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01-09-2007 | Original Article

Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model

Authors: Kartal Hakan Yildiz, Ferruh Gezen, Merih Is, Selma Cukur, Murat Dosoglu

Published in: European Spine Journal | Issue 9/2007

Abstract

This study examined the preventive effects of the local application of mitomycin C (MMC), 5-fluorouracil (5-FU), and cyclosporine A (CsA) in minimizing spinal epidural fibrosis in a rat laminectomy model. Thirty-two 2-year-old male Wistar albino rats, each weighing 400 ± 50 g, were divided into four equal groups: sham, MMC, 5-FU, and CsA. Each rat underwent laminectomy at the L5–L6 lumbar level. Cotton pads (4 × 4 mm²) soaked with MMC (0.5 mg/ml), 5-FU (5 ml/mg), or CsA (5 mg/ml) were placed on the exposed dura for 5 min. Thirty days after surgery, the rats were killed and the epidural fibrosis, fibroblast density, inflammatory cell density, and arachnoid fibrosis were quantified. The epidural and arachnoid fibroses were reduced significantly in the treatment groups compared to the sham group. Fibroblast cell density and inflammatory cell density were decreased significantly in the MMC and 5-FU groups, but were similar in the sham and CsA groups. The decreased rate of epidural fibrosis was promising. Further studies in humans are needed to determine the short- and long-term complications of the agents used here.

Abitbol JJ, Lincoln TL, Lind BI, Amiel D, Akeson WH, Garfin SR (1994) Preventing postlaminectomy adhesion. A new experimental model. Spine 19:1809–1814PubMedCrossRef

Alkalay RN, Kim DH, Urry DW, Xu J, Parker TM, Glazer PA (2003) Prevention of postlaminectomy epidural fibrosis using bioelastic materials. Spine 28:1659–1665PubMedCrossRef

Aydin Y, Ziyal IM, Duman H, Turkmen CS, Basak M, Sahin Y (2002) Clinical and radiological results of lumbar microdiskectomy technique with preserving of ligamentum flavum comparing to the standard microdiskectomy technique. Surg Neurol 57:5–13PubMedCrossRef

Bagci G, Yucel I, Duranoglu Y (1999) The effect of cyclosporin A on cultured rabbit subconjunctival fibroblast proliferation. Ophthalmologica 213:114–119PubMedCrossRef

Barbera J, Gonzalez J, Esquerdo J, Broseta J, Barcia-Salorio JL (1978) Prophylaxis of the laminectomy membrane. An experimental study in dogs. J Neurosurg 49:419–424PubMed

Benoist M, Ficat C, Baraf P, Cauchoix J (1980) Postoperative lumbar epiduro-arachnoiditis. Diagnostic and therapeutic aspects. Spine 5:432–436PubMedCrossRef

Burton CV, Kirkaldy-Willis WH, Yong-Hing K, Heithoff KB (1981) Causes of failure of surgery on the lumbar spine. Clin Orthop Relat Res 157:191–199PubMed

Chang BS, Brown PR, Sieber A, Valdevit A, Tateno K, Kostuik JP (2004) Evaluation of the biological response of wear debris. Spine J 4(6 Suppl):239S–244SPubMedCrossRef

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 126:468–474PubMedCrossRef

10.

Cook SD, Prewett AB, Dalton JE, Whitecloud TS 3rd (1994) Reduction in perineural scar formation after laminectomy with polyactive membrane sheets. Spine 19:1815–1825PubMedCrossRef

11.

Coskun E, Suzer T, Topuz O, Zencir M, Pakdemirli E, Tahta K (2000) Relationships between epidural fibrosis, pain, disability, and psychological factors after lumbar disc surgery. Eur Spine J 9:218–223PubMedCrossRef

12.

Dogulu F, Kurt G, Emmez H, Erdem O, Memis L, Baykaner K, Ceviker N (2003) Topical mitomycin C-induced inhibition of postlaminectomy peridural fibrosis in rabbits. J Neurosurg 99(1 Suppl):76–79PubMed

13.

Einhaus SL, Robertson JT, Dohan FC Jr, Wujek JR, Ahmad S (1997) Reduction of peridural fibrosis after lumbar laminotomy and discectomy in dogs by a resorbable gel (ADCON-L). Spine 22:1440–1447PubMedCrossRef

14.

Gill GG, Scheck M, Kelley ET, Rodrigo JJ (1985) Pedicle fat grafts for the prevention of scar in low-back surgery. A preliminary report on the first 92 cases. Spine 10:662–667PubMedCrossRef

15.

Gilman AG, Rall Tw, Nies AS, Taylor P (eds) (1992) Goodman and Gilman’s “The Pharmacological Basis of Therapeutics”, 8th edn. McGraw-Hill, New York, vol 2, pp 1247–1248

16.

He Y, Revel M, Loty B (1995) A quantitative model of post-laminectomy scar formation. Effects of a nonsteroidal anti-inflammatory drug. Spine 20:557–563PubMedCrossRef

17.

Jayson MI (1992) The role of vascular damage and fibrosis in the pathogenesis of nerve root damage. Clin Orthop Relat Res 279:40–48PubMed

18.

Joshi AB, Parrish RK 2nd, Feuer WF (2005) 2002 survey of the American Glaucoma Society: practice preferences for glaucoma surgery and antifibrotic use. J Glaucoma 14:172–174PubMedCrossRef

19.

Key JA, Ford LT (1948) Experimental intervertebral-disc lesions. J Bone Joint Surg Am 30:621–630

20.

