Discoidin domain receptor 1 as a promising biomarker for high-grade gliomas.

Background: Two fundamental challenges in the current therapeutic approach for central nervous system tumors are the tumor heterogeneity and the absence of specific treatments and biomarkers that selectively target the tumor tissue. Therefore, we aimed to investigate the potential relationship between discoidin domain receptor 1 (DDR1) expression and the prognosis and characteristics of glioma patients. Materials and Methods: Tissue and serum samples from 34 brain tumor patients were evaluated for DDR1 messenger ribonucleic acid levels in comparison to 10 samples from the control group, and Kaplan-Meier survival analysis has performed. Results: DDR1 expression was observed in both tissue and serum samples of the patient and control groups. DDR1 expression levels in tissue and serum samples from patients were higher in comparison to the control group, although not statistically significant (P > 0.05). A significant correlation between tumor size and DDR1 serum measurements at the level of 0.370 was reported (r = 0.370; P = 0.034). The levels of DDR1 in serum showed a positive correlation with the increasing size of tumor. The results of the 5-year survival analysis depending on the DDR1 tissue levels showed a significantly higher survival rate (P = 0.041) for patients who have DDR1 tissue levels above cutoff value. Conclusions: DDR1 expression was significantly higher among brain tumor tissues and serum samples and its levels showed a positive correlation with the increased size of tumor. This study can be a starting point, since it investigated and indicated, for the first time, that DDR1 can be a novel therapeutic and prognostic target for aggressive high-grade gliomas.

The Efficiency of Simultaneous Systemic and Topical Use of Tranexamic Acid in Spinal Fusion Surgery.

BACKGROUND AND AIM: Multilevel posterior spinal fusion surgery in adults is associated with significant intra- and postoperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent for reducing blood loss and allogenic blood transfusion. The purpose of this study was to evaluate the efficiency of TXA in reducing blood loss and improving hematologic parameters in adult patients undergoing posterior thoracic/lumbar instrumented spinal fusion surgery. PATIENTS AND METHODS: This is a retrospective observational study comparing the intra- and postoperative hemodynamic findings of two groups treated with and without TXA. The study included 112 adult patients receiving elective posterior thoracic/lumbar instrumented spinal fusion surgery. The patients were evaluated in terms of age, gender, type of surgery, intraoperative blood loss, pre- and postoperative hemoglobin (Hb) and hematocrit values, postoperative systemic anticoagulant use, intra- and postoperative use of blood products, and the volume of the drainage fluid as an indicator of postoperative blood loss. The TXA group received preoperative 10 mg/kg intravenous TXA, another dose of 10 mg/kg/h in isotonic solution during the operation, and local administration of TXA before the closure of the surgical site (1g in patients undergoing surgery in ≤3 segments, and 2g in patients undergoing surgery in ≥4 segment group). RESULTS: Intra- and postoperative blood loss and need for transfusion were significantly lower in the TXA group. Fifty-three of 112 patients required intra- and postoperative transfusion, and postoperative anticoagulants were given to 25/112 patients. The postoperative Hb level was lower, and the difference of pre- and postoperative Hb values was higher in the non-TXA group (not significant). CONCLUSION: Simultaneous systemic and topical application of TXA is a safe and efficient blood conservation strategy for adult patients undergoing major multilevel spinal surgery.

The Results of Using a Transforaminal Lumbar Interbody Fusion Cage at the Upper Lumbar Level.

Aim The aim of this study is to apply surgical treatments to upper lumbar disc hernias in order to provide lumbar stability and lumbar lordosis using a transforaminal lumbar interbody fusion (TLIF) cage and to preserve the success rate of surgical results by protecting neural structures without excessive subject tension. Material and methods Between 2012 and 2017, 32 patients who had undergone an operation for upper lumbar disc herniation and who had received a transforaminal lumbar interbody fusion cage using a posterior technique were evaluated retrospectively. Results The radiological and clinical findings, surgical methods, and results of the patients were evaluated. In our study, 25 (78.1%) of the patients with upper lumbar disc hernias who were evaluated retrospectively were female and seven (21.9%) were male. Their average age was 55.43 years. The average follow-up was 21.75 months. The most common complaints were lower back pain, leg pain, and claudication. In the findings from neurological examinations, a positive result on the femoral stretching test occurred in 30 (93.7%) patients. In the degenerative spinal structure of patients at the L1-2 and L2-3 levels, a transforaminal lumbar interbody fusion was performed via a wide laminectomy with posterior stabilization due to a wide-bottomed disc hernia and stenosis. Only one of the patients with a neurological deficit still had a motor deficit after surgery. Conclusion While planning a surgery for upper lumbar disc hernias, the anatomical features of this region and the patients' radiological and neurological findings should be carefully evaluated. If TLIF is performed during upper lumbar region surgery, it may be preferable to perform it using a posterior technique.

