RETRACTED ARTICLE: Urinary nerve growth factor: a biomarker for overactive bladder in children? A meta-analysis and trail sequential analysis

A cloacal anomaly is not a disorder of sex development Abstract Aim of the study Misdiagnosing a cloaca as a disorder of sex development may lead to inappropriate testing, treatment, and negative emotional consequences to families. We were impressed by the fact that a significant number of patients suffering from a cloaca were referred to us with the diagnosis of a “disorder of sex development” previously referred as “ambiguous genitalia” or “intersex”. On re-evaluation, none of them truly had a disorder of sex differentiation. This prompted us to conduct the following retrospective review to try to find the cause of the misdiagnosis and the way to prevent it. Methods A retrospective review of our colorectal database was performed to identify the total number of patients with cloacas and the number initially diagnosed as “ambiguous genitalia, intersex”/disorder of sex development. The external appearance of their genitalia and unnecessary testing or treatment received were recorded. Main results A total of 605 patients with cloacas were identified. Of these, 77 (12.7%) were referred to us with the diagnosis of “ambiguous genitalia” and 13 of them (17%) went on to receive an intervention that was not indicated: karyotyping (10), steroids (3), and ovarian biopsy (1). The karyotype result in all patients was XX. The misdiagnosis was triggered by the external appearance of the perineum, simulating a case of virilization with a hypertrophic clitoris, but was simply prominent labial skin. Careful examination of the perineal structure allowed us to determine that it consisted of folded skin with no evidence of corpora. Conclusion Patients born with a cloaca are at risk for mismanagement from being erroneously labeled as disorders of sex development. The diagnosis of a cloacal anomaly is a clinical one. The practitioner must distinguish between phallus-like clitoral hypertrophy and a normal clitoris with prominent labial skin.

Vaginal reconstruction for distal vaginal atresia without anorectal malformation: is the approach different? Abstract Introduction Distal vaginal atresia is a rare condition and treatment approaches are varied, usually driven by symptoms. Methods A retrospective review was performed to identify patients with distal vaginal atresia without anorectal malformation. Data collected included age and symptoms at presentation, type and number of operations, and associated anomalies. Results Eight patients were identified. Four presented at birth with a hydrocolpos and four presented with hematometrocolpos after 12 years of age. Number of operations per patient ranged from one to seven with an average of three. The vaginal reconstruction was achieved by perineal vaginal mobilization in four patients and abdomino-perineal approach in four patients. One patient, with a proximal vagina approximately 7 cm from the perineum, required partial vaginal replacement with colon. In addition, she had hematometrocolpos with an acute inflammation at the time of reconstruction despite menstrual suppression and drainage which may have contributed to the difficulty in mobilizing the vagina. In five patients, distal vaginal atresia was an isolated anomaly. In the other three cases, associated anomalies included: mild hydronephrosis that improved after hydrocolpos decompression (2), cardiac anomaly (2), and vertebral anomaly (1). Conclusion In this series, a distended upper vagina/uterus was a common presentation and the time of reconstruction was driven by the presence of symptoms. Drainage of the hydrocolpos/hydrometrocolpos with menstrual suppression in post-pubertal patients, followed by further work-up, and planned reconstruction is a good surgical strategy.

Ectopic ureters in anorectal malformations Abstract Purpose The literature about ectopic ureters in anorectal malformations is limited. Repair of an anorectal malformation may require dissection near the normal or abnormal insertion of the ureters. Knowledge of the presence and location of ectopic ureters may prevent intraoperative injury. We aim to describe the incidence and location of ectopic ureters in patients with anorectal malformations and to characterize associated renal anomalies. Methods This is an IRB-approved retrospective study of patients with anorectal malformations and ectopic ureters identified in our colorectal database. Results Of 2283 patients with anorectal malformation, 79 (3.5%) had ectopic ureter(s). Of those, 29% had bilateral ectopic ureters. Nearly all (87%) of bilateral ectopic ureters occurred in females. Ectopic ureters most commonly inserted into the bladder neck (33%), vagina (15%), or urethra (13%). Renal dysfunction was noted in a high proportion of patients. The majority (59%) of ectopic ureters were associated with dysfunction of the ipsilateral kidney. Interestingly, 29% of patients with unilateral ureteral ectopia had an abnormal contralateral kidney. Only 22 patients (28%) had two normal kidneys, and 5 (6%) had documented renal failure with 2 (2.5%) requiring renal transplant. This compares to a transplant rate of 0.6% among anorectal malformation patients without ectopic ureter. Conclusions The incidence of ectopic ureter is 3.5% among anorectal malformation patients. Cloaca and recto-bladder neck fistula are the types of anorectal malformation with higher incidence. Ureteral ectopia seems to confer an increased risk of renal failure. Identifying ectopic ureters is important for surgical planning and monitoring renal function vigilantly.

