Mitomycin C und Wundheilung

Zusammenfassung

Mitomycin C (MMC) wird in der Onkologie als Chemotherapeutikum verwendet. Seine Metaboliten binden an DNA-Moleküle und induzieren DNA-Quervernetzungen. MMC interferiert so mit der DNA-, RNA- und Proteinsynthese. Hierdurch hemmt MMC das Wachstum und die Teilung von Fibroblasten, den Schlüsselzellen von Wundheilung und Narbenbildung. Als Besonderheit hemmt MMC insbesondere die Synthese von Proteinen der Zellzwischensubstanz wie Fibronektin und Kollagen, die im Rahmen der Wundheilung wesentliche Funktionen ausüben. Aufgrund dieser Eigenschaften ist MMC grundsätzlich in der Lage, die Bildung von übermäßigen Narben, Adhäsionen, Synechien und Restenosierungen nach Eingriffen im Kopf-Hals-Bereich zu reduzieren. In folgendem Fortbildungsbeitrag werden die Ergebnisse experimenteller und klinischer Untersuchungen zur topischen Anwendung von MMC berichtet.

Abstract

Mitomycin C (MMC) is frequently used in combination chemotherapy. Its metabolites bind to DNA-molecules and causes DNA crosslinking, which interferes with the synthesis of DNA, RNA and proteins. MMC is thus able to reduce fibroblast proliferation. Moreover, MMC particularly inhibits the synthesis of extracellular matrix proteins including fibronectin and various collagens. These properties have been demonstrated in several experimental studies. Beside its merits in treatment of malignancies, MMC may thus be useful to prevent hypertrophic scars and keloids, adhesions and ostial restenosis following head and neck surgical procedures. Clinically, MMC has been applied to prevent scarring after ophthalmologic surgery. Recent experimental and clinical trials investigating the effects of MMC on wound healing following head and neck surgical procedures are reviewed.

Schlüsselwörter

Wundheilung - Nasennebenhöhlenchirurgie - Mitomycin C - Narben - Stenosen - Adhäsionen

