The effects of mitomycin-C and stenting on airway wound healing after laryngotracheal reconstruction in a pig model

Abstract

Objective: To assess the effects of mitomycin-C (MTC) and endoscopic stenting on airway wound healing after laryngotracheal reconstruction. Design: A prospective, blinded, randomized controlled animal study. Subjects: Twenty-six domestic pigs ( Sus scrofula) divided into four groups. Interventions: Each animal underwent single-stage laryngotracheal reconstruction (SSLTR) with auricular cartilage grafts and stenting. Group 1 animals were sacrificed on postoperative day 3, and group 2 animals on postoperative day 7. On postoperative day 7, groups 3 and 4 underwent endoscopy, stent removal, and application of MTC (0.5 mg/ml) or placebo (normal saline). Group 3 animals were sacrificed on postoperative day 14, group 4 animals on day 21. Two additional animals from each experimental group were prepared for election microscopy studies. Segments of reconstructed airway were evaluated grossly and histologically for all animals. Additional tonometric evaluation was performed on two stents to determine their compressive strength. Main outcome measures: Healing, reepithelization, graft incorporation, and airway diameter. Results: Two-thirds of the animals demonstrated some degree of stent collapse on endoscopy. Granulation tissue formation was seen in all animals, and resolved with stent removal. No animal experienced airway compromise due to granulation tissue formation. Stenting was seen to induce a submucosal fibroproliferative response and scarring, with loss of normal glandular architecture, in all animals. MTC did not affect the acute inflammatory response, reepithelization of the graft site, or formation of the subepithelial fibroproliferative response. MTC treated animals, however, demonstrated better graft incorporation with fibrocartilage proliferation of the graft. Untreated animals demonstrated liquefactive necrosis of the graft, without evidence of neochondrification of the graft. Conclusions: The pig airway is an adequate model of wound healing following SSLTR and stenting. Metallic ballon expandable stents can be successfully used following SSLTR, allowing for immediate postoperative extubation. However, the formation of a submucosal fibroproliferative response and mucosal scarring seen in our study raises some concerns with the current stent design. Before stenting is widely clinically applied, the optimum stent design needs to be developed. Finally, MTC seems to prevent the liquefactive necrosis of SSLTR grafts and promote neochondrification, allowing improved graft incorporation. Further studies are needed to asses the long-term effects of MTC on healing and restenosis, and its effects on cartilage growth and formation, following SSLTR.