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Aim: This study aimed to develop a universally applicable core set of quality indicators for Hirschsprung's disease care through a consensus-driven process, to standardise and improve care quality across Europe., Methods: A modified Delphi method was used to achieve consensus among healthcare professionals (HPs) and patient representatives (PRs) across Europe. Participants completed three rounds of anonymous surveys, rating quality indicators for Hirschsprung's disease care. A systematic literature review informed the initial item list. Results were analysed using predefined criteria, and a final consensus meeting established the core set of indicators., Results: An international panel of 8 PRs and 96 multidisciplinary health care professionals representing 59 European hospitals completed all questionnaires, eventually including 12 baseline characteristics and 39 indicators. Six of the top 10 indicators were commonly prioritised by both groups. The remaining items were refined through debate and finalised during a consensus meeting., Conclusion: This study established a core set of 12 baseline characteristics and 14 quality indicators for evaluating Hirschsprung's disease care. These indicators will support benchmarking and continuous quality improvement within the European Paediatric Surgical Audit framework, ultimately enhancing outcomes and care for children with Hirschsprung's disease., (© 2025 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: This study explored prenatal ultrasound markers in patients with anorectal malformations (ARMs)., Methods: All patients treated for ARM in our institution from January 2014 to December 2021 with an available expert fetal anomaly scan (eFAS) were reviewed. The eFAS images were assessed to evaluate the fetal anus, specifically by identifying hyperechoic anal mucosa surrounded by hypoechoic anal sphincter, referred to as "target sign" (TS). Furthermore, indirect signs of ARM were assessed and correlated with postnatal clinical symptoms., Results: Of the 115 patients treated for ARM, 32 mothers underwent eFAS. TS was assessed in 22 fetuses, of which 17 (77.3%) had an absent or abnormal TS. Of the patients with a postnatally confirmed complex type of ARM, 90% had an absent or abnormal TS. One or more indirect signs of ARM were found in 16 out of 32 fetuses (50.0%), comprising echogenic bowel (n = 3), echogenic meconium (n = 2), dilated intestines (n = 7), echo-lucent cavity behind the urinary bladder (n = 4), abnormal external genitalia (n = 6), and polyhydramnios (n = 5)., Conclusion: This retrospective cohort study provides valuable insights into the potential role of TS assessment and indirect signs in the prenatal diagnosis of ARM. Future studies should further validate our findings and elicit whether TS assessment should be incorporated into prenatal screening protocols., (© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Introduction: Children with inflammatory bowel disease (IBD) need surgery whenever medical therapy fails. The postoperative course is frequently accompanied by symptoms suggestive of infection, such as fever. The aim of our study was to analyze the postoperative course after bowel resection in pediatric IBD patients in relation to postoperative infections., Methods: All our pediatric IBD patients who underwent a bowel resection between 2012 and 2022 were retrospectively reviewed. Clinical data regarding surgery and the postoperative course were analyzed. The primary outcomes were signs and symptoms indicative of infection, such as fever, surgical site infection, and abscesses., Main Results: One hundred patients underwent an IBD-related resection, of whom 69 for Crohn's disease. A total of 42 postoperative infections occurred in 26 patients, most commonly a superficial surgical site infection (38 %). Out of 48 patients who experienced postoperative fever, 52 % had an actual infection, compared to 2 % of those without fever (p < 0.001). Preoperative use of immunomodulating therapy was not associated with higher complication rates. In 35 of 48 patients with fever (73 %) laboratory tests were done as a consequence of postoperative fever, with no differences in complication rates between patients with extremely high (>200 mg/L) and high (<200 mg/L) C-reactive protein levels., Conclusions: Occurring in over a quarter of patients, postoperative infections are common in children after undergoing IBD-related bowel resection. Postoperative fever is indicative of an infection in half of the patients. Laboratory tests, such as serum C-reactive protein, do not seem to contribute to differentiating between complicated and non-complicated course after surgery in these patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis., Methods: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements., Results: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus., Conclusions: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center., Type of Study: Clinical consensus statement., Level of Evidence: 3a., Competing Interests: Declaration of competing interest All contributing authors have submitted a declaration of interest form. No competing interests were noticed, all declarations are available on request., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Serum alpha-fetoprotein (AFP) is often used as tumour marker for recurrent sacrococcygeal teratoma (SCT). We aimed to assess the normal dynamics of serum AFP levels after initial resection and diagnostic accuracy of serum AFP levels the follow-up for recurrence in SCT., Methods: This retrospective study included 57 patients treated for SCT in the six pediatric surgical centers in the Netherlands from 1980 to 2018., Main Results: 57 patients were included in the study of whom 19 children developed 20 recurrences at a median of 14.0 months after initial resection. No significant difference was found in serum AFP level dynamics between the recurrence and non-recurrence group after initial resection (p = 0.950). Serum AFP levels did not significantly increase before recurrence (p = 0.106) compared to serum AFP levels of children without recurrence at the same time. However, serum AFP levels did significantly increase in malignant recurrences (n = 7) (p = 0.03) compared to patients without recurrence. A cut-off value of 55 μg/L was found to be predictive for recurrent SCT with an Area Under the Curve (AUC) of 0.636 with sensitivity of 50% and specificity of 100%., Conclusion: Dynamics of serum AFP levels are not different between patients with and without recurrence after initial resection of SCT. Serum AFP levels are not predictive for mature or immature recurrent SCT and normal AFP levels do not rule out recurrent SCT. However, serum AFP levels exceeding 55 μg/L can indicate recurrent SCT, especially malignant recurrences., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The variation in standardized, well-defined parameters in Hirschsprung's disease (HSCR) research hinders overarching comparisons and complicates evaluations of care quality across healthcare settings. This review addresses the significant variability observed in these parameters as reported in recent publications. The goal is to compile a list of commonly described baseline characteristics, process and outcome measures, and to investigate disparities in their utilization and definitions. A systematic review of literature on the primary care process for HSCR was performed according to PRISMA guidelines. Relevant literature published between 2015 and 2021 was obtained by combining the search term "Hirschsprung's disease" with "treatment outcome," "complications," "mortality," "morbidity," and "survival" in Medline, Embase, and the Cochrane Library. We extracted study characteristics, reported process and outcome parameters, and patient and disease characteristics. We extracted 1,026 parameters from 200 publications and categorized these into patient characteristics ( n  = 226), treatment and care process characteristics ( n  = 199), and outcomes ( n  = 601). A total of 116 parameters were reported in more than 5% of publications. The most frequently reported characteristics were sex (88%), age at the time of surgery (66%), postoperative Hirschsprung-associated enterocolitis (64%), type of repair (57%), fecal incontinence (54%), and extent of aganglionosis (51%). This review underscores the pronounced variation in reported parameters within HSCR studies, highlighting the necessity for consistent, well-defined measures and reporting systems to foster improved data interpretability. Moreover, it advocates for the use of these findings in the development of a Core Indicator Set, complementing the recently developed Core Outcome Set. This will facilitate quality assessments across pediatric surgical centers throughout Europe., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: To assess the number, characteristics, and functional short-, and midterm outcomes of patients with rectal atresia (RA) and stenosis (RS) in the ARM-Net registry., Methods: Patients with RA/RS were retrieved from the ARM-Net registry. Patient characteristics, associated anomalies, surgical approach, and functional bowel outcomes at 1 and 5-year follow-up were assessed., Results: The ARM-Net registry included 2619 patients, of whom 36 (1.3%) had RA/RS. Median age at follow-up was 7.0 years (IQR 2.3-9.0). Twenty-three patients (63.9%, RA n = 13, RS n = 10) had additional anomalies. PSARP was the most performed reconstructive surgery for both RA (n = 9) and RS (n = 6) patients. At 1-year follow-up, 11/24 patients with known data (45.8%, RA n = 5, RS n = 6) were constipated, of whom 9 required stool softeners and/or laxatives. At 5-year follow-up, 8/9 patients with known data (88.9%, RA n = 4, RS n = 4) were constipated, all requiring laxatives and/or enema., Conclusion: RA and RS are rare types of ARM, representing 1.3% of patients in the ARM-Net registry. Additional anomalies were present in majority of patients. Different surgical approaches were performed as reconstructive treatment, with constipation occurring in 46% and 89% of the patients at 1 and 5-year follow-up. However, accurate evaluation of long-term functional outcomes remains challenging., (© 2023. The Author(s).)

