[Role of perimatrix fibroblasts in development of acquired middle ear cholesteatoma. A hypothesis].

Universitäts-HNO-Klinik Würzburg.
HNO (Impact Factor: 0.42). 06/1998; 46(5):494-501.
Source: PubMed

ABSTRACT The epithelial pathogenesis of acquired cholesteatoma has been widely accepted, but clinical and experimental data have not been able to answer questions like: How does a cholesteatoma start or grow or how is bone resorption of conducted? From our own experiments and literature a new hypothesis of cholesteatoma origin and growth is drawn. Three prerequisites are necessary for development: (1) the unique anatomical situation at the ear-drum (two different epithelial layers close together); (2) chronic destruction of the submucosal tissue in the middle ear (infection, inflammation); (3) wound healing (proliferation phase). Destruction of the submucosal space by middle ear infection and cell necrosis starts the wound healing cascade. In wound healing generally the connective tissue fibroblasts and macrophages play a pivotal role. Cytokines of the wound healing thought to promote the re-epithelization of the mucosal defect and scar tissue development act upon the intact squamous cell layer of the outer surface of the ear-drum at the same time. Thereby a proliferation of the undamaged epithelial layer is induced. Cholesteatoma matrix is always surrounded by a layer of connective tissue, the perimatrix. Persistence of the inflammation causes permanent wound healing in the perimatrix, proliferation of the fibroblasts (granulation tissue) and proliferation of the epithelium (matrix). It is speculated that by virtue of wound healing cytokines of fibroblasts and macrophages are the driving forces of cholesteatoma origin, growth and bone destruction.

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    ABSTRACT: The quantification of angiogenesis and metalloproteinases may be useful in cholesteatoma behavior assessment as markers of its aggressiveness. The objective of this study is to compare markers CD31, MMP2 and MMP9 in pediatric and adult patients. This study is based on cross-sectional studies of pediatric (<or=18 years old) and adult groups (>or=19 years old). Samples of 120 cholesteatomas were fixed in 10% formol, prepared on five slides of each sample through habitual histological techniques, and number of blood vessels (CD31), marking with MMP2 and MMP9, number of matrix cells and thickness at perimatrix cell were observed. Data were analyzed through SPSS using Spearman and Mann-Whitney coefficients. Cholesteatomas were equally distributed: 60 in pediatric patients (11.77 +/- 3.57 years); 60 in adult patients (38.29 +/- 14.51 years). When correlating the number of blood vessels and metalloproteinases with perimatrix thickness, we obtained the following values: pediatric CD31, 7 (4-11); adult CD31, 4 (0-10) (P = 0.044); pediatric cytoplasmatic MMP2, 1 (0-3); adult cytoplasmatic MMP2, 0 (0-1) (P = 0.006); pediatric nuclear MMP2, 0 (0-1); adult nuclear MMP2, 0 (0-1) (P = 0.056); pediatric MMP9, 2 (0-4); adult MMP9, 0 (0-4) (P = 0.049). In conclusion, pediatric cholesteatomas present a more exacerbated inflammatory degree, produce more metalloproteinases, factors that, when combined, could characterize pediatric cholesteatomas as more aggressive than adult cholesteatomas.
    Archives of Oto-Rhino-Laryngology 04/2009; 266(10):1553-61. · 1.29 Impact Factor
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    ABSTRACT: Anomalous proliferation of the cholesteatoma epithelium is caused by extrinsic factors such as toxins or bacterial antigens combined with lytic enzymes, lymphokines and cytokines released from the inflammatory infiltrate. This could explain the close relationship between the aggressiveness of cholesteatoma and repeated bacterial superinfection, therefore it is very important to know the bacteria involved in order to control the regrowth of skin following surgery, reduce the aggressive potential of the cholesteatoma and limit the incidence of complications. This study focused on 70 females and 80 males aged between 15 and 65 years, affected by cholesteatomatous otitis media; all underwent bacteriological examination of the auricular secretion. The floral bacteria which proved to play the most important role (60.3%) were the aerobic type and the highest levels were those of Pseudomonas aeruginosa (31.1%) followed by Staphylococcus aureus (19.1%), Proteus mirabilis (7.7%), Escherichia coli (1.4%) and Klebsiella pneumoniae (1%). Anaerobic floral bacteria were found in a fairly high percentage of cases (38.2%); in particular, anaerobic gram-positive cocci (Peptococcus 12.4% and Peptostreptococcus in 4.8% of cases), Bacteroides (12.4%), Clostridium (3.8%), Fusobacterium (2.9%) and Propionobacterium (1.9%) were isolated. In 3 cases of mycetes (1.4%) only Aspergillus, in association with Pseudomonas and Staphylococcus, was identified. The study showed, then, how effective second generation fluoroquinolones and third generation cephalosporins are (the latter being used in pre-adolescent children), the reason being that these antibiotics work not only on Pseudomonas and Staphylococcus, but also on the anaerobic bacteria.
    Acta otorhinolaryngologica Italica: organo ufficiale della Società italiana di otorinolaringologia e chirurgia cervico-facciale 08/2009; 29(4):197-202. · 0.79 Impact Factor
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    ABSTRACT: Copyright: © 2012 Frickmann H, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    Otolaryngology 01/2012; S5(001):1.