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This Asia‐Pacific (AP) AMS 800™ artificial urinary sphincter (AUS) consensus statement aims to provide a set of practical recommendations to assist surgeons with the AMS 800 device surgery. The AP consensus committee consisted of key opinion leaders with extensive experience with AMS 800 surgery across several AP countries. The panel reviewed and discussed relevant findings with emphasis on locoregional and specific clinical challenges relevant to the AP region. Recommendations were made in key areas namely (1) patient selection and informed consent process; (2) preoperative assessment; (3) dealing with co‐existing urological disorders; (4) surgical principles and intraoperative troubleshooting; (5) postoperative care; (6) special populations; and (7) cost analysis and comparative review. The AMS 800 device should be offered to males with moderate to severe stress urinary incontinence (SUI). Full informed consent should be undertaken, and emphasis is placed on surgical contraindications and high‐risk candidates. The presence of a surgical mentor or referral to experts is recommended in complex AUS candidates. Preoperative cystoscopy with or without multichannel urodynamic study is necessary and patients with pre‐existing urological disorders should be treated adequately and clinically stable before surgery. Adherence to strict patient selection and safe surgical principles are critical to ensure excellent clinical outcomes and minimize complications. Given that InhibiZone‐coated device is not available in many AP countries, the use of prophylactic antibiotics pre‐and post‐operatively are recommended. The AMS 800 device should be prepared according to the manufacturer's guidelines and remains a cost‐effective treatment for male SUI. The AMS 800 device remains the surgical benchmark for male SUI but is associated with certain mechanical limitations and a unique set of complications. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the surgical and quality‐of‐life outcomes of artificial urinary sphincter implantation in patients with diabetes mellitus (DM). Subanalyses were performed using the same population as that in our previous multicenter, prospective, observational study. Methods: A total of 135 male patients who underwent primary artificial urinary sphincter implantation were divided into two groups: those with and without DM. The revision‐free rates, that is, the percentage of patients who did not require revision surgery, were compared between patients with and without DM. The number of urinary pads required per day, International Consultation on Incontinence Questionnaire‐Short Form, and King's Health Questionnaire were used to compare the continence status and quality of life (QOL) between the two groups preoperatively and at 1, 3, and 12 months after surgery. Results: Revision‐free rates were significantly lower in the DM group (83.9%, 77.4%, and 67.8% at 1, 2, and 3 years after implantation, respectively) than in the non‐DM group (95.5%, 92.5%, and 85.5% at 1, 2, and 3 years after implantation, respectively). Both continence status and QOL, assessed by questionnaires, markedly improved after surgery in patients with and without DM. Conclusions: Despite differences in the durability of the artificial urinary sphincters, patients with DM can obtain as much benefit from artificial urinary sphincter implantation regarding continence and quality‐of‐life improvement as patients without DM. Therefore, DM was not considered a comorbidity that contraindicated artificial urinary sphincter implantation. Additional large‐scale studies are required to verify our findings. [ABSTRACT FROM AUTHOR]

Diagnostic methods for CP have not been established.4 Thus, we proposed "The Project to Develop a Novel Diagnostic Tool for Chronic Prostatitis" to enable the easy diagnosis of CP by patients and medical professionals who are not urologists. Crowdfunding may also be effective for raising nonmedical professionals' awareness regarding CP. Abbreviation & Acronym CP chronic prostatitis Obtaining research grants is a critical global issue for researchers.1 In Japan, research grants are typically provided using public funds, such as the JSPS KAKENHI Grant, or given by public interest foundations. [Extracted from the article]

The present article is an abridged English translation of the Japanese Clinical Guidelines for Female Lower Urinary Tract Symptoms (second edition), published in September 2019. These guidelines consist of a total of 212 pages and are unique worldwide in that they cover female lower urinary tract symptoms other than urinary incontinence. They contain two algorithms for "primary treatment" and "specialized treatment," respectively. These guidelines, consisting of six chapters, address a total of 26 clinical questions including: (i) treatment algorithms; (ii) what are female lower urinary tract symptoms?; (iii) epidemiology and quality of life; (iv) pathology and illness; (v) diagnosis; and (vi) treatment. When the patient's symptoms mainly involve voiding and post‐micturition symptoms, specialized treatment should be considered. In the event of voiding symptoms concurrent with storage symptoms, residual urine should be measured; if the residual urine volume is <100 mL, then diagnosis and treatment for storage symptoms is prioritized, and if the volume is ≥100 mL, then specialized treatment should be considered. When storage symptoms are the primary condition, then the patient is subject to the primary treatment algorithm. Specialized treatment for refractory overactive bladder includes botulinum toxin injection and sacral nerve stimulation. For stress urinary incontinence, surgical treatment is indicated, such as urethral slings. The two causes of voiding symptoms and post‐micturition symptoms are lower urinary tract obstruction and detrusor underactivity (underactive bladder). Mechanical lower urinary tract obstruction, such as pelvic organ prolapse, is expected to improve with surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β) production. Results In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. Conclusions We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival.

