Lessons from a large nationwide cohort of 350 children with ovarian mature teratoma: A study in favor of ovarian-sparing surgery.

BACKGROUND: Ovarian mature teratoma (OMT) is a common ovarian tumor found in the pediatric population. In 10%-20% of cases, OMT occurs as multiple synchronous or metachronous lesions on ipsi- or contralateral ovaries. Ovarian-sparing surgery (OSS) is recommended to preserve fertility, but total oophorectomy (TO) is still performed. DESIGN: This study reviews the clinical data of patients with OMT, and analyzes risk factors for second events. A national retrospective review of girls under 18 years of age with OMTs was performed. Data on clinical features, imaging, laboratory studies, surgical reports, second events and their management were retrieved. RESULTS: Overall, 350 children were included. Eighteen patients (5%) presented with a synchronous bilateral form at diagnosis. Surgery was performed by laparotomy (85%) and laparoscopy (15%). OSS and TO were performed in 59% and 41% of cases, respectively. Perioperative tumor rupture occurred in 23 cases, independently of the surgical approach. Twenty-nine second events occurred (8.3%) in a median time of 30.5 months from diagnosis (ipsilateral: eight cases including one malignant tumor; contralateral: 18 cases; both ovaries: three cases). A large palpable mass, bilateral forms, at diagnosis and perioperative rupture had a statistical impact on the risk of second event, whereas the type of surgery or approach did not. CONCLUSION: This study is a plea in favor of OSS as the first-choice treatment of OMT when possible. Close follow-up during the first 5 years is mandatory considering the risk of 8.3% of second events, especially in cases with risk factors.

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.

Preoperative Topical Estrogen Treatment vs Placebo in 244 Children With Midshaft and Posterior Hypospadias.

PURPOSE: Urethral fistula and dehiscence are common after hypospadias surgery. Preoperative androgens have been considered to reduce these complications although this consideration is not evidence-based. Dermatologists have reported the benefits of topical estrogens on skin healing. We investigated whether the preoperative use of topical promestriene could reduce healing complications in hypospadias surgery. Our primary objective was to demonstrate a reduction of healing complications with promestriene vs placebo. Impact on reoperations and other complications, clinical tolerance, bone growth, and biological systemic effects of the treatment were also considered. METHODS: We conducted a prospective, randomized, placebo-controlled, double-blind, parallel group trial between 2011 and 2015 in 4 French centers. One-stage transverse preputial island flap urethroplasty (onlay urethroplasty) was selected for severe hypospadias. Promestriene or placebo was applied on the penis for 2 months prior to surgery. The primary outcome was the presence of postoperative urethral fistula or dehiscence in the first year postsurgery. For safety reasons, hormonal and anatomical screenings were performed. RESULTS: Out of 241 patients who received surgery, 122 patients were randomized to receive placebo, and 119 patients received promestriene. The primary outcome was unavailable for 11 patients. Healing complications were assessed at 16.4% (19/116) in the placebo vs 14.9% (17/114) in the promestriene arm, and the odds ratio adjusted on center was 0.93 (95% confidence interval 0.45-1.94), P = 0.86. CONCLUSIONS AND RELEVANCE: Although we observed an overall lower risk of complications compared to previous publications, postsurgery complications were not different between promestriene and placebo, because of a lack of power of the study or the inefficacy of promestriene.

Surgery is not superior to dilation for the management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome: a multicenter comparative observational study in 131 patients.

