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The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion.

Objective: The term bowel management refers to an individualized program for fecal incontinent patients. The main principle is the administration of fluid to wash out the colon, either transanally or antegrade through a stoma. Method: A literature search was performed to find the best method to keep fecal incontinent children clean. Results: Bowel management with an individually determined amount of fluid, either by abdominal radiographs or hydrosonography, showed better success rates compared with transanal enemas with an estimated amount of fluid. Furthermore, transanal enemas had higher success rates compared with bowel management with antegrade continence enemas and showed fewer complications. Conclusion: To improve a child’s quality of life an antegrade continence enema can be considered. Before surgery it has to be shown that a bowel management with rectal irrigations works. The indication for a surgical approach for bowel management has to be set carefully. Conservative measures must be tried first. Keywords: anorectal malformation, antegrade continence enema, bowel management, fecal incontinence

A multicystic tumor of the right neck was detected in a girl at 29 weeks of gestation by fetal ultrasound and magnetic resonance imaging (MRI). The baby was delivered by cesarean section at week 37 of gestation. The newborn adapted well, with minimal compromise of breathing and drinking. Postnatal ultrasound and MRI revealed a cervical lymphangioma measuring 60.5 × 60.6 × 41.2 mm. We performed subtotal resection of the tumor when the girl was 34 days. As a complication of surgical resection, the girl developed ipsilateral Horner's syndrome. In the postoperative period, her curled hair turned straight at the side of the head affected by Horner's syndrome. At the age of 2.5 years, ultrasonic imaging revealed the presence of three cysts measuring 3 mm in diameter each. Horner's syndrome had improved, and the texture of the girl's hair had become curly again on both sides.

Laparoscopic hernia repairs are used increasingly in children. The purpose of this single-center cohort observational research study was to analyze the outcome of children treated surgically for unilateral or bilateral inguinal hernia using laparoscopy. We did a STROBE-compliant retrospective outcome analysis of pediatric, laparoscopic hernia repair. Consecutive laparoscopic herniorrhaphies in 123 children done between March 2, 2010, and March 1, 2014, were included in this analysis. Data analysis was based on reviewing the hospital records and a prospective questionnaire. We evaluated postoperative hernia recurrence rate, occurrence of postoperative complications, duration of postoperative pain medication, and wound cosmesis. We first performed laparoscopic inguinal herniorrhaphy according to the techniques described by Schier et al and Becmeur et al in March 2010. We treated 46 girls and 77 boys with laparoscopically confirmed inguinal hernias, and their ages ranged from 0 to 16 years. Of these, 77 children suffered from unilateral hernias, 30 from unilateral hernias with contralateral patency of the vaginal process, and 16 from indirect bilateral hernias. The median follow-up interval was 38 months (range: 13–58 months). Overall, 8 (6.5%) of these 123 patients experienced a recurrence of the inguinal hernia. Two patients (1.6%) suffered a postoperative infection. Postoperative pain medication was administered by parents for 1 to 3 days in 67 (63.8%) of the 105 families who answered the question, and no pain medication was administered by 5 (4.0%) parents. Wound cosmesis was rated by the parents as invisible or barely visible in 106 (86.2%) of 123 patients and esthetically disturbing in 4 (3.2%) children. Laparoscopic inguinal hernia repair carries a learning curve and is safe and efficient in children thereafter. Further prospective studies are required to evaluate the long-term outcome of laparoscopic inguinal hernia repair in children.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fisher's exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Background and aims Detection of intestinal ischemia is often delayed causing extensive complications. Serum citrulline is an important parameter for bowel integrity and functionality; however, no data is available on its response on postoperative intestinal impairment in children. The aim of this study was to evaluate the native effects of intestinal surgery on the postoperative citrulline course in children.

Background Association between chronic airway diseases (CAD) and gastroesophageal reflux disease (GERD) is well described, but causality has not yet been conclusively established. This study evaluates the therapeutic significance of laparoscopic Thal fundoplication in children with CAD and diagnosed GERD. Methods We performed a retrospective analysis of 182 neurologically nonimpaired children, all with medically refractory CAD and GERD undergoing laparoscopic Thal fundoplication. The clinical response, ability to wean oral and inhaled medication and satisfaction with postoperative results were evaluated. Results Main symptoms disappeared completely in 68.7% of patients and were markedly improved in a further 22% of patients following surgery. Complete discontinuation of medication was achieved in 70.1–96.4% of cases and reduced in a further 1.8–23.5%. One intraoperative complication occurred (gastric perforation), however no conversion to laparotomy was necessary. Postoperative Dumping Syndrome occurred in 1% of cases and was managed dietetically. Prolonged postoperative dysphagia occurred in 4.3% of patients, but disappeared within 8weeks in all but one case. Conclusions Our study suggests that Thal fundoplication in neurologically nonimpaired children with CAD and documented GERD is effective and safe. Children unresponsive to preoperative medical management showed significant improvement in airway symptoms together with a marked reduction in the need for medication. We conclude that laparoscopic Thal fundoplication represents a significant treatment worthy of consideration in this group of patients.

