To clarify specific mechanisms underlying cholesteatoma-induced bone destruction, surgical specimens of middle ear inflammatory granulation tissue with or without cholesteatoma were maintained in vitro and the bone-resorbing activity in their culture supernatants was analyzed by means of calcium release from mouse calvaria. Almost the same levels of bone-resorbing activity and prostaglandin (PG) E2 were found in the supernatants of both types of tissue. By contrast, aural polyp tissue yielded hardly any such activity or PGE2. Under the influence of indomethacin, however, only tissue with cholesteatoma produced considerable bone resorption activity, whereas PGE2 production was suppressed completely. Such activity in the cholesteatoma culture supernatant was not due to contamination of endotoxin and proved to be blocked by the introduction of anti-interleukin (IL)-1 alpha antibody into the calvarial assay system. Anti-IL-1 beta antibody had no effect on such activity. Interleukin-1 alpha was detected only in cholesteatoma tissue culture supernatants by means of enzyme-linked immunosorbent assay and by bioassay. These data suggest that the bone destruction in otitis media with cholesteatoma may be attributed to IL-1 alpha in addition to PGE2.
The mean of the postoperative hearing gain was 10.3 dB and no cases of postoperative hearing loss were observed. Although postoperative re-perforation was found in 18 cases (24.0%), the re-perforation was closed in 16 of these cases in the outpatient department by the same procedure using frozen autologous tissue that had been harvested previously in surgery. Including these cases, the total success rate was 97.3%.
Organic acids in the contents of the cholesteatoma sac from 28 cases were studied by gas chromatographic technique. Five volatile fatty acids (acetate, propionate, isobutyrate, butyrate and isovalerate) and lactate were detected in large amounts, which may lower the pH of the cholesteatoma content. These acids were considered to be derived from products of anaerobic microorganisms. Therefore, the contents from 12 cases were cultured anaerobically in a glove box. Obligate microorganisms were identified in 92% of the cases and Peptococcus, Bacteroides, and Clostridium species were frequently isolated. In vitro, such obligate anaerobes produced various organic acids from the cholesteatoma content. Facultatives such as Staphylococcus aureus and Proteus mirabilis produced acetate in the content under aerobic and anaerobic conditions, whereas no organic acid was produced by Pseudomonas aeruginosa. Organic acids in the cholesteatoma content could be fermentative products made by the microorganisms, anaerobes and facultatives, which use the content as a substrate for acid production.
Severe bone destruction in a cholesteatoma is one of the characteristic clinical features. To clarify the mechanism of bone destruction in cholesteatoma, the matrix of cholesteatoma and the attached bone, obtained during middle ear surgery, was observed by light microscope. Rupture of the epithelial lining in a cholesteatoma and the escaping contents (keratin), which gave rise to intense characteristic granulations in subepithelial tissue, were found. Furthermore bone destruction was always found at the site of subepithelial tissue of cholesteatoma. From these facts, the escape of contents from the sac of cholesteatoma into the subepithelial layer is considered to be an important factor in the mechanism of bone destruction.
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