Nezih Oktar

Spinal hydatid disease

Vertebral hydatid cysts are rare and found in less than 1% of all the cases of hydatidosis. Neural compression is common in vertebral hydatidosis. The prognosis is generally regarded as very poor. This paper examines the natural history and complications which may arise during the treatment of vertebral hydatid cyst, and discusses their treatment. Thirteen cases of hydatid disease affecting the vertebrae are presented. The patients were admitted with symptoms of spinal cord compression. Twelve were treated by laminectomy and one by costotransversectomy. Low back pain radiating to the legs and lower extremity weakness were the predominant symptoms. Different degrees of pareses were present in 12 patients. Nine patients had impaired sensation in lower extremities. In 13 patients, 27 operations were performed. The major complication of surgery was the death of one patient due to the formaline irrigation. The surgical goal should be an extensive removal of the cysts and affected bone. The surgical area needs to be irrigated with hypertonic saline. Mebendazole or albendazole therapy seems to retard the recurrences and control the disease.

Surgery of intramedullary spinal cord tumors

The diagnosis and management of intramedullary spinal cord tumors have been significantly influenced by new diagnostic and surgical tools such as MRI, ultrasonic aspiration, intraoperative ultrasound, and evoked potential monitoring. In this study we compared the surgical results of our earlier cases using conventional methods with more recent cases using these new methods. We report our experience based on 44 adult cases. Histologic diagnosis revealed ependymoma (20 cases), astrocytoma (15 cases), glioblastoma multiforme (1 case), and other histologic diagnoses (8 cases). We performed 20 gross total resections, 19 partial resections, and 5 biopsies. The mean follow-up period was 25.8 months (3 months-10 years). Surgical results were improvement in 11 patients (25%), stabilization in 24 (54%), and deterioration in 9 (20%). The first 28 cases (group A) were diagnosed using conventional ventional myelography and CT myelography. The more recent 16 cases (group B) were diagnosed with MRI and operated on using techniques such as ultrasonic aspiration, intraoperative monitoring and ultrasound imaging. Radical surgery (total excison) was performed in 36% (n=10) of group A, while it was possible in 62% (n=10) of group B. Deterioration after operation was noted in 28% (n=8) of group A, but only 6.2% (n=1) of group B. These results stress the importance of a preoperative MRI scan and the positive effects of intraoperative ultrasound imaging, ultrasonic aspiration, and evoked potential monitoring on surgical results. With the help of these tools, most intramedullary spinal cord tumors may be diagnosed and treated surgically with significantly decreased risk. Radical surgery was possible in as many as 62% of our more recent patients. Partial resection with radiotherapy should be confined to patients with high-grade astrocytomas.

Online electrochemical monitoring of nitric oxide during photodynamic therapy

Photodynamic therapy (PDT), as a novel treatment modality, is based on the use of a photosensitizing agent with an excitation light source for the treatment of various malignancies. Its effect is mediated through reactive oxygen species and nitric oxide (NO), which are shown to be present in apoptosis. Individual differences among patients and even in different areas of the same tumor in one patient may cause a major problem with PDT: dose calculation during application of the light. An electrochemical sensor is proposed for online monitoring of NO generation as a solution of this problem. 5-Aminolevulinic acid (ALA) was administered as the photosensitizer in rat cerebellum. An amperometric sensor, selective to NO, was designed and tested both in vitro and in vivo during PDT. ALA-mediated PDT resulted in rapid generation of NO, starting as early as the application of light on the tissue. Simultaneous amperometric recordings have been carried out for 5 min during PDT. The progressive increase in NO concentration peaked at 1.10 min and then the response current began to decrease until it reached a plateau at around 70% of its peak value. This study, for the first time, electrochemically demonstrates the generation of NO during PDT. Rapid and stable responses obtained by the experimental setup confirmed that this method could be used as an online monitoring system for PDT-mediated apoptosis.

Multicellular tumour spheroids derived from human brain tumours.

Multicellular tumour spheroids were prepared from a total of 46 human brain tumour biopsies by collagenase digestion and plating into agar coated flasks. Both primary malignant and secondary tumours formed spheroids with some correlation between the malignancy of tumour and the ability to undergo spheroid formation. The spheroids were capable of progressive growth, the rate of which was dependent, to some extent, on environmental conditions and was reflected by an increase in cell number within the spheroids. Spheroids prepared in this way may prove to be useful models for in vitro chemosensitivity and the general biology of brain tumours.

Local interstitial chemotherapy with sustained release bucladesine in de novo glioblastoma multiforme: a preliminary study.

This clinical study was designed to evaluate the safety and efficacy of the sustained release form of dibutryl adenosine-3′,5′-cyclic monophosphate (dB-cAMP, bucladesine) placed in the tumor resection cavity at the time of recurrence of the de novo glioblastoma multiforme (GBM) patients.In a randomized prospective manner, 40 patients who were diagnosed as GBM in their first operations were included in this study. Four different therapy protocols were used: First group of 10 patients had tumor resection only. Second group assessed had only systemic chemotherapy as six i.v. infusions of fotémustine after tumor resection. Third group had implantation of bucladesine-loaded biodegradable polymeric sustained release (bcl-SR) pellets while the last group received six i.v. infusions of systemic fotémustine as in the second group in addition to local implantation of bcl-SR pellets. A biodegradable polymer, poly-dl-lactide-co-glycolide with molecular weight of 80 000, was used as carrier matrix for the drug with an approximately 4–5 months of release time. Maximal doses of 20 mg of bucladesine with a mean dose of 15.5 mg were implanted. No bone marrow suppression occurred and there were no wound infections as far as the local bucladesine-loaded polymer therapy is concerned.In this randomized prospective trial of local interstitial chemotherapy with long acting bcl-SR did show a statistically significant delay of recurrence on the treatment of GBM patients. Best treatment results obtained from the local bcl-SR + systemic fotémustine treated group in which survival rate estimated by the Kaplan–Meier method was 70% in de novo GBM at 12 months.

