Junya Hata

Progressive vascular damage may lead to bladder underactivity in rats.

PURPOSE We assessed whether progressive vascular damage causes bladder underactivity in rats. MATERIALS AND METHODS Adult 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. RESULTS Iliac 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. CONCLUSIONS Pelvic arterial occlusive disease plus vascular endothelial dysfunction may cause progressive vascular damage resulting in bladder dysfunction that develops from bladder hyperactivity to bladder underactivity.

Association Between Postoperative Pelvic Anatomic Features on Magnetic Resonance Imaging and Lower Tract Urinary Symptoms After Radical Prostatectomy

OBJECTIVE To elucidate the etiology of lower urinary tract symptoms (LUTS) after radical prostatectomy, the present study investigated associations between postoperative urethral and vesical anatomic features on magnetic resonance imaging (MRI) and LUTS. PATIENTS AND METHODS Fifty consecutive patients undergoing radical prostatectomy also underwent preoperative and postoperative MRI. Preoperative MRI only evaluated preoperative membranous urethral length (MUL). Postoperative MRI evaluated postoperative MUL, posterior-urethral vesical angle, depth of the urethrovesical junction (UVJ), and urinary pooling inside the urethra and bladder neck configuration. At the same time as postoperative MRI, International Prostate Symptom Score (IPSS), quality of life index, continence grade, and uroflowmetry parameters were investigated. Associations between preoperative or postoperative MRI variables and questionnaire results or uroflowmetry were analyzed to examine the relationships between the morphology of urethral and vesical anatomic features and LUTS. RESULTS Preoperative and postoperative MRI variables were not significantly associated with IPSS total score or uroflowmetry results. Urinary pooling inside the urethra was significantly associated with urgency score in the IPSS (P = .005). Postoperative MUL (P <.001), depth of the UVJ (P = .002), and urinary pooling inside the urethra (P = .04) were significantly associated with continence grade. CONCLUSION Urinary pooling inside the urethra might induce urgency, and postoperative MUL and depth of UVJ were related to urinary incontinence. Avoiding damage to the nerves involved in continence to prevent inflow of urine into the urethra, preservation of MUL, and development of procedures to prevent descent of the bladder neck during surgery are therefore recommended.

The great East Japan earthquake affected the laboratory findings of hemodialysis patients in Fukushima

BackgroundThe aim of the present study was to investigate the impact of the Great East Japan Earthquake on laboratory findings in chronic hemodialysis (HD) patients in Fukushima.MethodsChanges in laboratory findings and cardiothoracic ratio (CTR) between before and after the earthquake were retrospectively analyzed in 90 adult HD patients with end-stage renal disease (ESRD). Two hospitals located within 80 km from the Fukushima Daiichi Nuclear Power Plant, where American government recommended to evacuate from the area, participated in the study. HD duration was shortened by 0.5-1 hour for 1 month after the earthquake. Multivariate analyses were performed to identify the factors contributing to change of measurement values.ResultsBlood urea nitrogen (BUN) value was significantly transiently decreased for 1-2 weeks after the earthquake (P=0.002). In multivariate analysis, age showed a tendency to be related to the decrease of BUN level (P=0.05). Hematocrit value was significantly elevated after two months compared with that at baseline (P=0.02), although the elevation was small. The other measured values and CTR were not significantly changed compared with those before the earthquake.ConclusionsLaboratory findings and CTR did not worsen despite the shortening of HD duration. Hence, in this disaster, as far as chronic HD patients with ESRD were concerned, it was possible for the duration of HD treatment to be safely decreased.

