[No abstract available

* At the time of this consultation, these definitions are not included in the current ICS terminology. RECOMMENDATIONS OF THE INTERNATIONAL SCIENTIFIC COMMITTEE 2. EVALUATION The following phrases are used to classify diagnostic tests and studies: • A highly recommended test is a test that should be done on every patient. This section should also be read in conjunction with the relevant committee reports. RECOMMENDATIONS OF THE INTERNATIONAL SCIENTIFIC COMMITTEE 6. ANORECTAL PHYSIOLOGY TESTING Endocoil MRI has high accuracy for detecting anal sphincter injury but is second line after endoanal ultrasound. Patients with faecal incontinence may benefit from assessment with MRI, particularly those with anorectal malformations and/or previous anal sphincter surgery. Defaecography may be useful and is recommended in patients with faecal incontinence, who have failed conservative therapies, and are possible candidates for laparoscopic ventral rectopexy. * Consider CONTINENCE PRODUCTS for temporary support during treatment Recent VVF Primary simple Consider Catheter, evaluate weekly Established VVF Primary complex Healed Persistant leakage Recurrence Post-irradiation Vaginal repair Consider timing Surgical repair Consider timing Consider interposition material If small, consider catheter, evaluate weekly Surgical repair 6-12 months Consider interposition material Surgical repair Consider timing Consider interposition material Assess fistula closure & assess continence status MANAGEMENT OF IATROGENIC URETERIC FISTULAE HISTORY CLINICAL ASSESSMENT MANAGEMENT* PRESUMED DIAGNOSIS Extra-urethral vaginal urinary leakage and/or signs of ureteric obstruction Clinical examination Urethro-cystoscopy Imaging (Xray/CT/ MRI, US) Evaluate upper urinary tract obstruction * Consider CONTINENCE PRODUCTS for temporary support during treatment Ureterovaginal fistula Endoluminal technique (stenting, nephrostomy) for at least 6 weeks Unable to stent (initially)... Re-evaluate for fistula closure, ureteric obstruction Persisting fistula or ureteric obstruction Ureteric reimplantation (open, laparoscopic or robotic) Healed Long-term follow-up for stricture and hydropephrosis * Consider CONTINENCE PRODUCTS for temporary support during treatment Patient education, adequate fibre diet and fluid intake; regular bowel care, preferably ± 3 times a week

Objective  To determine whether suburothelial interstitial cells of the human bladder express gap junctions, and if so, to establish their extent and composition, using immunocytochemistry, confocal microscopy and electron microscopy. Materials and methods  Bladder tissue was obtained at cystectomy; the tissue was: (i) frozen for cryosectioning and Northern blot analysis; (ii) fixed and embedded for standard thin‐section electron microscopy; and (iii) processed using low‐denaturation conditions in Lowicryl for immunogold‐label electron microscopy. Cryosections were immunofluorescently labelled using antibodies against connexins 43, 40 and 45, vimentin, desmin and c‐Kit ligand, and examined by confocal microscopy. Double labelling was used to determine the spatial relationship of labelling for connexin43 with that of vimentin and desmin. Thin‐section electron microscopy was used to investigate interstitial cell ultrastructure and permit unequivocal identification of gap junctions, and immunogold labelling of Lowicryl sections was applied to localize connexin43. Results  Immunoconfocal microscopy showed prominent labelling for the gap junction protein, connexin43, in a suburothelial band of cells that was also strongly positive for vimentin. The connexin43/vimentin‐positive cells showed only weak labelling for desmin and c‐Kit ligand, and were immunonegative for connexins 40 and 45. Northern blotting showed a corresponding abundance of connexin43 transcript in the mucosal layer but not the detrusor layer of the bladder wall. Electron microscopy revealed abundant gap junctions, recognized by their pentalaminar structure, between the cell processes of interstitial cells in the suburothelial zone. That these interstitial cell gap junctions were the source of the connexin43 immunolabelling observed by immunoconfocal microscopy was confirmed by immunogold labelling in sections of Lowicryl‐embedded tissue examined by electron microscopy. Conclusion  A network of interstitial cells, extensively linked by connexin43‐containing gap junctions, is located beneath the urothelium in human bladder. As gap junctions provide pathways for direct cell‐to‐cell communication, the interstitial cellular network may operate as a functional syncytium, integrating signals and responses in the bladder wall.