Background Infantile hypertrophic pyloric stenosis (IHPS) is a disorder of young children (aged one year or less) and can be treated by laparoscopic (LP) or open (OP) longitudinal myotomy of the pylorus. Since the first description in 1990, LP is being performed more often worldwide. Objectives To compare the efficacy and safety of open versus laparoscopic pyloromyotomy for IHPS. Search methods We conducted a literature search on 04 February 2021 to identify all randomised controlled trials (RCTs), without any language restrictions. We searched the following electronic databases: MEDLINE (1990 to February 2021), Embase (1990 to February 2021), and the Cochrane Central Register of Controlled Trials (CENTRAL). We also searched the Internet using the Google Search engine (www.google.com) and Google Scholar (scholar.google.com) to identify grey literature not indexed in databases. Selection criteria We included RCTs and quasi-randomised trials comparing LP with OP for hypertrophic pyloric stenosis. Data collection and analysis Two review authors independently screened references and extracted data from trial reports. Where outcomes or study details were not reported, we requested missing data from the corresponding authors of the primary RCTs. We used a random-effects model to calculate risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. Two review authors independently assessed risks of bias. We used GRADE to assess the certainty of the evidence for all outcomes. Main results The electronic database search resulted in a total of 434 records. After de-duplication, we screened 410 independent publications, and ultimately included seven RCTs (reported in 8 reports) in quantitative analysis. The seven included RCTs enrolled 720 participants (357 with open pyloromyotomy and 363 with laparoscopic pyloromyotomy). One study was a multi-country trial, three were carried out in the USA, and one study each was carried out in France, Japan, and Bangladesh. The evidence suggests that LP may result in a small increase in mucosal perforation compared with OP (RR 1.60, 95% CI 0.49 to 5.26; 7 studies, 720 participants; low-certainty evidence). LP may result in up to 5 extra instances of mucosal perforation per 1,000 participants; however, the confidence interval ranges from 4 fewer to 44 more per 1,000 participants. Four RCTs with 502 participants reported on incomplete pyloromyotomy. They indicate that LP may increase the risk of incomplete pyloromyotomy compared with OP, but the confidence interval crosses the line of no effect (RR 7.37, 95% CI 0.92 to 59.11; 4 studies, 502 participants; low-certainty evidence). In the LP groups, 6 cases of incomplete pyloromyotomy were reported in 247 participants while no cases of incomplete pyloromyotomy were reported in the OP groups (from 255 participants). All included studies (720 participants) reported on postoperative wound infections or abscess formations. The evidence is very uncertain about the effect of LP on postoperative wound infection or abscess formation compared with OP (RR 0.59, 95% CI 0.24 to 1.45; 7 studies, 720 participants; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on postoperative incisional hernia compared with OP (RR 1.01, 95% CI 0.11 to 9.53; 4 studies, 382 participants; very low-certainty evidence). Length of hospital stay was assessed by five RCTs, including 562 participants. The evidence is very uncertain about the effect of LP compared to OP (mean difference -3.01 hours, 95% CI -8.39 to 2.37 hours; very low-certainty evidence). Time to full feeds was assessed by six studies, including 622 participants. The evidence is very uncertain about the effect of LP on time to full feeds compared with OP (mean difference -5.86 hours, 95% CI -15.95 to 4.24 hours; very low-certainty evidence). The evidence is also very uncertain about the effect of LP on operating time compared with OP (mean difference 0.53 minutes, 95% CI -3.53 to 4.59 minutes; 6 studies, 622 participants; very low-certainty evidence). Authors' conclusions Laparoscopic pyloromyotomy may result in a small increase in mucosal perforation when compared with open pyloromyotomy for IHPS. There may be an increased risk of incomplete pyloromyotomy following LP compared with OP, but the effect estimate is imprecise and includes the possibility of no difference. We do not know about the effect of LP compared with OP on the need for re-operation, postoperative wound infections or abscess formation, postoperative haematoma or seroma formation, incisional hernia occurrence, length of postoperative stay, time to full feeds, or operating time because the certainty of the evidence was very low for these outcomes. We downgraded the certainty of the evidence for most outcomes due to limitations in the study design (most outcomes were susceptible to detection bias) and imprecision. There is limited evidence available comparing LP with OP for IHPS. The included studies did not provide sufficient information to determine the effect of training, experience, or surgeon preferences on the outcomes assessed.

Hybrid lesions (HLs) have elements of congenital pulmonary airway malformation and extrapulmonary sequestration (EPS) and belong to the congenital lung lesions. EPS usually arises in the thorax or the abdomen but rarely in the diaphragm. The preoperative diagnostic work-up based on chest radiograph, ultrasound (US) and CT often shows imprecise results. Therefore, the exact localisation of the lesion can only be ascertained intraoperatively. Here we present a patient, with an intradiaphragmatic HL, and demonstrate the difficulties of surgical decision making regarding the localisation of the lesion and discuss the value of minimal invasive surgery.

Long-term enteral nutrition in chronically ill, malnourished children represents a clinical challenge if adequate feeding via nasogastric or gastrostomy tubes fails. We evaluated the usefulness and complications of a new type of surgical jejunostomy that allows for easier positioning and replacement of the jejunal feeding tube in children. We surgically inserted replaceable jejunal feeding tubes (RJFT) connected to a guide thread which exited through a separate tiny opening of the abdominal wall. In a retrospective case series, we assessed the effectiveness and complications of this technique in severely ill children suffering from malnutrition and complex disorders. Three surgical complications occurred, and these were addressed by reoperation. Four children died from their severe chronic disorders within the study period. The RJFT permitted continuous enteral feeding and facilitated easy replacement of the tube. After the postoperative period, jejunal feeding by RJFT resulted in adequate weight gain. This feeding access represents an option for children in whom sufficient enteral nutrition by nasogastric tubes or gastrostomy proved impossible. Further studies are required to investigate the safety and effectiveness of this surgical technique in a larger case series.

Background: Anorectal malformations (ARM) have a prevalence of around 1 in 2500 live births. In around 50% of patients, the malformation is isolated, while in the remainder it arises within the context of complex genetic abnormalities or a defined genetic syndrome. Recent studies have implicated rare copy number variations (CNVs) in both isolated and nonisolated ARM, and identified plausible candidate genes. Methods: In the present study, array-based molecular karyotyping was performed to identify causative CNVs in 32 sporadic ARM patients with comorbid abnormalities of the central nervous system (CNS). This phenotype was selected to enrich for rare CNVs, since previous research has implicated rare CNVs in both CNS abnormalities and ARM. Results: In five patients, a probable disease-causing CNV was identified (del6q14.3q16.3, del14q32.2, del17q12q21.2, and two patients with del22q11.21). In three of these patients, the CNVs were de novo. For the remaining two patients, no parental DNA was available. Deletions at 22q11.21 and 6q14.3 have been associated with both CNS abnormalities and ARM. In contrast, deletions at 14q32.2 have only been described in patients with CNS abnormalities, and the del17q12q21.2 is a novel CNV. Expression studies in mice suggest that NEUROD2 and RARA, which reside within the newly identified del17q12q21.2 region, are candidate genes for the formation of microcephaly and ARM. Conclusion: The present data suggest that CNVs are a frequent cause of the ARM with CNS abnormalities phenotype, and that array-analysis is indicated in such patients. Birth Defects Research (Part A) 103:235–242, 2015. © 2014 Wiley Periodicals, Inc.

Background The acronym VATER/VACTERL association describes the combination of at least three of the following cardinal features: vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. Although fibroblast growth factor-8 (FGF8) mutations have mainly found in patients with Kallmann syndrome, mice with a hypomorphic Fgf8 allele or complete gene invalidation display, aside from gonadotropin-releasing hormone deficiency, parts or even the entire spectrum of human VATER/VACTERL association. Methods We performed FGF8 gene analysis in 49 patients with VATER/VACTERL association and 27 patients presenting with a VATER/VACTERL-like phenotype (two cardinal features). Results We identified two heterozygous FGF8 mutations in patients displaying either VATER/VACTERL association (p.Gly29_Arg34dup) or a VATER/VACTERL-like phenotype (p.Pro26Leu) without limb anomalies. Whereas the duplication mutation has not been reported before, p.Pro26Leu was once observed in a Kallmann syndrome patient. Both our patients had additional bilateral cryptorchidism, a key phenotypic feature in males with FGF8 associated Kallmann syndrome. Each mutation was paternally inherited. Besides delayed puberty in both and additional unilateral cryptorchidism in one of the fathers, they were otherwise healthy. Serum hormone levels downstream the gonadotropin-releasing hormone in both patients and their fathers were within normal range. Conclusion Our results suggest FGF8 mutations to contribute to the formation of the VATER/VACTERL association. Further studies are needed to support this observation.

