To assess the efficacy of adjuvant MMC in the endoscopic treatment of airway stenoses.
Data sources:
PubMed/MEDLINE, Cochrane Library, Scopus, Embase, and Google Scholar databases.
Review methods:
A literature search was conducted following PRISMA guidelines. The PICOS tool was used to determine the eligibility criteria for this study. A single arm meta-analysis was performed for stenosis resolution, the rate of patients requiring multiple endoscopic procedures, and the rate of patients requiring other surgical treatments.
Results:
A total number of 358 patients (median age: 48.0 years; 95% CI 44.8-50.8) were included. The median follow-up was 25.2 months (n = 244/358; 95% CI 15.4-38.3). Overall, the cumulative stenosis resolution rate was 76.37% (n = 187/254; 95% CI 59.72-89.64), the rate of patients requiring multiple endoscopic procedures was 52.33% (n = 131/260; 95% CI 32.03-72.25), and the rate of patients requiring other surgical treatments was 4.08% (n = 26/310; 95% CI 0.37-11.48). The median intervention-free interval was 366 days (n = 155/358; 95% CI 270-696).
Conclusions:
Current evidence does not allow definitive conclusions regarding the efficacy of adjuvant MMC in reducing recurrence or prolonging intervention-free intervals in airway stenosis. Further well-designed prospective studies are needed to clarify the role of MMC and to inform evidence-based guidelines for patient selection and treatment use.
GrilloHC.The history of tracheal surgery. Chest Surg Clin N Am. 2003;13(2):175-189. doi:10.1016/s1052-3359(03)00002-4
2.
OssoffRHTuckerGFJrDuncavageJ. AToohillR. J.Efficacy of bronchoscopic carbon dioxide laser surgery for benign strictures of the trachea. Laryngoscope. 1985;95(10):1220-1223. doi:10.1288/00005537-198510000-00015
3.
SimpsonGTStrongMSHealyGBShapshaySMVaughanCW.Predictive factors of success or failure in the endoscopic management of laryngeal and tracheal stenosis. Ann Otol Rhinol Laryngol. 1982;91(4 Pt 1):384-388. doi:10.1177/000348948209100412
4.
ShapshaySMBeamisJFJrHybelsRLBohigianRK.Endoscopic treatment of subglottic and tracheal stenosis by radial laser incision and dilation. Ann Otol Rhinol Laryngol. 1987;96(6):661-664. doi:10.1177/000348948709600609
5.
SupanceJS.Antibiotics and steroids in the treatment of acquired subglottic stenosis. A canine model study. Ann Otol Rhinol Laryngol. 1983;92(4 Pt 1):377-382. doi:10.1177/000348948309200417
6.
CroftCBZubKBorowieckiB.Therapy of iatrogenic subglottic stenosis: a steroid/antibiotic regimen. Laryngoscope. 1979;89(3):482-489. doi:10.1288/00005537-197903000-00016
7.
ViveirosFGomesJOliveiraA, et al. Topical application of mitomycin-C as an adjuvant treatment to bronchoscopic procedures in post-intubation tracheal stenosis. Rev Port Pneumol. 2013;19(6):276-280. doi:10.1016/j.rppnen.2013.10.003
8.
HataTSanoYSugawaraR, et al. Mitomycin, a new antibiotic from streptomyces. Int J Antibiot. 1956;9:141-146.
9.
TomaszMPalomY.The mitomycin bioreductive antitumor agents: cross-linking and alkylation of DNA as the molecular basis of their activity. Pharmacol Ther. 1997;76(1-3):73-87. doi:10.1016/s0163-7258(97)00088-0
10.
WardRFAprilMM. Mitomycin-C in the treatment of tracheal cicatrix after tracheal reconstruction. Int J Pediatr Otorhinolaryngol. 1998;44(3):221-226. doi:10.1016/s0165-5876(98)00061-5
11.
EliasharRGrossMMalyBSichelJY.Mitomycin does not prevent laryngotracheal repeat stenosis after endoscopic dilation surgery: an animal study. Laryngoscope. 2004;114(4):743-746. doi:10.1097/00005537-200404000-00028
12.
ShvidlerJBothwellNECableB.Refining indications for the use of mitomycin C using a randomized controlled trial with an animal model. Otolaryngol Head Neck Surg. 2007;136(4):653-657. doi:10.1016/j.otohns.2006.10.037
13.
PerepelitsynIShapshaySM.Endoscopic treatment of laryngeal and tracheal stenosis-has mitomycin C improved the outcome?Otolaryngol Head Neck Surg. 2004;131(1):16-20. doi:10.1016/S0194-5998(04)01136-2
14.
ReichertLKZhaoASGalatiLTShapshaySM.The efficacy of mitomycin C in the treatment of laryngotracheal stenosis: results and experiences with a difficult disease entity. ORL J Otorhinolaryngol Relat Spec. 2015;77(6):351-358. doi:10.1159/000439174
15.
