Turker Kilic

Tumor Necrosis Factor α is a Key Modulator of Inflammation in Cerebral Aneurysms

OBJECTIVE: Although intracranial aneurysms (IAs) are a major public health problem in the United States, few etiological factors are known. Most aneurysms remain asymptomatic until they rupture, producing subarachnoid hemorrhage, one of the most severe forms of stroke. Despite the technical advances in endovascular and microsurgical treatment, these patients still have high mortality and morbidity rates. Hence, the biology of aneurysm formation and growth is of intense interest. The presence of T and B lymphocytes, as well as macrophages, in human IA tissues suggests a role for inflammation in IA pathogenesis. However, the types of cytokines that are involved and regulated during cerebral aneurysm formation and growth are not known. To study the underlying pathogenesis of IA, we analyzed the expression of cytokines that participate in proinflammatory and anti-inflammatory responses. METHODS: Polymerase chain reaction was used to assess relative messenger ribonucleic acid expression levels of cytokines and an apoptotic modulator, Fas-associated death domain protein. Western blot analysis was used to determine protein expression from these genes. RESULTS: We show that the proinflammatory cytokine, tumor necrosis factor α and its proapoptotic downstream target, Fas-associated death domain protein, are increased in human aneurysms. In contrast, interleukin 10, which is secreted predominantly by T helper 2 cells, was absent in aneurysms. Polymerase chain reaction-derived gene expression data were confirmed by Western blotting using specific antibodies. CONCLUSION: Increased tumor necrosis factor α and Fas-associated death domain protein may have deleterious primary and secondary effects on cerebral arteries by promoting inflammation and subsequent apoptosis in vascular and immune cells, thereby weakening vessel walls.

Outcome determinants of pterional surgery for tuberculum sellae meningiomas

SummaryBackground. Current literature on tuberculum sellae meningiomas is very heterogenous due to wide variation in nomenclature, diagnostic and operative techniques. The aim of this study is specifically to analyze the results of pterional craniotomy for tuberculum sellae meningiomas. A homogenous cohort of 42 consecutively operated tuberculum sellae meningioma cases are reviewed with special emphasis on the effects of pterional microsurgery on visual outcome. Methods. This is a retrospective clinical analysis. 42 consecutive patients operated upon during the period of 15 years in a single institution using standard imaging protocols and pterional microsurgery are presented and effect of various variables on visual outcome analysed. Findings. 81% of the patients presented with visual symptoms. The mean duration of symptoms was 12 months. Tumour volumes ranged from 7.5 to 210 mm3. A right sided pterional microsurgery was used in all patients. Complete resection rate was 81%. Vision improved in 58%, worsened in 14%. Non-visual morbidity was 7.1% and mortality was 2.4%. The follow up period of patients ranged from 3 to 192 months (median: 30 months). The mean was 37.5 months (SD = ±36.7 months) and a recurrence rate of 2.4% was observed. Conclusions. A standard pterional craniotomy using microsurgical technique provides the necessary exposure enabling total removal while keeping the complications to a minimum. Upon analysis of our findings we found that patient age of more than 60, duration of visual symptoms longer than 1 year, severe visual symptomatology, predominantly vertical growth, presence of significant peri-tumoural oedema, absence of an intact arachnoid plane and subtotal removal were correlated with a dismal visual outcome.

Multimodality management of 26 skull-base chordomas with 4-year mean follow-up: experience at a single institution

