Efficacy and safety of intravesical dimethyl sulfoxide treatment for patients with refractory Hunner-type interstitial cystitis: Real-world data postofficial approval in Japan.

OBJECTIVES: To examine real-world data regarding intravesical dimethyl sulfoxide (DMSO) therapy after official approval as a treatment for Hunner-type interstitial cystitis (HIC) in Japan. METHODS: This single institution, retrospective observational study was conducted between 2021 and 2022 to evaluate the outcomes of 30 patients with refractory HIC who received intravesical DMSO therapy according to the approved standardized regimen: administration of DMSO every 2 weeks for a total of 12 weeks. Treatment outcomes were evaluated using a 7-graded global response assessment scale, O'Leary and Sant's symptom and problem indices (OSSI/OSPI), the overactive bladder symptom score (OABSS), an 11-point pain intensity numerical rating scale, quality of life (QOL) score, and frequency volume chart variables. Related complications were also documented. RESULTS: The response rates at 2, 4, 6, 8, 10, and 12 weeks were 36.7%, 43.3%, 53.3%, 60.0%, 70.0%, and 70.0%, respectively. Compared with baseline, OSSI/OSPI, pain intensity, urinary frequency, and the QOL score improved significantly from 4 weeks of treatment. The OABSS score and functional bladder capacity also showed a tendency toward moderate improvement, but the difference was not significant. The mean duration of symptom relapse after termination of treatment was 6.4 ± 3.9 months. No patients discontinued treatment due to adverse events, although acute bladder irritation during infusion was noted in 21 patients (70%), which disappeared within 3 days. CONCLUSIONS: This study verifies the safety, moderately durable efficacy, and tolerability of the standard intravesical treatment with DMSO for HIC in Japan.

Survival improvement over time in renal cell carcinoma treated with nephrectomy: A longitudinal propensity score-matched study.

OBJECTIVE: Surgical treatment for renal cell carcinoma (RCC) has drastically evolved for the past 30 years. However, survival outcomes of RCC according to times have not been fully elucidated, especially in the real-world setting. This study aimed to assess the survival improvement over time in RCC treated with nephrectomy by analyzing a longitudinal cohort using propensity score matching (PSM). METHODS: We retrospectively reviewed 960 patients with RCC who underwent radical or partial nephrectomy between 1981 and 2018. Patients were divided into two groups according to the time of surgery (1981-1999 vs. 2000-2018). Using PSM, overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were compared between the two groups. RESULTS: Overall, 255 and 705 patients underwent surgery in the earlier (1981-1999) and recent (2000-2018) eras, and PSM derived a matched cohort of 466 patients (233 patients per each group). All patients in the earlier era cohort received open surgeries, whereas about a half (47.4%) of patients in the recent era cohort received minimally-invasive (laparoscopic/robotic) surgeries. After PSM, 137 (29.4%) patients developed recurrence, 105 (22.5%) died of RCC, and 113 (24.2%) died from other causes, with a median follow-up period of 90 months. The recent era cohort had significantly longer OS, CSS, and RFS than the earlier era cohort. CONCLUSIONS: Patients with RCC treated in the recent era (2000-2018) showed significantly longer survival than those treated in the earlier era (1981-1999). The improved survival might be attributable to the prevalence of minimally-invasive (laparoscopic/robotic) surgeries.

Clinical manifestations of interstitial cystitis and bladder pain syndrome: Analysis of a patient registry in Japan.

OBJECTIVE: To describe clinical manifestations of patients with interstitial cystitis and bladder pain syndrome (IC/BPS) using a patient registry in Japan. METHODS: This retrospective cohort study utilized a patient registry supported by the Japanese Ministry of Health, Labor, and Welfare. Patients were classified as IC or BPS based on cystoscopic findings. Data on demographics, comorbidities, symptom severity, pain intensity, and bladder function were collected and we evaluated the differences in clinical characteristics between IC and BPS, and used multivariate analysis to search for additional factors that might contribute to pain. RESULT: A data set comprising 529 patients was obtained from 14 university hospitals. 66.5% of the cases were classified as IC and 33.5% as BPS. IC patients were significantly aged and female-dominant. Comorbidities such as autoimmune diseases were more prevalent in IC patients. All of the symptom severity, quality of life impairment, and bladder function were significantly worse in patients with IC. Urinary frequency and maximum voided volume on the Frequency-volume chart were 18.8 times and 15.0 times, and 160.9 and 214.1 mL, respectively. Bladder capacity under anesthesia was 293.8 and 472.6 mL, respectively. Maximum voided volume and the number of Hunner lesions were significant predictors of pain in IC patients. CONCLUSION: The analysis revealed clinical manifestations of IC/BPS using the largest cohort in Japan. The results indicated higher age, higher female proportion, and higher symptomatic and functional severity in IC patients compared to BPS.

