CASE-CONTROL STUDY IS BEST FOR BASIC FIBROBLAST GROWTH FACTOR REPAIRING HUMAN CHRONIC TYMPANIC MEMBRANE PERFORATION

Abstract

To the Editor: We would like to address the article entitled “Application of regenerative treatment for tympanic membrane perforation with cholesteatoma, tumor, or severe calcification” by Kanemaru et al. (1). The study is excellent. This study suggested that gelatin sponge with basic fibroblast growth factor (b-FGF) is useful not only for patients with simple tympanic membrane perforations (TMPs) but also for those with cholesteatomas, tumors, or severe calcification without requiring conventional surgical procedures (1). However, the confounding factors and short follow-up times affected the assessment of effect of b-FGF repairing chronic TMPs. This is a single institution and none clinical controlled trial. In this study, the regenerative treatment for TMP with cholesteatoma, tumor, or severe calcification included the use of a gelatin sponge immersed in b-FGF and fibrin glue. Whether bFGF alone is sufficient for the repair of chronic TMPs or whether it is necessary to add one of these other materials is unclear. Previous clinical studies have shown that the use of a gelatin sponge alone facilitates the healing of chronic TMPs (2). In addition, in the clinical studies of b-FGF on human traumatic TMPs, early studies have shown that a single application of b-FGF improves the closure rate and shortens the closure time of traumatic TMPs compared with spontaneous healing (3). However, in subsequent controlled studies, groups treated with topical application of b-FGF did not have a better closure rate or shorter closure time than patients in the ofloxacin otic group (4). Clinical and experimental studies have shown that topical application of ofloxacin otic solution aids the healing of the eardrum (5–7). Thus, a clinical case-control study comparing the curative effects of bFGF-immersed gelatin sponge with those of ofloxacin otic solution for the treatment of chronic TMPs is needed. If the healing rates of the two treatments are similar, then the topical application of b-FGF cannot be recommended. On the other, traumatic TMPs was different from TMPs with chronic suppurative otitis media, recent studies have demonstrated that topical application of EGF can promote the healing of traumatic human TMPs (8) but this is not the case for chronic TMPs (9). The biological half-life of b-FGF is short, only 12 hours (10). Clinical studies on using b-FGF to treat traumatic TMPs have shown that daily continuous application of b-FGF keeps the eardrum moist, which promotes healing of the TMP (3,4). The authors (1) have described the use of a b-FGF-infiltrated gelatin sponge during 3 weeks of treatment. Although this material slowly releases b-FGF, most of the b-FGF will flow into the nasopharynx, through the Eustachian tube, with only a small amount remaining in the middle ear. In addition, most gelatin sponge-infiltrated b-FGF dries out within 3 to 4 days (3). Thus, whether only one application of b-FGF can promote chronic TMP healing remains to be verified. In addition, the follow-up time was short. The authors reported the success rate of 91% at 6 months (1). However, Hakuba et al. investigated chronic TMPs treated with atelocollagen immersed in b-FGF, and reported a success rate of 92.0% at 6 months (11) but 66.0% at 1 year (12). Thus, the long-term advantages of bFGF await clarification. The authors did not describe whether the severe calcification needs to be removed for the TMPs with severe calcification. Clinical studies have shown that severe calcification is related to a high risk of healing failure in TMPs treated with b-FGF (12,13). In summary, while b-FGF may indeed be an excellent biological material for the repair of human chronic TMPs, this must still be demonstrated in case-control trials conducted at multiple centers with a large number of patients and in studies with a longer follow-up.