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Objectives The effects of human papillomavirus (HPV) infection on male reproductive parameters are currently a matter of controversy. In order to clarify the issue in Japanese infertile men, the prevalence and localization of HPV in semen, sperm parameters, and superoxide dismutase (SOD) activity in seminal plasma were examined in 216 Japanese infertile men. Methods DNA was extracted from liquid-based cytological semen samples. The β-globin gene was amplified by polymerase chain reaction (PCR), and HPV-DNA was amplified using nested PCR with MY09/MY11 as outer primers and GP5+/GP6+ as inner primers. HPV genotyping was performed in the HPV-positive samples. In addition, SOD levels in seminal plasma were analysed quantitatively. In-situ hybridization (ISH) was performed to localize HPV-DNA in sperm from HPV-positive samples. Results Any-risk and high-risk prevalence rates of HPV in semen were 12.5% and 6.9%, respectively. No significant difference in the prevalence of HPV was observed between azoospermic and non-azoospermic subjects. Among non-azoospermic patients, those with HPV detected in semen had significantly lower sperm motility and concentration compared with subjects without HPV detected in semen. SOD levels in seminal plasma were significantly higher in HPV-positive patients compared with HPV-negative patients. ISH analysis of HPV-positive samples revealed that HPV-DNA was localized to the head and mid-piece of sperm. HPV-DNA was present in the sperm of young infertile men. Conclusion HPV infection of sperm was associated with reduced sperm motility and concentration, and resulted in an increase in seminal SOD activity.

The mammalian target of rapamycin (mTOR) and associated phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway is commonly up-regulated in cancer, including bladder cancer. mTOR complex 2 (mTORC2) is a major regulator of bladder cancer cell migration and invasion, but the mechanisms by which mTORC2 regulates these processes are unclear. A discovery mass spectrometry and reverse-phase protein array-based proteomics dual approach was used to identify novel mTORC2 phosphoprotein targets in actively invading cancer cells. mTORC2 targets included focal adhesion kinase, proto-oncogene tyrosine-protein kinase Src, and caveolin-1 (Cav-1), among others. Functional testing shows that mTORC2 regulates Cav-1 localization and dynamic phosphorylation of Cav-1 on Y14. Regulation of Cav-1 activity by mTORC2 also alters the abundance of caveolae, which are specialized lipid raft invaginations of the plasma membrane associated with cell signaling and membrane compartmentalization. Our results demonstrate a unique role for mTORC2-mediated regulation of caveolae formation in actively migrating cancer cells.

To conduct a prospective randomized trial to evaluate the efficacy of a novel prophylactic procedure for inguinal hernia (IH) after transperitoneal robot-assisted radical prostatectomy (RARP).The prophylactic procedure for IH after RARP involved the dissection of the peritoneum ∼5 cm outward from internal inguinal ring (IIR), separating the spermatic cord and vessels from the peritoneum. This was randomly performed on one side (left or right).A total of 148 cases were included, and IH after RARP was observed in 19 (12.8%) cases, with 11 (7.4%) cases in the right side only, 3 (2.0%) in the left side only, and 5 (3.4%) bilaterally. IHs developed in 9 (6.1%) sides that underwent prophylactic procedure and in 15 (10.1%) that did not. Kaplan-Meier curve analysis revealed no significant difference between the preventive and nonpreventive sides (p = 0.197). Based on the observation during laparoscopic hernioplasty, the prophylactic procedure that strengthened the abdominal wall was by adhesion conglutination of the exfoliated peritoneum in the effective side, and IIRs were opened and developed IH in the ineffective sides. Predictive factors for IH after RARP were not found using Cox proportional hazard model.The preventive procedure for IH used in this study reduced the incidence of IH after RARP, but the difference was not significant.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Background The efficacy and safety of keishibukuryogan, a traditional Japanese medicine, were investigated for the treatment of hot flashes in prostate cancer (PC) patients receiving androgen deprivation therapy. Methods Thirty patients were enrolled and orally administered 2.5 g keishibukuryogan three times daily for 12 weeks. The frequency, strength, and duration of hot flashes were self-evaluated by the patients in a diary every 4 weeks. All patients also completed a questionnaire to determine their aging male symptoms (AMS) scale score and underwent blood biochemical testing. Results Twenty-five patients completed the 12-week treatment. Hot flash strength significantly improved 4, 8, and 12 weeks after treatment. Their frequency was significantly reduced at the 8-week visit, and duration was significantly shorter after the 8-week visit. In addition, the score of the AMS somatic subscale was improved at the 8- and 12-week visits. Among the somatic items, questions 3 (excessive sweating) and 5 (increased need for sleep) were significantly improved. Obesity, radiation, and a longer duration of PC were predictive factors for treatment response. Prostate specific antigen and total testosterone levels were unchanged, and no patients had severe adverse effects. Conclusions Keishibukuryogan was an effective and safe treatment for hot flashes in PC patients.