Introduction:  To investigate the current experience of the ARM-Net Consortium in the management of epididymo-orchitis (EO) in patients with anorectal malformations (ARMs), and to identify specific risk factors and the need for urological care involvement., Materials and Methods:  We retrospectively collected data of EO in patients with ARM between 2015 and 2019. Data on urological aspects, ARM type, surgical approach, associated anomalies, diagnosis, and treatment of EO were collected and analyzed., Results:  Twenty-nine patients were reported by 12 centers. Twenty-six patients with EO (90%) had ARM with a rectourinary fistula. Median age at first EO was 2 years (range: 15 days-27 years). Twenty patients (69%) experienced multiple EO, and 60% of recurrences were ipsilateral. Associated urological anomalies included vesicoureteral reflux (48%), urethral anomalies (41%), neurogenic bladder (41%), and ectopic vas (10%). A positive urine culture during EO was present in 69%. EO was treated with antibiotics (90%), limiting surgical exploration to 14%. Prevention of recurrences included surgery (bulking agents 15%, vasectomy 15%, and orchiectomy 5%) and antibiotic prophylaxis (20%)., Conclusion:  Urologists may encounter patients with EO in ARM patients, frequently with positive urine culture. An appropriate urologic work-up for most ARM patients is necessary to identify and treat underlying risk factors. A practical scheme for the work-up is suggested for a close collaboration between pediatric surgeons and urologists., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Hirschsprung disease (HD) requires surgical resection of affected bowel, but the current evidence is inconclusive regarding the optimal age for resection. The aim of this study was to assess whether age at resection of the aganglionic segment is a determinant for surgical outcomes., Methods: A cross-sectional cohort study was done including all consecutive patients with HD between 1957 and 2015, aged 8 years or older (n = 830), who were treated in 1 of the 6 pediatric surgical centers in the Netherlands. Outcome measures were mortality, postoperative complications, stoma rate and redo surgery rate, retrieved from the medical records. Additionally, constipation and fecal incontinence rate in long term were assessed with the Defecation and Continence Questionnaire (DeFeC and P-DeFeC)., Results: The medical records of 830 patients were reviewed, and 346 of the 619 eligible patients responded to the follow-up questionnaires (56%). There was a small increase in the risk of a permanent stoma [odds ratio (OR) 1.01 (95% confidence interval {CI}: 1.00-1.02); P = 0.019] and a temporary stoma [OR 1.01 (95% CI: 1.00-1.01); P = 0.022] with increasing age at surgery, regardless of the length of the aganglionic segment and operation technique. Both adjusted and unadjusted for operation technique, length of disease, and temporary stoma, age at surgery was not associated with the probability and the severity of constipation and fecal incontinence in long term., Conclusions: In this study, we found no evidence that the age at surgery influences surgical outcomes, thus no optimal timing for surgery for HD could be determined., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

