Gökalp Silav

The effect of polymorphisms in the promoter region of the MMP-1 gene on the occurrence and invasiveness of hypophyseal adenoma

BackgroundThe matrix metalloproteinase-1 enzyme (MMP-1, also called collagenase 1) plays a key role in turnover of collagen fibers in the intercellular matrix. Insertion of a guanine residue was found within the promoter region of the MMP-1 gene. We found that MMP-1 levels increased approximately twofold over normal when this insertion was present, enabling MMP-1 to facilitate tumor invasion and metastasis. MMP-1 is also believed to play a role in tumor development. The aim of our study is to investigate the effect of polymorphisms in the promoter region of the MMP-1 gene on the development of benign and invasive hypophyseal adenomas.Patients and methodsThirty patients with hypophyseal adenomas diagnosed by radiological examination underwent surgical removal, and the diagnosis was confirmed using immunohistochemical staining of the pathology specimens. We found that ten of these patients had invasive adenomas confirmed by radiological examination and immunohistochemical staining. DNA isolation was performed on all specimens, and 5-cc venous blood samples were obtained from all patients as well as 30 volunteers using the Qiagen QIAquick kit. Promoter regions of MMP-1 genes from the DNA samples were amplified using polymerase chain reaction (PCR) and primers designed for the site-directed mutation method. Following PCR, a guanine residue within the promoter region of the MMP-1 gene was identified using the restriction fragment length polymorphism method and the ALU I restriction enzyme. Three genotypes were detected in a genotyping assay: 2G/2G, 1G/2G, and 1G/1G.ResultsOf the surgically treated patients, 36.6% had the 2G/2G genotype, 46.6% had the 1G/2G genotype, and 16.6% had the 1G/1G genotype. The 2G allele frequency was found to be 83.4%. In 90% of cases of invasive adenoma, a homozygous 2G/2G genotype was detected.DiscussionThe risk for development of hypophyseal adenoma may be greater in patients with the 2G allele. In cases of existing hypophyseal adenoma, those with the homozygous 2G allele tend to be invasive.

Nocardial Cerebral Abscess Associated with Mycetoma, Pneumonia, and Membranoproliferative Glomerulonephritis

ABSTRACT Nocardial brain abscesses remain a clinical challenge. We successfully treated a patient with nocardial brain abscess, mycetoma, pneumonia, and glomerulonephritis. Nocardial soft tissue involvement, mycetoma, is well known. However, the fact that actinomycetoma can metastasize may not be as well appreciated. The association between nocardiosis and glomerulonephritis should be better clarified.

Chiari Malformation Type III and Results of Surgery: A Clinical Study

Background: The characteristics of Chiari malformation type III and its treatment are evaluated in this study. Radiological and surgical findings were correlated and the benefits of the therapy are discussed. Methods: Eight patients (6 males, 2 females) with Chiari malformation type III were studied. All patients underwent surgery to remove encephalocele along with neural tissue and to repair the dura and the skin. Associated pathologies such as hydrocephalus, tethered cord syndrome and syringomyelia were also surgically treated. Follow-up was based on the evaluation of postoperative motor and mental development, as well as on magnetic resonance imaging findings. Results: Ventriculoperitoneal shunt malfunction in 2 patients was the only surgical complication. One patient died 10 days after the operation, 7 patients survived, and the outcome of 2 patients was quite poor because of severe mental retardation and neurological deficits at the beginning. In the remaining patients, motor and mental development was normal, and the neurological outcome was satisfactory. Conclusion: Surgery in the newborn period, initial severity of neurological deficits, the presence of intermittent apnoea, delayed treatment of hydrocephalus and the amount of neuronal tissue within the excised encephalocele were determined as unfavourable prognostic factors for the outcome. If the appropriate surgical procedure is done at the right time, the outcome of the Chiari malformation type III patient can be satisfactory with a low mortality rate.

Diagnosis and management of pituitary abscess: a case series and review of the literature.