BackgroundWhile enhanced recovery after surgery (ERAS) programs are the standard for perioperative management, special nutritional care has to be administered to malnourished patients and those at metabolic risk with special regard to patients with postoperative complications.MethodsExisting guidelines of the German and European societies of nutritional medicine (DGEM and ESPEN) on enteral and parenteral nutrition in surgery were merged and in accordance with the principles of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF, German Association of the Scientific Medical Societies) and Arztliches Zentrum fur Qualitat in der Medizin (AeZQ, German Agency for Quality in Medicine) revised and extended.Results and discussionThe working group developed 41 consensus-based recommendations for perioperative nutrition. The recommendation strength is: 9x A (recommendation based on significant good quality literature containing at least one randomized controlled trial), 12x B (recommendation based on well-designed trial without randomization), 13x C (recommendation based on expert opinions and/or clinical experience of respected authorities) and 7x CCP (clinical consensus point).ConclusionEven in patients without obvious malnutrition perioperative nutritional support is indicated when oral food intake is not feasible or inadequate for a longer period of time.

BackgroundThe prodrug metamizole is frequently dosed intravenously (IV) for postoperative pain in children of all ages, despite its off-label use in infants < 1 year. We aimed to investigate the pharmacokinetics (PK) of the main metabolite of metamizole, 4-aminoantipyrine (MAA), in children aged 3–72 months following IV dosing.Methods10 mg/kg metamizole was administered IV for postoperative analgesia. PK samples were drawn at 5 predefined time points. PK of the main active metabolite MAA and three other metabolites was characterized by both non-compartmental (NCA) and population PK analysis (PPK). AUC0-inf of MAA was calculated by NCA for two age cohorts (3–23 months, 2–6 years) and compared to the 80–125% range of adult dose-adjusted reference exposure (AUCref). PPK investigated age and weight dependency of the kinetics, and dosing strategies to achieve equivalent adult exposure in children.ResultsA total of 25 children aged 5 months - 5.8 years (7.8–24.8 kg) with at least one plasma concentration sample were included in PPK, 19 children who had 5 predefined samples up to 10 h post-dose were included in NCA. AUC0-inf of MAA in children of 2–6 years was 29.8 (95%CI 23.3–38.1) mg/L*h, significantly lower than AUCref(80%-125% range: 39.2–61.2 mg/L*h). AUC0-inf of MAA in infants of 3–23 months was 42.5 (95%CI 15.7–115.4) mg/L*h, overlapping with AUCref. The large variability observed in infants could be partially explained by covariates body weight and age.ConclusionsKinetics of the main active metabolite MAA depends on age in infants and children. MAA exposure after a single IV dose of 10 mg/kg metamizole in infants < 1 year of age was higher compared to an equal dose in adults and older children. This suggests that the optimal dose for this age group to achieve equivalent exposure compared to adults is lower than currently recommended.Disclosure(s)Nothing to disclose.

Elastic stabile intramedullary nailing (ESIN) is a well-established method to stabilize diaphyseal fracture of the femur (DFF) in children. We aimed to evaluate the minimal medullary canal diameter (MMCD) of the fractured femur relative to the diameter of the nails. We also analyzed the real

Fragestellung: Enhanced recovery after surgery (ERAS) Programme sind der Standard im perioperativen Management. Berucksichtigt werden muss der nachgewiesene Einfluss einer krankheitsassoziierten Mangelernahrung auf die postoperative Morbiditat und Letalitat. So bedurfen Patienten mit metabolischem Risiko oder manifester Mangelernahrung sowie solche Patienten mit postoperativen Komplikationen besonderer ernahrungsmedizinischer Aufmerksamkeit. Methodik: Die bestehenden Leitlinien der deutschen und europaischen ernahrungsmedizinischen Fachgesellschaften (DGEM, ESPEN) zur enteralen und parenteralen Ernahrung wurden zusammengefuhrt und in Einklang mit den prozeduralen Vorgaben der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) und des Arztlichen Zentrums fur Qualitat in der Medizin (AZQ) aktualisiert und erweitert. Ergebnisse: Von der Arbeitsgruppe wurden 41 in der Leitlinienkonferenz konsentierte Empfehlungen zur perioperativen Ernahrung mit folgender Empfehlungsstarke erarbeitet: 9-mal A (Empfehlung basiert auf schlussiger Literatur guter Qualitat, die mind. eine randomisierte Studie enthalt), 12-mal B (Empfehlung basiert auf gut durchgefuhrten, nicht randomisierten Studien), 13-mal C (Empfehlung basiert auf Berichten und Meinungen von Expertenkreisen und/oder klinischen Erfahrungen anerkannter Autoritaten) und 7-mal KKP (klinischer Konsenspunkt). Schlussfolgerung: Eine perioperative supplementierende kunstliche Ernahrung ist auch bei Patienten ohne offensichtliche Mangelernahrung indiziert, sofern vorhersehbar ist, dass der Patient fur eine langere postoperative Zeitdauer unfahig zur adaquaten oralen Kalorienzufuhr sein wird.

MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes ( c-Met and YB1 ) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box–binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

Item does not contain fulltext Anorectal malformations (ARMs) comprise a broad spectrum of conditions ranging from mild anal anomalies to complex cloacal malformations. In 40-50% of cases, ARM occurs within the context of defined genetic syndromes or complex multiple congenital anomalies, such as VATER/VACTERL (vertebral defects [V], ARMs [A], cardiac defects [C], tracheoesophageal fistula with or without esophageal atresia [TE], renal malformations [R], and limb defects [L]) association. Here, we report the identification of deletions at chromosome 13q using single nucleotide polymorphism-based array analysis in two patients with mild ARM as part of VATER/VACTERL and VATER/VACTERL-like associations. Both deletions overlap the previously defined critical region for ARM. Heterozygous Efnb2 murine knockout models presenting with mild ARM suggest EFNB2 as an excellent candidate gene in this region. Our patients showed a mild ARM phenotype, closely resembling that of the mouse. We performed a comprehensive mutation analysis of the EFNB2 gene in 331 patients with isolated ARM, or ARM as part of VATER/VACTERL or VATER/VACTERL-like associations. However, we did not identify any disease-causing mutations. Given the convincing argument for EFNB2 as a candidate gene for ARM, analyses of larger samples and screening of functionally relevant non-coding regions of EFNB2 are warranted. In conclusion, our report underlines the association of chromosome 13q deletions with ARM, suggesting that routine molecular diagnostic workup should include the search for these deletions. Despite the negative results of our mutation screening, we still consider EFNB2 an excellent candidate gene for contributing to the development of ARM in humans. (c) 2013 Wiley Periodicals, Inc.

Background: Adenomas of the adrenal gland are rare causes of virilization in childhood. Case Report: A girl aged 2 years and 4 months presented with pubarche, distinct clitoral hypertrophy, tall stature, and increased height velocity. Plasma testosterone and dehydroepiandrosterone were elevated. Androgens remained unchanged after adrenocorticotropic hormone, and dexamethasone administrations. Ultrasound examination and magnetic resonance imaging indicated an extra-adrenal mass adjacent to the left adrenal gland, which was removed by endoscopic surgery. However, plasma androgens remained elevated and 131I-iodomethyl-norcholesterol scintigraphy revealed tracer enhancement in the right adrenal gland, which was consecutively removed. Virilization regressed after extirpation of the adenomas and height velocity normalized. Results: Histology revealed a circumscribed adenoma in the right adrenal gland and an epithelial mass with adrenal cortical cells in the left-sided ectopic tumor. In the ectopic tumor, melanocortin 2 receptor expression was augmented threefold compared to the control, indicating adrenal origin. Conclusions: In this young girl, virilization is due to concomitant ectopic and intra-adrenal adenomas of the adrenal cortex. By melanocortin 2 receptor expression, it was confirmed that the ectopic adenoma derived from the adrenal cortex. Specific scintigraphy, if available, assists in allocating the source of androgen hypersecretion.