Objective: To carry out an exploratory assessment of the efficacy and safety of TAS‐303, a noradrenaline reuptake inhibitor, in women with stress urinary incontinence. Methods: In a double‐blind, placebo‐controlled, early phase II study, women with stress urinary incontinence and stress urinary incontinence‐predominant mixed urinary incontinence were randomized to a placebo or TAS‐303 (3 or 6 mg) once daily for 8 weeks. The main efficacy end‐points were mean percentage change in incontinence episode frequency per 24 h from baseline to week 8 (the primary end‐point) and week 4. Results: At week 8, the mean percentage change in incontinence episode frequency per 24 h was −34.73% in the TAS‐303 3 mg group, −35.41% in the TAS‐303 6 mg group and −28.07% in the placebo group (differences vs placebo, not significant). In patients with stress urinary incontinence, or incontinence episode frequency less than two episodes per 24 h at baseline, TAS‐303 significantly reduced incontinence episode frequency versus placebo after 4 weeks; some secondary end‐points also showed a tendency to improve in the same subgroups. No serious adverse events (e.g. central nervous system or cardiovascular effects) were observed; TAS‐303 was well tolerated and had a favorable safety profile. Conclusion: These findings suggest that TAS‐303 is effective for improving stress urinary incontinence symptoms in some subgroups of patients with stress urinary incontinence. Therefore, further research is warranted. [ABSTRACT FROM AUTHOR]

Aim: To examine the symptoms and noninvasive test parameters that clinically differentiate detrusor underactivity (DU) from bladder outlet obstruction (BOO) without using a pressure‐flow study (PFS) in male patients with lower urinary tract symptoms. Methods: We examined 909 men who underwent PFS and also had the following data: International Prostate Symptom Score (IPSS), free uroflowmetry, postvoid residual (PVR), and prostate volume (PV). Using these data, significant symptoms and noninvasive test parameters that clinically differentiate DU from BOO were examined. Results: Significant parameters between DU patients and BOO patients were older age, smaller PV, and lower urgency symptom score (IPSS Q4). Optimal cutoff values were determined using receiver operating characteristic curves (≥74 years old, PV ≤ 34.8, and IPSS Q4 ≤ 1) and patients were categorized on the basis of the number of significant factors. The probability of DU or BOO in patients with three significant factors were 77% and 34%, respectively. Conclusion: Three factors (older age, smaller PV, and fewer urgency symptom) were the predictive factors to differentiate DU from BOO, which might be useful for estimating the probability of DU in clinical practice without a PFS. [ABSTRACT FROM AUTHOR]

Aims: To present the development of the International Consultation on Incontinence Questionnaire‐underactive bladder (ICIQ‐UAB) as the first patient reported outcome measure for the assessment of the symptoms and impact on the health‐related quality of life of UAB developed in‐line with the Food and Drug Administration Guidance for Industry. Methods: Draft items were developed following 44 semi‐structured concept elicitation interviews in the UK and refined using 36 cognitive interviews. A pilot study was designed to assess the draft ICIQ‐UAB's initial psychometric properties with 54 patients recruited from European hospitals. Further concept elicitation interviews were also carried out with 11 patients in the US and 10 patients in Japan. All participants had a prior urodynamic diagnosis of detrusor underactivity. Results: The cognitive interviews confirmed the initial items to be understood and interpreted as intended. Pilot testing showed that both internal consistency (Cronbach's α ≥ 0.85) and test‐retest reliability (stable patients; intraclass correlation coefficient ≥ 0.88) were high. The interviews in the US and Japan elicited symptoms and impacts that support previous findings in the UK and provided further insight into the experiences of patients in those countries. The developmental ICIQ‐UAB was refined using the evidence from all substudies. Conclusions: The validity and reliability of the ICIQ‐UAB were supported in a pilot study setting and the wider cultural applicability by the additional interviews in the US and Japan. Following further validation in future clinical trials, the developmental ICIQ‐UAB is envisaged as an important tool for the monitoring of future UAB treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Z-360 is an orally active cholecystokinin-2 (CCK2)/gastrin receptor antagonist currently under development as a therapeutic drug for pancreatic cancer. It was previously reported that Z-360 treatment in combination with gemcitabine prolonged the survival period in a lethal pancreatic cancer xenograft model in mice. In a phase Ib/IIa clinical study, Z-360 treatment displayed a trend of reduced pain in patients with advanced pancreatic cancer in combination with gemcitabine including analgesics such as opioids. Here, we investigated