Khaw PT, Doyle JW, Sherwood MB, Grierson I, Schultz G, McGorray S (1993) Prolonged localized tissue effects from 5-minute exposures to fluorouracil and mitomycin C. Arch Ophthalmol 111:263–267PubMed

21.

Kim KD, Wang JC, Robertson DP, Brodke DS, Olson EM, Duberg AC, BenDebba M, Block KM, diZerega GS (2003) Reduction of radiculopathy and pain with Oxiplex/SP gel after laminectomy, laminotomy, and discectomy: a pilot clinical study. Spine 28:1080–1087PubMedCrossRef

22.

Kitano T, Zerwekh JE, Edwards ML, Usui Y, Allen MD (1991) Viscous carboxymethylcellulose in the prevention of epidural scar formation. Spine 16:820–833PubMedCrossRef

23.

Lama PJ, Fechtner RD (2003) Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol 48:314–346PubMedCrossRef

24.

Langenskiold A, Kiviluoto O (1976) Prevention of epidural scar formation after operations on the lumbar spine by means of free fat transplants. A preliminary report. Clin Orthop Relat Res 115:92–95PubMed

25.

LaRocca H, Macnab I (1974) The laminectomy membrane. Studies in its evolution, characteristics, effects and prophylaxis in dogs. J Bone Joint Surg Br 56B:545–550PubMed

26.

Lee HM, Yang KH, Han DY, Kim NH (1990) An experimental study on prevention of postlaminectomy scar formation. Yonsei Med J 31:359–366PubMed

27.

Lee JY, Stenzel W, Ebel H, Wedekind C, Ernestus RI, Klug N (2004) Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats. J Neurosurg 100(1 Suppl Spine):52–55PubMed

28.

Long DM, Filtzer DL, BenDebba M, Hendler NH (1988) Clinical features of the failed-back syndrome. J Neurosurg 69:61–71PubMed

29.

Maroon JC, Abla A, Bost J (1999) Association between peridural scar and persistent low back pain after lumbar discectomy. Neurol Res 21:S43–S46PubMedCrossRef

30.

Mietz H, Krieglstein GK (1998) Three-year follow-up of trabeculectomies performed with different concentrations of mitomycin-C. Ophthalmic Surg Lasers 29:628–634PubMed

31.

Mikawa Y, Hamagami H, Shikata J, Higashi S, Yamamuro T, Hyon SH, Ikada Y (1986) An experimental study on prevention of postlaminectomy scar formation by the use of new materials. Spine 11:843–846PubMedCrossRef

32.

Murayama T, Takahashi N, Ikoma N (1996) Cytotoxicity and characteristics of mitomycin C. Ophthalmic Res 28:153–159 PubMedCrossRef

33.

Nussbaum CE, McDonald JV, Baggs RB (1990) Use of Vicryl (polyglactin 910) mesh to limit epidural scar formation after laminectomy. Neurosurgery 26:649–654PubMedCrossRef

34.

Park YK, Kim JH, Chung HS (2002) Outcome analysis of patients after ligament-sparing microdiscectomy for lumbar disc herniation. Neurosurg Focus 13(2):E4PubMed

35.

Petri JB, Schurk S, Gebauer S, Haustein UF (1998) Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats. Eur J Dermatol 8:104–113PubMed

36.

Quist JJ, Dhert WJ, Meij BP, Visser WJ, Oner FC, Hazewinkel HA, Verbout AJ (1998) The prevention of peridural adhesions. A comparative long-term histomorphometric study using a biodegradable barrier and a fat graft. J Bone Joint Surg Br 80:520–526PubMedCrossRef

37.

Robertson JT, Meric AL, Dohan FC Jr, Schweitzer JB, Wujek JR, Ahmad S (1993) The reduction of postlaminectomy peridural fibrosis in rabbits by a carbohydrate polymer. J Neurosurg 79:89–95PubMedCrossRef

38.

Robertson JT(1996) Role of peridural fibrosis in the failed back: a review. Eur Spine J 5:S2–6PubMedCrossRef

39.

Ross JS, Robertson JT, Frederickson RC, Petrie JL, Obuchowski N, Modic MT, deTribolet N (1996) Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. ADCON-L European Study Group. Neurosurgery 38:855–861PubMedCrossRef

40.

Songer MN, Ghosh L, Spencer DL (1990) Effects of sodium hyaluronate on peridural fibrosis after lumbar laminotomy and discectomy. Spine 15:550–554PubMedCrossRef

41.

Songer MN, Rauschning W, Carson EW, Pandit SM (1995) Analysis of peridural scar formation and its prevention after lumbar laminotomy and discectomy in dogs. Spine 20:571–580PubMedCrossRef

42.

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

43.

Wujek JR, Ahmad S, Harel A, Maier KH, Roufa D, Silver J (1991) A carbohydrate polymer that effectively prevents epidural fibrosis at laminectomy sites in the rat. Exp Neurol 114:237–245PubMedCrossRef

44.

Yoon PS, Singh K (2004) Update on antifibrotic use in glaucoma surgery, including use in trabeculectomy and glaucoma drainage implants and combined cataract and glaucoma surgery. Curr Opin Ophthalmol 15:141–146PubMedCrossRef

Title: Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model
Authors: Kartal Hakan Yildiz
Ferruh Gezen
Merih Is
Selma Cukur
Murat Dosoglu
Publication date: 01-09-2007
Publisher: Springer-Verlag
Published in: European Spine Journal / Issue 9/2007
Print ISSN: 0940-6719
Electronic ISSN: 1432-0932
DOI: https://doi.org/10.1007/s00586-007-0344-8

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Mitomycin C, 5-fluorouracil, and cyclosporin A prevent epidural fibrosis in an experimental laminectomy model

Abstract

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