Item does not contain fulltext The acronym VATER/VACTERL association describes the combination of at least three of the following congenital anomalies: vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). We aimed to identify highly penetrant de novo copy number variations (CNVs) that contribute to VATER/VACTERL association. Array-based molecular karyotyping was performed in a cohort of 41 patients with VATER/VACTERL association and 6 patients with VATER/VACTERL-like phenotype including all of the patients' parents. Three de novo CNVs were identified involving chromosomal regions 1q41, 2q37.3, and 8q24.3 comprising one (SPATA17), two (CAPN10, GPR35), and three (EPPK1, PLEC, PARP10) genes, respectively. Pre-existing data from the literature prompted us to choose GPR35 and EPPK1 for mouse expression studies. Based on these studies, we prioritized GPR35 for sequencing analysis in an extended cohort of 192 patients with VATER/VACTERL association and VATER/VACTERL-like phenotype. Although no disease-causing mutation was identified, our mouse expression studies suggest GPR35 to be involved in the development of the VATER/VACTERL phenotype. Follow-up of GPR35 and the other genes comprising the identified duplications is warranted.

Purpose The aim of the study was to investigate the regeneration and migration of neuronal progenitor cells of the enteric nervous system during wound healing after intestinal anastomosis in the rat ileum. Methods Experiments were performed in a rat model of ileoileal anastomosis. Rats were humanely killed on day 2 or day 10 after anastomosis, and the anastomotic region was compared with ileum of healthy rats. Immunofluorescent staining was performed with protein gene product 9.5, nestin, and S100 antibodies. Ganglia of the anastomotic region in both the myenteric and submucosal plexus were counted, and their diameters were measured and compared between groups. Results Analysis of number and diameter of ganglia in both myenteric and submucosal plexus showed individual alterations as a reaction to the surgical manipulation. Significantly less ganglia were found in the submucosal plexus in the operated groups at both day 2 (p Conclusion Our findings suggest a regenerative potential of the enteric nervous system after the surgical ileoileal anastomosis. The myenteric plexus appears to recover faster than the submucosal plexus. This recovery might be driven by nestin-positive neuronal progenitor cells.

Stabilization of diaphyseal long-bone fractures using elastic stable intramedullary nails (ESIN) in children promises early mobilization and rapid resumption of full weight bearing. We evaluated the duration of postoperative functional rehabilitation after ESIN, measured by the time from stabilization until first partial weight bearing, full weight bearing, and resumption of school sports. Fifty children with unstable, displaced fractures of the femur or lower leg treated with ESIN between 2002 and 2012 were included in this retrospective analysis. We classified fractures according to the pediatric comprehensive classification of fractures (PCCF). Thirty-five children sustained a femur fracture, and 15 children had a fracture of the lower leg or tibia. The surgeons in charge applied an additional plaster cast in 7 of 15 children who suffered a lower leg fracture. The postoperative time interval until full weight bearing in the group of children who had suffered transverse or short oblique femur fractures was significantly shorter (median: 4.4 weeks; range: 0.1–9.1 weeks) than that in the group who had sustained more complex fracture patterns (median: 6.8 weeks; range: 2.9–13.9 weeks; P = 0.04). Similarly, transverse and short oblique lower leg and tibia fractures required less time until full weight bearing (median: 4.1 weeks; range 2.7–6.0 weeks) than complex lower leg fractures (median: 6.1 weeks; range: 1.3–12.9 weeks; P = 0.04). ESIN proved fairly effective in restoring full weight bearing in transverse or short oblique fractures of the lower extremities but was less effective in complex fractures.

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1–60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7–12 years. Lymphatic vessel density is much lower and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches.

In order to prevent stricture of the neoanus after surgical correction, regular dilatation is recommended. There is a lack of knowledge about the performance of anal dilatation and the occurrence of pain. The aim of our investigation was to describe the practice of dilatation and to identify possible risk factors for painful procedures. Congenital Uro-Rectal Malformations Network is a German interdisciplinary multicenter research network. With standard questionnaires, physicians interviewed 243 patients and/or their parents at home, additional 103 patients born since 2009 were assessed through their treating physicians. In total, 88 % of the patients received dilatations. Treatment lasted for 7 months in median (range 1–156 months), until the age of 13 months (range 1–171 months). In 69 % painful dilatation was reported; without a significant differences in age or gender. In 32 % bleeding was reported. In 30 % at least one dilatation was performed under general anesthesia. In 11 % some kind of analgesia was used. Type of fistula, dilatations lasting longer than 10 months and Hegar size above 15 were relevant factors for experience of pain. There were about 16 % postoperative strictures of the neoanus, without reported differences in dilatation procedures; but there was a relation to type of malformation. Considering the high number of painful treatments, predictors for painful dilatations should be further clarified through standardized documentation and prospective evaluation in order to improve follow-up.

Because of anatomical and physiological similarities to humans, porcine small bowel transplantation (SBTx) can be used as an appropriate experimental model in the field of surgical research. Various approaches to SBTx have been described in literature. The aim of this work is to present a review of different surgical techniques of SBTx which have been developed using the porcine model. Our analysis of Medline-cited studies dealing with different techniques of SBTx in porcine models was particularly focused on surgical aspects. With regard to graft procurement and enterectomy, the reported techniques vary widely. Arterial reconstruction is mainly conducted by performing the anastomosis between the superior mesenteric artery (SMA) of the donor and SMA or infrarenal aorta of the recipient. Alternatively, an aortic segment of the donor can be anastomosed to the infrarenal aorta of the recipient. Venous anastomosis is frequently performed between the superior mesenteric vein (SMV) of the donor and SMV or the inferior vena cava (IVC) of the recipient. Some studies also report venous anastomosis between the portal vein of the donor and the recipient. Bowel continuity is then restored by end-to-end or end-to-side anastomosis. Remarkable results were generated thanks to improved techniques which include proximal side-to-side ileo-ileal anastomosis with double-barrel ileostomy, or so-called “Paul-Mikulicz-Ileostomy”. Most frequently used were jejunostomy and the “Bishop-Koop-Ileostomy” - where the proximal part of the bowel is anastomosed end-to-side to the distal part, which is then exteriorized as an ostomy. Based on the techniques presented in this review, one must select the most suitable surgical technique of porcine SBTx among those various models.

