Toshihiko Masago

Effect of the rho-kinase inhibitor hydroxyfasudil on bladder overactivity: an experimental rat model.

Objectives:  To investigate the effects of the rho‐kinase inhibitor hydroxyfasudil on bladder overactivity in cyclophosphamide (CYP)‐induced cystitis.

High neutrophil‐to‐lymphocyte ratio predicts poor clinical outcome in patients with castration‐resistant prostate cancer treated with docetaxel chemotherapy

To evaluate the prognostic significance of the neutrophil‐to‐lymphocyte ratio in patients receiving chemotherapy with docetaxel for castration‐resistant prostate cancer.

Low pre-operative levels of serum albumin predict lymph node metastases and ultimately correlate with a biochemical recurrence of prostate cancer in radical prostatectomy patients

Introduction To date, only few studies focusing on the issue of host general and immune activity have been performed in localized prostate cancer (PCa). The aim of this study was to elucidate potent non tumor–related biomarkers that express aggressiveness of PCa treated by radical prostatectomy (RP). Materials and methods Data from 179 patients who underwent RP were analyzed. The correlations between various kinds of non tumor–related factors in addition to tumor–related factors and biochemical recurrence (BCR) were analyzed. The correlations between pre–, intra– and post–operative factors were also analyzed. Results Thirty–two cases (17.9%) had a BCR. The factors found to be significantly predictive of BCR using a Cox–proportional hazard model were the pre–operative serum prostate specific antigen (PSA) level and the existence of pathological lymph node metastasis (LNM). A low pre–operative serum albumin level (<4.0 g/dl) was significantly correlated with BCR univariately. Logistic regression analysis revealed that a low pre–operative serum albumin level, an American Society of Anesthesiologists (ASA) score above class 2, and a Gleason score above 8 in the biopsy specimens were significantly predictive of pathological LNM. Conclusions Tumor–related characteristics are more important for predicting BCR. However, our results suggest that low pre–operative serum albumin level may indicate extensive disease of clinically localized PCa and may ultimately be correlated with BCR. Although multiple reasons may account for the significance of the serum albumin level, it is noteworthy that delayed diagnostic and therapeutic procedures in comorbid patients with low serum albumin levels may lead to PCa progression.

Robot-assisted radical prostatectomy in an initial Japanese series: the impact of prior abdominal surgery on surgical outcomes.

To evaluate the influence of prior abdominal surgery on surgical outcomes of robot‐assisted radical prostatectomy in an early single center experience in Japan.

The Role of Staging MRI in Predicting Apical Margin Positivity for Robot-Assisted Laparoscopic Radical Prostatectomy

Purpose: To investigate the association between apical margin positivity and preoperative magnetic resonance imaging (MRI) in patients who have undergone robot-assisted laparoscopic radical prostatectomy (RARP). Patients and Methods: From September 2010 through November 2012, we treated 84 Japanese men with clinically localized prostate cancer with RARP. The excised specimens, which were divided into right and left fragments, were evaluated for the presence of positive surgical margins (PSMs) and preoperative MRI findings. Results: The overall PSM rate was 21.4% (18 of 84 patients), 83.3% (15 of 18 cases) of which were situated in the apex. Evaluating the prostate divided into right and left fragments, the PSM rate was 10.7% at the apex (18 of 168 fragments). Cancer was suspected via preoperative MRI in 39 fragments (23.2%) and detected in the prostatic apex by prostate biopsy in 67 fragments (39.9%). Multiple regression analysis revealed that MRI and nerve-sparing procedures significantly indicate apical margin positivity (p = 0.005). Conclusions: The prostatic apex is the most common location of PSMs after RARP. Our results demonstrate that preoperative MRI for cancer of the prostatic apex may provide substantial information and enable complete cancer clearance.

Oncological and functional outcomes after radical nephrectomy for renal cell carcinoma: A comprehensive analysis of prognostic factors

To investigate mortality rates and to comprehensively analyze prognostic indicators after radical nephrectomy for renal cell carcinoma.

Anatomical dimensions using preoperative magnetic resonance imaging: Impact on the learning curve of robot‐assisted laparoscopic prostatectomy

To evaluate the impact of anatomical dimensions as measured using preoperative magnetic resonance imaging on the outcomes of robot‐assisted laparoscopic prostatectomy.