Gynecological anomalies in patients with anorectal malformations Abstract Purpose The association of gynecological anomalies in all anorectal malformations (ARM) is firmly established. Our goal is to study this pathology in our patients to focus attention to this important issue. Methods Retrospective study of female patients operated for ARM and who underwent magnetic resonance imaging in our center. The type of malformation, the presence and type of vaginal, uterine, tubaric and urological anomalies were studied. Results 63 patients were included: 34.9% cloaca, 28.6% vestibular and 12.7% perineal. Half of patients had some type of müllerian anomaly; 19 vaginal, most frequent being the longitudinal vaginal septum (66.7%); 30 had uterine alterations, most frequent being the uterus didelphys (60%). Eighty percent of patients with complex ARM (cloaca, exstrophy) presented some type of gynecological malformation compared to 21.8% found in simple ARM (stenosis, perineal, vestibular) (p < 0.001). Vaginal anomalies are associated with a uterine anomaly in 100% of cases. Conversely, patients with uterine anomalies have concurrent vaginal anomaly in 63.3% of cases. Conclusion Screening for gynecological anomalies is indicated in all patients with ARM. We recommend a vaginal examination in any girl with ARM during definitive repair and a subsequent MRI during follow-up. Collaboration with a gynecologist is essential.

Anal duplication: is surgery indicated? A report of three cases and review of the literature Abstract Aim of the study Anal canal duplications (ACDs) are extremely rare with only approximately 90 cases described in the literature. We report on three additional patients. Methods Cases were analyzed to evaluate presenting symptoms, physical exam and MRI findings. A comprehensive literature review was performed to compare our patients to previously described cases. IRB approval was obtained for this study (19-0394). Main results The first female patient presented with an asymptomatic ACD at 2 years old. The second patient was a 13-year-old female with perianal drainage that was initially mistaken for a fistula-in-ano and ultimately found to have an ACD associated with a dermoid cyst. Both posterior midline duplications shared a common wall with the rectum, but did not communicate with it. The ACDs and dermoid cyst were successfully excised through a posterior sagittal approach with no postoperative complications. Histology demonstrated the presence of both squamous epithelium and transitional anal epithelium in each case. The third patient was 8 months old and had a tethered cord, hemisacrum, presacral mass, and anal duplication that was initially undiagnosed. These results corroborate patterns identified in other reports of ACDs with over 90% being female and in the posterior midline. The majority are asymptomatic, but may present with symptoms of local or even systemic infection. Conclusion An opening in the midline posterior to the anus should raise clinical suspicion for anal canal duplication. An associated presacral mass must be ruled out. Complete excision through a posterior sagittal approach is recommended upon diagnosis to avoid symptomatic presentations. The key part of the operation is the separation of the ACD from the posterior rectal wall.

Non-financial conflicts of interest: contribution to a surgical dilemma by the European Reference Networks for Rare Diseases Abstract Purpose Conflicts of interest can impede both research and medical treatment. The European Reference Networks require their members to deal with financial and non-financial conflicts according to an explicit protocol. In a literature review, we identified relevant interests in paediatric surgery, and drafted such a policy. Methods We conducted a Pubmed query and identified additional publications based on the content of the papers. Results 58 titles were identified. According to their abstracts, 10 publications were studied in full text. A scientific taxonomy does not yet exist, but a variety of factors are mentioned. Non-financial conflicts of interest are addressed less accurately and less frequently than financial ones, especially regarding surgical treatment. Since the clinical effect of surgical volume was identified as being relevant, additional 29 respective publications were analysed. This volume-quality relationship causes conflicts of interest for the many surgeons treating a broad spectrum of rare conditions. We present a recommendation that may guide referral of patients requiring complex surgery to centres with a higher volume. Conclusions Non-financial conflicts of interest need to be dealt with more accuracy, especially with regard to surgery in rare, complex congenital conditions. The European Reference Networks offer a framework to mitigate these conflicts.

