EFFECTS OF TOPICAL APPLICATION OF MITOMYCIN-C AND 5-FLUOROURACIL ON MYRINGOTOMY IN RATS

Abstract

In Reply: We appreciate Dr. Eken's critical letter to the editor regarding our recent publication and the good review of laser myringotomy. First of all, simple myringotomy and laser myringotomy were not compared in our study. We used mitomycin C (MMC) and 5-fluorouracil with simple myringotomy. As a result, we have found that MMC may prolong myringotomy patency time for about 6 weeks. As we mentioned in our article, Estrem and Batra (1) perforated the tympanic membranes of 60 rats by potassium-titanyl-phosphate laser, applied 2 mg/mL topical MMC, and divided rats into 4 groups according to exposure time and repeat application. The median patency time of the single 10-minute application was 6.5 weeks; of the single 20-minute application, 5.5 weeks; of the biweekly 10-minute-application, 6.5 weeks; and of the biweekly application, for 20 and 10 minutes, was 8.5 weeks. The median patency time of the control group was determined to be 1.5 weeks. We think that this article has proven that the patency time produced by KTP laser alone is very close to that of simple myringotomy, and increased exposure time or repeat application of MMC did not statistically alter the patency rate. Therefore, we think that usage of KTP laser in myringotomy is not effective in prolonging the patency time, and that topical MMC application in appropriate dosage may lengthen the patency time up to 6.5 weeks. When we reviewed studies about myringotomy, mean closure time is mostly between 1 and 3 weeks in laser myringotomy (2,3), and 1 and 3 weeks in thermal myringotomy (4). However, when we quickly checked literature about MMC application with simple myringotomy or myringotomy by using laser-thermal equipments, mean closure time is more than 5 weeks (Table 1). Along with the literature, we think that MMC is superior to laser and thermal myringotomy. A novel study that was conducted on 180 ears of 96 patients showed that MMC can prolong myringotomy closure time in patients with otitis media with effusion (mean, 5.3 wk) and in patients with recurrentacute otitis media (mean, 7 wk) (5). Ragab (5) and Jasir et al. (6) found that the dose of 0.4 mg/mL MMC is almost the optimal dose, and the novel study used the same dose in patients. There is a concentration-response curve for topical MMC when used for prolonging myringotomy patency in concentrations up to 0.4 mg/mL. Higher concentrations do not appear to prolong patency and are usually associated with otorrhea, suggesting middle ear toxicity. Also, Jang et al. (7) reported that topical application of MMC in 0.4 mg/mL concentration for 10 minutes has the highest antiproliferative effect on cultured human tympanic membrane fibroblasts. Myringotomy closure time after MMC application depends on some parameters: size of myringotomy, shape of myringotomy, MMC concentration, MMC application way, MMC application duration, status of middle ear (healthy or not), and the species on which the study was applied. Therefore, all studies should be analyzed under the guidance of these parameters. So, our results were expected to be longer because we used topical application of MMC in 0.4 mg/mL concentration. CO2 laser myringotomy experience in our clinic on rats showed that it may prolong myringotomy patency time at least 2.5 weeks (8). However, our results with MMC were longer compared with laser myringotomy. As a result, our mean duration of patency time with MMC is similar to other studies using MMC either with laser or not, and there is no contradiction with previous reports. We have to emphasize that there are a few studies using only MMC after myringotomy, and there are a lot of studies using only laser. In most of these, laser prolongs myringotomy closure time by approximately 2 weeks. In Dr. Eken's literature list, we may easily see that argon and KTP lasers were used with MMC. Therefore, the results are probably dependent on MMC. Our idea is that when MMC is used in proper dosage and duration after simple myringotomy, it may prolong myringotomy patency time as much as that of MMC after laser myringotomy.TABLE 1: Patency duration of myringotomy with different techniquesThanks for your kind interest. Engin Çekin, M.D. Hakan Cincik, M.D. Gülhane Military Medical Academy Haydarpasa Training Hospital Department of Ear, Nose, and Throat Istanbul, Turkey