Masanori Nomiya

Urinary incontinence after robot-assisted radical prostatectomy: pathophysiology and intraoperative techniques to improve surgical outcome.

Robot‐assisted radical prostatectomy has been shown to have comparable and possibly improved postoperative continent rates compared with retropubic and laparoscopic radical prostatectomy. However, postoperative urinary incontinence has remained one of the most bothersome postoperative complications. The basic concept of the intraoperative technique to improve postoperative urinary continence is to maintain as normal anatomical and functional structure in the pelvis as possible. Therefore, improved knowledge of the normal structure in the pelvis should lead to a greater understanding of the pathophysiology of urinary incontinence, and further development of intraoperative techniques to improve the outcomes of urinary continence. It might be necessary to carry out three steps to realize improvement of the early return of urinary continence after robot‐assisted radical prostatectomy: (i) preservation (bladder neck, neurovascular bundle, puboprostatic ligament, pubovesical complex, and/or urethral length, etc.); (ii) reconstruction (posterior and/or anterior reconstruction, and/or reattachment of the arcus tendineus to the bladder neck, etc.); and (iii) reinforcement (bladder neck plication and/or sling suspension, etc.). On the basis of these steps, further modifications during robot‐assisted radical prostatectomy should be developed to improve urinary continence and quality of life after robot‐assisted radical prostatectomy.

Progressive vascular damage may lead to bladder underactivity in rats.

PURPOSEnWe assessed whether progressive vascular damage causes bladder underactivity in rats.nnnMATERIALS AND METHODSnAdult male Sprague Dawley® rats were divided into 4 groups. Controls received a regular diet and tap water. The L-NAME group received a 2% cholesterol diet and L-NAME (3 mg/ml) dissolved in drinking water. The arterial injury group underwent balloon endothelial injury of the common iliac arteries and received a 2% cholesterol diet and tap water after injury. The arterial injury/L-NAME group also received L-NAME dissolved in drinking water. At 8 weeks urodynamics were performed, bladder tissue was harvested for pharmacological studies, and the iliac arteries and bladders were histologically examined.nnnRESULTSnIliac arteries from the injury and injury/L-NAME groups showed neointimal formation and luminal occlusion but arteries from the L-NAME group did not. In the L-NAME and injury groups bladder capacity and voided volume were less than in controls. Conversely, in the injury/L-NAME group these cystometric parameters were significantly greater than in the other groups. Post-void residual volume in the injury/L-NAME group tended to increase compared with the other groups. Contractile responses of bladder strips to various stimuli in the L-NAME, injury and injury/L-NAME groups were significantly less than in controls and the lowest in the injury/L-NAME group. The injury and injury/L-NAME groups showed a significantly increased percent of collagen compared to controls.nnnCONCLUSIONSnPelvic arterial occlusive disease plus vascular endothelial dysfunction may cause progressive vascular damage resulting in bladder dysfunction that develops from bladder hyperactivity to bladder underactivity.

Alpha1-Adrenoceptor Antagonists Improve Bladder Storage Function Through Reduction of Afferent Activity in Rats With Bladder Outlet Obstruction†‡

Using a rat BOO model, we determined whether α1‐adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract.

Protective Effect of a β3-Adrenoceptor Agonist on Bladder Function in a Rat Model of Chronic Bladder Ischemia

BACKGROUNDnThe β3-adrenoceptor (AR) agonist mirabegron has been introduced as a treatment for the overactive bladder. Its effects on the function of the ischemic bladder are not known.nnnOBJECTIVEnTo investigate the effect of mirabegron in a rat model of chronic ischemia-related bladder dysfunction.nnnDESIGN, SETTING, AND PARTICIPANTSnMale Sprague-Dawley rats were divided into three groups: control (n=10), arterial endothelial injury (AI; n=16), and AI with mirabegron treatment (AI-mirabegron; n=10). AI and AI-mirabegron groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-mirabegron rats received mirabegron (10mg/kg/d) orally for 8 wk. The control group received a regular diet.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnAfter 8 wk, urodynamic investigation was performed in awake animals. Pharmacologic in vitro studies and histologic examination of the iliac arteries and bladders were performed.nnnRESULTS AND LIMITATIONSnIliac arteries from both AI and AI-mirabegron rats displayed neointimal formation and luminal occlusion. Micturition interval (MI), bladder capacity (Bcap), and voided volume (VV) in the AI group were significantly less than in the control group (p<0.01). In the AI-mirabegron group, MI, Bcap, and VV were significantly larger than in the AI group (p<0.05) but significantly less than in the control group (p<0.05). Contractile responses of bladder strips to potassium chloride, electrical field stimulation, and carbachol were significantly lower after AI than in controls; responses in preparations from AI-mirabegron-treated animals were similar to those of controls. The AI group showed a significantly higher percentage of collagen (28.6 ± 1.57%) compared with the controls (8.65 ± 0.67%) and AI-mirabegron-treated animals (17.2 ± 2.32%). The mirabegron dose used in this study may potentially limit the translational value of the results.nnnCONCLUSIONSnIn the chronically ischemic rat bladder, treatment with mirabegron seems to protect bladder function and morphology, resulting in reduced bladder hyperactivity. If the results are valid for humans, they support β3-AR agonism as a potential treatment of chronic ischemia-related bladder dysfunction.

