Effect of 5-fluorouracil in cholesteatoma development in an animal model

This investigation was designed to evaluate the effects of the antimetabolite 5-fluorouracil (5-FU) on cholesteatoma formation in a chinchilla model. The animals received middle ear applications of propylene glycol according to a procedure previously shown to produce cholesteatomas in 60% to 70% of animals. A 5% solution of 5-FU was then applied to the lateral surface of the tympanic membrane (TM) and, after 1 month, temporal bones were taken for histologic study. No macroscopically visible cholesteatomas were present in any of the 16 temporal bones included in the study. However, microscopic invasion of epidermis to the medial side of the TM was observed in four specimens; perforations were present in three of these. Although there was considerable variability in the response to 5-FU application, the majority of specimens showed little or no proliferation of connective tissue in the lamina propria of the TM. In the four specimens in which epidermis reached the medial side of the TM, it did so either by migration through microscopic breaks in the fibrous layer or via TM perforations. Thus, 5-FU did not completely inhibit migration of epidermis into the middle ear. However, the results of this study indicate that it does tend to reduce the proliferation of TM epidermis and connective tissue, thereby reducing the likelihood of cholesteatoma formation in the experimental model.