Laparoscopic Versus Open Nissen Fundoplication in Infants After Neonatal Laparotomy

BACKGROUND: Nissen fundoplication is an effective treatment of gastroesophageal reflux in infants. Laparoscopic procedures after previous laparotomy are technically more challenging. The role of laparoscopic Nissen fundoplication after neonatal laparotomy for diseases unrelated to reflux is poorly described. METHODS: This was a retrospective review of open vs laparoscopic Nissen fundoplication in infants after neonatal laparotomy. Of 32 infants who underwent neonatal laparotomy, 26 required a surgical antireflux operation within the first year of life. Twelve infants underwent laparoscopic Nissen fundoplication versus 14 infants who underwent open Nissen fundoplication. Parameters like age, weight, operative time, number of previous operations, length of stay following fundoplication, time to feedings, and complications were compared between the 2 groups. RESULTS: No statistically significant differences existed between most of the parameters compared following laparoscopic vs open Nissen fundoplication. No conversions to open procedures were necessary in infants undergoing laparoscopic fundoplication, and these infants resumed enteral feeds earlier than those who underwent the open procedure. CONCLUSION: Laparoscopic compared with open Nissen fundoplication performed in infants after a neonatal laparotomy were comparable procedures across most data points studied. However, a laparoscopic fundoplication did allow for earlier return to enteral feeds compared with the open approach. Laparoscopic Nissen fundoplication is technically feasible, safe, and effective in the treatment of gastroesophageal reflux in infants with a previous neonatal laparotomy

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10-8), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH

Triple fistula: management of a double tracheoesophageal fistula with a third H-type proximal fistula

Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a relatively common congenital condition in which there have been several described anatomical variants. The most common type, EA with distal TEF, comprises more than 75% of cases in many reports. Less commonly, a smaller proximal pouch fistula (H-type) will be associated with this most common variant in 1.4% of these cases. Only 2% of all cases of EA/TEF will have 2 large fistulas between the trachea and esophagus in which the end of the upper esophageal pouch connects terminally to the midtrachea and the distal esophagus arises from the trachea near the carina. Here we describe the management of an infant with this type of EA/TEF who was also found to have an H-type TEF of the proximal trachea. The combination of this type of EA/TEF with an associated H-type TEF or triple fistula has been previously described in the literature in only 1 other patient. © 2007 Elsevier Inc. All rights reserved

Thoracoscopic aortopexy for vascular compression of the trachea: Approach from the right

Tracheomalacia resulting from vascular compression of the trachea may require aortopexy for symptomatic relief. Several operative approaches have been described for infants and children. The authors describe the technique of aortopexy by means of a right-sided thoracoscopic method as the initial approach to relieve tracheal compression in 2 children. Intraoperative bronchoscopy is mandatory to assess the adequacy of aortopexy prior to the completion of suture placement. This procedure was very successful in relieving tracheal compression in a 17-month-old boy with an aberrant innominate artery take-off and in a 2-year and 7-month-old boy with a history of esophageal atresia/ tracheoesophageal fistula repair and severe tracheomalacia. A right-sided thoracoscopic approach to aortopexy in infants with severe tracheomalacia may be successfully performed as the initial operative intervention in infants with vascular compression of the trachea. © 2008 Mary Ann Liebert, Inc

Role of nitric oxide and peroxynitrite in gut barrier failure

Bacterial translocation (BT) may be a normal physiologic process that is important for mucosal antigen sampling in the gut. However, physiologic insults such as endotoxemia, hemorrhagic shock, or necrotizing enterocolitis (NEC) may lead to pathologic BT and thus contribute to the pathogenesis of nosocomial infection. The mechanism may involve accelerated enterocyte apoptosis at the intestinal villus apex resulting, at least transiently, in a "bare area" at the villus tip where bacteria can attach and traverse the epithelium. Evidence suggests that sustained upregulation of the inducible isoform of nitric oxide synthase (NOS-2) co-localizes with enterocyte apoptosis and immunoreactivity to 3-nitrotyrosine, the footprint of peroxynitrite (ONOO-), a potent oxidant formed by the reaction of nitric oxide (NO) with superoxide. We propose that the bare area at the villus apex is caused by apoptosis of enterocytes that have migrated from the base of the crypts to the villus apex and are shed into the intestinal lumen. These bare areas, and thus the degree of BT, may be the result of an imbalance between enterocyte proliferation and apoptosis. We postulate that normal enterocyte apoptosis is mediated by the caspase cascade, whereas enterocyte proliferation and differentiation in the crypt may be regulated by tyrosine kinase-dependent signaling pathways. Both of these cellular pathways may be influenced by overproduction of NO and its metabolite ONOO-. Therefore, sustained NO production and ONOO- formation occurring in inflammatory states may differentially accelerate apoptosis in the villus apex and/or inhibit proliferation at the base of the crypts resulting in expanded extrusion zones at the villus tip and accelerated BT