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Objectives: To evaluate the efficacy of intravesical KRP-116D, 50% dimethyl sulfoxide solution, in interstitial cystitis/bladder pain syndrome patients with Hunner lesions (Hunner-type interstitial cystitis), and to evaluate the correlations between efficacy variables and global response assessment to determine what constitutes a minimal clinically important change., Methods: We performed a post hoc analysis of the Japanese phase III trial of KRP-116D. Changes at Week 12 from baseline in objective and subjective outcomes were compared between the KRP-116D and placebo groups in Hunner-type interstitial cystitis or non-Hunner-type interstitial cystitis patients. Correlations between efficacy variables at Week 12 and global response assessment were analyzed. Area under the receiver operating characteristic curve and the cut-off value of efficacy valuables were calculated to determine clinically meaningful changes., Results: The effectiveness of intravesical treatment with KRP-116D was demonstrated in Hunner-type interstitial cystitis, but not in non-Hunner-type interstitial cystitis patients. Global response assessment was closely correlated with subjective outcomes including O'Leary-Sant Interstitial Cystitis Symptom Index, O'Leary-Sant Interstitial Cystitis Problem Index, and a numeric rating scale for bladder pain, but was less correlated with voiding variables including micturition frequency, voided volume, and maximum voided volume. In the receiver operating characteristic curve analyses, the cut-off value for the O'Leary-Sant Interstitial Cystitis Symptom Index was -5 (sensitivity 81.3%, specificity 83.3%)., Conclusions: Clinical benefit of intravesical KRP-116D in Hunner-type interstitial cystitis patients was confirmed in this post hoc analysis. A five-point reduction in O'Leary-Sant Interstitial Cystitis Symptom Index is a clinically meaningful indicator for assessing patient satisfaction with KRP-116D treatment in patients with Hunner-type interstitial cystitis., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

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., (© 2021 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

The clinical guidelines for interstitial cystitis and related symptomatic conditions were revised by updating our previous guidelines. The current guidelines define interstitial cystitis/bladder pain syndrome as a condition with chronic pelvic pain, pressure or discomfort perceived to be related to the urinary bladder accompanied by other urinary symptoms, such as persistent urge to void or urinary frequency in the absence of confusable diseases. The characteristic symptom complex is collectively referred as hypersensitive bladder symptoms. Interstitial cystitis/bladder pain syndrome is divided into Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis and bladder pain syndrome represent interstitial cystitis/bladder pain syndrome with Hunner lesions and interstitial cystitis/bladder pain syndrome without Hunner lesions, respectively. So-called non-Hunner-type interstitial cystitis featured by glomerulations or bladder bleeding after distension is included in bladder pain syndrome. The symptoms are virtually indistinguishable between Hunner-type interstitial cystitis and bladder pain syndrome; however, Hunner-type interstitial cystitis and bladder pain syndrome should be considered as a separate entity of disorder. Histopathology totally differs between Hunner-type interstitial cystitis and bladder pain syndrome; Hunner-type interstitial cystitis is associated with severe inflammation of the urinary bladder accompanied by lymphoplasmacytic infiltration and urothelial denudation, whereas bladder pain syndrome shows little pathological changes in the bladder. Pathophysiology would also differ between Hunner-type interstitial cystitis and bladder pain syndrome, involving interaction of multiple factors, such as inflammation, autoimmunity, infection, exogenous substances, urothelial dysfunction, neural hyperactivity and extrabladder disorders. The patients should be treated differently based on the diagnosis of Hunner-type interstitial cystitis or bladder pain syndrome, which requires cystoscopy to determine the presence or absence Hunner lesions. Clinical studies are to be designed to analyze outcomes separately for Hunner-type interstitial cystitis and bladder pain syndrome., (© 2020 The Japanese Urological Association.)

Objective: To evaluate the predictive factors for comorbidity of Hunner-type interstitial cystitis in patients with chronic prostatitis/chronic pelvic pain syndrome using urethrocystoscopy., Methods: Thirty-two male patients were included in this study. Between April 2012 and April 2016; they were diagnosed with chronic prostatitis/chronic pelvic pain syndrome according to the National Institutes of Health classification. Their symptoms were not improved by 3 months of behavioral and pharmacological therapies. They all underwent narrow band imaging-assisted urethrocystoscopy to assess whether the presence of Hunner's lesions correlated with other variables., Results: Thirteen out of 32 patients (41%) had Hunner's lesions. Of the variables, maximal voided volume per micturition (106 ± 29 mL vs 171 ± 61 mL) and bladder capacity (267 ± 121 mL vs 407 ± 137 mL) were significantly smaller in patients with Hunner's lesions compared to those without. Other variables, apart from age, were not significantly different. Furthermore, patients with voided volume less than 150 mL were more likely to have Hunner's lesions than those with voided volume exceeding 150 mL., Conclusions: Hunner-type interstitial cystitis is a common comorbidity among patients with refractory chronic prostatitis/chronic pelvic pain syndrome. In cases where voided volume is small, performing narrow band imaging-assisted urethrocystoscopy would be very helpful for detecting bladder mucosal changes such as Hunner's lesions., (Editorial material and organization © 2019 The Japanese Urological Association. Copyright of individual abstracts remains with the authors.)

