Efficacy and safety of intravesical instillation of KRP-116D (50% dimethyl sulfoxide solution) for interstitial cystitis/bladder pain syndrome in Japanese patients: A multicenter, randomized, double-blind, placebo-controlled, clinical study.

OBJECTIVE: To evaluate the efficacy and safety of intravesical KRP-116D, 50% dimethyl sulfoxide solution compared with placebo, in interstitial cystitis/bladder pain syndrome patients. METHODS: Japanese interstitial cystitis/bladder pain syndrome patients with an O'Leary-Sant Interstitial Cystitis Symptom Index score of ≥9, who exhibited the bladder-centric phenotype of interstitial cystitis/bladder pain syndrome diagnosed by cystoscopy and bladder-derived pain, were enrolled. Patients were allocated to receive either KRP-116D (n = 49) or placebo (n = 47). The study drug was intravesically administered every 2 weeks for 12 weeks. RESULTS: For the primary endpoint, the change in the mean O'Leary-Sant Interstitial Cystitis Symptom Index score from baseline to week 12 was -5.2 in the KRP-116D group and -3.4 in the placebo group. The estimated difference between the KRP-116D and placebo groups was -1.8 (95% confidence interval -3.3, -0.3; P = 0.0188). Statistically significant improvements for KRP-116D were also observed in the secondary endpoints including O'Leary-Sant Interstitial Cystitis Problem Index score, micturition episodes/24 h, voided volume/micturition, maximum voided volume/micturition, numerical rating scale score for bladder pain, and global response assessment score. The adverse drug reactions were mild to moderate, and manageable. CONCLUSIONS: This first randomized, double-blind, placebo-controlled trial shows that KRP-116D improves symptoms, voiding parameters, and global response assessment, compared with placebo, and has a well-tolerated safety profile in interstitial cystitis/bladder pain syndrome patients with the bladder-centric phenotype.

Superiority of dutasteride 0.5 mg and tamsulosin 0.2 mg for the treatment of moderate-to-severe benign prostatic hyperplasia in Asian men.

OBJECTIVES: To assess the effectiveness and safety of dutasteride 0.5 mg + tamsulosin 0.2 mg combination compared with tamsulosin 0.2 mg in Asian men with moderate-to-severe benign prostatic hyperplasia. METHODS: A 4-week, single-blind, placebo, run-in was followed by a 2-year double-blind randomized controlled trial in men age ≥50 years with symptomatic benign prostatic hyperplasia, International Prostate Symptom Score ≥12, prostate volume ≥30 cc, prostate-specific antigen ≥1.5 and ≤10 ng/mL, peak urinary flow >5 and ≤15 mL/s, and voided volume of ≥125 mL. Participants were randomized to oral daily dutasteride 0.5 mg + tamsulosin 0.2 mg combination or tamsulosin 0.2 mg. The primary efficacy end-point was change in International Prostate Symptom Score at year 2. RESULTS: Data from 607 participants showed a significant reduction in International Prostate Symptom Score (P < 0.05) at month 24, along with greater improvements (P ≤ 0.006) in peak urinary flow at every assessment and significant prostate volume reduction at months 12 and 24 (P < 0.001) in the combination group. Combination therapy was associated with a significant reduction in the risk of acute urinary retention or benign prostatic hyperplasia-related surgery (P = 0.012), primarily due to a significant reduction in the risk of acute urinary retention (P = 0.005). The safety and tolerability profile of combination therapy was consistent with the known profiles for the individual monotherapies. CONCLUSIONS: Dutasteride 0.5 mg + tamsulosin 0.2 mg combination therapy showed better clinical outcomes than tamsulosin 0.2 mg monotherapy, making it an effective and safe treatment option for Asian men with moderate-to-severe benign prostatic hyperplasia.

[MASSIVE HEMORRHAGE FROM THE FISTULA FORMATION BETWEEN CUTANEOUS URETEROSTOMY AND INFERIOR EPIGASTRIC ARTERY: A CASE REPORT].

A 87-year-old man received radical nephroureterectomy for right renal pelvic cancer in 2009 and left cutaneous ureterostomy after radical cystectomy for bladder cancer in 2013. He visited the hospital for exchanging a 7 or 8 Fr single-J catheter every 2 to 4 weeks. Eleven months after the 2nd operation, massive bleeding from the stoma occurred when ureteral catheter was exchanged. Contrast-enhanced computed tomography showed that left inferior epigastric artery was located close to left ureter. Angiography of the left inferior epigastric artery didn't show an obvious fistula, but revealed the stoma was surrounded by ramified new blood vessels from left inferior epigastric artery. We suspected a rupture of the vessels and performed embolization for the branch of inferior epigastric artery to left ureter. This embolization made it possible for the bleeding to be controlled. Massive bleeding from the branch of inferior epigastric artery is very rare, and we report the case and review the literature.

Efficacy and safety of dutasteride on prostate cancer risk reduction in Asian men: the results from the REDUCE study.