In the past, an anteriorly located anus was often misdiagnosed and treated as an anorectal malformation (ARM) with a perineal fistula (PF). The paper aims to define the criteria for a normal anus, an anterior anus (AA) as an anatomic variant, and milder types of ARM such as congenital anal stenosis (CAS) and PF. An extensive literature search was performed by a working group of the ARM-Net Consortium concerning the subject "Normal Anus, AA, and mild ARM". A consensus on definitions, clinical characteristics, diagnostic management, and treatment modalities was established, and a diagnostic algorithm was proposed. The algorithm enables pediatricians, midwives, gynecologists, and surgeons to make a timely correct diagnosis of any abnormally looking anus and initiate further management if needed. Thus, the routine physical inspection of a newborn should include the inspection of the anus and define its position, relation to the external sphincter, and caliber. A correct diagnosis and use of the presented terminology will avoid misclassifications and allow the initiation of correct management. This will provide a reliable comparison of different therapeutic management and outcomes of these patient cohorts in the future.

Introduction: Familial occurrence of Hirschsprung's disease may have a positive effect on patients' ability to cope with the disease. The aim was to compare long-term bowel function and generic quality of life between patients with familial and non-familial Hirschsprung's disease., Methods: This was a nationwide, cross-sectional study in which we included all 830 Hirschsprung patients of 8 years and older who had undergone surgery between 1957 and 2015. We excluded patients with a permanent stoma, intellectual disability, or an unknown or foreign address. We requested patients to complete the validated pediatric or adult Defecation and Fecal Continence questionnaire and the Child Health Questionnaire Child Form-87, or the World Health Organization Quality of Life-100 Assessment Instrument., Results: We analyzed 336 Hirschsprung patients, 15.8% of whom were familial cases and 84.2% were non-familial cases. After adjusting for aganglionic length, sex, and age, patients with familial Hirschsprung's disease were twice more likely to suffer from constipation (OR = 2.47, 95% CI, 1.21-5.05, p = 0.013). The quality of life of the pediatric patients was comparable, but in adult patients the energy/fatigue, thinking/learning/concentration, and work capacity facets showed better scores in the familial patients with Hirschsprung's disease of the rectosigmoid ( p = 0.029, p = 0.024, p = 0.036, respectively)., Conclusions: Different facets of generic quality of life are better in adult patients with familial Hirschsprung's disease of the rectosigmoid. It seems that familial experience with the disease influences patients' coping abilities positively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Verkuijl, Meinds, van der Steeg, Sloots, van Heurn, de Blaauw, van Gemert, Witvliet, Vermeulen, Trzpis and Broens.)

Objectives: Knowledge on long-term outcomes in patients with Hirschsprung disease is progressing. Nevertheless, differences in outcomes according to aganglionic lengths are unclear. We compared long-term bowel function and generic quality of life in Hirschsprung patients with total colonic or long-segment versus rectosigmoid aganglionosis., Methods: In this nationwide, cross-sectional study participants with proven Hirschsprung disease received the Defecation and Fecal Continence questionnaire, and the Child Health Questionnaire Child Form-87, or the WHO Quality of Life-100. We excluded deceased patients, patients who were younger than 8 years, lived abroad, had a permanent enterostomy, or were intellectually impaired., Results: The study population (n = 334) was operated for rectosigmoid (83.9%), long-segment (8.7%), or total colonic aganglionosis (7.5%). Fecal incontinence in general was not significantly different between the three groups, but liquid fecal incontinence was significantly associated with total colonic aganglionosis (odds ratio [OR] = 6.00, 95% confidence interval [CI] 2.07-17.38, P = 0.001). Regarding constipation, patients with total colonic or long-segment aganglionosis were less likely to suffer from constipation than the rectosigmoid group (OR = 0.21, 95% CI, 0.05-0.91, P = 0.038 and OR = 0.11, 95% CI, 0.01-0.83, P = 0.032). Quality of life was comparable between the three groups, except for a lower physical score in children with total colonic aganglionosis (P = 0.016)., Conclusions: Over time Hirschsprung patients with total colonic or long-segment aganglionosis do not suffer from worse fecal incontinence in general. A difference in stool consistency may underlie the association between liquid fecal incontinence and total colonic aganglionosis and constipation in patients with rectosigmoid aganglionosis. Despite these differences, generic quality of life is comparable on reaching adulthood., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to 'missing heritability' in developmental defects.

Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. This study included three groups of patients, two groups without coding variants in disease associated genes: HSCR-AAM and HSCR patients without associated anomalies (HSCR-isolated). The third group consisted of all HSCR patients in which a confirmed pathogenic rare coding variant was identified. We compared these patient groups to unaffected controls. Predisposing haplotypes were determined, confirming that every HSCR subgroup had increased contributions of predisposing haplotypes, but their contribution was highest in isolated HSCR patients without RET coding variants. CNV profiling proved that specifically HSCR-AAM patients had larger Copy Number (CN) losses. Gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics were used to determine plausible candidate genes located within CN losses. Validation in zebrafish using CRISPR/Cas9 targeting confirmed the contribution of UFD1L, TBX2, SLC8A1, and MAPK8 to ENS development. In addition, we revealed epistasis between reduced Ret and Gnl1 expression and between reduced Ret and Tubb5 expression in vivo. Rare large CN losses-often de novo-contribute to HSCR in HSCR-AAM patients. We proved the involvement of six genes in enteric nervous system development and Hirschsprung disease., Competing Interests: The authors have declared that no competing interests exist.

Constipation and fecal incontinence are common problems in children after repair of an anorectal malformation (ARM). While many children can be effectively managed with an oral laxative regimen, others require a mechanical colonic washout to achieve social continence. Appendicostomy and cecostomy are two techniques which permit antegrade access to the colon for the purpose of enema delivery, which improves compliance and quality of life for patients and families. The purpose of this article is to review, using a case-based approach, the indications for placement of a channel for antegrade enema access, clinical scenarios in which one technique would be preferred over another, common complications following each procedure., (Copyright © 2020. Published by Elsevier Inc.)

Background: The VACTERL association (VACTERL) includes at least three of these congenital anomalies: vertebral, anal, cardiac, trachea-esophageal, renal, and limb anomalies. Assisted reproductive techniques (ART), pregestational diabetes mellitus, and chronic lower obstructive pulmonary disorders (CLOPD) have been associated with VACTERL. We aimed to replicate these findings and were interested in additional maternal risk factors., Methods: A case-control study using self-administered questionnaires was performed including 142 VACTERL cases and 2,135 population-based healthy controls. Multivariable logistic regression analyses were performed to estimate confounder adjusted odds ratios (aOR) and 95% confidence intervals (95%CI)., Results: Parents who used invasive ART had an increased risk of VACTERL in offspring (aOR 4.4 [95%CI 2.1-8.8]), whereas the increased risk for mothers with CLOPD could not be replicated. None of the case mothers had pregestational diabetes mellitus. Primiparity (1.5 [1.1-2.1]) and maternal pregestational overweight and obesity (1.8 [1.2-2.8] and 1.8 [1.0-3.4]) were associated with VACTERL. Consistent folic acid supplement use during the advised periconceptional period may reduce the risk of VACTERL (0.5 [0.3-1.0]). Maternal smoking resulted in an almost twofold increased risk of VACTERL., Conclusion: We identified invasive ART, primiparity, pregestational overweight and obesity, lack of folic acid supplement use, and smoking as risk factors for VACTERL., (© 2020 The Authors. Birth Defects Research published by Wiley Periodicals LLC.)

Aim: Male patients with anorectal malformations (ARM) are classified according to presence and level of the recto-urinary fistula. This is traditionally established by a preoperative high-pressure distal colostogram that may be variably interpreted by different surgeons. The aim of this study was to evaluate the inter- and intraobserver variation in the assessment by pediatric surgeons of preoperative colostograms with respect to the level of the recto-urinary fistula. Materials and Methods: Sixteen pediatric surgeons from 14 European centers belonging to the ARM-Net Consortium twice scored 130 images of distal colostograms taken in sagittal projection at a median age of 66 days of life (range: 4-1,106 days). Surgeons were asked to classify the fistula in bulbar, prostatic, bladder-neck, no fistula, and "unclear anatomy" example. Their assessments were compared with the intraoperative findings (kappa) for two scoring rounds with an interval of 6 months (intraobserver variation). Agreement among the surgeons' scores (interobserver variation) was also calculated using Krippendorff's alpha. A kappa over 0.75 is considered excellent, between 0.40 and 0.75 fair to good, and below 0.40 poor. Surgeons were asked to score the images in "poor" and "good" quality and to provide their years of experience in ARM treatment. Results: Agreement between the image-based rating of surgeons and the intraoperative findings ranges from 0.06 to 0.45 (mean 0.31). Interobserver variation is higher (Krippendorff's alpha between 0.40 and 0.45). Years of experience in ARM treatment does not seem to influence the scoring. The mean intraobserver variation between the two rounds is 0.64. Overall, the quality of the images is considered poor. Images categorized as having a good quality result in a statistically significant higher kappa (mean: 0.36 and 0.37 in the first and second round, respectively) than in the group of bad-quality images (mean: 0.25 and 0.23, respectively). Conclusions: There is poor agreement among experienced pediatric colorectal surgeons on preoperative colostograms. Techniques and analyses of images need to be improved in order to generate a homogeneous series of patients and make comparison of outcomes reliable., (Copyright © 2020 Midrio, van Rooij, Brisighelli, Garcia, Fanjul, Broens, Iacobelli, Giné, Lisi, Sloots, Fascetti Leon, Morandi, van der Steeg, Giuliani, Grasshoff-Derr, Lacher, de Blaauw and Jenetzky.)

