Outcomes of detrusorectomy in neurogenic bladders: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aims to assess the outcomes of detrusorectomy in children with neurogenic bladder (NB). MATERIALS AND METHODS: A search was performed in PUBMED, EMBASE and the Cochrane Library database in August 2023. The following search terms were used: "detrusorectomy", "detrusorotomy", "auto-augmentation". The two main primary outcomes were improvement in bladder capacity and bladder compliance after intervention. Outcomes were dichotomized into favorable and unfavorable. The secondary outcomes were the effect of postoperative bladder cycling on bladder compliance and bladder capacity and complications. RESULTS: 258 references were screened for inclusion, of these 242 were excluded. 8 of the remaining 16 studies were included for the qualitative and quantitative analysis. All studies were retrospective case series studies (165 patients). Median follow-up time varied between studies (1.75-11.1 years), while two studies reported a mean follow-up time of 8.1 years. Using a random effects meta-analysis, the overall rate for unchanged or improved bladder capacity was 95% (Proportion[CI]: 0.95 [0.61; 1.00]). The overall rate for improved bladder compliance after detrusorectomy was 67% (Proportion[CI]: 0.67 [0.26; 0.92)) (Summary Fig). In the bladder cycling group improved compliance was found in 89% of patients (Proportion[CI]: 0.89 [0.41; 0.99]), whereas it was 21% in the non-cycling group (Proportion[CI]: 0.21 [0.04; 0.61]) (p = 0.0552). Bladder cycling did not affect bladder capacity as the overall rate for unchanged or improved bladder capacity was 98% (Proportion[CI]: 0.98 [0.35; 0.92]) in the cycling and 73% (Proportion[CI]: 0.73 [0.46; 0.90]) in the non-cycling group (p > 0.05). Overall complications were encountered in 16 (9.7%) patients, with major complications (stones, bladder perforations) detected only in 5(3%) patients. DISCUSSION: Detrusorectomy leads to an improved bladder compliance in 67% of children. As such, detrusorectomy proves to be a viable procedure to enhance bladder compliance or to cure overactivity. Importantly, the beneficial effect of detrusorectomy on bladder compliance seems to be long-lasting. Bladder capacity remained unchanged or improved in almost all patients undergoing detrusorectomy. Postoperative bladder cycling was effective in improving bladder compliance outcome compared to the non-cycling group. Proper patient selection is the key to good postoperative outcomes. CONCLUSIONS: Detrusorectomy enhances bladder compliance in pediatric neurogenic bladders. Postoperative bladder cycling improves bladder compliance and the overall complication rate of the procedure is low. Therefore, detrusorectomy should be considered a valuable therapeutic option in the comprehensive management of neurogenic bladders in children.

Dextranomer Endoscopic Injections for the Treatment of Urinary Incontinence in Bladder Exstrophy-epispadias Complex.

PURPOSE: Since bladder neck dextranomer/hyaluronic acid copolymer (Deflux) injections can improve urinary incontinence of various etiologies, we hypothesized that incontinent children with bladder exstrophy-epispadias complex would benefit from dextranomer/hyaluronic acid copolymer. We aimed to analyze dextranomer/hyaluronic acid copolymer efficacy and predictors of treatment success in bladder exstrophy-epispadias complex. MATERIALS AND METHODS: Incontinent bladder exstrophy-epispadias complex children aged >4 years undergoing dextranomer/hyaluronic acid copolymer injections in our hospital between October 1997 and January 2021 were included. Medical history, continence, and bladder capacity before injections were recorded. Postoperatively, patients were categorized as "dry," "significantly improved," or "failure." Postoperative complications, bladder emptying mode, and bladder capacity were reported. Failure-free survival was estimated by Kaplan-Meier models. RESULTS: Altogether, 58 patients (27 male epispadias, 9 female epispadias, 22 bladder exstrophy) underwent 105 injections at median age of 8.5 (interquartile range 5.8-12) years. Previous bladder neck reconstruction had been performed in 38 (66%) and 33 (57%) received multiple injections. Complications occurred in 9%. Five-year failure-free survival was 70% (standard error 9.1) in males epispadias compared to 45% (9.0) in females and exstrophy patients (P = .04). Previous bladder neck reconstruction associated with improved 5-year failure-free survival in females and exstrophy patients (58%, SE 11) but not in male epispadias (75%, SE 11). CONCLUSIONS: Dextranomer/hyaluronic acid copolymer injections provided satisfactory and lasting continence in over half of bladder exstrophy-epispadias complex patients. While injections were successful in male epispadias regardless of bladder neck reconstruction timing, results were better in bladder exstrophy and female epispadias after previous bladder neck reconstruction.

