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OBJECTIVE The objective of this study was to assess the prevalence and spectrum of spinal dysraphism in a cohort of children with cloacal exstrophy (CEX) using MRI. METHODS Children with CEX presenting between 1999 and 2019 with baseline spinal MRI were included. The images were reviewed in consensus to assess the type of dysraphism. The dysraphisms were initially reviewed and described based on their descriptive anatomy, and then classified according to anomalies of gastrulation, primary neurulation, or secondary neurulation. RESULTS Thirty-four children were included. Thirty-three of these children had closed spinal dysraphism, and 1 had a normal spine. Of the 33 cases of closed spinal dysraphism, the conus and/or filum terminale were involved in all cases. The most common malformations were spinal lipoma (n = 20) and terminal myelocystocele (n = 11). The lipomas were heterogeneous: 4 dorsal, 9 transitional, 4 chaotic, and 3 terminal. A large subgroup (10/20, 50%) within the lipomas had an unusual morphology of noncontiguous double lipomas, the proximal fat related to the conus and the distal fat within the filum. These were difficult to characterize using existing classifications. In 2 cases, only a thickened filum was noted. The majority of these malformations were compatible with a disorder of secondary neurulation. CONCLUSIONS Complex spinal dysraphisms are consistently associated with CEX. The unusual dysraphism patterns found in this group of patients highlight the limitations of current embryological classifications. Given the propensity for neurological deterioration in this group of patients, spinal MRI should be routinely performed. The type and distribution of malformations seen have implications for the wider understanding of the pathogenesis and classification of lumbosacral lipomas.

Ultrasound scanning is a cornerstone of modern antenatal care, enabling the detection of fetal abnormalities such as congenital disease, chromosomal defects and growth-disorders as well as maternal diseases such as pre-eclampsia. As technology and techniques evolve, care paradigms and clinical guidance must be re-evaluated with current literature so as to provide expectant parents with the highest quality of care. We present here the current state of the literature, the conflict between guidance and research endeavours and present suggestions for future study.

Simple Summary Disorders of bladder function can result from congenital spinal cord developmental defects and can remain in a significant number of patients despite surgical improvements to repair the primary defect. We studied the ability of bladder wall muscle from such patients to contract, a function essential to void collected urine and avoid urinary tract infections and potential damage to the kidneys. Tissue was taken when patients were several years old, at the time of surgical operations to improve bladder function. This tissue would otherwise have been discarded and was collected with the full ethical approval and consent of parents or guardians. We found that the ability of the bladder wall samples to contract was impaired and was generally stiffer; both of which would make it more difficult for the bladder to void urine. These functional changes were associated with a replacement of muscle with connective tissue (fibrosis). The experiments provide a pathway to devise strategies that might improve bladder function in these patients through reversal of the intrinsic tissue pathways that increase fibrosis. Abstract Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.

Aim To audit restructuring of out-patient clinics at GOSH during the COVID-19 pandemic with the aim of evaluating service delivery and business continuity, focussing specifically on the utility of telephonic clinics Methods We focussed on paediatric urology out-patient clinics at GOSH The electronic patient records were accessed to acquire numbers of clinics and patients booked, total face-toface and telephonic clinic attendances and DNA (did not attend) percentages Three- monthly blocks were evaluated: April-June 2020, spanning the first peak of the pandemic, April-June 2019 in the preceding year to match activity, and then subsequently the period July-September 2020 to evaluate how the services settled in the post-pandemic phase The audit was registered with the GOSH Clinical Audit Department Significance of difference between study groups was examined by Student's t-test Results Total of 95 clinics were booked with 874 patients during the pandemic block with 80 6% (N=705) done telephonically The DNA rate during this time was 11 5% Comparingly, in the same calendar period of 2019, 79 clinics had been booked with all (100%, N=848) patients seen face-to-face The DNA rate was 11 2% In the three post-pandemic months this year, 101 clinics with 1171 patients were booked, 60 5% of these being telephonic, and total DNA was significantly reduced to 5 9% (p