Clinical Outcomes of Incidental Dural Tears During Lumbar Microdiscectomy.

BACKGROUND: A dural tear (DT) is the most commonly encountered complication during lumbar spine surgery. The incidence of DT increases depending on the complexity of the surgical procedure and the presence of a DT is related to a poor outcome and patient satisfaction. OBJECTIVES: This study aimed to determine the incidence and clinical outcomes of DTs in those patients who undergo lumbar disc surgery. METHODS: We retrospectively reviewed consecutive patients who underwent surgery for the management of a primary single-level lumbar disc herniation at a single institution between 2004 and 2014. Among the studied population, those with DTs were included in the study group. An age- and sex-matched group of randomly selected patients who underwent the same level and type of lumbar spine surgery, but did not develop DTs, were assigned as the control group. The outcomes were compared at 12 months postoperatively between the groups. RESULTS: A total of 5,476 consecutive patients (2,608 female, 2,868 male; mean age, 54 ± 11.45 [range, 21-86] years) underwent surgery for primary single-level lumbar disc herniation. DT was noted in 192 (2.85%) cases. Of these, 102 patients with complete data were included in the DT group. The DT group had a significantly increased length of hospital stay (p = 0.001). Also, the duration of bed rest in the hospital was significantly higher in patients wherein DT was repaired using hemostatic material and fibrin glue, compared to the patients with primary closure with suturing of the tear. CONCLUSION: Incidental DTs, if recognized and treated appropriately, will not lead to poor clinical results and do not adversely impact postoperative outcomes.

Immunohistochemical Grading of Epidural Fibrosis with CD105 Antibody.

OBJECTIVE: Grading of epidural fibrosis (EF) is usually performed by histopathologic staining in experimental studies. Immunohistochemical methods for grading are not available in routine practice yet. In our study, the effect of tranexamic acid (TXA), a commonly used hemostatic agent in surgical interventions, was evaluated for use against the development of EF with classical histopathologic methods and immunohistochemistry using the CD105 antibody, a marker of angiogenesis. METHODS: Sixteen rats were used. The rats were assigned to 2 groups, control and TXA. Laminectomy was performed on the control group. In the treatment group, laminectomy + topical TXA was applied. After sacrificing the rats in the sixth week, histopathologic and immunohistochemical examinations and grading of the EF tissue were performed. RESULTS: Conventional histopathologic parameters of fibroblast count, intensity of fibrosis density, and inflammatory cell density, as well as immunohistochemical evaluation with CD105, showed that the grading of EF was comparable between groups I and II (P < 0.001). DISCUSSION: The results of our study have demonstrated that CD105 is compatible with the conventional histopathologic grading methods and can be used as a marker to determine the grades of angiogenesis and fibrosis in experimental studies. The results of our study have also shown that TXA, administered locally for hemostasis, reduces the grade of EF in rats following laminectomy. TXA has been observed to cause no toxic effects on neural tissue as it is already commonly used in clinical practice.

Effect of Cetuximab on the Development of Epidural Fibrosis Based on CD105 and Osteopontin Immunohistochemical Staining.

STUDY DESIGN: The effect of cetuximab on the development of epidural fibrosis (EF) was assessed using immunohistochemical methods as well as antibodies for CD105 and osteopontin (OPN). OBJECTIVE: The goal of this study was to assess of EGFR inhibition for the postoperative treatment of fibrosis. SUMMARY OF BACKGROUND DATA: 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. Many agents have been tested to prevent the development of EF. EGFR, a multi-functional transmembrane glycoprotein, causes cell growth, proliferation, and EF by interacting with epidermal growth factor and TGF-ß1. The inhibition of postoperative fibrosis using cetuximab, an epidermal growth factor receptor blocker, is theoretically possible. However, this has not been tested to date. METHODS: Sixteen Wistar-Albino rats were divided into two groups, namely, control and cetuximab groups. L1-2 laminectomy alone was performed in both groups, and topical cetuximab was applied to the treatment group. After 6 weeks, rats were sacrificed and examined histopathologically and immunohistochemically; EF tissue was also graded. Statistical significance was accepted at P < 0.05. RESULTS: Fibroblast counts and fibrosis density, determined by histopathologic examination, and EF, according to immunohistochemical assessment based on CD105, were found to be higher in the treatment group than in the control group, and this was statistically significant (P < 0.001). Based on OPN staining, the results were consistent with classical methods, and no significant difference was detected among the groups (P = 0.358). CONCLUSION: Our study revealed that cetuximab inhibits the development of EF and that CD105, and not OPN, is a reliable marker for grading EF. In addition, cetuximab did not result in toxic, systemic side effects in surrounding tissues. LEVEL OF EVIDENCE: N/A.