SummaryObjective. To analyze a series of patients with pathologically confirmed skull-base chordoma, and to develop an algorithm for the management of this challenging disease based on the data, our experience, and the current literature. Material and methods. Between the years 1986 and 2001, 26 chordoma patients received multimodality treatment with various combinations of conventional surgery, skull-base surgical techniques, and gamma-knife surgery at the Marmara University Faculty of Medicine. A total of 57 procedures (43 tumor excision surgeries, 7 gamma-knife procedures, and 7 other operations to treat complications) were performed. The mean follow-up period was 4 years (48.5 months). Karnofsky scoring was used to follow the patients’ clinical conditions, and magnetic resonance image analysis was used to measure tumor volume over time. Results. Seven patients died during follow-up. Two of the deaths were due to surgical complications, four resulted from clinical deterioration related to tumor recurrence, and one was unrelated to neoplasia. The rate of tumor recurrence after the first surgical treatment was 58%. Residual tumor volume was lower in the cases in whom skull-base approaches were used as first-line management. The 19 survivors showed little change in clinical status from initial diagnosis to the most recent follow-up check. The mean follow-up time after gamma-knife treatment was 23.3 months. During this period, mean tumor volume increased 28% above the mean volume at the time of gamma-knife surgery. The mean Karnofsky score decreased by 6% during the same time frame. Conclusions. The most effective first-line treatment for chordoma patients is surgery. The findings for residual tumor volume indicated that skull-base approaches are the best surgical option, and the complication rates for these techniques are acceptable. However, it is rare that surgery ever biologically eradicates this disease, and the data showed that these chordomas almost always progress if the tumor volume at the time of diagnosis exceeds 20 cm3. Based on our experience and the biological character of the disease, we now advocate radiosurgical treatment (gamma-knife in our case) immediately after the first-line skull-base surgery when the tumor residual volume is <30 cm3.

Pituitary adenomas treated with gamma knife radiosurgery: volumetric analysis of 100 cases with minimum 3 year follow-up.

OBJECTIVE To analyze pituitary adenoma volume changes after gamma knife radiosurgery (GKRS) in patients with 3 years of follow-up and to investigate factors that might affect these changes. METHODS Between January 1997 and March 2004, a total of 1930 patients were treated in the Gamma Knife Unit of the Marmara University Department of Neurosurgery in Istanbul, Turkey. Three hundred sixty of these patients had pituitary adenomas (PAs). This prospectively designed clinical study documents the radiological-volumetric analysis for the first 100 of these patients with PAs who had a minimum of 3 years of follow-up and met the study requirements. Each tumor was assessed with serial magnetic resonance imaging scans after radiosurgery; at each time point, adenoma volume was expressed as a percentage of the tumors initial volume. Volume changes were investigated relative to margin dose, the cavernous sinus infiltration, and endocrinological type of adenoma. RESULTS At the end of the first year after GKRS, the PA volumes had decreased to approximately 90% of the initial volume on average. The corresponding approximate averages for the ends of Years 2 and 3 were 80 and 70% of the initial volume, respectively. At 3 years after GKRS, the PAs in the group with a peripheral dose of less than 17 Gy were reduced to approximately 80% of the initial volume on average. In contrast, the tumors in the patients with marginal doses of 21 to 23 Gy were reduced to approximately 60% of the initial volume at this stage. The adenomas treated with the highest marginal doses (>27 Gy) showed the earliest volume decreases after GKRS (6–9 mo after the procedure). Cavernous sinus noninfiltrating adenomas showed greater volume decreases after GKRS; on average, these masses were reduced to approximately 50% of their initial volume at 3 years. In contrast, the PAs that had infiltrated the cavernous sinus had only dropped to approximately 80% of their initial volume at this stage. The growth hormone-secreting PAs showed the maximum volume decrease with GKRS. On average, these lesions were approximately 60% of their initial volume at the 3-year stage. The nonfunctioning tumors and the prolactin-secreting adenomas showed similar volume changes over time. On average, these tumors had dropped to approximately 75 and 70% of the initial volume, respectively, by 3 years after GKRS. CONCLUSION Gamma knife radiosurgery halts the growth of pituitary adenomas. Cavernous sinus extension and margin dose are the most important determinants of adenoma volume after this type of therapy.

