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Robot-assisted radical prostatectomy (RARP) has enabled steady and stable surgical procedures due to both meticulous maneuvers and magnified, clear, 3-dimensional vision. Therefore, better surgical outcomes have been expected with RARP than with other surgical modalities. However, even in the RARP era, post-prostatectomy incontinence has a relatively high incidence as a bothersome complication. To overcome post-prostatectomy incontinence, it goes without saying that meticulous surgical procedures and creative surgical procedures, i.e., "Preservation", "Reconstruction", and "Reinforcement" of the anatomical structures of the pelvis, are most important. In addition, medication and appropriate pad usage might sometimes be helpful for patients with post-prostatectomy incontinence. However, patients who have 1) BMI > 26 kg/m(2), 2) prostate volume > 70 mL, 3) eGFR < 60 mL/min, or a 4) Charlson comorbidity index > 2 have a tendency to develop post-prostatectomy incontinence despite undergoing the same surgical procedures. It is important for patients who have a high risk for post-prostatectomy incontinence to be given information about delayed recovery of post-prostatectomy incontinence. Thus, not only the surgical procedures, but also a comprehensive approach, as mentioned above, are important for post-prostatectomy incontinence.

Heparan sulfate-specific endosulfatase-2, SULF-2, can modulate the signaling of HSPG-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCCs) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCCs with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested. High SULF-2 expression was correlated with an early clinical stage and less invasive pathological factors. Low SULF-2 expression was correlated with an advanced stage and higher invasive factors. Three-year cancer-specific survival (CSS) for high SULF-2 RCCs and low SULF-2 RCCs were 100% and 71.4%, respectively (log-rank p = 0.0019), with a significantly shorter CSS observed in low SULF-2 RCC patients. The influence of SULF-2 expression level on Wnt/VEGF/FGF signaling, cell viability and invasive properties was examined in three RCC cell lines, Caki-2, ACHN and 786-O, using a SULF-2 suppression model involving siRNA or a SULF-2 overexpression model involving a plasmid vector. High SULF-2 expression enhanced Wnt signaling and Wnt-induced cell viability, but not cell invasion. In contrast, low levels of SULF-2 expression significantly enhanced both cell invasion and viability through the activation of VEGF/FGF pathways. RCCs with lower SULF-2 expression might have a higher potential for cell invasion and proliferation, leading to a poorer prognosis via the activation of VEGF and/or FGF signaling. This article is protected by copyright. All rights reserved.

Objectives To characterize the molecular features of benign prostatic hyperplasia by carrying out a gene expression profiling analysis in a rat model. Methods Fetal urogenital sinus isolated from 20-day-old male rat embryo was implanted into a pubertal male rat ventral prostate. The implanted urogenital sinus grew time-dependently, and the pathological findings at 3 weeks after implantation showed epithelial hyperplasia as well as stromal hyperplasia. Whole-genome oligonucleotide microarray analysis utilizing approximately 30 000 oligonucleotide probes was carried out using prostate specimens during the prostate growth process (3 weeks after implantation). Results Microarray analyses showed 926 upregulated (>2-fold change, P < 0.01) and 3217 downregulated genes (

Purpose: Bladder ischemia and oxidative stress contribute to the pathogenesis of bladder dysfunction caused by bladder outlet obstruction. H2 reportedly acts as an effective antioxidant. We investigated whether oral ingestion of H2 water would have a beneficial effect on bladder function in a rat model of bladder outlet obstruction.Materials and Methods: H2 water was made by dissolving H2 gas in ordinary drinking water using a hydrogen water producing apparatus. The bladder outlet obstruction model was surgically induced in male rats. Rats with obstruction were fed H2 water or ordinary drinking water. On week 4 postoperatively cystometry was performed. Oxidative stress markers and the bladder nerve growth factor level were determined. Bladder tissues were processed for pharmacological studies and histological analysis.Results: The micturition interval and micturition volume significantly decreased in obstructed rats given ordinary drinking water. These decreases were significantly suppressed by oral inges...