INTRODUCTION AND OBJECTIVE:The patients in some instances experienced hypotension after the oral administration of 5-aminolevulinic acid. In this study, we analyzed the pre- and intraoperative bloo...

Objective The present study aimed to investigate human papillomavirus (HPV) prevalence and identify risk factors for HPV detection in urine samples among heterosexual men attending urological clinics. Materials and Methods Spot urine samples including initial stream were collected from 845 participants, and the cell pellets were preserved into liquid-based cytological solution. After DNA extraction from each sample, HPV-DNA amplification and genotyping were performed using Luminex multiplex polymerase chain reaction. Participants completed a questionnaire on their age, education, smoking status, sexuality, age of sexual debut, marital status, and present history of sexually transmitted infections. Results Data from 803 patients were included in the analysis. Overall HPV and high-risk (HR) HPV prevalence in urine samples were 6.2% and 3.1%, respectively. HPV and HR-HPV prevalences were the highest in men with urethritis, and were significantly higher than those without urethritis. HPV detection was the most common in men aged 40–49 years, although significant detection differences were not age-related. Urethritis was an independent risk factor for HPV detection from urine samples, with an odds ratio (OR) of 4.548 (95%CI; 1.802–11.476) (p = 0.001). On the other hand, a sub-analysis excluding men with urethritis demonstrated that prostate cancer was a significant risk factor for HPV detection, with OR of 2.844 (95%CI; 1.046–7.732) (p = 0.0410), whereas was not a significant risk for HR-HPV detection in urine samples. Conclusion Prostate cancer may represent a risk factor for HPV detection in the urine of men without urethritis. Registration of clinical trials The authors did not register to Clinical Trial because this is observational and cross-sectional study.

We investigated the effect of testosterone replacement therapy (TRT) on glycemic control and sexual function among hypogonadal men with type 2 diabetes mellitus (T2DM). From the EARTH study, 86 patients (47 in the TRT and 39 in the non-TRT groups) with a diagnosis of T2DM were extracted. We collected data on waist circumference, body mass index, body fat volume, free testosterone, hemoglobin (Hb), fasting blood sugar, and hemoglobin A1c (HbA1c) at baseline and after 12 months. Aging Male Symptoms (AMS) score and International Prostate Symptom Score were obtained. Sexual function was assessed by questions 15 (sexual ability), 16 (morning erections), and 17 (sexual desire) of AMS subscores. The TRT group received intramuscular testosterone enanthate (250 mg) injections every 4 weeks for 12 months. Body fat percentage, Hb, and HbA1c were significantly improved in the TRT group. In addition, sexual ability and frequency, and sexual desire showed a significant improvement in the TRT group after 1 year TRT. On the other hand, any parameters including glycemic control and sexual functions were not significantly improved in non-TRT groups. One-year TRT can improve sexual function and glycemic control among hypogonadal men with T2DM.

Although reports have shown evidence for penile length (PL) shortening after radical prostatectomy (RP), the association between neoadjuvant androgen deprivation therapy (NADT) and PL after RP has yet to be determined. This study evaluates chronological changes in PL after NADT and RP. Stretched PLs (SPLs) of 143 patients, 41 of whom had undergone NADT, were measured before, 10 days after, and 1, 3, 6, 9, 12, 18, and 24 months after RP. Chronological erectile function and testosterone levels were then evaluated. SPL was shortest 10 days after RP in both the NADT (-) and NADT (+) groups and gradually recovered in length thereafter. SPL in the NADT (-) group was significantly longer than that in the NADT (+) group before RP. However, no significant differences in SPLs were found between both groups 6 months after RP. Although all subjects in the NADT (+) group had testosterone levels of