Experience of a single institution treating foramen magnum meningiomas

Despite the introduction of skull base approaches, there is still controversy in the optimum surgical management of foramen magnum meningiomas. Between January 1990 and January 2003, 22 patients underwent 23 surgical procedures with a diagnosis of foramen magnum meningioma at Marmara University, Department of Neurosurgery. The suboccipital approach was used for 2 posteriorly located tumors with radiological total removal. The paramedian suboccipital approach was replaced by the far-lateral modification in the treatment of ventral meningiomas. 1 of the 20 ventral tumors was operated twice. The classical suboccipital approach was followed by the far-lateral modification. A gross-total removal was achieved in 21 patients. The overall morbidity was 32%. No specific and clinically significant complications attributable to the far-lateral modification were observed. The far-lateral approach has improved the success of surgery in ventrally located lesions. The posterior suboccipital approach is still indicated in the removal of lesions placed posterior to the dentate ligament.

Comparison of Endoscopic Transnasal and Transoral Approaches to the Craniovertebral Junction

OBJECTIVE The study compared the endoscopic anatomy of the transnasal and transoral approaches to the craniovertebral junction (CVJ). METHODS Structures examined and compared with both the straight and angled telescopes in 10 cadaveric specimens included the pharyngeal walls and adjacent musculature, resected anterior arch of the axis and odontoid, cruciform, axial, and apical ligaments, clival and dural openings, and the intradural exposure. RESULTS There is considerable overlap at the pharyngeal level in the structures that can be viewed by the transoral and transnasal routes. The transoral approach provides a wider corridor with less restricted manipulation of instruments than the transnasal approach, but the transnasal approach provides a better view of the clivus, upper part of the CVJ, and the structures posterior to the removed odontoid and anterior arch of C1. Combining the two approaches provides significantly better access to the midline anterior CVJ than either approach alone, allows the scopes to be advanced in one cavity and the surgical instruments in the other cavity, and reduces the need to split the palate, tongue, or mandible in order to reach the target area. The transnasal approach also allows access to the superior part of the occipital condyles, paraclival areas, and hypoglossal canals without removal of the condyles, but these structures can be exposed by the transoral route only after at least partial removal of the condyles. CONCLUSION The endoscopic transoral and transnasal approaches to the CVJ should be viewed as complementary routes as opposed to strict alternatives.

Tenascin in meningioma: Expression is correlated with anaplasia, vascular endothelial growth factor expression, and peritumoral edema but not with tumor border shape

OBJECTIVE : Tenascin is an extracellular matrix glycoprotein that is expressed during embryogenesis, inflammation, angiogenesis, and carcinogenesis. The aim of this study was to investigate how tenascin expression relates to histological grade, angiogenesis, and radiological findings in meningiomas. Methods: Twenty typical, 20 atypical, and 5 malignant meningiomas were studied retrospectively. Tenascin expression and vascular endothelial growth factor (VEGF) expression in the tumor tissue were investigated by immunohistochemistry. Tenascin messenger ribonucleic acid expression was also studied by comparative reverse transciptase-polymerase chain reaction. Magnetic resonance images from each case were assessed for peritumoral edema and tumor border shape. Results: The atypical and malignant meningiomas showed higher levels of tenascin expression than the typical meningiomas. The more sensitive messenger ribonucleic acid-based methods confirmed this finding. Tenascin expression was correlated with peritumoral edema and VEGF expression byt not with tumor border shape. In the 13 tumors with marked tenascin expression, peritumoral edema was Grade 0 in one, Grade 1 in three, and Grade 2 in nine specimens. In the same 13 tumors, VEGF expression was Grade 1 in five and Grade 2 in eight specimens, and the findings for tumor border shape were Grade 0 in seven, Grade 1 in four, and Grade 2 in two speciemens. Conclusion: In meningiomas, tenascin expression is correlated with anaplasia, tumor-associated edema, and VEGF expression but not with tumor border shape. This protein may play a role in the neoplastic and/or angiogenic processes in atypical and malignant meningiomas and may thus be a potential target for meningioma therapy.

Radiosurgical treatment of cavernous sinus cavernous haemangiomas.