Introduction In recent years digital pathology is evolving into the standard of care for the histology laboratory workflow; allowing remote reporting of cases, improved record keeping, and accountability in reporting (1). Digital pathology allows us to bring quantitative and advanced analysis to the histopathology field. Machine learning has been implemented to segment features of whole slide images (WSI), with a U-net architecture (2) accurately segmenting glomeruli, tubuli and interstitium (3). Here we create a workflow for automated glomerular annotation and deliver number and shape of glomeruli metrics to the pathologist. Materials and Methods Anonymised Haematoxylin and Eosin (H&E) stained, archival diagnostic paediatric renal biopsy samples from Great Ormond Street Hospital were imaged on an Aperio CS2 slide scanner at 40x magnification. Glomeruli were manually annotated using ImageScope software and image patches (2048 × 2048) with annotation masks saved to the training database which was used to train a U-net model. A pipeline was developed using Python to take WSIs, export tiles which feed the trained U-net to generate predictions. Prediction tiles are recombined into a mask indicating the presence of glomeruli. This was converted into WSI annotation format using the bounding polygons of positive mask regions. Results The mean dice score for all test image patches (n=384) was 0.71 for glomerular segmentation. The network identified 106 glomeruli with 8 false positives and 8 false negatives for the testing WSIs (N=3). The speed of image annotation on a CPU was 13.63±1.31 minutes (mean±SD, n=3); producing annotations for a 18000 × 203000 pixel WSI. Discussion U-net segmentation of histopathology features in WSI renal biopsies is readily incorporable into the histology pipeline and can be used to produce annotation files before reaching the pathologist. A quantitative glomerular count can improve the reproducibility of reports and lead to a better-informed treatment plan for the patient.

Summary Introduction Posterior urethral valves (PUV) is the most common cause of congenital bladder outflow obstruction with persistent lower urinary tract and renal morbidities. There is a spectrum of functional bladder disorders ranging from hypertonia to bladder underactivity, but the aetiology of these clinical conditions remains unclear. Aims and objectives We tested the hypothesis that replacement of detrusor muscle with non-muscle cells and excessive deposition of connective tissue is an important factor in bladder dysfunction with PUV. We used isolated detrusor samples from children with PUV and undergoing primary or secondary procedures in comparison to age-matched data from children with functionally normal bladders. In vitro contractile properties, as well as passive stiffness, were measured and matched to histological assessment of muscle and connective tissue. We examined if a major pathway for fibrosis was altered in PUV tissue samples. Methods Isometric contractions were measured in vitro in response to either stimulation of motor nerves to detrusor or exposure to cholinergic and purinergic receptor agonists. Passive mechanical stiffness was measured by rapid stretching of the tissue and recording changes to muscle tension. Histology measured the relative amounts of detrusor muscle and connective tissue. Multiplex quantitative immunofluorescence labelling using five epitope markers was designed to determine cellular pathways, in particular the Wnt-signalling pathway, responsible for any changes to excessive deposition of connective tissue. Results and Discussion PUV tissue showed equally reduced contractile function to efferent nerve stimulation or exposure to contractile agonists. Passive muscle stiffness was increased in PUV tissue samples. The smooth muscle:connective tissue ratio was also diminished and mirrored the reduction of contractile function and the increase of passive stiffness. Immunofluorescence labelling showed in PUV samples increased expression of the matrix metalloproteinase, MMP-7; as well as cyclin-D1 expression suggesting cellular remodelling. However, elements of a fibrosis pathway associated with Wnt-signalling were either reduced (β-catenin) or unchanged (c-Myc). The accumulation of extracellular matrix, containing collagen, will contribute to the reduced contractile performance of the bladder wall. It will also increase tissue stiffness that in vivo would lead to reduced filling compliance. Conclusions Replacement of smooth muscle with fibrosis is a major contributory factor in contractile dysfunction in the hypertonic PUV bladder. This suggests that a potential strategy to restore normal contractile and filling properties is development of the effective use of antifibrotic agents. Download : Download high-res image (132KB) Download : Download full-size image Summary Figure .