Ileocolic intussusception is the invagination of ileum into the colon. In a subset of patients, the disease is caused by mesenteric lymphadenopathy in response to (viral) infection. We present a case of an ileocolic intussusception necessitating surgery in a 7-month-old immunocompetent infant with concurrent primary wild-type varicella-zoster virus (VZV) infection, in whom chickenpox rash developed 2 days after surgery. Detailed in situ analyses of resected intestine for specific cell type markers and VZV RNA demonstrated VZV-infected lymphocytes and neurons in the gut wall and in ganglion cells of the myenteric plexus., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management., Aims: This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders., Methods: Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted., Results: Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion., Conclusion: In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.

Background: The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods: Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL ( n = 211), ARM ( n = 204), and EA/TEF ( n = 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results: In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified in SALL1, SALL4 , and MID1 , genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions: None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families., (Copyright © 2020 van de Putte, Dworschak, Brosens, Reutter, Marcelis, Acuna-Hidalgo, Kurtas, Steehouwer, Dunwoodie, Schmiedeke, Märzheuser, Schwarzer, Brooks, de Klein, Sloots, Tibboel, Brisighelli, Morandi, Bedeschi, Bates, Levitt, Peña, de Blaauw, Roeleveld, Brunner, van Rooij and Hoischen.)

Background: The most frequent complication after esophageal atresia repair remains anastomotic stricture formation. The initial treatment is endoscopic dilatation. Intralesional steroid injection (ISI) might be an effective adjuvant treatment in case of recurrent strictures. In this series we present our initial experience with this intervention., Methods: Data on primary surgery, stricture treatment, postoperative complications, outcome and growth were retrospectively collected from electronic patient records. Findings were analyzed by descriptive statistics and mixed model analysis., Results: Between 2014 and 2017, ISI was performed for severe recurrent anastomotic strictures in six patients (median age at injection 12.4 (2.1-34.7) months) after a median of 6 (2-20) dilatations. In five patients ISI was successful and the stenosis was cleared. No postoperative complications were reported, especially none related to acute adrenal suppression. Comparing the year before with the year after ISI, a significant positive change for weight (r = 0.70, p = 0.003) was calculated versus a negative change for height (r = -0.87, p = 0.003)., Conclusions: We found ISI to be an effective adjuvant treatment to recurrent anastomotic stricture dilatation after esophageal atresia repair, without postoperative complications or symptoms of adrenal suppression. It remains important, however, to monitor growth effects. Further evaluation is required in a large prospective study., Type of Study: Treatment study, Level IV (case series)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Congenital perineal lesions are rare and can occur along with other birth defects such as anorectal malformations (ARMs) and urogenital anomalies. A colorectal hamartoma associated with a urogenital anomaly without ARM is extremely rare. We recently treated a newborn with posterior hypospadias and a solid perineal mass diagnosed as a colorectal hamartoma., Competing Interests: Conflict of Interest None.

Background:  In 2011, we implemented a new video-based system for quality control of laparoscopic pyloromyotomy. More than 3 years later, we evaluated how the implementation had gone and assessed its usability in predicting postoperative outcomes., Materials and Methods:  Four key point images or short video-segments were to be recorded perioperatively: prepyloromyotomy, parallel-mobility testing, perforation testing, and postpyloromyotomy. Data of all 134 patients undergoing laparoscopic pyloromyotomy from September 2011 to December 2014 were analyzed retrospectively. Five pediatric surgeons independently assessed the anonymized operative images for predicting reoperation and time to full-enteral feeding., Results:  The percentage of operations during which images were recorded increased from 45% in 2012 to 75% in 2014. Over the study period, one or more images were recorded in 89 of the 134 (66%) patients. In only 17 of 89 patients (19%), all four images were documented. The key point images or videos were made for prepyloromyotomy in 49%, parallel-mobility testing in 85%, perforation testing in 42%, and postpyloromyotomy in 94% of 89 patients. Five patients (3.7%) were reoperated for incomplete pyloromyotomy ( N  = 4) or mucosal perforation ( N  = 1). Images were recorded during the first operation in four of the five reoperated patients. The need of reoperation was correctly predicted for two of the four patients. Full-enteral feeding within 24 hours was correctly predicted for 67% of the patients (range: 47-88%)., Conclusion:  The increase in recorded images over the years is promising. The implementation of the quality control system did not contribute to a significant decrease in the complication rate, which was already very low. Still, reoperation or a protracted postoperative course could only be predicted with moderate accuracy from the operative images, therefore, for now the use of perioperative images in a medicolegal setting should be advised against. Improved compliance with image recording and better instructions for evaluating the images might improve the usefulness of perioperative images in, e.g., telementoring, education, and medicolegal practice., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: The impact of perioperative care interventions on postreconstructive complications and short-term colorectal outcome in patients with anorectal malformation (ARM) type rectovestibular fistula is unknown., Methods: An ARM-Net consortium multicenter retrospective cohort study was performed including 165 patients with a rectovestibular fistula. Patient characteristics, perioperative care interventions, timing of reconstruction, postreconstructive complications and the colorectal outcome at one year of follow-up were registered., Results: Overall complications were seen in 26.8% of the patients, of which 41% were regarded major. Differences in presence of enterostomy, timing of reconstruction, mechanical bowel preparation, antibiotic prophylaxis and postoperative feeding regimen had no impact on the occurrence of overall complications. However, mechanical bowel preparation, antibiotic prophylaxis ≥48 h and postoperative nil by mouth showed a significant reduction in major complications. The lowest rate of major complications was found in the group having these three interventions combined (5.9%). Multivariate analyses did not show independent significant results of any of the perioperative care interventions owing to center-specific combinations. At one year follow-up, half of the patients experienced constipation and this was significantly higher among those with preoperative mechanical bowel preparation., Conclusions: Differences in perioperative care interventions do not seem to impact the incidence of overall complications in a large cohort of European rectovestibular fistula-patients. Mechanical bowel preparation, antibiotic prophylaxis ≥48 h, and postoperative nil by mouth showed the least major complications. Independency could not be established owing to center-specific combinations of interventions., Type of Study: Treatment study., Level of Evidence: III., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Anorectal malformations (ARM) are rare congenital malformations, resulting from disturbed hindgut development. A genetic etiology has been suggested, but evidence for the involvement of specific genes is scarce. We evaluated the contribution of rare and low-frequency coding variants in ARM etiology, assuming a multifactorial model., Methods: We analyzed 568 Caucasian ARM patients and 1,860 population-based controls using the Illumina HumanExome Beadchip array, which contains >240,000 rare and low-frequency coding variants. GenomeStudio clustering and calling was followed by re-calling of 'no-calls' using zCall for patients and controls simultaneously. Single variant and gene-based analyses were performed to identify statistically significant associations, applying Bonferroni correction. Following an extra quality control step, candidate variants were selected for validation using Sanger sequencing., Results: When we applied a MAF of ≥1.0%, no variants or genes showed statistically significant associations with ARM. Using a MAF cut-off at 0.4%, 13 variants initially reached statistical significance, but had to be discarded upon further inspection: ten variants represented calling errors of the software, while the minor alleles of the remaining three variants were not confirmed by Sanger sequencing., Conclusion: Our results show that rare and low-frequency coding variants with large effect sizes, present on the exome chip do not contribute to ARM etiology., Competing Interests: The authors have declared that no competing interests exist.

