Contractile and Structural Properties of Detrusor from Children with Neurogenic Lower Urinary Tract Dysfunction.

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.

The efficacy of onabotulinumtoxinA in patients with previous failed augmentation cystoplasty: Cohort series and literature review.

AIMS: To investigate the role of onabotulinumtoxinA (BTX-A) injections in patients with failed augmentation cystoplasty for neuropathic or idiopathic detrusor overactivity (NDO or IDO). METHODS: A retrospective review of all cystoplasty patients who underwent onabotulinumtoxinA injection at a tertiary center between 2008 and 2019 was performed. Details including indications and time from cystoplasty, video-urodynamic parameters, onabotulinumtoxinA dose, and clinical outcomes were analyzed. Telephone interview was performed for patients that requested repeat onabotulinumtoxinA injections. The interview included a modified PGIC7 and UDI6 questionnaires. A positive clinical response was considered improvement of overactive symptoms sufficient to merit repeat onabotulinumtoxinA injection and a modified PGIC7 of four or above. RESULTS: Thirty patients were identified (11 men and 19 women). The indications for augmentation were IDO (n = 18) or NDO (n = 12). Mean age at the time of cystoplasty was 42 years (range, 10-61). Interval between cystoplasty and initial onabotulinumtoxinA was 98 months (range, 3-271). Video-urodynamics before onabotulinumtoxinA revealed low compliance in 13 patients, DO in 22 patients, and combined low compliance/DO in 10. The median maximum cystometric bladder capacity was 338 mL (range, 77-570 mL). Thirteen patients responded to onabotulinumtoxinA injections. Higher peak DO pressure was associated with a significantly higher chance that the patient would experience benefit from the injections P = .026). The patients that responded to onabotulinumtoxin A underwent a total of 115 procedures (mean, 8.8 injections) over a mean 88 months (range, 20-157 months). CONCLUSIONS: Forty-three percent of patients responded well to intra-detrusor onabotulinumtoxinA injections. This avoided the need for more invasive surgery and had a positive impact on their quality of life.

Transitional Urology.

The field of transitional urology has taken on an increasing importance in recent years as more individuals with congenital urologic issues are living and thriving into adulthood. This article reviews the transitional process itself including barriers to successful transition and the consequences of failing to properly transition. Also provided is a broad overview of the urologic issues faced by patients who may benefit from lifelong care and the providers who will be helping them with transition and assuming their care.

Functional properties and connective tissue content of pediatric human detrusor muscle.

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,ß-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+ transients to carbachol, α,ß-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.

Evaluation of retained testes in adolescent girls and women with complete androgen insensitivity syndrome.

PURPOSE: To evaluate the magnetic resonance (MR) imaging appearance of the testes in women with complete androgen insensitivity syndrome (CAIS), including any benign or malignant changes. MATERIALS AND METHODS: This was a retrospective review of the testicular MR images and histologic reports from 25 patients with CAIS who chose to retain their testes beyond age 16 years and who were imaged between January 2004 and December 2010. Ethical approval was obtained, and informed consent was obtained from each subject to review the medical records, images, and histologic slides and reports. Imaging and histologic findings were compared. RESULTS: Twelve patients (mean age, 24 years; age range, 18-39 years) retained their testes and 13 (mean age, 22 years; age range, 17-37 years) eventually underwent gonadectomy. Review of the MR images showed that testicular parenchyma was heterogeneous in 30 of 46 testes (65%). The most common changes on MR images included simple-looking paratesticular cysts (34 of 46 testes, 74%) and low-signal-intensity, well-defined Sertoli cell adenomas (26 of 46 testes, 56%). Correlation of the histologic and MR imaging findings showed that MR imaging could correctly depict the presence or absence of Sertoli cell adenomas in 19 of 23 testes (83%). Paratesticular cysts were correctly detected in 22 of 23 testes (96%). Microscopic examination showed that the testes were composed of atrophic seminiferous tubules, whereas germ cells were found in 13 of 26 testes (50%). All paratesticular cysts were confirmed to be benign; however, a focus of intratubular germ cell neoplasia was found in a Sertoli cell adenoma. Premalignant foci were detected in three patients, two with intratubular germ cell neoplasia and one with sex cord tumor with annular tubules. No invasive cancers were found. CONCLUSION: MR imaging is accurate in the detection of testicular changes, including paratesticular cysts and Sertoli cell adenomas. Although these changes are usually benign, Sertoli adenomas can sometimes harbor premalignant lesions. MR imaging cannot depict premalignant changes; therefore, the standard of care for patients with CAIS should remain gonadectomy after puberty.

A tertiary experience of vesico-vaginal and urethro-vaginal fistula repair: factors predicting success.

OBJECTIVE: To review the outcomes of all patients referred with vesico-vaginal (V VF) and urethro-vaginal (UVF) fistulae to a tertiary centre, and to investigate the patient, fistula and surgical factors relevant to success. PATIENTS AND METHODS: We reviewed retrospectively the case-notes of 41 consecutive patients (32 with V VF; nine with UVF) treated between January 2000 and January 2006. RESULTS: All patients were tertiary referrals, eight after failed local repairs. Four patients were unsalvageable and had a supravesical diversion. In all there were 47 repairs (23 transvaginal; 24 transabdominal) on 37 patients by two specialist surgeons. The fistula was closed in 92%; five V VF and one UVF required a second procedure, and one V VF a third procedure. One patient with a V VF awaits a second attempt at repair. In one V VF (one attempt) and one UVF (three attempts) the procedure failed and the patient had a diversion. A transvaginal approach cured all 11 patients with a V VF and eight of nine with a UVF, whilst an abdominal approach used for larger/complex fistulae was successful in 18 of 24 (75%) attempts (P = 0.13). The major determinants of success were fistula size (>3 cm; P = 0.02) and the availability of tissue for interposition. V VF repairs using Martius/omental interposition were mostly successful, whilst abdominal repairs in which omentum was unavailable tended to fail (37.5% cure; P = 0.002). CONCLUSIONS: Despite varied aetiology, V VF/UVF were repaired successfully in 92% of patients. Complex (V VF) fistulae were challenging and a quarter of these required more than one attempt. Failure of repair was more likely in larger fistulae (>3 cm) requiring an abdominal approach, if omental interposition was not possible. Good-quality tissue interposition for complex fistula is essential for a successful outcome.