruitment is 2 years and 6 months. DISCUSSION: Thus far, there have been no prospective head-to-head studies comparing enzalutamide and abiraterone. This ENABLE study will clarify which agent should be prioritized for CRPC patients and enable clinicians to decide the appropriate treatment before chemotherapy. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center identifier UMIN000015529 . Registrated 11/1/2014.

Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program.

PURPOSE: To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening. METHODS: We enrolled 8086 men aged 55-69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated. RESULTS: Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0-0.4, 0.5-0.6, 0.7-0.8, and 0.9-1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0-0.6 ng/mL compared with 0.7-1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0-0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7-1.0 ng/mL. CONCLUSIONS: Our study demonstrated that men with baseline PSA levels of 0.0-0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

Effects of testosterone replacement therapy on hypogonadal men with osteopenia or osteoporosis: a subanalysis of a prospective randomized controlled study in Japan (EARTH study).

OBJECTIVE: We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis. METHODS: From our previous EARTH study population, 74 patients with a clinical diagnosis of osteopenia or osteoporosis and hypogonadism were included in this study, as the TRT (n = 35) and control (n = 34) groups. The TRT group was administered 250 mg of testosterone enanthate injection every 4 weeks for 12 months. The BMD, waist circumference, body mass index, body fat percentage, and muscle volume were measured at baseline and at 12 months. Blood biochemical data, including total cholesterol, triglycerides, HDL-cholesterol, hemoglobin A1c, and adiponectin values were also evaluated. RESULTS: At the 12-month visit, BMD significantly increased in both groups. However, comparisons on changes of parameter values from baseline to the 12-month visit between the TRT and control groups were significantly different in BMD (5.0 ± 5.0 vs. 3.0 ± 3.2; p = .0434) and in adiponectin value (-0.90 ± 3.33 vs. 0.10 ± 2.04; p = .0192). There were no significant changes in other parameters. CONCLUSIONS: TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.

Human papillomavirus prevalence in the anus and urine among HIV-infected Japanese men who have sex with men.

BACKGROUND: The present study investigated human papillomavirus (HPV) prevalence in anal and urine samples, and evaluated cytological findings among human immunodeficiency virus (HIV)-infected Japanese men who have sex with men (MSM). METHODS: A total of 148 patients were enrolled. Anal and urine samples were collected from each participant, and a HPV-DNA test and genotyping were performed using flow-through hybridization. In addition, anal cytology was evaluated based on Papanicolaou staining. Questionnaires regarding lifestyle habits and sexual behavior were obtained. RESULTS: The ß-globin gene was positive in 131 (88.5%) anal samples and 139 (94.0%) urine samples. Among the ß-globin-positive samples, the HPV prevalence in anal and urine samples was 80.9% and 30.9%, respectively. High-risk HPV (HR-HPV) was detected in 57.3% of anal samples and 20.9% of urine samples. Among 122 adequate cytological samples, anal cytological abnormalities were observed in 99 cases (81.1%). Anal cytological tests revealed that atypical squamous cells of an undetermined significance (ASCUS) were detected in 57 (46.7%) patients, followed by low-grade squamous intraepithelial lesions (SIL) in 35 (28.7%), high-grade SIL in five (4.1%), and atypical squamous cells cannot exclude high-grade SIL (ASC-H) in two (1.6%), respectively. The nadir counts of CD4-positive T-lymphocyte less than 200 µL and anal HR-HPV infection were independent risk factors for anal cytological atypia over ASC-H. CONCLUSIONS: The present study demonstrated high HPV prevalence in the anus and urine, and showed a high incidence of anal cytological atypia associated with HR-HPV infections among HIV-infected MSM patients.

A replication study of a candidate locus for follicle-stimulating hormone levels and association analysis for semen quality traits in Japanese men.

In men, follicle-stimulating hormone (FSH) acts on the seminiferous tubules and enhances spermatogenesis. Recently, a candidate locus (rs2414095) for FSH levels was identified by a genome-wide association study (GWAS) in Chinese men. The rs2414095 single-nucleotide polymorphism (SNP) is found on the third intron of the cytochrome P450, family 19, subfamily A, peptide 1 (CYP19A1) gene encoding an aromatase. In the present study, we performed a replication study in 1687 Japanese men (901 from cohort 1 and 786 from cohort 2) to assess whether this SNP is associated with circulating FSH levels. Furthermore, we investigated whether the rs2414095 SNP is correlated with semen quality traits in 2015 Japanese men (1224 from cohort 1 and 791 from cohort 2). The rs2414095 SNP was significantly associated with circulating FSH levels (ßSTD=0.15, P=9.7 × 10-5), sperm concentration (ßSTD=0.073, P=0.032) and total sperm number (TSN) (ßSTD=0.074, P=0.027) in a combined analysis of the two Japanese male cohorts. We successfully replicated, in Japanese men, the results of the previous GWAS for the rs2414095 SNP in Chinese men, and found that the rs2414095 SNP was related with sperm production.

