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Left-right patterning disturbance can cause severe birth defects, but it remains least understood of the three body axes. We uncovered an unexpected role for metabolic regulation in left-right patterning. Analysis of the first spatial transcriptome profile of left-right patterning revealed global activation of glycolysis, accompanied by right-sided expression ofBmp7and genes regulating insulin growth factor signaling. Cardiomyocyte differentiation was left-biased, which may underlie the specification of heart looping orientation. This is consistent with knownBmp7stimulation of glycolysis and glycolysis suppression of cardiomyocyte differentiation. Liver/lung laterality may be specified via similar metabolic regulation of endoderm differentiation.Myo1d, found to be left-sided, was shown to regulate gut looping in mice, zebrafish, and human. Together these findings indicate metabolic regulation of left-right patterning. This could underlie high incidence of heterotaxy-related birth defects in maternal diabetes, and the association of PFKP, allosteric enzyme regulating glycolysis, with heterotaxy. This transcriptome dataset will be invaluable for interrogating birth defects involving laterality disturbance.

Neuroblastoma, the most common extracranial solid malignancy in children, accounts for 15% of pediatric cancer deaths despite multimodal therapy including surgical resection. Unfortunately, complete surgical resection remains challenging due to encasement of major neurovascular structures, unclear tumor margins, and remote nodal disease. While mouse models of neuroblastoma are extremely valuable for studying tumor biology and medical treatments, the small size renders the mouse model insufficient to evaluate novel surgical therapy.Here, we have developed a novel rat model of neuroblastoma to facilitate further development of surgical treatment. Human neuroblastoma cells (SK-N-BE(2)) were injected into the adrenal gland of RNU nude rats. They developed 2 cm xenograft tumors at 5 weeks which were easily identifiable on MRI imaging and on visual inspection. The rats began losing weight and neared end stage at 7 weeks, at which point surgical resection was attempted. While surgical resection was technically feasible, the rats were too frail to survive surgery at the late stage. The pathology of the tumors was consistent with neuroblastoma: small round blue cells with strong PHOX2B staining. Thus, we present a novel rat neuroblastoma model that can be used for development of surgical techniques, such as the use of intraoperative contrast agents.

The survival of childhood Wilms tumor is currently around 90%, with many survivors reaching reproductive age. Chemotherapy and radiotherapy are established risk factors for gonadal damage and are used in both COG and SIOP Wilms tumor treatment protocols. The risk of infertility in Wilms tumor patients is low but increases with intensification of treatment including the use of alkylating agents, whole abdominal radiation or radiotherapy to the pelvis. Both COG and SIOP protocols aim to limit the use of gonadotoxic treatment, but unfortunately this cannot be avoided in all patients. Infertility is considered one of the most important late effects of childhood cancer treatment by patients and their families. Thus, timely discussion of gonadal damage risk and fertility preservation options is important. Additionally, irrespective of the choice for preservation, consultation with a fertility preservation (FP) team is associated with decreased patient and family regret and better quality of life. Current guidelines recommend early discussion of the impact of therapy on potential fertility. Since most patients with Wilms tumors are prepubertal, potential FP methods for this group are still considered experimental. There are no proven methods for FP for prepubertal males (testicular biopsy for cryopreservation is experimental), and there is just a single option for prepubertal females (ovarian tissue cryopreservation), posing both technical and ethical challenges. Identification of genetic markers of susceptibility to gonadotoxic therapy may help to stratify patient risk of gonadal damage and identify patients most likely to benefit from FP methods.

In this study, we evaluated the impacts of ad libitum feedings on outcomes following laparoscopic pyloromyotomy in patients with infantile hypertrophic pyloric stenosis.Pediatric patients with infantile hypertrophic pyloric stenosis who underwent laparoscopic pyloromyotomy were included. Patients were stratified into ad libitum and structured feeding groups. Primary outcomes were times from surgery completion to goal feeding and discharge.A total of 336 patients were included in the study with 63 patients (18.8%) in the ad libitum feeding group. The ad libitum feeding group experienced significantly shorter times from surgery completion to both goal feedings (10.7 h vs 18.7 h; p 0.001) and hospital discharge (21.6 h vs 23.1 h; p = 0.008) compared to the structured protocol group. Postoperative emesis (47.% vs 30.8%; p = 0.011) was higher in the ab libitum cohort, but the rates of return to an emergency department and/or readmission (4.8% vs 2.2%; p = 0.26) were similar.Ad libitum feeding after pyloromyotomy decreases time to reach goal feeding and hospital discharge. While it may contribute to a higher incidence of emesis, it does not appear to significantly increase hospital readmission. Ad libitum feeding appears to be a safe and beneficial alternative to structured feeding protocols following pyloromyotomy.III.

Hirschsprung disease is characterized by the absence of ganglion cells in the enteric nervous system. Inability to pass meconium in the neonatal period, enterocolitis, bowel obstruction, or chronic constipation in older infants and children may be the presenting symptoms. Once diagnosed, surgical intervention is always required. Successful resection of all portions of aganglionic intestine may be accomplished through multiple surgical techniques. Depending upon the surgical approach required, regional anesthesia may be indicated to assist with pain control postoperatively. This chapter describes Hirschsprung disease and considers a variety of questions related to its diagnosis and treatment, as well as risks related to surgery, including anaphylaxis, laparoscopic complications, vascular injury, epidural complications, and issues related to neuraxial analgesia.