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.

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.

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 Reduction of epidural fibrosis after laminectomy in rabbits by omental free graft

2013 ◽  
Vol 58 (No. 1) ◽  
pp. 25-31 ◽  
Author(s):  
N. Brkljaca Bottegaro ◽  
J. Kos ◽  
B. Pirkic ◽  
O. Smolec ◽  
Z. Grabarevic ◽  
...  
Keyword(s):  
Foreign Body ◽  
Dura Mater ◽  
Foreign Body Reaction ◽  
Fibrous Tissue ◽  
Scar Tissue ◽  
Control Group ◽  
Epidural Fibrosis ◽  
Free Graft ◽  
Increased Risk ◽  
Experimental Group

Epidural fibrosis is an extradural scar tissue formed after a laminectomy procedure. It is associated with persistent pain after spinal surgery and an increased risk of complications during revision surgery. The aim of this study was to determine the preventive effects of local application of an omental free graft in minimising spinal epidural fibrosis in a rabbit laminectomy model. Twenty two rabbits were randomly divided in two groups, a control group of seven and an experimental group of 15 animals. A dorsal laminectomy at levels L<sub>1</sub> to L<sub>3 </sub>was performed on each rabbit of both groups. Prior to the laminectomy procedure, the animals from the experimental group were submitted to a laparotomy in order to obtain the free omental graft. The graft was then applied to the same animal at the dural deffect. All rabbits were euthanised six weeks after surgery and spine segments L<sub>1</sub> to L<sub>3</sub> were removed. Histological sections were evaluated for fibrosis intensity at the laminectomy level, the adhesion degree between dura mater and fibrous tissue and the presence of the foreign body reaction. A statistically significant correlation was established for the foreign body reaction presence and belonging to the group, which can be explained by the omental effects on inflammation reduction and healing promotion. The degree of adhesion between the dura mater and fibrous tissue and the intensity of the fibrous tissue at the laminectomy level were lower in the experimental group although the differences were not statistically significant. The use of free omental grafts is thus a promising technique in epidural fibrosis prevention.

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

scholarly journals Mast cells in the pathophysiology of Duchenne muscular dystrophy in Golden Retriever dogs

2020 ◽  
Vol 40 (10) ◽  
pp. 791-797
Author(s):  
Isabela M. Martins ◽  
Lygia M.M. Malvestio ◽  
Jair R. Engracia-Filho ◽  
Gustavo S. Claudiano ◽  
Flávio R. Moraes ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Mast Cells ◽  
Muscular Dystrophy ◽  
Fibrous Tissue ◽  
Control Group ◽  
Golden Retriever ◽  
Collagenous Tissue ◽  
Muscle Types ◽  
Muscle Groups

ABSTRACT: The Golden Retriever muscular dystrophy (GRMD) is one of the best models of Duchenne muscular dystrophy (DMD), with similar genotypic and phenotypic manifestations. Progressive proliferation of connective tissue in the endomysium of the muscle fibers occurs in parallel with the clinical course of the disease in GRMD animals. Previous studies suggest a relationship between mast cells and the deposition of fibrous tissue due to the release of mediators that recruit fibroblasts. The aim of this study was to evaluate the presence of mast cells and their relationship with muscle injury and fibrosis in GRMD dogs of different ages. Samples of muscle groups from six GRMD and four control dogs, aged 2 to 8 months, were collected and analyzed. The samples were processed and stained with HE, toluidine blue, and Azan trichrome. Our results showed that there was a significant increase in infiltration of mast cells in all muscle groups of GRMD dogs compared to the control group. The average number of mast cells, as well as the deposition of fibrous tissue, decreased with age in GRMD dogs. In the control group, all muscle types showed a significant increase in the amount of collagenous tissue. This suggests increased mast cell degranulation occurred in younger GRMD dogs, resulting in increased interstitial space and fibrous tissue in muscle, which then gradually decreased over time as the dogs aged. However, further studies are needed to clarify the role of mast cells in the pathogenesis of fibrosis.

scholarly journals Intraoperative topical administration of mitomycin C, in different concentrations, on the cicatrization of mioplasties of the dorsal rectus of rabbits