Trans-Pacific variation in outcomes for men treated with primary androgen-deprivation therapy (ADT) for prostate cancer.

OBJECTIVES: To compare directly survival outcomes of primary androgen-deprivation therapy (PADT) in Japan, where this treatment is endorsed by guidelines, with outcomes in the USA, where it is not. PATIENTS AND METHODS: Data were compared between men receiving PADT in the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and the Japanese Cancer of the Prostate (J-CaP) registry database. Competing risks regression was used to assess prostate cancer-specific mortality (CSM), adjusting for age, Japan Cancer of the Prostate Risk Assessment (J-CAPRA) score, diagnosis year, and treatment type [combined androgen blockade (CAB) vs castration monotherapy], comorbidity, and practice type. RESULTS: Men on PADT in J-CaP (13 880 men) were older than those in CaPSURE (1633 men), and had higher-risk disease (mean J-CAPRA score 3.8 vs 2.1, P < 0.001). They more often received CAB: 66.9% vs 46.4% (P < 0.001). Despite different risk profiles between the cohorts, CSM was similar on univariate analysis (log-rank P = 0.88). On multivariable regression, the subhazard ratio for CSM was 0.52 for J-CaP vs CaPSURE (95% confidence interval 0.40-0.68). CONCLUSIONS: Men on PADT in Japan have less than half the adjusted CSM than those in the USA. These findings support both existing guidelines endorsing PADT in Asia and discouraging its use in the West. Elucidating the reasons behind these substantial differences, which probably include both genetic and dietary/environmental factors, may help explain the varying epidemiology of prostate cancer on either side of the Pacific.

Clinical outcomes and nadir prostate-specific antigen (PSA) according to initial PSA levels in primary androgen deprivation therapy for metastatic prostate cancer.

PURPOSE: To investigate the clinical outcomes of metastatic prostate cancer patients and the relationship between nadir prostate-specific antigen (PSA) levels and different types of primary androgen deprivation therapy (PADT). This study utilized data from the Japan Study Group of Prostate Cancer registry, which is a large, multicenter, population-based database. METHODS: A total of 2982 patients treated with PADT were enrolled. Kaplan-Meier analysis was used to compare progression-free survival (PFS) and overall survival (OS) in patients treated using combined androgen blockade (CAB) and non-CAB therapies. The relationships between nadir PSA levels and PADT type according to initial serum PSA levels were also investigated. RESULTS: Among the 2982 enrolled patients, 2101 (70.5 %) were treated with CAB. Although CAB-treated patients had worse clinical characteristics, their probability of PFS and OS was higher compared with those treated with a non-CAB therapy. These results were due to a survival benefit with CAB in patients with an initial PSA level of 500-1000 ng/mL. Nadir PSA levels were significantly lower in CAB patients than in non-CAB patients with comparable initial serum PSA levels. CONCLUSIONS: A small survival benefit for CAB in metastatic prostate cancer was demonstrated in a Japanese large-scale prospective cohort study. The clinical significance of nadir PSA levels following PADT was evident, but the predictive impact of PSA nadir on OS was different between CAB and non-CAB therapy.

Validation of TNM classification for metastatic prostatic cancer treated using primary androgen deprivation therapy.