Objective: Suplatast tosilate, a Th2 cytokine inhibitor, was predicted to relieve interstitial cystitis symptoms. Four studies with suplatast tosilate in Japanese interstitial cystitis patients have been conducted: a single-arm clinical study, a phase II dose-ranging trial, a phase III trial with placebo, and a second phase PIII trial with placebo. Treatment efficacy was observed in the first two studies; however, in the phase PIII trials, no significant difference in interstitial cystitis symptom score changes was observed between suplatast tosilate and placebo. We summarized these four studies to investigate factors causing the difference in observed efficacy., Methods: Placebo effects in the first two studies and differences regarding study design between the four studies were considered to be possible factors. Therefore, placebo effects were investigated by comparing interstitial cystitis symptom score changes, and the study designs were compared to investigate the effects on observed efficacy., Results: Interstitial cystitis symptom score changes in the phase PII treatment groups increased in a dose-dependent manner and showed an almost linear relationship with interstitial cystitis symptom score changes observed in placebo groups of 2 phase PIII studies. A major difference regarding the phase PIII study design was the use of diagnostic hydrodistention. Diagnostic hydrodistention and its washout period were applied only in the phase PIII trials., Conclusions: Comparison of interstitial cystitis symptom score changes suggested that the placebo effect was very small. Use of diagnostic hydrodistention was considered to be a major difference in the population characteristics of the studies and may have resulted in different observed efficacies. Diagnostic hydrodistention, which potentially influences the treatment effect, is probably not essential for trials of suplatast in interstitial cystitis patients., (Editorial material and organization © 2019 The Japanese Urological Association. Copyright of individual abstracts remains with the authors.)

Objective: To investigate the efficacy of urine alkalization therapy using citrates in patients with hypersensitive bladder syndrome., Methods: A total of 76 patients with urinary frequency were assessed for their symptoms using a 2-day voiding diary as well as the urine pH at each voiding during the screening period. Their symptoms were also assessed by pain score, King's health questionnaire, and O'Leary-Sant symptom and problem index scores. Finally, 50 patients were evaluated for changes in symptoms after oral treatment with citrates for 2-4 weeks after the screening period., Results: After the treatment, significant increases in the urine pH (from 5.8 ± 0.4 to 6.3 ± 0.4; increment of 0.5 ± 0.4; P < 0.01), and significant decreases in the number of micturitions per day (from 14.5 ± 6.5 to 13.5 ± 5.9; P = 0.02) and the number of episodes of pain/discomfort per day (from 7.8 ± 6.8 to 6.1 ± 7.1; P = 0.02) were observed. In the King's health questionnaire, the sleep/energy domain score was significantly improved (from 60.0 ± 25.0 to 50.3 ± 29.6; P < 0.01). In a subgroup analysis based on urine pH (urine pH <6.2 and ≥6.2), significant improvements in the voiding symptoms, the sleep/energy domain score and the O'Leary-Sant problem index were observed in the group with urine pH of ≥6.2. There were statistically significant differences between the subgroups in the volume per voiding, maximum volume per voiding and the problem index. In addition, the subgroup, in which patients had pain in the screening period, showed statistically significant improvements in the number of micturitions per day, episodes of pain/discomfort per day, the sleep/energy domain score and the problem index., Conclusions: Urine alkalization therapy is likely to be effective in the treatment for hypersensitive bladder syndrome., (© 2013 The Japanese Urological Association.)