2008 ◽  
Vol 38 (1) ◽  
pp. 129-135
Author(s):  
Fabrício Villela Mamede ◽  
Bianca da Costa Martins ◽  
Ana Letícia Groszewicz Souza ◽  
Adriana Torrecilhas Jorge Brunelli ◽  
Karina Pontin ◽  
...  
Keyword(s):  
Side Effects ◽  
Mitomycin C ◽  
Immunohistochemical Study ◽  
Rectus Muscle ◽  
Topical Administration ◽  
Physiological Solution ◽  
Histological Evaluation ◽  
Control Group ◽  
Fibroblast Growth ◽  
Superior Rectus Muscle

Myoplasties of the extraocular muscle may cause adhesions between the operated muscle and the adjacent tissues, commonly generating cicatricial strabismus. With the purpose of reducing to a minimum the occurrence of adhesion, the effects of mitomycin C, an antifibrotic agent, were studied in concentrations of 0.008%, 0.02%, and 0.04% applied during intraoperative of myoplasties of the superior rectus muscle of rabbits. Fifty six animals were divided in five groups. During the postoperative, the operated areas were washed with physiological solution. Eye drop instillation to prevent inflammation and bacterial infection were used. The method to analyze the results consisted of clinical and histological evaluation and statistical analyzes. We also evaluated at the same time the amount of basic fibroblast growth factor (FGF-2) by immunohistochemical study. Clinically, more adhesions were found in the eyes of the control group than in the groups of treated eyes. However there was no significant statistics difference between the two groups (P>0.05). Histologically, mitomycin C caused a delayed cicatrization in the mioplastic areas, specially in the group who received the 0.02% concentration. The immunohistochemical showed FGF-2 marking in fibroblasts and macrophages, but between the groups there wasn't no difference. Based on those results, mitomycin C in the utilized concentrations was capable of delaying the cicatrization and consequently avoid the secondary strabismus without undesirable side effects.

Intraoperative Application of Mitomycin C in the Surgical Treatment of Pterygium

1998 ◽  
Vol 8 (3) ◽  
pp. 153-156 ◽  
Author(s):  
A. Demirok ◽  
S. Simsek ◽  
A. Çinal ◽  
T. Yasar
Keyword(s):  
Statistical Analysis ◽  
Surgical Treatment ◽  
Side Effects ◽  
Mitomycin C ◽  
Surgical Excision ◽  
Control Group ◽  
Exact Test ◽  
Pterygium Surgery ◽  
Group 1

Purpose To investigate the effectiveness of intraoperative mitomycin C in pterygium surgery. Methods The effectiveness of intraoperatively administered mitomycin C and the occurrence of postoperative complications were evaluated in 17 patients with two recurrences of pterygium. The authors employed the “bare-sclera technique” and placed a sterile sponge soaked in a 0.02% mitomycin C solution intraoperatively in the episcleral space for 3 minutes. The control group (15 patients) underwent only surgical excision. Patients were followed for 21 to 30 months. Results The pterygium recurred in one (5.9%) of the 17 patients in group 1 and in six (40%) of the 15 controls. Statistical analysis using Fisher's exact test showed a significant (p=0.027) reduction of recurrences of pterygium in the group treated intraoperatively with mitomycin C. No serious complications or side effects arose during the follow-up period. Conclusions Mitomycin C administered intraoperatively can be considered an effective treatment to improve the success rate after surgical excision.

scholarly journals Evaluation of salivary flow in patients during head and neck radiotherapy

2003 ◽  
Vol 17 (2) ◽  
pp. 156-160 ◽  
Author(s):  
Paulo Rogério Ferreti Bonan ◽  
Fábio Ramoa Pires ◽  
Márcio Ajudarte Lopes ◽  
Osvaldo Di Hipólito Jr
Keyword(s):  
Squamous Cell Carcinoma ◽  
Side Effects ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Salivary Flow ◽  
Neck Squamous Cell Carcinoma ◽  
Control Group ◽  
Head And Neck Radiotherapy

Radiotherapy is frequently employed for the treatment of head and neck squamous cell carcinoma. Among the side effects, xerostomia is one of the most important. With the objective of evaluating the role of radiotherapy in salivary flow, we performed three salivary sample collections: at the beginning of, during, and immediately after radiotherapy. The results showed that the salivary flow values of the first collection were very similar to those of the control group. However, during treatment, there was a significant decrease of the salivary flow (p = 0.0008), which continued low immediately after radiotherapy (p = 0.0009). Our study showed that radiotherapy leads to an important reduction of salivary flow during and after radiotherapy.

