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Background: Adults with esophageal atresia (EA) require a multidisciplinary follow-up approach, taking into account gastroesophageal problems, respiratory problems and psychosocial wellbeing. Too little is known about the full scope of these individuals’ healthcare needs. We aimed to map all medical and psychosocial needs of adults with EA and their family members, and to formulate healthcare recommendations for daily practice. Methods: A qualitative study was performed, using data from recorded semi-structured interviews with two focus groups, one consisting of adult patients with EA (n = 15) and one of their family members (n = 13). After verbatim transcription and computerized thematic analysis, results were organized according to the International Classification of Functioning, Disability and Health. Ethical approval had been obtained. Results: Healthcare needs were described through 74 codes, classified into 20 themes. Most important findings for patients included the impact of gastrointestinal and pulmonary problems on daily life, long-term emotional distress of patients and parents and the need of a standardized multidisciplinary follow-up program during both child- and adulthood. Conclusion: The focus groups revealed numerous physical and mental health problems, as well as social difficulties, that require attention from different healthcare providers. We have formulated several healthcare recommendations that physicians may use in long-term follow-up.

Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are relatively frequently occurring foregut malformations. EA/TEF is thought to have a strong genetic component. Not much is known regarding the biological processes disturbed or which cell type is affected in patients. This hampers the detection of the responsible culprits (genetic or environmental) for the origin of these congenital anatomical malformations. Therefore, we examined gene expression patterns in the TEF and compared them to the patterns in esophageal, tracheal and lung control samples. We studied tissue organization and key proteins using immunohistochemistry. There were clear differences between TEF and control samples. Based on the number of differentially expressed genes as well as histological characteristics, TEFs were most similar to normal esophagus. The BMP-signaling pathway, actin cytoskeleton and extracellular matrix pathways are downregulated in TEF. Genes involved in smooth muscle contraction are overexpressed in TEF compared to esophagus as well as trachea. These enriched pathways indicate myofibroblast activated fibrosis. TEF represents a specific tissue type with large contributions of intestinal smooth muscle cells and neurons. All major cell types present in esophagus are present-albeit often structurally disorganized-in TEF, indicating that it

Introduction: To date, no consensus has been reached on the optimal management of congenital lung abnorm

The potential for malignant degeneration is the most common reason for some practitioners to resect asymptomatic congenital pulmonary airway malformations (CPAMs). We aimed to investigate the potential of various immunohistochemical (IHC) and genomic biomarkers to predict the presence of mucinous proliferations (MPs) in CPAM. Archival CPAM tissue samples were re-assessed and underwent IHC analysis using a panel of differentiating markers (TTF1/CDX2/CC10/MUC2/MUC5AC/p16/p53/DICER1). In each sample, intensity of IHC staining was assessed separately in normal lung tissue, CPAM, and MP tissue, using a semiquantitative approach. Likewise, next-generation targeted sequencing of known adult lung driver mutations, including KRAS/BRAF/EGFR/ERBB2, was performed in all samples with MP and in control samples of CPAM tissue without MP. We analyzed samples of 25 CPAM type 1 and 25 CPAM type 2 and found MPs in 11 samples. They were all characterized by strong MUC5AC expression, and all carried a KRAS mutation in the MP and adjacent nonmucinous CPAM tissue, whereas the surrounding normal lung tissue was negative. By contrast, in less than half (5 out of 12) control samples lacking MP, the CPAM tissue also carried a KRAS mutation. KRAS mutations in nonmucinous CPAM tissue may identify lesions with a potential for malignant degeneration and may guide histopathological assessment and patient follow-up.

Background: Endoscopic dilatation is the first-line treatment of stricture formation after esophageal atresia (EA) repair. However, there is no consensus on how to perform these dilatation procedures which may lead to a large variation between centers, countries and doctor’s experience. This is the first cross-sectional study to provide an overview on differences in endoscopic dilatation treatment of pediatric anastomotic strictures worldwide. Methods: An online questionnaire was sent to members of five pediatric medical networks, experienced in treating anastomotic strictures in children with EA. The main outcome was the difference in endoscopic dilatation procedures in various centers worldwide, including technical details, dilatation approach (routine or only in symptomatic patients), and adjuvant treatment options. Descriptive statistics were performed with SPSS. Results: Responses from 115 centers from 32 countries worldwide were analyzed. The preferred approach was balloon dilatation (68%) with a guidewire (66%), performed by a pediatric gastroenterologist (n = 103) or pediatric surgeon (n = 48) in symptomatic patients (68%). In most centers, hydrostatic pressure was used for balloon dilatation. The insufflation duration was standardized in 59 centers with a median duration of 60 (range 5–300) seconds. The preferred first-line adjunctive treatments in case of recurrent strictures were intralesional steroids and topical mitomycin C, in respectively 47% and 31% of the centers. Conclusions: We found a large variation in stricture management in children with EA, which confirms the current lack of consensus. International networks for rare diseases are required for harmonizing and comparing the procedures, for which we give several suggestions.

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. Results: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). Conclusions: This large

INTRODUCTION: Pectus excavatum repair is associated with substantial postoperative pain, despite the use of epidural analgesia and other analgesic regimens. Perioperative recorded music interventions have been shown to alleviate pain and anxiety in adults, but evidence for children and adolescents is still lacking. This study protocol describes a randomised controlled trial that evaluates the effects of recorded music interventions on postoperative pain relief in children and adolescents after pectus excavatum repair. METHODS: A multicentre randomised controlled trial was set

In children, intense levels of anxiety during anesthetic induction are associated with a higher risk of pain, poor recovery, and emergence delirium. Therefore, it is important to identify these high-risk children at hospital arrival. The current study examined internalizing behavior (Child Behavior Checklist, CBCL) and state anxiety measures (modified Yale Preoperative Anxiety Scale, mYPAS, and State Trait Anxiety Inventory for Children, STAIC) at hospital arrival as predictors of anxiety during induction of anesthesia. One hundred children (aged 4 to 12 years) undergoing elective daycare surgery were included. The STAIC and mYPAS at hospital arrival were significant predictors of anxiety during induction, whereas CBCL was not. The STAIC state form at hospital arrival was the strongest predictor and could be used to identify children who will experience intense levels of anxiety during anesthetic induction, with sufficient to good diagnostic accuracy. Using the STAIC at hospital arrival allows targeted interventions to reduce anxiety in children.