Robot-assisted radical cystectomy is a promising alternative to open surgery in the Japanese population with a high rate of octogenarians

BackgroundJapanese patients who undergo radical cystectomy have a unique feature, i.e., the ratio of octogenarians is higher than in Western patients because of the aging Japanese population. The purpose of this study was to compare perioperative outcomes, complications, and oncologic outcomes between robot-assisted radical cystectomy and open radical cystectomy.MethodsFrom 2010−2015, 20 (of which 8 were octogenarians) and 40 (of which 11 were octogenarians) patients underwent robot-assisted radical cystectomy and open radical cystectomy, respectively.ResultsThere was no significant difference in terms of patient demographics between the two surgical cohorts, regardless of patient age. In the octogenarian patient cohort, the rates of previous abdominal surgery and the median age-adjusted Charlson comorbidity index were higher. The median estimated blood loss, transfusion rate and the days to resumption of a regular diet were significantly lower in the robot-assisted radical cystectomy cohort, regardless of patient age. Robot-assisted radical cystectomy significantly decreased grade II or higher complications, but there were no significant differences in terms of decreasing grade III or higher complications, regardless of patient age. Positive surgical margin and the mean number of lymph nodes removed were similar between the two surgical cohorts, regardless of patient age.ConclusionAlthough robot-assisted radical cystectomy has a short history in Japan, the outcomes were generally comparable to those of previous studies. In a country that is aging rapidly like Japan, robot-assisted radical cystectomy could be a valid option for the management of muscle-invasive and high-risk superficial bladder cancer.

Apoptotic Action of Botulinum Toxin on Detrusor Muscle in Rats

Aims: To examine botulinum toxin A (BTX-A)-induced apoptosis in the detrusor muscle in male rats. Methods: The bladder wall and prostate in adult male Sprague-Dawley rats were injected with BTX-A (10 U at each site). Tissues were harvested after 2 weeks, then the effects of BTX-A on proliferative and apoptotic indices were determined using proliferative cell nuclear antigen and TUNEL staining, respectively. In addition, real-time polymerase chain reaction was used to measure mRNA expressions of the apoptosis-related gene, bcl-2, and BAX in detrusor muscle. Results: Although bladder weight was significantly increased in the BTX-A group compared to controls, no significant changes in prostate weight were identified. While significant increases in proliferative cells were apparent in the vesical mucosa after staining, no significant changes were noted in apoptotic or proliferative cells in detrusor muscle or prostate. In addition, no significant changes between the BTX-A group and controls were seen for mRNA expressions of bcl-2/β-actin or BAX/β-actin in detrusor muscle. Conclusions: The lack of significant changes in cellular dynamics of the detrusor muscle in the current study suggests that BTX-A injection into detrusor muscle for overactive bladder may not induce bladder atrophy.

MP60-20 IDENTIFICATION OF MICRORNA REGULATING SUNITINIB RESISTANCE IN RENAL CELL CARCINOMA CELLS

patients have distal metastasis at the time of diagnosis. Despite great improvement in therapeutic treatment including molecular targeted therapy, the prognosis of patients with distant metastases remains unfavorable. HOX transcript antisense RNA (HOTAIR) is one of the long non-coding RNAs (lncRNAs). Accumulating evidence demonstrates that HOTAIR plays essential roles in cancer development and metastasis in several types of cancer such as lung cancer and gastric cancer. However, the precise mechanism by which HOTAIR enhances cancer malignancy is still unknown, especially in RCC. The object of this study is to elucidate the function of HOTAIR in RCC. METHODS: The tumor and adjacent normal renal tissues were obtained with informed consent from 64 patients who underwent radical or partial nephrectomy in Miyagi Cancer Center. All tumor tissues were diagnosed pathologically as clear cell renal cell carcinoma. We evaluated the clinical correlates of HOTAIR expression determined by realtime PCR using RNA extracted from the tumor and normal tissues. The functional role of HOTAIR was examined using HOTAIR-overexpressing or knockdown human renal cell carcinoma cell lines (ACHN, A498 and Caki-1). RESULTS: The expression of HOTAIR was significantly correlated with tumor nuclear grade, lymph node metastasis, lung metastasis, and AJCC stage. Migration capacity was enhanced in a HOTAIR-depending manner in vitro. Overexpression of HOTAIR in human renal cell carcinoma accelerated tumorigenicity in immunodeficient mice. Microarray analysis revealed that Insulin Growth Factor Binding Protein 2 (IGFBP2) gene was up-regulated in HOTAIR-overexpressing cells, which was validated by real-time PCR and Western blotting. Co-expression of IGFBP2 and HOTAIR was observed in clinical samples (P 1⁄4 0.04, Fisher0s exact test). Enhanced migration activity in HOTAIR-expressing cells was attenuated by IGFBP2knockdown. CONCLUSIONS: We newly identified IGFBP2 as a downstream molecule of HOTAIR, which is involved in migration capacity. Our findings suggest that a HOTAIR-IGFBP2 axis plays critical roles in RCC progression, and serves as a novel therapeutic target for advanced RCC treatment.