Enhanced Recovery After Surgery (ERAS) is an approach to major elective surgery which integrates a series of strategies to improve patient experience and clinical outcomes. This is achieved by ensuring the delivery of evidence-based care – doing the right things, at the right time, more of the time. It is well established in adult practice and has been shown to reduce length of stay and complication rates and improved patient satisfaction. Despite robust evidence of benefits in adult surgical patients, there are only a handful of successful applications of ERAS protocols in the paediatric population. The few studies in general surgery and urology, all showed a decrease in length of stay and no increase in adverse incidents. Based on historical audit, we identified that patients having bladder augmentation surgery may benefit from the implementation of an ERAS protocol. Bladder augmentation is a urological procedure to increase the size of the bladder using small or large bowel. Audit data revealed that this cohort of patients did not initiate oral intake until Day 3 post-op and only started mobilising on Day 4 after the operation. Mean length of hospital stay was 9 days with a range of 7–11 days. We set up a multidisciplinary team including paediatric urologist, anaesthetist, nurses, dietician and physiotherapist to develop a formal protocol for ERAS in bladder augmentation surgery. We focused on four key elements: 1) Pre-operative planning and patient education, 2) Reducing the stress of surgery 3) Structured approach to peri and post-operative management 4) Early mobilisation and resumption of oral intake. We have launched a pilot study for which we are in the data collection phase. Early results are promising, with a reduction to mean length of stay to 8 days, earlier mobilisation and time to oral intake

Ultrasound scanning is a cornerstone of modern antenatal care, enabling the detection of fetal abnormalities such as congenital disease, chromosomal defects and growth-disorders as well as maternal diseases such as pre-eclampsia. As technology and techniques evolve, care paradigms and clinical guidance must be re-evaluated with current literature so as to provide expectant parents with the highest quality of care. We present here the current state of the literature, the conflict between guidance and research endeavours and present suggestions for future study.

Summary Purpose There is a paucity of recent evidence regarding long-term urological and sexual outcomes following surgery for Hirschsprung disease (HD). We aimed to undertake a systematic review of all HD literature to define these outcomes. Materials and methods A systematic literature search was conducted on studies from 1966 to 2014. Relevant articles were assessed for urological/sexual operative complications and functional sequelae. Studies were analysed in qualitative (Rangel score) and quantitative syntheses. Results Initially 257 reports were assessed, with 24 studies were eligible for inclusion (1972–2014). Mean study quality was 16.5 ± SD 4.8 (range 6–23), indicating overall fair/poor quality. Ten studies (1021 patients) reported operative complications, with ureteric/urethral/vaginal injury occurring in seven (0.7%) patients. In three studies, the primary outcome was urological functional assessment. From 17 studies, 52/2546 patients (2.0%) had reported urinary incontinence. In infants, absent spontaneous erections post-operatively was reported in 3/203 patients (1.5%, 5 studies); of these 3, parents did not note spontaneous erections pre-operatively either. In older patients, erectile dysfunction occurred in 6/498 (1.2%) males. Other sexual outcomes were reported in 10 studies, with 5/10 studies (416 patients) reporting no erectile dysfunction. In the other studies reports ranged from non-specified sexual dysfunction in one study to diverse sexual related problems in nine (7.8%) of their patients in another. Conclusions Urological/sexual outcomes are rarely reported after HD surgery (24 studies over 42 years). Study quality is usually poor and a large proportion of the studies are more than 30 years old. In the majority of series it is unclear whether urological and sexual function impairments were not present or if they were not assessed. Prospective reporting of urological/sexual outcome is required, in particular in the era of new surgical techniques/approaches to HD.

Summary Introduction Bladder exstrophy is a congenital anomaly involving foetal exposure and protrusion of the open bladder through an incomplete lower abdominal wall. Techniques to surgically correct exstrophy after birth have greatly improved, but it still presents a major challenge to achieve continence and a good quality of life for patients and their families as the pathophysiology of bladder dysfunction is unknown. Objectives A multimodal approach was used to characterise the histological and biomechanical properties of exstrophy detrusor. These were correlated with myocyte responses to agonists and an evaluation of developmental signalling pathways to evaluate the cause of bladder dysfunction in exstrophy. Study design Detrusor muscle specimens were obtained during corrective surgery from four exstrophy groups: neonatal (1–3 days, n = 8), younger children (7 months–5 years, n = 13) and older children (8–14 years, n = 11) undergoing secondary procedures and cloacal exstrophy (16 days–9 years, n = 9); control specimens were obtained from children (3 months–9 years, n = 14) undergoing surgery for other pathologies but with normal bladder function. Five lines of experiments were undertaken: measurement of connective tissue to detrusor muscle ratio, contractile responses to electrical and agonist stimulation; in vitro biomechanical stiffness, intracellular Ca2+ responses to contractile agonists and immunohistochemistry for proteins (MMP-7, cyclinD1, β-catenin and c-myc) involved in fibrosis generation. Exstrophy data were compared with those from the control group. Results Exstrophy tissue demonstrated reduced smooth muscle compared with connective tissue, reduced contractile responses and greater mechanical stiffness. However, intracellular Ca2+ responses to agonists were maintained. These changes were greatest in neonatal and cloacal exstrophy samples and least in those from older paediatric bladders. Immunolabelled MMP-7, β-catenin and c-myc were reduced in exstrophy samples. Discussion These results highlight the reality that newborns with exstrophy have significantly reduced compliance and bladder underactivity, which may persist or return to normal values with surgery and age. The primary cause of underactivity is increased connective tissue in relation to detrusor muscle; however, detrusor myocyte function remains normal. Finally, the increase of the smooth muscle content in the paediatric bladder group indicates a remodelling response of the bladder to surgical correction and time. Excess gestational fibrosis is associated with changed expression of key proteins in the Wnt-signalling pathway, a potential aetiological factor and therapeutic target. Conclusion Results point to connective tissue deposition as the primary pathological process that determines bladder function with normal myocyte function. Future research that reduces connective tissue deposition may lead to improvement in outcomes for these children. Download : Download high-res image (124KB) Download : Download full-size image

