Effect of Mitomycin-C on Vocal Fold Healing in a Canine Model

Abstract

For evaluation of the effect of topical mitomycin-C on vocal fold healing and return of function after surgical excision of mucosa, 6 dogs underwent suspension microlaryngoscopy with bilateral microflap excision of vocal fold mucosa. Topical mitomycin-C, a chemotherapeutic agent and a fibroblast inhibitor, was applied randomly to one side, with the contralateral side serving as the control. Laryngeal videostroboscopy (LVS) was performed on each animal before the operation, at 2 weeks, and before sacrifice at 4 weeks. Both functional analysis with LVS and histologic analysis were performed in a blinded fashion to determine the effect of mitomycin-C on healing. Histologic analysis was augmented with computer morphometrics. The LVS revealed diminished mucosal wave vibration in the vocal folds treated with mitomycin-C, as well as a more atrophic appearance to the vibratory surface. The vocal folds treated with mitomycin-C showed fewer fibroblasts and less collagen within the superficial layer of the lamina propria than the control vocal folds (p < .05, Student's t-test, paired analysis). Inflammatory infiltrate was not significantly different between the two sides. Consistent with the known suppression of fibroblast proliferation by mitomycin-C, the treated vocal folds showed less connective tissue response to the surgical injury. In contrast to the reported positive effects of mitomycin-C on tracheal and glottic stenosis, the observed decrease in the healing response in the present study had negative consequences on the vocal fold vibratory pattern.