the mechanism of analgesic action of Z-360 in a severe cancer-induced pain model in mice, which is considered to be opioid-resistant, by examining ephrin B1 gene expression, N-methyl-D-aspartate receptor NR2B subunit phosphorylation, and interleukin-1β (IL-1β) production. Results: In a mouse model of cancer-induced pain, ephrin B1 gene expression in dorsal root ganglia (DRGs) and the phosphorylation of NR2B in the spinal cord were induced. Z-360 treatment inhibited both ephrin B1 gene expression and the phosphorylation of NR2B. In addition, IL-1β production increased in the cancer-inoculated hind paw of mice, but could be suppressed by treatment with Z-360. Moreover, we observed that the CCK1 receptor antagonist devazepide similarly suppressed up-regulation of ephrin B1 gene expression and IL-1β production, and that the intraperitoneal injection of sulfated CCK-8 induced the production of IL-1β in the cancer-inoculated region. Conclusions: We have identified a novel pain cascade, in which IL-1β production in cancer-inoculated regions induces ephrin B1 gene expression in DRGs and then ephrin B1 enhances the tyrosine phosphorylation of NR2B via Eph B receptor in the spinal cord. Notably, Z-360 relieves cancer-induced pain by preventing this pain cascade through the suppression of IL-1β production, likely via the blockade of CCK1 receptor. The pre-clinical results presented here support the analgesic action of Z-360 in pancreatic cancer patients with severe, opioid-resistant pain. Pre-clinical and clinical results have demonstrated that Z-360 combined with gemcitabine represents a promising pancreatic cancer therapy approach with characteristic analgesic effects in addition to the prolongation of survival. [ABSTRACT FROM AUTHOR]

Aims To investigate the association of both the urodynamic profiles and patterns of detrusor overactivity (DO) with the severity of the symptoms related to overactive bladder (OAB) in men with benign prostatic enlargement (BPE) associated with DO. Methods A total of 777 men with symptomatic BPE who had undergone transurethral resection of the prostate (TURP) were retrospectively analyzed. All 231 cases of the 317 cases associated with DO were enrolled into the final analysis. The severity of the preoperative symptoms related to OAB were graded based on the International Prostate Symptoms Score (IPSS). The correlation between DO profiles and the severity of OAB related symptoms were analysed using Spearman's correlation test while the association of the DO patterns with the severity of symptoms related OAB were analysed using the Mann Whitney test. Values of P less than 0.05 were considered to be statistically significant. Results A significant negative correlation was found between the severity of nocturia symptoms and bladder filling volume at the beginning of the first DO. The severity of nocturia symptoms, the amplitude of DO pressure and DOtime were significantly increased with increasing age. The severity of nocturia symptom was significantly higher in single DO in comparison to that in multiple DO. Conclusions The significant association of the severity of nocturia symptoms with bladder filling volume at the beginning of the first DO, age and the number of DO pattern was established. The amplitude and duration of DO may affect the severity of the symptoms. Neurourol. Urodynam. 28:953-958, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims To identify the prognostic variables concerning the improvement of overactive bladder syndrome (OAB) related symptoms following a transurethral resection of the prostate (TURP) in patients with benign prostatic obstruction (BPO). Methods A retrospective review was conducted in 298 patients with BPO who had undergone TURP. All patients had completed the preoperative evaluations including OAB related symptoms and full urodynamics, as well as symptomatic assessment postoperatively. OAB related symptoms were defined by the International Prostate Symptom Score questionnaires (questions 2, 4 and 7 stand for frequency, urgency and nocturia). They were divided into three categories based on an individual score ≧3 for on urgency, frequency and nocturia in the preoperative state. The association between the baseline variables and the improvement in each symptom score was analyzed. Results A multivariate analysis suggested that the baseline degree of detrusor contractility was consistently associated with the improvement in each OAB symptom (The odds ratio in normal/weak detrusor: 9.5, 3.4, 3.0 for score on urgency, frequency and nocturia, respectively). Both the patient's age (Odds ratio: 0.93) and the maximum flow rate (Odds ratio: 0.20) influenced the improvement in the score on nocturia. Conclusion The observation of a positive and consistent correlation between the baseline degree of detrusor contractility and the improvement in OAB related symptoms, suggests that good detrusor contractility is essential for the symptomatic benefits after the surgical relief of bladder outlet obstruction. Aging males with good urinary flow rates appear to experience a reduced improvement of nocturia symptoms after undergoing TURP. Neurourol. Urodynam. 