Background: Postoperatively, young infants are admitted overnight in view of the risk for respiratory complications such as desaturation and apnea. This risk seems much lower than previously reported. Until what age this risk persists, and which infants might actually qualify for day-care treatment, is unknown., Methods: We retrospectively reviewed medical charts from preterm infants <45 weeks postconceptional age (PCA), 45-60 weeks PCA, and term infants <3 months admitted overnight after inguinal hernia repair, from January 2011 to December 2015 in a large tertiary children's hospital. Postoperative complications (divided into respiratory, circulatory, neurologic, and other), recurrence, and reoperation were documented and compared between groups., Results: Medical charts of 485 patients were reviewed. Postoperative respiratory complications (mainly desaturations or apnea) had been documented for 27 of 76 (35.5%) preterm infants <45 weeks PCA, for 13 of 221 (5.9%) preterm infants 45-60 weeks PCA, and for 3 of 188 (1.6%) term infants (P < .001). An analysis of the 221 preterm infants 45-60 weeks PCA showed statistically significantly more respiratory complications in 76 infants with a respiratory history (eg, bronchopulmonary dysplasia) compared with the others (respectively 13.2% vs 0.7%; P < .001). In these infants, lower gestational age at the time of surgery was statistically significantly predictive for the development of respiratory complications (odds ratio [OR], 0.68 [95% confidence interval {CI}, 0.52-0.89]; P = .005), but respiratory history (OR, 3.50 [0.34-36.28]; P = .294) and American Society of Anesthesiologists (ASA) physical status (OR, 1.54 [95% CI, 0.31-7.65]; P = .598 for ASA physical status II and OR, 6.11 [95% CI, 0.76-49.05]; P = .089 for ASA physical status III) were not predictive., Conclusions: Incidence of postoperative respiratory complications is high in preterm infants <45 weeks PCA requiring postoperative overnight saturation and heart rate monitoring. Incidence of postoperative complications in preterm born infants 45-60 weeks PCA varies. Gestational age and possibly presence of respiratory history can be used to estimate the need for overnight admission in these infants. Postoperative respiratory complications after inguinal hernia repair in ASA physical status I and II term born infants >1 month of age are uncommon, which justifies day-care admission for this type of surgical procedure.

