MUC-FIRE: Study protocol for a randomized multicenter open-label controlled trial to show that MUCous FIstula REfeeding reduces the time from enterostomy closure to full enteral feeds.

Background: After enterostomy creation, the distal bowel to the ostomy is excluded from the physiologic passage of stool, nutrient uptake, and growth of this intestinal section. Those infants frequently require long-term parenteral nutrition, continued after enterostomy reversal due to the notable diameter discrepancy of the proximal and distal bowel. Previous studies have shown that mucous fistula refeeding (MFR) results in faster weight gain in infants. The aim of the randomized multicenter open-label controlled MUCous FIstula REfeeding ("MUC-FIRE") trial is to demonstrate that MFR between enterostomy creation and reversal reduces the time to full enteral feeds after enterostomy closure compared to controls, resulting in shorter hospital stay and less adverse effects of parenteral nutrition. Methods/Design: A total of 120 infants will be included in the MUC-FIRE trial. Following enterostomy creation, infants will be randomized to either an intervention or a non-intervention group.In the intervention group, perioperative MFR between enterostomy creation and reversal will be performed. The control group receives standard care without MFR.The primary efficacy endpoint of the study is the time to full enteral feeds. Secondary endpoints include first postoperative bowel movement after stoma reversal, postoperative weight gain, and days of postoperative parenteral nutrition. In addition adverse events will be analyzed. Discussion: The MUC-FIRE trial will be the first prospective randomized trial to investigate the benefits and disadvantages of MFR in infants. The results of the trial are expected to provide an evidence-based foundation for guidelines in pediatric surgical centers worldwide. Trial registration: The trial has been registered at clinicaltrials.gov (number: NCT03469609, date of registration: March 19, 2018; last update: January 20, 2023, https://clinicaltrials.gov/ct2/show/NCT03469609?term=NCT03469609&draw=2&rank=1).

Diagnosis and Therapy of Female Genital Malformations (Part 1). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019).

Objectives Female genital malformations may take the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and adnexa, the clinical picture of malformations may vary greatly. Depending on the extent of the malformation, organs of the urinary system or associated malformations may also be involved. Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed using a structured consensus process with neutral moderation and voted on. Recommendations The guideline is the first comprehensive presentation of the symptoms, diagnosis and treatment options for female genital malformations. Additional chapters on classifications and transition were included.

Diagnosis and Therapy of Female Genital Malformations (Part 2). Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/052, May 2019).

Objectives Female genital malformations may be present in the form of individual entities, they may involve neighboring organs or they may occur in the context of complex syndromes. Given the anatomical structures of the vulva, vagina, uterus and uterine appendages, the clinical picture of malformations varies greatly. Methods This S2k-guideline was developed by representative members from different medical specialties and professions as part of the guidelines program of the DGGG, SGGG and OEGGG. The recommendations and statements were developed and voted on using a structured consensus process with neutral moderation. Recommendations This guideline is the first comprehensive summary of female genital malformations from infancy to adulthood which covers clinical examinations, diagnostic workups and treatment options. Additional chapters have been included on complex urogenital malformations, vascular malformations, psychosomatic care, and tumor risk.

Human exome and mouse embryonic expression data implicate ZFHX3, TRPS1, and CHD7 in human esophageal atresia.

INTRODUCTION: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development. METHODS: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal. RESULTS: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants. CONCLUSION: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.

Surgical Management of Neurogenic Sphincter Incompetence in Children.

We report on the results of a literature review regarding the indications and results of operations to increase bladder outlet resistance to achieve dryness in children with neurogenic sphincter incompetence (NSBD). The relative advantages and disadvantages of injection of bulking agents, periurethral slings, bladder neck reconfiguration, artificial sphincters, and bladder neck closure based on a literature review and our combined clinical experience are discussed. Based on this review and our experience, we propose that periurethral injection of bulking agents is not justified as a primary treatment. Likewise, operations that reconfigure the bladder neck are not very useful since most patients also require bladder augmentation and an abdominal catheterizable channel. Bladder neck slings with autologous tissues are effective, mostly in females bur in the majority of patients a bladder augmentation is necessary. There is a role also for implantation of artificial urinary sphincters but when done as an isolated procedure, close monitoring to detect possible detrusor changes is needed. Bladder neck closure is an effective measure when other methods have failed.

Effectiveness of Prenatal Intervention on the Outcome of Diseases That Have a Postnatal Urological Impact.