Background Molecular classification of bladder cancer has been increasingly proposed as a potential tool to predict clinical outcomes and responses to chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) inhibition as a chemotherapeutic strategy and characterized the expression profile of mTOR signaling targets in representative bladder cancer cell lines from basal, luminal, and either basal/luminal (“non-type”) molecular subtypes. Materials and methods Protein and mRNA expression of mTOR signaling components from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype (T24 and J82) bladder cancer cell line subtypes were determined by Western blot and database mining analysis of the Cancer Cell Line Encyclopedia. Cell viability following treatment with either, Torin-2 or KU-0063794, 2 dual mTOR complex 1/2 inhibitors, was determined by MTT assay. Immunoblot analysis of cells treated with Torin-2 or KU-0063794 was performed to determine the effects of mTOR inhibition on expression and phosphorylation status of mTOR signaling components, Akt, 4E-BP1, and ribosomal protein S6. Results Molecular subtypes of bladder cancer cell lines each exhibited a distinct pattern of expression of mTOR-associated genes and baseline phosphorylation level of Akt and 4E-BP1. Cells with low levels of Akt Ser-473 phosphorylation were more resistant to the cytotoxic effects of mTOR inhibition with Torin-2, but not KU-0063794. Exposure to Torin-2 and KU-0063794 both potently and rapidly inhibited phosphorylation of Akt Ser-473 and Thr-308, and 4E-BP1 T37/46 in cell lines that included basal and nontype subtypes. Conclusions Differential gene expression and protein activity associated with mTOR signaling is observed among bladder cancer cell lines stratified into basal, luminal, and nontype subtypes. Urothelial carcinomas characterized by high baseline Akt Ser-473 phosphorylation may be best suited for targeted mTOR therapies.

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 β-globin gene was positive in 131 (88.5%) anal samples and 139 (94.0%) urine samples. Among the β-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.

Objective: To measure changes in penile length (PL) over time before and after radical prostatectomy (RP), and to investigate the underlying mechanisms for these changes. Patients and Methods: The stretched PL (SPL) of 102 patients was measured before, 10 days after, and at 1, 3, 6, 9, 12, 18 and 24 months after RP. The perpendicular distance from the distal end of the membranous urethra to the midline of the pelvic outlet was measured on mid-sagittal magnetic resonance imaging (MRI) slice at three time points: preoperatively; 10 days after RP; and 12 months after RP. Pre- and postoperative SPLs were compared using paired Student's t-test. Predictors of PL shortening at 10 days and at 12 months after RP were evaluated on univariate and multivariate analyses. Results: The SPL was shortest 10 days after RP (mean PL shortening from preoperative level: 19.9 mm), and gradually recovered thereafter. SPL at 12 months after RP was not significantly different from preoperative SPL. On MRI examination, the distal end of membranous urethra was found to have moved proximally (mean proximal displacement: 3.9 mm) at 10 days after RP, and to have returned to the preoperative position at 12 months after RP. On univariate analysis, only the volume of the removed prostate was a predictor of SPL change at 10 days after surgery; on multivariate analysis, the association was not statistically significant. No predictor of SPL change was found at 12 months after RP. Conclusion: The SPL was shortest at 10 days after RP and gradually recovered thereafter in the present study. Anatomically, the glans and corpus spongiosum surrounding the urethra are an integral structure, and the proximal urethra is drawn into the pelvis during urethrovesical anastomosis. This is the first report showing that slight vertical repositioning of the membranous urethra after RP causes changes in SPL over time. These results can help inform patients about changes in penile appearance after RP. © 2017 BJU International., Embargo Period 12 months

Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.

Introduction Renal transplantation often causes polyuria, and a Foley catheter is typically placed after transplantation. A urethral stricture often makes it difficult to insert a normal diameter urethral catheter. Case presentation We report on the case of a 16-year-old adolescent male with a history of hypospadias surgery who underwent a cystostomy during renal transplantation. A cystostomy was placed during transplantation because of stricture of the pendulous urethra. Urine leakage into the retroperitoneum occurred after cystostomy catheter removal. An 8-Fr urethral catheter was placed, and urine was aspirated to prevent drainage failure. Voiding cystourethrography performed after 2 weeks showed that there was no leakage. After that, the patient had no trouble with urination. Conclusion A cystostomy may be one strategy for renal transplantation patients with a urethral stricture. Urine leak can occur because of the delay in wound healing caused by immunosuppressive therapy. Therefore, cystostomy management strategies should be considered carefully.