Symptomatic Parapelvic Cysts in Children: Anatomical and Histological Features, Diagnostic Pitfalls and Urological Management.

BACKGROUND: Symptomatic parapelvic cysts (PPC) are rare entities. Our objective is to highlight specific features of PPC to avoid a misdiagnosis of UPJ obstruction. METHODS: We retrospectively reviewed the records of children managed between 2012-2017. RESULTS: All four patients (18 months-8 years) presented with acute renal colic with a large intra-sinusal liquid mass (42-85 mm) on ultrasound, evoking a diagnosis of UPJ obstruction. On preoperative renal scintigraphy (n = 3) there was no dilatation of the renal pelvis and ipsilateral differential function was impaired in 2. Diagnosis of PPC was suspected preoperatively in three children (CT scan (n = 1); MRI (n = 2)) and made peri-operatively (n = 1). Preoperative retrograde pyelography (n = 3) and a further intraoperative retrograde pyelography with methylene blue (n = 1) did not identify communication with the cyst. No renal pelvis was identified in two patients. De-roofing of the cyst was curative in all cases at 5 years mean follow-up (no leakage, cyst recurrence or loss of function) and all 4 patients became asymptomatic after surgery. Histology demonstrated a single flat epithelial cell layer. Renal function normalized in one patient but remained impaired in the other. CONCLUSION: In case of symptoms of UPJ obstruction with a medial renal liquid mass on ultrasound, PPC should be considered when no dilatated pelvis on renal scan is identified. In such cases, a complementary imaging work-up is mandatory prior to surgery.

What makes the bladder neck sling procedure a success in a selected population of children and adolescents? A STROBE-compliant investigation.

INTRODUCTION: Achievement of continence in children suffering from neurogenic bladder dysfunction or severe urogenital malformation is of fundamental importance to the wellbeing of affected children and their families. A valid approach to treating incontinence with hypoactive sphincter is the placement of a bladder neck sling thus increasing outlet resistance of the bladder. OBJECTIVES: In this retrospective study in children and adolescents, we aimed to assess the outcome of bladder neck sling procedures conducted at our institution. In addition, we aimed to identify predictors of the successful correction of incontinence. PATIENTS AND METHODS: We treated 36 patients (25 girls, 11 boys, aged 5.0-19.7 years). In total, 32 (88.9%) patients suffered from neurogenic incontinence. Overall, 16 patients had previously received unsuccessful injection of bulking agent into the bladder neck. For the bladder neck sling, we used a fascial strip of rectus abdominis muscle (n = 29), detrusor muscle (n = 6), or combined fascial and detrusor strip (n = 1). In 8 (22.2%) patients, the surgical procedure involved wrapping the strip around the bladder neck, while in 6 (16.7%) patients, the bladder neck was suspended with the sling. In 22 (61.1%) patients, the two techniques were combined. Overall, 22 (61.1%) and 9 (25.0%) patients additionally underwent enterocystoplasty or detrusorotomy, respectively. We assessed urinary continence of our patients after 3-6 months (first evaluation) and ≥12 months (final evaluation). We classified the state of continence as 'dry' (dry for >3 h between catheterizations and dry at night), 'significantly improved' (minimal incontinence, no more than one protective pad per day, interval of at least 3 h between catheterizations, dry at night, and no demand for additional treatment), or 'wet'. Bladder neck sling treatment was considered successful if the patient was rated as 'dry' or 'significantly improved'. RESULTS: At the first evaluation, the bladder neck sling procedure proved successful in 19 (52.8%) patients. Enterocystoplasty significantly increased the success rate compared to detrusorotomy or no bladder augmentation (68.1% vs. 28.6%; p = 0.04). The remaining 17 patients who were still classified as wet after bladder neck sling placement subsequently underwent one or more additional interventions, i.e. implant injection (n = 11), bladder augmentation (n = 10), and/or sling replacement (n = 5). At the final evaluation after a median follow-up of 64.5 months (range, 12-181 months), continence without sling replacement was achieved in 29 (80.6%) of the 36 patients. CONCLUSION: In our study population, bladder neck sling placement achieved good results in the treatment of severe organic urinary incontinence with hypoactive sphincter. To optimize treatment outcome, bladder neck sling placement should be combined with enterocystoplasty.