Propranolol has recently been reported to be a highly effective treatment for infantile hemangioma (IH) and is emerging as a first-line therapy. This study reports the observations after completed propranolol therapy in 55 patients. Propranolol was administered in a dosage of 2 mg/kg per day with initial monitoring of vital signs. Therapy duration was planned for 4 to 6 months; if there was significant relapse, the period of treatment was extended. The mean age of 55 patients at the beginning of the treatment was 6 months (52.7%4 mos, 30.9% 4-9 mos, 16.3%9 mos). Thirteen patients (21.7%) showed a reaction possibly due to the medication, but we did not observe any life-threatening adverse effects. The therapy was interrupted due to temporary aggravation of preexisting bronchial asthma in one child. The initially administered dosage was adjusted to the increase of weight in 21 patients (38.2%), but most did not require a dosage adjustment despite somatic growth. Mean duration of treatment was 6 months; younger patients needed longer treatment periods. Response to treatment was favorable; eight (14.5%) showed total regression and 46 (83.4%) partial regression, and one (1.8%) had no response. Propranolol is an efficacious therapy for severe IH. Risks and complications appear moderate. If indicated, therapy should be initiated early to minimize the extent of residual changes. Young patients show quick and extended benefit. Prospective controlled trails are necessary to observe the effects on a long-term basis.

The aim of the German Network for Congenital Uro-REctal Malformations is to collect data of affected patients with anorectal malformation (ARM) or extrophy–epispadias complex, and to investigate molecular causes, clinical implications, and psychosocial outcome. The current issue was to assess the postoperative sequelae related to lower urinary tract dysfunction in patients with ARM. Two hundred and sixty-seven patients with ARM (112 females, 155 males, median age 6 years, range 0–56 years) were investigated via standardized case report forms comprising interview, analysis of medical data, and personal questionnaires. Thirty-two patients (12%, 23 males, 9 females) suffered from neurogenic bladder dysfunction, mainly associated with recto-urethral fistula (11 cases, 34%), and recto-vesical fistula (6 cases, 19%). Sixty-eight patients (26%, 35 males, 57 females) have experienced lifetime urinary tract infection, primarily associated with recto-urethral fistula (21 cases, 31%), and vestibular fistula (13 cases, 19%). According to type of operation, the highest number of postoperative urologic problems was reported after abdominosacroperineal pull-through. Besides reconstructing the ARM, another main goal is the preservation of lower urinary tract function. In our data, there seems to be a close correlation between operative strategies and postoperative complications.

INTRODUCTION Neuroblastoma (NB) is one of the most common malignant tumors in infancy. The commonly used International Neuroblastoma Staging System is not suitable for determining the surgical risks. To address this, we aimed to evaluate the correlation between so-called image-defined risk factors (IDRFs) and the surgical risks in abdominal neuroblastoma. MATERIAL AND METHODS We evaluated 60 cases who underwent surgical intervention and examined the pre-surgical radiological imaging to look for IDRFs and surgical complications in children with abdominal neuroblastoma. RESULTS The MRI- and CT-scans showed a total of 122 IDRFs in 39 cases. Complete resection was carried out in 50%, partial excision in 32%, and biopsy in 18% of cases. Total resection was possible in 100% of cases with no IDRF. Where IDRFs were present, total resection was only possible in 26% of cases (p

De Novo Duplication of 18p11.21–18q12.1 in a Female With Anorectal Malformation Charlotte Schramm, Markus Draaken, Enrika Bartels, Thomas M. Boemers, Eberhard Schmiedeke, Sabine Grasshoff-Derr, Stefanie M€arzheuser, Stuart Hosie, Stefan Holland-Cunz, Friederike Baudisch, Lutz Priebe, Per Hoffmann, Alexander M. Zink, Hartmut Engels, Felix F. Brockschmidt, Stefan Aretz, Markus M. N€othen, Michael Ludwig, and Heiko Reutter* Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany Department of Pediatric Surgery and Pediatric Urology, Children’s Hospital, Cologne, Germany Department of Pediatric Surgery and Urology, Center for Child and Adolescent Health, Hospital Bremen-Mitte, Bremen, Germany Department of Pediatric Surgery, University Hospital W€urzburg, W€urzburg, Germany Department of Pediatric Surgery, Campus Virchow Clinic, Charit e University Hospital Berlin, Berlin, Germany Department of Pediatric Surgery, Klinikum Schwabing, Technische Universit€at M€unchen, M€unchen, Germany Department of Pediatric Surgery, University of Heidelberg, Heidelberg, Germany Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany Department of Neonatology, Children’s Hospital, University of Bonn, Bonn, Germany

Aim: The aim of the retrospective study was to evaluate complications and outcome of children in whom an intestinal anastomosis had been performed at age younger than 1 year. Patients and Methods: Data were collected both retrospectively and by interviewing the parents. For the retrospective analysis, the underlying disease, biometric data, technical information about the anastomoses, associated illnesses, and complications were evaluated. In the parent interviews, the present quality of life and the state of health of the children were evaluated. Results: From 1997 to 2007, intestinal anatomoses had been performed in 131 children for various reasons. There were no complications in 81.7% of the patients; 17 children received reoperation. In only 5 cases were anastomotic complications the reasons for the reoperation. Only 7.3% of the 77 interviewed families believe that their child has severe or relevant restrictions in daily life. Conclusions: Among 131 children in whom an intestinal bowel anastomosis procedure was performed at age younger than 1 year, only 5 (3.2%) experienced complications associated with the anastomosis. The children are in good physical condition and have an excellent quality of life.

Eine traumatische Ellenbogenluxation ist im Kindesalter ein relativ seltenes Ereignis mit einer Inzidenz von 3–6% aller Ellenbogenverletzungen. In der Literatur wird selten das Outcome nach einer Ellenbogenluxation im Kindesalter beschrieben. Die vorliegende Studie schliest retrospektiv 33 Kinder mit einer Ellenbogenluxation ein, die in den Jahren 2001 bis 2008 in unserer Klinik behandelt worden sind. Alle Ereignisse waren einseitig, ein Kind (3%) erlitt ein ipsilaterales Rezidiv 9 Wochen nach dem Erstereignis. Von den Patienten wiesen 70% eine Begleitfraktur auf: 55% hatten eine Epicondylus-ulnaris-Abrissfraktur, 6% eine Fraktur des Epicondylus radialis und 9% eine weitere Fraktur. Eine offene Reposition mit Osteosynthese erforderten 83% aller Frakturen. Nach durchschnittlich 4,5 Jahren wurden 20 Kinder (61%) klinisch nachuntersucht. Sie zeigten kein Gelenkinstabilitaten und nur geringe klinische Einschrankungen des Bewegungsumfangs. Der etablierte Mayo-Ellenbogen-Score zeigte gute bis exzellente Ergebnisse bei allen Kindern. Trotz eines starken Gelenktraumas mit haufigen Begleitfrakturen sind posttraumatische Funktionsdefizite nach Ellenbogenluxationen im Kindesalter selten einschrankend, unabhangig von der Begleitfraktur. Die Rezidivhaufigkeit ist gering und Instabilitaten wurden nicht beobachtet.