PURPOSE: The current tumor-node-metastasis (TNM) classification system has been used for many years. The prognosis of patients with metastatic prostate cancer (mPC) treated using primary androgen deprivation therapy (PADT) was analyzed according to the TNM classification. METHODS: A total of 5618 cases with lymph node metastases only (N1M0), non-regional lymph node metastasis (M1a), bone metastasis (M1b), and distant metastasis (M1c) were selected from the Japanese Study Group of Prostate Cancer database. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were calculated using Kaplan-Meier analysis. The influence of clinical variables on patient prognosis was evaluated using the Cox proportional hazard regression model. RESULTS: The 5-year OS, CSS, and PFS were 76.0, 83.2, and 38.8% in N1M0, 57.5, 69.0, and 23.0% in M1a, 54.0, 63.1, and 23.0% in M1b, and 40.0, 51.5, and 16.6% in M1c, respectively. OS, CSS, and PFS worsened as the stages progressed. OS, CSS, and PFS were all significantly worse in N1M1b compared with N0M1b. Multivariate analysis revealed that OS and CSS were worse in patients with a Gleason score ≥8 and that combined androgen blockade (CAB) treatment provided better OS than non-CAB treatments at any tumor stage. However, OS and CSS were worse in individuals with a prostate-specific antigen >100 ng/ml only in M1b. CONCLUSIONS: Patient prognosis worsened with stage progression; therefore, current TNM classification system of mPC for PADT was shown to be trustworthy. Each PC cell that develops bone or lymphoid metastasis may exhibit different characteristics.

Effects of dutasteride on lower urinary tract symptoms: a prospective analysis based on changes in testosterone/dihydrotestosterone levels and total prostatic volume reduction.

This study analyzed the effects of dutasteride on lower urinary tract symptoms based on the association between changes in the total testosterone (TT)/dihydrotestosterone (DHT) levels and total prostate volume (TPV) reduction. Sixty participants diagnosed with benign prostatic hyperplasia were given 0.5 mg of dutasteride daily for 52 weeks. Measures of TT and DHT levels, TPV and uroflowmetry were obtained before and after dutasteride treatment. Forty-three patients demonstrated a TPV reduction of ≥5% (Group 1), whereas the remaining 17 patients demonstrated a TPV reduction of <5% (Group 2). DHT suppression and DHT/TT ratio at baseline were significantly higher in Group 1 than Group 2. International Prostate Symptom Scores (IPSS) and uroflowmetry were significantly improved in both groups. In Group 2, nine patients demonstrated some improvement in IPSS (Group 2A), whereas eight did not (Group 2B). The rate of TT increase and improvement in voiding symptoms were significantly higher in Group 2A than Group 2B. Dutasteride-induced TPV reduction is dependent on individual 5-α reductase inhibitor activity. Some patients demonstrating smaller dutasteride-induced TPV reduction may experience an improvement in voiding symptoms owing to an increased level of testosterone.

The correlation between highly sensitive C-reactive protein levels and erectile function among men with late-onset hypogonadism.

We investigated the correlation between highly sensitive C-reactive protein (hs-CRP) levels and erectile function, and assessed the clinical role of hs-CRP levels in men with late-onset hypogonadism (LOH) syndrome. For 77 participants, we assessed Sexual Health Inventory for men (SHIM) score, Aging Male Symptoms (AMS) score and International Prostate Symptom Score (IPSS). We also evaluated free testosterone (FT), hs-CRP, total cholesterol, triglyceride levels, high density lipoprotein cholesterol, hemoglobin A1c, body mass index, waist size and blood pressure. We attempted to identify parameters correlated with SHIM score and to determine the factors affecting cardiovascular risk based on hs-CRP levels. A Spearman rank correlation test revealed that age, AMS score, IPSS and hs-CRP levels were significantly correlated with SHIM score. Age-adjusted analysis revealed that hs-CRP and IPSS were the independent factors affecting SHIM score (r= -0.304 and -0.322, respectively). Seventeen patients belonged to the moderate to high risk group for cardiovascular disease, whereas the remaining 60 belonged to the low risk group. Age, FT value and SHIM score showed significant differences between the two groups. A multivariate regression analysis demonstrated that SHIM score was an independent factor affecting cardiovascular risk (OR: 0.796; 95%CI: 0.637-0.995).

Use of preoperative factors including urodynamic evaluations and nerve-sparing status for predicting urinary continence recovery after robot-assisted radical prostatectomy: Nerve-sparing technique contributes to the reduction of postprostatectomy incontinence.

