Fumitaka Shimizu

Impact of Dry Ejaculation Caused by Highly Selective α1A-blocker: Randomized, Double-blind, Placebo-controlled Crossover Pilot Study in Healthy Volunteer Men

INTRODUCTION Dry ejaculation with loss of seminal emission is reported in patients who have been administered silodosin, an alpha1A-adrenoceptor antagonist. AIM We investigated the impact of dry ejaculation caused by orally administered silodosin on orgasmic function. METHODS In a double-blind crossover study, 50 healthy volunteer men were randomly assigned to receive either a single dose of 4-mg silodosin or placebo with 3 days of washout before crossover. Subjects masturbated 4 hours after administering agents. MAIN OUTCOME MEASURES Numerical rating scale (NRS) score from 0 (highest) to 10 (lowest) for subjective quality of orgasm, the subjective number of contractions of the bulbocavernosus/pelvic floor muscles, and the amount of semen were examined. Results. After the administration of silodosin, the NRS score worsened by 1.3 points (P = 0.003), the number of contractions of the bulbocavernosus/pelvic floor muscles decreased by about 1 (P = 0.003), and there was a decrease of 1.8 mL in the amount of semen produced (P < 0.0001). Eleven men overall (22%) on silodosin administration had less than a 50% decrease from baseline in the amount of semen. CONCLUSIONS Silodosin may adversely affect the subjective orgasmic function by causing an abnormal ejaculation with decreased (or no) semen discharge and a decrease in the number of bulbocavernosus/pelvic floor muscle contractions. Semen passing through the urethra and sufficient rhythmic contraction of the muscle of the pelvic floor may contribute to the subjective pleasure of orgasm.

Stone attenuation value and cross-sectional area on computed tomography predict the success of shock wave lithotripsy.

Purpose To identify the parameters on noncontrast computed tomography (NCCT) that best predict the success of shock wave lithotripsy (SWL). Materials and Methods We reviewed the records of 75 patients who underwent SWL for urinary calculi measuring 5 to 20 mm. Using NCCT images, we estimated the largest stone cross-sectional area and contoured the inner edge of the stone. Clinical outcome was classified as successful (stone-free or <4 mm in diameter) or failed (stone fragments, ≥4 mm). The impact of preoperative parameters was evaluated by univariate and multivariate analysis. Results The overall success rate was 73.3%. Average stone attenuation value, stone length, and stone cross-sectional area in the success and failure groups were 627.4±166.5 HU (Hounsfield unit) vs. 788.1±233.9 HU (p=0.002), 11.7±3.8 mm vs. 14.2±3.6 mm (p=0.015), and 0.31±0.17 cm2 vs. 0.57±0.41 cm2 (p<0.001), respectively. In the multivariate analysis, stone attenuation value was the only independent predictor of SWL success (p=0.023), although stone cross-sectional area had a tendency to be associated with SWL success (p=0.053). Patients were then classified into four groups by using cutoff values of 780 HU for stone attenuation value and 0.4 cm2 for cross-sectional area. By use of these cutoff values, the group with a low stone attenuation value and a low cross-sectional area was more than 11.6 times as likely to have a successful result on SWL as were all other groups (odds ratio, 11.6; 95% confidence interval, 3.9 to 54.7; p<0.001). Conclusions Stone attenuation value and stone cross-sectional area are good predictors of extracorporeal SWL outcome.

Factors Associated with Variation in Utility Scores among Patients with Prostate Cancer

OBJECTIVE We aimed to assess the effects of age, comorbidity, and disease-specific functions on utility scores derived from three methods on prostate cancer. METHODS A total of 330 Japanese prostate cancer patients were asked to answer self-administered questionnaires. Community-weighted utility scores were derived from the EuroQoL-5D (EQ-5D) and the Short Form-36 (SF-36), while the patients directly elicited utility score was derived from time trade-off technique. Univariate and multivariate analyses were performed to examine the relation between covariates and utility scores. We assigned age, the Index of Co-existent Disease, and disease-specific functions including sexual, urinary, bowel, and hormonal function as covariates. RESULTS Bowel and hormonal function were related to utility scores, while age and sexual function were not. Comorbidities were more closely related to utility scores derived from EQ-5D and SF-36. CONCLUSIONS These results contribute to an understanding of which factor has an impact on utility scores in patients with prostate cancer.

