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    Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature
    (GEORG THIEME VERLAG KG, 2021-01-01) Sari, Ramazan; Altinoz, Meric A.; Ozlu, Eylem Burcu Kahraman; Sav, Aydin; Danyeli, Ayca Ersen; Baskan, Ozdil; Er, Ozlem; Elmaci, Ilhan
    Despite most of the prolactinomas can be treated with endocrine therapy and/or surgery, a significant percentage of these tumors can be resistant to endocrine treatments and/or recur with prominent invasion into the surrounding anatomical structures. Hence, clinical, pathological, and molecular definitions of aggressive prolactinomas are important to guide for classical and novel treatment modalities. In this review, we aimed to define molecular endocrinological features of dopamine agonist-resistant and aggressive prolactinomas for designing future multimodality treatments. Besides surgery, temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide therapy, estrogen pathway modulators, progesterone antagonists or agonists, mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib, everolimus, and metformin are tested in preclinical models, anecdotal cases, and in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing hormone, TGF beta and PRDM2 may seem like possible future targets for managing aggressive prolactinomas. Lastly, we discussed our management of a unique prolactinoma case by asking which tumors' proliferative index (Ki67) increased from 5-6\% to 26\% in two subsequent surgeries performed in a 2-year period, exerted massive invasive growth, and secreted huge levels of prolactin leading up to levels of 1 605 671ng/dl in blood.
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    Desmoplastic infantile ganglioglioma: Report of an unusual case with a cranial defect
    (MEDKNOW PUBLICATIONS \& MEDIA PVT LTD, 2014-01-01) Basaran, Recep; Cakir, Fatma Betul; Isik, Nejat; Sav, Aydin; Elmaci, Ilhan
    Desmoplastic infantile ganglioglioma (DIG) is a rare tumor that typically occurs in infants under the age of 24 months. These tumors commonly have a good prognosis after surgical resection despite their aggressive radiological appearances. Clinical signs are due to the large size of the tumor and include increased head circumference, bulging fontanel, sunset sign and seizures. We report an unusual DIG case who presented with parietal bulging associated with a bony defect. The patient was thought to have a leptomeningeal cystic formation, but on his cranial magnetic resonance imaging (MRI), we observed a centrally and homogeneously gadolinium-enhanced lesion fixed to the dura by its solid component. A surgical gross total resection was performed, and no residual tumor was observed on follow-up.
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    Investigation of ACE Genome Insertion/Deletion Correlation with Immunohistochemical Profile in Pituitary Adenomas
    (TURKISH NEUROSURGICAL SOC, 2013-01-01) Altas, Murat; Bayrak, Omer Faruk; Serefhan, Alpay; Silav, Gokalp; Coskun, Kerim Kenan; Cerci, Ajlan; Isik, Nejat; Elmaci, Ilhan
    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
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    The Surgical Treatment of Plagiocephaly
    (TURKISH NEUROSURGICAL SOC, 2011-01-01) Silav, Gokalp; Avci, Gulden; Akan, Mithat; Taylan, Gaye; Elmaci, Ilhan; Akoz, Tayfun
    AIM: Anterior plagiocephaly usually occurs with premature synostosis of the ipsilateral half of the coronal suture. The forehead is flattened on the affected side, with a backward and upward displacement of the affected orbit. The bulging of the calvaria may occur in the contralateral parietal area. MATERIAL and METHODS: This article presents the surgical techniques used over 7 years to treat plagiocephalic children. Eleven patients with unilateral coronal synostosis treated during 2003-2010 were analyzed retrospectively. The study included reviews of pre and postoperative computed tomography scans, operative techniques, clinical outcomes and complications. Unilateral orbital advancement with ``tongue in groove{''} was performed in 5, and bilateral orbital advancement in 6 cases. Pre and postoperative anthropometric measurements were used to document the amount of advancement of the elevated and recessed orbita, and the amount of withdrawal of the contralateral side. RESULTS: The mean age of the patients at time of surgery was 11 months. The preoperative values of the orbital height and retrusion were 0.68 cm and 1.87 cm, respectively. They were recorded as -0.1cm and 0,63 cm, postoperatively. Mean follow-up was 36 months, neither neurological sequelae nor other significant complications were encountered. CONCLUSION: The surgical corrections have resulted in significant improvements in skull shape and high patient/parent satisfaction.
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    Diagnosis and Management of Pituitary Abscess: A Case Series and Review of the Literature
    (TURKISH NEUROSURGICAL SOC, 2013-01-01) Altas, Murat; Serefhan, Alpay; Silav, Gokalp; Cerci, Ajlan; Coskun, Kerim Kenan; Elmaci, Ilhan
    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 Goztepe 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.
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    Progesterone at high doses reduces the growth of U87 and A172 glioblastoma cells: Proteomic changes regarding metabolism and immunity
    (WILEY, 2020-01-01) Altinoz, Meric A.; Ucal, Yasemin; Yilmaz, Muazzez C.; Kiris, Irem; Ozisik, Ozan; Sezerman, Ugur; Ozpinar, Aysel; Elmaci, Ilhan
    While pregnancy may accelerate glioblastoma multiforme (GBM) growth, parity and progesterone (P4) containing treatments (ie, hormone replacement therapy) reduce the risk of GBM development. In parallel, low and high doses of P4 exert stimulating and inhibitory actions on GBM growth, respectively. The mechanisms behind the high-dose P4-suppression of GBM growth is unknown. In the present study, we assessed the changes in growth and proteomic profiles when high-dose P4 (100 and 300 mu M) was administered in human U87 and A172 GBM cell lines. The xCELLigence system was used to examine cell growth when different concentrations of P4 (20, 50, 100, and 300 mu M) was administered. The protein profiles were determined by two-dimensional gel electrophoresis in both cell lines when 100 and 300 mu M P4 were administered. Finally, the pathways enriched by the differentially expressed proteins were assessed using bioinformatic tools. Increasing doses of P4 blocked the growth of both GBM cells. We identified 26 and 51 differentially expressed proteins (fc > 2) in A172 and U87 cell lines treated with P4, respectively. Only the pro-tumorigenic mitochondrial ornithine aminotransferase and anti-apoptotic mitochondrial 60 kDa heat shock protein were downregulated in A172 cell line and U87 cell line when treated with P4, respectively. Detoxification of reactive oxygen species, cellular response to stress, glucose metabolism, and immunity-related proteins were altered in P4-treated GBM cell lines. The paradox on the effect of low and high doses of P4 on GBM growth is gaining attention. The mechanism related to the high dose of P4 on GBM growth can be explained by the alterations in detoxification mechanisms, stress, and immune response and glucose metabolism. P4 suppresses GBM growth and as it is nontoxic in comparison to classical chemotherapeutics, it can be used as a new strategy in GBM treatment in the future.