AIMS: To examine which preoperative factors, including urodynamic evaluations, and operative procedures could predict continence status after robot-assisted radical prostatectomy (RARP) in this study. MATERIALS AND METHODS: Univariate and multivariate logistic regression analyses of preoperative factors such as age, body mass index, prostate-specific antigen level before biopsy, prostate size before surgery, membranous urethral length measured using magnetic resonance imaging (MRI), bladder compliance and maximum urethral closure pressure (MUCP) measured by urodynamic study (UDS), and nerve-sparing (NS) status predicting 24-hr pad test >2 g/day at 1 year after RARP were examined in 111 patients enrolled in this study. RESULTS: The number of patients with incontinence at 1 year after RARP was 39 (35.1%). The only predictive factor for urinary continence was NS grades. To investigate the contribution of NS to urinary continence, 84 patients underwent UDS three times; before, immediately after, and 1 year after RARP. Chronological UDS revealed that recovery patterns of storage and voiding functions were the same among non-NS, unilateral-NS, and bilateral-NS groups, and that higher degrees of NS contributed to lesser decreases in MUCP and longer functional urethral length (FUL) after RARP. CONCLUSION: Preoperative factors, including the results of UDS, could not predict continence 1 year after RARP. The NS procedure contributed to continence status. NS favorably affected MUCP and FUL; however, it did not affect bladder function after RARP. Neurourol. Urodynam. 35:1034-1039, 2016. © 2015 Wiley Periodicals, Inc.

High urinary flow in women with stress incontinence: corrected flow-age nomogram evaluation after a transobturator tape procedure.

INTRODUCTION AND HYPOTHESIS: We noninvasively compared urinary flow in both pre- and post-transobturator tape (TOT) procedures in stress urinary incontinence (SUI) patients using previously reported corrected flow-age nomograms in healthy women. METHODS: This retrospective cohort study included patients who underwent a successful TOT procedure to treat SUI. Non-instrumented uroflowmetry was performed before and 3 months after surgery. Corrected maximum flow rate (cQmax) and average flow rate (cQave) were calculated using Qmax/√voided volume (VV) and Qave/√VV respectively. The ratio of corrected flow to age-adjusted corrected flow in healthy women was calculated in each patient. Each parameter was compared against pre-TOT and 3-months post-TOT values. RESULTS: Sixty-two patients were eligible for study inclusion. All urinary flow parameters were significantly higher pre-TOT than at 3 months post-TOT. The number of patients with cQmax and cQave over mean flow-age nomogram, compared with healthy women, before the TOT procedure decreased 3 months post-TOT; however, in many patients, cQmax and cQave were higher than in the corrected flow-age nomogram post-TOT. No significant difference in the ratio of cQmax to age-adjusted cQmax between pre- and post-TOT in the normal urinary flow group was observed, but significantly decreased in the high urinary flow group 3 months after TOT. CONCLUSIONS: Urinary flow rates were higher in SUI patients compared with age-matched controls and successful TOT procedures normalized urinary flows in patients with high urinary flow. A simple evaluation of urinary flow using a corrected flow-age nomogram may be clinically useful in SUI patients.

A multicenter phase I/II study of enzalutamide in Japanese patients with castration-resistant prostate cancer.

BACKGROUND: The safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of enzalutamide were investigated in patients with castration-resistant prostate cancer (CRPC) in Japan through a multicenter phase I/II study. METHODS: In phase I, patients with progressive metastatic CRPC received single, then multiple, ascending doses of enzalutamide 80, 160 or 240 mg/day. After assessment of tolerability at multiple doses of 160 mg/day for 4 weeks, post-docetaxel patients with CRPC and measurable disease were enrolled into phase II; receiving long-term administration of enzalutamide 160 mg/day. RESULTS: Nine and 38 patients were enrolled in phase I and II, respectively. During phase I, enzalutamide was well tolerated in each cohort; PK parameters were similar to those of non-Japanese populations in other studies. By week 12, overall response rate was 5.3 % and clinical benefit rate was 47.4 %. Prostate-specific antigen response rate (≥50 % reduction from baseline) was 28.9 %. Treatment-emergent adverse events reported in >20 % of patients in phase II were decreased weight, decreased appetite and constipation. No seizures were observed. CONCLUSION: Enzalutamide at 160 mg/day was well tolerated, with PK and safety profiles similar to the non-Japanese population. Anti-tumor activity was observed in post-docetaxel Japanese patients with metastatic CRPC. Apparent differences in anti-tumor activity compared with the AFFIRM study (a phase III trial in a diverse population of patients with CRPC post-docetaxel) may be attributed to differences in treatment history prior to starting enzalutamide. Particularly in Japan, the influence of sequence in hormone treatments, including combined androgen blockade therapy, should be considered. TRIAL REGISTRATION: ClinicalTrials.gov NCT01284920.