Es wird der Fall eines Fruhgeborenen vorgestellt, welches nach Thrombosierung der A. femoralis dexter durch Minderperfusion des rechten Beines eine grosflachige Haut- und Unterhautnekrose entwickelte. Nach Nekrosektomie und simultaner Anwendung von Integra® und Vakuumtherapie konnten Spalthaut transplantiert und der Weichteildefekt erfolgreich gedeckt werden. Im vorliegenden Beitrag wird erstmals uber Schwierigkeiten und Erfahrungen mit dieser sekundaren Wunddeckung in minderperfundiertem Gewebe im Fruhgeborenenalter berichtet.

Bei einem 16-jahrigen Jungen wurden 3 blauliche, teils schmerzhafte, subkutane Raumforderungen reseziert. Die Histologie ergab multiple, disseminierte Glomustumoren. Es handelt sich um seltene benigne Weichgewebstumoren, ausgehen von den Glomuskorperchen, welche die Thermoregulation v. a. an den Akren steuern. Glomustumoren treten meist solitar bei Frauen im Erwachsenenalter auf, nur in 10 % der Falle wird ein multiples Vorkommen beobachtet, dann v. a. bei mannlichen Jugendlichen. Die Therapie der Wahl ist die Exzision. Die Rezidivrate betragt 12–50 %.

Fast-Track-Protokolle in der Kinderchirurgie sind fur einzelne Prozeduren gerechtfertigt. Bei groseren Operationen im Neonaten- und Sauglingsalter ist eine aufwendige postoperative Betreuung notwendig, die starre Fast-Track-Protokolle nicht sinnvoll erscheinen lassen. Bei sehr vielen Eingriffen im Kindesalter sind die Ablaufe bereits so gestrafft, dass Fast-Track-Protokolle keine weitere wesentliche Verkurzung des stationaren Aufenthaltes mit sich bringen wurden. Die veroffentlichten Fast-Track-Erfahrungen fur das Kindesalter zeigen, dass die Methode fur einzelne Indikationen durchfuhrbar und sicher ist. Die Komplikationsquoten und Wiederaufnahmeraten sind gering. Die perioperativen Ablaufe konnen anasthesiologisch durch kurzere Nuchternzeiten, die Umgehung des Aufwachraumes und den Einsatz suffizienter, nebenwirkungsarmer Analgetika im Sinne von Fast Track angepasst werden. Gerade fur das Kindesalter muss jedoch die individuelle Anpassung an die Bedurfnisse des einzelnen Patienten gewahrleistet sein.

Die Autoren stellen Kasuistiken zweier Kinder mit der Diagnose „synovialer Weichteiltumor am Sprunggelenk“ vor. Synoviale Weichteiltumoren des Sprunggelenks sind im Kindesalter selten. Die Symptome sind unspezifisch, sodass die klinische Diagnosefindung schwierig ist. In beiden Fallen stellten sich die Kinder primar bei schmerzhafter Schwellungen nach Trauma vor, was die Diagnosefindung zusatzlich erschwerte. Bei protrahiertem klinischem Verlauf ist bei Kindern an die seltene Differentialdiagnose der synovialen Weichteiltumoren zu denken.

Introduction: 3D imaging and surgical planning for the treatment of embryonal tumors using different techniques (CT versus MRI) are presently under discussion. Up to now, the main focus has been on visualizing the anatomy. Contrast medium dynamics have not been taken into consideration. The aim of the present study was to establish the technical means of integrating the 3D images from functional MRI data into the anatomical images and to determine clinical applications for this approach. Material and Methods: In 11 patients (mean age: 2.4 years) with solid tumors, 26 diagnostic MRI examinations were performed for primary diagnosis, treatment monitoring, or as part of the surgical planning. Seven children presented with neuroblastomas, three with Wilms' tumor, and one with advanced bilateral nephroblastomatosis. The MRI data were acquired using a 1.5-T system. For post-processing, we used volume rendering software, including an evaluation of perfusion. By using color-coded parametric images and integrating functional information, perfusion could be visualized and used for interactive surgical planning. Macroscopic and microscopic sections served as the gold standard for assessing tissue viability. Results: We were able to integrate the dynamic data into the anatomical images for all patients. A good agreement was found between the results of surgical planning, including perfusion mapping, with the surgical site, subsequently produced macroscopic sections and the results of random microscopic examinations. Conclusions: Perfusion mapping using color-coded parametric images of pediatric abdominal tumors extends the diagnostic techniques currently available. We provide first proof of the possibility of integrating functional information into 3D MR images in children. Monitoring the treatment of nephroblastoma and surgical planning for pediatric embryonal tumors represent potential applications of this technique.

Der Ablauf der Operationsplanung und die Verwendung bildgebender Verfahren sowie der Einsatz computerassistierter 3D-Visualisierung bei abdominalen Tumoren werden in den padiatrischen Zentren unterschiedlich gehandhabt. Mittels einer multizentrischen Umfrage wurden die derzeit ubliche Operationsplanung und die Akzeptanz der 3D-Visualisierung evaluiert. Fragebogen wurden an 100 kinderchirurgische Abteilungen in Deutschland, Osterreich und der Schweiz geschickt. Die Fragen bezogen sich auf die klinikspezifisch durchgefuhrte Diagnostik, Operationsplanung, den Einsatz und die Akzeptanz von computerunterstutzten Methoden. Von den 39 antwortenden Kliniken fuhren 35 abdominale Tumoroperationen durch. Als wichtigster Aspekt der Operationsplanung wird in 94% die Darstellung des Abstands des Tumors zu den umliegenden Gefasen gesehen. Nur 57% der Befragten finden dies durch die herkommliche Bildgebung gut beantwortet. In der Erhebung wurden in 20 der 35 Kliniken 3D-Programme verwendet. 88% der antwortenden Kliniken erwarten einen Vorteil in der Operationsplanung durch eine 3D-Visualisierung. Die Akzeptanz von 3D-Verfahren in der Operationsplanung fur das Kindesalter ist anhand unserer Auswertung zu erkennen. Der Stellenwert dieser Methode kann jedoch nur durch den standigen Einsatz und Weiterentwicklungen verbessert werden.