Anterior urethral syringocele is an uncommon congenital deformity characterized by cystic dilatation of bulbourethral gland ducts and is usually asymptomatic. We present a case on 4-day-old male neonate who presented with bilateral antenatal hydroureteronephrosis and renal impairment and found to have urethral syringocele and posterior urethral valves.

The apparent incidence of antenatally diagnosed congenital lung malformations (CLM) is rising (1 in 3000), and the majority undergo elective resection even if asymptomatic. Thoracoscopy has been popularized, but early series report high conversion rates and significant complications. We aimed to perform systematic review/meta-analysis of outcomes of thoracoscopic vs open excision of asymptomatic CLMs.A systematic review according to PRISMA guidelines was performed. Data were extracted for all relevant studies (2004-2015) and Rangel quality scores calculated. Analysis was on 'intention to treat' basis for thoracoscopy and asymptomatic lung lesions. Meta-analysis was performed using the addon package METAN of the statistical package STATA14™; p0.05 was considered significant.36 studies were eligible, describing 1626 CLM resections (904 thoracoscopic, 722 open). There were no randomized controlled trials. Median quality score was 14/45 (IQR 6.5) 'poor'. 92/904 (10%) thoracoscopic procedures were converted to open. No deaths were reported. Meta-analysis showed that regarding thoracoscopic procedures, the total number of complications was significantly less (OR 0.63, 95% CI 0.43, 0.92; p0.02, 12 eligible series, 912 patients, 404 thoracoscopic). Length of stay was 1.4days shorter (95%CI 2.40, 0.37;p0.01). Length of operation was 37 min longer (95% CI 18.96, 54.99; p0.01). Age, weight, and number of chest tube days were similar. There was heterogeneity (IA reduced total complication rate favors thoracoscopic excision over thoracotomy for asymptomatic antenatally diagnosed CLMs. Although operative time was longer, and open conversion may be anticipated in 1/10, the overall length of hospital stay was reduced by more than 1day.4 (based on lowest level of article analyzed in meta-analysis/systematic review).

The functional properties of human pediatric detrusor smooth muscle are poorly described, in contrast to those of adult tissue. Characterization is necessary for more informed management options of bladder dysfunction in children. We therefore compared the histological, contractile, intracellular Ca2+concentration responses and biomechanical properties of detrusor biopsy samples from pediatric (3–48 mo) and adults (40–60 yr) patients who had functionally normal bladders and were undergoing open surgery. The smooth muscle fraction of biopsies was isolated to measure proportions of smooth muscle and connective tissue (van Gieson stain); in muscle strips, isometric tension to contractile agonists or electrical field stimulation and their passive biomechanical properties; in isolated myocytes, intracellular Ca2+concentration responses to agonists. Pediatric detrusor tissue compared with adult tissue showed several differences: a smaller smooth muscle-to-connective tissue ratio, similar contractures to carbachol or α,β-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+transients to carbachol, α,β-methylene ATP, raised K+concentration or caffeine, but smaller nerve-mediated contractions and greater passive stiffness with slower stress relaxation. In particular, there were significant atropine-resistant nerve-mediated contractions in pediatric samples. Detrusor smooth muscle from functionally normal pediatric human bladders is less contractile than that from adult bladders and exhibits greater passive stiffness. Reduced bladder contractile function is not due to reduced smooth muscle contractility but to greater connective tissue deposition and to functional denervation. Significant atropine resistance in pediatric detrusor, unlike in adult tissue, demonstrates a different profile of functional neurotransmitter activation. These data have implications for the management of pediatric bladder function by therapeutic approaches.

