Background: To coordinate and align the content for registration of cholesteatoma care. Methods: Systematic Delphi consensus procedure, consisting three rounds: two written sessions followed by a... Show moreBackground: To coordinate and align the content for registration of cholesteatoma care. Methods: Systematic Delphi consensus procedure, consisting three rounds: two written sessions followed by a face-to-face meeting. Before this procedure, input on important patient outcomes was obtained. Consensus was defined as at least 80% agreement by participants. Hundred-thirty-six adult patients who had undergone cholesteatoma surgery and all ENT surgeons of the Dutch ENT Society were invited. The consensus rounds were attended by ENT surgeons with cholesteatoma surgery experience. Feasibility and acceptability of outcome measures and reporting agreements were assessed in round 1 by 150 ENT surgeons. In round 2 definitions were narrowed and context information to interpret outcome measure were questioned. In round 3, the results, amendments, and the open-ended points were discussed to reach agreement. Results: Most important outcome measures are: 1) the presence or absence of a cholesteatoma in the first 5 years after surgical removal of cholesteatoma, 2) hearing level after surgical removal of cholesteatoma, and 3) the documented assessment of patient's complaints with a validated patient reported outcome measures questionnaire (PROM). Furthermore, consensus was reached on the registration of cholesteatoma type (residual/recurrent), localization of cholesteatoma, and reporting of the presence of cholesteatoma in the follow-up. Conclusion: Consensus was reached on the content and method of registration of cholesteatoma care based on patient's and ENT surgeons input. Three outcome measures were defined. National agreements on the method and content of registration will facilitate monitoring and feedback to the ENT surgeon about the cholesteatoma care. Show less
Cholesteatoma is a benign, gradually expanding destructive epithelial lesion of the temporal bone, often accompanied with inflammation. The complications can be severe, e.g., destruction of the... Show moreCholesteatoma is a benign, gradually expanding destructive epithelial lesion of the temporal bone, often accompanied with inflammation. The complications can be severe, e.g., destruction of the ossicular chain and otic capsule with consecutive hearing loss. Several hypotheses for the pathogenesis of human cholesteatoma have been proposed but are still controversial. In this thesis, protein signaling pathways were investigated which are involved in different aspects of cholesteatoma pathogenesis, such as hyperproliferation, aberrant differentiation, and extra-cellular matrix deposition. In cholesteatoma epithelium increased expressions of those proteins were found which are involved in proliferation (Ki-67), cell cycle arrest (p53, p21), early terminal differentiation (involucrin) and survival (pAKT). The proteins of which the expressions were decreased were those concerning late terminal differentiation (filaggrin) and apoptosis (active caspase 3). Moreover, increased activation of MAPK- and its association with TGF_ cellular signaling cascades were demonstrated. In cholesteatoma stroma, increased extracellular matrix deposition, visualized by accumulation of EDA-Fibronectin, was present. These results were placed in the context of the interconnected signaling processes of wound healing. Concluding: cholesteatoma behaves as a chronic wound in which a persistent inflammation appears to be a contributing factor to its chronicity. Research into pharmacological interventions aimed at control of inflammation is recommended. Show less