Impact of sorafenib on epidural fibrosis: An immunohistochemical study.

AIM: To determine if sorafenib, an antineoplastic agent, could prevent the development of spinal epidural fibrosis (EF). METHODS: The study used CD105 and osteopontin antibodies in an immunohistochemical approach to quantify EF that occurred as a consequence of laminectomy in rats. Wistar albino rats (n = 16) were divided into two groups: control (L1-2 level laminectomy only) and sorafenib treatment (L1-2 level laminectomy + topical sorafenib). The animals were euthanatized after 6 wk, and the EF tissues were examined for histopathological changes after immunohistochemical staining. The EF grades were assigned to the tissues, and the treatment and control groups were compared. RESULTS: The EF thickness, inflammatory cell density, and arachnoid adherences determined by light microscopy were significantly higher in the control group compared to the sorafenib-treated group. Based on fibrosis scores, the extent of EF in the treatment group was significantly lower than in the controls. Immunohistochemical staining for CD105 to identify microvessels revealed that the EF grades based on vessel count were significantly lower in the treatment group. Staining for osteopontin did not show any significant differences between the groups in terms of the extent of EF. The staging of EF based on vascular counts observed after immunohistochemical staining for CD105, but not for osteopontin, was compatible with conventional staging methods. Neither toxic effects on tissues nor systemic side effects were observed with the use of sorafenib. CONCLUSION: Local administration of sorafenib significantly reduced post-laminectomy EF. Decreased neovascularization in spinal tissue may be due to the sorafenib-induced inhibition of vascular endothelial growth factor.

Evaluation of Bevacizumab for the Treatment of Epidural Fibrosis by Immunohistochemical Staining for CD105 and Osteopontin.

AIM: To evaluate bevacizumab for epidural fibrosis (EF) treatment in an experimental rat model using histopathology as well as immunohistochemical staining for CD105 and osteopontin (OPN). MATERIAL AND METHODS: Sixteen Wistar Albino rats underwent either laminectomy alone to induce EF (group I, control) or laminectomy plus local bevacizumab treatment (group II). The degree of EF was compared between groups using the current histopathological grading method as well as immunohistochemistry for CD105 and OPN. In addition, the consistency of EF staging using CD105 and OPN expression was compared to that using histopathology. RESULTS: The grade of EF was significantly lower in group II than in group I based on the fibroblast count and fibrosis density determined using histopathology, as well as by CD105 expression determined using immunohistochemistry. In contrast, OPN expression was not a reliable marker for EF evaluation because it did not show a significant difference between the two groups. CONCLUSION: Bevacizumab prevents EF development as assessed using both histopathology and CD105 expression. CD105 is a potentially reliable marker for the immunohistochemical grading of EF, in contrast to OPN.

Morphometric Analysis of the Effects of Manuka Honey on Vasospastic Femoral Arteries in Rats: An Experimental Study.

OBJECTIVES: The aim of this study was to determine if Manuka honey, a potent anti-inflammatory and antioxidant agent, had any effect on the development of vasospasm in an experimental subarachnoidal hemorrhage model constructed in rat femoral arteries. METHODS: Twenty-four Wistar Albino strain rats were divided into 3 groups: Group 1 was the control group (n=8), Group 2 was the vasospasm group (n=8), and group 3 was the treatment group (n=8). The wall thickness (W) of the femoral arteries and the luminal diameter (L) were measured using morphometric methods. The data were analyzed with statistical software. The Mann-Whitney U-test was used to compare independent groups and Bonferroni post hoc analysis was used for multiple comparison tests. Significance for all of the results was established at p<0.05. RESULTS: A statistically significant intergroup difference was detected in the mean L and W (p<0.001, p=0.001, respectively). The mean L value in Group 2 was statistically significantly less than that of Groups 1 and 3, while the mean W value was significantly greater (p<0.001 for all). However, no statistically significant difference was detected between Groups 1 and 3 with respect to the mean L and W values (p=0.064, p=0.954, respectively). CONCLUSION: Manuka honey exerts an antioxidant and anti-inflammatory effect via inhibition of inflammatory cytokines, including plasma tumor necrosis factor alpha, interleukin (IL)-1 beta, IL-6, and the lipid peroxidation level. This study statistically demonstrated that the anti-inflammatory and antioxidant properties of Manuka honey successfully inhibited the development of vasospasm in an experimentally induced vasospasm model in the femoral arteries of rats.