Background: Patients born with esophageal atresia (EA) have a higher incidence of infantile hypertrophic pyloric stenosis (IHPS), suggestive of a relationship. A shared etiology makes sense from a developmental perspective as both affected structures are foregut derived. A genetic component has been described for both conditions as single entities and EA and IHPS are variable components in several monogenetic syndromes. We hypothesized that defects disturbing foregut morphogenesis are responsible for this combination of malformations. Methods: We investigated the genetic variation of 15 patients with both EA and IHPS with unaffected parents using exome sequencing and SNP array-based genotyping, and compared the results to mouse transcriptome data of the developing foregut. Results: We did not identify putatively deleterious de novo mutations or recessive variants. However, we detected rare inherited variants in EA or IHPS disease genes or in genes important in foregut morphogenesis, expressed at the proper developmental time-points. Two pathways were significantly enriched (p < 1 × 10−5): proliferation and differentiation of smooth muscle cells and self-renewal of satellite cells. Conclusions: None of our findings could fully explain the combination of abnormalities on its own, which makes complex inheritance the most plausible genetic explanation, most likely in combination with mechanical and/or environmental factors. As we did not find one defining monogenetic cause for the EA/IHPS phenotype, the impact of the corrective surgery could should be further investigated.

Congenital diaphragmatic hernia (CDH) is associated with high mortality rates and significant pulmonary morbidity, mainly due to disrupted lung development related to herniation of abdominal organs into the chest. Pulmonary hypertension is a major contributor to both mortality and morbidity, however, treatment modalities are limited. Novel prenatal and postnatal interventions, such as fetal surgery and medical treatments, are currently under investigation. Until now, the perinatal stabilisation period immediately after birth has been relatively overlooked, although optimising support in these early stages may be vital in improving outcomes. Moreover, physiological parameters obtained from the perinatal stabilisation period could serve as early predictors of adverse outcomes, thereby facilitating both prevention and early treatment of these conditions. In this review, we focus on the perinatal stabilisation period by discussing the current delivery room guidelines in infants born with CDH, the

Exercise capacity deteriorates in school-aged children born with major anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. The aim of the present study was to evaluate whether exercise capacity can be improved in the short term and long term in children born with anatomical foregut anomalies and/or treated with extracorporeal membrane oxygenation. Therefore, we evaluated two different interventions in this single-blinded randomized controlled trial. Forty participants were randomly assigned to group A: standardized anaerobic high-intensity interval training plus online lifestyle coaching program, B: online lifestyle coaching program only, or C: standard of care. Inclusion criteria were as follows: score ≤−1 standard deviation (SD) on the Bruce protocol. Exercise capacity was assessed at baseline (T0), after 3 months (T1), and after 12 months (T2). Exercise capacity improved over time: mean (SD) standard deviation score (SDS) endurance time: T0 −1.91 (0.73); T1 −1.35 (0.94); T2 −1.20 (1.03): both P <.001. No significant differences in maximal endurance time were found at T1 (group A-C: estimated mean difference (SDS): 0.06 P =.802; group B-C: −0.17 P =.733) or T2 (group A-C: −0.13 P =.635; group B-C: −0.18 P =.587). Exercise capacity improved significantly over time, irrespective of the study arm. Not only residual morbidities may be responsible for reduced exercise capacity. Parental awareness of reduced exercise capacity rather than specific interventions may have contributed. Monitoring of exercise tolerance and providing counseling on lifestyle factors that improve physical activity should be part of routine care, and aftercare should be offered on an individual basis.

Objective: To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach-bladder distance, using three-dimensional (3D) ultrasound. Methods: This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography-based Automated Volume Count. The shortest stomach-bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach-bladder distance. Results: We included 79 affected fetuses. Sixty-six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach-bladder distance decreased (both P <.001). The developmental changes did not differ significantly between fetuses with simple and complex gastroschisis, neither for fetal stomach volume (P =.85), nor for stomach bladder distance (P =.78). Conclusion: Fetal stomach volume and stomach-bladder distance, measured during pregnancy using 3D ultrasonography, do not predict complex gastroschisis.

BACKGROUND: Medical procedures often evoke pain and anxiety in pediatric patients. Virtual reality (VR) is a relatively new intervention that can be used to provide distraction during, or to prepare patients for, medical procedures. This meta-analysis is the first to collate evidence on the effectiveness of VR on reducing pain and anxiety in pediatric patients undergoing medical procedures. METHODS: On April 25, 2018, we searched EMBASE, MEDLINE, CENTRAL, PubMed, Web of Science, and PsycINFO with the keywords “VR,” “children,” and “adolescents.” Studies that applied VR in a somatic setting with participants ≤21 years of age were included. VR was defined as a fully immersive 3-dimensional environment displayed in surround stereoscopic vision on a head-mounted display (HMD). We evaluated pain and anxiety outcomes during medical procedures in VR and standard care conditions. RESULTS: We identified 2889 citations, of which 17 met our inclusion criteria. VR was applied as distraction (n = 16) during venous access, dental, burn, or oncological care or as exposure (n = 1) before elective surgery under general anesthesia. The effect of VR was mostly studied in patients receiving burn care (n = 6). The overall weighted standardized mean difference (SMD) for VR was 1.30 (95% CI, 0.68–1.91) on patient-reported pain (based on 14 studies) and 1.32 (95% CI, 0.21–2.44) on patient-reported anxiety (based on 7 studies). Th

