Effect of Mitomycin in the Surgical Treatment of Tracheal Stenosis

Abstract

To assess the capacity of high and low doses of the antimitotic drug mitomycin to prevent laryngeal stenosis in an animal model. Methods: A prospective, randomized, double-blind, controlled study was carried out. End-to-end anastomosis was performed in 18 rabbits after tracheal annulus resection to produce inflammation. There were 3 treatment groups: topical saline (isotonic sodium chloride solution) and low-dose (0.2 mg/mL) and high-dose (0.5 mg/ mL) topical mitomycin. Results: A total of 107 procedures were performed: 54 surgical procedures, 35 fibrobronchoscopies, and 18 biopsies. The effect of mitomycin was dose related. In the high-dose mitomycin group, most rabbits progressed to stenosis with a percentage decrease in airway diameter that was significantly greater than in the other 2 groups (P Ͻ.001). The mean (SD) percentage of maximum stenosis in the high-dose group was 51%(22%). In the lowdose and saline groups, it was 18% (13%) and 16% (9%), respectively. No significant differences in tracheal stenosis between the low-dose mitomycin and saline groups were observed. Blinded histopathological analysis also showed no significant differences between the saline group and the low-dose mitomycin group. Compared with the other 2 groups, the high-dose mitomycin group had a significant increase in fibroproliferative tissue (P Ͻ.001). Conclusion: These results suggest that topical mitomycin is not effective for avoiding tracheal stenosis and may provoke the opposite effect if the dose is not carefully selected.

Effects of Pirfenidone and Collagen-Polyvinylpyrrolidone on Macroscopic and Microscopic Changes, TGF-β1 Expression, and Collagen Deposition in an Experimental Model of Tracheal Wound Healing

“…This finding agrees with those of other studies that investigated the complications caused by topical MMC application in tracheal lesions [8, 20]. Conversely, the low levels of inflammation and fibrosis in the groups treated with Collagen-PVP and PFD may have been due to the anti-inflammatory and fibrinolytic effects of both drugs [1, 2, 11, 22], which prevent the accumulation of granulation tissue at the tracheal lesion site.…”

“…Animals in groups I and III developed more severe histological inflammation because the treatments applied in these groups do not exhibit anti-inflammatory activity, and our findings corroborate other studies of the use of MMC for the treatment of TS that reported that this drug causes lesion site irritation up to two months after its application, which favors inflammation [8, 20]. Conversely, animals treated with Collagen-PVP developed mild-to-moderate inflammation because this drug exhibits anti-inflammatory properties over short and long periods of administration, as previously observed in clinical and experimental studies of patients with rheumatoid arthritis, hypertrophic skin scars, scleroderma, bedsores, and posttracheoplasty scars [10, 25, 26].…”

“…Similarly, another study of a murine model of bleomycin-induced pulmonary fibrosis reported that treatment with this compound decreases the presence of edema caused by the lesion after 10 days, which most likely explains the decreased inflammation of the tracheal mucosa and stridor [16]. Conversely, in group III, stridor persisted for three weeks because MMC has no anti-inflammatory effect and even causes wound site irritation, fibrinoid detritus accumulation, and tissue granulation after two months of application, as reported by Roh et al [8] and Iñiguez-Cuadra et al [20], who clinically and experimentally studied the effects of MMC on the airway.…”

Subglottic stenosis: A ten‐year review of treatment outcomes

“…It is used by many otolaryngologists with the theoretical benefit that it decreases fibroblast activity and therefore decreases scar formation and restenosis. Although there have been multiple animal and human studies published to look at the efficacy of topical mitomycin, its benefit remains controversial . In our series, there was no statistical difference between the need for second surgery or time interval between surgeries with use of mitomycin C. A nonsignificant trend was actually found that patients who received mitomycin C had a higher probability of needing another surgery.…”

“…Although there have been multiple animal and human studies published to look at the efficacy of topical mitomycin, its benefit remains controversial. 1,[4][5][6][7][8][9][10][11][12][13][14] In our series, there was no statistical difference between the need for second surgery or time interval between surgeries with use of mitomycin C. A nonsignificant trend was actually found that patients who received mitomycin C had a higher probability of needing another surgery. The use of mitomycin C did tend to occur in patients with more severe stenosis, which may create a selection bias and limit any conclusions regarding its efficacy in this series.…”