Duodenal Atresia-Tandler’s “Epithelial Plug Stage” Revisited

Background: Duodenal atresia is the most common type of intestinal atresia. Pathogenesis of duodenal atresia can be explained by an embryological theory that involves persistent physiologic epithelial occlusion (“epithelial plug”), first published in 1900. Tandler’s developmental arrest theory has been accepted by the majority of recognized modern textbooks to date. The aim of the presented study is to re-evaluate the relevance of Tandler’s observations. Method: Tandler’s paper was reviewed retrospectively and discussed from the point of view of subsequent research. Results and Discussion: Local epithelial proliferation, vacuolization failure and mesenchyme ingrowth may continuously serve as a partly convincing but incomplete embryologic model to explain membranous duodenal atresia. Tandler’s theory has some weak points regarding the epithelial-mesenchymal interaction, the predisposition of the post-ampullary region, the association of duodenal atresia with other malformations and trisomy 21, and familial occurrence. Shrinkage artifacts, misinterpretation of a three-dimensional problem investigated with a two-dimensional tool (light microscope), animal studies, and the lack of apoptosis call the real existence of a solid stage in early duodenal embryology into question. Conclusion: More sophisticated morphologic, genetic and molecular-biological investigations revealed new insights regarding endoderm to mesoderm signaling as an important key to the pathogenesis of duodenal atresia.