In pediatric oncology patients, hemorrhagic cystitis can be a life-threatening complication of bone marrow transplantation, chemotherapy, and radiation therapy. The treatment of this condition is often challenging and includes intravesical irrigation with aluminum, embolization, endoscopic laser coagulation, hydrostatic pressure, use of hyperbaric oxygen, instillation of formalin, prostaglandins, and oral sodium pentosan polysulfate. Although the efficacy of aluminum irrigation is well documented for the management of hemorrhagic cystitis in adults, there are limited reports describing its use in children. The potential multisystem toxic effects of aluminum are well described and the range and progression of aluminum toxicity can be devastating. We report a case of a 9-year-old girl suffering from acute lymphocytic leukemia with hemorrhagic cystitis. Although the symptoms resolved after intravesical aluminum treatment, she developed significant aluminum toxicity. We have reviewed the literature relating to aluminum toxicity in the pediatric age group and present our recommendations for the effective and safe use of aluminum in this cohort of patients.

This is the first reported case of rhabdomyosarcoma presenting as a mass protruding from the urethral meatus present at birth. A male neonate was transferred to a tertiary pediatric urology center on day 4 of life where the mass was surgically excised. Histology confirmed an embryonal rhabdomyosarcoma and chemotherapy commenced. The patient completed chemotherapy at the age of 8 months. The child is now 3.5 years old and well with no recurrence of disease.

Rhabdomyosarcoma is the most common soft tissue sarcoma, representing 10-15% of all malignant solid tumours in children and can occur in any site. The prognosis for rhabdomyosarcoma of the prostate has improved significantly in the last few decades. The management involves a combination of chemotherapy, radiotherapy and surgery. Several approaches to resect the prostate in adults have been described. These include radical retropubic, transperineal, posterior sagittal as well as the transpubic approach. In the child, the transpubic approach allows direct access to the prostate and proximal urethra whilst obviating problems noted in adults. We describe this approach to the prostate in a 3-year-old boy.

Mullerian duct remnants presenting in childhood are often diagnosed incidentally and when symptomatic, typically present with recurrent infection and/or voiding disturbances. We present a rare unusual case of a male neonate who presented with a prenatally detected large pelvic cyst that turned out to be a giant prostatic utriculus.

An imperforate hymen associated with urinary retention, bilateral hydronephrosis, and bilateral hydrosalpinx is extremely rare in the neonatal period. We present a case of a 2-day-old neonate with a marked interlabial swelling causing urinary retention. Imaging revealed hydrometrocolpos, hydrosalpinx, and bilateral hydronephrosis. Her symptoms resolved after hymenectomy.

Many institutions have reported varied levels of success with ureterocystoplasty. Recently, there have been concerns regarding the efficacy of ureterocystoplasty as a form of bladder augmentation. We report our long-term functional outcomes with the procedure based on the experience of a single surgeon.A total of 17 procedures were performed during a 12-year period. Of the patients 10 had posterior urethral valves, 3 had bladder exstrophy, 2 had a neuropathic bladder, 1 had a cloacal anomaly and 1 had a left ectopic ureter. Mean patient age at operation was 5.9 years (range 0.3 to 14.2). All patients underwent preoperative ultrasound, urodynamic studies and radionuclide scanning. Postoperative urodynamics were performed at 6 months.Followup ranged from 0.5 to 11.5 years (mean 4.5). Nine patients underwent ureterocystoplasty with preservation of the ipsilateral kidney, and 1 underwent ureterocystoplasty alone and had a solitary right kidney. The remaining 7 patients underwent ureterocystoplasty with ipsilateral nephrectomy. Postoperatively, the mean bladder capacity improved from 125 to 292 ml, while the mean end filling pressure decreased from 72 to 22 cm H(2)O. Mean preoperative system compliance was 2.1 ml/cm H(2)O, which increased to 16.2 ml/cm H(2)O postoperatively. A total of 13 patients did not require further augmentation surgery. The remaining 4 patients had high pressure and poorly compliant bladders, and underwent ileocystoplasty. Subsequent postoperative nucleotide scans in these 4 patients demonstrated stable upper tracts with good drainage.Based on our results, ureterocystoplasty provides durable functional urodynamic improvement in patients with a megaureter.