The present study investigated the prevalence of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, M. hominis, and Ureaplasma spp. (biovars 1 and 2) in Japanese HIV-positive men who have sex with men (MSM). One-hundred-and-six Japanese HIV-infected MSM patients were enrolled. Anal and urine samples were collected and DNA testing for each microorganism was performed. Questionnaires regarding lifestyle habits and sexual behavior were administered. The prevalence of N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, and Ureaplasma spp. in the anus was 5.6%, 8.9%, 4.4%, 5.6%, and 8.9%, respectively. A history of genital warts was an independent risk factor for detection of Mycoplasma spp. and Ureaplasma spp. The prevalence of these microorganisms in the anus of asymptomatic Japanese HIV-positive MSM was relatively high in agreement with previous reports from other countries.

OBJECTIVE To analyze perioperative blood pressure in patients undergoing transurethral resection of bladder tumor with photodynamic diagnosis. METHODS A total of 109 consecutive patients who underwent photodynamic diagnosis-assisted transurethral resection of bladder tumor at Kanazawa University, Kanazawa, Ishikawa, Japan, were included in this study and considered as the photodynamic diagnosis group. Clinical data were collected, and perioperative systolic bladder pressure and vasopressor usage were analyzed. In contrast, consecutive patients who previously underwent conventional transurethral resection of bladder tumor (without the use of oral 5-aminolevulinic acid) were used as the control group. RESULTS The systolic blood pressure before anesthesia, lowest systolic blood pressure from the anesthesia induction to the start of operation and lowest systolic blood pressure during operation were significantly lower in the photodynamic diagnosis group. The rate of vasopressor use was significantly higher in the photodynamic diagnosis group. On multivariate analysis, we found that general anesthesia and regular use of renin-angiotensin system inhibitor were associated with an increased risk of hypotension (lowest systolic blood pressure from the anesthesia induction to the start of operation

Background/aim This study aimed to evaluate the therapeutic effect of enzalutamide (ENZ) or abiraterone acetate (ABI) on bone metastasis in castration-resistant prostate cancer (CRPC), using bone scan index (BSI). Materials and methods Treatment outcomes for 31 patients who had undergone ENZ or ABI treatment were examined for CRPC with bone metastases. Cox proportional-hazards regression models were used to investigate the association between overall survival (OS) and clinical characteristics. Results Median OS after ENZ or ABI treatment was 29 months. Considering the flare phenomenon, BSI in 17 (55%) patients decreased following treatment. In multivariate analysis, low baseline BSI value and a decrease in BSI following treatment were associated with longer OS (hazard ratio [HR]=8.009; p=0.35 and HR=7.025; p=0.045*, respectively). Conclusion Low BSI value before ENZ/ABI treatment and a decrease in BSI following ENZ or ABI treatment are independent predictors of longer OS. BSI could be useful for risk assessment of CRPC patients with bone metastases.

BACKGROUND/AIM To evaluate our initial experience with radium-223 chloride (Ra-223). MATERIALS AND METHODS A total of 26 castration-resistant prostate cancer (CRPC) patients with bone metastases, treated with Ra-223 at our hospital were evaluated. This study aimed to observe adverse events (AEs) and changes in serum markers, and Bone Scan Index (BSI). Additionally, the relationship between these values and OS was investigated. RESULTS The observed AEs mainly included fatigue and nausea. Alkaline phosphatase (ALP) and bone-type alkaline phosphatase (BAP) levels decreased following the treatment; however, those of PSA and 1-CTP tended to increase, regardless of Ra-223 administration. Overall survival (OS) was significantly improved in cases with a baseline BSI value of

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 patient...

Background/aim To evaluate the treatment outcomes, toxicity and health-related quality of life (HRQOL) in prostate cancer (PCa) patients who underwent single-fraction high-dose-rate brachytherapy (single-fraction HDR-BT) with external beam radiotherapy (EBRT). Materials and methods From April 2014 to October 2017, treatment outcomes and toxicity of 85 patients who underwent single-fraction HDR-BT of 13 Gy, followed by 46 Gy EBRT in 23 fractions, were examined. HRQOL of 53 patients was evaluated using the Expanded Prostate Cancer Index Composite (EPIC), International Prostate Symptom Score (IPSS)/QOL index, International Index of Erectile Function 5 (IIEF-5), and 36-Item Short Form Survey (SF-36) scores through one year. Results The median follow-up period was 28.8 months. Only three patients had biochemical recurrence. Toxicities included less than grade 3 lower urinary tract symptoms and grade 1 diarrhea. Urethral stricture, a problem related to late toxicity in conventional HDR-BT, was not observed. The urinary and bowel functions in EPIC scores significantly worsened until three or six months after treatment, respectively. Conclusion Single-fraction HDR-BT with EBRT showed promising biochemical control, tolerant toxicities, and preservation of HRQOL, and can be efficiently performed in a shorter time than conventional HDR-BT.