A clinical guideline and algorism for interstitial cystitis and hypersensitive bladder syndrome has been developed by a group of East Asian urologists as a revised form of the Japanese guideline for interstitial cystitis. The guideline defines interstitial cystitis (IC) as a disease of the urinary bladder diagnosed by 3 requirements; 1) a characteristic complex of lower urinary tract symptoms, 2) bladder pathology such as Hunner's ulcer and bladder bleeding after overdistension, and 3) exclusions of confusable diseases. The characteristic symptom complex is termed as hypersensitive bladder syndrome (HBS), which is defined as bladder hypersensitivity, usually associated with urinary frequency, with or without bladder pain. For the definite diagnosis of IC, cytoscopy or hydrodistension is crutial; HBS is the diagnosis when IC is suspected but not confirmed by the 3 requirements. Numerous therapeutic options are available; however, most of them lack in high level of evidence, leaving a few as recommended therapies. Etiology of IC are multifactorial; the interaction among nervous, immune and endocrine factors forms a vicious cycle, provocating and maintaining inflammatory reactions in the bladder. The inclusion and efficacy criteria for clinical trials should be standardized to enhance the clinical research for this disabling disease, which has proved to be more prevalent than previously believed.

Objective: To examine the expression profiles of the proteins translated from Acpin1 mRNA in germ cells., Methods: Northern and western blotting of various tissues and immunohistochemical analysis of germ cells were carried out in a mouse model., Results: ACPIN1 protein was transcribed from the longer, 3' open reading frame (ORF) of Acpin1. An alternative-splicing variant, Acpin1vs, contained only the smaller, 5' ORF of the full-length Acpin1 gene. Its gene product, SAGSIN1, was expressed specifically in salivary glands. Retrotransposed regions of Acpin1 homology were also detected in various chromosomes, and intronless paralogous genes on the X chromosome were expressed in the testis and other tissues. The genomic structure of Acpin1 is highly conserved in mammals., Conclusion: The two ORFs on the Acpin1 mRNA are independently translated in differentiated cells. Analysis of gene Acpin1 might clarify the molecular mechanism of spermatogenesis.

Interstitial cystitis (IC) is a disease of the urinary bladder with lower urinary tract symptoms such as urinary frequency, bladder hypersensitivity and/or bladder pain and resultant serious impairment of quality of life. In Japan, assuming that IC is very rare, research activity and medical care of IC have been sparse until 2001, when the Society of Interstitial Cystitis of Japan (SICJ) and a patient support group were founded.(1,2) Subsequently the International Consultation on Interstitial Cystitis Japan (ICICJ) was held in Kyoto in 2003.(3) On the other hand, the etiology of IC has not been well clarified, which complicates its diagnosis and treatment at clinical settings. We have thus developed the Japanese Clinical Guideline,(4) which is targeted at healthcare professionals including specialists in urology and women's health care who may engage in the diagnosis and treatment of IC. This article is the English translation of a shortened version of the Guideline for convenience of readers worldwide.

Objectives: Diagnosing the bladder lesions associated with interstitial cystitis/painful bladder syndrome (IC/PBS) is sometimes difficult for general urologists. We therefore aimed to develop an IC/PBS diagnosis method using a cystoscope with a narrow-band imaging (NBI) system that can detect mucosal angiogenic lesions., Methods: Fifty-two subjects suspected of having IC between October 2006 and June 2007 were included in this study. There were 49 women and three men, ranging in age from 19 through 85 with an average age of 59. First, conventional cystoscopy under spinal anesthesia was performed to examine the ulcerative lesions by a urological specialist. Then, other health care professionals made a separate observation of capillary-rich areas of the superficial layer of the bladder mucosa by cystoscopy with the NBI system., Results: Among the 52 patients, 37 cases were found to have ulcers by conventional cystoscopy, which were also recognized as capillary-rich brownish areas using the NBI system (100% accuracy); 13 cases were found to have NBI-positive areas without ulcer, which were coincided with those with petechial hemorrhages and glomerulations following subsequent hydrodistention; and two cases of normal mucosa were detected. Furthermore, six cases of bladder cancer (carcinoma in situ) were detected by biopsies that were obtained from the ulcerative lesions positively identified by NBI cystoscopy., Conclusions: Examining the urinary bladder mucosa with a flexible cystoscope with the NBI system makes it possible to easily detect ulcers of bladder mucosa and areas with angiogenesis. Therefore, it is considered that the use of a flexible cystoscope with the NBI system is highly practical for the IC/PBS diagnosis.

