Tsuyoshi Majima

Periurethral injection of autologous adipose‐derived regenerative cells for the treatment of male stress urinary incontinence: Report of three initial cases

Objectives:  To report a novel cell therapy using autologous adipose tissue‐derived regenerative cells for male stress urinary incontinence caused by urethral sphincteric deficiency, and the outcomes in the initial cases undergoing periurethral injection of adipose tissue‐derived regenerative cells.

Regenerative treatment of male stress urinary incontinence by periurethral injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11 patients.

To assess the efficacy and safety of a novel cell therapy for male stress urinary incontinence consisting of periurethral injection of autologous adipose‐derived regenerative cells, and to determine the 1‐year outcomes.

Characterization of bladder and external urethral activity in mice with or without spinal cord injury—a comparison study with rats

To clarify the lower urinary tract function in mice, we compared bladder and urethral activity between rats and mice with or without spinal cord injury (SCI). Female Sprague-Dawley rats and C57BL/6N mice were divided into five groups:1) spinal intact (SI) rats,2) SI mice,3) pudendal nerve transection (PNT) SI mice,4) spinal cord injury (SCI) rats, and 5) SCI mice. Continuous cystometry (CMG) and external urethral sphincter (EUS)-electromyogram (EMG) analyses were conducted under an awake, restrained condition. During voiding bladder contractions, SI animals exhibited EUS bursting with alternating active and silent periods, which, in rats but not mice, coincided with small-amplitude intravesical pressure oscillations in CMG recordings. In SI mice with bursting-like EUS activity, the duration of active periods was significantly shorter by 46% (32 ± 5 ms) compared with SI rats (59 ± 9 ms). In PNT-SI mice, there were no significant differences in any of cystometric parameters compared with SI mice. In SCI rats, fluid elimination from the urethra and the EUS bursting occurred during small-amplitude intravesical pressure oscillations. However, SCI mice did not exhibit clear EUS bursting activity or intravesical pressure oscillations but rather exhibited intermittent voiding with slow large-amplitude reductions in intravesical pressure, which occurred during periods of reduced EUS activity. These results indicate that EUS pumping activity is essential for generating efficient voiding in rats with or without spinal cord injury. However, EUS bursting activity is not required for efficient voiding in SI mice and does not reemerge in SCI mice in which inefficient voiding occurs during periods of reduced tonic EUS activity.

Growth Pattern, an Important Pathologic Prognostic Parameter for Clear Cell Renal Cell Carcinoma

OBJECTIVES To assess the validity of growth pattern as a unique prognostic parameter for clear cell renal cell carcinoma (ccRCC). METHODS In total, 561 patients with pathologic tumor stage 1 (pT1), pT2, and pT3a ccRCC without preoperative metastasis were evaluated. Clinicopathologic parameters, including pathologic tumor stage, Fuhrman grade, tumor necrosis, lymphovascular invasion, and growth pattern, were analyzed to predict disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS Growth patterns were defined as follows: expansive included tumors with well-circumscribed margins without normal renal tissue in the tumor, and infiltrative involved tumors with ill-circumscribed margins or normal renal tissue in the tumors. In multivariate analysis, Fuhrman grade, tumor necrosis, and growth pattern were useful predictors of DFS, whereas Fuhrman grade and growth pattern were useful predictors of CSS, although only 30 cases showed the infiltrative pattern. CONCLUSIONS Growth pattern can be considered a new prognostic parameter for ccRCC.

Influence of E. coli-induced prostatic inflammation on expression of androgen-responsive genes and transforming growth factor beta 1 cascade genes in rats

Prostatic inflammation is reportedly associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen‐responsive genes and growth factors in the rat prostate.

Renal parenchymal volume increases after contralateral nephrectomy: assessment using three-dimensional ultrasonography.

We investigated the relationship between changes in renal parenchymal volume (RPV) and renal function after a unilateral nephrectomy. In all 46 consecutive patients undergoing unilateral nephrectomy were included. Three‐dimensional ultrasonography was performed before surgery (n = 46) and at 4.3 ± 1.9 h (n = 46), 2 days (n = 39), and 7 days (n = 43) after surgery to determine RPV. The mean RPV of the remaining kidney was 104.7 mL before surgery, 116.1 mL (+13.2%) at 4.3 h, 122.7 mL (+18.2%) at 2 days, and 117.6 mL (+13.3%) at 7 days after surgery. Sequential volume measurements during surgery (n = 5) revealed that the transection of the renal artery was followed by an increase in RPV on the contralateral side at 60−90 min. Multivariate regression analysis revealed that RPV was positively associated with the single‐kidney glomerular filtration rate (GFR) and body surface area in both the preoperative and postoperative states. An increase in the single‐kidney GFR was not seen at 2 years in patients with an RPV increase of <5% at 1 week (102.9 ± 8.4%, P = 0.322), but was still significant in the other patients (115.5 ± 21.0%, P < 0.001). These findings suggest that kidney volume may increase due to enlargement of the vascular bed caused by increased renal blood flow during the acute phase. Thereafter, histological hypertrophic responses may replace the hemodynamic changes in the chronic phase.