BACKGROUND: Vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome can be managed either by various surgeries or dilation. The choice still depends on surgeon's preferences rather than on quality comparative studies and validated protocols. OBJECTIVE: We sought to compare dilation and surgical management of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser syndrome, in terms of quality of life, anatomical results, and complications in a large multicenter population. STUDY DESIGN: Our multicenter study included 131 patients >18 years, at least 1 year after completing vaginal agenesis management. All had an independent gynecological evaluation including a standardized pelvic exam, and completed the World Health Organization Quality of Life instrument (general quality of life) as well as the Female Sexual Function Index and Female Sexual Distress Scale-Revised (sexual quality of life) scales. Groups were: surgery (N = 84), dilation therapy (N = 26), and intercourse (N = 20). One patient was secondarily excluded because of incomplete surgical data. For statistics, data were compared using analysis of variance, Student, Kruskal-Wallis, Wilcoxon, and Student exact test. RESULTS: Mean age was 26.5 ± 5.5 years at inclusion. In all groups, World Health Organization Quality of Life scores were not different between patients and the general population except for lower psychosocial health and social relationship scores (which were not different between groups). Global Female Sexual Function Index scores were significantly lower in the surgery and dilation therapy groups (median 26 range [2.8-34.8] and 24.7 [2.6-34.4], respectively) than the intercourse group (30.2 [7.8-34.8], P = .044), which had a higher score only in the satisfaction dimension (P = .004). However, the scores in the other dimensions of Female Sexual Function Index were not different between groups. The Female Sexual Distress Scale-Revised median scores were, respectively, 17 [0-52], 20 [0-47], and 10 [10-40] in the surgery, dilation therapy, and intercourse groups (P = .38), with sexual distress in 71% of patients. Median vaginal depth was shorter in dilatation therapy group (9.6 cm [5.5-12]) compared to surgery group (11 cm [6-15]) and intercourse group (11 cm [6-12.5]) (P = .039), but remained within normal ranges. One bias in the surgery group was the high number of sigmoid vaginoplasties (57/84, 68%), but no differences were observed between surgeries. Only 4 patients achieved vaginas <6.5 cm. Delay between management and first intercourse was 6 months (not significant). Seventy patients (53%) had dyspareunia (not significant), and 17 patients all from the surgery group had an abnormal pelvic exam. In the surgery group, 34 patients (40.5%) had complications, requiring 20 secondary surgeries in 17 patients, and 35 (42%) needed postoperative dilation. In the dilation therapy group, 13 (50%) needed maintenance dilation. CONCLUSION: Surgery is not superior to therapeutic or intercourse dilation, bears complications, and should therefore be only a second-line treatment. Psychological counseling is mandatory at diagnosis and during therapeutic management.

Urachal rhabdomyosarcoma in childhood: a rare entity with a poor outcome.

BACKGROUND/PURPOSE: Rhabdomyosarcoma (RMS) of the urachus is rare and gathered in the "abdominal and other locations" group for oncological treatment purpose, and therefore not well characterized. Our aim was to assess the clinical and prognostic specific features of urachal primary RMS in childhood. METHODS: We retrospectively reviewed the charts of 8 patients with an urachal RMS treated between 1984 and 2013 in two Pediatric Oncology Departments. Median follow-up was 42 months (18-100). RESULTS: Urachal RMSs were embryonal in 6, alveolar in 1, and not otherwise specified in 1. Age at diagnosis was 4.4 years (2.6-6). All patients had advanced locoregional extension (IRS IIIIV) and 1 had distant metastasis. All had chemotherapy and surgical resection. Six had external radiotherapy. Four had extensive peritoneal recurrence including 2 with distant metastasis, within a median of 25 months (11-82) after the end of treatment. One had metastatic progression under primary treatment. Four of them died between 18 and 57 months after diagnosis, and 1 is still under treatment for a late recurrence. Only 3 are free of disease after 3.3 to 7.9 years of follow-up. CONCLUSIONS: Pediatric urachal cancer is rare and poorly identified. In our series, RMS was exclusive in this location. Locoregional extension was always advanced. Prognosis was poor despite current multimodal therapy. We underline the need for new therapeutical strategies.

Wandering spleen in children: multicenter retrospective study.

Wandering spleen in children is a rare condition. The diagnosis is difficult, and any delay can cause splenic ischemia. An epidemiologic, semiological, and surgical diagnosis questionnaire on incidence of wandering spleen in children was sent to several French surgical teams. We report the results of this multicenter retrospective study. Fourteen cases (6 girls, 8 boys) were reported between 1984 and 2009; the age range varies between 1-day-old and 15 years; 86% were seen in the emergency department. Ninety-three percent had diffuse abdominal pain. For 57% of the cases, it was their first symptomatic episode of this type. No diagnosis was established based on the clinical results alone. All patients had presurgical imaging diagnosis. Open surgery was performed on 64% cases. Forty-three had splenectomy for splenic ischemia. Thirty-six percent had splenopexy, 14% had laparoscopic gastropexy, and 7% had spleen repositioning and regeneration. Complications were noted in 60% of the cases resulting in postsplenopexy splenic ischemia. Early diagnosis and surgery are the best guarantee for spleen preservation. Even if the choice of one technique, splenopexy or gastropexy, can be argued, gastropexy has the advantage of avoiding splenic manipulation and restoring proper physiologic anatomy. When there is no history of abdominal surgery, laparoscopy surgery seems the best procedure.