Key words

sinus surgery - mitomycin C - wound healing - scarring - stenosis - adhesions

Literatur

• 1 Scheithauer M, Riechelmann H. Übersicht Teil I: Grundlagen der kutanen Wundheilung.  Laryngo Rhino Otol. 2003;  82 31-35
• 2 Scheithauer M, Riechelmann H. Übersicht Teil II: Die gestörte kutane Wundheilung.  Laryngo Rhino Otol. 2003;  82 36-39
• 3 Cummings J, Spanswick V J, Smyth J F. Re-evaluation of the molecular pharmacology of mitomycin C.  Eur J Cancer. 1995;  31A 1928-1933
• 4 Chen T, Kunnavatana S S, Koch R J. Effects of mitomycin-C on normal dermal fibroblasts.  Laryngoscope. 2006;  116 514-517
• 5 Rahal A, Peloquin L, Ahmarani C. Mitomycin C in sinus surgery: preliminary results in a rabbit model.  J Otolaryngol. 2001;  30 1-5
• 6 Ferguson B, Gray S D, Thibeault S. Time and dose effects of mitomycin C on extracellular matrix fibroblasts and proteins.  Laryngoscope. 2005;  115 110-115
• 7 Porter G T, Gadre S A, Calhoun K H. The effects of intradermal and topical mitomycin C on wound healing.  Otolaryngol Head Neck Surg. 2006;  135 56-60
• 8 Gray S D, Tritle N, Li W. The effect of mitomycin on extracellular matrix proteins in a rat wound model.  Laryngoscope. 2003;  113 237-242
• 9 Ribeiro F A, Guaraldo L, Borges J P, Zacchi F F, Eckley C A. Clinical and histological healing of surgical wounds treated with mitomycin C.  Laryngoscope. 2004;  114 148-152
• 10 Sewall G K, Robertson K M, Connor N P, Heisey D M, Hartig G K. Effect of topical mitomycin on skin wound contraction.  Arch Facial Plast Surg. 2003;  5 59-62
• 11 Stewart C E, Kim J Y. Application of mitomycin-C for head and neck keloids.  Otolaryngol Head Neck Surg. 2006;  135 946-950
• 12 Talmi Y P, Orenstein A, Wolf M, Kronenberg J. Use of mitomycin C for treatment of keloid: a preliminary report.  Otolaryngol Head Neck Surg. 2005;  132 598-601
• 13 Sanders K W, Gage-White L, Stucker F J. Topical mitomycin C in the prevention of keloid scar recurrence.  Arch Facial Plast Surg. 2005;  7 172-175
• 14 Singh G, Wilson M R, Foster C S. Mitomycin eye drops as treatment for pterygium.  Ophthalmology. 1988;  95 813-821
• 15 Chen C W, Huang H T, Bair J S, Lee C C. Trabeculectomy with simultaneous topical application of mitomycin-C in refractory glaucoma.  J Ocul Pharmacol. 1990;  6 175-182
• 16 Eliashar R, Eliachar I, Esclamado R, Gramlich T, Strome M. Can topical mitomycin prevent laryngotracheal stenosis?.  Laryngoscope. 1999;  109 1594-1600
• 17 Simpson C B, James J C. The efficacy of mitomycin-C in the treatment of laryngotracheal stenosis.  Laryngoscope. 2006;  116 1923-1925
• 18 Rahbar R, Valdez T A, Shapshay S M. Preliminary results of intraoperative mitomycin-C in the treatment and prevention of glottic and subglottic stenosis.  J Voice. 2000;  14 282-286
• 19 Rahbar R, Shapshay S M, Healy G B. Mitomycin: effects on laryngeal and tracheal stenosis, benefits, and complications.  Ann Otol Rhinol Laryngol. 2001;  110 1-6
• 20 Rahbar R, Jones D T, Nuss R C, Roberson D W, Kenna M A, McGill T J, Healy G B. 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;  128 401-406
• 21 Hartnick C J, Hartley B E, Lacy P D, Liu J, Bean J A, Willging J P, Myer C M3, Cotton R T. Topical mitomycin application after laryngotracheal reconstruction: a randomized, double-blind, placebo-controlled trial.  Arch Otolaryngol Head Neck Surg. 2001;  127 1260-1264
• 22 Hueman E M, Simpson C B. Airway complications from topical mitomycin C.  Otolaryngol Head Neck Surg. 2005;  133 831-835
• 23 Rombaux P, de Toeuf C, Hamoir M, Eloy P, Bertrand B, Veykemans F. Transnasal repair of unilateral choanal atresia.  Rhinology. 2003;  41 31-36
• 24 Prasad M, Ward R F, April M M, Bent J P, Froehlich P. Topical mitomycin as an adjunct to choanal atresia repair.  Arch Otolaryngol Head Neck Surg. 2002;  128 398-400
• 25 You Y A, Fang C T. Intraoperative mitomycin C in dacryocystorhinostomy.  Ophthal Plast Reconstr Surg. 2001;  17 115-119
• 26 Roozitalab M H, Amirahmadi M, Namazi M R. Results of the application of intraoperative mitomycin C in dacryocystorhinostomy.  Eur J Ophthalmol. 2004;  14 461-463
• 27 Estrem S A, Batra P S. Preventing myringotomy closure with topical mitomycin C in rats.  Otolaryngol Head Neck Surg. 1999;  120 794-798
• 28 Estrem S A, Vanleeuwen R N. Use of mitomycin C for maintaining myringotomy patency.  Otolaryngol Head Neck Surg. 2000;  122 8-10
• 29 Jassir D, Buchman C A, Gomez-Marin O. Safety and efficacy of topical mitomycin C in myringotomy patency.  Otolaryngol Head Neck Surg. 2001;  124 368-373
• 30 Jassir D, Odabasi O, Gomez-Marin O, Buchman C A. Dose-response relationship of topically applied mitomycin C for the prevention of laser myringotomy closure.  Otolaryngol Head Neck Surg. 2003;  129 471-474
• 31 Babu S C, Kartush J M, Patni A. Otologic effects of topical mitomycin C: phase I-evaluation of ototoxicity.  Otol Neurotol. 2005;  26 140-144
• 32 Ragab S M. The effect of radiofrequency and mitomycin C on the closure rate of human tympanostomy.  Otol Neurotol. 2005;  26 355-360
• 33 Banthia V, Selesnick S H. Mitomycin-C in the postsurgical ear canal.  Otolaryngol Head Neck Surg. 2003;  128 882-886
• 34 Battelino S, Hocevar-Boltezar I, Zargi M. Intraoperative use of mitomycin C in fibrous atresia of the external auditory canal.  Ear Nose Throat J. 2005;  84 776-779
• 35 Hosemann W. Die endonasale Chirurgie der Nasennebenhöhlen - Konzepte, Techniken, Ergebnisse, Komplikationen, Revisionseingriffe.  Eur Arch Otorhinolaryngol Suppl. 1996;  1 155-269
• 36 Ramadan H H. Surgical causes of failure in endoscopic sinus surgery.  Laryngoscope. 1999;  109 27-29
• 37 Weber R, Mai R, Hosemann W, Draf W, Toffel P. The success of 6-month stenting in endonasal frontal sinus surgery.  Ear Nose Throat J. 2000;  79 930-938
• 38 Rajapaksa S P, Ananda A, Cain T M, Oates L, Wormald P J. Frontal ostium neo-osteogenesis and restenosis after modified endoscopic Lothrop procedure in an animal model.  Clin Otolaryngol Allied Sci. 2004;  29 386-388
• 39 Kark L R, Karp J M, Davies J E. Platelet releasate increases the proliferation and migration of bone marrow-derived cells cultured under osteogenic conditions.  Clin Oral Implants Res. 2006;  17 321-327
• 40 Hu D, Sires B S, Tong D C, Royack G A, Oda D. Effect of brief exposure to mitomycin C on cultured human nasal mucosa fibroblasts.  Ophthal Plast Reconstr Surg. 2000;  16 119-125
• 41 Ingrams D R, Volk M S, Biesman B S, Pankratov M M, Shapshay S M. Sinus surgery: does mitomycin C reduce stenosis?.  Laryngoscope. 1998;  108 883-886
• 42 Park S W, Koo B S, Park Y H, Jin Y D, Rha K S. Effect of topical mitomycin C for antrostomy in rabbit with sinusitis.  Eur Arch Otorhinolaryngol. 2006;  263 917-923
• 43 Amonoo-Kuofi K, Lund V J, Andrews P, Howard D J. The role of mitomycin C in surgery of the frontonasal recess: a prospective open pilot study.  Am J Rhinol. 2006;  20 591-594
• 44 Chung J H, Cosenza M J, Rahbar R, Metson R B. Mitomycin C for the prevention of adhesion formation after endoscopic sinus surgery: a randomized, controlled study.  Otolaryngol Head Neck Surg. 2002;  126 468-474
• 45 Kim S T, Gang I G, Cha H E, Ha J S, Chung Y S. Effect of mitomycin C on the size of antrostomy after endoscopic sinus surgery.  Ann Otol Rhinol Laryngol. 2006;  115 673-678
• 46 Anand V K, Tabaee A, Kacker A, Newman J G, Huang C. The role of mitomycin C in preventing synechia and stenosis after endoscopic sinus surgery.  Am J Rhinol. 2004;  18 311-314