Objective: To determine the predictive value of the fetal omphalocele circumference/abdominal circumference (OC/AC) ratio for type of surgical closure and survival and to describe the trajectory of OC/AC ratio throughout gestation. Methods: This cohort study included all live-born infants prenatally diagnosed with an omphalocele in our tertiary centre (2000–2017) with an intention to treat. The OC/AC ratio and liver position were determined using 2D ultrasound at three periods during gestation (11–16, 17–26, and/or 30–38 weeks). Primary outcome was type of closure; secondary outcome was survival. In the secondary analyses, the predictive value of the OC/AC-ratio trend for type of closure and survival was assessed. Results: Primary closure was performed in 37/63 (59%) infants, and 54/63 (86%) survived. The OC/AC ratio was predictive for type of closure and survival in all periods. Optimal cut-off values for predicting closure decreased throughout gestation from 0.69 (11–16 weeks) to 0.63 (30–38 weeks). Repeated OC/AC-ratio measurements were available in 33 (73%) fetuses. The trend of the OC/AC ratio throughout gestation was not significantly associated with type of closure. All infants without liver herniation underwent primary closure. Conclusion: Type of omphalocele surgical closure and survival can be predicted prenatally on the basis of the OC/AC ratio and liver herniation independent of associated anomalies. Learning objective: The reader will be able to use the OC/AC ratio throughout gestation in all omphalocele cases for prediction of type of closure and survival and thus patient counselling.

Objective: Children with congenital diaphragmatic hernia (CDH) suffer from long-term pulmonary morbidity. Longitudinal data of exercise capacity in these children are lacking. We hypothesized that exercise capacity would be impaired in children with CDH and deteriorates over time. We evaluated exercise capacity and its determinants in CDH patients longitudinally until 12 years of age. Design: Prospective longitudinal follow-up study in tertiary university hospital. Patients: One hundred and fourteen children with CDH born between 1999 and 2012. Methods: Exercise capacity was evaluated using the Bruce treadmill-protocol at the ages of 5, 8, and 12 years. Primary outcome parameter was standard deviation score (SDS) of maximal endurance time. Data were analyzed by using linear mixed models. Results:A total of 107 children (30 treated with extracorporeal membrane oxygenation [ECMO]) performed 191 reliable exercise tests. At ages 5, 8, and 12 years, the mean (95%CI) SDS endurance time was −0.44 (−0.65 to −0.24); −1.01 (−1.23 to −0.78); −1.10 (−1.40 to −0.80), respectively, all less than zero (P < 0.001). Exercise capacity declined significantly over time irrespective of ECMO-treatment (5-12 years: non-ECMO P = 0.015; ECMO P = 0.006). Duration of initial hospital stay and diffusion capacity corrected for alveolar volume were associated with SDS endurance time (P < 0.001 and P = 0.039). Conclusions: In CDH patients exercise capacity deteriorates between 5 and 12 years of age, irrespective of ECMO-treatment. CDH patients may benefit from long-term assessments of exercise capacity with timely intervention.

Objective: Children with congenital diaphragmatic hernia (CDH) are at risk for pulmonary morbidity. Data on longitudinal evaluation of lung function in CDH are scarce. We hypothesized that CDH patients would have impaired lung function that worsens over time. We evaluated lung function and its determinants at ages 8 and 12 years. Methods: Dynamic and static lung volumes, and diffusion capacity were measured. Extracorporeal membrane oxygenation (ECMO) treatment, the standardized European neonatal treatment protocol, patch repair, duration of ventilation, type of initial mechanical ventilation, and nitric oxide treatment were entered as covariates in linear mixed models with standard deviation score (SDS) lung function parameters (FEV1, FEF 25-75, and K CO) as dependent variables. Results: Seventy-six children (27 ECMO-treated) born between 1999 and 2009 performed 113 reliable lung function tests. Severity of airflow obstruction deteriorated significantly from age 8 to 12 years: estimated mean difference (95% confidence interval [CI]) SDS FEV1 was −0.57 (−0.79 to −0.36) and SDS FEF25-75 was −0.63 (−0.89 to −0.37), both P <.001. Static lung volumes were within normal range and unchanged over time: estimated mean difference (95% CI) SDS TLC −0.27 (−0.58 to 0.04); P =.085. SDS KCO was below normal at 8 and 12 years and remained stable: −0.06 (−0.22 to 0.35); P =.648. These observations were irrespective of ECMO treatment. FEV1 and FEF25-75 were negatively associated with duration of ventilation (P <.001). Baseline data were not related with TLC or KCO. Conclusions: CDH patients should be followed into adulthood as they are at risk for worsening airflow obstruction and decreased diffusion capacity at school age, irrespective of ECMO treatment.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare and lethal disorder mainly involving the vascular development of the lungs. Since its first description, significant achievements in research have led to a better understanding of the underlying molecular mechanism of ACD/MPV and genetic studies have identified associations with genomic alterations in the locus of the transcription factor FOXF1. This in turn has increased the awareness among clinicians resulting in over 200 cases reported so far, including genotyping of patients in most recent reports. Collectively, this promoted a better stratification of the patient group, leading to new perspectives in research on the pathogenesis. Here, we provide an overview of the clinical aspects of ACD/MPV, including guidance for clinicians, and review the ongoing research into the complex molecular mechanism causing this severe lung disorder.

Objectives: To compare the prenatal frame of reference of omphalocele (ie, survival of fetuses) with that after birth (ie, survival of liveborn neonates), and to assess physical growth and neurodevelopment in children with minor or giant omphalocele up to 2 years of age. Design: We included fetuses and neonates diagnosed in 2000-2012. Physical growth (SD scores, SDS) and mental and motor development at 12 and 24 months were analysed using general linear models, and outcomes were compared with reference norms. Giant omphalocele was defined as defect ≥5 cm, with liver protruding. Results: We included 145 fetuses and neonates. Of 126 (87%) who were diagnosed prenatally, 50 (40%) were liveborn and 35 (28%) survived at least 2 years. Nineteen (13%) neonates were diagnosed after birth. Of the 69 liveborn neonates, 52 (75%) survived and 42 children (81% of survivors) were followed longitudinally. At 24 months, mean (95% CI) height and weight SDS were significantly below 0 in both minor (height: -'0.57 (-'1.05 to -0.09); weight: -'0.86 (-'1.35 to -0.37)) and giant omphalocele (height: -'1.32 (-'2.10 to -0.54); weight: -'1.58 (-'2.37 to -0.79)). Mental development was comparable with reference norms in both groups. Motor function delay was found significantly more often in children with giant omphalocele (82%) than in those with minor omphalocele (21%, P=0.002). Conclusions: The prenatal and postnatal frames of reference of omphalocele differ considerably; a multidisciplinary approach in parental counselling is recommended. As many children with giant omphalocele had delayed motor development, we recommend close monitoring of these children and early referral to physical therapy.