Aims To evaluate urinary incontinence using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), daily pad use, and 24-h pad weight test before and after radical prostatectomy (RP) chronologically, and the correlation between them. Methods ICIQ-SF and questions on daily pad use provided subjective, and 24-h pad weight test for objective evaluation. Results In total, 258 cases were recruited. The continence rate at 12 months after RP was 67% for no pad use, 87% for security 1 pad/day, and 94% for 1 pad/day. The median ICIQ-SF total score before and at 1, 3, 6, and 12 months after RP was 0, 10, 7, 5, and 4, respectively. Incontinence patterns differed when comparing ICIQ-SF results pre- and post-RP. Significant correlation existed between the ICIQ-SF total score, 24-h pad weight test, and daily pad use; however, point distribution on each scatter plot varied widely. Comparing results before and at 12 months after RP revealed complete recovery for 35% of patients from the ICIQ-SF total score, 67% from daily pad use, and 64% from the 24-h pad weight test. A combination of all 3 showed a recovery of preoperative levels in 29% of patients. Conclusions ICIQ-SF was effective and convenient for evaluating UI, including the pattern of UI, after RP. Significant correlation, but wide variations, among ICIQ-SF, daily pad use, and the 24-h pad weight test existed. The best evaluation method would be the one that can compare UI status pre- and post-RP using the ICIQ-SF and 24-h pad weight test.

Objective To assess the chronological changes in urinary incontinence and urethral function before and after radical prostatectomy (RP), and to compare the findings of pelvic magnetic resonance imaging (MRI) before and after RP to evaluate the anatomical changes. Patients and methods In total, 185 patients were evaluated with regard to the position of the distal end of the membranous urethra (DMU) on a mid-sagittal MRI slice and urethral sphincter function using the urethral pressure profilometry. The patients also underwent an abdominal leak point pressure test before RP and at 10 days and 12 months after RP. The results were then compared with the chronological changes in urinary incontinence. Results The MRI results showed that the DMU shifted proximally to an average distance of 4 mm at 10 days after RP and returned to the preoperative position at 12 months after RP. Urethral sphincter function also worsened 10 days after RP, with recovery after 12 months. The residual length of the urethral stump and urinary incontinence were significantly associated with the migration length of the DMU at 10 days after RP. The residual length of the urethral stump was a significant predictor of urinary incontinence after RP. Conclusion This is the first study to elucidate that the slight vertical repositioning of the membranous urethra after RP causes chronological changes in urinary incontinence. A long urethral residual stump reduces urinary incontinence after RP.

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. © 2015 Wiley Periodicals, Inc., Embarogo Period 12 months

We investigated the effects of testosterone replacement therapy (TRT) on bone mineral density (BMD) among hypogonadal men with osteopenia/osteoporosis.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.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.TRT for 12 months could improve BMD with a decrease in adiponectin levels among hypogonadal men with osteopenia/osteoporosis.

金沢大学医薬保健研究域医学系, To clarify the recent trends in prostate-specific antigen (PSA) distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml⁻¹ in 2000, and gradually decreased to approximately 1.30 ng ml⁻¹ in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml⁻¹ in 2000, and there was no remarkable change during the study period. The 95 th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng ml⁻¹, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

This study was performed to determine the associations between human papillomavirus (HPV) infection and cytological changes in the male glans and urethral samples. Two rubbed samples of the glans and distal urethra were collected from 160 patients with urethritis, and the collected cells were placed into preservative solution for liquid-based cytology. DNA was extracted from all samples, and β-globin gene amplification, HPV-DNA test, and HPV genotyping were performed. After papanicolaou staining of each sample, cytological findings were assessed based on nine non-classic signs, and compared with the results of HPV-DNA test. Among the β-globin positive samples, HPV (any type) was detected in 33 and 25% of the glans and urethra samples, respectively. High-risk HPV-DNA was detected in 25 and 15% of the glans and urethra samples, respectively. In the glans samples, cytological signs of HPV infection were observed in 17% of low-risk HPV-positive samples and in 58% of high-risk HPV-positive samples. Cytological atypia suspected to indicate penile intraepithelial neoplasia were observed in 17 and 33%, respectively. On the other hand, abnormal cells were observed in 29% of low-risk HPV-positive and 83% of high-risk HPV-positive urethral samples. Cytological atypia suspected to be urethral intraepithelial neoplasia was observed in 29 and 65%, respectively. In situ hybridization demonstrated the presence of HPV-DNA in the morphologically abnormal cells in 31 and 35% of high-risk HPV-positive glans and urethral samples, respectively. Cytological changes similar to cervical intraepithelial neoplasia in females could be detected in the HPV-positive glans and urethral samples. Diagn. Cytopathol. 2014;42:491–497. © 2013 Wiley Periodicals, Inc.