BACKGROUND To investigate the possible pathogenesis of the benign prostatic enlargement (BPE) induced by local atherosclerosis, the association between local atherosclerosis and prostatic enlargement was investigated, and molecular biological analyses were performed using human prostatectomy specimens. METHODS A total of 69 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) participated in this prospective study. To evaluate actual local atherosclerosis, prostatic arteries were removed during RARP. Microscopic assessment of local atherosclerosis was classified as one of three degrees of narrowing (minimal, moderate, and severe) according to the degree of obstruction of the inner cavity of the prostatic artery. The expressions of several mediators related to chronic ischemia and cell proliferation of the prostate were investigated by immunohistochemistry. RESULTS The median age of the present cohort was 68 (range: 55-75) years. Although there was no relationship between local atherosclerosis and lower urinary symptoms evaluated by questionnaires, local atherosclerosis was significantly more severe in patients who had a history of treatment for benign prostatic hyperplasia (P = 0.02). Prostate size was significantly larger in the severe local atherosclerosis group than in the minimal and moderate local atherosclerosis groups (P

Objectives To determine whether lysophosphatidic acid activates the mitogen-activated protein kinase and increases DNA synthesis in human bladder smooth muscle cells, and to examine the involvement of lysophosphatidic acid and lysophosphatidic acid receptor in mechanical stretch-induced mitogen-activated protein kinase activation in cultured human bladder smooth muscle cells. Methods TaqMan reverse transcription polymerase chain reaction was used to determine the mRNA expression levels of six lysophosphatidic acid receptor subtypes. Mitogen-activated protein kinase activity enhanced by either lysophosphatidic acid or mechanical stretch was measured by western blotting. The effect of lysophosphatidic acid on DNA synthesis was assessed by 5-bromo-2’-deoxy-uridine incorporation assay. Results Lysophosphatidic acid 1 subtype mRNA was predominantly expressed (96%). Lysophosphatidic acid activated the mitogen-activated protein kinase in a concentration-dependent manner. C-jun NH2-terminal kinase showed the highest activity among the three subsets of the mitogen-activated protein kinase family members (c-jun NH2-terminal kinase, extracellular signal-regulated kinases, p38). Lysophosphatidic acid also increased incorporation of 5-bromo-2’-deoxy-uridine. These responses were suppressed by Ki16425 (lysophosphatidic acid receptor antagonist). Mechanical stretch mainly induced c-jun NH2-terminal kinase activation. This activation was partially inhibited by Ki16425. Conclusions Lysophosphatidic acid might activate the c-jun NH2-terminal kinase component of the mitogen-activated protein kinase family and DNA synthesis through lysophosphatidic acid receptors (presumably, through lysophosphatidic acid 1) in human bladder smooth muscle cells. The present study also implicates the involvement of lysophosphatidic acid and lysophosphatidic acid receptors in mechanical stretch-induced c-jun NH2-terminal kinase activation. Lysophosphatidic acid receptor can be partially activated by mechanical stretching through lysophosphatidic acid-dependent or independent mechanism.

Lymphoepithelioma is a malignant epithelial tumor in the nasopharynx characterized by prominent lymphoid infiltration. Carcinomas that resemble lymphoepitheliomas have been called lymphoepithelioma-like carcinomas and have been reported in other organs. A tumor in the bladder is categorized by the percentage of the total area occupied by the lymphoepithelioma-like carcinoma pattern, with the prognosis dependent on the percentage. We present an 81-year-old man with stage 3 chronic obstructive pulmonary disease and a history of aortic aneurysm repair. The computed tomography scans indicated thickening and irregularity of the bladder wall, with left external iliac lymph node metastasis. His diagnosis was bladder cancer, and the clinical stage was evaluated as T3N1M0. Transurethral resection of the bladder tumor was performed, and the pathological specimen showed that the tumor was composed of undifferentiated malignant cells with sheets and nests arranged in a syncytial pattern, as well as an urothelial carcinoma lesion. A prominent lymphoid reaction accompanied the tumor. The pathological diagnosis was focal-type lymphoepithelioma-like carcinoma containing a component of urothelial carcinoma G3>G2. His general condition was such that he could not tolerate radical cystectomy or systemic chemotherapy. External beam radiotherapy (total 60 Gy) was given to the bladder, including the lymph node metastatic lesion. No cancer recurrence was detected by regular follow-up computed tomography and cystoscopy. He eventually died of other causes 48 months later. Although treatment for focal lymphoepithelioma-like carcinoma generally requires multifocal therapies, in the present case, the bladder became tumor free. We also summarize previously reported lymphoepithelioma-like carcinoma cases treated with radiotherapy.