Extracorporeal Shockwave Lithotripsy for Cystine Stones in Children: An Observational, Retrospective, Single-Center Analysis.

Purpose: Cystinuria is a genetic disorder characterized by a defective reabsorption of cystine and dibasic amino acids leading to development of urinary tract calculi from childhood onward. Cystine lithiasis is known to be resistant to fragmentation. The aim was to evaluate our long-term experience with extracorporeal shockwave lithotripsy (ESWL) used as first-line urological treatment to treat cystine stones in children. Methods: We retrospectively reviewed the charts of all children who underwent ESWL for cystine stone. We assessed the 3-month stone-free rate, according to age, younger (group 1) or older (group 2) than 2 years old. Results: Between 2003 and 2016, 15 patients with a median (IQR) age at first treatment of 48 (15-108) months underwent ESWL in monotherapy. Median age was, respectively, 15 and 108 months in each group. The median (IQR) stone burden was 2,620 (1,202-8,265) mm3 in group I and 4,588 (2,039-5,427) mm3 in group II (p = 0.96). Eleven patients had bilateral calculi. ESWL was repeated on average 2.4 times, with a maximum of 4 for patients of group I, and 4.8 times, with a maximum of 9 for group II (p > 0.05). ESWL in monotherapy was significantly more efficient to reach stone-free status for children under 2 years of age: 83% vs. 6.2% (p = 0.040). The median (IQR) follow-up of the study was 69 (42-111) months. Conclusion: ESWL appears as a valid urological option for the treatment of cystine stones, in young children. Even if cystine stones are known to be resistant to fragmentation, we report 83% of stone-free status at 3 months with ESWL used in monotherapy in children under 2 years old with cystinuria. In older children, the success rate is too low to recommend ESWL as a first line approach.

Comparison of antegrade and retrograde endoscopic injection techniques for neurogenic sphincteric incontinence in children with neurogenic bladder.

INTRODUCTION/BACKGROUND: Urinary incontinence is common in children with neuropathic bladder. Results of endoscopic injections of bulking agents in the bladder neck are promising but it remains unclear whether they should be performed an antegrade or retrograde fashion. OBJECTIVE: Our aim was to compare the antegrade and retrograde endoscopic injection techniques for the treatment of urinary incontinence. STUDY DESIGN: A prospective study evaluating bladder neck dextranomer-hyaluronic acid polymer injections for urinary incontinence in children with neurogenic bladder was initiated in 1997. Children with normal bladder capacity and compliance and without uncontrolled detrusor overactivity or previous bladder neck surgery were included. Patients were classified as success (dry or significantly improved, the latter defined as no need for more than one pad per day, continent during night, and patient seeking no further treatment) or failure at regular follow-up visits. RESULTS: During 1997-2016, 34 children underwent endoscopic treatment in a retrograde while 17 children in antegrade fashion (mean age 11 years, range 5-20). Most patients (n = 47/51) had neuropathic bladder due to congenital malformations, 13 (25%) had had previous bladder augmentation, and 19 (37%) were in wheelchair. Sex, age, etiology of neurogenic bladder, degree of physical impairment, or era of treatment (1997-2012 vs. 2012-2016) had no influence on success rates (Summary Table). After mean follow-ups of 69 (range 12-156) months, success rates were 71% for the antegrade and 53% for the retrograde technique (p = 0.366). Mean number of injections to obtain success was similar between the techniques (1.4 vs. 1.2). While the proportion of dry patients was similar between the two techniques (35%), the proportion of significantly improved patients tended to be higher after antegrade than retrograde injections (35% vs. 18%, p = 0.181). DISCUSSION: Better visualization of the bladder neck may explain the tendency for improved results of antegrade compared to retrograde technique. Further studies in larger patient samples are needed to define the optimal endoscopic injection technique. CONCLUSION: Long-term results of the antegrade endoscopic bladder neck injections of dextranomer-hyaluronic acid polymer for urinary incontinence in children with neurogenic bladder are promising.