The aims of the study were to investigate desirable evaluation methods for post-prostatectomy incontinence (PPI) by analyzing the urinary status before robot-assisted radical prostatectomy (RARP).Questionnaires were evaluated from 155 patients prior to operation. The 24-h pad test before RARP revealed a weight of 1.1 g. The mean scores were as follows: total International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score, 1.2; total International Prostate Symptom Score (IPSS), 10.0; IPSS quality of life, 2.7; Overactive Bladder Symptom Score (OABSS), 2.9; and Expanded Prostate Cancer Index Composite urinary summary, 92.8. The abdominal leak point pressure test in 111 patients before RARP was negative in all cases. Desirable evaluation methods for PPI should be based on a combination of subjective and objective evaluations and comparisons between pre- and post-RP. ICIQ-SF is considerably convenient for evaluating incontinence, and the 24-h pad test enables evaluation of the incontinence volume in a highly objective manner.

Loss of argininosuccinate synthetase 1 (ASS1), a key enzyme for arginine synthesis, occurs in many cancers, making cells dependent on extracellular arginine and targetable by the arginine-degrading enzyme pegylated arginine deiminase (ADI-PEG 20). We evaluated ASS1 expression and effects of ASS1 loss in bladder cancer which, despite affecting >70,000 people in the United States annually, has limited therapies. ASS1 loss was identified in conventional and micropapillary urothelial carcinoma, small cell, and squamous cell carcinoma subtypes of invasive bladder cancer, as well as in T24, J82, and UM-UC-3 but not in 5637, RT112, and RT4 cell lines. ASS1-deficient cells showed preferential sensitivity to ADI-PEG 20, evidenced by decreased colony formation, reduced cell viability, and increased sub-G1 fractions. ADI-PEG 20 induced general control nonderepressible 2–dependent eukaryotic initiation factor 2α phosphorylation and activating transcription factor 4 and C/EBP homologous protein up-regulation, associated with caspase-independent apoptosis and autophagy. These effects were ablated with selective siRNA silencing of these proteins. ASS1 overexpression in UM-UC-3 or ASS1 silencing in RT112 cells reversed these effects. ADI-PEG 20 treatment of mice bearing contralateral flank UM-UC-3 and RT112 xenografts selectively arrested tumor growth in UM-UC-3 xenografts, which had reduced tumor size, reduced Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. This suggests that ASS1 loss occurs in invasive bladder cancer and is targetable by ADI-PEG 20.

Despite the development of recent imaging modalities, certain pathological misdiagnoses remain for surgical specimens of presumed small renal cell carcinomas (RCCs). In the present study, a retrospective analysis of benign pathological lesions diagnosed as small RCC prior to surgery was performed. In total, the cases of 196 sporadic renal tumors that was surgically treated as clinical T1a RCCs were reviewed, and the accuracy of the pathological diagnoses was calculated. The pre-operative findings for benign pathological lesions was investigated, and the lesions were observed in 13 (6.63%) of the 196 tumors. Pre-operative computed tomography images were obtained in all cases, and magnetic resonance images were available in 10 cases. The diagnostic accuracy of imaging modalities was significantly lower in the tumors with a diameter of ≤20 mm. In all cases, the possible pathological diagnosis of RCC could not be excluded even by retrospective imaging analysis. Several benign pathological lesions were found in small renal masses presumed to be clinical T1a RCC. In conclusion, there may be limitations to the pre-operative imaging for certain types of small renal mass.