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.

Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies.

PURPOSE: We systematically characterized gene expression, inflammation and neovascularization in patients with interstitial cystitis/bladder pain syndrome to obtain biological evidence supporting diagnosis and classification. MATERIALS AND METHODS: We sequenced RNA obtained from bladder mucosal biopsies of 33 patients with 3 subtypes of interstitial cystitis/bladder pain syndrome, including Hunner lesions in 12, no Hunner lesions in 11 but with glomerulations and neither Hunner lesions nor glomerulations in 10, and 9 controls. Differentially expressed genes of each subtype were searched to identify subtype specific biological pathways and candidate genes important for pathogenesis. Candidate genes were validated by quantitative polymerase chain reaction and immunohistochemistry. Digital immunohistochemical quantification was performed to assess subepithelial lymphoplasmacytic cell and microvessel density. Relationships between candidate gene over expression and symptom severity were explored. RESULTS: Patients with Hunner lesions showed a distinct gene expression profile associated with significant up-regulation of biological processes involving immune responses and infection, and an increase in subepithelial lymphoplasmacytic cell and microvessel density. Over expression of 2 candidate genes, VEGF and BAFF, correlated with symptom severity. Meanwhile, the gene expression profiles of patients with the 2 subtypes without Hunner lesions were similar to those of controls. No difference in biological pathways or subepithelial lymphoplasmacytic cell and microvessel density were detected between these 2 subtypes and controls. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome with Hunner lesions shows distinct genomic and histological features associated with immune responses and infection. In addition, VEGF and BAFF are potential disease biomarkers and therapeutic targets. This subtype should be considered separate from the syndrome.

Longitudinal change of comprehensive lower urinary tract symptoms and various types of urinary incontinence during robot-assisted radical prostatectomy.

AIMS: To clarify longitudinal change of lower urinary tract symptoms (LUTS) and various types of urinary incontinence following robot-assisted radical prostatectomy (RARP) using validated questionnaires. MATERIALS AND METHODS: The core lower urinary tract symptom score (CLSS) and the International Consultation on Incontinence Questionnaire (ICIQ)-Short Form (SF) questionnaires were administered to 607 consecutive, treatment-naïve men receiving RARP before and after surgery. The time course of comprehensive LUTS and various types of urinary incontinence, including stress-, urgency-, and urinary incontinence with no obvious reason, were evaluated. Continence recovery rates were compared for the different types of incontinence using Cox hazard regression analysis. RESULTS: After surgery, stress urinary incontinence (SUI) was reported most frequently (32% of cases) as the chief complaint with the most impact on daily life, as assessed by the CLSS questionnaire, followed by urgency urinary incontinence (UUI; 27% of cases). The rates of continence recovery differed among the different types of urinary incontinence, such as after urinating, when dressed, when asleep, when physically active or exercising, when coughing or sneezing, before reaching the toilet, and for no obvious reason. Incontinence for no obvious reason at 1 month after RARP was a strongest prognostic factor of delayed continence recovery (hazard ratio, 0.61; P < 0.0001), whereas patients reporting SUI and UUI gradually regained continence. CONCLUSIONS: Further time course on continent recovery after RARP would be more precisely predictable based on the incontinence status at one month postoperatively. Especially, incontinence with no obvious reason would be a significant factor for delayed recovery.

Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type interstitial cystitis.