In der Chirurgie ist die Bedeutung des Ernah−rungsstatus fur die postoperative Morbiditatund Letalitat bei verschiedenen Krankheitsbil−dern retrospektiv [1±6] und auch prospektiv[7±22] gezeigt worden.Haufig ist das Bestehen einer MangelernahrungAusdruck der Grunderkrankung z.B. eines Tu−morleidens oder einer chronischen Organinsuffi−zienz [22±31] (s. auch entsprechende Kapitel).So ist die Mangelernahrung besonders relevantfur die Prognose nach Organtransplantation[32±41]. Der Ernahrungsstatus beeinflusst auchwesentlich die Morbiditat in der Chirurgie alterMenschen [42].Rasche Rekonvaleszenz nach chirurgischen Ein−griffen (¹Enhanced Recovery after Surgery =ERAS“) ist die Voraussetzung fur die auch okono−misch gebotene Senkung der Krankenhausver−weildauer. Insbesondere nach Koloneingriffen istder sog. ¹Fast Track“ zum Masstab des postope−rativen Managements geworden. Grundlage istim multimodalen Vorgehen die perioperativsparsame Volumenzufuhr, adaquate Schmerz−therapie vor allem mittels epiduraler Anasthesieunter Minimierung der Gabe von Opioiden, Gabevon Antiemetika und Peristaltika. Ziel ist der fru−hestmogliche orale Kostaufbau mit Vollmobili−sierung.Die Indikationen fur eine kunstliche Ernahrungsind auch in der Chirurgie die Prophylaxe und Be−handlung von Katabolie und Mangelernahrung.Dies betrifft vor allem perioperativ ¹substitutiv“den Erhalt des Ernahrungszustandes zur Verhin−derung einer Mangelernahrung. Kriterien des Er−folgs fur die ¹therapeutische“ Indikation einer PEsind unter Berucksichtigung okonomischer Im−plikationen, die sogenannten OutcomeparameterMorbiditat, Krankenhausverweildauer und Leta−litat. Bei ¹palliativer“ Indikation und poststatio−nar steht neben der Verbesserung des Ernah−rungsstatus die Lebensqualitat im Vordergrund[43±55].

Several oxygen-dependent factors, e.g., CAIX (carbonic anhydrase IX) or phosphoglycerate kinase 1 (PGK1) interacting with the CXCR4/SDF1 axis (chemokine receptor 4/stromal cell derived factor 1) have been shown to be involved in processes of tumour pathology including tumourigenicity, tumour cell dissemination and poor survival in several solid tumour entities. The aim of the current study was to evaluate the influence of the hypoxia-inducible factors CAIX and PGK1 on progression of neuroblastoma and to evaluate the clinical relevance of possible therapeutic approaches. Expression of hypoxia-dependent factors PGK1 and CAIX was examined in neuroblastoma specimen, was correlated with clinical parameters, and was studied in neuroblastoma cells. The impact of these hypoxic factors was evaluated by proliferation assays under targeted therapy. Expression of hypoxia-dependent factors was found in 50 % of neuroblastoma specimen. In neuroblastoma cells, CAIX and PGK1 expression is up regulated under hypoxia and correlates with response to targeted anti-proliferative treatment. The negative impact on survival, although significant for both CAIX and PGk1, appears to be stronger for CAIX. Our results show that the hypoxic factors in the tumour`s microenvironment further the progression of tumour disease. This strengthens the perspectives for additive novel therapeutic approaches targeting hypoxia-dependent factors in this childhood disease.

Introduction: Metastasized pancreatic neuroendocrine tumors are extremely rare malignancies, especially in children. Therefore, therapeutic options are limited, and few standardized therapy regimens exist. Case presentation: We report a case of a 14-year-old white girl. In 2011 she was diagnosed with a metastasized, well-differentiated pancreatic neuroendocrine tumor with expression of synaptophysin and chromogranin A. We describe her clinical course with special attention to her individual therapeutic regimens while bringing together several disciplines of medicine. Conclusions: In patients such as ours, surgical intervention may be the only therapy that will lead to long-term survival.

Insufficient data are available to determine the most suitable extent of intestinal resection required to induce short-bowel syndrome (SBS) in pigs. This study aimed to compare the three main SBS-models published.A 75%, 90%, or 100% mid-intestinal resection was performed in groups of n = 5 pigs each. Clinical (body weight, stool consistency) and biochemical (serum eletrolytes, citrulline, albumin, prealbumin, and transferrin) parameters were determined daily, functional (D-xylose resorption) and histological (intestinal villus length) parameters were determined after 2 weeks. A t-test and ANOVA were used for statistical analysis.Only in the 100% group, we observed a persistent weight loss (13.6 ± 3.8%) and diarrhea, as well as a decrease in prealbumin-levels (41%) and transferrin levels (33%). Serum electrolytes remained stable in all groups during the observation period. Citrulline stabilized at different levels (100% group 13.9 ± 1.0 μmol/L; 90% group 18.8 ± 1.0 μmol/L; 75% group 26.3 ± 1.4 μmol/L; all p.05). D-xylose resorption was lowest in the 100%, followed by 90% and 75% group (100% group 32.8 ± 4.9 mg/L; 90% group 50.0 ± 19.6 mg/L; 75% group 57.8 ± 8.8 mg/L; p = .393). Intestinal villus length decreased in all groups (100% group 11.0%; 90% group 14.0%; 75% group 19.1%).75% intestinal resection is less suitable as an SBS model, as animals tend to recover remarkably. The 90% model is suitable for longer-term studies, as animals might survive longer due to partial compensation. Due to severe nutritional, biochemical, and physiological derangements, the 100% model can only be used for acute experiments and those immediately followed by small bowel transplantation.

Background The calcium-sensing receptor (CaSR) is a calcium (Ca2+) sensitive G protein-coupled receptor implicated in various biological processes. In particular, it regulates Ca2+/Mg2+- homeostasis and senses interstitial Ca2+ levels and thereby controls downstream signalling cascades. Due to its expression in the gut epithelium, the enteric nervous system and smooth muscles and its key function in regulation and coordination of muscular contraction and secretion, it represents an excellent candidate gene to be investigated in the pathophysiology of irritable bowel syndrome (IBS). Disturbed CaSR structure and function may impact gastrointestinal regulation of muscular contraction, neuronal excitation and secretion and consequently contribute to symptoms seen in IBS, such as disordered defecation as well as disturbed gut motility and visceral sensitivity. Methods We have therefore genotyped the functional CASR SNP rs1801725 in three case control samples from the UK, Belgium and the USA. Results Genotype frequencies showed no association in the three genotyped case–control samples, neither with IBS nor with IBS subtypes. Conclusions Although we could not associate the SNP to any of the established bowel symptom based IBS subtypes we cannot rule out association to altered Ca2+ levels and disturbed secretion and gut motility which were unfortunately not assessed in the patients genotyped. This underlines the necessity of a more detailed phenotyping of IBS patients and control individuals in future studies.

Carbonic anhydrase IX (CAIX) is involved in pathological processes including tumorgenicity, metastases and poor survival in solid tumors. Twenty-two neuroblastoma samples of patients who were surgically treated at the University Medical Center Hamburg-Eppendorf were evaluated immunohistochemically for expression of CAIX. Results were correlated with clinical parameters and outcome. Neuroblastoma Kelly and SH-EP-Tet-21/N cells were examined for CAIX expression and inhibited with specific inhibitors, FC5-207A and FC8-325A. 32% of neuroblastoma tumors expressed CAIX. This was significantly associated with poorer survival. Kelly and SH-EP-Tet-21/N cells showed a major increase of CAIX RNA under hypoxic conditions. Proliferation of Kelly cells was significantly decreased by CAIX inhibitors, FC5-207A and FC8-325A, while proliferation of SH-EP-Tet-21/N cells was only significantly affected by FC8-325A. CAIX is a potent biomarker that predicts survival in neuroblastoma patients. CAIX-targeted therapy in neuroblastoma cell lines is highly effective and strengthens the potential of CAIX as a clinical therapeutic target in a selected patient collective.

