, Volume 31, Issue 7, pp 1512-1517
Date: 30 May 2007

Reduced Neuronal Innervation in the Distal End of the Proximal Esophageal Atretic Segment in Cases of Esophageal Atresia with Distal Tracheoesophageal Fistula

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Esophageal dysmotility is a common occurence after surgical repair of proximal esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). The etiology of this motility disorder, however, remains controversial. Esophageal dysmotility also is present in isolated TEF or EA before surgery, suggesting a congenital cause. However, there is no information available in the literature with regard to the intramural nervous system of the human esophagus in EA-TEF.

Patients and Methods

We examined the distal end of proximal esophageal atretic segment of neonates undergoing EA-TEF repair for intrinsic neuronal innervation. Using specific antibodies, we studied neuronal markers of specimens from nine cases of EA-TEF and 9 cases of normal esophagus by immunohistochemistry using neurofilament (NF), synaptophysin (SY), S100, and glial cell line-derived neurotrophic factor (GDNF).


In the atretic segment, specimens staining with hematoxylin and eosin showed that there were marked hypoganglionosis and immature ganglion cells in the myenteric plexus. GDNF immunoreactivity in the atretic esophagus were markedly reduced in both the muscular layer and myenteric plexus. SY and NF-immunorective nerve fibers were distributed throughout the myenteric plexus of the normal esophagus, but the scarcity of these immunoreactive nerve fibers in the atretic esophagus was apparent. In contrast, the density of immunorective nerve fibers for S100 in the myenteric plexus and muscular layer was increased in the distal end of the atretic esophagus.


We concluded that the distribution of ganglion cells and some nerve fibers in the distal end of the atretic esophageal segment is deficient. Inadequate and abnormal neuronal innervation of the esophagus could be related to the esophageal dysmotility seen in EA. Because GDNF is a survival factor for central and peripheral neurons, defective expression of GDNF could have an important role in the defective and/or abnormal neuronal innervation of atretic esophageal segment.