Masao Kataoka

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.

Expression and Function of LPA1 in Bladder Cancer

PURPOSE LPA is one of several physiologically active lipid mediators that promote cell proliferation and invasion, and are present in serum, ascites and urine. LPA receptor is a G-protein coupled receptor that is considered a potential therapeutic target for some malignant cancers. We evaluated the expression of LPA receptors in bladder cancer and the effect of LPA in bladder cancer invasion. MATERIALS AND METHODS Using real-time polymerase chain reaction and immunohistochemical staining we determined LPA receptor expression in bladder cancer specimens from patients with bladder cancer, including 12 with Ta or T1 and 15 with T2-T4 disease. ROCK expression, myosin light chain phosphorylation and Matrigel™ invasion assays were done and morphological observations were made to assess LPA effects in T24 cells, which were derived from bladder cancer. RESULTS Notably LPA1 mRNA expression was significantly higher in muscle invasive bladder cancer specimens than in nonmuscle invasive specimens. Strong LPA1 expression was evident on cell membranes in muscle invasive specimens. T24 cell invasion was increased by LPA treatment and invasiveness was decreased by LPA1 siRNA or LPA1 inhibitor. LPA treatment increased ROCK1 expression and myosin light chain phosphorylation, and induced morphological changes, including lamellipodia formation and cell rounding. CONCLUSIONS Results indicate that LPA signaling via LPA1 activation promoted bladder cancer invasion. LPA1 might be useful to detect bladder cancer with highly invasive potential and become a new therapeutic target for invasive bladder cancer treatment.

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.

Involvement of angiotensin II type 1 receptor on pathological remodeling and dysfunction in obstructed bladder

Objectives:  To determine whether long‐term administration of an angiotensin II type 1 receptor antagonist improves morphology and function in obstructed bladders.

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.

External beam radiotherapy for focal lymphoepithelioma-like carcinoma in the urinary bladder: a case report and literature review.

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.

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.

Does Body Habitus of Patients Affect Operative Difficulty During Retroperitoneal Laparoscopic Radical Nephrectomy

BACKGROUND AND PURPOSE 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. PATIENTS AND METHODS 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 P<0.05 was considered significant. RESULTS 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. CONCLUSION 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.

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.