We reviewed the literature addressing outcomes of fetal intervention of conditions that require post-natal urological management including lower urinary tract obstruction, hydrometrocolpos, congenital adrenal hyperplasia, and myelomeningocele. Despite several decades of fetal intervention for these conditions, benefits remain elusive in part because of the enormous difficulty of conducting prospective randomized studies. In this review, we reached the following conclusions: Prenatal intervention in lower urinary tract obstruction (LUTO) improves survival in the worst cases by improving pulmonary function and it may be advantageous for renal function, particularly in patients with adverse urine parameters.Prenatal treatment of female fetuses at risk of having congenital adrenal hyperplasia (CAH) reduces virilization. Non-invasive fetal DNA analysis allows earlier diagnosis, reducing the risk of treating with dexamethasone males and non-affected fetuses.Fetal treatment of myelomeningocele (MMC) is gaining momentum. Prospective studies including standardized urologic evaluation will determine if the encouraging results reported by some hold on the long term follow-up.

Results of Onlay Preputial Flap Urethroplasty for the Single-Stage Repair of Mid- and Proximal Hypospadias.

AIMS: To report current results of preputial flap onlay urethroplasty using the principle of the total preputial flap (TPF) for the one-stage repair of mid- and proximal hypospadias. METHODS: This study was a retrospective chart review of patients in a prospectively kept database of all hypospadias operations performed at two institutions from January 1 2011 to August 2017. Inclusion criteria: all patients who underwent hypospadias repair using a preputial only flap urethroplasty based on the principle of the TPF. Demographic data, duration of follow-up, complications, and reoperations were recorded. A successful result was considered to be a straight penis, a glanular meatus, and absence of voiding symptoms. Whenever possible an uroflow was obtained during the follow-up visits. RESULTS: Forty-nine children met the inclusion criteria. All patients had marked penile curvature. Three patients had chromosomal abnormalities. The mean age at the time of surgery was 22 months (11-110) and the mean duration of follow-up 23.4 months (1-79). In 48 cases, the urethral plate could be preserved without dividing it. The penile curvature was corrected with chordectomy alone in 10 patients, 38 required a dorsal plication of the tunica albuginea, and 1 required an additional ventral dermal graft. In 38 patients (77.5%), the initial operation was successful, and no further operations were needed. There were eight urethrocutaneous fistulas, three dehiscences of the glans approximation. One patient suffered a wound infection and partial loss of the flap. CONCLUSION: One-stage repair of mid- and proximal hypospadias preserving the urethral plate and using a TPF for the urethroplasty and coverage of the ventral penis is successful in 77.5% of cases. Complications in the remaining patients were easily managed or did not require treatment. Compared to a planned two-stage approach, the technique described in this report resulted in significantly fewer procedures till complete resolution of the problem.

Needs Assessment in Care of Adults With Anorectal Malformations and Exstrophy-Epispadias Complex in Germany.

Introduction: Medical needs of adults with anorectal malformations (ARM) and the exstrophy-epispadias complex (EEC) are not fully understood. Therefore, the aim of the study was to evaluate how affected individuals get along with the current national medical care and what their medical or social long-term requirements are. Patients and Methods: Between 11/2014-07/2016 all adult members (≥18 years, ARM n = 113, EEC n = 126) of the German self-help organizations SoMA e.V. and Blasenekstrophie/Epispadie e.V. were contacted via email or post and asked to fill out an anonymous online questionnaire regarding medical requirements, treatment satisfaction, daily life impairment and expectations regarding physicians soft skills. The results were compared between both groups and male and female participants. Results: 56 participants with ARM (median age 26 years, IQR 19-38) and 52 participants with EEC (median age 31 years, IQR 22-37) filled in the questionnaire completely. Forty-five percent of the ARM and 67% of the EEC participants contacted an urologist. A general surgeon was visited by 23% of the ARM individuals, a peadiatric surgeon by 20%. Although 60% of the females with ARM and 82% of the females with EEC assessed gynecological counseling as helpful or neutral, a small subgroup of ARM females (n = 6, 16%; 70% non-isolated ARM or ARM with Hirschsprung disease and additional associated anomalies) were not satisfied. The majority of both groups reported no or only minor daily life impairment (p = 0.38). Professional knowledge, paying attention to patients' concerns, having empathy and taking enough time was important for over 90% of all participants. Thirty-eight percent of the ARM and 27% of the EEC individuals needed psychological support. Most medical consultations were judged to be helpful. Conclusion: Although adults with ARM and EEC being a self-help organization member and thus well informed and generally cope well, participants expressed their wish for expert counseling regarding family planning, reconstructive procedures, continence management, urological care and social welfare issues. Furthermore, specific expert consultations for gynecological issues in a subgroup of ARM females, mainly non-isolated, might be required. Actual needs of adults with rare conditions must be better clarified to improve medical care beyond childhood and adolescence.

The BULT Method for Pediatric Minilaparoscopic Pyeloplasty in Infants: Technique and Results.

