Yoshifumi Kadono

Tranilast inhibits hormone refractory prostate cancer cell proliferation and suppresses transforming growth factor β1-associated osteoblastic changes

Tranilast is a therapeutic agent used in treatment of allergic diseases, although it has been reported to show anti‐tumor effects on some cancer cells. To elucidate the effects of tranilast on prostate cancer, we investigated the mechanisms of its anti‐tumor effect on prostate cancer.

Risedronate Recovers Bone Loss in Patients With Prostate Cancer Undergoing Androgen-deprivation Therapy

OBJECTIVES To perform a prospective observational study between risedronate and no risedronate (control) groups to determine the effectiveness of risedronate against bone loss in patients with prostate cancer (PCa) receiving androgen-deprivation therapy (ADT). ADT for PCa has iatrogenic complications (eg, bone loss and fracture). METHODS We enrolled 60 Japanese patients with PCa who were receiving ADT or were newly scheduled for ADT. The lumbar spine bone mineral density (BMD) was determined by dual-energy x-ray absorptiometry. Patients with a BMD <90% of the young adult mean received risedronate. We analyzed 29 and 27 patients in the risedronate and control groups, respectively. The BMD, urinary deoxypyridinoline, and serum bone alkaline phosphatase were measured as bone turnover markers at 6 and 12 months. RESULTS The BMD/young adult mean ratio correlated inversely with the duration of ADT. The initial mean BMD was significantly lower in the risedronate group than in the control group (1.02 +/- 0.19 vs 1.19 +/- 0.16 g/cm(2)). We focused on patients treated with ADT for >6 months. The mean percentage of changes in the BMD/young adult mean ratio of the risedronate and control groups was +2.6 +/- 4.5% and -2.8 +/- 2.6% after 1 year, respectively (P = .0001). The urinary deoxypyridinoline and bone alkaline phosphatase in the risedronate group decreased significantly after 12 months compared with the levels in the controls. CONCLUSIONS The results of our study have shown that oral administration of risedronate is effective for the recovery of ADT-induced bone loss in patients with PCa.

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.

Chronological urodynamic evaluation of changing bladder and urethral functions after robot-assisted radical prostatectomy

OBJECTIVE To examine chronological changes in urethral and bladder functions before, immediately after, and 1 year after robot-assisted radical prostatectomy (RARP), urodynamic studies were prospectively performed. METHODS Sixty-three consecutive patients underwent pressure-flow studies, urethral pressure profiles, and abdominal leak point pressure (ALPP) tests 1-2 days before, immediately after, and 1 year after RARP. RESULTS The mean bladder compliance was 28.3 mL/cm H₂O before RARP; it worsened to 16.3 mL/cm H₂O immediately after RARP and recovered to 27.1 mL/cm H₂O at 1 year. The mean detrusor pressure at maximum flow rate was 61.9 cm H₂O before RARP; it decreased to 34.3 cm H₂O immediately after RARP and remained at 35.6 cm H₂O at 1 year. The mean maximum urethral closure pressure was 84.2 cm H₂O before RARP; it decreased to 33.4 cm H₂O immediately after RARP and recovered to 63.0 cm H₂O at 1 year. Intrinsic sphincter deficiency (ISD) evaluated by the ALPP test was observed in 53 patients immediately after RARP, although no patient showed ISD before RARP. ISD remained in 7 patients at 1 year. Both ALPP and maximum urethral closure pressure at 1 year were significant factors for continence in multivariate analysis. CONCLUSION Urethral sphincter and bladder function worsen immediately after RARP and recover over time. The bladder storage function after RARP returns to almost the same level before RARP, and the voiding function improves compared with the condition before RARP; however, the urethral sphincter function does not return to its preoperative level. Urethral sphincter dysfunction is considered the main factor for urinary incontinence after RARP.

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

To examine which preoperative factors, including urodynamic evaluations, and operative procedures could predict continence status after robot‐assisted radical prostatectomy (RARP) in this study.

Cardiovascular and respiratory effects of the degree of head-down angle during robot-assisted laparoscopic radical prostatectomy

Robot‐assisted laparoscopic radical prostatectomy (RALP) requires a steep Trendelenburg position and CO2 pneumoperitoneum for several hours to secure the surgical visual field. The present study was performed to investigate the influence of each angle of Trendelenburg position during RALP on cardiovascular and respiratory homeostasis.

The relationship between prostate-specific antigen and TNM classification or Gleason score in prostate cancer patients with low prostate-specific antigen levels

Prostate‐specific antigen (PSA) is a useful biomarker for risk classification in patients with prostate cancer. However, it is unclear whether a correlation exists between low PSA levels (<10 ng/ml) at diagnosis and prognosis.

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

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

Effects of dutasteride on lower urinary tract symptoms and general health in men with benign prostatic hypertroplasia and hypogonadism: a prospective study.

Abstract Introduction: We investigated the effects of the relative increase in testosterone by dutasteride administration in patients with benign prostatic hyperplasia and hypogonadism on urinary symptoms or androgen-responsive general health. Methods: Seventy-six patients were enrolled, and were taking 0.5 mg dutasteride daily for 52 weeks. Before and after treatment, all participants underwent blood test, and body mass index, prostate volume (PV), bone mineral density (BMD), post-voiding residual (PVR) volume, and muscle volume were measured. All patients responded to the questionnaires: International prostatic symptom score (IPSS), Overactive Bladder Symptom score (OABSS). Patients were divided into two groups according to the increase rate of total testosterone (TT): group A, ≥20% increase in TT level; group B, <20% increase or decrease. Results: Baseline TT and free testosterone (FT) levels were significantly lower in group A than group B. Both groups showed marked improvement in PV and PVR. Group A showed significant improvement in IPSS and OABSS with a significant increase of FT level, whereas group B showed no significant change. Dutasteride treatment contributed to a significant increase in BMD in group A. Conclusions: Dutasteride treatment significantly improved urinary symptoms and BMD in patients with low baseline serum TT and FT levels.

Exogenous SPARC Suppresses Proliferation and Migration of Prostate Cancer by Interacting With Integrin β1

The matricellular protein secreted protein acidic and rich in cysteine (SPARC) plays an important role on tumor metastasis and progression in several cancers. However, the roles of SPARC in prostate cancer (PCa) remain unclear.