Endoscopic Endonasal Transclival Resection of the Upper Clival Meningioma.

In recent years, endoscope use for the excision of brain stem lesions or those localized to the anterior part of the brain stem has started. In this paper, a case of upper clival meningioma resected through the endoscopic endonasal transclival route has been presented with illustrations, and live surgery videos demonstrating the surgery step-by-step. A 35-year-old male patient presented with dysphagia and impaired consciousness. Magnetic resonance imaging (MRI) showed a mass lesion with a wide base located at the clivus and anterior part of brain stem. Following surgical preparations, the mass was resected through the endoscopic endonasal transclival route. Presigmoid and lateral suboccipital approaches are the most popular methods for petroclival tumors. However, the disadvantages are restricted surgical corridor to reach the anterior lesions of the brain stem, and surgical manipulations that should be performed between the cranial nerves to gain access into the pathological structures. The alternative endoscopic endonasal transclival method, which is preferred to reach these lesions anteriorly, does not have these disadvantages. The endoscopic endonasal transclival route is suitable for meningiomas located in the retroclival area. With advances in endoscopic technology and surgical experience, full endoscopic endonasal transclival approach will be an alternative for the treatment of posterior circulation aneurysms, most of the extradural and intradural lesions of the ventral aspect of brain stem, and neuralgia secondary to vascular compression.

Epithelioid hemangioendothelioma of the craniocervical junction; case report and review.

Epithelioid hemangioendotheliomas are uncommon vascular neoplasms and their spinal location is even rarer. We report clinical course of a 31-year-old man with an epithelioid hemangioendothelioma at the cranio-cervical junction. A cervical magnetic resonance imaging revealed tumor that caused posterior cervical cord compression. C1,2,3 total laminectomy and surgical excision of the tumor was performed. Postoperative external beam radiation was performed on the surgical field especially around the right vertebral artery. At 2-year follow-up there was no neurological deficit and no tumor recurrence.

Anterior cervical fusion with interbody cage containing beta-tricalcium phosphate: Clinical and radiological results.

AIM: Beta tricalcium phosphate (beta-TCP) is an osteoconductive, resorbable material. Its clinical effectiveness has been proved in many indications. This study was clinical and radiographic study report obtained in patients undergoing anterior cervical discectomy and fusion ACDF in which PEEK cages were filled beta-TCP in an injectable form. MATERIAL AND METHODS: Between January 2010 and June 2011, 16 consecutive patients underwent ACDF using PEEK cages with beta-TCP. The cohort compromised 10 men and 6 women with a mean age of 45.2 years. The surgery was performed when the patient had myelopathy or radiculopathy with progressive neurological deficit, or failure of conservative treatment (a minimum of 3 months). The patients were evaluated by Odom criteria preoperatively and postoperative 3rd, 6th, 12th and 24th months. Preop and postop pain was evaluated with visual analogue scala (VAS). Disc height and fusion success rates were evaluated. RESULTS: Preoperative average VAS score was 7.9 (7-10) for neck pain and 8 (7-10) for arm pain. At the final follow-up, these scores became 1.5 and 1.4 for neck and arm pain, respectively. The average improvement rate was 81% for neck pain and 82.5% for arm pain. Postop ODOM's criteria main rate was 3.4. Bone fusion was achieved in 14 segments (70%) at 3rd month, 19 segments (95%) at 12th month follow-up assessment. CONCLUSION: Clinical and radiological results revealed that B-TCP is a good alternative synthetic fusion material for cervical interbody fusion. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Late Postoperative Rhinological Complications After Microscopic Transnasal Hypophysectomy.

