Yasuhiko Igawa

Objectives: To evaluate the outcomes of partial and total cystectomy in patients with refractory Hunner‐type interstitial cystitis (HIC).Methods: Patients with end‐stage HIC who underwent supratrigonal partial cystectomy with augmentation ileocystoplasty (PC‐CP) or total cystectomy with ileal conduit (TC‐IC) were identified retrospectively. Changes in the 11‐point numerical rating scale of bladder pain and in 7‐grade quality of life (QOL) scores were evaluated. Changes in the O'Leary and Sant's Symptom Index (OSSI) and O'Leary and Sant's Problem Index (OSPI) were analyzed in patients with PC‐CP. Peri‐ and postoperative complications and patient satisfaction with overall outcomes were examined.Results: Four patients (one female) underwent PC‐CP and 13 (nine females) underwent TC‐IC. Bladder pain persisted in three PC‐CP patients, but resolved completely in all TC‐IC patients. Pain scale and QOL scores improved significantly in patients with TC‐IC (P < .01), but not in those with PC‐CP. OSSI/OSPI scores did not improve significantly in patients with PC‐CP. Three PC‐CP patients required clean intermittent catheterization due to voiding dysfunction or persistent pain. Two TC‐IC patients developed stricture of the ureteroileal anastomosis, resulting in permanent placement of a ureteral stent in one case and nephrostomy in the other. Satisfaction rate was higher in the TC‐IC than in the PC‐CP group (76.9% vs 25.0%, P < .05).Conclusions: TC‐IC provided reliable pain relief and improved QOL in patients with end‐stage HIC, but the small case number and limited methodology restrict interpretation of the results. Further studies are needed to identify appropriate candidates and optimal surgical procedures.

Background: Vulvar Paget’s disease (VPD) is a rare malignant disorder originating in the external genitalia. It occasionally invades into urethral or vaginal mucosa of female, making surgical treatment more complicating. In case of urethral invasion of Paget’s cells, systematic mapping biopsy of urethral mucosa is the standard of care to determine the range of surgical resection. Resection of urethral mucosa and simple skin grafting often result in urethral stricture after surgery, which severely deteriorates patient’s quality of life. Case presentation: We applied a new technique of advancement urethral meatoplasty using buccal mucosa, in two Japanese cases of VPD with urethral invasion. After broad resection of vulvar skin together with the urethral mucosa, buccal mucosa was implanted between advanced urethral mucosa and skin graft. In both cases, we could prevent urethral stricture one year and two years after surgery, respectively. Conclusion: This technique prevented urethral stricture after surgery and could be a useful technique as part of urethroplasty for VPD.

Objective To study the role of transient receptor potential melastatin 2 in bladder function and inflammation‐associated hypersensitivity. Methods We evaluated physiological function of the bladder and intravesical lipopolysaccharide‐induced inflammatory nociceptive responses in female wild‐type and transient receptor potential melastatin 2‐knockout mice. In vivo frequency/volume and decerebrated unanesthetized cystometry measurements, as well as in vitro detrusor strip functional studies, were carried out to evaluate bladder function. Mice received intravesical lipopolysaccharide (2.0 mg/mL) or saline instillation to evaluate responses to bladder inflammation. Voiding and bladder pain‐like behaviors, cystometry measurements and histological evaluation were carried out before and after intravesical lipopolysaccharide instillation. Results Few phenotypic differences in in vivo and in vitro physiological function were found between the two genotypes. Comparison of measurements taken before and 24–48 h after intravesical lipopolysaccharide instillation showed that voiding parameters did not change in transient receptor potential melastatin 2‐knockout mice, whereas an increased voiding frequency was observed in wild‐type mice. At 24 h after intravesical lipopolysaccharide instillation, the numbers of bladder pain‐like behaviors and of infiltrated inflammatory cells in the bladder submucosal layer were significantly increased, and the voided volume and the intercontraction interval were significantly decreased on cystometry measurements in wild‐type mice compared with those in both transient receptor potential melastatin 2‐knockout mice and in wild‐type mice treated with saline instillation. Conclusions Although the physiological roles of transient receptor potential melastatin 2 channels in the bladder might be limited, inflammation and associated hypersensitivity of the bladder caused by intravesical lipopolysaccharide instillation are attenuated in transient receptor potential melastatin 2‐knockout mice, suggesting pathophysiological roles of transient receptor potential melastatin 2 channels in these processes.

