Samuel Razmi

Introduction: Traditionally in human embryogenesis, the esophagus and trachea develop side by side and separate at around weeks four to six. Tracheoesophageal fistula is a rare birth defect (1:3500-4500) that occurs when the esophagus and trachea anastomose during embryogenesis^1,2,3.  In extremely rare cases (1:20,000), the gap between the esophagus and trachea is too large to be surgically repaired. These cases are known as long-gap esophageal atresia^2,3,4. There are no currently agreed upon treatment options for this condition, thus a molecular understanding of why this specific subset of tracheoesophageal fistula develops is necessary to elucidate future treatment options⁵. Methods: A retrospective review was conducted of all literature that investigated the mechanisms of long-gap tracheoesophageal fistula vs. tracheoesophageal fistula. Results: In mouse models exploring the development of long-gap esophageal atresia, researchers found that Adriamycin impacts the location of the notochord and simultaneous disrupts the Sonic hedgehog gene (Shh), thus implicating the Shh role and embryonic position of the notochord as a potentiating factor for long-gap tracheoesophageal atresia formation¹. Further studies looking at Shh gene implication in long-gap tracheoesophageal atresia found that disruptions of the Shh receptor Gli-2 may also play a role in the formation of this condition⁶. Other studies found that exogenous Shh can rescue disease models^6,7. Two promising studies were found that utilized swine models to successfully create animal and cellular scaffold models of this condition which may usher in an era of necessary animal research to better understand this condition^7,8. Finally, studies have shown that the use of botulinum toxin injections have a positive effect on stretch characteristics of esophageal tissue in rat models, thus elucidating a potential treatment option for this condition^9,10. Conclusion:  The mechanisms of the development of long-gap tracheoesophageal atresia share many similarities with those of non long-gap tracheoesophageal atresia, yet traverse a distinct and unique pathway. As a relatively poorly understood area of congenital abnormalities, there is still much to be uncovered about this extremely rare clinical presentation.

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8. Jensen T, Wanczyk H, Sharma I, Mitchell A, Sayej WN, Finck C. Polyurethane scaffolds seeded with autologous cells can regenerate long esophageal gaps: An esophageal atresia treatment model. Journal of pediatric surgery. 2019;54(9):1744-1754. doi:10.1016/J.JPEDSURG.2018.09.024
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