Feasibility and safety of magnetic-end double-J ureteral stent insertion and removal in children.

PURPOSE: The need for surgical removal of a double-J ureteral stent (DJUS) is considered one of its disadvantages. Apart from increased cost, repeated exposure to general anesthesia is a concern in children. Alternative techniques have been described, all failing to become integrated into mainstream practice. Stents with a distal magnetic end, although introduced in the early 1980s, have only recently gained acceptance. We report the feasibility and safety of insertion and removal of a magnetic-end double-J ureteral stent (MEDJUS) in a pediatric population. MATERIALS AND METHODS: We retrospectively analyzed the use of the Magnetic Black-Star Urotech® MEDJUS between 11/2016 and 12/2019 in children. Stents were removed in the outpatient clinic using a transurethral catheter with a magnetic tip. RESULTS: MEDJUS insertion was attempted in 100 patients (65 boys). Mean age was 7.8 years (0.5-18). The stent was placed in an antegrade procedure (n = 47), by a retrograde route (n = 10), and during open surgery (n = 43). Stent insertion was successful in 84 cases (84%). All 16 failures occurred during the antegrade approach in laparoscopic pyeloplasty, with inability to push the stent and its magnet through the ureterovesical junction in 14. Magnetic removal was attempted in 83 patients, successful in 81 (98%). There was no added morbidity with the MEDJUS. CONCLUSIONS: The use of MEDJUS is a safe and effective strategy that obviates the need for additional general anesthesia in children. Its insertion is similar to that with regular DJUS, and its easy and less time-consuming removal benefits both the patient and the hospital and validates its clinical use.

Retroperitoneal Approach for Ureteropelvic Junction Obstruction: Encouraging Preliminary Results With Robot-Assisted Laparoscopic Repair.

Introduction stating the aim of the study: Robot-assisted laparoscopic pyeloplasty (RALP) is gaining acceptance among pediatric urologists. Few studies have evaluated the retroperitoneal approach for RALP. We share our experience from the first 2 years of a multidisciplinary pediatric robotic program in our center. Patients (or Materials) and Methods: We performed a retrospective analysis of prospectively collected data of children undergoing RALP for ureteropelvic junction obstruction (n = 50). Diagnosis was confirmed by ultrasound and Tc-99m mercaptoacetyltriglycine renal scan or MRI; the same criteria were used to evaluate outcome. Surgical approach was chosen according to a specific algorithm. Transperitoneal approach (n = 13) was reserved for horseshoe kidney, ectopic kidney, and redo surgery. We analyzed the 37 cases performed by a lateral retroperitoneal approach. Dismembered pyeloplasty was done for all cases and anastomosis was performed using a running monofilament 6/0 absorbable suture. All were drained by double J stent. Patient data, operating room parameters and postoperative course were recorded. Results: The median age was 7.9 years (5.1-13.8); the youngest was 2 years old. The median weight was 23 kg (17-41) with the smallest weighing 12.4 kg. Aberrant crossing vessels were present in 18 children. Median set-up time, from skin incision until the end of the 4-port insertion, was 33 min (29-48). Median surgeon's console time was 151 min (136-182). No conversion to an open procedure was necessary. The postoperative course was free of complications, except urinary tract infection in 6 children. All but 4 patients were discharged on day one. Median follow-up was 9 months (5-13). Redo pyeloplasty was not required. Practical training of other colleagues was possible after 10 cases performed by the same surgeon. Conclusion: These preliminary results suggest that retroperitoneal RALP in children is feasible, safe and effective. It is an excellent option with ideal anatomical exposure. Longer term results as well as continued practice will identify and overcome any challenges and enable surgical mastery of this procedure which is still evolving.

The TALE homeodomain of PBX1 is involved in human primary testis-determination.

