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获得性胆脂瘤发病机制的新理论:黏膜牵引。

A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction.

作者信息

Jackler Robert K, Santa Maria Peter L, Varsak Yasin K, Nguyen Anh, Blevins Nikolas H

机构信息

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, U.S.A.

Department of Otolaryngology-Head and Neck Surgery, Oregon Health and Science University, Portland, Oregon, U.S.A.

出版信息

Laryngoscope. 2015 Aug;125 Suppl 4:S1-S14. doi: 10.1002/lary.25261. Epub 2015 May 25.

Abstract

OBJECTIVES/HYPOTHESIS: Although the migration of its squamous outer surface of the tympanic membrane has been well characterized, there is a paucity of data available concerning the migratory behavior of its medial mucosal surface. Existing theories of primary acquired cholesteatoma pathogenesis do not adequately explain the observed characteristics of the disease. We propose a new hypothesis, based upon a conjecture that mucosal membrane interactions are the driving force in cholesteatoma.

STUDY DESIGN

A retrospective chart review and a prospective observational cohort study in rats.

METHODS

After developing the new theory, it was tested through both clinical and experimental observations. To evaluate whether impairment of middle ear mucociliary migration would influence cholesteatoma formation, a retrospective chart review evaluating cholesteatoma occurrence in a sizable population of patients with either primary ciliary dyskinesia (PCD) or cystic fibrosis (CF) was performed. To study mucosal migration on the medial aspect of the tympanic membrane, ink tattoos were monitored over time in a rat model.

RESULTS

No cholesteatomas were identified in either PCD patients (470) or in CF patients (1,910). In the rat model, mucosa of the posterior pars tensa migrated toward the posterior superior quadrant, whereas the mucosa of the anterior pars tensa migrated radially toward the annulus.

CONCLUSION

Mucosal coupling with traction generated by interaction of migrating opposing surfaces provides the first comprehensive theory that explains the observed characteristics of primary acquired cholesteatoma. The somewhat counterintuitive hypothesis that cholesteatoma is fundamentally a mucosal disease has numerous therapeutic implications.

摘要

目的/假设:虽然鼓膜鳞状外表面的迁移已得到充分表征,但关于其内侧黏膜表面的迁移行为的数据却很匮乏。现有的原发性后天性胆脂瘤发病机制理论并不能充分解释该疾病观察到的特征。我们基于黏膜相互作用是胆脂瘤形成的驱动力这一推测提出了一个新的假设。

研究设计

一项回顾性病历审查和一项对大鼠的前瞻性观察队列研究。

方法

在提出新理论后,通过临床和实验观察对其进行检验。为评估中耳黏液纤毛迁移受损是否会影响胆脂瘤形成,对大量原发性纤毛运动障碍(PCD)或囊性纤维化(CF)患者的胆脂瘤发生情况进行了回顾性病历审查。为研究鼓膜内侧的黏膜迁移,在大鼠模型中对墨水纹身进行了长期监测。

结果

在PCD患者(470例)或CF患者(1910例)中均未发现胆脂瘤。在大鼠模型中,紧张部后部的黏膜向后上象限迁移,而紧张部前部的黏膜则呈放射状向鼓环迁移。

结论

黏膜与迁移的相对表面相互作用产生的牵引力耦合,提供了第一个全面解释原发性后天性胆脂瘤观察到的特征的理论。胆脂瘤从根本上说是一种黏膜疾病这一有点违反直觉的假设具有许多治疗意义。

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