Objectives The Japan Cancer of the Prostate Risk Assessment was developed as a risk stratification instrument for patients undergoing primary androgen deprivation therapy. However, there have been no studies to validate the accuracy of the Japan Cancer of the Prostate Risk Assessment in predicting clinical outcomes. We examined whether the clinical outcomes of patients treated with combined androgen blockade could be stratified using the Japan Cancer of the Prostate Risk Assessment. Methods A total of 319 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist plus bicalutamide were included in this analysis. Progression-free survival, cause-specific survival and overall survival were compared among patients divided according to the prostate-specific antigen level at diagnosis, Gleason score on biopsy specimens, tumor–nodes–metastasis classification and Japan Cancer of the Prostate Risk Assessment score. Results The median age of the patients was 75 years, and the median prostate-specific antigen at diagnosis was 25.4 ng/mL. A total of 102 patients (32.0%) had lymph node and/or distant metastases. On univariate analysis, the factors adopted in the Japan Cancer of the Prostate Risk Assessment points were significant predictors of progression-free survival. On multivariate analysis, clinical T stage and M stage were significant predictors of progression-free survival. The probabilities of progression-free survival and cause-specific survival were significantly different among the groups categorized according to the Japan Cancer of the Prostate Risk Assessment risk strata. The probability of overall survival in the low-risk group was higher than in the other groups. Conclusions The progression-free survival, cause-specific survival and overall survival of prostate cancer patients treated by combined androgen blockade with bicalutamide were stratified by the Japan Cancer of the Prostate Risk Assessment. The Japan Cancer of the Prostate Risk Assessment score is clinically useful as a predictor of the prognosis of prostate cancer treated with combined androgen blockade.

金沢大学医薬保健研究域医学系, Liquid-based urine cytology (LB-URC) was evaluated for cytological diagnosis and detection of human papillomavirus (HPV), Mycoplasma, and Ureaplasma. Midstream urine samples were collected from 141 male patients with urethritis and 154 controls without urethritis, and sediment cells were preserved in liquid-based cytology solution. Urethral swabs from urethritis patients were tested for the presence of Neisseria gonorrhoeae and Chlamydia trachomatis. Papanicolaou tests were performed for cytological evaluation. HPV, Mycoplasma, and Ureaplasma genomes were determined by PCR-based methods, and localization of HPV DNA in urothelial cells was examined by in situ hybridization (ISH). The β-globin gene was positive in 97.9% of LB-URC samples from urethritis patients and in 97.4% of control samples, suggesting that high-quality cellular DNA was obtained from the LB-URC samples. HPV DNA was detected in 29 (21.0%) urethritis cases and in five (3.3%) controls (P

Background Oropharyngeal squamous cell carcinoma (OSCC) has shown a gradual increase in male predominance due to the increasing incidence of human papillomavirus (HPV)-associated OSCC. However, the mode of HPV transmission to the oral cavity is poorly understood, and little is known about the epidemiology of oral HPV infection in men. The prevalence rates of HPV, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp. were compared in the oropharynx (oral cavity) and urine of male Japanese patients attending a sexually transmitted disease clinic. Methods The study population consisted of 213 men aged 16 – 70 years old (mean: 34.4 years old). Oropharyngeal gargles and urine were collected, and sedimented cells were preserved in liquid-based cytology solution. After DNA extraction, β-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was determined by HPV GenoArray test. Results β-Globin was positive in 100% and 97.7% of oral and urine samples, respectively. HPV detection rates were 18.8% and 22.1% in oral and urine samples, respectively, suggesting that the prevalence of HPV infection in the oral cavity was similar to that in the urinary tract. N. gonorrhoeae was more prevalent in oral (15.6%) than urine samples (9.1%), whereas C. trachomatis was detected more frequently in urine (15.9%) than oral samples (4.2%). The detection rates of M. genitalium, M. hominis, and Ureaplasma spp. were 5.2%, 10.3%, and 16.0% in oral samples, and 7.7%, 6.3%, and 19.2% in urine, respectively. There were no significant differences in the detection rates of Mycoplasma spp. and Ureaplasma spp. between anatomical locations. The distribution of HPV types were similar in oral and urine samples, and HPV16 was the most common type. The majority of men with HPV infection in both the oral cavity and urine had concordant oral and urinary HPV infection. The presence of urinary HPV infection was an independent risk factor of oral HPV infection, with an odds ratio of 3.39 (95% CI: 1.49 – 7.71), whereas oral gonococcal infection was inversely correlated with oral HPV infection (odds ratio: 0.096; 95% CI: 0.01 – 0.77). Conclusions Oral HPV infection commonly occurs in sexually active men, and is significantly correlated with urinary HPV infection.