Management of fetal extraperitoneal rectal perforation: a case series and review of the literature Abstract Purpose Fetal extraperitoneal rectal perforation (FERP) is an extremely rare entity. The objective of this report is to review the available literature on this condition and to add our experience with four additional cases managed at our institution. Methods A literature search was performed for journal articles addressing this condition. Management strategies and outcomes were then analysed, together with additional information provided from retrospective record review of four cases managed at our institution. Results A total of 18 patients were identified and included, 14 from the literature and 4 from our records. Initial investigations varied between authors with contrast enema being the most frequently performed study (7/18). All patients were treated with faecal diversion via colostomy formation. Exploratory laparotomy was performed in 6 cases, perineal debridement and washout in 9 cases while drains were left in situ in 14 cases. At 3–6 months of age, a distal contrast study was performed before closure of colostomy. Conclusion Although FERP is a rarely encountered clinical condition, timely recognition and appropriate management can result in good outcomes. Diagnosis can be achieved based on clinical and abdominal X-ray features alone. General management principles involve a diverting colostomy and extended drainage with closure of the colostomy 3–6 months later.

Urinary nerve growth factor: a biomarker for detrusor overactivity in children? A meta-analysis and trail sequential analysis Abstract Purpose Based on, previously, a systematic review, urinary nerve growth factor (NGF) has emerged as one potentially noninvasive biomarker for detrusor overactivity (DO) in adults. We performed this systematic review to explore if NGF is a biomarker for DO in children. Methods A literature search was conducted in PubMed, Embase, Web of science, and Cochrane Library. Copies of all relevant articles were retrieved for quality assessment and data abstraction by two reviewers. Primary outcome was pooled standardized mean difference (SMD) for NGF/Cr (NGF normalized to urine creatinine) level between DO group and controls. Results Three case–control studies published from 2012 to 2016 were included with 74 patients and 70 controls. Children with DO had a significant higher baseline urinary NGF/Cr level compared to controls (SMD = 2.48, 95%CI = 0.85–4.10, P < 0.01). After treatment, the level of NGF/Cr decreased significantly compared to baseline level at 6th month time points (SMD = 0.94, 95%CI = 0.03–1.86, P = 0.04). We calculated the required information size to 99 patients for comparison of urinary NGF/Cr level between DO and controls by trail sequential analysis (TSA). Conclusion Based on this systematic review, NGF/Cr may be a noninvasive biomarker for DO in children in the future. However, based on TSA, more original studies are needed to clarify the role of NGF/Cr in the biomarker effect.

Laparoscopic versus open inguinal hernia repair in children: which is the true gold-standard? A systematic review and meta-analysis Abstract Purpose Hernia repair is one of the most common operations performed in children. Traditionally, an open surgical approach has been utilized; however, laparoscopic repair has been gaining favour within the surgical community. We aimed to determine whether open or laparoscopic hernia repair is optimal for pediatric patients by comparing recurrence rates and other outcomes. Methods We searched CENTRAL, MEDLINE, and EMBASE from 1980 onwards, including studies that compared laparoscopic and open repair for pediatric inguinal hernia. Results Our initial search yielded 345 unique citations. Of these, we reviewed the full text of 28, and included 21 in meta-analysis. The results showed that patients who underwent laparoscopic surgery were more likely to experience wound infection (p = 0.003), but less likely to experience ascending testis (p = 0.05) and metachronous hernia (p = 0.0002). There were no differences in recurrence rates (p = 0.95), surgical time (p = 0.55), length of hospitalization (p = 0.50), intra-operative injury, bleeding, testicular atrophy, or hydrocele. Conclusion Laparoscopic and open surgeries are equivalent in terms of recurrence rates, surgical time, and length of hospitalization. Laparoscopic repair is associated with increased risk of wound infection, but decreased risk of ascending testis. Laparoscopic surgery allows the opportunity to explore and repair the contralateral side, preventing metachronous hernia. Level of Evidence III.