Human sex-determination is a poorly understood genetic process, where gonad development depends on a cell fate decision that occurs in a somatic cell to commit to Sertoli (male) or granulosa (female) cells. A lack of testis-determination in the human results in 46,XY gonadal dysgenesis. A minority of these cases is explained by mutations in genes known to be involved in sex-determination. Here, we identified a de novo missense mutation, p.Arg235Gln in the highly conserved TALE homeodomain of the transcription factor Pre-B-Cell Leukemia Transcription Factor 1 (PBX1) in a child with 46,XY gonadal dysgenesis and radiocubital synostosis. This mutation, within the nuclear localization signal of the protein, modifies the ability of the PBX1 protein to localize to the nucleus. The mutation abolishes the physical interaction of PBX1 with two proteins known to be involved in testis-determination, CBX2 and EMX2. These results provide a mechanism whereby this mutation results specifically in the absence of testis-determination.

Imported Schistosomiasis in Children: Clinical, Diagnostic Aspects And Outcome in 5 Tertiary Hospitals in France.

The objective of this retrospective study is to describe imported schistosomiasis in children in the Paris region between 2010 and 2015. Forty children with a diagnosis of schistosomiasis were included. Thirty-seven (93%) had a chronic urinary form with hematuria. The lost-to-follow up rate for the second consultation was 25%. The diagnosis and management of imported schistosomiasis must be improved-notably by raising awareness among clinicians and providing families with more information.

Efficacy and Safety of Continuous Subcutaneous Infusion of Recombinant Human Gonadotropins for Congenital Micropenis during Early Infancy
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BACKGROUND: Early postnatal administration of gonadotropins to infants with congenital hypogonadotropic hypogonadism (CHH) can mimic minipuberty, thereby increasing penile growth. We assessed the effects of gonadotropin infusion on stretched penile length (SPL) and hormone levels in infants with congenital micropenis. METHODS: Single-center study including 6 males with micropenis in case of isolated CHH (n = 4), panhypopituitarism (n = 1), and partial androgen insensitivity syndrome (PAIS; n = 1). Patients were evaluated at baseline, monthly and at the end of the study through a clinical examination (SPL, testicular position and size), serum hormone assays (testosterone, luteinizing hormone, follicle-stimulating hormone, inhibin B, anti-Müllerian hormone [AMH]), and ultrasound of penis/testes. RESULTS: In CHH, significant increases occurred in serum testosterone (from undetectable level to 3.5 ± 4.06 ng/mL [12.15 ± 14.09 nmol/L]), SPL (from 13.8 ± 4.5 to 42.6 ± 5 mm; p < 0.0001), inhibin B (from 94.8 ± 74.9 to 469.4 ± 282.5 pg/mL, p = 0.04), and AMH (from 49.6 ± 30.6 to 142 ± 76.5 ng/mL, p = 0.03). Micropenis was corrected in all patients, except one. On treatment, in the patient with PAIS, SPL was increased from 13 to 38 mm. CONCLUSIONS: Early gonadotropin infusion is a safe, well-tolerated and effective treatment. The effect in PAIS has not been reported previously. Long-term follow-up is needed to assess the impact, if any, on future fertility and reproduction.
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Familial forms of disorders of sex development may be common if infertility is considered a comorbidity.

BACKGROUND: Families with 46,XY Disorders of Sex Development (DSD) have been reported, but they are considered to be exceptionally rare, with the exception of the familial forms of disorders affecting androgen synthesis or action. The families of some patients with anorchia may include individuals with 46,XY gonadal dysgenesis. We therefore analysed a large series of patients with 46,XY DSD or anorchia for the occurrence in their family of one of these phenotypes and/or ovarian insufficiency and/or infertility and/or cryptorchidism. METHODS: A retrospective study chart review was performed for 114 patients with 46,XY DSD and 26 patients with 46,XY bilateral anorchia examined at a single institution over a 33 year period. RESULTS: Of the 140 patients, 25 probands with DSD belonged to 21 families and 7 with anorchia belonged to 7 families. Familial forms represent 22% (25/114) of the 46,XY DSD and 27% (7/26) of the anorchia cases. No case had disorders affecting androgen synthesis or action or 5 α-reductase deficiency. The presenting symptom was genital ambiguity (n = 12), hypospadias (n = 11) or discordance between 46,XY karyotyping performed in utero to exclude trisomy and female external genitalia (n = 2) or anorchia (n = 7). Other familial affected individuals presented with DSD and/or premature menopause (4 families) or male infertility (4 families) and/or cryptorchidism. In four families mutations were identified in the genes SRY, NR5A1, GATA4 and FOG2/ZFPM2. Surgery discovered dysgerminoma or gonadoblastoma in two cases with gonadal dysgenesis. CONCLUSIONS: This study reveals a surprisingly high frequency of familial forms of 46,XY DSD and anorchia when premature menopause or male factor infertility are included. It also demonstrates the variability of the expression of the phenotype within the families. It highlights the need to the physician to take a full family history including fertility status. This could be important to identify familial cases, understand modes of transmission of the phenotype and eventually understand the genetic factors that are involved.