Objectives: First desire to void (FDV) is defined as the first feeling that would lead the patient to pass urine. The aim of the present study is to identify the brain regions activated during FDV., Methods: Six healthy right-handed male volunteers, aged 31-40 years, agreed to participate in this study. Rather than inserting a urethral catheter, we used a urinary volume monitoring unit and a self-adhesive external condom catheter for this study. Positron emission tomography (PET) scans obtained in the FDV and post-voiding (absence of urge to void) (REST) states were analyzed and compared., Results: First desire to void state was associated with increased blood flow in the right and left cerebellum, right parahippocampal gyrus (Brodmann area [BA] 30), left superior frontal gyrus (BA9), and left cingulate gyrus (BA32). Rest state was associated with decreased blood flow in the right superior temporal gyrus (BA22), right uncus (BA28), right cingulate gyrus (BA32), left middle temporal gyrus (BA21), and left medial frontal gyrus (BA25). According to region of interest analysis, regional cerebral blood flow of the periaqueductal grey and pons was significantly increased at FDV as opposed to REST., Conclusions: We located possible brain activity associated with the FDV sensation. Combined activation of the right and left cerebellum, parahippocampal gyrus, superior frontal gyrus, and left cingulate gyrus could be associated with FDV.

Objectives: We investigated the characteristics of recent male and female patients diagnosed with interstitial cystitis (IC), then investigated which therapy was chosen by the attending urologist., Methods: Materials were 282 IC patients diagnosed and treated during the past 3 years (sampling from Japanese IC database). Gender, age, medical history and predominant symptoms were investigated. In addition, we investigated the interval before a diagnosis was established. In laboratory findings, we investigated voided volume, urinalysis findings and cystoscopic findings. Regarding therapy, we investigated which therapy was chosen as the first line., Results: The gender ratio was about 1.0:5.6 (male : female). Regarding age distribution, patients in their 60s were the most frequent (65 cases, 31.3%). The interval before diagnosis of IC was 36.5 months on average (1-360 months). Regarding medical history, intrapelvic surgery was the most common and repeated urinary tract infection was next. The most frequent symptom was urinary frequency (295 cases, 98.3%). Urinary urgency was noted in 186 cases (62%) and supra-pubic pain was noted in 125 cases (41.6%). The once voided volume was 104.3 mL on average (50-200 mL). The most common cystoscopic finding was glomerulation (158 cases). Ulcer was present in only 19 cases. The most widely carried out therapy was hydrodistension (208 cases, 67.9%). Oral suplatast tosilate (197 cases, 65.6%), antihistamine (77 cases, 25.6%) and intravesical dimethylsulfoxide (69 cases, 23%) followed., Conclusions: Regarding characteristics, the age distribution was older than other countries. The most frequent symptom was urinary frequency. Oral suplatast tosilate was one of the popular therapies in Japan.

The association between idiopathic inflammatory myositis and cancer is well recognized. Most descriptions have been of dermatomyositis-associated cancer, however, a few have been of polymyositis-associated adrenal cancer. Here, we report a 69-year-old man in whom polymyositis-associated adrenal cancer was diagnosed. The patient complained of difficulty with walking and with standing unassisted. Physical examination and electrophysiological studies revealed an abnormality of the proximal muscles. Serum levels of creatine kinase and lactic dehydrogenase were increased. Imaging studies showed a solid tumor measuring 14 x 9 cm in the retroperitoneum. After surgical excision of the tumor, including the left kidney, the serum levels of creatine kinase and lactic dehydrogenase normalized, and symptoms of myositis disappeared.

Background: We compared the clinical effects and impact on quality of life (QOL) of patients who received a 3-month course of flutamide monotherapy before radical prostatectomy with those who received a 3-month course of luteinizing hormone-releasing hormone (LHRH) agonist monotherapy., Methods: Thirty-seven patients with non-metastatic prostate cancer were enrolled in this study (19, flutamide; 18, LHRH agonist). The rates of change of serum prostate-specific antigen (PSA) and testosterone levels, downsizing of prostate volume, the rate of organ confined disease, adverse effects and perioperative scores measured using the European Organization for Research and Treatment of Cancer Prostate Cancer Quality of Life Questionnaire (EORTC-P) and the Sapporo Medical University Sexual Function Questionnaire (SMUF) were analyzed., Results: At radical prostatectomy, pathological variables were not significantly different in the two groups. Serum testosterone level was significantly higher (mean 359.2 compared to 10.5, P < 0.001), complete response rate of PSA (13% compared to 57%, P = 0.028) and rate of downsizing of prostate volume (mean, -17.7% compared to -35.4%, P = 0.038) were significantly lower in the flutamide group than in the LHRH group. After neoadjuvant hormone therapy, the scores on the sexual problem domain of EORTC-P (P = 0.033) and sexual desire score of SMUF (P = 0.021) were significantly higher in the flutamide group than in the LHRH group. At a median follow-up of 34 months after prostatectomy, biochemical failure-free survival rate in the flutamide group did not differ from that in the LHRH group., Conclusion: This study suggests that flutamide monotherapy can be an acceptable modality as an option for neoadjuvant hormone therapy.