Overriding TKI resistance of renal cell carcinoma by combination therapy with IL-6 receptor blockade

Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens. Cell proliferation and signal transduction activity were then quantified after co-treatment with tocilizumab, an IL-6R inhibitor, in vitro and in vivo. 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. Using a mouse xenograft model we can show that a combination therapy with tocilizumab and low dosage of sorafenib suppresses 786-O tumor growth, reduces AKT-mTOR pathway and inhibits angiogenesis in vivo more efficient than sorafenib alone. Furthermore FDG-PET imaging detected early decrease of maximum standardized uptake values prior to extended central necrosis.Our findings suggest that a combination therapy of IL-6R inhibitors and TKIs may represent a novel therapeutic approach for RCC treatment.Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy. Interleukin-6 (IL-6) is considered to be associated with poor prognosis in RCCs. We therefore hypothesized that TKI resistance and IL-6 secretion are causally connected. We first analyzed IL-6 expression after TKI treatment in RCC cells and RCC tumor specimens. Cell proliferation and signal transduction activity were then quantified after co-treatment with tocilizumab, an IL-6R inhibitor, in vitro and in vivo. 786-O RCC cells secrete high IL-6 levels after low dose stimulation with the TKIs sorafenib, sunitinib and pazopanib, inducing activation of AKT-mTOR pathway, NFκB, HIF-2α and VEGF expression. Tocilizumab neutralizes the AKT-mTOR pathway activation and results in reduced proliferation. Using a mouse xenograft model we can show that a combination therapy with tocilizumab and low dosage of sorafenib suppresses 786-O tumor growth, reduces AKT-mTOR pathway and inhibits angiogenesis in vivo more efficient than sorafenib alone. Furthermore FDG-PET imaging detected early decrease of maximum standardized uptake values prior to extended central necrosis. Our findings suggest that a combination therapy of IL-6R inhibitors and TKIs may represent a novel therapeutic approach for RCC treatment.

Pelvic Arterial Occlusive Disease Affects the RhoA/Rho-Kinase Pathway in Bladder Smooth Muscle

PURPOSE We investigated the effect of pelvic arterial occlusive disease on the RhoA/Rho-kinase pathway in a rat model of chronic bladder ischemia. MATERIALS AND METHODS Male adult Sprague Dawley® rats at age 16 weeks were divided into arterial endothelial injury and control groups. The injury group underwent balloon endothelial injury of the bilateral iliac arteries and received a 2% cholesterol diet to induce pelvic arterial occlusive disease. The control group received a regular diet. At 8 weeks cystometrograms were performed. Bladder tissue was harvested for pharmacological studies and Western blot. RESULTS Cystometrograms showed significantly lower bladder capacity in the arterial endothelial injury group than in controls. Organ bath studies revealed significantly decreased phasic contractions induced by carbachol in bladder strips from the injury group than from controls. In controls bladder strip tonic contractions induced by carbachol were significantly decreased compared with phasic contractions. However, no significant difference was observed between phasic and tonic contractions in the injury group. The Rho-kinase inhibitor Y-27632 produced a concentration dependent decrease in tonic contractions, which was more pronounced in the injury group. Western blot showed significantly increased RhoA and Rho-kinase β expression in the injury group. CONCLUSIONS Our results suggest that pelvic arterial occlusive disease can affect the RhoA/Rho-kinase pathway in the bladder. This pathway might possibly be involved in the maintenance of tonic contraction and contribute to the bladder hyperactivity caused by pelvic arterial occlusive disease.

The Effect of the Vesical Adaptation Response to Diuresis on Lower Urinary Tract Symptoms after Robot-Assisted Laparoscopic Radical Prostatectomy: A Pilot Proof of Concept Study.

Background When urine output increases, voided volume at each voiding also increases in normal subjects. This is generally understood as a vesical adaptation response to diuresis (VARD). Because lower urinary tract symptoms (LUTS) are supposed to be improved by the change in bladder function after robot-assisted laparoscopic radical prostatectomy (RARP), the aim of the present study was to investigate whether VARD is involved in the improvement of LUTS after RARP. Methods 100 consecutive patients who underwent RARP and had the International Prostate Symptom Score (IPSS), quality of life (QOL) index, a frequency-volume chart (FVC), uroflowmetry, and post-voided residual urine (PVR) available were evaluated before and after RARP. This cohort was divided into patients with and without preoperative LUTS according to the preoperative IPSS total score. VARD was defined as the presence of a significant correlation between the urine output rate and voided volume at each voiding (R2>0.2). Results In patients with preoperative LUTS, the IPSS total, storage, and voiding symptom scores were significantly improved after RARP (all P<0.001). The QOL index was also significantly improved after RARP (P<0.05). Although VARD was not seen before RARP (R2 = 0.05), it was seen after RARP (3 months R2 = 0.22, 12 months R2 = 0.23). PVR was significantly reduced after RARP (P = 0.004). Conclusions Improvement of LUTS was seen with acquisition of VARD after RARP. As a result, urinary QOL was also improved in patients with preoperative LUTS. RARP might be an effective procedure for amelioration of LUTS by the acquisition of VARD.

