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

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

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A safe treatment option for intraperitoneal rhabdomyosarcoma in children below 5 years of age.

Advanced and relapsed intraperitoneal rhabdomyosarcomas in young children represent an oncological challenge and options for local tumor control are limited. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is commonly used in advanced peritoneal tumors in adults. However, no studies are available regarding CRS and HIPEC in young children. We report our experiences treating six patients with intraperitoneal rhabdomyosarcoma with CRS and HIPEC using cisplatin and doxorubicin focusing on safety and outcomes. No procedure-associated mortalities occurred and no major short- or long-term toxicities were recorded. All patients showed no evidence of disease after 12-month median (7-41) follow-up.

Hybrid interventions for catheter placement in pediatric intestinal rehabilitation patients with end-stage venous access.

PURPOSE: The purpose of this study is to analyze the combined approach of endovascular and open surgical procedures for insertion of permanent central venous catheters in children with intestinal failure and end-stage venous access. METHODS: Data of 14 children (16 interventions) with intestinal failure and end-stage venous access, treated within the pediatric intestinal rehabilitation program at our institution between September 2011 and November 2016, were retrospectively reviewed. The patients underwent hybrid endovascular/open surgical approaches for insertion of central venous catheters. Access to central veins was established through endovascular intervention; catheter placement was achieved with combined interventional and surgical measures depending on the individual vascular conditions. RESULTS: Median age at intervention was 47months (interquartile range (IQR),29-74), median time for interventions was 66min (IQR,42-111). Catheter placement was successfully achieved in all patients. The median dose of irradiation during angiography was 0.2Gy*cm2 (IQR, 0.2-0.6), no complications occurred during or after interventions. CONCLUSIONS: Hybrid endovascular/open surgical procedures can be successfully applied for restoring or maintaining permanent central venous catheters in children with intestinal failure and end-stage venous access. These approaches are a valuable contribution in intestinal rehabilitation programs contributing to a further decrease of the need for intestinal transplantation in affected patients. TYPE OF STUDY: Treatment Study. LEVEL OF EVIDENCE: Level IV.

Phosphatidylcholine kinetics in neonatal rat lungs and the effects of rhuKGF and betamethasone.

Surfactant, synthesized by type II pneumocytes (PN-II), mainly comprises phosphatidylcholine (PC) and is essential to prevent neonatal respiratory distress. Furthermore, PC is essential to lung tissue growth and maintenance as a membrane component. Recent findings suggest that the lung contributes to systemic lipid homeostasis via PC export through ABC-A1 transporter expression. Hence it is important to consider pharmacological interventions in neonatal lung PC metabolism with respect to such export. Five-day-old rats were treated with carrier (control), intraperitoneal betamethasone, subcutaneous recombinant human keratinocyte growth factor (rhuKGF), or their combination for 48 h. Animals were intraperitoneally injected with 50 mg/kg [D9-methyl]choline chloride 1.5, 3.0, and 6.0 h before death at day 7, and lung lavage fluid (LLF) and tissue were harvested. Endogenous PC, D9-labeled PC species, and their water-soluble precursors (D9-)choline and (D9-)phosphocholine were determined by tandem mass spectrometry. Treatment increased secreted and tissue PC pools but did not change equilibrium composition of PC species in LLF. However, all treatments increased specific surfactant components in tissue. In control rats, peak D9-PC in lavaged lung was reached after 3 h and was decreased at 6 h. Only 13% of this net loss in lavaged lung was found in LLF. Such decrease was not present in lungs treated with betamethasone and/or with rhuKGF. D9-PC loss at 3-6 h and PC synthesis calculated from D9 enrichment of phosphocholine indicated that daily synthesis rate is higher than total pool size. We conclude that lung tissue contributes to systemic PC homeostasis in neonatal rats, which is altered by glucocorticoid and rhuKGF treatment.

rhKGF stimulates lung surfactant production in neonatal rats in vivo.

Surfactant deficiency and bronchopulmonary dysplasia (BPD), major obstacles in preterm infants, are addressed with pre- and postnatal glucocorticoids which also evoke harmful catabolic side-effects. Keratinocyte growth factor (KGF) accelerates surfactant production in fetal type II pneumocytes (PN-II), protects epithelia from injury and is deficient in lungs developing BPD, highlighting its potential efficacy in neonates. Neonatal rats were treated with recombinant human (rh)KGF, betamethasone, or their combination for 48 hr prior to sacrifice after which body weight, surfactant, and tissue phosphatidylcholines (PC) were investigated at postnatal d3, d7, d15, and d21. Pneumocyte proliferation, surfactant protein (SP) expression and SP-B/C in lung lavage fluid (LLF) were also determined at d7 and d21 to identify broader surfactant changes occurring at the beginning and end of the initial alveolarization phase. While all treatments increased secreted surfactant PC, BM compromised animal growth whereas rhKGF did not. At d3 rhKGF was more effective in male compared to female rats. Single treatments became less effective towards d21. Neither treatment altered PC composition in LLF. BM inhibited PN-II proliferation and increased surfactant PCs at the expense of tissue PCs. rhKGF however increased surfactant PCs without decreasing other PC species. Whereas SP-B/C gene expression was induced by all treatments, the changes in secreted SP-B/C mirrored those observed for surfactant PC. Our results encourage investigation of the mechanisms by which rhKGF improves surfactant homoeostasis, and detailed examination of its efficacy in neonatal lung injury models with a view to implementing it as a non-catabolic surfactant-increasing therapeutic in neonatal intensive care.