Sox2 is a Sry-box containing family member of related transcription factors sharing homology in their DNA binding domain. Sox2 is important during different stages of development, and previously we showed that Sox2 plays an important role in branching morphogenesis and epithelial cell differentiation in lung development. The transcriptional activity of Sox2 depends on its interaction with other proteins, leading to ‘complex-specific’ DNA binding and transcriptional regulation. In this study, we generated a mouse model containing a biotinylatable-tag targeted at the translational start site of the endogenous Sox2 gene (bioSox2). This tag was biotinylated by the bacterial birA protein and the resulting bioSox2 protein was used to identify associating partners of Sox2 at different phases of lung development in vivo (the Sox2 interactome). Homozygous bioSox2 mice are viable and fertile irrespective of the biotinylation of the bio tag, indicating that the bioSox2 gene is normally expressed and the protein is functional in all tissues. This suggests that partners of Sox2 are most likely able to associate with the bioSox2 protein. BioSox2 complexes were isolated with high affinity using streptavidin beads and analysed by MALDI-ToF mass spectrometry analysis. Several of the identified binding partners are already shown to have a respiratory phenotype. Two of these partners, Wdr5 and Tcf3, were validated to confirm their association in Sox2 complexes. This bioSox2 mouse model will be a valuable tool for isolating in vivo Sox2 complexes from different tissues.

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung hypoplasia. The relative contribution of these three elements can vary considerably in individual patients. Most affected children suffer primarily from the associated PH, for which the therapeutic modalities are limited and frequently not evidence based. The vascular defects associated with PH, which is characterised by increased muscularisation of arterioles and capillaries, start to develop early in gestation. Pulmonary vascular development is integrated with the development of the airway epithelium. Although our knowledge is still incomplete, the processes involved in the growth and expansion of the vasculature are beginning to be unravelled. It is clear that early disturbances of this process lead to major pulmonary growth abnormalities, resulting in serious clinical challenges and in many cases death in the newborn. Here we provide an overview of the current molecular pathways involved in pulmonary vascular development. Moreover, we describe the abnormalities associated with CDH and the potential therapeutic approaches for this severe abnormality.

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with significant mortality. Objectives: The aim of this study was to determine if there were trends in survival over the last decade and to compare patient populations, treatment options, and survival rates between 4 high-volume centres, and hence determine which factors were associated with survival. Methods: In 4 high-volume CDH centres from the CDH EURO Consortium, data from all CDH patients born between 2004 and 2013 were analysed. The predictive value of variables known at birth and the influence of centre-specific treatments (extracorporeal membrane oxygenation, ECMO, and foetoscopic endotracheal occlusion, FETO) on survival were evaluated in multivariable logistic regression analyses. Results: Nine hundred and seventy-five patients were included in the analysis, of whom 274 (28.1%) died. ECMO was performed in 259 patients, of whom 81 (31.3%) died. One hundred and forty-five patients (14.9%) underwent FETO, and from those 76 patients (52.4%) survived. Survival differed significantly between years (p = 0.006) and between the 4 centres (p < 0.001). In the multivariable logistic regression analysis, lung-to-head ratio, gestational age at birth, ECMO, centre of birth, and year of birth were significantly associated with survival, whereas FETO was not. Conclusions: The patient populations were different between centres, which influenced outcomes. There was a significant variability in survival over time and between centres, which should be taken into consideration in the planning of future trials.

Aim This study aims to define patterns of Hirschsprung disease (HD) management. Methods An online questionnaire was sent to all European Paediatric Surgeons' Association (EUPSA) members. Results A total of 294 members (61 countries) answered (response rate: 61%). Diagnosis: All respondents perform rectal biopsies (61% rectal suction [RSBs], 39% open full-thickness), 96% contrast enema, and 31% anorectal manometry. At RSB, 17% take the most distal biopsy 1 cm above the dentate line, 34% take 2 cm, 30% take 3 cm, and 19% take > 3 cm. Rectal biopsy staining's are hematoxylin/eosin (77%), acetylcholinesterase (74%), calretinin (31%), S100 (2%), nicotinamide adenine dinucleotide-tetrazolium reductase (2%), succinate dehydrogenase (1%), and neuron-specific enolase (1%). A total of 85% respondents recognize entities including hypoganglionosis (69%), intestinal neuronal dysplasia (55%), and ultrashort segment HD (50%). Surgery: Pull-through (PT) is performed at diagnosis by 33% or delayed by 67% (4 months or > 5 kg). Awaiting definitive surgery, 77% perform rectal irrigations, 22% rectal dilatation/stimulations, and 33% perform a stoma. The preferred type of PT is the Soave approach (65%), performed with transanal technique by 70% respondents. If symptoms persist after PT, most opt for conservative approach (enemas/laxatives = 76%; botulinum toxin = 27%), 30% would redo the PT. Total colonic aganglionosis: PT is performed in neonates (4%), at 1 to 6 months (29%), 6 to 12 months (37%) or older (30%). If required, a stoma is sited in the ileum (31%), according to intraoperative biopsies (54%), macroscopic impression (13%), and radiology (2%). Duhamel PT is performed by 52%, Soave by 31%, and Swenson by 17%. Overall, 31% would perform a J-pouch. Conclusions Most aspects of HD management lack consensus with wide variations in obtaining a diagnosis. Transanal Soave PT is the most common technique in standard segment HD. Guidelines should be developed to avoid such variability in

Objective: To assess the predictive value of observed-to-expected lung-to-head ratio (O/E LHR) for surviva

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.

