[Role of perimatrix fibroblasts in development of acquired middle ear cholesteatoma. A hypothesis].
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 aim of this study was to understand the historical development of the knowledge of cholesteatoma. Review of the literature from 1683 to 1999 concerning the date-related knowledge of cholesteatoma. In 1683, Duverney first described a temporal bone tumor probably corresponding to a cholesteatoma. Until 1838, when Müller coined the term cholesteatoma, nothing new about this condition appeared in medical publications. After 1838, three main theories about the pathogenesis of cholesteatoma were published. Virchow, in 1855, considered cholesteatoma to be a tumor arising from the metaplasia of mesenchymal cells to epidermal cells, growing then as tumoral cells. Gruber, Wendt, and von Troeltsch, in 1868, considered cholesteatoma to be the result of a metaplasia not of bone cells but of tympanic mucosa cells into a malpighian epithelium. Politzer, in 1869, assumed that cholesteatoma was a glandular neoplasm of middle ear mucosa. Bezold and Habermann, in 1889, considered cholesteatoma to be the result of migration of the external ear canal epidermis into the tympanic cavity via a marginal perforation after acute or chronic otitis. It took 40 years of discussions about these three theories to finally confirm that Habermann and Bezold were correct. The knowledge of cholesteatoma has evolved with other medical branches. As otologists began to monitor their patients in vivo, not limiting their observations to temporal bone dissections, the genesis of cholesteatoma became well understood. Today, with immunology and new histopathologic techniques, it is anticipated that we will learn much more about cholesteatoma.Ontology & Neurotology 12/2001; 22(6):723-30. · 2.01 Impact Factor
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ABSTRACT: Chronic epitympanic otitis media, or chronic suppurative osteitis, is a destructive form of chronic middle-ear inflammation. The therapy of choice is complete surgical removal of the squamous epithelium from the middle ear. It is often impossible to inspect all areas of the middle ear with the posterior canal wall intact. Not all recesses can be reliably monitored with the microscope, particularly in the area of the antrum and hypotympanum. Residual squamous epithelium here causes frequent recurrences following cholesteatoma surgery. This study examines the effect of argon and diode lasers on cholesteatoma tissue. The aim is to develop a laser treatment selectively directed against cholesteatoma cells that can be performed after cholesteatoma surgery to eliminate any residual squamous epithelium. Intraoperatively harvested monolayer-cultured cholesteatoma cells stained in vivo with various absorption enhancers served as the in vitro examination model. Argon (499 nm) and diode lasers (810 nm) were applied since their irradiation has an appropriate tissue penetration depth and is absorbed by various chromophores such as neutral red (475-500 nm), fluorescein (488 nm), and indocyanine green (790-810). Intracellular staining of cultured cells increased the optical density at the wavelength corresponding to the dye. Neutral red damaged 50-60% of cultured cells merely by intracellular accumulation at high concentrations. An additive cell destruction of about 30% was achieved by also applying argon laser irradiation. Fluorescein diacetate caused no appreciable stain-induced damage to cultured cholesteatoma cells. Argon laser irradiation destroyed up to 60% of the cultures. Indocyanine green resulted in only minor damage to cultured cells. The diode laser destroyed up to 60% of the irradiated cells. Selective staining of cholesteatoma cells was not achieved with any of the dyes examined. Thus, other stained tissue could be damaged. Staining and subsequent laser irradiation destroys up to 60% of cultured cholesteatoma cells. Unstained irradiated cells are not affected. Indocyanine green and fluorescein are nontoxic and may thus be used as absorption enhancers. The diode and argon lasers appear to be basically suitable. Cell staining is not selective, i.e., other tissues would also be stained and damaged. To avoid such unwanted damage, it would be desirable to couple the chromophore to a specific antibody that binds only to cholesteatoma cells.Lasers in Medical Science 02/2005; 19(4):248-56. · 2.40 Impact Factor
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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