AIM Pituitary abscess is a disorder characterized with central nervous system (CNS) infection, mass effect, and endocrine dysfunction. These abscesses generally occur due to hematogenous spread in conditions such as paranasal sinusitis, sepsis, and where the blood brain barrier breaks down. This paper aims to discuss four cases of preoperatively diagnosed pituitary abscess in the light of the literature. MATERIAL AND METHODS Following detailed clinical and hormonal examinations and imaging tests, 210 cases of pituitary adenoma and other sellar pathologies were operated on at the Neurosurgery clinic of Göztepe Training and Research Hospital. RESULTS All the patients showed fever, systemic signs of toxemia and endocrine dysfunction at the time of diagnosis. In these cases, a preoperative diagnosis of the disease was made thanks to characteristic MRI findings. The four cases were operated by the transnasal transsphenoidal approach and histopathological and microbiological studies were performed for surgical specimens. CONCLUSION Pituitary abscesses are rare disorders responsible for a high mortality risk. Mortality and morbidity can be reduced by early surgical drainage and appropriate antibiotic treatments. Additionally, these cases should be closely followed-up in terms of pituitary insufficiency, surgical complications and infection.

Microsurgical management of non-neurofibromatosis spinal schwannoma

INTRODUCTION The aim of this study is to assess the clinical properties and surgical results of patients diagnosed with spinal schwannomas without neurofibromatosis (NF) properties. PATIENTS AND METHODS The data obtained from 35 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. 35 patients underwent surgery for spinal schwannoma at our institution between January 1997 and 2010. The data were gathered retrospectively from medical records and included clinical presentation, tumor location and post-operative complications. All cases were surgically excised, and they were confirmed to be schwannomas by pathologists with histopathological sections in paraffin stained with hematoxylin-eosin. RESULT We treated 35 (20 males and 15 females) patients with spinal schwannomas. The mean age of the patients was 47.2 (between 13 and 76) years. Of the cases, six schwannomas were located in the cervical spine, four in the thoracic spine, two in cervico-thoracic area, 10 in the thoraco-lumbar area and 13 in the lumbar spine. Two patients had malignant schwannomas that were recurrent. Of the 35 cases, the schwannomas were intradural-extramedullary in 30 cases (86%), intradural-intramedullar in 2 cases (6%), and extradural in 3 cases (9%). CONCLUSION Spinal schwannomas may occur at any level of the spinal axis and are most frequently intradural-extramedullary. The most common clinical presentation is pain. Most of the spinal schwannomas in non-NF patients can be resected completely without or with minor post-operative deficits. This knowledge may help us to create a strategy for total resection of a spinal schwannomas.

Relation of apparent diffusion coefficient with Ki-67 proliferation index in meningiomas

OBJECTIVE The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and apparent diffusion coefficient (ADC) values of low-grade and atypical/anaplastic (high-grade) meningiomas. METHODS Pre-operative diffusion-weighted imaging and histopathological evaluation of 44 patients with meningiomas were performed retrospectively. Regions of interest (ROIs) were manually drawn on the ADC images. In total six ROI measurements were taken in three consecutive slices, and the average of the mean ADC value was used. The relationship between the ADC and Ki-67 values was investigated, and the ADC values of the low-grade and high-grade meningiomas were compared. RESULTS 31 (70%) patients had low-grade the meningiomas. 10 (23%) patients had atypical and 3 (7%) had anaplastic meningiomas. ADC values of the low-grade and high-grade meningiomas were 0.81 ± 0.12 × 10(-3) and 0.66 ± 0.08 × 10(-3) mm(2) s(-1), respectively. Ki-67 proliferation indexes were 2.19% ± 1.14% for low-grade and 11.20% ± 9.80% for high-grade meningiomas. A statistically significant negative correlation between Ki-67 proliferation index and ADC values of the low-grade and high-grade meningiomas was detected (r(2) = 0.326, p < 0.001). High-grade meningiomas had lower ADC values than that of low-grade meningiomas. There was statistically significant difference between the ADC values of the low-grade and high-grade meningiomas (p < 0.001). CONCLUSION Our data provide an inverse correlation between the ADC and Ki-67 proliferation index values of meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning. ADVANCES IN KNOWLEDGE The purpose of this study was to investigate the relationship between Ki-67 proliferation indexes and ADC values of low-grade and atypical/anaplastic (high-grade) meningiomas. In addition, we compared the ADC and Ki-67 proliferative index values of the low-grade and atypical/anaplastic (high-grade) meningiomas. We concluded that there was an inverse correlation between the ADC and Ki-67 proliferation index values in meningiomas, and we have found statistically significant difference between the ADC values of the low-grade and high-grade meningiomas. ADC values can be used for histopathological characterization of the meningiomas and pre-surgical planning.

Management of failed cranioplasty.