Objectives The repair of severe primary hypospadias represents a major surgical challenge. After initial enthusiasm for single-stage procedures, many paediatric urologists have turned to the alternative two-stage approach after experiencing disappointing results. A single surgeon's experience of the two-stage procedure is reported. Methods Between 1998 and 2003, 62 boys underwent a two-stage reconstruction for primary hypospadias. Indications for staged repair included proximal meatus (mid-shaft [18 patients], peno-scrotal [23] or perineal [two]), moderate or severe chordee (38 patients), poor glans groove, and lichen sclerosis. Inner prepuce was the graft of choice. Median age was 27.6 months at completion of surgery and median follow-up was 26 months. Results All grafts took well and none of the 62 patients needed revision. One patient developed a haematoma. Maturation of the graft for at least six months ensured the best conditions for the second-stage closure. Overall the cosmetic and functional results after the second stage were excellent. The outcomes were determined by the parents' and surgeon's assessment of function and the cosmetic appearance. Complications included partial glans dehiscense (three patients), residual mild curvature (three) and meatal stenosis (three). Conclusion The two-stage repair has proved to be a reliable and reproducible technique with a low complication rate in a difficult cohort of hypospadias patients. Inner preputial skin grafts take very successfully on the ventral surface of the penis, and splitting the glans enables a slit-like meatus to be achieved. Excellent cosmetic results can be anticipated.

We report a 7-year-old boy who had antenatally diagnosed and postnatally confirmed asymptomatic right congenital hydronephrosis secondary to ureteropelvic junction obstruction with the anteroposterior diameter ranging from 7 to 15 mm on serial ultrasound scans till the age of 6 years. He then presented with recurrent attacks of Dietl's crisis almost every month in the seventh year of his life and eluded diagnosis for over a year at various national hospitals, and ended up with an international referral to us. Investigations of the acute attacks clinched the diagnosis of ureteral polyp causing intermittent crisis and he underwent segmental resection and reconstruction in the form of dismembered Anderson-Hyne pyeloplasty with good recovery. Our case revealed that prenatally detected hydronephrosis may worsen after spontaneous postnatal improvement and a polyp acting as a flip valve may produce intermittent hydronephrosis and symptoms later in life. The child should undergo urgent investigations during acute symptoms.

Purpose We have shown the paediatric exstrophy bladder is significantly hypocontractile in comparison to the normal paediatric bladder despite isolated single detrusor cells functioning normally. The aim of this study was to test the hypothesis that the visco-elastic properties of the paediatric bladder contribute to this observed difference in contractility. Material and Methods Ethical committee approval and patient consent were obtained. Full thickness bladder samples were obtained from patients with a bladder exstrophy and from normal bladders (control) during open surgery (n = 9,11 respectively). Detrusor strips were superfused with a buffered physiological solution. One end of the muscle strip was tied to an isometric force transducer; the other end to a hook, the position of which could be adjusted in the horizontal plane by a voltage-operated solenoid. Incremental changes in muscle strain were generated by imposing square voltage waves on the solenoid for 50 seconds duration, then returning to steady state length with continuous force measurement during this period. The resultant changes to muscle stress were recorded and the viscous and elastic workload was calculated. Significance of differences (p Results The lengths were not significantly different between groups. The elastic and viscous component (mN.s/mg) was significantly greater in the exstrophy group at every strain when compared to the control group. The time constant was not significantly different between groups. Conclusions The elastic and viscous workload is increased and the tissue is mechanically stiffer in bladder exstrophy. This corroborates clinical urodynamic data that the exstrophy bladder is poorly compliant.