We reviewed retrospectively the results of transperitoneal minilaparoscopic pyeloplasty in children younger than 2 years. The surgical technique utilized as well as the retrograde placement of the stent is described in detail. Twenty-four consecutive children with a mean age of 7.9 months (range 1-23), a mean weight of 7.4 kg (range 4-12), and a mean follow-up of 18 months (range 3-59) are included. Preoperative grade of dilatation was 3.8 (SFU scale) and postoperatively improved to 1.5. The AP diameter of the pelvis decreased from a mean of 28-9 mm. In 83% of cases, there was complete resolution of hydronephrosis (grades 0-2) and the rest showed improvement. There was one conversion to open surgery in a child with a horseshoe kidney. There was one omental prolapse though a port site in a child in whom an inappropriate drain was used. There were no stent-related complications and no reinterventions for persistent or recurrent obstruction. Given these outcomes, low complication rate and excellent cosmetic results, we recommend transperitoneal minilaparoscopy with a double J stent and a perirenal drain for infants requiring pyeloplasty.

Should CAH in Females Be Classified as DSD?

Great controversies and misunderstandings have developed around the relatively recently coined term disorders of sex development (DSD). In this article, we question the wisdom of including XX individuals with congenital adrenal hyperplasia (CAH) in the DSD category and develop arguments against it based on the published literature on the subject. It is clear that females with CAH assigned the female gender before 24 months of age and properly managed retain the female gender identity regardless of the Prader grade. Females with CAH and low Prader grades have the potential for a normal sexual and reproductive life. Those with greater degrees of prenatal androgen exposure (Prader grades IV and V) raised as females also identify themselves as females but experience more male-like behavior in childhood, have a greater rate of homosexuality, and have greater difficulty with vaginal penetration and maintaining pregnancies. Improvement in surgical techniques, better endocrinological, psychological, and surgical follow-up may lessen these problems in the future. Given the fact that the term DSD includes many conditions with problematic gender identity and conflicts with the gender assigned at birth, it may be appropriate to exclude females with CAH from the DSD classification.

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

Total preputial flap: a reliable and versatile technique for urethral and penile reconstruction.

We revisit the technique of total preputial flap (TPF) and its application for urethroplasty, penile skin coverage of both and present our results in 43 patients (41 hypospadias, 2 epispadias). There were no instances of flap necrosis. In patients without prior attempts at reconstruction (n = 36), we observed four urethrocutaneous fistulas. TPF allowed the repair of cases of proximal hypospadias in one stage with an acceptable complication rate.

Implementation of fast-track pediatric surgery in a German nonacademic institution without previous fast-track experience.

Fast-track concepts in pediatric surgery were established in a university hospital in consecutive studies within several years. They significantly reduced the length of hospitalization compared with German institutions without fast-track protocols. The aim of this study was to assess the implementation process of fast-track in a German nonacademic department of pediatric surgery without previous fast-track experience. All patients undergoing four types of operations (appendectomy, hypospadias repair, pyloromyotomy, and fundoplication) from February 2011 to January 2012 were included in this prospective study. Fast-track included detailed clinical pathways and specific pain treatment protocols using validated pain scales according to age. Mobilization and oral nutrition were started 2 hours postoperatively and documented with established scores. The length of hospital stay was compared with data from other hospitals with conventional treatment using information from the German reimbursement system (German diagnosis-related groups [G-DRG]) and with the hospital stay of patients from the corresponding university hospital undergoing fast-track treatment for the same procedures during the same study period. Two weeks after discharge, a questionnaire was completed by the patients/parents. A total of 143 patients with a mean age of 7.9 ± 5.0 years underwent fast-track treatment. The mean pain intensity during the immediate postoperative period was 1.7 ± 2.1 in patients < 4 years and 2.3 ± 2.1 in patients ≥ 4 years on a 10-point scale. Full mobilization was reached after a mean duration of 2.3 ± 2.0 days while full oral nutrition was completed after a mean duration of 1.8 ± 1.4 days. There were no complications associated with fast-track. The mean hospital stay was 5.8 ± 3.4 days which was not significantly different compared with G-DRG data from other hospitals without fast-track. This was in contrast to the mean hospital stay of patients from the corresponding university hospital (5.6 ± 3.0 days vs. G-DRG 6.9 ± 3.2 days, p < 0.05). After 2 weeks, patients/parents were highly satisfied with fast-track (mean score of 8.6 ± 1.4 on a 1-10-point scale) and 95.2% claimed that they would choose it again. Fast-track concepts can be applied in a nonacademic department of pediatric surgery without previous fast-track experience and with excellent patient/parent satisfaction. However, the G-DRG system interferes with concepts of early discharge of patients. Modifications of the reimbursement modalities within the German health care system seem to be mandatory.