Intrinsic esophageal innervation in esophageal atresia without fistula

Abstract

Esophageal atresia and tracheo-esophageal fistula (EA + TEF) are often associated with malformations of neural crest origin. Esophageal innervation is also derived from the neural crest and it is abnormal in EA + TEF in which there is motor dysfunction. Our aim was to examine the intrinsic esophageal innervation in children with isolated EA in which different embryogenic mechanisms might be involved. Specimens from the proximal and distal esophageal segments of 6/35 patients who had esophageal replacement for isolated EA between 1965 and 2006 were suitable for the study. They were sectioned and immunostained with anti-neurofilament (NF) and anti-S-100 antibodies. The muscle and neural surfaces on each section were measured with the assistance of image processing software. The surface of the ganglia and the number of neurons per ganglion were determined at high power microscopy. The findings were compared with those of six autopsy specimens from newborns dead of other diseases by means of standard statistical tests and a significance threshold of P < 0.05. Unmatched age/size of babies in isolated EA and control groups precluded comparison of the relative surfaces occupied by neural elements. Patients with pure EA had denser fibrilar network and larger ganglia than controls. The number of neurons/ganglion were similar in both groups although the cells from EA patients were larger. The findings were similar at both esophageal levels studied. In spite of methodologic biases, it seems that intrinsic esophageal fibrilar network is denser and the intramural ganglia larger with larger cells in patients with pure EA than in controls on both esophageal ends of the organ. These neural anomalies are only in part reminiscent of those described in regular EA/TEF but may as well explain esophageal dysfunction in patients with repaired isolated EA.

Anti-reflux surgery for patients with esophageal atresia

“…19,20 This is due to the deficient arrangement of the muscle layers and damage to the innervation of the repaired esophagus in EA/TEF. Extrinsic innervation by branches of the vagus and laryngeal nerves, 21 and also intrinsic innervation 22,23 are congenitally deficient in EA. Similar anomalies can be reproduced in the rat and mouse models of the malformation.…”

Defective upper gastrointestinal function after repair of combined esophageal and duodenal atresia

“…Cranial displacement of the gastroesophageal junction owing to traction on the distal esophagus to achieve anastomosis, disproportion between the upper pouch and the fistula, and damage to esophageal innervation during dissection are some of the factors that may disturb the mechanisms that prevent GER [6]. In addition, the anomalous extrinsic and intrinsic innervation [7][8][9][10], the abnormal gastric motility with delayed gastric emptying associated with a slower myoelectric gastric activity undoubtedly plays a crucial role in the pathogenesis of GER in these patients [11][12][13][14][15][16]. Survivors of the repair of isolated duodenal atresia also suffer significant gastrointestinal morbidity such as megaduodenum (up to 95%), bile reflux gastritis (up to 45%), esophagitis and gastritis (up to 35%), GER (up to 17%), and delayed transit (up to 12%) [4,17,18].…”

Oesophageal atresia associated with congenital oesophageal stenosis

“…The bathing of the anastomotic line in stomach acid results in an increased incidence of stricture and leak. Tension on the anastomosis causing shortened intra-abdominal oesophageal length and blunting of the angle of His,14 intrinsic oesophageal dysmotility, intrinsic innervation disorders,15 denervation from extensive oesophageal pouch dissection and gastric dysmotility16 all contribute to the pathogenesis of gastro-esophageal reflux disease (GERD) in EA.…”