Predictive parameters of response to desmopressin in primary nocturnal enuresis.

INTRODUCTION/BACKGROUND: Many recent treatment guidelines have advocated the importance of a full noninvasive medical evaluation. To individualize treatment, special emphasis must be put on recording of the maximum voided volume (MVV) and nocturnal diuresis in a diary or frequency/volume chart. OBJECTIVE: The aim of this study was to identify any possible predictive factors to desmopressin response. STUDY DESIGN: This study is a re-analysis of a prospective, open-label, multinational, phase-IV study evaluating ≤6 months of treatment with desmopressin tablets for children with primary nocturnal enuresis. The children were enrolled between April 2002 and December 2004 from 86 centers in four countries: UK, Canada, Germany and France. A total of 936 children were screened; 744 children aged 5-15 years participated in the study. Of these, 471 children completed the study with 6 months follow-up and recording in a frequency/volume chart. All children experienced six or more wet nights during the 14-day screening period. Exclusion criteria were: organic pathology, treatment for enuresis within the past year, previous treatment for enuresis for >4 weeks, diurnal symptoms, renal or central diabetes insipidus and the use of systemic antibiotics or other drugs known to affect desmopressin activity. The predictive value of number of wet nights a week, fluid intake, daytime voiding frequency and diuresis was investigated by performing a multinomial logistic regression. RESULTS: Of the demographic variables, age was the only significant predictor for response to desmopressin. Controlling for age, the significant predictive variables were: number of wet nights a week, average voided volume daytime, maximum voided volume daytime, total daytime diuresis, nocturnal diuresis (see Figure), maximum voided volume 24 h and total 24 h diuresis. More than 80% of the children had no nocturnal polyuria and a low maximum voided volume. DISCUSSION: Performing a secondary analysis is a limitation because the original study was not designed for that. A new prospective study is ethically hardly defendable for children if data are available from previous literature [1]; therefore, a re-analysis was the appropriate choice. The study confirms the predictive value of age, number of wet nights a week and nocturnal diuresis [1,2]. CONCLUSIONS: The study demonstrates that desmopressin response rates are higher in children with greater age, limited number of wet nights a week and nocturnal polyuria. Only a minority of a primary nocturnal enuresis population, based on history alone, had nocturnal polyuria. The majority had a low maximum voided volume. The results clearly stress the importance of a frequency/volume chart for individualizing therapy to the characteristics, thereby resulting in elevated success rates. Registration number of clinical trial: Clinical Trials.gov NCT00245479.

Safety profile of desmopressin tablet for enuresis in a prospective study.

INTRODUCTION: This pre-specified sub-study of the desmopressin response in primary nocturnal enuresis study (DRIP study) evaluates the safety profile of the oral desmopressin tablet in children with primary nocturnal enuresis. Endpoints are adverse events and change in body mass index. METHODS: The DRIP study was an open-label, intention-to-treat, phase IV, multi-national study. Overall, 936 patients were screened and 744 children aged 5-15 years with previously untreated primary nocturnal enuresis were eligible to receive the study medication desmopressin once daily as an oral tablet formulation. At each visit, adverse events were questioned and observed signs or symptoms were recorded. RESULTS: Overall, 222 (30%) patients experienced 404 treatment-emergent adverse events. The proportion of patients experiencing treatment-emergent adverse events was similar regardless of patient gender or age. Most treatment-emergent adverse events were experienced in three system organ classes: gastrointestinal disorders; infections and infestations; and respiratory, thoracic and mediastinal disorders and were considered unrelated to the study drug. There was a slight increase in body mass index from screening levels during the study, however, clinically not significant. CONCLUSION: Desmopressin tablet treatment is well tolerated in children with primary nocturnal enuresis, regardless of patient gender or age. FUNDING: The desmopressin response in primary nocturnal enuresis study (DRIP- study) was funded by Ferring.