Postoperative urinary incontinence exacerbates nocturia-specific quality of life after robot-assisted radical prostatectomy

To elucidate the effect of postoperative urinary incontinence on nocturia‐related quality of life after robot‐assisted radical prostatectomy.

Timing of Urinary Pad Exchanges Was the Most Important Factor Affecting Quality of Life in the Early Postoperative Period After Robot-Assisted Laparoscopic Radical Prostatectomy.

PURPOSE The aim of the present study is to investigate the effect of pad use for postprostatectomy incontinence on urinary quality of life (QoL) after robot-assisted laparoscopic radical prostatectomy (RARP) in the early postoperative period. METHODS Ninety patients underwent RARP simultaneously completed International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and modified pad use questionnaire that evaluated pad use and urinary QoL and a 24-hour pad test. Pad use was also assessed by pad form, pad size, the number of pad exchanges per day, and the timing of pad exchanges (i.e., to what extent the pad was wet when the patients exchanged it.). The investigation involved patients visiting the outpatient clinic for the first time after RARP. The association between pad use and urinary QoL was investigated. RESULTS The mean frequency of pad exchanges was 2±2/day. The mean 24-hour pad test was 139±193 g/day. Multivariate analyses revealed the timing of pad exchanges was significantly associated with QoL on the ICIQ-SF and the modified pad use questionnaire (P=0.007 and P<0.001, respectively) and the number of pad exchanges per day was significantly associated with QoL on the ICIQ-SF (P=0.01); QoL worsened with pad wetness and increasing frequency of pad exchange. The other factors relating to pad use were not significantly associated with aggravation of QoL. CONCLUSIONS In the early postoperative period after RARP, the timing of pad exchanges was the most important factor affecting QoL. Namely, patients with postprostatectomy incontinence should wear the appropriate size of pad according to the volume of urinary incontinence and exchange pads when the pad is not too wet. On the other hand, pad form, pad size, and volume of urinary incontinence were not associated with decreased QoL.

Case of possible multiple system atrophy with a characteristic imaging finding of open bladder neck during storage phase as an initial sign

Multiple system atrophy is a neurodegenerative disease that affects autonomic and motor systems. Patients with multiple system atrophy usually experience lower urinary tract symptoms, which sometimes appear as an initial symptom before the emergence of the generalized symptoms. An open bladder neck during the filling phase on video urodynamic study is one characteristic imaging finding after the diagnosis of multiple system atrophy, but has not previously been reported at an early phase of the disease. We report a case in which an open bladder neck was observed on several imaging modalities before generalized symptoms emerged. Because occult neurogenic bladder might exist in patients whose lower urinary tract symptoms are resistant to pharmacotherapy, we report this case to raise awareness of the importance of sufficient imaging evaluations. An open bladder neck might be an important imaging finding for diagnosing multiple system atrophy, irrespective of the presence of generalized symptoms. This finding could help avoid false diagnosis and unnecessary treatment.

The impact of nerve‐sparing robot‐assisted radical prostatectomy on lower urinary tract function: Prospective assessment of patient‐reported outcomes and frequency volume charts

To elucidate the effects of a nerve‐sparing (NS) procedure on lower urinary tract symptoms (LUTS) and urinary function after robot‐assisted radical prostatectomy (RARP), the associations between the NS procedure and LUTS and urinary function were investigated.