Top

European Archives of Oto-Rhino-Laryngology

Published in:

Open Access 01-03-2010 | Review Article

Topical use of MMC in the upper aerodigestive tract: a review on the side effects

Authors: Egbert J. D. Veen, Frederik G. Dikkers

Published in: European Archives of Oto-Rhino-Laryngology | Issue 3/2010

Abstract

Not much is known about the side effects of mitomycin C (MMC), an anti-fibrogenetic agent, in the upper aerodigestive tract. However, its use in ophthalmology is widely known and without quantitatively important side effects. A literature review was performed for side effects of MMC in the upper aerodigestive tract. Forty-six articles, describing the use of MMC to prevent scarring, were retracted from PubMed. Thirty-two are human studies. MMC is used in different concentrations (0.1–10 mg/ml) with different application times (2–5 min) and frequencies (up to 4 times). Five hundred and thirty-eight patients were included in those publications, of whom 19 developed side effects (3.53%). No side effects developed in studies, where post-application irrigation with saline was reported. The longest mean follow-up period is 75.5 months. Direct relations between the reported side effects and MMC seem absent in most studies. Serious complications seem to occur when MMC is used in high concentrations. Unfortunately, sometimes crucial information is lacking. One patient was described who supposedly developed laryngeal carcinoma after repeated treatment of hyperkeratosis and anterior commissure webbing. Animal studies show that excessive fibrin production can lead to acute airway obstruction. In conclusion, topical application of MMC on a wound with consecutive irrigation with saline can be performed safely to prevent scar formation in circular structures of the upper aerodigestive tract. Long-term yearly control of the application site seems advisable.

Djordjevic B, Kim JH (1968) Different lethal effects of mitomycin C and actinomycin D during the division cycle of HeLa cells. J Cell Biol 38:477–482CrossRefPubMed

Hu D, Sires BS, Tong DC, Royack GA, Oda D (2000) Effect of brief exposure to mitomycin C on cultured human nasal mucosa fibroblasts. Ophthal Plast Reconstr Surg 16:119–125CrossRefPubMed

Rahbar R, Jones DT, Nuss RC, Roberson DW, Kenna MA, McGill TJ, Healy GB (2002) 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 128:401–406PubMed

Hardillo J, Vanclooster C, Delaere PR (2001) An investigation of airway wound healing using a novel in vivo model. Laryngoscope 111:1174–1182CrossRefPubMed

Ferguson B, Gray SD, Thibeault S (2005) Time and dose effects of mitomycin C on extracellular matrix fibroblasts and proteins. Laryngoscope 115:110–115CrossRefPubMed

Khong JJ, Muecke J (2006) Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia. Br J Ophthalmol 90:819–822CrossRefPubMed

Kopp ED, Seregard S (2004) Epiphora as a side effect of topical mitomycin C. Br J Ophthalmol 88:1422–1424CrossRefPubMed

Tabatabaie SZ, Heirati A, Rajabi MT, Kasaee A (2007) Silicone intubation with intraoperative mitomycin C for nasolacrimal duct obstruction in adults: a prospective, randomized, double-masked study. Ophthal Plast Reconstr Surg 23:455–458CrossRefPubMed

Yildirim C, Yaylali V, Esme A, Ozden S (2007) Long-term results of adjunctive use of mitomycin C in external dacryocystorhinostomy. Int Ophthalmol 27:31–35CrossRefPubMed

10.

Afzal NA, Albert D, Thomas AL, Thomson M (2002) A child with oesophageal strictures. Lancet 359:1032CrossRefPubMed

11.

Agrawal N, Morrison GA (2006) Laryngeal cancer after topical mitomycin C application. J Laryngol Otol 120:1075–1076CrossRefPubMed

12.

Mathiasen RA, Cruz RM (2005) Asymptomatic near-total airway obstruction by a cylindrical tracheal foreign body. Laryngoscope 115:274–277CrossRefPubMed

13.

Monnier P (2000) Prevention of cicatricial stenosis of the larynx resulting from intubation. Ned Tijdschr KNO-heelk 6:123–125

14.

Penafiel A, Lee P, Hsu A, Eng P (2006) Topical mitomycin-C for obstructing endobronchial granuloma. Ann Thorac Surg 82:e22–e23CrossRefPubMed

15.

Phillips PS, monoo-Kuofi K, Hore ID, Atherton DJ, Albert DM (2006) Successful treatment of laryngeal stenosis in laryngo-onycho-cutaneous syndrome with topical mitomycin C. Pediatr Dermatol 23:75–77CrossRefPubMed

16.

Roh JL (2006) Application of mitomycin C after endoscopic lysis of congenital laryngeal web combined with epiglottic hypoplasia in a middle-aged man. Acta Otolaryngol 126:438–441CrossRefPubMed

17.