Komplexe Operationen bei ausgepragten pathologischen Veranderungen anatomischer Strukturen des kindlichen Abdomens benotigen eine exakte Operationsvorbereitung. 3D-Visualisierung und computerassistierte Operationsplanung anhand von CT-Daten finden fur schwierige chirurgische Eingriffe bei Erwachsenen in zunehmendem Mase Anwendung. Aus strahlenhygienischen Grunden und bei besserer Weichteildifferenzierung ist jedoch neben der Sonographie die Magnetresonanztomographie (MRT) bei Kindern das Diagnostikum der Wahl. Die 3D-Visualisierung dieser MRT-Daten ist dabei jedoch aufgrund vielfaltiger Schwierigkeiten bisher nicht durchgefuhrt worden, obwohl sich das Gebiet embryonaler Fehlbildungen und Tumoren geradezu anbietet. Vorgestellt wird eine weiterentwickelte und an die Fragestellungen der abdominellen Kinderchirurgie angepasste, sehr leistungsstarke raycastingbasierte 3D-volume-rendering-Software (VG Studio Max 1.2). Mit speziell entwickelten Bearbeitungsalgorithmen wird beispielhaft ein ausgereiftes Operationsplanungssystem demonstriert. Durch Praktikabilitat und hohe Visualisierungsqualitat mit ausgesprochenem Informationsgewinn hat das vorgestellte Operationsplanungssystem einen festen Stellenwert im klinischen Alltag erlangt.

The human enteric nervous system (ENS) descends from migrating neural crest cells (NCC) and is structured into different plexuses embedded in the gastrointestinal tract wall. The development of this entity strongly depends on the supply of an appropriate support with trophic factors during organogenesis. The lack of important factors, such as glial cell line-derived neurotrophic factor, leads to severe disturbances in the ENS and, thus, to motility disorders in children. The isolation of neuronal precursor cells as well as their transplantation after expansion in vitro is therefore a hopeful new approach concerning all forms of dysganglionosis in children. We therefore established a way to isolate and expand precursor cells from the developing and postnatal human ENS. Bowel samples were obtained from human fetuses and children (from the 9th week of gestation to 5 years postnatal). Myenteric plexus was isolated by enzymatical digestion and cultivated until spheroid aggregates, the so-called neurospheres, developed. These neurospheres could be differentiated and also be transplanted after dissociation into aganglionic bowel in vitro. Enteric neurospheres could be grown from different gestational ages, including postmortem material. Undifferentiated proliferating precursor cells were kept in culture for up to 72 days and could be differentiated in neurons and glial cells in vitro. The first results using isolated enteric neurospheres in aganglionic bowel are quite promising and are a basis to develop an appropriate cell therapy for all kinds of dysganglionosis, especially for cases where a surgical approach is not sufficient or not even possible.

Motility disorders of the human intestine are so variable that they cannot be diagnosed by just one technique. Their aetiology is obviously so varied that they have to be approached with a broad range of technical methods. These reach from the simple haematoxylin-stained section to the isolation of stem or precursor cells. In this study, various methods to investigate the enteric nervous system and its surrounding tissue are demonstrated. While sections from paraffin-embedded material or cryostat sections provide only a two-dimensional perspective of the ENS, the whole-mount method yields three-dimensional perspectives of large areas of the gut wall. The three-dimensional impression can even be enhanced by electron microscopy of the isolated ENS. Dynamical aspects of ENS development can be tackled by in vitro studies. The myenteric plexus can be isolated and cultivated under the influence of the microenvironment (protein extracts). Although the postnatal myenteric plexus is not fully developed, the choice of embryological neuronal cells seems to be more effective for certain approaches. They can be isolated from the embryonic mouse gut and cultivated under the influence of various factors. This method seems to us a valuable tool for the investigation of the aetiology of motility disorders, although only a "complete" approach which considers all available methods will yield at the end a clear understanding which might lead to new therapeutical concepts.

The aim of this study was to identify clinical signs and symptoms of ovarian torsion (OT) in children and to develop a simple predictive score. A chart review of patients with acute adnexal pathologies treated at the University Children's Hospital Basel, Switzerland, between March 2006 and June 2015 was performed. Medical records were screened for demographic and clinical data. These included clinical symptoms, laboratory studies, imaging, and type of treatment. The diagnosis OT was defined as intraoperative visualization of the torsed ovary around its pedicle at least 360 degrees. Variables predictive for OT were identified and the following score for the likelihood of having OT was developed: age (points = number of years) minus 3 points (if vomitus = “yes”) and plus 1 point (if “pain duration >12 hours”). A total of 80 patients with acute adnexal pathologies were identified. OT was recorded in 17 (21%) cases and ovarian cysts (OC) only in 63 (79%) cases. Patients who presented with OT were significantly younger than patients with OC only (P = .001). Correspondingly, 11 (65%) of the patients with OT had no menarche compared to 3 (5%) patients with OC only (P = .001). Vomiting (P = .001), a shorter pain duration (P = .01), and an elevated C-reactive protein (CRP) (P = .01) were observed significantly more often in patients with OT. The sensitivity of a positive OT score was 0.81 and increased to 1.00 if restricted to girls between 2 to 12 years of age. The presence of vomiting, short duration of abdominal pain, and elevated CRP level have a predictive value for the diagnosis of OT. In these patients, an exploratory laparoscopy should be conducted without delay. The presented OT score appears to be a helpful tool in diagnosing OT in children.

We describe a term born boy of non-consanguineous Swiss parents with tetrahydrobiopterine (BH4)-responsive Phenylketonuria (PKU) and Hirschsprung disease with unusual neonatal presentation. The child presented with floppiness, irritability, recurrent bilious vomiting and failure to pass meconium until 32 hours after birth, resulting in the clinical suspicion of an intoxication-type metabolic disease such as maple syrup urine disease (MSUD). Although the slightly elevated branched-chain amino acids in newborn screening on the fourth day of life initially supported the clinical suspicion of MSUD, the elevated Phenylalanine (Phe) of 650 µmol/L, low Tyrosine (Tyr) of 30 µmol/L, and a Phe/Tyr ratio of 22, led to the diagnosis of PKU. BH4-testing resulted in a significant decrease of Phe from 1011 to 437 µmol/L within 24 h. Urinary pterins and dihydropteridine reductase (DHPR) activity were normal, supporting the diagnosis of BH4-responsive PKU. Dietary restriction of Phe was initiated immediately, but oral feeding turned out to be difficult because of gastrointestinal symptoms. Intestinal motility disorder was suspected due to distended abdomen, obstructive symptoms and radiological findings with dilated intestinal loops and lack of intestinal gas in the anorectal region. Hirschsprung disease was confirmed by rectal suction biopsies and treated by a laparoscopically-assisted transanal pull-through (de la Torre) procedure. The boy is additionally compound heterozygous for two mutations in the phenylalanine hydroxylase (PAH) gene, which confirmed BH4-responsive PKU. It is the first case to be described in the literature of the comorbidity of PKU and Hirschsprung disease.