Objectives: To compare the clinical characteristics of three groups of female patients with interstitial cystitis/bladder pain syndrome (IC/BPS) classified according to the presence or absence of Hunner lesions (HL) and glomerulations.Methods: The clinical records of 100 female patients with IC/BPS who underwent their first bladder hydrodistension at our institution were retrospectively reviewed. They were divided into patients having (HL–IC; n = 57) or lacking (BPS; n = 43) HL. BPS patients were further classified as those with (29) and without (14) glomerulations. Among these three subtypes, demographics, comorbidities, symptom parameters including a visual analog scale for pain scores, O'Leary and Sant Symptom and Problem (OSSI/OSPI) Indices, frequency volume chart variables, and bladder capacity at hydrodistension were compared.Results: HL–IC patients were older and had higher OSSI/OSPI scores, greater daytime frequency and nocturia, reduced maximum and average voided volumes, and smaller bladder capacity at hydrodistension compared with BPS patients. Pain intensity and illness duration were comparable among the three groups. HL–IC patients had autoimmune disorders as comorbidities more often, but had psychiatric disorders and irritable bowel syndrome less often compared with BPS patients. No discernible differences in clinical characteristics of symptom severity and comorbid disorders were evident between BPS patients with and without glomerulations.Conclusions: The presence of HL is associated with distinctive clinical characteristics, while glomerulations are not in female patients with IC/BPS. The presence of HL, but not glomerulations, is a robust phenotypic feature of IC/BPS in women.

We evaluated pathophysiological characteristics of the lower urinary tract dysfunction in a streptozotocin (STZ)-induced diabetic rat model. STZ (60 mg/kg) was injected intraperitoneally into male Wistar rats. In vitro bladder muscle strip experiments, in vivo cystometry, and simultaneous recordings of bladder pressure + urethral perfusion pressure (BP + UPP) with or without intravenous administration of L-arginine (300 mg/kg) or tadalafil (0.03 mg/kg) were performed at several time points. In vitro muscle strip experiments demonstrated that diabetic rats had significantly higher contractile responses to carbachol at 4–16 weeks, and a tendency for higher contractile responses to electrical field stimulation at 4–12 weeks, but this was reversed at 16 weeks. Diabetic rats had significant increases in voided volume, residual volume, bladder capacity, maximal voiding pressure, and amplitude and frequency of non-voiding contractions at 16 weeks. Tadalafil decreased the residual volume in diabetic rats. Diabetic rats had significantly higher UPP nadir and mean UPP during high-frequency oscillation at 16 weeks, which were reversed by tadalafil or L-arginine administration. The present results suggest that urethral relaxation failure, probably related to impairment of the NO/cGMP signalling pathway, rather than bladder contractile dysfunction may be a prominent cause for voiding dysfunction in STZ-induced chronic diabetic rats.

β₃‐Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β₃‐adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β₃‐adrenoceptor agonist, are considerably lower than the EC₅₀ for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β₃‐adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression of ACh release from the parasympathetic nerves during the storage phase and inhibition of micro‐contractions through β₃‐adrenoceptors on detrusor smooth muscle cells or suburothelial interstitial cells. Implications of possible desensitization of β₃‐adrenoceptors in the bladder upon prolonged agonist exposure and possible causes of rarely observed cardiovascular effects of mirabegron are also discussed.Linked Articles: This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

Objective: This study examined the accuracy of a new portable ultrasound bladder scanner, the Lilium α‐200 (Lilium Otsuka, Kanagawa, Japan), by evaluating the correlation between bladder volumes periodically measured by the Lilium α‐200 and instilled volume during video‐urodynamic studies (V‐UDS).Methods: Using the Lilium α‐200, fluid volume was measured prospectively in the bladders of patients with lower urinary tract dysfunction during V‐UDS. This was done both immediately after micturition (for assessment of post‐void residual [PVR] volume) and at 1‐minute intervals during filling cystometry with patients in the supine position. These measurements were then compared with the PVR volume obtained directly by catheter drainage and instilled volume during cystometry using paired t tests and Spearman's rank correlation.Results: Fifteen male patients (median age 70.5 years; range 18‐84 years) were included in the study. The PVR volume measured by the Lilium α‐200 was strongly correlated with that obtained by catheter drainage (r = 0.94; P < 0.0001). There was a strong correlation between instilled and bladder volumes measured by the Lilium α‐200 at every minute during and at the end of instillation (281 measurements in 15 patients; r = 0.86; P < 0.0001). However, the relative error of bladder volumes measured by the Lilium α‐200 during cystometry showed considerable variation (mean [± SD] 5.6 ± 62.9%).Conclusions: Bladder volumes measured periodically by the Lilium α‐200 during cystometry were strongly correlated with actual PVR or instilled volumes. However, they showed considerable variation and may not predict actual volume accurately. The Lilium α‐200 is feasible for obtaining an approximate measure of bladder volume.