Inadequacy of Prostate-Specific Antigen Doubling Time Estimates Calculated Using an Ultrasensitive Assay of Prostate-Specific Antigen for Biochemical Failure after Radical Prostatectomy

Background: The objective of this study was to evaluate the adequacy in calculating prostate-specific antigen doubling time (PSADT) using an ultrasensitive assay of prostate-specific antigen (PSA) for biochemical failure after radical prostatectomy (RP). Methods: In this research, we included 52 consecutive patients who experienced more than or equal to three consecutive increases in ultrasensitive PSA values after RP at two institutions. PSADT is to be calculated by fitting a linear model to post-nadir longitudinal logarithm ultrasensitive PSA (lnPSA) values. The goodness of fit of linear model for longitudinal lnPSA values was evaluated by applying a mixed effect model for all patients or two groups divided by median PSADT. Results: Median PSADT was 4.7 months. A mixed effect model showed that the fit of linear model for longitudinal lnPSA values was not good in lower ultrasensitive PSA values for all patients (p < 0.0001) or the group with a value longer than the median PSADT (p < 0.0001), while it was not worse for the group with a value shorter than the median PSADT (p = 0.079). Conclusions: These findings suggest that calculating PSADT using an ultrasensitive assay for biochemical failure after RP may still be open for discussion.

Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-muscle Invasive Bladder Cancer in Asia.

Background Some risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence. Methods The analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan–Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital. Findings There were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P < 0.001). Interpretation As the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC. Funding None.

Sarcopenia is a poor prognostic factor of castration-resistant prostate cancer treated with docetaxel therapy

Background Sarcopenia is a geriatric syndrome that is characterized by the gradual muscle loss and frailty in the elderly. Meanwhile, the prevalence of prostate cancer is on the rise worldwide. Mainstay treatments for metastatic prostate cancer are androgen-deprivation therapy and taxane-based chemotherapy. Owing to the indolent nature of prostate cancer, these treatments tend to be long-lasting, giving rise to the problem of tolerance to the treatments. Especially given the fact that long-term chemotherapy is closely associated with muscle loss, we aimed to elucidate the correlation between chemotherapy and sarcopenia in the clinical setting. Materials and methods This study was a retrospective study. Participants with castration-resistant prostate cancer were recruited from November 2009 to September 2015. Participants were recruited at two hospitals, Juntendo and Teikyo University Hospital, Tokyo, Japan. Participants were 77 Japanese males with castration-resistant prostate cancer who underwent docetaxel chemotherapy. Sarcopenia was defined as L3-psoas muscle index < 5.7 cm2/m2. We statistically investigated whether the existence of sarcopenia has an impact on the survival time, and identified potential covariates that affect it. Results Out of 77 patients, 26 patients (34%) were diagnosed as sarcopenia. Analysis showed that sarcopenia is independently associated with mortality risk (hazards ratio = 2.74, P = 0.0055). Sarcopenic patients showed significant decrease in body mass index, pretreatment hemoglobin, C-related protein, and L3-psoas muscle index as compared with nonsarcopenic patients. The median observation period was 499 days (330–790). Thirty-five patients (45%) died of prostate cancer during that period. Sarcopenic patients showed significantly shorter survival time after the initiation of docetaxel treatments (P = 0.0055). Conclusion Sarcopenia is an independent predictive factor for a poor tolerance to docetaxel treatment. Given that cessation of the treatment leads to death from the disease, our study identified sarcopenia as an independent factor that raises mortality risk.