SimpsonCBJamesJC.The efficacy of mitomycin-C in the treatment of laryngotracheal stenosis. Laryngoscope. 2006;116(10):1923-1925. doi:10.1097/01.mlg.0000235934.27964.88
16.
RahbarRShapshaySMHealyGB.Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications. Ann Otol Rhinol Laryngol. 2001;110(1):1-6. doi:10.1177/000348940111000101
17.
QueirogaTLOCataneoDCMartinsRHGReisTACataneoAJM. Mitomycin C in the endoscopic treatment of laryngotracheal stenosis: systematic review and proportional meta-analysis. Int Arch Otorhinolaryngol. 2020;24(1):e112-e124. doi:10.1055/s-0039-1700582
18.
LiberatiAAltmanDGTetzlaffJ, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100. doi:10.1371/journal.pmed.1000100
19.
MethleyAMCampbellSChew-GrahamCMcNallyRCheraghi-SohiS.PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews. BMC Health Serv Res. 2014;14:579. doi:10.1186/s12913-014-0579-0
20.
SlimKNiniEForestierDKwiatkowskiFPanisYChipponiJ.Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712-716. doi:10.1046/j.1445-2197.2003.02748.x
21.
SchulzKFAltmanDGMoherD.CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. PLoS Med. 2010;7(3):e1000251. doi:10.1371/journal.pmed.1000251
22.
RussoEAccoronaRIoccaO, et al. Does tumor volume have a prognostic role in oropharyngeal squamous cell carcinoma? A systematic review and meta-analysis. Cancers. 2022;14(10):2465. doi:10.3390/cancers14102465
23.
KoberTTrelleSEngertA.Reporting of randomized controlled trials in Hodgkin lymphoma in biomedical journals. J Natl Cancer Inst. 2006;98(9):620-625. doi:10.1093/jnci/djj160
24.
McGrathSZhaoXQinZZSteeleRBenedettiA.One-sample aggregate data meta-analysis of medians. Stat Med. 2019;38(6):969-984. doi:10.1002/sim.8013
25.
RückerGSchwarzerGCarpenterJOlkinI.Why add anything to nothing? The arcsine difference as a measure of treatment effect in meta-analysis with zero cells. Stat Med. 2009;28(5):721-738. doi:10.1002/sim.3511
26.
VeronikiAAJacksonDViechtbauerW, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. 2016;7(1):55-79. doi:10.1002/jrsm.1164
27.
CochranWG.The combination of estimates from different experiments. Biometrics. 1954;10(1):101-129.
28.
JacksonDWhiteIRRileyRD.Quantifying the impact of between-study heterogeneity in multivariate meta-analyses. Stat Med. 2012;31(29):3805-3820. doi:10.1002/sim.5453
29.
ViechtbauerWCheungMW.Outlier and influence diagnostics for meta-analysis. Res Synth Methods. 2010;1(2):112-125. doi:10.1002/jrsm.11
30.
BaujatBMahéCPignonJHillC.A graphical method for exploring heterogeneity in meta-analyses: application to a meta-analysis of 65 trials. Stat Med. 2002;21(18):2641-2652. doi:10.1002/sim.1221
31.
PetersJLSuttonAJJonesDRAbramsKRRushtonL.Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676-680. doi:10.1001/jama.295.6.676
32.
CataneoDCXimenesAMGCataneoAJM. Mitomycin C in the endoscopic treatment of tracheal stenosis: a prospective cohort study. J Bras Pneumol. 2018;44(6):486-490. doi:10.1590/S1806-37562017000000423
33.
HuanNNgKLNasaruddinMZMuhammadNADautUNAbdul RahamanJA.Topical mitomycin-C as an adjuvant to multimodal endoscopic treatment for tracheobronchial stenosis secondary to endobronchial tuberculosis. Respirol Case Rep. 2021;9(3):e00711. doi:10.1002/rcr2.711
34.
HuemanEMSimpsonCB.Airway complications from topical mitomycin C. Otolaryngol Head Neck Surg. 2005;133(6):831-835. doi:10.1016/j.otohns.2005.07.031
35.
MadanKAgarwalRAggarwalANGuptaD.Utility of rigid bronchoscopic dilatation and mitomycin C application in the management of postintubation tracheal stenosis: case series and systematic review of literature. J Bronchology Interv Pulmonol. 2012;19(4):304-310. doi:10.1097/LBR.0b013e3182721290
36.
NouraeiSASinghAPatelAFergusonCHowardDJSandhuGS.Early endoscopic treatment of acute inflammatory airway lesions improves the outcome of postintubation airway stenosis. Laryngoscope. 2006;116(8):1417-1421. doi:10.1097/01.mlg.0000225377.33945.14
37.
