The effect of mitomycin C in reducing epidural fibrosis after lumbar laminectomy in rats

2006 ◽  
Vol 5 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Jin-Yul Lee ◽  
Werner Stenzel ◽  
Peter Impekoven ◽  
Martin Theisohn ◽  
Hartmut Stützer ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Fibrous Tissue ◽  
Lumbar Spine Surgery ◽  
Severe Bleeding ◽  
Epidural Fibrosis ◽  
Mr Images ◽  
Radiological Investigation ◽  
Similar Treatment ◽  
Failed Back Syndrome ◽  
Spinal Epidural

Object xtensive epidural fibrosis after lumbar spine surgery might be an important underlying cause of failed-back syndrome. Based on previously obtained data, the effect of mitomycin C (MMC) in a concentration of 0.1 mg/ml on spinal epidural fibrosis in a rat laminectomy model was investigated in a large series. Methods ighty adult Wistar rats underwent lumbar laminectomy. In 40 rats, MMC in a concentration of 0.1 mg/ml was locally applied to the laminectomy sites. No similar treatment was performed in the other 40 rats. At intervals from one to 12 weeks after laminectomy, both macroscopic and histological evaluations were performed. For radiological investigation, 10 rats underwent magnetic resonance (MR) imaging at 6 weeks postoperatively. Furthermore, the concentration of MMC in cerebrospinal fluid (CSF) and serum was determined 12 hours postoperatively in seven rats. Due to ease of absorption, high levels of MMC were rapidly detectable in serum, whereas the values obtained from the CSF were markedly lower. In the majority of MMC-treated laminectomy sites, epidural scarring was significantly reduced and dural adhesions were absent, in comparison with control sites (p < 0.001), as confirmed by MR images. Accordingly, the macroscopic dissection of epidural fibrous tissue to reexpose the dura mater was performed more easily and without severe bleeding in these rats. The healing of skin and the lumbar fascia was not affected, and dural leakage was not observed. All control sites showed dense epidural fibrosis with marked dural adherence. Conclusions n this experimental model, it was shown that locally applied MMC in a concentration of 0.1 mg/ml effectively reduces epidural fibrosis and dural adherence without side effects in rats that underwent lumbar laminectomy.

The role of mitomycin C in reducing recurrence of epidural fibrosis after repeated operation in a laminectomy model in rats

2006 ◽  
Vol 4 (4) ◽  
pp. 329-333 ◽  
Author(s):  
Jin-Yul Lee ◽  
Werner Stenzel ◽  
Mario Löhr ◽  
Hartmut Stützer ◽  
Ralf-Ingo Ernestus ◽  
...  
Keyword(s):  
Side Effects ◽  
Mitomycin C ◽  
Fibrous Tissue ◽  
Scar Tissue ◽  
Lumbar Spine Surgery ◽  
Control Group ◽  
Epidural Fibrosis ◽  
The Reformation ◽  
Secondary Procedures

Object Extensive peridural fibrosis after lumbar spine surgery may contribute to poor outcome and recurrent symptoms leading to repeated operation. Secondary procedures are considerably hampered by the presence of scar tissue. Moreover, after excision of the peridural scar, the fibrous tissue may recur, leading to unsuccessful surgical outcome. Mitomycin C (MMC), an alkylating antibiotic substance isolated from Streptomyces caespitosus, potentially suppresses fibroblast proliferation after surgical intervention. The authors investigated the effect of MMC on the reformation of epidural fibrosis in a laminectomy model in rats. Methods Twenty-four Wistar rats underwent a repeated lumbar laminectomy 3 months after the first operation. In 12 rats, MMC in a concentration of 1 mg/ml was locally applied to the laminectomy site. No treatment was performed in the control group of the other 12 rats. All rats underwent clinical evaluation. Mobility ratings and any evidence of neurological deficit were recorded. Twelve weeks after the second operation, the animals were killed for histological examination. The extent of epidural fibrosis and dural adherence was evaluated. All MMC-treated animals showed reduced epidural scarring, compared with the control group. In nine MMC-treated rats (75%), dural adhesions were moderate. In contrast, all control sites showed dense epidural fibrosis with marked dural adherence. No side effects of the treatment were observed. Conclusions In this experimental study, MMC in a concentration of 1 mg/ml locally applied significantly reduced recurrence of epidural fibrosis and dural adhesions without any side effects after repeated spinal surgery in a laminectomy model in rats.

