Dynamic Regulation of Caveolin-1 Phosphorylation and Caveolae Formation by Mammalian Target of Rapamycin Complex 2 in Bladder Cancer Cells.

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.

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.

Prevalence of N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis and Ureaplasma spp. in the anus and urine among Japanese HIV-infected men who have sex with men.

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.

A Case Report of Chyloretroperitoneum Post Living-Donor Transplantation.

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.

Evaluating urinary incontinence before and after radical prostatectomy using the international consultation on incontinence questionnaire-short form.

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.

Intraoperative hypotension caused by oral administration of 5-aminolevulinic acid for photodynamic diagnosis in patients with bladder cancer.

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 <80 mmHg). CONCLUSIONS: Oral intake of 5-aminolevulinic acid can obviously cause a drop in intraoperative blood pressure in patients undergoing transurethral resection of bladder tumor. Therefore, urologists and anesthesiologists should consider withdrawal of renin-angiotensin system inhibitors and monitor the blood pressure during photodynamic diagnosis-assisted transurethral resection of bladder tumor.

Argininosuccinate Synthetase 1 Loss in Invasive Bladder Cancer Regulates Survival through General Control Nonderepressible 2 Kinase-Mediated Eukaryotic Initiation Factor 2α Activity and Is Targetable by Pegylated Arginine Deiminase.

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.

Investigating the mechanism underlying urinary continence recovery after radical prostatectomy: effectiveness of a longer urethral stump to prevent urinary incontinence.

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.

Risk factors for human papillomavirus detection in urine samples of heterosexual men visiting urological clinics in Japan.

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.

Changes in penile length after radical prostatectomy: investigation of the underlying anatomical mechanism.

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.

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.

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.

Prevalence of human papillomavirus infection in the oropharynx and urine among sexually active men: a comparative study of infection by papillomavirus and other organisms, including Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma spp., and Ureaplasma spp.

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, ß-globin and infectious organisms were analyzed by a PCR-based method. The HPV genotype was determined by HPV GenoArray test. RESULTS: ß-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.

Japan Cancer of the Prostate Risk Assessment for combined androgen blockade including bicalutamide: clinical application and validation.

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.

Efficacy of keishibukuryogan for hot flashes in prostate cancer patients receiving androgen deprivation therapy: a sub-analysis focusing on hormonal and cytokine levels.

Background: The current study attempted to elucidate the mechanisms of keishibukuryogan (TJ-25) efficacy by focusing on hormonal and cytokine levels. This is a sub-analysis of serum hormonal and cytokine levels extracted from the single-arm prospective study. Methods: Twenty-five participants were administrated TJ-25 at a dose of 2.5 g three times daily for 12 weeks, and competed for a diary of their hot flashes conditions. Various hormonal and cytokine values, including interleukin (IL)-8 and tumor necrosis factor-α (TNF-α), were measured at the baseline and 12-week visits. The correlation of hot flashes with hormonal and cytokine levels at baseline was investigated. As part of the responder analyses, all participants were divided into two groups based on the median baseline values of all hormones and cytokines at baseline, and the change amounts in strength and frequency of hot flashes from baseline to 12-week visits in both groups were compared. Furthermore, a correlation in change amounts (Δ values) by TJ-25 administration between hot flashes and each parameter was also conducted. Results: Hot flashes intensity was inversely related to estradiol levels (r=-0.433, P=0.019), and frequency was inversely related to progesterone levels (r=-0.415, P=0.025). In the responder analyses, the effectiveness of TJ-25 for hot flash strength increased in the patients with higher levels of TNF-α at baseline (P=0.0372). TJ-25 was more efficient in frequency in the patients with higher levels of IL-8 (P=0.0312). TJ-25 efficacy, on the other hand, was not significantly associated with changes in any hormonal or cytokine levels between the baseline and 12-week visits. However, ΔIL-8 and ΔTNF-α were not significantly correlated with Δstrength and Δfrequency of hot flashes by TJ-25 administration. Conclusions: Hot flashes were inversely correlated with estradiol and progesterone levels. TJ-25 was more effective in patients with higher TNF-α and IL-8 levels, with no significant change in serum levels caused by the treatment. The suggestive mechanism for the effects of keishibukuryogan is that this drug doesn't suppress the production of IL-8 and TNF-α, but may inhibit some actions of these cytokines.

Liquid-based urine cytology as a tool for detection of human papillomavirus, Mycoplasma spp., and Ureaplasma spp. in men.

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 ß-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 < 0.05). HPV type 16 (HPV 16) was most commonly found in urethritis patients. Cytological evaluations could be performed for 92.1% of urethritis patients and 64.3% of controls. Morphological changes suggestive of HPV infection were seen in 20.7% of the HPV-positive samples, and ISH demonstrated the presence of HPV DNA in both squamous and urothelial cells in HPV-positive samples. Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum were detected in 14.5%, 10.9%, 6.5%, and 12.3% of urethritis patients, respectively. The prevalence rates of these microorganisms (except Ureaplasma parvum) were significantly higher in urethritis cases than controls (P < 0.05). LB-URC is applicable for detection of HPV, Mycoplasma, and Ureaplasma. HPV infection occurs in urothelial cells, especially in gonococcal urethritis.

Clinicopathological outcomes of clinical T1a renal cell carcinoma by tumor size.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Human papillomavirus detected in sperm of Japanese infertile males affects reproductive parameters.

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 ß-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.

A novel risk classification score for malignant ureteral obstruction: a multicenter prospective validation study.

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 < 0.0001). In 217 patients with ureteral stenting, median ureteral stent failure-free survival times of good, intermediate, and poor risk groups were 385, 183, and 57 days, respectively (P < 0.0001). Limitations include the limited ethnicity and the extended duration of study enrollment. The novel PLaCT risk classification score could divide MUO patients into three risk groups with distinct survival times and ureteral stent patencies. This score will aid in establishing prognosis and treatment strategy for all physicians engaged in cancer treatment.