BACKGROUND: Since mortality in congenital diaphragmatic hernia (CDH) is decreasing, morbidity such as neurodevelopmental outcome is becoming increasingly important. OBJECTIVES: We evaluated neurodevelopmental outcome in high-risk CDH patients treated according to the CDH EURO Consortium standardized treatment protocol. METHODS: This observational, prospective cohort study was conducted in two European centers. Neurodevelopment of 88 patients (Rotterdam n = 49; Rome n = 39) was assessed at 12 and 24 months with the Bayley Scales of Infant Development (BSID)-II-NL (Rotterdam) or BSID-III (Rome). Data of the centers were analyzed separately. RESULTS: Cognition was normal in 77.8% of children from Rotterdam and in 94.8% from Rome at 12 months, and in 70.7 and 97.4%, respectively, at 24 months. Motor function was normal in 64.3% from Rotterdam and in 81.6% from Rome at 12 months and in 45.7 and 89.8%, respectively, at 24 months. Longer length of hospital stay (LoS) was associated with worse cognitive outcome and motor function; LoS, low socioeconomic status, and ethnicity were associated with lower cognition. CONCLUSIONS: At 2 years, most CDH patients have normal cognition, but are at risk for motor function delay. Due to differences in outcomes between centers, careful interpretation is needed before conclusions can be drawn for other centers. Future multicenter collaboration should not only focus on standardization of postnatal care, but also on international standardization of follow-up to identify risk factors and thereby reduce morbidity.

Oesophageal atresia (OA) with or without tracheoesophageal fistula (TOF) are rare anatomical congenital malformations whose cause is unknown in over 90% of patients. A genetic background is suggested, and among the reported genetic defects are copy number variations (CNVs). We hypothesized that CNVs contribute to OA/TOF development. Quantifying their prevalence could aid in genetic diagnosis and clinical care strategies. Therefore, we profiled 375 patients in a combined Dutch, American and German cohort via genomic microarray and compared the CNV profiles with their unaffected parents and published control cohorts. We identified 167 rare CNVs containing genes (frequency<0.0005 in our in-house cohort). Eight rare CNVs - in six patients - were de novo, including one CNV previously associated with oesophageal disease. (hg19 chr7:g.(143820444-143839360)-(159119486-159138663)del) 1.55% of isolated OA/TOF patients and 1.62% of patients with additional congenital anomalies had de novo CNVs. Furthermore, three (15q13.3, 16p13.3 and 22q11.2) susceptibility loci were identified based on their overlap with known OA/TOF-associated CNV syndromes and overlap with loci in published CNV association case-control studies in developmental delay. Our study suggests that CNVs contribute to OA/TOF development. In addition to the identified likely deleterious de novo CNVs, we detected 167 rare CNVs. Although not directly disease-causing, these CNVs might be of interest, as they can act as a modifier in a multiple hit model, or as the second hit in a recessive condition.

Evidence on the clinical effectiveness of probiotics in the prevention of necrotising enterocolitis (NEC) in preterm infants is conflicting and cohort studies lacked adjustment for time trend and feeding type. This study investigated the association between the introduction of routine probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum; Infloran ®) on the primary outcome 'NEC or death'. Preterm infants (gestational age <32 weeks or birth weight <1500 gram) admitted before (Jan 2008-Sep 2012; n = 1288) and after (Oct 2012-Dec 2014; n = 673) introduction of probiotics were compared. Interrupted time series logistic regression models were adjusted for confounders, effect modification by feeding type, seasonality and underlying temporal trends. Unadjusted and adjusted analyses showed no difference in 'NEC or death' between the two periods. The overall incidence of NEC declined from 7.8% to 5.1% (OR 0.63, 95% CI 0.42-0.93, p = 0.02), which was not statistically significant in the adjusted models. Introduction of probiotics was associated with a reduced adjusted odds for 'NEC or sepsis or death' in exclusively breastmilk-fed infants (OR 0.43, 95% CI 0.21-0.93, p = 0.03) only. We conclude that introduction of probiotics was not associated with a reduction in 'NEC or death' and that type of feeding seems to modify the effects of probiotics.

Background: Thoracoscopic surgery is an increasingly popular surgical technique to repair congenital diaphragmatic hernia (CDH). However, acidosis during surgery and the higher recurrence rate are considerable risk factors. The aim of this retrospective study is to compare the outcome of open versus thoracoscopic repair of the diaphragm in neonates with CDH with the same degree of cardiovascular and pulmonary illness who meet the criteria for thoracoscopic repair. Methods: Retrospective analysis of all patients of two large national reference centers for CDH born in the years 2008 through 2012, and meeting the criteria for surgical repair on cardiopulmonary and physiological criteria according to the CDH EURO consortium consensus and meeting the criteria for thoracoscopic repair according to the review by Vijfhuize et al. The surgical technical aspects were comparable in both centers. Results: 108 patients were included, of whom 75 underwent thoracoscopic repair and 34 underwent open repair. The gestational age and lung-to-head ratio were significantly lower and stay on the ICU significantly longer in the open-repair group. The operation time was longer (178 vs. 150 min, p = .012) and the recurrence rate higher (18.9 vs. 5.9 %, p = .036) in the thoracoscopic-repair group. The arterial pH, pO2, pCO2 and base excess before and after thoracoscopic repair were all significantly different. Conclusion: After critical selection for thoracoscopic repair of left-sided CDH based on the patient’s preoperative condition, the outcomes of open repair were almost identical to those of thoracoscopic repair. A notable exception is the recurrence rate, which was significantly higher in the thoracoscopic-repair group. For the time being, thoracoscopic primary closure seems a safe and effective procedure, but efficacy of thoracoscopic patch repair has not been established.

