Kazuyoshi Shigehara

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study.

Purpose. We performed a randomised controlled study regarding the effects of androgen replacement therapy (ART) on lower urinary tract symptoms (LUTS) in hypogonadal men with benign prostate hypertrophy (BPH). Methods. Fifty-two patients with hypogonadism and BPH were randomly assigned to receive testosterone (ART group) as 250 mg of testosterone enanthate every 4 weeks or to the untreated control group. We compared International Prostate Symptom Score (IPSS), uroflowmetry data, post-voiding residual volume (PVR) and systemic muscle volume at baseline and 12 months after treatment. Results. Forty-six patients (ART group, n = 23; control, n = 23) were included in the analysis. At the 12-month visit, IPSS showed a significant decrease compared with baseline in the ART group (15.7 ± 8.7 vs. 12.5 ± 9.5; p < 0.05). No significant changes were observed in the control group. The ART group also showed improvement in maximum flow rate and voided volume (p < 0.05), whereas no significant improvements were observed in the controls. PVR showed no significant changes in either group. In addition, the ART group showed significant enhancement of mean muscle volume (p < 0.05), whereas no significant changes were seen in the controls. Conclusion. ART improved LUTS in hypogonadal men with mild BPH.

Acute bacterial prostatitis after transrectal prostate needle biopsy: clinical analysis

We investigated the incidence and characteristics of acute bacterial prostatitis after transrectal prostate biopsy, based on urine and blood cultures, treatment method, and outcome. Four hundred and fifty-seven patients who underwent transrectal prostate biopsy in our hospital between November 2003 and October 2006 were reviewed. These patients were treated with 200 mg levofloxacin orally twice daily for 4 days, beginning 12 h before biopsy, and with 200 mg isepamicin sulfate given intravenously just before the biopsy. In patients who developed acute prostatitis urine and blood cultures were checked. All organisms isolated in urine or blood cultures were tested for antibiotic susceptibility of the 457 patients, first-biopsy was performed in 371 and re-biopsy was done in 86. Acute bacterial prostatitis developed in 6 patients (1.3%). Acute prostatitis developed after a first-biopsy in 2 patients (0.5%) and after re-biopsy in 4 patients (4.7%), showing a significant difference. All of the urine and blood cultures yielded levofloxacin-resistant Escherichia coli. Immediate intravenous cephalosporin or carbapenem was effective for all of these patients. We concluded that the use of levofloxacin could be a risk factor for acute bacterial prostatitis after transrectal prostate biopsy, due to an increase in fluoroquinolone-resistant E. coli in the rectum. The incidence of prostatitis was higher in re-biopsy patients. We consider that patients should receive levofloxacin for a shorter period before biopsy to avoid generating fluoroquinolone-resistant strains. Treatment with cephalosporin or carbapenem is recommended for patients with acute prostatitis after prostate biopsy.

Etiologic role of human papillomavirus infection in bladder carcinoma

The authors elucidated an etiologic role of human papillomavirus (HPV) infection in carcinoma of the bladder.

Prevalence of human papillomavirus infection in the urinary tract of men with urethritis

Objectives:  To investigate the prevalence of human papillomavirus (HPV) in the genital and urinary tract of men with urethritis.

Late-Onset Hypogonadism Syndrome and Lower Urinary Tract Symptoms

Androgen replacement therapy (ART) is a widely accepted form of treatment worldwide for aging men with late-onset hypogonadism (LOH) syndrome. Concurrent with the progressive decline in testosterone from middle age, there is a gradual increase in prostate volume, reflecting the development of benign prostatic hyperplasia (BPH). Prostate growth is dependent on the presence of androgens, and conversely, antiandrogen agents or orchidectomy can decrease prostate volume in patients with BPH. Thus, it is important to investigate whether ART could have any negative effects on prostatic disease or lower urinary tract symptoms (LUTS). Although only limited amounts of information on the correlations between androgen levels in aging men and clinical manifestations of LUTS are available, a few recent studies have suggested that testosterone levels may have some beneficial effects on various urinary functions in men. Androgen receptors are found in the urothelium, urinary bladder, prostate, and urethra, and testosterone could have an impact on the autonomic nervous system, bladder smooth muscle differentiation, nitric oxide synthase, phosphodiesterase-5 and Rho/Rho-kinase activities, and pelvic blood flow. In addition, some previous studies demonstrated that ART had little effect on LUTS or urinary function in aging men with LOH syndrome. Furthermore, some recent randomized controlled trials indicated that short-term ART may be effective in the improvement of LUTS in hypogonadal men with mild BPH. However, only limited information is available regarding the effects of longer-term ART or the safety of ART in men with severe BPH and LUTS, and further studies are required to reach more definitive conclusions.

