Mitomycin c and the Endoscopic treatment of laryngotracheal stenosis: Are two applications better than one?

Division of Otolaryngology/Head and Neck Surgery, University of Utah School of Medicine, The University of Utah, Salt Lake City, UT 84132, USA.
The Laryngoscope (Impact Factor: 2.14). 02/2009; 119(2):272-83. DOI: 10.1002/lary.20056
Source: PubMed


Endoscopic treatment of laryngotracheal stenosis by airway dilation, despite short-term improvement, is often associated with long-term relapse. Mitomycin-C (MMC) inhibits fibroblast proliferation and synthesis of extracellular matrix proteins, and thereby modulates wound healing and scarring. MMC application at the time of endoscopic dilation and laser surgery has been suggested to improve outcomes, but this has not been studied in a rigorous manner. This study examines the hypothesis that two topical applications of MMC given 3-6 weeks apart will result in decreased scarring/restenosis of the airway, when compared to a single topical application.
A randomized, prospective, double-blind, placebo-controlled clinical trial.
Twenty-six patients with laryngotracheal stenosis due to idiopathic subglottic stenosis, postintubation stenosis, or Wegener's granulomatosis entered a protocol to receive three endoscopic CO(2) laser and dilation procedures over a 3-month interval. At the first procedure, after radial CO(2) laser incision and airway dilation, all patients received topical application of MMC (0.5 mg/mL) to the airway lesion. One month later, a second endoscopic incision and dilation was performed and the patients were randomized to either a second application of mitomycin-C or to application of saline placebo. A third dilation procedure was performed 2 months later, without MMC application. Patients were followed for up to 5 years for relapse of airway stenosis with clinical symptoms sufficient to require a subsequent procedure.
The relapse rates at 1, 3, and 5 years were 7%, 36%, and 69% for patients treated with two applications of MMC compared to 33%, 58%, and 70% for patients treated with one application of MMC. The median interval to relapse was 3.8 years in the two-application group, compared with 2.4 years in the one-application group.
This prospective randomized double-blind placebo-controlled trial suggests that, in the endoscopic management of laryngotracheal stenosis, two applications of MMC given 3-4 weeks apart after airway radial incision and dilation reduces the restenosis rate for 2 to 3 years after treatment when compared to a single application. However, restenosis and delayed symptom recurrence continues so that at 5 years the relapse rates are the same. Thus, MMC may postpone, but does not prevent, the recurrence of symptomatic stenosis in the majority of patients.

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    • "Mucosal injury is the main contributing factor, causing fibroblast proliferation and collagen formation leading to scar formation and restenosis. Multiple groups have reported success with application of adjuvant treatments (antibiotics, steroids, mitomycin) [19] [20] [21]; however, it is difficult to determine the true efficacy of these adjuvant treatments without a multicenter randomized prospective study. We give perioperative antibiotics and steroids, and also use mitomycin (0.4 mg/ml, topical application for 4 min) to help decrease postoperative scar formation. "
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    ABSTRACT: OBJECTIVE: To assess the efficacy and safety of endoscopic management of subglottic stenosis both as a primary and as an adjunctive treatment in the pediatric population. METHODS: Retrospective review of pediatric patients with subglottic stenosis undergoing endoscopic airway procedures at a tertiary care pediatric medical center. Outcomes were assessed by systematic review to determine the success and failure of the endoscopic approach. RESULTS: Forty patients (22 male, 18 female) underwent endoscopic interventions for a diagnosis of subglottic airway stenosis between 2003 and 2006. Age ranged from 22 days old to 20 years old. Recorded degree of subglottic stenosis ranged from 10% to 99%. Fifty-three percent (21/40) had a history of prematurity, and 40% (16/40) had secondary airway diagnoses. Twenty-four patients underwent an endoscopic intervention initially (including laser or dilation, with or without topical mitomycin treatment), including four patients who underwent tracheostomy prior to the first endoscopic intervention. Sixteen underwent laryngotracheoplasty initially, including ten patients who underwent tracheostomy prior to the laryngotracheoplasty. Endoscopic treatment resulted in resolution of symptoms, and/or decannulation, and no further need for an open procedure in 58% of patients. Of the 24 patients undergoing endoscopic interventions initially, 14 patients underwent two or more endoscopic interventions, and 10 patients subsequently required tracheostomy or laryngotracheoplasty. When endoscopic procedures were used as an adjunct to laryngotracheoplasty, 60% (12/20) had resolution of symptoms, underwent decannulation, and did not require tracheostomy or revision laryngotracheoplasty. CONCLUSIONS: The endoscopic approach can be successful in the management of properly selected patients with subglottic stenosis, either as the initial treatment modality or as an adjunctive treatment in cases of re-stenosis after open airway surgery. The likelihood of success with a minimally invasive procedure as the primary treatment decreases with worsening initial grade of subglottic stenosis.
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    ABSTRACT: Hintergrund Ziel dieser Arbeit über Patienten mit symptomatischen subglottischen Trachealstenosen war die Beurteilung der Ergebnisse nach laserchirurgischer Auftrennung, kombiniert mit Applikation von Mitomycin C und/oder Triamcinolonacetonid. Material und Methoden Elf Patientinnen mit subglottischen Trachealstenosen wurden in 2 Gruppen unterteilt: idiopathische Trachealstenose (n = 6) und subglottische Stenose bekannter Ätiologie (n = 5, davon 4 mit M. Wegener und eine Patientin mit Polychondritis der Trachea). Drei Patientinnen zeigten Zeichen einer Refluxkrankheit. Die Auswertung erfolgte anhand des klinischen Bildes und des Atemwegswiderstands. Ergebnisse In allen Fällen wurde eine laserchirurgische Auftrennung der Stenose und die Applikation von Mitomycin C und Triamcinolonacetonid durchgeführt. Bei den Kontrolluntersuchungen in einem Beobachtungszeitraum von 7–72 Monaten wurde bei allen Patienten eine Verbesserung des Atemwegswiderstands sowie der klinischen Symptomatik festgestellt. Schlussfolgerung Eine oder mehrere CO2-Laserungen der stenotischen Bereiche, kombiniert mit intraläsionalen Steroidinjektionen und der topischen Anwendung von Mitomycin C, sind eine effektive Methode zur Behandlung von subglottischen Trachealstenosen. Die langfristige orale Steroidgabe und immunsuppressive Therapie sowie die Gabe von Protonenpumpenhemmern beeinflussen das postoperative Ergebnis ebenfalls positiv.
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    Seminars in Thoracic and Cardiovascular Surgery 09/2009; 21(3):278-83. DOI:10.1053/j.semtcvs.2009.06.004
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