_Purpose:_ Inguinal hernia repair is frequently performed in premature infants. Evidence on optimal management and timing of repair, as well as related medical costs is still lacking. The objective of this study was to determine the direct medical costs of inguinal hernia, distinguishing between premature infants who had to undergo an emergency procedure and those who underwent elective inguinal hernia repair. _Methods:_ This cohort study based on medical records concerned premature infants with inguinal hernia who underwent surgical repair within 3 months after birth in a tertiary academic children’s hospital between January 2010 and December 2013. Two groups were distinguished: patients with incarcerated inguinal hernia requiring emergency repair and patients who underwent elective repair. Real medical costs were calculated by multiplying the volumes of healthcare use with corresponding unit prices. Nonparametric bootstrap techniques were used to derive a 95 % confidence interval (CI) for the difference in mean costs. _Results:_ A total of 132 premature infants were included in the analysis. Emergency surgery was performed in 29 %. Costs of hospitalization comprised 65 % of all costs. The total direct medical costs amounted to €7418 per premature infant in the emergency repair group versus €4693 in the elective repair group. Multivariate analysis showed a difference in costs of €1183 (95 % CI −1196; 3044) in favor of elective repair after correction for potential risk factors. _Conclusion:_ Emergency repair of inguinal hernia in premature infants is more expensive than elective repair, even after correction for multiple confounders. This deserves to be

Esophageal atresia (EA) is a rare congenital anomaly. Enhanced operative techniques and intensive care treatment have improved survival among children with repaired EA (range, 93–95%). Many (up to 67%) suffer from gastroesophageal reflux (GER). The high incidence of GER and improved survival among EA patients raises concerns about an increased risk of developing Barrett esophagus (BE) and esophageal cancer. This review provides an overview of the prevalence of esophagitis, BE, and esophageal cancer in EA patients and outlines suggestions for future research. A literature search indeed revealed a higher prevalence of BE in EA patients than in the generalized population and that this condition occurs at a much younger age. It should be noted that in some studies gastric metaplasia without intestinal metaplasia is defined as BE. Gastric-type mucosa in columnar-lined esophagus is probably of less clinical importance in terms of the likelihood of malignant transformation. Its inclusion therefore confounds the risk of esophageal adenocarcinoma. A total of eight cases of esophageal carcinoma at a young age, either squamous cell carcinoma or adenocarcinoma, have been reported. These observations bear important implications prompting for early onset lifelong BE/ esophageal cancer surveillance to facilitate the diagnosis of (pre)neoplastic changes and early treatment.

Objective: The objective of this paper was to determine the effect of neuromuscular blockade (NMB) on working space in a porcine laparoscopy model. Background: Conflicting results on the effect of NMB on laparoscopic working space are found in literature. Almost all studies are limited by absence of objective assessment of working space or use surrogate outcomes. Methods: In a standardized porcine laparoscopy model, laparoscopic working-space dimensions with and without NMB were investigated in 16 animals using computed tomography at intra-abdominal pressures of 0, 5, 10, and 15 mmHg during multiple runs of abdominal insufflation. Results: No statistically significant effect of NMB on abdominal dimensions and laparoscopic working-space volume was found during CO2 pneumoperitoneum. In contrast, the effect of pre-stretching of the abdominal wall by a previous abdominal insufflation was found to be significant. Conclusions: This experimental study confirms the results from several clinical studies that NMB does not influence laparoscopic working space. Studies dealing with working space during laparoscopy should take note of pre-stretching bias.

The repair of cloacal malformations is most often performed using a posterior sagittal anorecto-vagino-urethroplasty (PSARVUP) or total urogenital mobilization (TUM) with or without laparotomy. The aim of this study was to systematically review the frequency and type of postoperative complication seen after cloacal repair as reported in the literature. A systematic literature search was conducted according to preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA). Eight records were eligible for this study which were qualitatively analyzed according to the Rangel score. Overall complication rates reported in included studies ranged from 0 to 57 %. After meta-analysis of data, postoperative complications were seen in 99 of 327 patients (30 %). The most common reported complications were recurrent or persistent fistula (n = 29, 10 %) and rectal prolapse (n = 27, 10 %). In the PSARVUP group, the complication rate was 40 % and in the TUM group 30 % (p = 0.205). This systematic review shows that postoperative complications after cloacal repair are seen in 30 % of the patients. The complication rates after PSARVUP and TUM were not significantly different. Standardization in reporting of surgical complications would inform further development of surgical approaches. Other techniques aiming to lower postoperative complication rates may also deserve consideration.

Background: Sacrococcygeal teratoma resection often brings changes in pelvic anatomy and physiology with possible consequences for defecation, micturition and sexual function. It is unknown, whether these changes have any gynecological and obstetric sequelae. Until now four pregnancies after sacrococcygeal teratoma resection have been described and cesarean section has been suggested to be the method of choice for delivery. We evaluated the pregnancy course and mode of delivery in women previously treated for a sacrococcygeal teratoma. Methods: The records of all patients who underwent sacrococcygeal teratoma resection after 1970 in one of the six pediatric surgical centers in the Netherlands were reviewed retrospectively. Women aged 18 years and older were eligible for participation. Patient characteristics, details about the performed operation and tumor histology were retrieved from the records. Consenting participants completed a questionnaire addressing fertility, pregnancy and delivery details. Results: Eighty-nine women were eligible for participation; 20 could not be traced. Informed consent was received from 41, of whom 38 returned the completed questionnaire (92.7%). Thirteen of these 38 women conceived, all but one spontaneously. In total 20 infants were born, 17 by vaginal delivery and 3 by cesarean section, in one necessitated by previous intra-abdominal surgery as a consequence of sacrococcygeal teratoma resection. Conversion to a cesarean section was never necessary. None of the 25 women without offspring reported involuntary childlessness. Conclusions: There are no indications that resection of a sacrococcygeal teratoma in female patients is associated with reduced fertility: spontaneous pregnancy is possible and vaginal delivery is safe for mother and child, irrespective of the sacrococcygeal teratoma classification or tumor histology.

The adult lung contains several distinct stem cells, although their properties and full potential are still being sorted out. We previously showed that ectopic Sox2 expression in the developing lung manipulated the fate of differentiating cells. Here, we addressed the question whether fully differentiated cells could be redirected towards another cell type. Therefore, we used transgenic mice to express an inducible Sox2 construct in type II pneumocytes, which are situated in the distal, respiratory areas of the lung. Within three days after the induction of the transgene, the type II cells start to proliferate and form clusters of cuboidal cells. Prolonged Sox2 expression resulted in the reversal of the type II cell towards a more embryonic, precursor-like cell, being positive for the stem cell markers Sca1 and Ssea1. Moreover, the cells started to co-express Spc and Cc10, characteristics of bronchioalveolar stem cells. We demonstrated that Sox2 directly regulates the expression of Sca1. Subsequently, these cells expressed Trp63, a marker for basal cells of the trachea. So, we show that the expression of one transcription factor in fully differentiated, distal lung cells changes their fate towards proximal cells through intermediate cell types. This may have implications for regenerative medicine, and repair of diseased and damaged lungs.