Objective To investigate the effect of fasudil, a Rho-kinase inhibitor, on chronic ischemia-related bladder dysfunction. Materials and Methods Male Sprague-Dawley rats (16 weeks old) were divided into control, chronic bladder ischemia (CBI), and CBI with fasudil treatment (CBI-Fa) groups. The CBI and CBI-Fa groups underwent balloon endothelial injury of bilateral iliac arteries and received a 2% cholesterol diet for 8 weeks after the procedure to induce CBI. The CBI-Fa group was given oral fasudil (30 mg/kg/day) using zonde for 8 weeks after the procedure. The control group received a regular diet for 8 weeks. After cystometry in a conscious state, rats from each group were euthanized, and the bladders and common iliac arteries were harvested for pharmacologic and histologic examination. Results Mean wall thickness of the common iliac arteries was significantly greater in the CBI group than in controls. Contractile responses of muscle strips were significantly lower in CBI group rats than in controls. In the CBI group, micturition interval was significantly shorter, and bladder capacity was significantly lower compared with those in controls. In the CBI-Fa group, arterial wall thickening was significantly suppressed compared with the CBI group. Significant improvements in muscle strip contractility and cystometric parameters were seen in the CBI-Fa group compared with the CBI group. Conclusion Our results suggest that chronic treatment with fasudil could prevent neointimal formation in arteries and bladder dysfunction in this rat model. Fasudil may be therapeutically useful in protecting bladder function in chronically ischemic bladders.

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy-seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy-proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.

We 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.The 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.The 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.Results suggest that in ischemic conditions α1-adrenoceptor antagonists such as silodosin may improve bladder function by restoring bladder blood flow.

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.

Because of the limited working space available during retroperitoneal laparoscopic radical nephrectomy (LRN), the body habitus of the patient is likely to affect the risk of operative difficulties. This study sought to determine whether anthropometric measurements based on CT and abdominal radiography could be used to predict operative difficulties during retroperitoneal LRN.Between August 2004 and January 2012, 96 consecutive patients with preoperative CT and abdominal radiography examinations underwent retroperitoneal LRN for a T(1) or T(2) stage renal tumor at our institution. The association between anthropometric measurements and demographics of patients and operative duration, estimated blood loss (EBL), and perioperative complications were retrospectively analyzed. Multivariate analysis was performed, and P0.05 was considered significant.Anterior perirenal fat distance (P=0.016) and distance from the 12th rib to the iliac crest (P=0.038) were independently associated with operative duration. Only anterior perirenal fat distance (P=0.001) was independently associated with EBL. No intraoperative complications and reoperations occurred. The occurrence or severity of postoperative complications was not significantly associated with anthropometric measurements. Body mass index ≥25.0 kg/m(2) was not significantly associated with operative difficulties.The anterior perirenal fat distance and the distance from the 12th rib to the iliac crest can be used to predict operative difficulties during retroperitoneal LRN.

Objectives To elucidate the effect of postoperative urinary incontinence on nocturia-related quality of life after robot-assisted radical prostatectomy. Methods A total of 100 consecutive patients who underwent robot-assisted radical prostatectomy completed a nocturia quality of life questionnaire score and a frequency-volume chart before and after surgery. These patients were divided into two groups by continence status (continent and incontinent) according to the number of pad exchanges per day and the 1-h pad test after surgery. Assessment was carried out before surgery, and then at 3 and 12 months after surgery. Results The Nocturia Quality of Life questionnaire total score and the Bother/Concern subscore were significantly lower in incontinent patients at 3 and 12 months after surgery (Nocturia Quality of Life questionnaire total score: Bother/Concern subscores P = 0.006: P = 0.04 at 3 months after surgery; and P = 0.04: P = 0.02 at 12 months). Both nocturnal maximum voided volume and nocturnal frequency were not significantly different between continent and incontinent patients. On multivariate analysis, nocturnal urinary frequency (P = 0.01) and urinary incontinence (P = 0.005) were significantly associated with nocturia-specific quality of life. Conclusions Although the number of nocturia episodes was not significantly different between the continent and incontinent patients after surgery, the Nocturia Quality of Life questionnaire score was significantly worse in incontinent patients. In these patients, other than the number of nocturia episodes, psychological stress might worsen the Nocturia Quality of Life questionnaire score. Therefore, prevention of post-prostatectomy incontinence might be important to avoid aggravating the Nocturia Quality of Life questionnaire score.

