Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis

THIEME e112 Systematic Review Mitomycin C in the Endoscopic Treatment of Laryngotracheal Stenosis: Systematic Review and Proportional Meta-Analysis Thereza L. O. Queiroga1 Antônio J. M. Cataneo2 Daniele C. Cataneo2 Regina H. G. Martins1 1 Department of Otorhinolaryngology and Head and Neck Surgery, Faculdade de Ciências Médicas e Biológicas de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil 2 Department of Surgery, Faculdade de Ciências Médicas e Biológicas de Botucatu, Universidade Estadual Paulista, Botucatu, São Paulo, Brazil Tarcisio A. Reis2 Address for correspondence Regina H. G. Martins, MD, PhD, Departamento de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço, Faculdade de Ciências Médicas e Biológicas de Botucatu, Universidade Estadual Paulista, Distrito de Rubião Junior s/n, 18618-970, Botucatu, SP, Brazil (e-mail: ). Int Arch Otorhinolaryngol 2020;24(1):e112–e124. Abstract Keywords ► laryngotracheal stenosis ► mitomycin C ► systematic review ► dilation ► endoscopic treatment Introduction Mitomycin C is a natural antibiotic that has been used to inhibit the proliferation of fibroblasts in scar tissue. Objective To evaluate the effectiveness and safety of topical Mitomycin C as an adjuvant in the endoscopic treatment of laryngotracheal stenoses. Data synthesis A systematic review of experimental or observational studies that have evaluated the treatment of laryngotracheal stenoses with the use of topical Mitomycin C was performed. Databases researched: LILACS, PubMed, Embase, Cochrane and Web of Science. Outcomes: resolution (symptom-free time
one year), number of procedures required, and complications resulting from the procedure. A total of 15 studies (involving 387 patients) were selected. Mitomycin C was administered to every patient in 11 studies, and in 4 other studies, the patients were separated into 2 groups, 1 receiving mitomycin C, and the other not. The resolution of the stenosis evaluated in 12 studies in which the patients received mitomycin C was of 69% (95% confidence interval [95%CI]: 61–76%; I2 ¼ 17.3%). A total of 52% of the patients (95%CI: 39–64%, 11 studies; I2 ¼ 64.7%) were submitted to a single endoscopic procedure, and 48% (95%CI: 36–61%, 11 studies; I2 ¼ 64.7%) were submitted to more than 1 procedure. Complications (mediastinal and subcutaneous emphysema, dysphonia, laceration or vocal fold paralysis and acute light obstruction) were reported in 9% of the patients (95%CI: 3–18%, 9 studies; I2 ¼ 79.8%). Conclusions The evidence suggests that mitomycin C is an effective and safe option in the endoscopic treatment of laryngotracheal stenosis. Introduction The increasing number of patients with postintubation laryngotracheal stenosis has been a challenge because of the lack of an effective treatment modality. The objective of an effective laryngotracheal stenotic treatment should be to received March 28, 2019 accepted September 10, 2019 DOI https://doi.org/ 10.1055/s-0039-1700582. ISSN 1809-9777. ensure adequate airway diameter to allow ventilation and provide symptom relief, which are not achieved in most patients. In many cases, endoscopic treatments and open surgical techniques are used in the same patient; however, when surgical resection is not indicated, endoscopic treatment options are adopted, which have an immediate effect.1 Copyright © 2020 by Thieme Revinter Publicações Ltda, Rio de Janeiro, Brazil Mitomycin C in Laryngotracheal Stenosis Topical agents have been used as adjuvants in endoscopic treatment, aiming to minimize recurrence rates and prolong the symptom-free period after the intervention. The adjuvant options studied in animal and human models include steroid injections, topical mitomycin C (MMC), topical heparin, 5-fluorouracil, and halofuginone.2 Of these options, MMC is highlighted as an antibiotic and antineoplastic agent that inhibits the proliferation of fibroblasts, thereby modulating the healing processes. There is a long history of studies published regarding laryngology research on the effect of MMC on laryngotracheal lesion models in dogs, rabbits, pigs, and rats. The success rate in maintaining the dilation of the stenosis over a long period ranges from 40% to 70%, with an average of 50%.3 Satisfactory results have expanded the search for methods to improve the success rate,3 but the overall results of the use of MMC in humans are conflicting. Although surgical resection of laryngotracheal stenosis with end-to-end anastomosis is effective, conservative options are necessary to treat patients for whom surgery is not indicated. Therefore, the present systematic review was conducted to evaluate the efficacy of MMC as an adjuvant in the endoscopic treatment of laryngotracheal stenosis. Review of the Literature Methodology The present systematic review included studies published on the use of topical MMC in the endoscopic treatment of laryngotracheal stenosis. The study design (review of the literature) enabled the exemption of approval from the Research Ethics Committee. Inclusion criteria: experimental or observational studies (with at least 5 participants per group, with more than 80% of the patients being adolescents or adults, excluding studies that only address children) evaluating endoscopic interventions with adjuvant topical MMC being at least one of the treatment options for laryngotracheal stenosis. Participants: patients with laryngotracheal stenosis. Interventions: endoscopic interventions (mechanical dilation; use of electric scalpel, argon, harmonic, or laser; and cryotherapy) in which MMC was administered to at least one participant group. Outcomes: the primary outcomes include complete or partial resolution of laryngotracheal stenosis, characterized by symptom-free period
1 year; the secondary outcomes include the number of procedures with or without the administration of MMC (single or multiple procedures); and complications characterized by the need for immediate intervention or other procedures (acute obstruction, tracheostomy, dysphonia, subcutaneous emphysema, vocal fold laceration, temporary vocal paralysis, among others). We conducted a search for relevant literature on the following electronic databases: PubMed (from 1966 to November 27, 2018); Embase (from 1973 to November 27, 2018); LILACS (from 1982 to November 27, 2018); Cochrane (from 1993 to November 27, 2018); Web of Science (from 1900 to November 27, 2018); and Clinical Trials (accessed on November 27, 2018). The following search terms were used to find studies on the Medline (PubMed) database: (tracheal stenosis or stenoses, Queiroga et al. tracheal or stenosis, tracheal or tracheal stenoses) and (bronchoscopy or bronchoscopies or bronchoscopic surgical procedures or bronchoscopic surgical procedure or surgical procedure, bronchoscopic or surgical procedures, bronchoscopic or bronchoscopic surgery or bronchoscopic surgeries or surgeries, bronchoscopic or surgery, bronchoscopic) and (...truncated)