AIM: To investigate the feasibility of chemokines and cytokines potentially elevated in the bladder tissue of Hunner type interstitial cystitis (HIC) as urinary markers for distinguishing HIC from non-Hunner type interstitial cystitis (NHIC) METHODS: Urine specimens were collected from 41 HIC patients, 25 NHIC patients, and 31 healthy volunteers (control). The supernatants of urine specimens were subjected to ELISA kits for measurements of 10 cytokines and chemokines, whose gene expression was known to be elevated in HIC bladder tissue. Urinary levels normalized by urinary creatinine (Cr) concentration were compared among three groups. Efficiency in differentiating IC and IC subtypes was explored by ROC analysis. The correlation of marker levels with symptom severity, assessed by O'Leary-Sant's symptom index (OSSI) and problem index (OSPI), was examined. RESULTS: The urinary levels of CXCL10 and NGF were significantly higher in HIC than NHIC. CXCL10 and NGF differentiated HIC against NHIC with AUC of 0.78 and 0.68, respectively. Combination of CXCL10 and NGF levels yielded an AUS of 0.81. The CXCL10 cut-off of 53.2 pg/mg Cr had sensitivity of 46.1%, specificity of 93.7%, positive predictive value of 97.7%, and negative predictive value of 60.0%. The urinary level of other cytokines showed no significant difference between HIC and NHIC. Significant correlation with symptoms was detected for CXCL10 alone. CONCLUSION: The results suggested that increased urinary level of CXCL10 combined with or without high NGF level could be a promising supplementary biomarker for differentiating HIC from NHIC with modest sensitivity and high specificity.

Digital quantitative analysis of mast cell infiltration in interstitial cystitis.

AIMS: To evaluate the significance of mast cell infiltration in interstitial cystitis (IC) by comparison with equally inflamed controls using a digital quantification technique. METHODS: Bladder biopsy specimens from 31 patients with Hunner type IC and 38 patients with non-Hunner type IC were analyzed. Bladder biopsy specimens from 37 patients without IC, including 19 non-specific chronic cystitis ("non-IC cystitis") specimens and 18 non-inflamed bladder ("normal bladder") specimens, were used as controls. Mast cell tryptase-, CD3-, CD20-, and CD138-immunoreactive cells were quantified using digital image analysis software to evaluate both mast cell and lymphoplasmacytic cell densities. Mast cell and lymphoplasmacytic cell densities were counted independently in the entire lamina propria and detrusor areas and compared among the four groups. RESULTS: In the lamina propria, there were no significant differences in mast cell and lymphoplasmacytic cell densities between Hunner type IC and non-IC cystitis or between non-Hunner type IC and normal bladder specimens. In the detrusor, the mast cell densities were not significantly different among the four groups. Mast cell density was correlated with lymphoplasmacytic cell density, but not with clinical parameters. CONCLUSIONS: Mast cell density is not significantly different between IC specimens and non-IC control specimens with a similar degree of background inflammation. The intensity of mast cell infiltration generally correlated with that of lymphoplasmacytic cells. We conclude that mast cell count is of no value in the differential diagnosis between IC and other etiologies.

Extent of Hunner lesions: The relationships with symptom severity and clinical parameters in Hunner type interstitial cystitis patients.

AIMS: To assess the clinical impact of Hunner lesions in patients with Hunner type interstitial cystitis (HIC). METHODS: The clinical records of 94 HIC patients who underwent their first hydrodistension (with lesion fulguration) were retrospectively reviewed. At surgery, the extent of each lesion was classified in terms of the relative involvement for the whole-bladder luminal surface; we defined four grades of involvement: <10%, 10-24%, 25-49%, and ≥50%; and two grades of severity: <25% (focal) and ≥25% (extensive). We examined the relationships between the extent of the lesions and all demographic characteristics, symptom scores, voiding symptoms, and bladder capacity. Factors predictive of the need for repeat hydrodistension were also explored. RESULTS: Symptom severity worsened as the lesional extent rose. Those with extensive lesions scored higher on the O'Leary and Sant Symptom (P = 0.004) and Problem Index scales (P < 0.001), the pain visual analog scale (P = 0.011), the International Prostate Symptom Score scale (P = 0.012), and a quality-of-life index (P = 0.020); and exhibited greater daytime urinary frequency (P = 0.040), more nocturia (P = 0.041), and a smaller bladder capacity (P = 0.007) than the focal group. No symptomatic or clinical parameters predicted the need for repeat hydrodistension. CONCLUSIONS: The extent of Hunner lesions was associated with both symptom severity and bladder capacity but not with other clinical parameters, including the need for repeat hydrodistension, in patients with HIC.