Periprostatic local anesthesia for transrectal ultrasound (TRUS)-guided prostate biopsy requires additional needle punctures and injection of local anesthetics into the periprostatic area. This study sought to determine the influence of periprostatic local anesthesia on the surgical difficulty of open radical prostatectomy (RP). A total of 241 consecutive patients who underwent TRUS-guided prostate needle biopsy were randomized to receive either periprostatic nerve block (Anesthesia group; n = 120) or no anesthesia (Control group; n = 121). After diagnosing localized prostate cancer, patients who underwent open RP without neoadjuvant androgen deprivation therapy were evaluated as to whether perioperative nerve block affected operative duration, estimated blood loss (EBL), positive margin rate or complications. Twenty-one patients in the Anesthesia group and 19 patients in the Control group were investigated in the current study. In assessing the patients who underwent open RP with or without periprostatic nerve block, no significant differences in operative duration, EBL, positive margin rate or complications were seen between groups. Periprostatic nerve block does not appear to affect perioperative outcomes after open RP.

Bladder hypertrophy and dysfunction are well-known bladder responses to outlet obstruction (i.e. urodynamic overload). Cardiac hypertrophy and heart failure are also caused by hemodynamic overload, and many basic and clinical studies suggest that the local renin-angiotensin system (RAS) has a crucial role in load-induced cardiac pathogenesis. The similarity of the response of the heart and the bladder to overload suggests that angiotensin II (AngII) may have a similar regulatory role in pathological remodeling, such as muscle growth and collagen production of the obstructed bladder. Previous in vitro studies show that angiotensin I is converted to AngII by angiotensin converting enzyme (ACE) or chymase, which exists in the human bladder. In addition, many studies using contractile responses to AngII, autoradiography, radioreceptor assay and mRNA expression demonstrate the presence of AngII receptor in the bladder from various animals and the human. Recent evidence indicates that AngII is released from bladder smooth muscle cells (SMCs) in response to a repetitive stretch stimulus, and subsequently activates AT1 in an autocrine fashion. This AT1 activation has been shown to mediate heparin-binding epidermal growth factor-like growth factor gene expression and to increase the DNA synthesis rate of bladder SMCs. Consistent with this in vitro study, previous studies and our preliminary data suggest the usefulness of AT1 antagonists or ACE inhibitor in bladder outlet obstruction of the rabbit and rat. Taken together, the local RAS contributes to structural and functional alterations in the bladder after obstruction.

Objectives: To determine whether long-term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders. Methods: Male Sprague–Dawley rats underwent surgery to produce bladder outlet obstruction (bladder outlet obstruction group; n = 32) or sham surgery (sham group; n = 16). A total of 2 weeks later, 16 bladder outlet obstruction-rats were given the AT1 antagonist, candesartan, subcutaneously (candesartan group) using an osmotic pump for 4 weeks; the remaining bladder outlet obstruction-rats received vehicle (bladder outlet obstruction group). A total of 6 weeks after surgery, we compared continuous cystometry, bladder weight, strip contraction, histology and messenger ribonucleic acid expression of growth factors, nicotinamide adenine dinucleotide phosphate oxidase 1 and renin–angiotensin system components among the three groups. Results: Bladder weights markedly increased with bladder outlet obstruction (578 ± 159 mg), and candesartan (344 ± 111 mg) suppressed this increase. Micturition pressure, which was significantly higher with bladder outlet obstruction, was unaffected by candesartan. The shortened micturition interval and decreased micturition volume with bladder outlet obstruction were significantly prolonged and increased by candesartan. Candesartan also significantly decreased residual urine. Histologically, the collagen fiber-to-muscle ratio was significantly increased with bladder outlet obstruction (0.85 ± 0.25) compared with the sham group (0.53 ± 0.18); this increase was suppressed by candesartan (0.49 ± 0.21). The messenger ribonucleic acid expression of heparin-binding epidermal growth factor-like growth factor, transforming growth factor-β1 and nicotinamide adenine dinucleotide phosphate oxidase 1 significantly increased with bladder outlet obstruction, but it was significantly reduced by candesartan. Compared with the bladder outlet obstruction group, candesartan increased the maximal contraction of bladder strips for all stimuli except for angiotensin II. Conclusion: These findings suggest that bladder angiotensin II type 1 receptors contribute to the pathophysiology of remodeling and dysfunction in obstructed bladder.