28:197-201, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Aims To investigate the associations of symptoms and the quality of life (QOL) with objective variables in a strictly selected large cohort of subjects with symptomatic benign prostatic obstruction (BPO). Methods A retrospective study was conducted in 557 males with BPO in whom a symptomatic improvement had been achieved by transurethral resection of the prostate (TURP), thus suggesting that their lower urinary tract symptoms were primarily due to BPO. The association between the preoperative International Prostate Symptom Score (IPSS) and QOL score with objective variables including the residual volumes, prostate size and urodynamic parameters was statistically analyzed. Results Maximum flow rate (Qmax) positively and a residual urine volume (PVR) negatively correlated with symptoms and QOL score. Detrusor overactivity (DO) also was weakly, but broadly associated with the symptoms. Degree of detrusor contractility and bladder capacity had a weak association with only some storage symptoms. The degree of bladder outlet obstruction (BOO) positively related to the scores on urgency, straining and total IPSS. Patients' age had positive correlation with the score on nocturia. The prostate volume was only negligibly correlated with either any symptoms or the QOL score. Conclusions Parameters, such as Qmax or PVR, obtained from the noninvasive urodynamics were most widely correlated with symptoms and QOL. Despite a large group with strict selection of men with LUTS possibly relating to BPO being studied, only weak association between the symptoms or QOL and objective parameters including urodynamics was confirmed. Neurourol. Urodynam. 27:222-225, 2008. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Overactive bladder (OAB), according to the International Continence Society (ICS) definition, is a symptom syndrome, with urgency as the cornerstone symptom. However, the word 'urgency' and its definition continue to be the subject of much debate and confusion. It is generally difficult for patients to differentiate urgency from normal urge, particularly when the desire to void is strong. To investigate the micturition behavior associated with OAB, we conducted a Patient Trust Study in 21 intelligent (i.e., to be 'trusted') female patients who could clearly and accurately discriminate between urgency and urge. The results showed that in 43% of patients seeking medical care, urgency episodes occurred less than once/day, and some patients had days without urgency. Our patients deferred voiding until bladder sensation was relatively strong, suggesting that coping was not common among these patients. Four of the 21 patients studied experienced spontaneous resolution of several urgency episodes. At volumes exceeding 40% of the maximum bladder volume (MBV), urgency episodes occurred frequently and independently of the bladder volume, indicating that 40% of the MBV may be a threshold of bladder volume to induce urgency. A linear relationship was observed between bladder volume and increasing bladder sensation. However, compared with normal subjects, urge sensation increased markedly at any given bladder volume among patients with OAB in our study. This hypersensitivity was observed in our patients regardless of urgency episodes. We therefore hypothesized that OAB may be more accurately defined as a hypersensitivity disorder rather than a syndrome characterized by urgency. Neurourol. Urodynam. 26:904-907, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Purpose. The characteristics of bile canalicular transport processes for xenobiotic taurine conjugates have not yet been clarified. To elucidate the biliary excretion characteristics of xenobiotic taurine conjugates, we investigated the transport of a novel thromboxane A2 receptor antagonist, Z-335, and its taurine conjugate (Z-335-Tau) across the bile canalicular membrane. Methods. We examined the uptake of Z-335 and Z-335-Tau by isolated bile canalicular membrane vesicles (CMVs) from Sprague Dawley and Eisai-hyperbilirubinemic rats (EHBRs) which EHBRs have a hereditary defect of canalicular multidrug resistance-associated protein 2 (Mrp2) function. Also, the in vitro and in vivo kinetics of Z-335-Tau uptake and excretion were compared. Results. Z-335 uptake by CMVs from normal rats exhibited marked ATP-dependence, whereas ATP-dependent uptake of Z-335 into CMVs from EHBRs was not observed. In contrast, Z-335-Tau uptake into CMVs from both normal rats and EHBRs was ATP dependent. The initial uptake velocity was concentration-dependent, with an in vitro Michaelis constant for initial uptake of 189 µM, which was similar to the in vivo value. Conclusions. The biliary excretion of Z-335 involves Mrp2, whereas that of Z-335-Tau involves active transport systems that remain intact in EHBRs and show marked ATP dependence, which ATPdependent transport is involved in the biliary excretion of Z-335-Tau in vivo. [ABSTRACT FROM AUTHOR]