Etiological role of human papillomavirus infection for inverted papilloma of the bladder

The status of human papillomavirus (HPV) infection in urothelial inverted papilloma was examined in the present study. Formalin‐fixed and paraffin‐embedded tissues from eight cases of inverted papilloma of the bladder were studied. The presence of HPV‐DNA was examined by modified GP5/6+PCR using archival tissue sections by microdissection. HPV genotype was determined with a Hybri‐Max HPV genotyping kit. Immunohistochemical analysis for p16‐INK4a, mcm7, HPV‐E4, and L1, and in situ hybridization for the HPV genome were performed. HPV was detected in seven of eight cases (87.5%) of inverted papilloma. Three cases were diagnosed as inverted papilloma with atypia, while the remaining five were typical cases. HPV‐18 was detected in two cases, including one inverted papilloma with atypia, and HPV‐16 was detected in four cases, including one inverted papilloma with atypia. Multiple HPV type infection was detected in one typical case and one atypical case. High‐risk HPV was present in all HPV‐positive cases. Cellular proteins, p16‐INK4a and mcm7, which are surrogate markers for HPV‐E7 expression, were detected in all HPV‐positive cases, and their levels were higher in inverted papilloma with atypia than in typical cases. In contrast, HPV‐E4 and L1, which are markers for HPV propagation, were observed in some parts of the typical inverted papilloma tissue. High‐risk HPV infection may be one of the causes of urothelial inverted papilloma, and inverted papilloma with atypia may have malignant potential. J. Med. Virol. 83:277–285, 2011.

Features of constitutive gr/gr deletion in a Japanese population

BACKGROUND The relationship between male infertility and gr/gr deletions that remove multiple genes of the Y chromosome varies among countries and populations. The aim of this study was to investigate the association between gr/gr deletions and spermatogenic phenotype in fertile and infertile Japanese men. METHODS The subjects were screened by sequence-tagged site (STS) analysis to detect gr/gr deletions, and haplogroups were assigned using eight highly informative markers. In total, 395 infertile men and 377 fertile men (controls) participated in our study. Of the 772 subjects, 260 individuals carried confirmed gr/gr deletions and were used in further analysis of deletion subtype and gene copy number, specifically loss and gain of CDY1 and DAZ copies. These 260 subjects were divided into a control group (n = 131) all with normozoospermia, and an infertile group (n = 129) with 89 infertile subjects exhibiting azoospermia (absence of sperm) and 40 exhibiting oligozoospermia (reduced sperm concentration). RESULTS There were gr/gr deletions in 33.7% (260/772) of all subjects and the deletions were widespread in haplogroup D (86.2%). There were no significant differences in the frequency of gr/gr deletions between the infertile and control groups. The gr/gr deletion subtypes were not distributed randomly among haplogroups; the CDY1a+ DAZ1/2 genes were deleted in 96.9% (217/224) of haplogroup D individuals, whereas the O lineage had a variety of gr/gr deletion types. The loss of CDY1a+ DAZ1/2 was not associated with spermatogenic impairment in haplogroup D (P = 0.33). CONCLUSIONS Taken together, gr/gr deletions in haplogroup D occur constitutively, are associated with the loss of CDY1a + DAZ1/2 and are phenotypically neutral. Further studies are needed to establish whether Y-linked compensatory factors outside the AZFc region can counteract the pathogenic effect of a gr/gr deletion in the D lineage.

Prevalence of genital Mycoplasma, Ureaplasma, Gardnerella, and human papillomavirus in Japanese men with urethritis, and risk factors for detection of urethral human papillomavirus infection

To analyze the risk factors for HPV infection in the urethra, we examined the prevalence of various microorganisms, for example Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Gardnerella vaginalis, and human papillomavirus (HPV) in Japanese male patients with urethritis, and investigated their sexual backgrounds. Rubbed samples obtained from the distal urethra and questionnaires regarding sexual activity and demographic information were collected from 176 participants. N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, U. urealyticum, U. parvum, G. vaginalis, and HPV were detected in 19, 26, 18, 12, 12, 8.5, 14, and 20%, respectively, of all cases in this study. Multivariate logistic regression analysis indicated that more than 4 sexual partners within the last year and presence of N. gonorrhoeae and/or C. trachomatis and/or M. genitalium infections were independent risk factors for urethral HPV infection, with odds ratios of 3.85 (95% CI 1.49–9.94) and 2.41 (95% CI 1.03–5.61), respectively. It is likely that urethral HPV detection is associated with current sexual activity and the presence of N. gonorrhoeae, C. trachomatis, and/or M. genitalium infections.

Increases in bone turnover marker levels at an early phase after starting zoledronic acid predicts skeletal-related events in patients with prostate cancer with bone metastasis.

Study Type – Prognosis (case series)

Liquid-Based Urine Cytology as a Tool for Detection of Human Papillomavirus, Mycoplasma spp., and Ureaplasma spp. in Men

ABSTRACT 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 < 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.