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. Methods: Male patients with lower urinary tract symptoms were examined with routine investigation. The severity of atherosclerosis was assessed by ultrasound examination of carotid artery. Patients were divided into two groups: control group and atherosclerosis group. The voiding function and storage function were compared between the two groups. Results: A total of 50 men (69.9 ± 9.1 years [mean ± standard deviation]) entered the study. There was no significant difference in age distribution (control group: 68.7 ± 7.6 years; atherosclerosis group: 72.5 ± 9.7 years) and prostate volume (control group: 26.5 ± 17.3 mL; atherosclerosis group: 22.2 ± 11.0 mL) between the two groups. In the voiding parameters, maximum flow rate in the atherosclerosis group (13.4 ± 5.5 mL/s, P < 0.05) was significantly lower than that in the control group (16.7 ± 7.7 mL/s). Postvoid residual urine volume showed no significant difference between the two groups. In the storage parameters, voided volume was significantly reduced in the atherosclerosis group (161.8 ± 46 mL, P < 0.05), as compared to control group (201.1 ± 78 mL). Moreover, daytime frequency was 7.13 ± 3.02 times in the control group, and significantly higher in the atherosclerosis group (8.75 ± 2.50 times, P < 0.05). Conclusion: Development of atherosclerosis impairs both voiding and storage function independently of age, suggesting atherosclerosis leads to lower urinary dysfunction.

Study Type – Symptom prevalence (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? Two large-scale studies evaluating male LUTS by cluster analysis have been reported. In these reports, male LUTS was classified into five clusters or into six clusters. Previous studies were based on data from population-based health surveys. To provide a better understanding of how male patients with LUTS experience symptoms as symptom clusters and to identify common combinations of LUTS, we performed a clinic-based survey. OBJECTIVE • To determine whether men with lower urinary tract symptoms (LUTS) in various combinations could be classified into characteristic symptom groups using cluster analysis. SUBJECTS AND METHODS • Secondary analysis of anonymous data from 10 434 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan was performed. Data were prospectively collected through the central register from men diagnosed with LUTS in 1100 medical institutions between October 2004 and March 2005. • Those who had received an α1-adrenoceptor antagonist within 1 week before the initial visit were excluded. • The survey items were International Prostate Symptom Score (IPSS), quality of life (QOL) score, and patient characteristics including age, bodyweight, body mass index, and LUTS-related comorbid conditions. • Data on IPSS items were used in a hierarchical cluster analysis (Ward's method). RESULTS • Of 10 434 men with LUTS, 9910 were included in the analysis after 5% data trimming (524 patients). Five symptom clusters were identified and the symptom types of each cluster were examined. • The largest cluster (27%) consisted of patients with multiple severe symptoms, i.e. complaining of six or more symptoms with a mean score ≥2.8. In contrast, the second smallest cluster (13%) consisted of patients with minimal symptoms, i.e. complaining of essentially one or two symptom with a mean score ≤2.1. • The other three clusters were labelled based on their dominant symptoms. The clusters were weak stream (27%), storage symptoms (21%) and voiding symptoms (12%). • The storage symptoms group was older, and had more comorbidities. • The distribution of the QOL score was different among the clusters, and the percentage of patients who were very dissatisfied was highest in the multiple severe symptoms group and lowest in the minimal symptoms group. CONCLUSIONS • Cluster analysis using the IPSS showed that men with LUTS can be classified into five characteristic symptom groups. • A new approach to symptom-based classification may be useful to elucidate the pathology of male LUTS and individualize the therapeutic strategy for affected patients, but further studies are needed.

Aims To develop a rat model of atherosclerosis-induced chronic bladder ischemia and investigate the effect of chronic bladder ischemia on voiding behavior and bladder function. Methods Adult male rats were divided into three groups. The arterial injury (AI) group underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet. The sham group underwent sham operation and received a 2% cholesterol diet. The control group received a regular diet. After 8 weeks, a metabolic cage study and cystometry were performed without anesthesia. Bladder blood flow was measured using a laser Doppler blood flowmeter. Histological examination of the iliac arteries and the bladder was performed. The bladder was also processed for immunohistochemical staining of oxidative stress markers. Results The metabolic cage study showed that in the AI group, voiding frequency significantly increased while voided volume significantly decreased. Cystometry showed that the frequency of reflex bladder contractions was significantly higher in the AI group. Filling-induced decrease in bladder blood flow was the greatest in the AI group. Histological study showed that in the AI group alone, atherosclerotic occlusion occurred in the iliac arteries as well as in the downstream bladder microvessels. Oxidative stress marker positive cells were more prevalent in the AI bladder than in the other bladders. Conclusions Combined with a high-cholesterol diet, endothelial injury of iliac arteries induced arterial occlusive disease in the downstream vessels and consequent bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor overactivity manifested as an increase in voiding frequency. Neurourol. Urodynam. 31:195–200, 2012. © 2011 Wiley Periodicals, Inc.