Purpose To review the results of Kelly soft tissue reconstruction for continence, following the completion of 50 consecutive cases in classic bladder exstrophy. Material and methods From 1999 to the present all patients with classic exstrophy have had a Kelly soft tissue reconstruction, following primary bladder closure at birth. There was no prior selection for bladder capacity. All are followed with bladder function assessments, clinical review and ultrasound. From the 50 patients with classic bladder exstrophy, 24 patients followed for more than 2 years are the subject of this review. Results There have been no major complications; in particular no corporal or glans loss following the radical mobilisation of the penis/clitoris and no new upper tract dilatation following the creation of outlet resistance. Of 11 patients followed more than 5 years; 8 are dry by day and void spontaneously. 4 are also dry by night. There are three failures. 1 boy has ADHD with severe constipation and continues to wear nappies, although he does have a dry interval. Another boy had a failed epispadias repair prior to recostruction and one girl failed to develop capacity after her procedure. Both have had ileocystoplasty/BNR/mitrofanoff and are dry with CIC. Of the 13 followed between 2 and 4 years, 4 have yet to attempt potty training. The remaining 9 are dry by day. 2 of these are also dry by night. Conclusions - This operation has a low complication rate in our hands. - Outlet resistance and a dry interval develops in the majority of cases. - Bladder capacity determines continence and seems to be improved with earlier intervention. - Conventional continence surgery is not hampered by a prior Kelly operation.

Purpose There is no information concerning the contractile and detrusor cell properties of detrusor smooth muscle from neonatal exstrophy bladders (NE). The aim of this study was to examine these properties of NE and compare them to those with normal bladder (N) function. Material and methods Following ethical approval and patient consent full thickness bladder samples were obtained from patients with NE and N. Detrusor strips were superfused at 37°C with HCO3/CO2 buffered physiological solution. Nerve-mediated responses were elicited by electrical field stimulation. Muscle-mediated responses were generated by carbachol and a,bmethylene-ATP (ABMA). Tension was normalised to unit cross-sectional area (mN.mm-2). Data is presented as mean±s.d. Detrusor cells were isolated using collagenase and loaded with a Ca2+ indicator (fura-2). The 340/380 ratio, a direct measure of intracellular calcium [Ca2+]i changes was measured following addition of carbachol, ABMA, and KCl. Significance of differences (p Results Nerve-mediated were significantly less (0.8±0.3 vs 2.9±4.7 mN.mm-2), as were the muscle-mediated responses (5.4±3.6 vs 30.8±22.2) in samples from NE compared to N (n=5, 20 respectively). The NE strips however were more sensitive after addition of carbachol (EC50s; 1.8±0.5 vs 3.2±1.2). Following addition of carbachol, ABMA, and KCl to isolated cells, [Ca2+]i transients were observed. The 340/380 ratios were not statistically significantly different between NE and N bladders (carbachol; 0.4 vs 0.4, ABMA; 0.7 vs 0.8, KCl; 0.4 vs 0.4, n=9,15 respectively). Conclusions The data show that contractile function is reduced in patients with NE compared to N. The detrusor cell function appears normal. Altered muscle-matrix interaction content and/or dysfunctional excitation-contraction coupling could play a role in this hypocontractility.

Purpose Mixed Gonadal Dysgenesis (MGD) is one of the more frequent intersex disorders. The most common genotype is 45XO/46XY mosaicism and these patients typically present with a streak gonad on one side and a palpable gonad on the other with hypospadias. Debate exists over the nomenclature and management of MGD. Many would advocate bilateral gonadectomy and a female sex of rearing. However little is known about the outcomes of these patients. Recent reports have demonstrated success with the male sex of rearing. Material and methods Retrospective analysis revealed 13 patients with MGD and a proven 45XO/46XY with complete records and documented follow-up. Case notes were evaluated for clinical presentation, investigation (biochemical, radiological, and histological) operative procedures and outcomes. Results Median age at presentation was 60 months (range; birth-11 years), and gender was assigned at a median of 2 days (range; 0-35 days). Nine cases presented with ambiguous genitalia at birth and referred for intersex evaluation. Four were initially assigned as males at birth but overall 9 were reared as males. Eight cases had unilateral palpable gonad and 4 had bilateral impalpable gonads. Three patients were gender reassigned to the female sex of rearing on the basis of an inadequate phallus. The median XO:XY ratio was 80:20 respectively. All patients had removal of streak gonads. Bilateral gonadectomy was performed in 5 cases and 8 had contralateral orchidopexy. The follow-up ranged from 10-144 months (median 63 months). Conclusions We are witnessing a paradigm shift in the management of children with MGD. Modern reconstructive surgical techniques are allowing more patients to be successfully reared as males.