This study was performed to determine the associations between human papillomavirus (HPV) infection and cytological changes in the male glans and urethral samples. Two rubbed samples of the glans and distal urethra were collected from 160 patients with urethritis, and the collected cells were placed into preservative solution for liquid-based cytology. DNA was extracted from all samples, and β-globin gene amplification, HPV-DNA test, and HPV genotyping were performed. After papanicolaou staining of each sample, cytological findings were assessed based on nine non-classic signs, and compared with the results of HPV-DNA test. Among the β-globin positive samples, HPV (any type) was detected in 33 and 25% of the glans and urethra samples, respectively. High-risk HPV-DNA was detected in 25 and 15% of the glans and urethra samples, respectively. In the glans samples, cytological signs of HPV infection were observed in 17% of low-risk HPV-positive samples and in 58% of high-risk HPV-positive samples. Cytological atypia suspected to indicate penile intraepithelial neoplasia were observed in 17 and 33%, respectively. On the other hand, abnormal cells were observed in 29% of low-risk HPV-positive and 83% of high-risk HPV-positive urethral samples. Cytological atypia suspected to be urethral intraepithelial neoplasia was observed in 29 and 65%, respectively. In situ hybridization demonstrated the presence of HPV-DNA in the morphologically abnormal cells in 31 and 35% of high-risk HPV-positive glans and urethral samples, respectively. Cytological changes similar to cervical intraepithelial neoplasia in females could be detected in the HPV-positive glans and urethral samples.

The Japan Cancer of the Prostate Risk Assessment was developed as a risk stratification instrument for patients undergoing primary androgen deprivation therapy. However, there have been no studies to validate the accuracy of the Japan Cancer of the Prostate Risk Assessment in predicting clinical outcomes. We examined whether the clinical outcomes of patients treated with combined androgen blockade could be stratified using the Japan Cancer of the Prostate Risk Assessment.A total of 319 patients with prostate cancer treated with luteinizing hormone-releasing hormone agonist plus bicalutamide were included in this analysis. Progression-free survival, cause-specific survival and overall survival were compared among patients divided according to the prostate-specific antigen level at diagnosis, Gleason score on biopsy specimens, tumor-nodes-metastasis classification and Japan Cancer of the Prostate Risk Assessment score.The median age of the patients was 75 years, and the median prostate-specific antigen at diagnosis was 25.4 ng/mL. A total of 102 patients (32.0%) had lymph node and/or distant metastases. On univariate analysis, the factors adopted in the Japan Cancer of the Prostate Risk Assessment points were significant predictors of progression-free survival. On multivariate analysis, clinical T stage and M stage were significant predictors of progression-free survival. The probabilities of progression-free survival and cause-specific survival were significantly different among the groups categorized according to the Japan Cancer of the Prostate Risk Assessment risk strata. The probability of overall survival in the low-risk group was higher than in the other groups.The progression-free survival, cause-specific survival and overall survival of prostate cancer patients treated by combined androgen blockade with bicalutamide were stratified by the Japan Cancer of the Prostate Risk Assessment. The Japan Cancer of the Prostate Risk Assessment score is clinically useful as a predictor of the prognosis of prostate cancer treated with combined androgen blockade.

We performed a retrospective review of clinical T1a renal cell carcinoma patients treated in our institution. The clinicopathological findings and patients' prognoses were analyzed according to tumor size, and risk factors for tumor recurrence were elucidated.A total of 140 cases of sporadic renal cell carcinoma with a diameter of 4 cm or less on computed tomography findings for preoperative evaluation were treated as clinical T1a. Patients underwent radical nephrectomy or nephron-sparing surgery, and were evaluated postoperatively every 3-6 months to screen for metastatic disease. Patients' medical records were reviewed retrospectively and the status of each patient was assessed.There were four cases of clinically metastatic disease at diagnosis. There were no correlations between tumor size and pathological stage, Fuhrman nuclear grade or histological type. The rate of cases with microvascular invasion on pathological findings increased according to tumor diameter. Disease recurrence occurred in six patients (5.7%) during a mean postoperative follow-up of 41.7 months. There was a significant difference in the recurrence-free rate between pT1a patients with a tumor diameter of 31 mm or more and other patient groups. In terms of microvascular invasion on histological findings, the probability of non-recurrence at 7 years was 0% for patients with and 92.9% for those without microvascular invasion.Among T1a renal cell carcinoma, tumors over 30 mm in diameter may have aggressive biological potential, possibly due to microvascular invasion. Long-term follow-up is needed for these tumors.