Background: It is unclear whether functional outcomes improve or deteriorate with age following surgery for Hirschsprung's disease. The aim of this cross-sectional study was to determine the long-term functional outcomes and quality of life (QoL) in patients with Hirschsprung's disease., Methods: Patients with pathologically proven Hirschsprung's disease older than 7 years were included. Patients with a permanent stoma or intellectual disability were excluded. Functional outcomes were assessed according to the Rome IV criteria using the Defaecation and Faecal Continence questionnaire. QoL was assessed by means of the Child Health Questionnaire Child Form 87 or World Health Organization Quality of Life questionnaire 100. Reference data from healthy controls were available for comparison., Results: Of 619 patients invited, 346 (55·9 per cent) responded, with a median age of 18 (range 8-45) years. The prevalence of constipation was comparable in paediatric and adult patients (both 22·0 per cent), and in patients and controls. Compared with controls, adults with Hirschsprung's disease significantly more often experienced straining (50·3 versus 36·1 per cent; P = 0·011) and incomplete evacuation (47·4 versus 27·2 per cent; P < 0·001). The prevalence of faecal incontinence, most commonly soiling, was lower in adults than children with Hirschsprung's disease (16·8 versus 37·6 per cent; P < 0·001), but remained higher than in controls (16·8 versus 6·1 per cent; P = 0·003). Patients with poor functional outcomes scored significantly lower in several QoL domains., Conclusion: This study has shown that functional outcomes are better in adults than children, but symptoms of constipation and soiling persist in a substantial group of adults with Hirschsprung's disease. The persistence of defaecation problems is an indication that continuous care is necessary in this specific group of patients., (© 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Background: Chronic respiratory diseases and use of antiasthmatic medication during pregnancy may both play a role in the etiology of congenital anorectal malformations (ARM). However, it is unclear, whether the medication use or the underlying condition would be responsible. Therefore, our aim was to unravel the role of maternal chronic respiratory diseases from that of antiasthmatic medication in the etiology of ARM., Methods: We obtained 412 ARM patients and 2,137 population-based controls from the Dutch AGORA data- and biobank. We used maternal questionnaires and follow-up telephone interviews to obtain information on chronic respiratory diseases, antiasthmatic medication use, and potential confounders. Multivariable logistic regression analyses were performed to estimate odds ratios (ORs) with 95% confidence intervals (95% CI)., Results: We observed higher risk estimates among women with chronic respiratory diseases with and without medication use (1.4 [0.8-2.7] and 2.0 [0.8-5.0]), both in comparison to women without a chronic respiratory disease and without medication use. Furthermore, increased ORs of ARM were found for women using rescue medication (2.4 [0.8-7.3]) or a combination of maintenance and rescue medication (2.5 [0.9-6.7]). In addition, increased risk estimates were observed for women having nonallergic triggers (2.5 [1.0-6.3]) or experiencing exacerbations during the periconceptional period (3.5 [1.4-8.6])., Conclusions: Although the 95% CIs of most associations include the null value, the risk estimates all point towards an association between uncontrolled chronic respiratory disease, instead of antiasthmatic medication use, with ARM in offspring. Further in-depth studies towards mechanisms of this newly identified risk factor are warranted., (© 2018 The Authors. Birth Defects Research published by Wiley Periodicals, Inc.)

Objective: To investigate the origin and outcome in a cohort of male and female fetuses with intra-abdominal cysts, in order to provide recommendations on management and to improve prenatal counselling., Methods: From 2002 to 2016, intra-abdominal cysts were detected by ultrasound in 158 fetuses. Cases with an umbilical vein varix were excluded. Fetal, neonatal, and maternal characteristics were retrieved from electronic patient files., Results: In female fetuses (n = 114), intra-abdominal cysts were diagnosed at a later gestational age compared with male fetuses (n = 44) (median 32.0 vs. 21.5 weeks, p < 0.001). The maximum prenatal cyst diameter was larger in female fetuses (median 35 vs. 17 mm, p < 0.001). Associated anomalies were less frequent in females (n = 15, 13.2%) compared with males (n = 15, 34.1%). In females (n = 114), most cysts were of ovarian origin (n = 81, 71.1%). Surgery was performed in 30 (26.3%) female and 15 (34.1%) male neonates (p = 0.33). Anorectal malformations were present in 6 cases and often not recognized prenatally., Conclusions: The differences in the origin of intra-abdominal cysts between male and female fetuses, resulting in differences in prenatal presentation and postnatal outcome should be taken into account in prenatal counseling within a multidisciplinary team. Evaluation of the fetal perianal muscular complex is indicated., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Aim: Total colonic aganglionosis (TCA) is a severe form of Hirschsprung's disease (HD) associated with a high morbidity. This study assessed long-term functional outcome and quality of life (QoL) of patients with TCA in a national consecutive cohort., Methods: Surgical and demographic characteristics in the medical records of all patients (n = 53) diagnosed with TCA between 1995 and 2015 were reviewed. Functional outcome of all nonsyndromal patients, aged ≥ 4 years (n = 35), was assessed using a questionnaire and in medical records. Generic and disease-specific QoL were assessed using standardized validated questionnaires., Results: Of 35 patients eligible for follow-up, 18 (51%) responded to the questionnaires. They were aged 4-19 years. A Duhamel procedure was performed in 67% of these patients and a Rehbein procedure was performed in 33%. In the questionnaire, 65% of the patients reported constipation, 47% faecal incontinence and 53% soiling. Moreover, 18% of patients used bowel management (flushing or laxatives) and 29% had an adapted diet only. Children and adolescents with TCA had worse perception of their general health and were more limited by bodily pain and discomfort compared with healthy peers. Their quality of life is influenced most by frequent complaints of diarrhoea and other physical symptoms., Conclusion: Children and adolescents with TCA report lower health-related QoL compared with healthy peers, especially in the physical domain. We suggest standardized follow-up and prospective longitudinal future research on functionality and QoL of these patients., (Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.)

Introduction: A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in childhood., Methods: All pediatric patients who underwent a surgical procedure for type I-IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (<30 days) and long-term (>30 days) complications were studied retrospectively., Results: Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0-17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up., Conclusion: Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery.