Robot-assisted radical prostatectomy significantly reduced biochemical recurrence compared to retro pubic radical prostatectomy.

BACKGROUND: The pathological and oncological outcomes of retro-pubic radical prostatectomy (RRP) and robot-assisted radical prostatectomy (RARP) have not been sufficiently investigated. METHODS: Treatment-naïve patients with localized prostate cancer (PC) (n = 908; RRP, n = 490; and RARP, n = 418) were enrolled in the study. The clinicopathological outcomes, rate and localization of the positive surgical margin (PSM), localization of PSM, and biochemical recurrence (BCR)-free survival groups were compared between RRP and RARP. RESULTS: The median patient age and serum PSA level (ng/mL) at diagnosis were 67 years and 7.9 ng/ml, respectively, for RRP, and 67 years and 7.6 ng/ml, respectively, for RARP. The overall PSM rate with RARP was 21%, which was 11% for pT2a, 12% for pT2b, 9.8% for pT2c, 43% for pT3a, 55% for pT3b, and 0% for pT4. The overall PSM rate with RRP was 44%, which was 12% for pT2a, 18% for pT2b, 43% for pT2c, 78% for pT3a, 50% for pT3b, and 40% for pT4. The PSM rate was significantly lower for RARP in men with pT2c and pT3a (p < 0.0001 for both). Multivariate analysis showed that RARP reduced the risk of BCR (hazard ratio; 0.6, p = 0.009). CONCLUSIONS: RARP versus RRP is associated with an improved PSM rate and BCR. To examine the cancer-specific survival, further investigations are needed.

Translation and reliability and validity testing of a Japanese version of the Intermittent Self-Catheterization Questionnaire among disposable and reusable catheter users.

AIMS: Quality of life in the context of intermittent self-catheterization varies depending on the type of catheter used. This study translated into Japanese, evaluated the feasibility, reliability, and validity of the Intermittent Self-Catheterization Questionnaire (ISC-Q) among users of both reusable and disposable catheters, and examined the differences of it between them. METHODS: Seventy patients (age mean ± SD: 62.8 ± 17.7 years) completed the Japanese version of the ISC-Q (J-ISC-Q) at baseline and 4 weeks later. Spearman's correlation coefficients between the J-ISC-Q, and Qualiveen® and the SF-12 were used for the translated scale's discriminant and convergent validity. Reliability was evaluated by intraclass correlation coefficients (ICC), the Bland-Altman method, and Cronbach's alpha. RESULTS: Participants answered all questionnaire items with no difficulties. Scores on the convenience domain were significantly higher among reusable compared to disposable catheter users (P = 0.039). The J-ISC-Q had significantly strong correlations with the Qualiveen® total scale (ρ = -0.712 to -0.237), but weak correlations with the SF-12 total scale (ρ = -0.231 to 0.474). Internal consistency was good (Cronbach's alphas > 0.706), and test-retest reliability was acceptable (ICC > 0.6) for the total scale and the four J-ISC-Q domains. The Bland-Altman analysis showed no systematic error between scores at baseline and 4 weeks later for the total scale and four domains of the J-ISC-Q. CONCLUSIONS: The J-ISC-Q has acceptable reliability and validity for assessing both reusable and disposable catheter users, and can be used to promote tailored individualized interventions based on the impact of catheter use.

Sleep Apnea and Circadian Extracellular Fluid Change as Independent Factors for Nocturnal Polyuria.

PURPOSE: We investigated the relationships among nocturnal polyuria, sleep apnea and body fluid volume to elucidate the pathophysiology of nocturia in sleep apnea syndrome. MATERIALS AND METHODS: We enrolled 104 consecutive patients who underwent polysomnography for suspected sleep apnea syndrome. Self-assessed symptom questionnaires were administered to evaluate sleep disorder and lower urinary tract symptoms, including nocturia. Voiding frequency and voided volume were recorded using a 24-hour frequency-volume chart. Body fluid composition was estimated in the morning and at night using bioelectric impedance analysis. Frequency-volume chart data were analyzed in 22 patients after continuous positive airway pressure therapy. RESULTS: Patients with nocturnal polyuria showed a higher apnea-hypopnea index (33.9 vs 24.2, p = 0.03) and a larger circadian change in extracellular fluid adjusted to lean body mass (0.22 vs -0.19, p = 0.019) than those without nocturnal polyuria. These relations were more evident in patients 65 years old or older than in those 64 years or younger. A multivariate linear regression model showed an independent relationship of nocturnal polyuria with the apnea-hypopnea index and the circadian change in extracellular fluid adjusted to lean body mass (p = 0.0012 and 0.022, respectively). Continuous positive airway pressure therapy significantly improved nocturnal polyuria and nocturia only in patients with nocturnal polyuria. CONCLUSIONS: This study identified sleep apnea and the circadian change in extracellular fluid as independent factors for nocturnal polyuria.

