Soichiro Ogawa

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.

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.

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.

A giant prostatic hyperplasia treated by open surgery.

We report a rare case of giant prostatic hyperplasia treated by open surgery. A 70-year-old man was suffering from macrohematuria. Computed tomography revealed a markedly enlarged prostate measuring 580 mL. The serum prostate-specific antigen level was 9.430 ng/mL. Prostatic biopsy showed benign prostatic hyperplasia. We perfomed retropubic open prostatectomy, since macrohematuria continued and he was also suffering from lower urinary tract symptoms. The adenoma was completely enucleated in one piece. The removed specimen was 13 × 11 × 6 cm in size and weighed 475 g. Histological examination also demonstrated prostatic fibromuscular hyperplasia. This is the 15th-heaviest adenoma ever reported in English-language journals. Transurethral surgical techniques or other minimally invasive approaches are performed for patients with small to medium-sized prostates. However, open surgery is recommended for markedly enlarged prostatic hyperplasia.

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.

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.

Possible effect of lysophosphatidic acid on cell proliferation and involvement of lysophosphatidic acid and lysophosphatidic acid receptors in mechanical stretch-induced mitogen-activated protein kinase.

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.