Further evidence for Zenker’s diverticulum in a slim woman with body figure predisposition: a case report and literature review

Zenker’s diverticulum (ZD) is a bag-like pharyngeal pouch that protrudes to the outside of the pharynx. It is thought to be an acquired disease that occurs following the dysfunction of laryngopharynx muscle, and certain body shapes may be predisposed to this condition. We report a 56-year-old female of slim build with ZD. Computed tomography scanning revealed a hypodense lesion on the left posterior side of her upper esophagus that was filled with air and had no obvious wall. To verify this finding, a barium esophagogram was carried out which showed a round pouch at the level of the 6th cervical vertebral body that communicated with the esophagus through a narrow neck. ZD was subsequently confirmed by endoscopy. These findings provide further evidence in support of a body shape predisposition for ZD.

654 PHARYNGEAL POUCH SURGERY IN OCTO- AND NONAGENARIANS IS SAFE AND EFFECTIVE: A MULTICENTER COMPARATIVE COHORT STUDY

Surgery is the only effective treatment strategy for a symptomatic pharyngeal pouch. However, octo- and nonagenarians are often denied referral to a surgeon because of perceived increased risks. Here, we examine the perioperative outcomes of pharyngeal pouch surgery in octo- and nonagenarians in comparison to patients under 80 years-of-age. Methods Analysis of a prospectively maintained database of 113 patients (≥80 years-of-age: 27, <80 years-of-age: 86) who underwent pharyngeal pouch surgery across seven hospitals from 1 January 2006 to 30 September 2020. Results Patients ≥80 years-of-age had comparable operative time, complication profile, intensive care admission, emergency reoperation, and revisional surgery as their younger counterparts. The severity of complications was not significantly different between the two age groups. No surgical mortality was recorded. Multivariate analysis demonstrated that diverticulectomy combined with cricopharyngeal myotomy independently predicted higher rates of complications (OR: 4.53, 95% CI: 1.43-14.33, p = 0.010), but also greater symptomatic improvement (OR: 4.36, 95% CI: 1.50-12.67, p = 0.007). Importantly, a greater proportion of octo- and nonagenarians experienced improved swallowing than patients <80 years-of-age (96.3% vs. 74.4%, p = 0.013). Advanced age was not predictive of complications on multivariate analysis. Conclusion In appropriately selected patients, pharyngeal pouch surgery can be safely offered to patients above 80 years-of-age resulting in significant improvement in their quality-of-life. These patients should not be denied surgery on the basis of advanced age alone.

EZH2 is required for parathyroid and thymic development through differentiation of the third pharyngeal pouch endoderm

The Ezh2 gene encodes a histone methyltransferase of the Polycomb Repressive Complex 2 that methylates histone H3 lysine 27. In this work we asked whether EZH2 has a role in the development of the pharyngeal apparatus and whether it regulates the expression of the Tbx1 gene, which encodes a key transcription factor required in pharyngeal development. To these ends, we performed genetic in vivo experiments with mouse embryos and we used mouse embryonic stem cell (ESC)-based protocols to probe endoderm and cardiogenic mesoderm differentiation. Results showed that EZH2 occupies the Tbx1 gene locus in mouse embryos, and that suppression of EZH2 was associated with reduced expression of Tbx1 in differentiated mESCs. Conditional deletion of Ezh2 in the Tbx1 expression domain, which includes the pharyngeal endoderm, did not cause cardiac defects but revealed that the gene has an important role in the morphogenesis of the 3rd pharyngeal pouch (PP). We found that in conditionally deleted embryos the 3rd PP was hypoplastic, had reduced expression of Tbx1, lacked the expression of Gcm2, a gene that marks the parathyroid domain, but expressed FoxN1, a gene marking the thymic domain. Consistently, the parathyroids did not develop, and the thymus was hypoplastic. Thus, Ezh2 is required for parathyroid and thymic development, probably through a function in the pouch endoderm. This discovery also provides a novel interpretational key for the finding of Ezh2 activating mutations in hyperparathyroidism and parathyroid cancer.

Pharyngeal pouches provide a niche microenvironment for arch artery progenitor specification

ABSTRACTThe paired pharyngeal arch arteries (PAAs) are transient blood vessels connecting the heart with the dorsal aorta during embryogenesis. Although PAA malformations often occur along with pharyngeal pouch defects, the functional interaction between these adjacent tissues remains largely unclear. Here, we report that pharyngeal pouches are essential for PAA progenitor specification in zebrafish embryos. We reveal that the segmentation of pharyngeal pouches coincides spatiotemporally with the emergence of PAA progenitor clusters. These pouches physically associate with pharyngeal mesoderm in discrete regions and provide a niche microenvironment for PAA progenitor commitment by expressing BMP proteins. Specifically, pouch-derived BMP2a and BMP5 are the primary niche cues responsible for activating the BMP/Smad pathway in pharyngeal mesoderm, thereby promoting progenitor specification. In addition, BMP2a and BMP5 play an inductive function in the expression of the cloche gene npas4l in PAA progenitors. cloche mutants exhibit a striking failure to specify PAA progenitors and display ectopic expression of head muscle markers in the pharyngeal mesoderm. Therefore, our results support a crucial role for pharyngeal pouches in establishing a progenitor niche for PAA morphogenesis via BMP2a/5 expression.