Hydrodistension with or without fulguration of hunner lesions for interstitial cystitis: Long-term outcomes and prognostic predictors.

AIMS: Hydrodistension of the bladder, with optional fulguration of Hunner lesions, is one of the recommended therapies for interstitial cystitis (IC). The aims of this study are to evaluate long-term outcomes of hydrodistension and identify outcome predictors. METHODS: The study cohort was 191 newly diagnosed IC patients (155 women and 36 men) who underwent hydrodistension with fulguration of Hunner lesions if detected between 2007 and 2013 at our institution. The primary outcome was therapeutic failure, which was defined as repeat hydrodistension, bladder instillation therapy, or narcotic use for pain control. Clinical features, including comorbidities and endoscopic findings, were analyzed along with the outcome. RESULTS: The cohort comprised 126 patients of Hunner type IC and 65 patients of non-Hunner type IC. The mean time to therapeutic failure was 28.5 months in Hunner type IC and 25.2 months in non-Hunner type IC. The therapeutic failure rate was higher in non-Hunner type IC at 17.3 months; however, the long-term outcomes reversed thereafter. The mean time to therapeutic failure was shorter in patients with lumbar spinal stenosis (LSS) or irritable bowel syndrome (IBS). Multivariate analysis identified LSS as a predictor for failure in Hunner type IC and non-Hunner type IC (HR = 18.8, P = 0.001; HR = 3.8, P = 0.028, respectively) and IBS in non-Hunner type IC (HR = 18.0, P = 0.008). CONCLUSIONS: Bladder hydrodistension, with fulguration of the Hunner lesions, improved IC symptoms. The outcome was worse in non-Hunner type IC shortly after hydrodistension but eventually comparable across the two types. Concomitant LSS and IBS were predictors for poor outcome. Neurourol. Urodynam. 35:965-969, 2016. © 2015 Wiley Periodicals, Inc.

Validation of an educational program balancing surgeon training and surgical quality control during robot-assisted radical prostatectomy.

OBJECTIVES: To establish a mentoring program that allows novice surgeons to use robotics while maintaining surgical quality during robot-assisted radical prostatectomy. METHODS: A total of 242 cases of robot-assisted radical prostatectomy for patients with localized prostate cancer were considered for this study. Each novice surgeon carried out a step-by-step robot-assisted radical prostatectomy procedure by following technical checkpoints and time limits that were established on the basis of previous surgical performance by a mentor. If technical checkpoints could not be accomplished, or the times were being exceeded, a mentor replaced the novice surgeon to finish the operative step or the surgery. Furthermore, if total blood loss exceeded 500 mL, a mentor completed the surgery. The primary end-point was the number of cases required for a new surgeon to successfully complete the entire robot-assisted radical prostatectomy procedure. Clinicopathological outcomes and any cases that deviated more than the standard deviation were also analyzed. RESULTS: Median patient age, serum prostate-specific antigen level (ng/mL), and Gleason score at diagnosis were 68 years, 7.6 and 7, respectively. Mean console and total operative times were 184 and 237 min, respectively. Mean perioperative blood loss was 300 mL. Seven out of eight new surgeons finished the total procedure after 10.7 cases (range 8-12). Four cases (1.7%) exceeded perioperative total blood loss and operative time. Positive surgical margin rates for total, T2, and T3 were 22, 9.3 and 47%, respectively. Positive surgical margin localized at bladder neck 19%, lateral lobe 39%, apex 32% and peripheral fat 9.4%. CONCLUSIONS: Herein we demonstrate an institutional mentoring program that effectively balances surgeon robot-assisted radical prostatectomy training and surgical quality control.