Objectives: To investigate the effects of long-term administration of the α1-adrenoceptor antagonist prazosin on afferent inputs from the lower urinary tract (LUT). Methods: Twenty female spontaneously hypertensive rats (SHR) were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or vehicle was administered via an osmotic pump. The effect of prazosin on urodynamic parameters was determined by continuous cystometry in conscious animals. After cystometry, rats were killed and c-fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. Results: The bladder contraction interval was significantly shorter in untreated SHR compared with WKY rats (2.36 ± 0 vs 4.27 ± 0.12 min, respectively; P

Introduction: To investigate the effects of long-term administration of the α1-adrenoceptor antagonist prazosin and the α2-adrenoceptor antagonist yohimbine on afferent inputs from the lower urinary tract by evaluating c-Fos expression in the spinal cord. Materials and Methods: Prazosin or yohimbine was administered for 4 weeks in rats using an osmotic pump. Effects of these agents on urodynamic parameters were determined by continuous cystometry in conscious rats. After cystometry, c-Fos expression in the dorsal horn of the L6 spinal cord was measured by immunohistochemistry. Results: The administration of prazosin (0.12 mg/kg/day) or yohimbine (0.10 mg/kg/day) significantly increased micturition interval and bladder capacity, but did not affect micturition pressure and residual urine volume. The numbers of c-Fos-positive neurons in the dorsal horn were significantly lower in rats that received prazosin than in controls. Yohimbine reduced the number of c-Fos-positive neurons in part of the dorsal horn. Conclusions: Long-term administration of prazosin and yohimbine at clinically recommended doses can exert inhibitory effects on afferent pathways from the lower urinary tract during the storage phase. These reductions of the afferent input result in the increased bladder capacity and increased micturition interval.

Interferon (IFN)-α is one of the most commonly used agents in immunotherapy for patients with advanced stage renal cell carcinoma. However, because of the drug resistance to IFN-α, its benefits are limited. In this study, we examined whether repression of suppressor of cytokine signaling (SOCS) proteins, which are involved in the IFN-induced signaling pathway, can overcome the IFN resistance of renal cell carcinoma. The effect of IFN-α on SOCS3 expression and cell proliferation was examined using IFN-resistant 786-O and IFN-sensitive ACHN cell lines. The effects of SOCS3-targeted siRNA on 786-O xenografts were determined by SOCS3 expression, morphological observation, and tumor volume. The SOCS3 mRNA expression level was significantly increased by IFN-α stimulation in 786-O, but not in ACHN cells. The overexpression of SOCS3 by gene transfection in ACHN cells significantly inhibited the growth-inhibitory effect of IFN-α. Suppression of SOCS3 expression in 786-O cells by siRNA activated the IFN signaling pathway through signal transducer and activator of transcription 1 phosphorylation and recovered sensitivity to IFN-α. An in vivo study indicated that co-administration of SOCS3-targeted siRNA promoted IFN-α-induced cell death and growth suppression in 786-O cell xenograft in nude mice. Morphological observation of the tumors revealed the inhibition of SOCS3-induced apoptosis, invasion of inflammatory cells and fibrosis. SOCS3 could be a key component in the resistance to IFN treatment of renal cell carcinoma. Silencing SOCS3 gene expression could be an effective strategy to enhance the antitumor effect of IFN in human renal cell carcinoma cells.

Aims 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. Materials and Methods Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO-rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post-drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c-Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre- and post-drug conditions. Results Metabolic cage study showed the voiding behavior of BOO-rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c-Fos-positive cell significantly increased in BOO-rats, while significantly decreased in those receiving αl-AR antagonists. Conclusions The present study demonstrates that α1-AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl-AR, particularly αlA-AR, may play an important role in the activation of the afferent pathway. Neurourol. Urodynam. 30:461–467, 2011. © 2010 Wiley-Liss, Inc.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate.

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.