Prophylaxis of the laminectomy membrane

1978 ◽  
Vol 49 (3) ◽  
pp. 419-424 ◽  
Author(s):  
José Barberá ◽  
José Gonzalez ◽  
José Esquerdo ◽  
Jaime Broseta ◽  
Juan Luis Barcia-Salorio
Keyword(s):  
Side Effects ◽  
Bone Graft ◽  
Periodic Acid ◽  
Scar Tissue ◽  
Control Group ◽  
Periodic Acid Schiff ◽  
Content Type ◽  
Laminectomy Membrane ◽  
Hematoxylin And Eosin ◽  
Fine Print

✓ Sixty laminectomies were performed in dogs to investigate the prevention of the laminectomy membrane and its side effects. These operations were distributed in six groups of 10, one was a control group, and in the others the bone defect was protected with different materials (Oxicel, Silastic, Dacron, methyl methacrylate, and Kiel bone graft). After a survival of 2 months, suboccipital myelography was performed, immediately after which the animals were sacrificed and the operated spinal slice obtained. The different radiographic densities of the tissues of each slice were calculated and the diverse histological nature identified by hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, and Gomori's reticulin stains. Only the acrylic plastic and the Kiel bone graft prevented expansion of the scar tissue inside the spinal canal and adhesions between the dura and the cicatricial overlying muscles. Therefore, the authors suggest that a solid barrier is necessary to effectively prevent the so-called “laminectomy membrane.”

scholarly journals Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study

2015 ◽  
Vol 22 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Semra Isık ◽  
M. Özgür Taşkapılıoğlu ◽  
Fatma Oz Atalay ◽  
Seref Dogan
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Sham Group ◽  
Fibrous Tissue ◽  
Fibroblast Cell ◽  
Control Group ◽  
Epidural Fibrosis ◽  
Sprague Dawley ◽  
Positive Effects

OBJECT Epidural fibrosis is nonphysiological scar formation, usually at the site of neurosurgical access into the spinal canal, in the intimate vicinity of and around the origin of the radicular sheath. The formation of dense fibrous tissue causes lumbar and radicular pain. In addition to radicular symptoms, the formation of scar tissue may cause problems during reoperation. The authors aimed to investigate the effects of cross-linked high-molecular-weight hyaluronic acid (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by using histopathological and biochemical parameters. METHODS Fifty-six adult female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups. Rats in the sham group (n = 14) underwent laminectomy and discectomy and received no treatment; rats in the control group (n = 14) underwent laminectomy and discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA group (n = 14) received HA treatment at the surgical area after laminectomy and discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and discectomy in addition to receiving treatment with cross-linked high-molecular-weight HA in the surgical area. All rats were decapitated after 4 weeks, and the specimens were evaluated histopathologically and biochemically. The results were statistically compared using the Mann-Whitney U-test. RESULTS Compared with the sham and control groups, the HA and HA gel groups showed significantly lower fibroblast cell density and tissue hydroxyproline concentrations (p < 0.05). There was statistically significant lower dural adhesion and foreign-body reaction between the control and HA gel groups (p < 0.05). Granulation tissue and epidural fibrosis were significantly lower in the HA and HA gel groups compared with the sham group (p < 0.05). There were no significant differences in any histopathological parameters or biochemical values between Groups 3 and 4 (p > 0.05). CONCLUSIONS Cross-linked high-molecular-weight HA had positive effects on the prevention of epidural fibrosis and the reduction of fibrotic tissue density. The efficacy of this agent should also be verified in further experimental and clinical studies.

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