EXCISION OF GIANT PELVIC LIPOSARCOMA NECESSITATING FEMORAL-FEMORAL ARTERY BYPASS AND GAUZE PACKING FOR ILIAC ARTERY INVOLVEMENT AND MASSIVE PRE-SACRAL BLEEDING-A CASE REPORT.

The patient is a 43-year-old male, presented with numbness of the left lower extremities. Imaging studies showed a pelvic tumor 20 cm in diameter, involving the left ureter, left common iliac vessels, left internal and external iliac vessels, and inferior mesenteric artery, which was deemed unresectable. Tumor biopsy confirmed liposarcoma. As chemotherapy was not effective, he was referred to us. Following femoral-femoral artery bypass in advance, the tumor was resected with the sigmoid colon, left kidney, ureter, left iliac vessels, and interior mesenteric artery. Removal of the tumor caused massive venous hemorrhage from the pre-sacral plexus, which was scarcely managed by gauze packing. Open abdominal management was selected to avoid abdominal compartment syndrome by severe intestinal edema. The packed gauze was retrieved on the fourth post-operative day, with laparotomy closed. The postoperative course was uneventful.

Combination of docetaxel, ifosfamide and cisplatin (DIP) as a potential salvage chemotherapy for metastatic urothelial carcinoma.

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicity of the combination of docetaxel, ifosfamide and cisplatin as salvage chemotherapy after failure of standard cisplatin-based regimens for metastatic urothelial carcinoma. METHODS: We prospectively administered docetaxel, ifosfamide and cisplatin chemotherapy to patients with metastatic urothelial carcinoma refractory to standard cisplatin-based regimens from 2003 to 2013. Patients who had received only adjuvant and/or neoadjuvant chemotherapy were excluded. Eligible patients received every 28 days docetaxel 60 mg/m(2) on Day 1, ifosfamide 1.0 g/m(2) on Days 2-6 and cisplatin 20 mg/m(2) on Days 2-6. The primary endpoints were progression-free survival and overall survival, calculated from the start of docetaxel, ifosfamide and cisplatin chemotherapy. Secondary endpoints included objective response and related toxicity. RESULTS: Twenty-six cases received a median of 3.0 cycles of docetaxel, ifosfamide and cisplatin chemotherapy (interquartile range: 2-5), resulting in a median progression-free survival of 3 months (interquartile range: 2-9.5 months) and median overall survival of 8.5 months (interquartile range: 6.5-18.75 months), respectively. Of 26 patients, seven (27%) achieved major treatment responses, with one complete response (4%) and six partial responses (23%). Most of Grade 3/4 toxicities were hematologic events, including leukopenia (77%), anemia (54%) and thrombocytopenia (46%). No death from toxicity was observed. CONCLUSIONS: Our results indicate that docetaxel, ifosfamide and cisplatin chemotherapy is a tolerable and moderately active regimen for metastatic urothelial carcinoma after failure of standard cisplatin-based regimens.

Video-urodynamic effects of mirabegron, a ß3 -adrenoceptor agonist, in patients with low-compliance bladder.

OBJECTIVES: To investigate video-urodynamic effects of mirabegron, a ß3 -adrenoceptor agonist, on low-compliance bladder. METHODS: We retrospectively reviewed nine patients (three men, six women, age 17-68 years) who had been diagnosed with lower urinary tract dysfunction with low-compliance bladder, and who underwent video-urodynamic study before and during administration of mirabegron 50 mg once daily. Urodynamic parameters were compared before and after treatment. RESULTS: Mirabegron treatment significantly increased first desire to void and cystometric capacity with an average increment of 80 mL (P = 0.027) and 123 mL (P = 0.005), respectively. Bladder compliance also significantly increased (mean value 8.1 mL/cmH2 O before, 18.2 mL/cmH2 O after, P = 0.024). In the six patients who had been taking anticholinergic agents at baseline video-urodynamic study and then switched to mirabegron, mean cystometric capacity and bladder compliance were also increased significantly from 208.3 to 346.8 mL (P = 0.015) and from 7.2 to 17.5 mL/cmH2 O (P = 0.047), respectively. Vesicoureteral reflux grade was improved in three of the four patients who had shown vesicoureteral reflux on cystography before treatment. CONCLUSIONS: Mirabegron improves cystometric capacity and bladder compliance, and it lowers vesicoureteral reflux grade in patients with low-compliance bladder. Thus, mirabegron might represent a good alternative drug for low-compliance bladder refractory to anticholinergic treatment.

