Abstract
Background
Mitomycin C (MMC) is an antimitotic drug that may, when applied topically, prevent postoperative stenosis. Its use remains controversial. This review aims to provide otolaryngologists with an update of the evidence on the applications of this agent in the nose and sinuses.
Methods
A systematic review was performed. Inclusion criteria were as follows: English literature, original articles, reviews, and case series. Exclusion criteria were as follows: animal and in vitro studies, nonendoscopic and nonsinonasal applications of MMC, and external lacrimal surgery. Studies that used other ways of dilating stenoses in conjunction with MMC were excluded.
Results
Out of 48 studies published, 9 fulfilled our inclusion criteria, totaling 322 patients. Eighty-five percent were primary and 15% were revision cases. Follow-up ranged from 1 to 42 months. Main outcome measures used were endoscopic examination, anatomical measurements, radiological scoring systems, dye tests, and subjective symptom resolution. Main overall outcomes from studies where extrapolation of data was feasible were (1) patency rate, which ranged from 63% to 94.4% (mean, 81.3%); (2) adhesions: 5.1% (MMC) vs 15.05 (control); and (3) stenosis: 14.05% (MMC) vs 32.6% (control).
Conclusions
There appears to be a favorable short-term effect of MMC, but no robust evidence regarding long-term prevention of restenosis. Larger homogenous and multicenter randomized trials are needed to assess the long-term effects of MMC in sinonasal surgery.
1
Introduction
Mitomycin C (MMC) is an alkylating antibiotic isolated from Streptomyces caespitosus . Apart from a common chemotherapeutic agent, MMC has been successfully used for years as a topical agent in eye surgery and, more recently, in esophageal and tracheal stenosis, where application onto cut mucosa seems to decrease restenosis . The exact mechanism of action is unknown, but it is possible that MMC has an antifibroblastic effect without inhibition of epithelialization . These novel applications of MMC have been, over the last decade, extended into the fields of plastic surgery and rhinology, especially endoscopic sinus surgery (ESS) and dacryocystorhinostomy (DCR) . The antiproliferative properties of MMC are supported by animal and experimental studies, but the clinical evidence is poor.
The aim of this systematic review is to assess the levels of evidence on the endonasal topical application of MMC to prevent stenosis and adhesions.
2
Methods
A systematic review of the literature by a Medline search was performed using the terms Mitomycin C , nose , sinuses , topical application , endoscopic sinus surgery , dacryocystorhinostomy , and stenosis . Inclusion criteria were as follows: English literature only. Original articles, reviews, and case series of both adult and pediatric population were included. Exclusion criteria were as follows: animal and in vitro studies, nonsinonasal applications of MMC, and external sinus and/or lacrimal approaches. Studies that used other ways of dilating stenoses (ie, stents, balloon sinoplasties) in conjunction with MMC were also excluded. Standard endonasal DCR approaches with bicanalicular or monocanalicular silicone intubation were included in the analysis.
2
Methods
A systematic review of the literature by a Medline search was performed using the terms Mitomycin C , nose , sinuses , topical application , endoscopic sinus surgery , dacryocystorhinostomy , and stenosis . Inclusion criteria were as follows: English literature only. Original articles, reviews, and case series of both adult and pediatric population were included. Exclusion criteria were as follows: animal and in vitro studies, nonsinonasal applications of MMC, and external sinus and/or lacrimal approaches. Studies that used other ways of dilating stenoses (ie, stents, balloon sinoplasties) in conjunction with MMC were also excluded. Standard endonasal DCR approaches with bicanalicular or monocanalicular silicone intubation were included in the analysis.
3
Results
Forty-eight studies were published from 1991 to 2009. Nine fulfilled our inclusion criteria. Selection bias, blinding of the results, lack of common outcome measures, and uncontrolled studies were some of the problems preventing a formal meta-analysis. Evidence-based “types” of studies appear in Table 1 . Total number of patients reviewed was 322. Two hundred seventy-four were primary cases (85%), and only 48 were revision cases (15%).
| Reference | Study type |
|---|---|
| Kim et al ⁎ | Double blinded, prospective, randomized controlled |
| Dolmetch et al | Prospective, nonrandomized |
| Konstantinidis et al ⁎ | Double blinded, prospective, randomized controlled |
| Nemet et al | Noncomparative case series |
| Amonoo-Kuofi et al | Prospective, open pilot |
| Kim et al ⁎ | Double blinded, prospective, randomized controlled |
| Gupta and Motwani ⁎ | Double blinded, prospective, randomized controlled |
| Chan et al ⁎ | Double blinded, prospective, randomized controlled |
| Chung et al ⁎ | Double blinded, prospective, randomized controlled |
Follow-up ranged from 1 to 42 months. Main outcome measures used were intra- and postoperative anatomical measurements, outpatient endoscopic examination, radiological scoring systems, dye tests, and subjective (patient) symptom resolution ( Table 2 ). The concentration of MMC ranged from a low of 0.3 mg/mL to a maximum concentration of 0.6 mg/mL, whereas the total dose applied ranged from 0.5 to 1.5 mL. The duration of the topical MMC application was 5 minutes in the majority of trials (7 of 9 studies) and 4 minutes in 2 studies. Application method was in the way of soaked cotton pledgets in 5 of 9 studies, ribbon gauze in 2 studies, and Merocel pack (Roche Diagnostics Ltd, West Sussex, United Kingdom) in 1 study. Anatomical areas assessed in the included studies were frontal sinus ostia, maxillary sinus ostia, and nasolacrimal ducts, whereas 1 study focused specifically on the presence or absence of postoperative adhesions ( Table 3 ).
| Reference | Type of operation | No. of patients | Duration of TOP (min) | FUp | Outcome measures |
|---|---|---|---|---|---|
| Kim et al ⁎ | ESS | 38 | 5 | 3 (min) | Ex, CT |
| Dolmetch et al | DCR | 71 | 5 | 12.3 (mean) | Ex, dye test, SR |
| Konstantinidis et al ⁎ | ESS | 30 | 5 | 7.2 (mean) | Ex CT, AN, SR |
| Nemet et al | DCR | 5 | 5 | 15.4 (mean) | Ex, dye test, SR |
| Amonoo-Kuofi et al | ESS | 28 | 5 | 19 (mean) | Ex |
| Kim et al ⁎ | ESS | 20 | 5 | 13.3 (mean) | Ex, MCST, AN |
| Gupta and Motwani ⁎ | ESS | 30 | 4 | 3 (max) | Ex, SR |
| Chan et al ⁎ | ESS | 45 | 4 | 1-6 (range) | Ex, AN |
| Chung et al ⁎ | ESS | 55 | 4 | 4.1 (mean) | Ex |
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