AIM Failed cranioplasty attempts may lead to numerous complications in a broad spectrum including cosmetic problems, infection, neurological deterioration and even death. Selection of the most appropriate surgical technique for second and further surgical attempts for these patients still remains a debate. We aimed to share our experience and technical pitfalls on management of failed cranioplasty, particularly for patients with large cranial defects. MATERIAL AND METHODS A retrospective data analysis of cranioplasty cases in our series was performed including the time period between 2002 and 2012. Patients required recurrent cranioplasty were analyzed in detail. RESULTS Totally, 101 patients underwent cranioplasty for bony defect. Of 101 patients, eleven required a revision surgery due to infection or spontaneous resorption of the bone flap. All patients underwent revision cranioplasty with pre-surgical plaster cast mold technique modified from previous studies and/or tissue expansion technique. Polymethyl-metacrylate (PMMA) was used as substitute for reconstructions. Mean follow-up was 36 months. Two out of eleven cases (18.1%) developed major complications, which led to further revision. At the end, a satisfactory reconstruction was achieved for all patients. CONCLUSION Our modified molded plaster cast technique is a safe and cost-effective approach for the revision of failed cranioplasty. We believe that the tissue expanding techniques have also great contribution to achieve successful results.

A Simple Technique for Bone Storage after Decompressive Craniectomy in Children

Cranial vault reconstruction in the pediatric population is a specialized procedure, which requires additional considerations. Generally, inherent difficulties of bone storage and cranioplasty are neglected in the literature. We present a simple method of bone storage and autologous cranioplasty in a small child with severe head injury. The child underwent surgical treatment with decompressive craniectomy. A bone flap was transversally divided into two pieces and stored under the galea. Bone storage and reconstruction of the cranial vault with our surgical technique is a safe, easy and cost-effective choice excluding the surgical trauma to obtain a new subcutanous pocket for bone storage in pediatric decompressive craniectomy patients.

Investigation of ACE genome insertion/deletion correlation with immunohistochemical profile in pituitary adenomas.

AIM The deletion polymorphism of the angiotensin-converting enzyme (ACE) genome causes neoplastic development in several organs by increasing the angiotensin 2 (A2) formation. In this study, we aimed to identify the ACE genome insertion/deletion polymorphism in pituitary adenomas and to compare it with the control group. MATERIAL AND METHODS Patients operated for pituitary adenomas were included in the study. Genomic DNA was extracted from tumoral tissues and peripheral blood samples of the patients by using the Miller method. Primary sequence was selected via targeting the polymorphic region of intron 16 of ACE genome 17q23. DNA samples were multiplied by PCR using HACE3s and HACE3as primers. RESULTS Twenty-one operated cases were studied. In the study group; 44 % of the patients were identified as D/D, 33% of them as I/D and 23% of them as I/I. In 60%, D allele was identified. According to immunohistochemical investigation, we found that 100% of the patients with Cushing adenoma were D/D alleles. CONCLUSION Presence of high rate of ACE genome deletion in patients with pituitary adenoma and grade 3-4 patients suggest that ACE genome polymorphism can be a risk factor for the development of pituitary adenomas.

Concurrent repair of orbital shallowness with craniosynostosis surgery: two late cases of simultaneous orbital decompression.

Early closure of cranial sutures results in various types of cranial vault deformities, named craniosynostosis. Although mostly associated with syndromic cases, bony orbit deformities such as exorbitism can be seen with various types of craniosynostosis. This condition can be associated with papilledema and besides its effect on the patients appearance can cause subluxation of the globe, lagophthalmos or keratitis resulting in corneal ulcers and ultimately loss of vision. Various techniques have been proposed for repair or exorbitism such as fronto-orbital advancement procedures, orbital wall decompression, periosteum scoring and tissue excision. Orbital periosteal scoring covering the globe can be extremely efficient for orbital fat decompression when combined with other orbital volume expanding procedures. We hereby present two late cases of craniosynostosis associated with bilateral exorbitism due to orbital shallowness for which cranial vault reconstruction was performed simultaneously with combinations of fronto-orbital advancement, orbital decompression and periosteal scoring. The late referral of these patients at ages older than the usual time of operation indication made the surgical procedure for craniosynostosis repair and exorbitism treatment challenging. The combined and simultaneous use of bone advancement, orbital wall decompression and specially periosteum scoring can be highly efficient in the treatment of exorbitism associated with craniosynostosis.