Botulinum toxin type A injection for refractory interstitial cystitis: A randomized comparative study and predictors of treatment response.

OBJECTIVES: To determine whether botulinum toxin type A can represent an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies. METHODS: This is a single-center, prospective, open labeled, randomized comparative study. Patients with refractory interstitial cystitis were randomly divided into two groups: immediate injection (group A) or 1-month delayed injection (group B) of botulinum toxin type A after allocation. The rate of treatment response (global response assessment ≥+1: slightly improved), and changes in symptom scores and frequency volume chart variables were compared between groups 1 month after allocation. Using subjects of both groups as a single cohort, predictive factors for treatment response at 1 month post-injection and the duration of response were explored. RESULTS: A total of 34 patients (group A n = 18, group B n = 16) were allocated. The response rate was significantly higher in group A than group B (72.2% vs 25.0%, P = 0.01). All symptom measures showed significant improvement in group A than group B. When both groups were combined as a single cohort, the response rate was 73.5% at 1 month, 58.8% at 3 months, 38.2% at 6 months and 20.6% at 12 months. The mean duration of response was 5.4 months. Multivariate analysis showed that past exposure to hydrodistension more than three times correlated with better outcomes. CONCLUSIONS: Botulinum toxin type A injection could be an alternative treatment option for patients with interstitial cystitis refractory to conventional therapies, especially for those who have received repeated hydrodistensions and transurethral fulguration.

[ADRENAL HEMORRHAGE: 6 CASES AND A REVIEW OF 57 REPORTED CASES].

PURPOSE: The guidelines on adrenal hemorrhage has not established in Japan. In this article, we discuss the management of adrenal hemorrhage. OBJECTS AND METHODS: We experienced 6 patients from November 2004 to September 2013 in The University of Tokyo Hospital and The Fraternity Memorial Hospital, and we searched 57 cases already reported in Japan by using Japan Medical Abstracts Society (http://search.jamas.or.jp/). So we analyzed total 63 adrenal hemorrhage cases in Japan. RESULTS: In 63 cases, 5 cases were performed TAE, 3 cases were performed emergent surgeries, 13 cases were managed conservatively and elective surgeries were performed in the other cases. 5 cases were fulfilled criteria for Hb < 10 g/dl and the maximum diameter of the hematoma > 10 cm. Of 5 cases, 4 cases were performed emergent hemostasis. CONCLUSIONS: Adrenal hemorrhages caused by metastatic tumor tend to be serious anemia. In addition, the most patients with adrenal hemorrhages, who had Hb < 10 g/dl and the maximum diameter of the hematoma > 10 cm, required immediate medical treatment, e.g. TAE or surgical hemostasis.

Improvement of symptoms of aging in males by a preparation LEOPIN ROYAL containing aged garlic extract and other five of natural medicines - comparison with traditional herbal medicines (Kampo).

"LEOPIN ROYAL®" (LER), a non-prescription health-promoting medication in Japan, is a preparation containing six natural medicines, namely, aged garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb. To determine the effect of LER on symptoms of aging in males, we conducted an open-labeled, randomized clinical trial using Kampo (mainly kamishoyosan) as a control. Forty-nine male patients (age, 62.7 (SD 11.8) years) with mild or more pronounced symptoms of aging were enrolled and randomly assigned to the LER (n = 24) or Kampo group (n = 25) for 6 months. The Aging Males' Symptoms (AMS) scale and the International Index of Erectile Function with 5 questions (IIEF-5) were tested at baseline, and after 3 and 6 months of administration of the medications. In the AMS scale, the somatic and psychological sub-scores and total score decreased depending on the time course in both groups. However, the decrease in the slope of the LER group was greater than that of the Kampo group. There was a significant difference between the groups and the group and month interaction (G × M), as revealed by a linear mixed model analysis (p < 0.05). The IIEF-5 score increased in the LER group (p = 0.02 with regard to G × M). In conclusion, the present results indicate that LER is possibly superior to mainly kamishoyosan on the rate of improvement of symptoms of aging, including erectile dysfunction, in males.