Survival rates in esophageal atresia (EA) patients have reached 90%. In long-term follow-up studies the focus has shifted from purely surgical or gastrointestinal evaluation to a multidisciplinary approach. We evaluated the long-term morbidity in adolescent and adult EA patients and discussed mainly nonsurgical issues. Dysphagia is common and reported in up to 85% of patients. In young adults gastroesophageal reflux disease occurs frequently with development of Barrett esophagus in 6% reported in different series. It is difficult to estimate respiratory morbidity from the literature because many different definitions, questionnaires, and study designs have been used. However, many patients seem to suffer from respiratory problems even into adulthood. In conclusion, morbidity is not only restricted to surgical problems but many different domains are involved. These are all related and together determine to a large extent the quality of life of EA patients and also of their families. We assume that a multidisciplinary care approach seems best to address their special needs.

Copy number variations (CNVs), either DNA gains or losses, have been found at common regions throughout the human genome. Most CNVs neither have a pathogenic significance nor result in disease-related phenotypes but, instead, reflect the normal population variance. However, larger CNVs, which often arise de novo, are frequently associated with human disease. A genetic contribution has long been suspected in VACTERL (Vertebral, Anal, Cardiac, TracheoEsophageal fistula, Renal and Limb anomalies) association. The anomalies observed in this association overlap with several monogenetic conditions associated with mutations in specific genes, e.g. Townes Brocks (SALL1), Feingold syndrome (MYCN) or Fanconi anemia. So far VACTERL association has typically been considered a diagnosis of exclusion. Identifying recurrent or de novo genomic variations in individuals with VACTERL association could make it easier to distinguish VACTERL association from other syndromes and could provide insight into disease mechanisms. Sporadically, de novo CNVs associated with VACTERL are described in literature. In addition to this literature review of genomic variation in published VACTERL association patients, we describe CNVs present in 68 VACTERL association patients collected in our institution. De novo variations (>30 kb) are absent in our VACTERL association cohort. However, we identified recurrent rare CNVs which, although inherited, could point to mechanisms or biological processes contributing to this constellation of developmental defects.

Background: Central venous catheter-associated bloodstream infections in children are an increasingly recognized serious safety problem worldwide, but are often preventable. Central venous catheter bundles have proved effective to prevent such infections. Successful implementation requires changes in the hospital system as well as in healthca

Background It has been suggested that the outcome of transanal endorectal pull-through for classic Hirschprung's disease can be improved by laparoscopically mobilizing the colon before the pullthrough. Methods Charts of 43 patients (2005-2009) with proven recto-sigmoid aganglionosis were retrospectively analyzed with respect to postoperative outcomes. Twenty-one had been treated with the transanal endorectal pull through (TERPT) and 22 with the laparoscopically assisted TERPT (LTERPT). Results Gender ratio, congenital anomalies, preoperative enterostomy, and follow up did not differ between the groups. More colon was resected in the TERPT group: median 25 cm vs. 15 cm in the L-TERPT group (p < 0.001). The TERPT-procedure took less time: median 153 min. vs. L-TERPT 263 min (p < 0.001). Postoperatively, three patients showed colonic torsions after TERPT (p = 0.07). The long-term clinical outcomes did not differ significantly between both groups. There was a significant association between length of resection and obstructive symptoms (OR = 0.92, p = 0.01). Conclusion Postoperative and clinical outcomes are similar using the TERPT or L-TERPT to correct classic segment Hirschsprung's disease. Prevention of colonic torsion should be the prime concern during the TERPT procedure. L-TERPT requires laparoscopic equipment and takes more operation time, whereas TERPT leaves no visible scars. The positive relation between the larger length of resection and obstructive symptoms requires additional research.

Background: Adequate working space is a prerequisite for safe and efficient minimal access surgery. No objective data exist in literature about the effect of mechanical bowel preparation (MBP) on working space in laparoscopic surgery. We objectively measured this effect with computed tomography in a porcine laparoscopy model. Methods: Using standardized anesthesia, twelve 20-kg pigs without MBP and eight 20-kg pigs with MBP were studied with computed tomography at intra-abdominal pressure (IAP) levels of 0, 5, 10, and 15 mmHg. Volumes and dimensions of the pneumoperitoneum were measured on reconstructed CT images and compared between the pigs with and those without MBP. Results: A reproducible and statistically significant increase of approximately 500 ml in pneumoperitoneum volume was found in the MBP group at all levels of IAP. This represents a 43 % relative increase at a pneumoperitoneum pressure of 5 mmHg, 21 % at IAP 10 mmHg, and 18 % at IAP 15 mmHg. Peak inspiratory pressure was lower at IAP 0 and 5 mmHg in the MBP group. Anteroposterior diameter in the group with MBP was lower at 0 mmHg, but abdominal dimensions were similar in both groups at all other IAPs. This shows that the gain in working space is due to a diminished volume of the intra-abdominal content and not to compression or displacement of the bowel. Conclusions: MBP increases working space by reducing bowel content. Especially at low intra-abdominal working pressures, the increase in working space associated with MBP could represent an important benefit in challenging laparoscopic surgery.