Salvado AR, Wang MB (2008) Treatment of complete nasal vestibule stenosis with vestibular stents and mitomycin C. Otolaryngol Head Neck Surg 138:795–796CrossRefPubMed

18.

Unal M (2004) The successful management of congenital laryngeal web with endoscopic lysis and topical mitomycin-C. Int J Pediatr Otorhinolaryngol 68:231–235CrossRefPubMed

19.

Ward RF, April MM (1998) Mitomycin-C in the treatment of tracheal cicatrix after tracheal reconstruction. Int J Pediatr Otorhinolaryngol 44:221–226CrossRefPubMed

20.

Zur KB, Putnam PE, Rutter MJ (2007) Combined retrograde and anterograde hypopharyngeal puncture and dilatation in a child with complete hypopharyngeal stenosis. Int J Pediatr Otorhinolaryngol 71:153–157CrossRefPubMed

21.

Dolmetsch AM, Gallon MA, Holds JB (2008) Nonlaser endoscopic endonasal dacryocystorhinostomy with adjunctive mitomycin C in children. Ophthal Plast Reconstr Surg 24:390–393CrossRefPubMed

22.

Hueman EM, Simpson CB (2005) Airway complications from topical mitomycin C. Otolaryngol Head Neck Surg 133:831–835CrossRefPubMed

23.

Isa AY, Macandie C, Irvine BW (2006) Nitinol stents in the treatment of benign proximal tracheal stenosis or tracheomalacia. J Laryngol Otol 120:32–37CrossRefPubMed

24.

Koshkareva Y, Gaughan JP, Soliman AM (2007) Risk factors for adult laryngotracheal stenosis: a review of 74 cases. Ann Otol Rhinol Laryngol 116:206–210PubMed

25.

Kubba H, Bennett A, Bailey CM (2004) An update on choanal atresia surgery at Great Ormond Street Hospital for children: preliminary results with mitomycin C and the KTP laser. Int J Pediatr Otorhinolaryngol 68:939–945CrossRefPubMed

26.

Amonoo-Kuofi K, Lund VJ, Andrews P, Howard DJ (2006) The role of mitomycin C in surgery of the frontonasal recess: a prospective open pilot study. Am J Rhinol 20:591–594CrossRefPubMed

27.

Nouraei SA, Singh A, Patel A, Ferguson C, Howard DJ, Sandhu GS (2006) Early endoscopic treatment of acute inflammatory airway lesions improves the outcome of postintubation airway stenosis. Laryngoscope 116:1417–1421CrossRefPubMed

28.

Perepelitsyn I, Shapshay SM (2004) Endoscopic treatment of laryngeal and tracheal stenosis-has mitomycin C improved the outcome? Otolaryngol Head Neck Surg 131:16–20CrossRefPubMed

29.

Valdez TA, Shapshay SM (2002) Idiopathic subglottic stenosis revisited. Ann Otol Rhinol Laryngol 111:690–695PubMed

30.

Gupta M, Motwani G (2006) Role of mitomycin C in reducing adhesion formation following endoscopic sinus surgery. J Laryngol Otol 120:921–923CrossRefPubMed

31.

Kim ST, Gang IG, Cha HE, Ha JS, Chung YS (2006) Effect of mitomycin C on the size of antrostomy after endoscopic sinus surgery. Ann Otol Rhinol Laryngol 115:673–678PubMed

32.

Rahbar R, Shapshay SM, Healy GB (2001) Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications. Ann Otol Rhinol Laryngol 110:1–6PubMed

33.

Roh JL, Yoon YH (2005) Prevention of anterior glottic stenosis after transoral microresection of glottic lesions involving the anterior commissure with mitomycin C. Laryngoscope 115:1055–1059CrossRefPubMed

34.

Roh JL, Kim AY (2005) Application of mitomycin C after transoral removal of submandibular stones and sialodochoplasty. Laryngoscope 115:915–918CrossRefPubMed

35.

Rosseneu S, Afzal N, Yerushalmi B, Ibarguen-Secchia E, Lewindon P, Cameron D, Mahler T, Schwagten K, Kohler H, Lindley KJ, Thomson M (2007) Topical application of mitomycin-C in oesophageal strictures. J Pediatr Gastroenterol Nutr 44:336–341CrossRefPubMed

36.

Anand VK, Tabaee A, Kacker A, Newman JG, Huang C (2004) The role of mitomycin C in preventing synechia and stenosis after endoscopic sinus surgery. Am J Rhinol 18:311–314PubMed

37.

Chan KO, Gervais M, Tsaparas Y, Genoway KA, Manarey C, Javer AR (2006) Effectiveness of intraoperative mitomycin C in maintaining the patency of a frontal sinusotomy: a preliminary report of a double-blind randomized placebo-controlled trial. Am J Rhinol 20:295–299CrossRefPubMed

38.

Chung JH, Cosenza MJ, Rahbar R, Metson RB (2002) Mitomycin C for the prevention of adhesion formation after endoscopic sinus surgery: a randomized, controlled study. Otolaryngol Head Neck Surg 126:468–474CrossRefPubMed

39.