Increased gap junction expression in lamina propria myofibroblasts and urothelial cells may be involved in detrusor overactivity, leading to incontinence. Immunohistochemistry was used to compare connexin (Cx) 26, 43, and 45 expression in the bladders of neonatal, adult, and spinal cord-transected rats, while optical imaging was used to map the spread of spontaneous activity and the effects of gap junction blockade. Female adult Sprague-Dawley rats were deeply anesthetized, a laminectomy was performed, and the spinal cord was transected (T8/T9). After 14 days, their bladders and those of age-matched adults (4 mo old) and neonates (7-21 day old) were excised and studied immunohistochemically using frozen sections or optically using whole bladders stained with voltage- and Ca(2+)-sensitive dyes. The expression of Cx26 was localized to the urothelium, Cx43 to the lamina propria myofibroblasts, and Cx45 to the detrusor smooth muscle. While the expression of Cx45 was comparable in all bladders, the expression of Cx43 and Cx26 was increased in neonate and transected animals. In the bladders of adults, spontaneous activity was initiated at multiple sites, resulting in a lack of coordination. Alternatively, in neonate and transected animals spontaneous activity was initiated at a focal site near the dome and spread in a coordinated fashion throughout the bladder. Gap junction blockade (18beta-glycyrrhetinic acid, 1 microM) abolished this coordinated activity but had no effect on the uncoordinated activity in adult bladders. These data suggest that coordinated spontaneous activity requires gap junction upregulation in urothelial cells and lamina propria myofibroblasts.

The Ca 2+ -regulating and electrophysiological properties of guinea-pig suburothelial myofibroblasts have been measured in order to investigate their potential role in the sensation of bladder fullness, due to their strategic position between the urothelium and afferent fibres. Previous work has shown that stretch of the bladder wall releases ATP. Cells that stain positively for vimentin were isolated. About 45% of cells (median membrane capacitance 13.3 pF) exhibited spontaneous depolarizations to about −25 mV with a physiological Cl − gradient (frequency 2.6 ± 1.5 min −1 , duration 14.5 ± 2.2 s, n = 15). Under voltage-clamp spontaneous inward currents (frequency 1.5 ± 0.2 min −1 , duration 14.5 ± 7.0 s, n = 18) were recorded, with a similar reversal potential. The spontaneous currents were preceded by intracellular Ca 2+ transients with a magnitude that was independent of membrane potential. All cells tested responded to ATP by generating an intracellular Ca 2+ transient, followed by inward currents; the currents had a similar reversal potential and slope conductance to their spontaneous counterparts. ATP-generated transients were mimicked by UTP and ADP but not by α,β-methylene-ATP (1-10 µM) or CTP (30 µM), indicating that ATP acts via a P2Y receptor. Transients were partially attenuated by 1 mM suramin but PPADS (80 µM) had no effect. These data indicate that ATP acts via a P2Y receptor, but responses were resistant to the P2Y 1 antagonist MRS2179. ATP-generated transients were abolished by intracellular perfusion with heparin and TMB-8 indicating that IP 3 was the intracellular second messenger. The reversal potentials of the spontaneous and ATP-generated currents were shifted by about +45 mV by a 12-fold reduction of the extracellular [Cl − ] and the currents were greatly attenuated by 1 mM DIDS. No transients were generated on exposure to the muscarinic agonist carbachol. We propose that these cells may play a regulatory step in the sensation of bladder fullness by responding to ATP. The precise mechanism whereby they couple urothelial ATP release to afferent excitation is the next step to be elucidated.