Effects of Silodosin, a Selective α1A-Adrenoceptor Antagonist, on Bladder Blood Flow and Bladder Function in a Rat Model of Atherosclerosis Induced Chronic Bladder Ischemia without Bladder Outlet Obstruction

PURPOSEnWe investigated the effects of the selective α1A-adrenoceptor antagonist silodosin on bladder blood flow and bladder function in a rat model of atherosclerosis induced chronic bladder ischemia without bladder outlet obstruction.nnnMATERIALS AND METHODSnThe chronic bladder ischemia model was prepared by creating balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, chronic bladder ischemia rats received silodosin subcutaneously at a rate of 0.1 or 0.3 mg/kg per day, or vehicle for 8 weeks. All groups received a 2% cholesterol diet throughout the experiment. For each α1-adrenoceptor subtype mRNA expression in bladder microvessels was examined by in situ hybridization. Bladder blood flow was measured using a laser speckle blood flow imager. Malondialdehyde in bladder tissue and 8-hydroxy-2-deoxyguanosine in urine were measured as markers of oxidative stress. A metabolic cage study and cystometry were performed in conscious rats.nnnRESULTSnThe expression of all α1-adrenoceptor subtype mRNA was observed in rat bladder microvessels. Silodosin abrogated the decreased bladder blood flow in the empty bladder and during bladder distention that were evident in rats with chronic bladder ischemia. Levels of oxidative stress markers in these rats were significantly decreased by silodosin administration. Silodosin ameliorated bladder dysfunction in rats with chronic bladder ischemia in the metabolic cage study and on cystometry.nnnCONCLUSIONSnResults suggest that in ischemic conditions α1-adrenoceptor antagonists such as silodosin may improve bladder function by restoring bladder blood flow.

Place of overactive bladder in male lower urinary tract symptoms

Lower urinary tract symptoms (LUTS) are highly prevalent in older men and women. Overactive bladder symptom syndrome (OAB) comprises the storage subset of LUTS and, in both sexes, is the most bothersome. The management of male LUTS has however, been disproportionately dominated in the past by an emphasis on prostatic pathology (bladder outlet obstruction (BOO) and prostatic enlargement). Pharmacotherapy that targets the prostate (e.g., α1-adrenoceptor antagonists) often fails to alleviate OAB symptoms, while many studies suggest that antimuscarinic therapy alone, or in combination with α1-adrenoceptor antagonists, can improve OAB symptoms in men with and without BOO. Recent studies suggest that arterial obstructive disease, such as atherosclerosis, may cause OAB in both men and women via ischemia, hypoxia and oxidative stress in the bladder. In this context, the use of phosphodiesterase inhibitors has been suggested to be a potential pharmacotherapy for men with LUTS. This article provides a review of the place of OAB in male LUTS and its treatment and provides an opportunity to draw data from a number of sources into one manuscript for critical review.

Impaired Detrusor Contractility in a Rat Model of Chronic Bladder Ischemia

OBJECTIVEnTo examine the effect of chronic ischemia associated with vascular disorders on bladder function, we investigated bladder contractility and changes in morphology and nerve distribution in a rat model of chronic bladder ischemia.nnnMETHODSnAdult male Sprague-Dawley rats were divided into arterial endothelial injury, sham, and control groups. The injury group underwent balloon endothelial injury of the iliac arteries and received a 2% cholesterol diet. The sham group was only incised bilaterally in the inguinal region and received the 2% cholesterol diet. The control group did not undergo any procedure and received a regular diet (0.09% cholesterol). All animals were euthanized after 8 weeks. Bladders were removed and weighed, and sections were used for muscle strip contraction and histologic analyses. Cross-sections of dissected common iliac arteries were examined histologically.nnnRESULTSnBladder contractile response and tension were significantly decreased in the injury group compared with the sham and control groups. Tissue from the injury group exhibited marked arterial occlusion with wall thickening. In the injury group, the collagen and muscle ratio (0.80 ± 0.12) was significantly greater than in the control (Pxa0= .01) and sham (Pxa0= .04) groups. Significantly fewer protein gene product 9.5 (PGP9.5)-positive nerve fibers were found in the injury group (513 ± 53) than in the control (Pxa0= .01) and sham (Pxa0= .03) groups.nnnCONCLUSIONnVascular occlusive disorders cause fibrosis and reduce the number of nerves innervating the bladder, which leads to decreased bladder contractility in a rat model of chronic bladder ischemia.

The Association between Severity of Atherosclerosis and Lower Urinary Tract Function in Male Patients with Lower Urinary Tract Symptoms

Objectives: The present study was undertaken to investigate the association between the severity of atherosclerosis and lower urinary tract function in male patients with lower urinary tract symptoms.

Involvement of stretch-induced Rho-kinase activation in the generation of bladder tone†‡

The present study investigated the role of the Rho‐kinase (ROK) pathway in the maintenance of bladder tone during the storage phase, and its effects on bladder compliance.

Association between polymorphism of beta3-adrenoceptor gene and overactive bladder

In human urinary bladder, beta3‐ARs play an important role in promoting detrusor relaxation during the storage phase of the micturition cycle. The present study investigated whether a Trp64Arg polymorphism of the gene encoding the beta3‐AR is associated with overactive bladder (OAB) syndrome.