An experimental trial of cyclic nucleotides on multicellular spheroids derived from human brain tumours

The effects of cyclic nucleotides, dibutyryl cyclic adenosine monophosphate and dibutyryl cyclic guanosine monophosphate (db-cAMP and db-cGMP), on the growth rate of multicellular tumour spheroids were evaluated by comparing the growth delay and colony forming efficiency in vitro. Multicellular tumour spheroids were derived directly from human brain tumours. To compare the chemotherapeutic effect of cyclic nucleotides, CCNU was used as a known effective cytotoxic drug on malignant gliomas.Significant growth delay was obtained by db-cAMP (p<0.001) while CCNU was tumouricidal rather then producing a delay in growth.of the tumpur spheroids. Db-cGMP found not to be effective in decreasing the growth rate of the tumour spheroids in vitro (p>0.2).The role of cyclic nucleotides in brain tumours is discussed on a review basis.

Primary glioblastoma of the Medulla Spinalis: A Report of Three Cases and Review of the literature

Primary spinal glioblastoma multiforme (spinal GBM) is not a very common entity. This paper presents an outline of this rare neoplasm, its clinical presentation, course, management and outcome and reports a 3-case series of spinal GBM. In this 3-case series with spinal GBM, one of the patients was operated for hydrocephalous 10 months later following the tumor surgery and another patient had cerebral metastasis after the surgery. In the postoperative period, two of the cases received radiotherapy and one received combined radiotherapy and chemotherapy with steroid therapy together following the tumor surgery. The review of the pertinent literature has revealed that due to the scarcity of the reported cases of primary spinal GBMs, this issue requires a closer look. GBM behaves more aggressive in medulla spinalis than it behaves when it originates from cerebrum. It may disseminate to the cerebrum during its course and it may cause hydrocephalus due to this dissemination (metastasis).

Assessment of genetic markers and glioblastoma stem-like cells in activation of dendritic cells

Glioblastoma (GBM) is the most common and aggressive intraparenchymal primary brain tumor in adults. The principal reasons for the poor outcomes of GBM are the high rates of recurrence and resistance to chemotherapy. The aim of this study was to determine the role of tailored cellular therapy for GBM with a poor prognosis and compare the activity of dendritic cells (DCs) that have encountered GBM cells. Detecting the correlations between methylation and expression of MGMT and PTEN genes and GBM cancer stem cells (CSCs) markers after co-cultures with a mononuclear cell cocktail are also aims for this study. Allogenic umbilical cord blood (UCB)-derived DCs were labeled with the CD11a and CD123 for immature DCs, and CD80 and CD11c for mature DCs. CD34, CD45, and CD56 cells were isolated from allogenic UCB for using in DCs maturation. GBM CSCs were detected with CD133/1 and CD111 antibodies after co-culture studies. DC activation was carried out via GBM cells including CD133 and CD111 cells and a mononuclear cells cocktail including CD34, CD45, and CD56 natural killer cells. Real-time PCR was performed to detect the expression and promoter methylation status of PTEN and MGMT genes. The expression of CSCs markers was found in all GBM cases, and a statistically significant correlation was found among them after co-culture studies. The most pronounced affinity of DCs to GBM cells was observed at dilutions between 1/4 and 1/256 in co-cultures. There was a statistically significant correlation between cellularity and granularity ratios for CD123 and CD11c. PTEN and MGMT gene expression and methylation values were evaluated with respect to CSCs expression and no statistical significance was found. Activation of DCs might associate with CSCs and the mononuclear cells cocktail including CD34, CD45, and CD56 cells which were obtained from allogenic UCB.

Management of Calvarial Tumors: A Retrospective Analysis and Literature Review.

AIM Tumors of various organs that metastasize to bone do not neglect calvarium as a target. The aim of this study was to characterize the calvarial tumors. MATERIAL AND METHODS We retrospectively reviewed 45 consecutive patients operated for calvarial masses from January 2002 till May 2012 at our hospital. Skull base tumors and patients ≤18 years were excluded. RESULTS Three groups of lesions were found - calvarial metastases (15/45), primary tumors (5/45) and tumor-like lesions (25/45). Malignant lesions were equitable by gender distribution, higher age of onset (median age of primary =55; secondary = 60 years) and benign lesions by younger age (median = 35) and female bias (18/25). Calvarial metastases mostly presented with local swelling (10/15), local pain (6/15) and rarely neurologic deficit. There was associated dural sinus thrombosis (4/20 of malignant; 1/25 of benign lesions) and osteolysis (3/5 primary malignant, 13/15 secondary and 18/25 of benign lesions). Complete surgical excision was possible with minimal morbidity in all except one patient and nil mortality. CONCLUSION Nearly half (20/45) of the calvarial lesions tend to be malignant with most of them presenting as silent painless masses. Surgical excision should be considered only after suitable investigation and appropriate neurosurgical set-up.