Background: Several studies have evaluated short-term neonatal outcome in infants with congenital lung lesions (CLL) but clinical course and lung function in the longer term have not yet been documented. We hypothesized that clinical course and lung function would be negatively affected by surgical resection. Objective: To evaluate respiratory symptoms and lung function longitudinally in the first year of life in infants with CLL, and to analyse differences herein between infants managed by observation only and infants whose affected lung parts were resected. Methods: We evaluated respiratory symptoms and lung function at 6 and 12 months in 30 patients with CLL. Functional residual capacity (FRCp) and maximal expiratory flow at functional residual capacity (V′maxFRC) were measured with body plethysmography. SD scores were calculated for V′maxFRC. Results: Prevalence of respiratory symptoms did not differ between the groups. Mean FRCp(95% CI) was 25.3 (23.3-27.3) in the group managed by observation versus 27.3 (25.1-29.6) in the group managed by surgery (p = 0.149). Mean (95% CI) SDS V′maxFRC was -1.45 (-1.84 to -1.06) versus -1.41 (-1.90 to -0.91) (p = 0.892). Lung function did not change significantly over the 6-month period. Conclusion: Surgical resection did not seem to have negatively affected the clinical course and lung function. We recommend pulmonary follow-up of all CLL patients into adulthood to further identify any long-term effects of CLL and observation or surgery. Copyright

Background: Respiratory morbidity has been described in patients who underwent repair of esophageal atresia as a neonate. We compared the influence of open thoracotomy or thoracoscopy on lung function, respiratory symptoms, and growth. Methods: Functional residual capacity (FRCp), indicative of lung volume, and maximal expiratory flow at functional residual capacity (V′maxFRC), indicative of airway patency, of 37 infants operated for esophageal atresia were measured with Masterscreen Babybody at 6 and 12 months. SD scores were calculated for V′maxFRC. Results: Repair was by thoracotomy in 21 cases (57%) and by thoracoscopy in 16 cases (43%). Lung function parameters did not differ between the types of surgery (FRCp; P =.384 and V′maxFRC; P =.241). FRCpvalues were in the upper normal range and increased from 6 to 12 months (22.5 and 25.4 mL/kg respectively, P =.010). Mean (SD) V′maxFRCwas below the norm without significant change in SD scores from 6 to 12 months (- 1.9 and - 2.3, respectively, P =.248). Neither lung function nor type of repair was associated with clinical evolution up to 2 years. Conclusion: Lung function during the first year was similar in EA infants repaired by thoracotomy or thoracoscopy. Ongoing follow-up including pulmonary function testing is needed to determine whether differences occur at a later age in this cohort.

Purpose The optimal timing of ostomy closure is a matter of debate. We performed a systematic review of outcomes of early ostomy closure (EC, within 8 weeks) and late ostomy closure (LC, after 8 weeks) in infants with necro-tizing enterocolitis. Methods PubMed, EMbase, Web-of-Science, and Cinahl were searched for studies that detailed time to ostomy closure, and time to full enteral nutrition (FEN) or complications after ostomy closure. Patients with Hirschsprung's disease or anorectal malformations were excluded. Analysis was performed using SPSS 17 and RevMan 5. Results Of 778 retrieved articles, 5 met the inclusion criteria. The median score for study quality was 9 [range 8-14 on a scale of 0 to 32 points (Downs and Black, J Epidemiol Community Health 52:377-384, 1998)]. One study described mean time to FEN: 19.1 days after EC (n = 13) versus 7.2 days after LC (n = 24; P = 0.027). Four studies reported complication rates after ostomy closure, complications occurred in 27 % of the EC group versus 23 % of the LC group.The combinedoddsratio(LCvs.EC) was 1.1[95 %CI 0.5, 2.5]. Conclusion Evidence that supports early or late closure is scarce and the published articles are of poor quality. There is no significant difference between EC versus LC in the complication rate. This systematic review supports neither early nor late ostomy closure.

Rede, Uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar met als leeropdracht kinderchirurgie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 12 mei 2011

This study evaluates whether, on the long run, in patients born with a giant omphalocele, the liver and other solid organs reach their normal position, shape, and size. Seventeen former patients with a giant omphalocele, treated between 1970 and 2004, were included. Physical examination was supplemented with ultrasonography for ventral hernia and precise description of the liver, spleen, and kidneys. The findings were compared with 17 controls matched for age, gender, and body mass index. We found an abnormal position of the liver, spleen, left kidney, and right kidney in eight, six, five, and four patients, respectively. An unprotected liver was present in all 17 patients and in 11 controls, the difference being statistically significant (p∈=∈0.04). In ten of the 11 patients with an incisional hernia, the liver was located underneath the abdominal defect. Conclusion: In all former patients with a giant omphalocele, an abnormal position of the liver and in the majority of them, an incisional hernia was also found. The liver and sometimes also the spleen and the kidneys do not migrate to their normal position. Exact documentation and good information are important for both the patient and their caretakers in order to avoid liver trauma.

Purpose: The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities. Methods: The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case-parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data. Results: Currently, 701 ARM cas

Purpose: After 25 years of practice and positive results of the Rehbein-procedure (RB) for children with Hirschsprung Disease (HD), we changed to the less invasive transanal endorectal pull through (TERPT). The aim of this study was to compare short- and mid-term complications of these two procedures in our patients with HD. Methods: Retrospective data of 50 HD patients were analyzed. Of these patients, 25 underwent RB (2000-2006) and in 25 the TERPT was performed (2005-2009). Medical records were reviewed to score complications and outcomes. Differences were analyzed using Chi-Square and Mann-Whitney U tests. Results: All RB patients (100%) were given a colostomy compared with four patients (16%) in the TERPT group (p < 0.001). The average age at surgery in the RB group was 191 days whereas this was 72 days in the TERPT group (p < 0.01). The mean length of time of surgery in the RB group (158 min) was not significantly different from that in the TERPT group (183 min). Ganglion cells were located in all specimens at the proximal end of the specimens. The median time to first feeding significantly decreased from 2 days (range 1-11) in the RB group to 1 day (range 1-3) in the TERPT group (p < 0.01). The median length of hospital stay decreased in the TERPT group (8 days) compared with the RB group (10 days) (p < 0.001). There was a significant reduction in postoperative obstructive symptoms during the first 6 months in the TERPT group (48%) compared with the RB group (84%) (p = 0.016). Postoperative enterocolitis decreased from 40% in the RB group to 24% in the TERPT group although this was not statistically significant. Conclusions: The introduction of TERPT reduced the need for colostomies; it shortened days to first feeding after surgery and reduced hospital stay. It also improved short-term outcome with less obstructive symptoms. We recommend TERPT surgery as a first choice in children with HD. we consider the RB now to be obsolete.