Introduction: Improving health-related quality of life (HRQoL) is increasingly recognized as an essential part of patient care outcome. Little is known about the effect of laparoscopic antireflux surgery (LARS) on the HRQoL in the pediatric patients. The aims of this study were to evaluate the effect of LARS on HRQoL in children with gastroesophageal reflux disease (GERD) and to identify predictors that influence HRQoL outcome after LARS., Methods: Between 2011 and 2013, 25 patients with therapy-resistant GERD [median age 6 (2-18) years] were included prospectively. Caregivers and children with normal neurodevelopment (>4 years) were asked to fill out the validated PedsQL 4.0 Generic Core Scales before and 3-4 months after LARS., Results: The PedsQL was completed by all caregivers (n = 25) and 12 children. HRQoL total score improved significantly after LARS, both from a parental (p = 0.009) and child's perspective (p = 0.018). The psychosocial health summary and physical health summary scores also improved significantly after LARS. HRQoL before and after LARS was significantly lower in children with impaired neurodevelopment (p < 0.001). However, neurodevelopment did not influence the effect of LARS on HRQoL. The only significant predictor for improvement in HRQoL after LARS was age at the time of operation (p = 0.001)., Conclusions: HRQoL significantly improves after LARS. Although children with impaired neurodevelopment had lower overall HRQoL, neurodevelopment by itself does not predict inferior improvement in HRQoL after LARS. Older children have a more favorable HRQoL outcome after LARS compared to younger children. This may suggest caution when considering LARS in younger GERD patients.

Introduction: Choledochal malformations (CMs) are increasingly diagnosed antenatally. There is a dilemma between early surgery to prevent CM-related symptoms and postponing surgery to reduce complications. We aimed to identify the optimal timing of surgery in asymptomatic neonates with antenatally diagnosed CM and to identify predictors for development of symptoms., Methods: Using the Netherlands Study group on CHoledochal Cyst/malformation (NeSCHoc) we retrospectively collected demographic, biochemical and surgical data from all Dutch patients with an antenatally detected CM., Results: Between 1989 and 2014, antenatally suspected CM was confirmed in 17 patients at a median age of 10days (1day-2months). Four patients developed symptoms directly after birth (24%). Thirteen patients (76%) remained asymptomatic. Two of these progressed to symptoms before surgical intervention at 0.7 and 2.1months resp. Postoperatively, four patients developed short-term complications and three developed long-term complications. Patients <5.6kg (the series median) showed more short-term complications (66%) when compared to patients >5.6kg (0%, p=0.02)., Conclusion: When not symptomatic within the first days of life, the majority of children with antenatally detected CM remains asymptomatic. Surgery might safely be delayed to the age of 6months or a weight of 6kg. Postponing surgery in the clinically and biochemical asymptomatic patient might decrease the complication rate., Levels of Evidence: Level III., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Esophageal intraluminal baseline impedance reflects the conductivity of the esophageal mucosa and may be an instrument for in vivo evaluation of mucosal integrity in children with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pump inhibitory (PPI) therapy resistant GERD. The effect of LARS in children on baseline impedance has not been studied in detail. The aim of this study was to evaluate the effect of LARS on baseline impedance in children with GERD., Methods: This is a prospective, multicenter, nationwide cohort study (Dutch national trial registry: NTR2934) including 25 patients [12 males, median age 6 (range 2-18) years] with PPI-resistant GERD scheduled to undergo LARS. Twenty-four hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after LARS. Baseline impedance was evaluated during consecutive 2-h intervals in the 24-h tracings., Results: LARS reduced acid exposure time from 8.5 % (6.0-16.2 %) to 0.8 % (0.2-2.8 %), p < 0.001. Distal baseline impedance increased after LARS from 2445 Ω (1147-3277 Ω) to 3792 Ω (3087-4700 Ω), p < 0.001. Preoperative baseline impedance strongly correlated with acid exposure time (r -0.76, p < 0.001); however, no association between symptomatic outcome and baseline impedance was identified., Conclusions: LARS significantly increased baseline impedance likely reflecting recovery of mucosal integrity. As the change in baseline impedance was not associated with the clinical outcome of LARS, other factors besides mucosal integrity may contribute to symptom perception in children with GERD.

Introduction: Laparoscopic antireflux surgery (LARS) in children primarily aims to decrease reflux events and reduce reflux symptoms in children with therapy-resistant gastroesophageal reflux disease (GERD). The aim was to objectively assess the effect and efficacy of LARS in pediatric GERD patients and to identify parameters associated with failure of LARS., Methods: Twenty-five children with GERD [12 males, median age 6 (2-18) years] were included prospectively. Reflux-specific questionnaires, stationary manometry, 24-h multichannel intraluminal impedance pH monitoring (MII-pH monitoring) and a 13 C-labeled Na-octanoate breath test were used for clinical assessment before and 3 months after LARS., Results: After LARS, three of 25 patients had persisting/recurrent reflux symptoms (one also had persistent pathological acid exposure on MII-pH monitoring). New-onset dysphagia was present in three patients after LARS. Total acid exposure time (AET) (8.5-0.8 %; p < 0.0001) and total number of reflux episodes (p < 0.001) significantly decreased and lower esophageal sphincter (LES) resting pressure significantly increased (10-24 mmHg, p < 0.0001) after LARS. LES relaxation, peristaltic contractions and gastric emptying time did not change. The total number of reflux episodes on MII-pH monitoring before LARS was a significant predictor for the effect of the procedure on reflux reduction (p < 0.0001)., Conclusions: In children with therapy-resistant GERD, LARS significantly reduces reflux symptoms, total acid exposure time (AET) and number of acidic as well as weakly acidic reflux episodes. LES resting pressure increases after LARS, but esophageal function and gastric emptying are not affected. LARS showed better reflux reduction in children with a higher number of reflux episodes on preoperative MII-pH monitoring.