OrtizRDominguezEDe La TorreC, et al. Early endoscopic dilation and mitomycin application in the treatment of acquired tracheal stenosis. Eur J Pediatr Surg. 2014;24(1):39-45. doi:10.1055/s-0033-1357754
38.
RahbarRJonesDTNussRC, et al. The role of mitomycin in the prevention and treatment of scar formation in the pediatric aerodigestive tract: friend or foe?Arch Otolaryngol Head Neck Surg. 2002;128(4):401-406. doi:10.1001/archotol.128.4.401
39.
RoedigerFCOrloffLACoureyMS.Adult subglottic stenosis: management with laser incisions and mitomycin-C. Laryngoscope. 2008;118(9):1542-1546. doi:10.1097/MLG.0b013e318179247a
40.
SchweinfurthJM.Endoscopic treatment of severe tracheal stenosis. Ann Otol Rhinol Laryngol. 2006;115(1):30-34. doi:10.1177/000348940611500105
41.
SmithMEElstadM.Mitomycin C and the endoscopic treatment of laryngotracheal stenosis: are two applications better than one?Laryngoscope. 2009;119(2):272-283. doi:10.1002/lary.20056
42.
TiranBParlukTKleinhendlerEManAFominISchwarzY.Fiberoptic bronchoscopic submucosal injection of mitomycin C for recurrent bening tracheal stenosis: a case series. Isr Med Assoc J. 2020;22(12):757-760.
43.
UbellMLEttemaSLToohillRJSimpsonCBMeratiAL.Mitomycin-c application in airway stenosis surgery: analysis of safety and costs. Otolaryngol Head Neck Surg. 2006;134(3):403-406. doi:10.1016/j.otohns.2005.10.057
44.
ValdezTAShapshaySM.Idiopathic subglottic stenosis revisited. Ann Otol Rhinol Laryngol. 2002;111(8):690-695. doi:10.1177/000348940211100806
45.
ViraDDeCondeAChhetriDK.Endoscopic management of supraglottic laryngopharyngeal stenosis. Otolaryngol Head Neck Surg. 2012;146(4):611-613. doi:10.1177/0194599811431684
46.
VorasubinNViraDJamalNChhetriDK.Airway management and endoscopic treatment of subglottic and tracheal stenosis: the laryngeal mask airway technique. Ann Otol Rhinol Laryngol. 2014;123(4):293-298. doi:10.1177/0003489414525340
47.
YungKCChangJCoureyMS.A randomized controlled trial of adjuvant mitomycin-c in endoscopic surgery for laryngotracheal stenosis. Laryngoscope. 2020;130(3):706-711. doi:10.1002/lary.28025
48.
ScholfieldDWWarnerEAhmedJGhufoorK.Subglottic and tracheal stenosis associated with coronavirus disease 2019. J Laryngol Otol. 2021;135(7):656-658. doi:10.1017/S0022215121001134
49.
MangiameliGPerroniGCostantinoA, et al. Analysis of risk factors for tracheal stenosis managed during COVID-19 pandemic: a retrospective, case-control study from two European Referral Centre. J Pers Med. 2023;13(5):729. doi:10.3390/jpm13050729
50.
SimpsonGTPolanyiTG.History of the carbon dioxide laser in otolaryngologic surgery. Otolaryngol Clin North Am. 1983;16(4):739-752.
51.
ShapshaySMBeamisJfJrDumonJF.Total cervical tracheal stenosis: treatment by laser, dilation, and stenting. Ann Otol Rhinol Laryngol. 1989;98(11):890-895. doi:10.1177/000348948909801110
52.
WhiteheadESalamMA.Use of the carbon dioxide laser with the Montgomery T-tube in the management of extensive subglottic stenosis. J Laryngol Otol. 1992;106(9):829-831. doi:10.1017/s0022215100121000
53.
CicconeAMDe GiacomoTVenutaF, et al. Operative and non-operative treatment of benign subglottic laryngotracheal stenosis. Eur J Cardiothorac Surg. 2004;26(4):818-822. doi:10.1016/j.ejcts.2004.06.020
54.
YamamotoTVaraniJSoongHKLichterPR.Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts. Ophthalmology. 1990;97(9):1204-1210. doi:10.1016/s0161-6420(90)32456-9
55.
CrowstonJGChangLHConstablePHDanielsJTAkbarANKhawPT.Apoptosis gene expression and death receptor signaling in mitomycin-C-treated human tenon capsule fibroblasts. Investig Ophthalmol Vis Sci. 2002;43(3):692-699.
56.
GelbardAFrancisDOSandulacheVCSimmonsJCDonovanDTOngkasuwanJ.Causes and consequences of adult laryngotracheal stenosis. Laryngoscope. 2015;125(5):1137-1143. doi:10.1002/lary.24956
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