OBJECTIVE: A post hoc analysis of Asian men in the REDUCE study was conducted to investigate whether the outcomes were in line with those of the overall population. METHODS: REDUCE was a 4-year international, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Inclusion criteria were men between 50 and 75 years of age, a serum prostate-specific antigen level of 2.5-10.0 ng/ml (50-60 years) or 3.0-10.0 ng/ml (>60 years), and a single, negative prostate biopsy (6-12 cores) within 6 months before enrollment. The primary endpoint was biopsy-detectable prostate cancer. This post hoc analysis included subjects who were recorded as Asian. RESULTS: A total of 134 Asians, including 57 Japanese, were randomized to the study treatment. During the study period, the incidence of prostate cancer in the placebo and dutasteride groups was 19.6% (11/56) and 9.3% (5/54), respectively (relative risk reduction, 54%; 95% confidence intervals, -27 to 83%, P = 0.12), in the Asian subpopulation. Fewer tumors with the Gleason scores of 7-10 and 8-10 were detected among dutasteride-treated men. Although the incidences of drug-related sexual adverse events were higher in the dutasteride group, only in rare occasions did they lead to drug discontinuation. CONCLUSIONS: The incidence of prostate cancer in the dutasteride group was lower than that in the placebo group, although the difference was not significant. These results paralleled those for the overall population and support the value of dutasteride for prostate cancer risk reduction in Asian men with an increased risk of prostate cancer.

[The effects of dutasteride on voiding and storage symptoms in men with benign prostatic hyperplasia].

We investigated the effects of dutasteride on voiding and storage symptoms by a post-hoc analysis from two randomized, placebo-controlled, parallel-group studies (Japanese phase II study and phase III study) which assessed the efficacy and safety of dutasteride in Japanese men with benign prostatic hyperplasia (BPH). Men aged 50 years and older, with a prostate volume of 30 cc or greater, an International Prostate Symptom Score (IPSS) of 8 or higher and maximal urinary flow rate of 15 ml/sec or lower were randomized to placebo or dutasteride groups. The number of subjects for the placebo and dutasteride groups was respectively 72 and 72 in the phase II study, and 185 and 193 in the phase III study. Questions 1, 3, 5 and 6 of IPSS were related to voiding symptoms, and Questions 2, 4 and 7 were related to storage symptoms. Changes between pre- and post-treatments were evaluated. In the phase II study, dutasteride significantly improved voiding symptoms and numerically improved storage symptoms compared with the placebo at week 24. In the phase III study, dutasteride significantly improved voiding and storage symptoms compared with the placebo after 52 weeks. These consistent results suggest that dutasteride is effective for both voiding and storage symptoms in Japanese men with BPH.

Up-titration of vardena fi l dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury.

AIM: Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed. METHODS: This was an open-label, multicenter, flexible dose, 12-week study in patients with ED due to SCI. Following a 4-week observation period, patients received vardenafil 10 mg for 4 weeks, and based on efficacy, tolerability and patient preference, doses for the remaining 8 weeks were decided by investigators. The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function. RESULTS: Ten patients took 10 mg all through the study, while 22 patients took 20 mg after completing 4 weeks' treatment with 10 mg. The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward (LOCF) in the former group and from 10.3 to 22.5 in the latter group, respectively. Importantly, there was a 5.0 point increase in erectile function domain score after up-titration in the latter group. Drug-related adverse events were observed in 22% of patients including hot flushes (9%) and headache (6%), but these were transient and mild in intensity. Serious adverse events and adverse events leading to discontinuation of the study drug were not reported. CONCLUSIONS: Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI. Of interest, erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg.

[Usefulness of lower ihfundibular length-to-diameter ratio as a predictor of lower pole stone clearance after extracorporeal shock wave lithotripsy; clinical research with two lithotriptors].

PURPOSE: Lower pole renal stones are well known to exhibit a poor stone clearance rate following extracorporeal shock wave lithotripsy (ESWL). In the present study, we analyzed several anatomical factors as predictors of lower pole stone clearance that may be used to indicate the usefulness and the universality of ESWL in such patients with two different lithotriptors. PATIENTS AND METHODS: 93 patients with a unilateral single lower pole stone of 2 cm. or less underwent ESWL using Piezolith 2500 or Medstone STS, were included in the study. An IVP was used to determine the lower infundibulopelvic angle, the caliceal pelvic height, the lower infundibular length, the lower infundibular diameter, the lower infundibular length-to-diameter ratio and the number of lower pole minor calyces. Stone-free status was assessed by a plain film with or without renal ultrasound. RESULTS: The stone clearance rate at the Piezolith 2500 group was 53.1% (34 of 64 patients), while was 51.7% (15 of 29 patients) at the Medstone STS group. In all cases, the overall stone clearance rate was 52.7% (49 of 93 patients). Age, laterality of the stone burden within the kidney and stone size were not different between the stone-free and residual stone groups. Multivariate logistic analysis revealed that length-to-diameter ratio was the most independent predictors of successful stone clearance at each group. The patients exhibited length-to-diameter ratio less than 7 achieved high stone clearance rates, greater than 72%. In contrast, the stone clearance rate was less than one third when length-to-diameter ratio was 7 or greater. Besides length-to-diameter ratio was strong prognostic factor in patients with stones 1 cm. or less and 1 to 2 cm at each group. CONCLUSION: From this study, it is apparent that successful ESWL is highly sensitive to the anatomy of the lower pole of the kidney. Especially, the lower infundibular length-to-diameter ratio is potentially useful and a universal predictor regardless of the kind of lithotriptors at least in patients with a lower pole radiopaque stone 2 cm. or less treated with ESWL.