Mitomycin C in preventing spinal epidural fibrosis in a laminectomy model in rats

2004 ◽  
Vol 100 (1) ◽  
pp. 52-55 ◽  
Author(s):  
Jin-Yul Lee ◽  
Werner Stenzel ◽  
Heinrich Ebel ◽  
Christoph Wedekind ◽  
Ralf-Ingo Ernestus ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Spinal Column ◽  
Failed Back Surgery Syndrome ◽  
Epidural Fibrosis ◽  
En Bloc ◽  
Content Type ◽  
Failed Back Surgery ◽  
Back Surgery ◽  
Spinal Epidural ◽  
Fine Print

Object. Extensive epidural fibrosis after lumbar surgery may be the underlying cause in most cases of failed—back surgery syndrome. Various materials have been used to prevent epidural fibrosis, but only moderate success has been shown. Mitomycin C, an alkylosing antibiotic substance isolated from Streptomyces caespitosus, potentially supresses fibroblast proliferation after surgery. In this study, the authors investigated the effect of mitomycin C by local application on spinal epidural fibrosis in a rat laminectomy model. Methods. Five Wistar rats underwent laminectomy at cervical, thoracic, and lumbar levels. Based on data obtained from ophthalmological studies, mitomycin C was applied to the laminectomy sites in various concentrations (0.01, 0.05, and 0.1 mg/ml). One laminectomy site in each rat was left untreated and thus served as a control. Evoked potentials were measured pre- and postoperatively, and all rats underwent clinical evaluation. Mobility status and evidence of neurological deficit were recorded. Twelve weeks later, the rats were killed, and the spinal column, including surrounding muscle tissue, was removed en bloc, decalcified, and fixed in formaldehyde. Epidural fibrosis was evaluated histologically. In all mitomycin C—treated laminectomy sites, epidural scarring was significantly reduced compared with control sites. Remarkably, dural adhesions were absent in laminectomy defects treated with mitomycin C concentrations of 0.05 and 0.1 mg/ml. Moderate to marked epidural fibrosis with adhesion to the dura mater was noted at sites receiving 0.01 mg/ml of mitomycin C. All control sites showed dense epidural fibrosis with marked dura adherence. Conclusions. In this experimental model, mitomycin C applied locally at a concentration of 0.1 mg/ml effectively reduced epidural fibrosis, completely avoided dural adherence, and induced no side effects.

Use of pimecrolimus to prevent epidural fibrosis in a postlaminectomy rat model

2009 ◽  
Vol 11 (6) ◽  
pp. 758-763 ◽  
Author(s):  
Berker Cemil ◽  
Kagan Tun ◽  
Erkan Kaptanoglu ◽  
Figen Kaymaz ◽  
Banu Cevirgen ◽  
...  
Keyword(s):  
Mitomycin C ◽  
Dura Mater ◽  
Inflammatory Diseases ◽  
Scar Tissue ◽  
Control Group ◽  
Epidural Fibrosis ◽  
Treatment Groups ◽  
Lumbar Level ◽  
Spinal Epidural ◽  
Preventive Effects

Object Epidural fibrosis is the scar tissue formed over the dura mater after a laminectomy. Extensive epidural fibrosis may be an important underlying cause of failed back syndrome. Pimecrolimus, an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory diseases. This study examined the preventive effects of the local application of pimecrolimus in minimizing spinal epidural fibrosis in a rat laminectomy model. Methods Thirty Wistar rats were divided into 3 equal groups: control, mitomycin C (MMC), and pimecrolimus groups. Each rat underwent a laminectomy at the L-3 lumbar level. In the experimental groups, a cotton pad soaked with MMC (0.5 mg/ml) or 5 mg pimecrolimus was placed on the exposed dura mater. No treatment was performed in the control group rats. Thirty days after surgery, the rats were killed and the dura mater thickness, epidural fibrosis, and arachnoidal involvement were quantified. Results The mean dura thickness was measured at 9.28 ± 3.39 μm in the MMC group and at 8.69 ± 2.32 μm in the pimecrolimus group, compared with 14.70 ± 4.14 μm in the control group. In addition, the epidural fibrosis and arachnoidal involvement were reduced significantly in the treatment groups compared with the control group. Conclusions In this animal model, it was shown that locally applied pimecrolimus effectively reduces epidural fibrosis and dural adherence in rats that underwent lumbar laminectomy. Mitomycin C was equally effective as pimecrolimus in reducing epidural fibrosis and dural adherence in this study.

scholarly journals New Insights from Immunohistochemistry for the Characterization of Epidural Scar Tissue

2013 ◽  
Vol 5;17 (5;9) ◽  
pp. 465-474
Author(s):  
Paulo Pereira
Keyword(s):  
Lumbar Spine ◽  
Spine Surgery ◽  
Fibrous Tissue ◽  
Scar Tissue ◽  
Nerve Fibers ◽  
Lumbar Spine Surgery ◽  
Pathophysiological Mechanism ◽  
Epidural Fibrosis ◽  
Lumbar Surgery ◽  
Transmission Electron