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    Intraoperative Neurophysiological Monitoring to Prevent New Neurological Deficits in Spinal Tumor Cases
    (TURKISH NEUROLOGICAL SOC, 2014-01-01) Aydinlar, Elif Ilgaz; Dikmen, Pinar Yalinay; Silav, Gokalp; Berkman, Mehmet Zafer; Elmaci, Ilhan; Ozgen, Serdar
    Objective: Intraoperative neurophysiological monitoring was carried out in patients with spinal cord tumors. These patients were retrospectively evaluated for new postoperative neurological deficits. Materials and Methods: A total of 32 spinal tumor cases (8 cervical, 14 thoracic, 10 lumbosacral), 17 male and 15 female, patients between 2-66 years of age (mean 44.1 +/- 20) operated in our center were evaluated. All of our cases were monitored with somatosensory evoked potentials (SEP) muscular motor evoked potentials (MEP) and free run electromyography. Spinal MEP (D wave), bulbocavernosus reflex (BCR) and pudendal SEP were obtained in appropriate cases. Results: Five cases presented with temporary new postoperative neurological deficits in the form of strength loss. Neurophysiological recordings of all of these patients showed either temporary or permanent deterioration during surgery. The tumor was removed completely or almost completely in 26, near-completely in 4 and partially in 2 cases and none of our cases had a new permanent deficit. Conclusion: The functional integrity of the lateral and dorsal columns of the spine can be assessed by SEP and muscular MEP recording. Additional information about the neurological tissue is given by spinal MEP, BCR and pudendal SEP in suitable cases. We did not experience any false positive or negative results in our cases and we believe that the combined use of intraoperative spinal and MEP in spinal column located tumors gives reliable information about postoperative neurological outcome.
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    Haemodynamic Augmentation in the Treatment of Vasospasm in Aneurysmal Subarachnoid Hemorrhage
    (TURKISH NEUROSURGICAL SOC, 2012-01-01) Gura, Melek; Elmaci, Ilhan; Cerci, Ajlan; Sagiroglu, Esra; Coskun, K. Kenan
    AIM: Hypertension, hypervolemia and hemodilution therapy is a common approach to cerebral vasospasm after subarachnoid haemorrhage. This study is designed to see the difference of moderate or aggressive hypervolemia supported with induced hypertension in symptomatic vasospasm detected with transcranial Doppler ultrasonography (TCD) measurements. MATERIAL and METHODS: Fifty eight patients who had aneurysm clipping and were admitted to the neurointensive care unit were treated with normovolemia and induced hypertension (n=35) or hypervolemia supported with induced hypertension (n=23) targeting a mean arterial pressure of 110-130 mm Hg and central venous pressure of 8-12 mm Hg. Daily TCD, fluid intake, fluid balance and haemodynamic values were recorded for 14 days. RESULTS: There were no differences detected in mean arterial pressure, central venous pressure, hematocrit values, fluid balance and middle cerebral artery flow velocities between the two groups through 14 days (p > 0.05). Hyponatremia, pulmonary edema and cerebral ischemia were observed as complications. CONCLUSION: Hypervolemia adds no benefit compared to normovolemia in the treatment of vasospasm occurred as a result of subarachnoid hemorrhage. Induced hypertension establishes the haemodynamic augmentation to prevent and treat vasospasm.
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    Correlation of Pulsatility Index with Intracranial Pressure in Traumatic Brain Injury
    (TURKISH NEUROSURGICAL SOC, 2011-01-01) Gura, Melek; Elmaci, Ilhan; Sari, Ramazan; Coskun, Nilufer
    AIM: In traumatic brain injury (TBI) patients, it is desired to monitor the intracranial pressure (ICP) to assess the cerebral haemodynamics and guide the therapy. The study was designed to see if the pulsatility index (PI) measured by transcranial Doppler ultrasonography (TCD) predicts information about ICP values. MATERIAL and METHODS: In 52 TBI patients with Glasgow Coma Scale (GCS) score < 9, invasive intracranial monitoring and TCD ultrasonography for PI were performed through five days. ICP, cerebral perfusion pressure (CPP), PI values were recorded and calculated. The correlation and regression analysis between ICP, PI and CPP were investigated in the whole group and in patients with a Glasgow Outcome Score (GOS) of 3-5. RESULTS: The decline in ICP and PI values was significant through five days. The correlation between ICP and PI was strongly significant (p < 0.0001) on days 1, 3 and 5. In patients with a GOS of 3-5, correlation of ICP and PI was also observed. The only significant correlation observed between CPP and PI was on days. CONCLUSION: The strong correlation observed between ICP and PI through the management period of TBI patients can lead us to use TCD ultrasonography-derived PI as a guide if invasive monitoring is not available.