Comparison of Silodosin and Naftopidil for Efficacy in the Treatment of Benign Prostatic Enlargement Complicated by Overactive Bladder: A Randomized, Prospective Study (SNIPER Study)

Purpose: We investigated the efficacy of 2 &agr;1‐blockers with different affinities for the &agr;1‐adrenoceptor subtypes silodosin and naftopidil in the treatment of benign prostatic enlargement complicated by overactive bladder. Materials and Methods: This was a prospective, open label, randomized, multicenter study of 350 outpatients with untreated benign prostatic enlargement associated with urinary urgency at least once per week and an OABSS (Overactive Bladder Symptom Score) of 3 or greater. Patients were randomly assigned to receive silodosin 8 mg per day or naftopidil 75 mg per day. Changes in parameters from baseline to 4 and 12 weeks were assessed based on I‐PSS (International Prostate Symptom Score), I‐PSS quality of life, OABSS and voiding functions measured by uroflowmetry. Results: On efficacy analysis a total of 314 patients were included in the 2 groups. No significant difference in adverse effects was observed between the groups. Mean I‐PSS and I‐PSS quality of life scores, and OABSS significantly improved in both groups. Statistically significantly greater improvement in the silodosin group than in the naftopidil group was observed in total OABSS (p = 0.03), I‐PSS quality of life score (p = 0.005) and OABSS urgency score (p <0.001) at 12 weeks. In regard to voiding function the maximum urinary flow rate showed significant improvements in both groups but the change in the maximum flow rate in the silodosin group at 12 weeks was significantly greater than in the naftopidil group (3.6 vs 2.1 ml per second). Conclusions: Silodosin, a pure &agr;1A‐adrenoceptor blocker, showed greater improvement in overactive bladder symptoms along with the urinary flow rate in patients with benign prostatic enlargement complicated by overactive bladder compared to naftopidil, an &agr;1D>A‐adrenoceptor blocker.

Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is an age‐related disease frequently associated with lower urinary tract symptoms (LUTS) that involves hyperplasia of both epithelial and stromal cells. Stromal fibrosis is a distinctive feature of BPH, but the exact mechanisms underlying this phenomenon are poorly understood.

Intravesical application of rebamipide suppresses bladder inflammation in a rat cystitis model.

PURPOSE We examined the effects of intravesical application of rebamipide (Otsuka Pharmaceutical, Tokyo, Japan) on bladder inflammation and overactivity in a chemically induced cystitis model. MATERIALS AND METHODS Female Sprague Dawley® rats under isoflurane anesthesia were injected with 150 mg/kg cyclophosphamide in the peritoneum, and 1 mM or 10 mM rebamipide or vehicle was administered in the bladder and remained for 1 hour. Control rats were injected with saline in the peritoneum and vehicle was administered in the bladder. The bladder was harvested at 48 hours. Hematoxylin and eosin staining was performed and the inflammation grade was assessed. The amount of myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proinflammatory cytokines were quantified using reverse transcriptase-polymerase chain reaction. Cystometrogram was done in awake rats 48 hours after cyclophosphamide treatment to measure voiding reflex parameters. RESULTS Histological evaluation revealed that bladder inflammation in cyclophosphamide treated rats was suppressed by rebamipide in a dose dependent manner. Up-regulated myeloperoxidase, IL-1β, IL-6 and TNF-α expression in cyclophosphamide treated rats was also suppressed in rebamipide treated rats. Cystometrogram demonstrated that the intercontraction interval decreased in cyclophosphamide treated rats but was prolonged by rebamipide. CONCLUSIONS Intravesical application of rebamipide suppressed bladder inflammation and overactivity in a dose dependent manner. This may provide a new treatment strategy for chemotherapy associated cystitis.

The role of capsaicin-sensitive C-fiber afferent pathways in the control of micturition in spinal-intact and spinal cord-injured mice

We examined bladder and urethral sphincter activity in mice with or without spinal cord injury (SCI) after C-fiber afferent desensitization induced by capsaicin pretreatment and changes in electrophysiological properties of mouse bladder afferent neurons 4 wk after SCI. Female C57BL/6N mice were divided into four groups: 1) spinal intact (SI)-control, 2) SI-capsaicin pretreatment (Cap), 3) SCI-control, and 4) SCI-Cap groups. Continuous cystometry and external urethral sphincter (EUS)-electromyogram (EMG) were conducted under an awake condition. In the Cap groups, capsaicin (25, 50, or 100 mg/kg) was injected subcutaneously 4 days before the experiments. In the SI-Cap group, 100 mg/kg capsaicin pretreatment significantly increased bladder capacity and decreased the silent period duration of EUS/EMG compared with the SI-control group. In the SCI-Cap group, 50 and 100 mg/kg capsaicin pretreatment decreased the number of nonvoiding contractions (NVCs) and the duration of reduced EUS activity during voiding, respectively, compared with the SCI-control group. In SCI mice, hexamethonium, a ganglionic blocker, almost completely blocked NVCs, suggesting that they are of neurogenic origin. Patch-clamp recordings in capsaicin-sensitive bladder afferent neurons from SCI mice showed hyperexcitability, which was evidenced by decreased spike thresholds and increased firing rate compared with SI mice. These results indicate that capsaicin-sensitive C-fiber afferent pathways, which become hyperexcitable after SCI, can modulate bladder and urethral sphincter activity in awake SI and SCI mice. Detrusor overactivity as shown by NVCs in SCI mice is significantly but partially dependent on capsaicin-sensitive C-fiber afferents, whereas the EUS relaxation during voiding is enhanced by capsaicin-sensitive C-fiber bladder afferents in SI and SCI mice.