Female epispadias management: perineal urethrocervicoplasty versus classical Young-Dees procedure.

PURPOSE: We compared the functional results of 1-stage perineal urethrocervicoplasty and vulvoplasty vs the classic Young-Dees procedure for incontinent female epispadias. MATERIALS AND METHODS: We treated 14 female patients with incontinent epispadias between 1997 and 2007, of whom 7 each underwent the Young-Dees procedure until 2004 (group 1) and 1-stage urethrocervicoplasty with vulvoplasty through a perineal subsymphyseal approach (group 2). We retrospectively compared patient age at surgery, bladder capacity, continence outcome and postoperative morbidity. RESULTS: The groups were comparable except for age at procedure. In group 1 vs 2 surgery was performed at a median age of 6 vs 4 years. In groups 1 and 2 median preoperative bladder capacity was 120 and 100 cc, and mean followup was 8 and 2.5 years, respectively. Six group 1 patients achieved continence, including 5 with overnight continence, but 5 required additional surgery to enhance continence or voiding, including pericervical injections of bulking agents (3), cervicotomy or urethral calibration (4) and enterocystoplasty (1). Two patients required long-term clean intermittent catheterization, 4 underwent upper tract dilation postoperatively and 4 had a total of 8 episodes of febrile urinary tract infection. Six group 2 patients were continent, including 3 with overnight continence (p = 1). None required clean intermittent catheterization even temporarily or any additional surgery (p = 0.02). Only 2 patients had a febrile urinary tract infection (p = 0.25). CONCLUSIONS: Reconstructing the bladder neck and urethra via a perineal approach for female epispadias is promising. Surgery may be performed earlier with similar continence results, less postoperative morbidity and less need for additional surgery. Long-term studies are needed to confirm these preliminary results.

Complete androgen insensitivity syndrome: diagnosis and management.

Complete androgen insensitivity syndrome (CAIS) is an X-linked genetic disorder affecting 46,XY individuals, characterized by the loss of function of the androgen receptor gene resulting in complete peripheral androgen resistance. Patients have a nonambiguous female phenotype with normal female external genitalia. Gonads are undescended testes (either intra-abdominal or inguinal), there is no uterus and the length of the vagina is usually very short. Gender identity is always female. This review focuses on the importance of accurate diagnosis of CAIS versus partial androgen insensitivity syndrome and other disorders of sex development by genotyping the androgen receptor, and raises issues of the optimal management of these patients. In the era of the Consensus Statement on Management of Intersex Disorders, we provide new insights into CAIS screening, surgical management of the gonads (balancing between hormonal production and malignancy risk) and of vaginal adequacy, and the ethics concerned with the disclosure to patients and their families.

Early elimination dysfunction associated with cephalic anomalies: is there a link?

UNLABELLED: Elimination dysfunction in children can be related to three main aetiologies: 1) spinal cord anomalies, 2) social and environmental disorders, and 3) syndromic elimination disorders. From this last group, we report cases of a previously undescribed combination of elimination disorders and cephalic anomalies symptoms which may constitute a proper entity for which conventional treatments may fail. A comprehensive review of congenital elimination disorders is given. PATIENTS AND METHODS: Six patients (four boys, two girls) presenting with early elimination dysfunction associated with cephalic anomalies were assessed and treated between 1994 and 2005. None presented with identified lower urinary tract obstruction or spinal cord anomalies. Follow up ranged between 5.5 and 11.5 (mean 6.7) years. RESULTS: All six had early elimination disorders, represented by urine retention, urinary tract infections, constipation and soiling. All had facial dysmorphy and cerebral anomalies with developmental delay of varying severity. All had a dilated urinary tract, with severe vesicoureteral reflux in five and one megaureter without reflux. All had abnormal renal isotope scans, two associated with chronic renal failure. The family medical history was significant in some cases. Treatment included early urinary diversion, and there was a high failure rate for ureteral reimplantation. CONCLUSION: The combination of congenital elimination dysfunction with facial anomalies, developmental retardation, cephalic anomalies, abnormal urinary tracts, without identified spinal cord disorders or lower urinary tract obstruction, may represent a defined population of children. Identification may lead to early elimination support measures including temporary bladder diversion, Mitrofanoff diversion, alpha blockers and bowel transit medications.

Long-term followup and comparison between genotype and phenotype in 29 cases of complete androgen insensitivity syndrome.