SummaryBackground. The objective of this report is to evaluate the effects of radiosurgery on cavernous sinus cavernous haemangiomas (CSCHs). Method. Five cases of CSCHs are presented in this report. One of them was diagnosed only neuroradiologically. Other patients underwent surgery and were then referred to Gamma Knife radiosurgery for residual tumours. The cohort consisted of 3 male and 2 female patients with median age of 42 (37–60). The volume of the tumours ranged between 3.8–6.5 cc. They were treated with a marginal dose of 14 to 16 Gy (mean 15 Gy). Findings. In the mean follow-up period of 32 months (6–52 months) all of the tumours decreased in size. There were no complications related to radiosurgery. Conclusion. Gamma Knife radiosurgery is an effective method in the treatment of CSCH, over the period of follow-up described.

Expression of growth factors and structural proteins in chordomas: basic fibroblast growth factor, transforming growth factor alpha, and fibronectin are correlated with recurrence.

OBJECTIVE To test the hypothesis that the expression of certain growth factors and/or structural proteins is correlated with the biological behavior of cranial base chordomas. METHODS The study investigated 14 pathological specimens of cranial base chordomas from patients who were monitored for at least 2 years after their initial operations. Some cases involved multiple tumor recurrences and multiple operations. For those patients, the time to recurrence after each operation was recorded and a mean value was calculated. Nine patients with mean times to recurrence of 24 months or more or with 24 months of follow-up monitoring without recurrence after single operations were designated the “good-prognosis” group. Five patients with mean times to recurrence of less than 24 months were designated the “poor-prognosis” group. In each case, only the specimen from the initial operation was studied. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of three growth factors and three structural proteins, i.e., basic fibroblast growth factor, transforming growth factor &agr;, vascular endothelial growth factor, fibronectin, collagen III, and collagen IV. Intensity of expression was graded by using a four-tier system (Grades 0, 1, 2, and 3). Levels of expression of the molecules in the two groups were evaluated and compared. RESULTS The mean transforming growth factor &agr; expression intensity grades for the good- and poor-prognosis groups were 0.8 and 2.6, respectively, and the corresponding mean basic fibroblast growth factor grades were 1.4 and 2.6. For both groups, the mean grade for vascular endothelial growth factor expression was 0.6. For fibronectin, the mean staining grades for the good- and poor-prognosis groups were 2.2 and 3.0, respectively. The corresponding mean intensities for collagen III were 1.1 and 0.8, and those for collagen IV were 2.5 and 2.6. CONCLUSION Our descriptive data from immunohistochemical analyses of chordomas suggest that high levels of transforming growth factor &agr; and basic fibroblast growth factor expression are linked to higher rates of recurrence. Strong fibronectin expression may also be a marker of aggressive biological behavior.

Anatomy of Cerebral Veins and Sinuses

The veins of the brain have no muscular tissue in their thin walls and possess no valves. They emerge from the brain and lie in the subarachnoid space. They pierce the arachnoid mater and the meningeal layer of the dura and drain into the cranial venous sinuses. The cerebral venous system can be divided into a superficial and a deep system. The superficial system comprises sagittal sinuses and cortical veins, which drain superficial surfaces of both cerebral hemispheres. The deep system consists of the lateral sinus, straight sinus and sigmoid sinus along with draining deeper cortical veins. Both of these systems mostly drain into internal jugular veins. Generally, venous blood drains into the nearest venous sinus or, in the case of blood draining from the deepest structures, into deep veins. The superficial cerebral veins are interlinked with anastomotic veins of Trolard and Labbé. Thus, the superolateral surface of the hemisphere drains into the superior sagittal sinus while the posteroinferior aspect drains into the transverse sinus. The veins of the posterior fossa are variable in course, and angiographic diagnosis of their occlusion is difficult. The entire deep venous system is drained by internal cerebral and basal veins, which join to form the great vein of Galen that drains into the straight sinus. Though variation in the superficial cerebral venous system is a rule, anatomic configuration of the deep venous system can be used as anatomic landmarks. Since thrombosis or surgical sacrifice of the cerebral veins may lead to venous infarction with serious complications, angiographic and surgical anatomy of the venous system should be seriously investigated for each individual patient.