The gH of CMV is a major target for strain-specific neutralizing antibodies. To verify whether there is a correlation between HLA-DR type and strain-specific antibodies, antibodies against CMV gH in potential donors and recipients for renal transplantation were investigated. Among 471 subjects, 404 (86%) showed reactivity to CMV gH, but no antibodies against gH were detected in 67 (14%) subjects. The positive rates were over 80% in most HLA subpopulations. Fewer subjects with HLA-DR10 and DR11 had antibodies to CMV gH than did those without HLA-DR10 and DR11. HLA-DR10 and DR11 may be associated with fewer/non-responders for strain-specific neutralizing antibodies.

Aims The present study investigated the effects of the bladder outlet obstruction (BOO) on the muscarinic receptor (MR)-coupled RhoA/Rho-kinase (ROK) pathway in the detrusor smooth muscle of the rat. Methods Detrusor muscle samples were obtained from bladders after 4 weeks of BOO and also from sham-operated control rats. Contractile responses to electrical field stimulation (EFS) and 1 μM carbachol (Cch) were determined in isolated detrusor strips. The effects of the ROK inhibitor Y-27632 on the Cch-induced phasic and sustained contractions were evaluated. Western blotting was used to determine the relative levels of RhoA expression and ROK isoform expression. Results Bladder weight increased significantly after 4 weeks of BOO. Contractile responses to EFS decreased significantly in detrusor muscle from the obstructed bladder. Cch (1 μM) induced a biphasic response consisting of an initial phasic contraction followed by a sustained contraction. Y-27632 attenuated the phasic and sustained contractions induced by Cch in both control and obstructed bladders. However, BOO caused a significant increase in contractile force during the sustained phase of the contractions induced by Cch. An inhibitory effect of Y-27632 on the sustained responses to Cch was significantly enhanced in the obstructed bladder. In accordance with the functional study, the expression of RhoA and ROK isoforms (both α and β) at the protein level significantly increased in the obstructed bladder. Conclusions These results suggest that the enhanced MR-coupled RhoA/ROK pathway contributes to the maintenance of contractile force in the obstructed bladder, as a compensatory mechanism for expelling the urine against the obstruction. Neurourol. Urodynam. 28:257–262, 2009. © 2009 Wiley-Liss, Inc.

新生児3症例に対し緩徐血液透析（以後CHD）を施行し2症例を救命しえたので報告する．症例1は出生体重2,720 gの新生児であり，日齢5に先天性代謝異常によるコントロール困難な高アンモニア血症を呈した．48時間のCHD後，高アンモニア血症から改善し経口内服薬に切り替え透析離脱可能となった．症例2は出生体重1,710 gの新生児であり日齢3に一過性高アンモニア血症にて40時間CHDを施行した．順調に高アンモニア血症から改善し透析より離脱した．症例3は出生時において重症新生児仮死と診断された症例であった．約9日間，透析療法を確実に施行することができたが救命しえなかった．今後新生児の救命率の向上により本症例のごとく血液浄化療法の必要とされる症例の増加が予想され，より安全で効率的な透析療法の確立が求められる．

Aims The present study investigated the effects of ovariectomy and estrogen replacement on the release of acetylcholine (Ach) from cholinergic neurons as well as on the tetrodotoxin (TTX)-insensitive stretch-induced Ach release in isolated rat detrusor. In addition, the above effects on rat micturition characteristics were also studied. Methods Thirty female rats randomly received a sham operation, ovariectomy, or ovariectomy plus estrogen replacement. Using metabolic cages, micturition parameters were recorded. Then, in vitro functional experiments that included the measurements of nerve-mediated detrusor muscle contraction, Ach release from nerve fibres, and stretch-induced TTX-insensitive Ach release were performed. Ach release was measured using microdialysis and high-performance liquid chromatography. Results Ovariectomized rats showed a significant decrease in voided volume and significant increase in 24-hr frequency of voiding. Ovariectomy caused the significant increase in both TTX-insensitive basal Ach release and TTX-insensitive stretch-induced Ach release. On the other hand, ovariectomy caused a significant decrease in Ach release from nerve fibres, resulting in the decrease in the contractile responses of detrusor muscle to electrical nerve stimulation. Estrogen replacement restored these alterations induced by ovariectomy. Conclusions Our findings showed that as a results of estrogen deficiency, Ach release from nerve fibres decreased, suggesting that this reduction of Ach released from cholinergic nerves may cause the decrease in detrusor contractility. Furthermore, this study also demonstrated that stretch-induced TTX-insensitive Ach release was increased by ovariectomy. This may be a contributing factor to the development of overactive bladder in elderly women. Neurourol. Urodynam. 26:1050–1055, 2007. © 2007 Wiley-Liss, Inc.