PURPOSE: Diagnosis and management of the complete androgen insensitivity syndrome have dramatically changed in the last few decades, with earlier diagnosis and the development of molecular biology. Some phenotypic features such as development of wolffian and mullerian remnants have been suggested to be an index of subtle residual androgen activity. Variations of these features clearly exist among patients and may influence treatment. Our aim was to assess the safety of keeping gonads in place for spontaneous puberty in a cohort of patients with genetically proved complete androgen insensitivity syndrome. In parallel to the risks of virilization at puberty and gonadal tumor some additional features, such as need for vaginal surgery, were investigated. MATERIALS AND METHODS: We studied the genotype, phenotype, anatomy of the internal and external genitalia, and clinical outcome of 29 cases of complete androgen insensitivity syndrome, managed by the same team from diagnosis (frequently in early childhood) to adulthood. RESULTS: All patients had a complete female phenotype. A total of 19 different mutations (including 7 unreported) were found. Each family presented with a different mutation. No somatic mosaicism was detected. Vas deferens and epididymis were found in all types of mutations (missense, nonsense and frameshift). Of the patients 23 were postpubertal (19 spontaneously). No postpubertal virilization occurred. Only 1 carcinoma in situ was detected (postpubertally). Vaginal surgery was rarely necessary. CONCLUSIONS: Our data advocate for keeping the gonads in the complete androgen insensitivity syndrome, at least until completion of spontaneous puberty. The risk of virilization at puberty should be ruled out for each androgen receptor mutation before management decisions and genetic counseling. Vaginal surgery should not be indicated as first line treatment.

Enhanced in situ expression of NF-kappaBp65 is an early marker of intestinal graft rejection in rats.

BACKGROUND: Although intestinal transplantation provides a unique situation of free access to the graft because of the presence of temporary enterostomas, evaluation of local immunosuppression is still an unresolved issue and may constitute one of the causes of grafting failure. AIMS: To study in a rat model of allogeneic intestinal transplantation the expression of transcription factors involved in lymphocyte activation in situ in the graft and to identify factors reflecting the efficiency of drug immunosuppression. METHODS: Intestinal transplantation was performed in a Brown Norway (RT1n-donors)-Lewis (RT1(l)-recipients) rat strain combination. The animals were treated with tacrolimus to induce tolerance or left untreated. Syngeneic intestinal grafts and intestine from donor rats with peritonitis were used as controls. NF-kappaBp65, p-c-Jun, interleukin 2 receptor (CD25), and major histocompatibility complex class II antigen (OX-6) expression was studied in graft biopsies on days 2 and 5 by immunohistochemistry. RESULTS: On day 2, before the onset of histologic signs of rejection, the number of cells expressing NF-kappaBp65 in the pericryptic lamina propria was significantly higher in untreated recipients of allogeneic grafts than in the other groups (P = .009). NF-kappaBp65 expression then fell between days 2 and 5 (P = .009). Classic markers of T-cell activation (CD25 and OX-6) were expressed during rejection in the lamina propria and on crypt enterocytes, respectively. p-c-Jun expression did not differ among the 3 groups. CONCLUSION: NF-kappaBp65 expression in intestinal grafts is a precocious sign of local activation during rejection and could thus serve to optimize the management of immunosuppressive therapy.

Impact of early screening for reflux in siblings on the detection of renal damage.

OBJECTIVE: To assess the impact of screening siblings after detecting significant vesico-ureteric reflux (VUR) and renal scarring, as such screening might identify patients with VUR before urinary tract infections develop, but might also detect clinically insignificant VUR. PATIENTS AND METHODS: We used a previously reported screening protocol to assess the clinical characteristics of patients, including the incidence of renal scarring, and their siblings, and compared the results. In all, 123 children were screened and 44 (36%) had VUR on voiding cystography. The median (range) age at screening was 9 (1-90) months. RESULTS: The grades of VUR detected were < III in 61% and > or = III in 39%; VUR was bilateral in 48%. In all, 37 siblings with VUR were assessed by ultrasonography; 70% were normal, including 12 (32%) children with VUR of grade > or = III. When used, renal scintigraphy was normal in 74% of siblings, vs 18% of index patients. However, when screened after 2 years old, siblings had twice the risk of already having renal damage on renal scintigraphy (P = 0.04). CONCLUSION: Early screening (< or = 2 years) appears to be more protective for avoiding renal damage than screening older patients. Thus we propose early screening in asymptomatic siblings to detect VUR before it becomes clinically significant.