AIM: Major complications of microscopic transnasal hypophyseal surgery (MTHS), such as cerebrospinal fluid rhinorrhea, carotid injury, and optic nerve injury, are very rare. However, late rhinological complications can be ignored because they are a minor cause of morbidity compared with major complications. In this study, we extensively examined postoperative rhinological complications in patients who underwent MTHS for pituitary adenoma. MATERIAL AND METHODS: Thirty-one patients diagnosed with pituitary adenoma, who underwent MTHS and whose preoperative nasal examinations were recorded between January 2007 and January 2014, were included in the study. A detailed rhinological examination of the patients was performed. RESULTS: A total of 12 of 31 patients (38.7%) had a perforated nasal septum, and synechiae were detected in the nasal cavities of 13 patients (42%). Anosmia occurred in three patients, hyposmia in two, and a nasal tip deflection and saddle nose deformity were detected in one patient with a perforated nasal septum. No perinasal loss of sense, oronasal fistula, or purulent secretion in the nasal cavity was found in any patient. CONCLUSION: The nasal structures, particularly the nasal septum mucosa, should be treated gently during MTHS. The nasal stages of the operation should be performed with the help of an otolaryngologist until adequate experience is gained.

Measuring serum matrix metalloproteinase-9 levels in peripheral blood after subarachnoid hemorrhage to predict cerebral vasospasm.

PURPOSE: We aimed to investigate serum levels of matrix metalloproteinase-9 in both subarachnoid hemorrhage and control groups for prediction of cerebral vasospasm in this study. METHODS: Venous serum matrix metalloproteinase-9 levels were prospectively measured four times (days 1, 3, 7, and 14) for 34 consecutive patients with subarachnoidal hemorrhage (n = 27) and for elective aneurysm clipping (control, n = 7). RESULTS: Vasospasm developed in 11/34 (32.4 %) patients between 3 and 10 days after subarachnoid hemorrhage (median 5.58 days), mean peak serum matrix metalloproteinase-9 compared with the non-vasospasm cohort. Matrix metalloproteinase-9 levels were higher in subarachnoid hemorrhage patients than in the controls. CONCLUSION: Increased serum matrix metalloproteinase-9 could be an accurate biomarker to predict the onset of cerebral vasospasm after subarachnoid hemorrhage.

Cement leakage and complication of liposarcoma spinal metastasis during vertebral augmentation procedure: a case report.

BACKGROUND: Liposarcoma is a malignant tumor of soft tissue. Myxoid/round cell liposarcoma has a tendency to spread to extrapulmonary sites but the spine is an unusual location even for metastasis. Metastatic bone tumors in the spine are painful. The vertebral body augmentation procedures for treating painful metastatic spinal lesions are minimally invasive and are good alternatives to open surgery. CASE PRESENTATION: A 41-year-old Turkish man was treated with radiofrequency tumor ablation and percutaneous vertebral augmentation for spinal metastasis. Asymptomatic perivertebral and segmental veins' cement leakage was detected on perioperative X-ray radiograms; at the follow-up computed tomography scan, no further migration of any cement material was seen, and his postoperative course was uneventful. CONCLUSIONS: The risk of cement leakage and embolism is increased with the treatment of some malignant lesions. The frequency of local leakage of bone cement is relatively high. Patients undergoing percutaneous vertebral augmentation of malignant spinal metastases need close monitoring. There is no agreement on the treatment strategy.

Epidural Hematoma Complication after Rapid Chronic Subdural Hematoma Evacuation: A Case Report.

BACKGROUND: Chronic subdural hematoma generally occurs in the elderly. After chronic subdural hematoma evacuation surgery, the development of epidural hematoma is a very rare entity. CASE REPORT: We report the case of a 41-year-old man with an epidural hematoma complication after chronic subdural hematoma evacuation. Under general anesthesia, the patient underwent a large craniotomy with closed system drainage performed to treat the chronic subdural hematoma. After chronic subdural hematoma evacuation, there was epidural leakage on the following day. CONCLUSIONS: Although trauma is the most common risk factor in young CSDH patients, some other predisposing factors may exist. Intracranial hypotension can cause EDH. Craniotomy and drainage surgery can usually resolve the problem. Because of rapid dynamic intracranial changes, epidural leakages can occur. A large craniotomy flap and silicone drainage in the operation area are key safety points for neurosurgeons and hydration is essential.

Two cases of arachnoid cyst complicated by spontaneous intracystic hemorrhage.

Arachnoid cysts are developmental anomalies which are usually asymptomatic. Intracystic hemorrhage after trauma is a well known complication; however, spontaneous intracystic hemorrhage is rare. This report presents two rare cases of arachnoid cyst complicated by spontaneous intracystic hemorrhage. The first patient was admitted following transient loss of consciousness and speech disturbance, and a subacute subdural hematoma at the left temporal region was diagnosed. The second patient presented with severe headache of four days duration and a subdural hematoma at the left temporoparietal region was diagnosed. In both the patients, both on radiological examination and during surgical intervention, hematomas were found to be intracystic.