A preliminary oncologic outcome and postoperative complications in patients undergoing robot-assisted radical cystectomy: Initial experience

Purpose Robot-assisted radical cystectomy (RARC) was originally intended to replace open radical cystectomy (ORC) as a minimally invasive surgery for patients with invasive bladder cancer. The purpose of this study was to evaluate the advantages of robotic surgery, comparing perioperative and oncologic outcomes between RARC and ORC. Materials and Methods Between June 2012 and August 2016, 49 bladder cancer patients were given a radical cystectomy, 21 robotically and 28 by open procedure. We compared the clinical variables between the RARC and ORC groups. Results In the RARC group, the median estimated blood loss (EBL) during cystectomy, total EBL, operative time during cystectomy, and total operative time were 0 mL, 457.5 mL, 199 minutes, and 561 minutes, respectively. EBL during cystectomy (p<0.001), total EBL (p<0.001), and operative time during cystectomy (p=0.003) in the RARC group were significantly lower compared with the ORC group. Time to resumption of a regular diet (p<0.001) and length of stay (p=0.017) were also significantly shorter compared with the ORC group. However, total operative time in the RARC group (median, 561 minutes) was significantly longer compared with the ORC group (median, 492.5 minutes; p=0.015). Conclusions This Japanese study presented evidence that RARC yields benefits in terms of BL and time to regular diet, while consuming greater total operative time. RARC may be a minimally invasive surgical alternative to ORC with less EBL and shorter length of stay.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis

To evaluate the clinical benefit of adjuvant platinum‐based chemotherapy after radical cystectomy for muscle‐invasive bladder cancer in routine clinical practice.

Disorganized Steroidogenesis in Adrenocortical Carcinoma, a Case Study.

Most adrenocortical carcinomas (ACCs) produce excessive amounts of steroid hormones including aldosterone, cortisol, and steroid precursors. However, aldosterone- and cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary aldosteronism and subclinical Cushing’s syndrome. Removal of the tumor cured both conditions. In order to examine the expression patterns of the steroidogenic enzymes responsible for adrenocortical hormone production, 10 tumor portions were immunohistochemically analyzed for aldosterone synthase (CYP11B2), 11β-hydroxylase (CYP11B1, cortisol-synthesizing enzyme), 3β-hydroxysteroid dehydrogenase (3βHSD, upstream enzyme for both CYP11B2 and CYP11B1), and 17α-hydroxylase/C17-20 lyase (CYP17, upstream enzyme for CYP11B1, but not for CYP11B1). CYP11B2, CYP11B1, and 3βHSD were expressed sporadically, and their expression patterns varied significantly among the different tumor portions examined. The expression of these enzymes was random and not associated with each other. CYP17 was expressed throughout the tumor, even in CYP11B2-positive cells. Small tumor cell populations were aldosterone- or cortisol-producing cells, as judged by 3βHSD coinciding with either CYP11B2 or CYP11B1, respectively. These results suggest that the tumor produced limited amounts of aldosterone and cortisol due to the lack of the coordinated expression of steroidogenic enzymes, which led to mild clinical expression in this case. We delineated the expression patterns of steroidogenic enzymes in ACC. The coordinated expression of steroidogenic enzymes in normal and adenoma cells was disturbed in ACC cells, resulting in the inefficient production of steroid hormones in relation to the large tumor volume.

Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study

Background: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. Methods: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0.5 or 1 mg/d between 2014 and 2017 in Juntendo University Nerima Hospital. Demographic and biochemical data including prostate-specific antigen (PSA) level were retrieved from the electronic medical records. Results: Fifty-three eligible patients (27 in ABI/PSL group and 26 in ABI/DEX group) were extracted from the records. Both groups showed no significant changes in serum potassium level before and after starting treatment. In the ABI/PSL group, 12 patients (46%) showed elevations of PSA and 7 patients (27%) discontinued treatment within 3 months. In contrast, in the ABI/DEX group, only 6 patients (25%) showed elevations of PSA and 3 patients (13%, all were given dexamethasone 1 mg/d) discontinued treatment. Conclusions: Dexamethasone and prednisolone may be equally effective in preventing abiraterone-induced hypokalemia.