Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 6, 2018; 6(9): 249-258
Published online Sep 6, 2018. doi: 10.12998/wjcc.v6.i9.249
Impact of sorafenib on epidural fibrosis: An immunohistochemical study
Osman Tanriverdi, Uzay Erdogan, Canan Tanik, Ilhan Yilmaz, Omur Gunaldi, Huseyin Utku Adilay, Ayca Arslanhan, Metehan Eseoglu
Osman Tanriverdi, Uzay Erdogan, Omur Gunaldi, Department of Neurosurgery and Psychiatry, University of Health Sciences, Bakırky Prof. Dr. Mazhar Osman Training and Research Hospital for Neurology, İstanbul 34303, Turkey
Canan Tanik, Department of Pathology, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34303, Turkey
Ilhan Yilmaz, Department of Neurosurgery, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34303, Turkey
Huseyin Utku Adilay, Department of Neurosurgery, Medical Faculty, Balıkesir University, Balıkesir 31300, Turkey
Ayca Arslanhan, Institute of Neurological Science, Marmara University, İstanbul 34303, Turkey
Metehan Eseoglu, Department of Neurosurgery, Medical Faculty, Medipol University, İstanbul 34303, Turkey
Author contributions: Tanriverdi O contributed to the conception, design, supervision and writing; Erdogan U contributed to the literature review and data collection; Tanik C contributed to the design, data collection, analysis and processing; Yilmaz I contributed to the writing and literature review; Gunaldi O contributed to the critical review and supervision; Adilay HU contributed to the data collection and materials; Arslanhan A contributed to the materials and data collection; Eseoglu M contributed to the literature review, materials and data collection.
Institutional animal care and use committee statement: Marmara University Local Ethics Committee for Animal Studies.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Osman Tanriverdi, MD, Doctor, Department of Neurosurgery and Psychiatry, University of Health Sciences, Bakırköy Prof. Dr. Mazhar Osman Training and Research Hospital for Neurology, Tevfik sağlam cad, No. 1, İstanbul 34303, Turkey. osmantanriverdi74@gmail.com
Telephone: +90-505-2964052
Received: April 27, 2018
Peer-review started: April 27, 2018
First decision: June 15, 2018
Revised: June 23, 2018
Accepted: July 31, 2018
Article in press: August 1, 2018
Published online: September 6, 2018
Processing time: 132 Days and 19.1 Hours
ARTICLE HIGHLIGHTS
Research background

Spinal epidural fibrosis (EF) is a natural consequence of surgical trauma arising after laminectomy. In this study, we asked whether sorafenib can prevent the development of EF post-laminectomy using an immunohistochemical approach to quantify EF with CD105 and osteopontin antibodies.

Research motivation

EF is one of most common causes of failed back surgery syndrome, which occurs after laminectomy. Numerous causes and mechanisms have been proposed to explain its development after laminectomy. As treatment approaches for EF are associated with high rates of complications and failed surgery, the main goal is the prevention of EF. Many methods and medicines have been tried in order to prevent the development of EF. Sorafenib is an antineoplastic medicine that has demonstrated preventive effects against fibrosis due to an antiangiogenic mechanism involving inhibition of vascular endothelial growth factor (VEGF).

Research objectives

The goal of this study was to assess VEGF inhibition for the postoperative treatment of fibrosis.

Research methods

Wistar albino rats (n = 16) were divided into two groups: control (laminectomy only) and sorafenib treatment (laminectomy + topical sorafenib). The animals were euthanatized after six weeks, and EF tissue was examined for histopathological changes after immunohistochemical staining and an EF grade was assigned. SPSS 15.0 for Windows (IBM, Armonk, NY, United States) was used for statistical analysis. Statistical significance was accepted as P < 0.05.

Research results

By light microscopy, EF thickness, inflammatory cell density and arachnoid adherences were higher in the control group compared to sorafenib-treated animals. Immunohistochemical staining for CD105 to identify microvessels revealed that EF grade was lower in the treatment group based on vessel count. Staining for osteopontin did not show any statistically significant differences in the extent of EF between groups. Significant differences in fibrosis score, fibroblast density, inflammatory cell density and CD105 immunostaining were observed between the sorafenib and control groups (P < 0.001). All control animals (Group I) received fibrosis scores of grade 3, while scores for sorafenib-treated animals (Group II) did not exceed grade 1 (P < 0.001). Fibroblast density was graded the highest in 100% of Group 1 animals but remained at grade 1 in Group II. Scores for inflammatory cell density were lowest in Group II but highest in Group I, as were scores for microvessel density assessed by CD105 immunostaining (P < 0.001). There was no significant difference in microvessel density scores between groups after osteopontin staining (P = 0.355). By light microscope, it could be seen that EF thickness, inflammatory cell density and arachnoidal adhesions were greater in control animals compared to Group II.

Research conclusions

In this study, we examined the efficacy of topical treatment with sorafenib for the prevention of EF in an animal laminectomy model and analyzed immunohistochemical methods for the assessment of microvessel density in fibrotic lesions compared to conventional measures of fibrosis staging. Our results demonstrated that topical sorafenib was effective in reducing EF after laminectomy, likely due to decreased neovascularization resulting from the antiangiogenic effect of sorafenib on VEGF activity. We further show that immunohistochemical assessment of microvessel density using anti-CD105 antibodies provided a new measure of fibrotic development that was compatible with conventional methods of fibrosis staging.

Research perspectives

In our study, the local application of sorafenib after laminectomy prevents EF. CD105 is a suitable marker for fibrosis, whereas osteopontin was not found to be reliable. Sorafenib was not observed to have any toxic effects or systemic side effects on normal tissues. Therefore, this application could be tested in clinical trials.