INTRODUCTION AND OBJECTIVES: Although bladder compliance has previously been considered a “static” urodynamic property, recent pre clinical studies have established that repeated passive fills of the bladder can acutely increase compliance. Moreover, acute compliance changes can be reversed by active contraction, a process we call “dynamic compliance.” In addition, compliance may be decreased in animal models of detrusor overactivity due to greater changes in dynamic compliance. The goal of this study was to identify and quantify dynamic compliance during urodynamics in patients with OAB. METHODS: Individuals with OAB defined as ICIq OAB question 5a 3 were enrolled in an IRB approved extended urodynamics protocol. An initial fill was used for clinical purposes and to determine cystometric capacity (Ccap). Four repeat fills were then initiated at a rate 10%Ccap/min as follows: 1) fill to 30% Ccap and passively empty via syringe aspiration, 2) fill to 60%Ccap and passively empty, 3) fill to Ccap and void (voluntary or involuntary) and 4) fill to Ccap and void. Extracted data from the bladder pressure (Pves) were graphed for each fill and data were then normalized to Pves at 75ml in fill 1 for statistical analysis. RESULTS: Five patients completed the study and had results available for analysis. In comparison to repeat fill 1, dynamic compliance was increased (lower Pves throughout filling) in subsequent fills (fills 2 and 3) (Figure 1A). This was likely due to strain softening during filling not restored by passive emptying. Voiding then occurred at the end of fill 3, and the final fill (fill 4) showed the reversibility of this process (decreased dynamic compliance). Normalized data at 75 ml infused volume (Figure 1B) showed increased dynamic compliance (decreased pressure/volume) after passive emptying (Fill #3: 0.69 0.10 vs. Fill #1: 1.0, p

Objective To present a new grouping of male patients with lower urinary tract symptoms (LUTS) based on symptom patterns and clarify whether the therapeutic effect of α1-blocker differs among the groups. Methods We performed secondary analysis of anonymous data from 4815 patients enrolled in a postmarketing surveillance study of tamsulosin in Japan. Data on 7 International Prostate Symptom Score (IPSS) items at the initial visit were used in the cluster analysis. IPSS and quality of life (QOL) scores before and after tamsulosin treatment for 12 weeks were assessed in each cluster. Partial correlation coefficients were also obtained for IPSS and QOL scores based on changes before and after treatment. Results Five symptom groups were identified by cluster analysis of IPSS. On their symptom profile, each cluster was labeled as minimal type (cluster 1), multiple severe type (cluster 2), weak stream type (cluster 3), storage type (cluster 4), and voiding type (cluster 5). Prevalence and the mean symptom score were significantly improved in almost all symptoms in all clusters by tamsulosin treatment. Nocturia and weak stream had the strongest effect on QOL in clusters 1, 2, and 4 and clusters 3 and 5, respectively. Conclusion The study clarified that 5 characteristic symptom patterns exist by cluster analysis of IPSS in male patients with LUTS. Tamsulosin improved various symptoms and QOL in each symptom group. The study reports many male patients with LUTS being satisfied with monotherapy using tamsulosin and suggests the usefulness of α1-blockers as a drug of first choice.

Aims 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. Methods This study involved 100 women with OAB and 101 healthy control women without OAB. Hair root samples were obtained from all subjects and used for beta3-AR gene analysis. Polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) analysis was performed to analyze a polymorphism in the gene of Trp64Arg. Results The overall frequency of the 64Arg variant (heterozygous plus homozygous) in OAB patients was 47% and significantly higher than the frequency of 22.8% found in non-OAB control women. Within OAB patients, numbers of micturitions per day, urgency episodes per day, and urgency incontinence episodes per day in the 64Arg variant carriers were not significantly different from those in the normal gene carriers. Conclusions This study shows that the Trp64Arg polymorphism in the beta3-AR gene is weakly but significantly associated with OAB syndrome. Neurourol. Urodynam. 33:400–402, 2014. © 2013 Wiley Periodicals, Inc.

We describe in this report the case of a renal aneurysm in a 42-year-old woman. The aneurysm measured 27 mm in diameter, and was sited at the first bifurcation of the renal artery. We performed laparoscopic nephrectomy, ex vivo angioplasty and renal autotransplant to avoid ischemic damage to the kidney during reconstruction. The patient recovered and was discharged from the hospital without any complications. Hence, we suggest these treatments can be effectively done in patients with complex renal aneurysms.