Background: The association between epidural fibrosis and recurrent symptoms after lumbar spine surgery remains a matter of debate in scientific literature and the underlying pathophysiological mechanism has not been clearly elucidated. Objective: To investigate the presence of nerve fibers and the expression of osteopontin in epidural fibrous tissue after lumbar surgery in humans. Study Design: Laboratory study of human tissue samples. Methods: Twenty-four patients with persistent or recurrent low back and/or leg pain after lumbar spine surgery, in whom no relevant findings were present on magnetic resonance imaging (MRI) besides epidural scar tissue, were submitted to epiduroscopy. Biopsy samples of epidural scar tissue resting in the posterior epidural and periradicular space were obtained from 15 patients, using an endoscopic grasping forceps, in locations where the stimulation with the tip of a Fogarty consistently reproduced pain. Biopsy samples were processed for examination under optical and transmission electron microscopes and under a fluorescence microscope after incubation in primary antibodies against beta3- tubulin or against osteopontin. Results: Optical and transmission electron microscopy revealed a homogeneous fibrous tissue rich in collagen and lacking nerve fibers. No immunofluorescence was present in any of the samples immunoreacted against beta3-tubulin. In the samples immunoreacted against osteopontin, a punctate signal was detected around the collagen fibers. Limitations: Being a human study, there was no control group, so it is not possible to determine the contribution of osteopontin in the formation of epidural fibrosis and its relation to the patients’ symptoms. Additional animal studies are needed to investigate these issues. Conclusion: Rather than direct stimulation of nociceptors in the epidural scar tissue, other factors should relate epidural fibrosis and recurrent symptoms after lumbar spine surgery. Osteopontin seems to play a role in the formation of epidural fibrosis. Key words: Osteopontin, failed back surgery syndrome, epidural fibrosis, immunofluorescence, beta3-tubulin, epiduroscopy, nerve fibers, lumbar surgery

The prevention effect of poly (l-glutamic acid)/chitosan on spinal epidural fibrosis and peridural adhesion in the post-laminectomy rabbit model

2014 ◽  
Vol 23 (11) ◽  
pp. 2423-2431 ◽  
Author(s):  
Chunbo Li ◽  
Hong Wang ◽  
Haifei Liu ◽  
Jingbo Yin ◽  
Lei Cui ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Rabbit Model ◽  
Epidural Fibrosis ◽  
Spinal Epidural

Spinal epidural fibrosis following hemostatic agent employment

2021 ◽  
pp. 1-5
Author(s):  
Ismail Bozkurt ◽  
Atilla Kazanci ◽  
Oktay Gurcan ◽  
Ahmet G. Gurcay ◽  
Ata T. Arikok ◽  
...  
Keyword(s):  
Hemostatic Agent ◽  
Epidural Fibrosis ◽  
Spinal Epidural

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

2007 ◽  
Vol 16 (9) ◽  
pp. 1525-1530 ◽  
Author(s):  
Kartal Hakan Yildiz ◽  
Ferruh Gezen ◽  
Merih Is ◽  
Selma Cukur ◽  
Murat Dosoglu
Keyword(s):  
Cyclosporin A ◽  
Mitomycin C ◽  
Epidural Fibrosis

scholarly journals Inhibition of epidural fibrosis after microendoscopic discectomy with topical application of mitomycin C: a randomized, controlled, double-blind trial

2013 ◽  
Vol 18 (5) ◽  
pp. 421-427 ◽  
Author(s):  
Lei Liu ◽  
Tao Sui ◽  
Xin Hong ◽  
Xiaotao Wu ◽  
Xiaojian Cao
Keyword(s):  
Adverse Effects ◽  
Mitomycin C ◽  
Quantitative Evaluation ◽  
Saline Group ◽  
Physical Symptoms ◽  
Grading System ◽  
Epidural Fibrosis ◽  
Significant Difference ◽  
Microendoscopic Discectomy

Object The authors conducted a study to evaluate the effects and the safety of locally applied mitomycin C (MMC) on epidural fibrosis after microendoscopic discectomy (MED). Methods Seventy-five patients undergoing single-level unilateral MED for lumbar disc herniation were randomly assigned to receive cotton wool impregnated with either 0.5 mg/ml MMC or saline applied at the site of discectomy for 5 minutes. Outcome measures included degrees of pain severity, functional disability, physical symptoms, and quantitative evaluation of postoperative epidural fibrosis shown on follow-up lumbar contrast-enhanced MRI. Results Sixty-two patients completed the follow-up. Neither serious drug adverse effects nor clinically significant laboratory adverse effects were observed. Patients in both groups showed similar clinical recoveries postoperatively. A statistically significant difference (p < 0.05) between the 2 treatments was shown in a quantitative evaluation of postoperative MRI-documented epidural fibrosis in the MMC group and the saline group using a modified grading system. The mean cross-sectional areas of epidural fibrosis were 7.32–70.06 mm2 in the MMC group and 22.94–90.48 mm2 in the saline group. The epidural fibrosis index ranged from 0.0296 to 0.3267 in the MMC group and from 0.1191 to 0.3483 in the saline group. A significant difference was also observed using the Ross grading system to evaluate postoperative MR images. Conclusions Although no benefit was observed clinically, the authors observed a notable reduction of epidural fibrosis after MED radiologically, with 0.5 mg/ml MMC locally applied and no clinical side effects. Clinical trial registration no.: ChiCTR-TRC-10001079 (http://www.chictr.org/cn/proj/show.aspx?proj=326).

Sign in / Sign up

Export Citation Format

Share Document