Hartnick CJ, Hartley BE, Lacy PD, Liu J, Bean JA, Willging JP, Myer CM III, Cotton RT (2001) Topical mitomycin application after laryngotracheal reconstruction: a randomized, double-blind, placebo-controlled trial. Arch Otolaryngol Head Neck Surg 127:1260–1264PubMed

40.

Konstantinidis I, Tsakiropoulou E, Vital I, Triaridis S, Vital V, Constantinidis J (2008) Intra- and postoperative application of Mitomycin C in the middle meatus reduces adhesions and antrostomy stenosis after FESS. Rhinology 46:107–111PubMed

41.

Hirshoren N, Eliashar R (2009) Wound-healing modulation in upper airway stenosis-Myths and facts. Head Neck 31:111–126

42.

Tabaee A, Brown SM, Anand VK (2007) Mitomycin C and endoscopic sinus surgery: where are we? Curr Opin Otolaryngol Head Neck Surg 15:40–43CrossRefPubMed

43.

Correa AJ, Reinisch L, Sanders DL, Huang S, Deriso W, Duncavage JA, Garrett CG (1999) Inhibition of subglottic stenosis with mitomycin-C in the canine model. Ann Otol Rhinol Laryngol 108:1053–1060PubMed

44.

Eliashar R, Eliachar I, Esclamado R, Gramlich T, Strome M (1999) Can topical mitomycin prevent laryngotracheal stenosis? Laryngoscope 109:1594–1600CrossRefPubMed

45.

Garrett CG, Soto J, Riddick J, Billante CR, Reinisch L (2001) Effect of mitomycin-C on vocal fold healing in a canine model. Ann Otol Rhinol Laryngol 110:25–30PubMed

46.

Gray SD, Tritle N, Li W (2003) The effect of mitomycin on extracellular matrix proteins in a rat wound model. Laryngoscope 113:237–242CrossRefPubMed

47.

Ingrams DR, Volk MS, Biesman BS, Pankratov MM, Shapshay SM (1998) Sinus surgery: does mitomycin C reduce stenosis? Laryngoscope 108:883–886CrossRefPubMed

48.

Iniguez-Cuadra R, San Martin PJ, Iniguez-Cuadra M, Zuniga ES, Jofre PD, Gonzalez BS, Guilemany Toste JM, Iniguez-Sasso R (2008) Effect of mitomycin in the surgical treatment of tracheal stenosis. Arch Otolaryngol Head Neck Surg 134:709–714CrossRefPubMed

49.

Rahal A, Peloquin L, Ahmarani C (2001) Mitomycin C in sinus surgery: preliminary results in a rabbit model. J Otolaryngol 30:1–5CrossRefPubMed

50.

Roh JL, Lee YW, Park CI (2006) Can mitomycin C really prevent airway stenosis? Laryngoscope 116:440–445CrossRefPubMed

51.

Roh JL, Kim DH, Rha KS, Sung MW, Kim KH, Park CI (2007) Benefits and risks of mitomycin use in the traumatized tracheal mucosa. Otolaryngol Head Neck Surg 136:459–463CrossRefPubMed

52.

Spector JE, Werkhaven JA, Spector NC, Huang S, Page RN, Baranowski B, Luther M, McGehee B, Reinisch L (1999) Preservation of function and histologic appearance in the injured glottis with topical mitomycin-C. Laryngoscope 109:1125–1129CrossRefPubMed

53.

Ragin CC, Modugno F, Gollin SM (2007) The epidemiology and risk factors of head and neck cancer: a focus on human papillomavirus. J Dent Res 86:104–114CrossRefPubMed

54.

Zeitels SM (1995) Premalignant epithelium and microinvasive cancer of the vocal fold: the evolution of phonomicrosurgical management. Laryngoscope 105:1–51CrossRefPubMed

Title: Topical use of MMC in the upper aerodigestive tract: a review on the side effects
Authors: Egbert J. D. Veen
Frederik G. Dikkers
Publication date: 01-03-2010
Publisher: Springer-Verlag
Published in: European Archives of Oto-Rhino-Laryngology / Issue 3/2010
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-009-1151-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Topical use of MMC in the upper aerodigestive tract: a review on the side effects

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2010

Identification of polymorphisms in the Toll-like receptor gene and the association with allergic rhinitis

Identification of polymorphisms in the RNase3 gene and the association with allergic rhinitis

Ultrasound-guided localisation of trachea for surgical tracheostomy

The effect of a Heat and Moisture Exchanger (Provox® HME) on pulmonary protection after total laryngectomy: a randomized controlled study

Evaluation of Eustachian tube function with perfect sequences: technical realization and first clinical results

Narrow band imaging and high definition television in the assessment of laryngeal cancer: a prospective study on 279 patients