An aggressive Cushing's syndrome originating from a rare thymic neuroendocrine tumor, controlled successfully with fluconazole and octreotide therapy before surgery.

ABSTRACT: Cushing's syndromes (CSs) due to the thymic neuroendocrine tumors are rarely seen. Here, a case of ectopic CS originating from an atypical neuroendocrine tumor has been presented. A 49-year-old woman was hospitalized with symptoms of fatigue, chest pressure, dyspnea, muscle weakness, and resistant hypertension. There was marked hyperpigmentation in the whole-body surface suggestive of adrenocorticotropic hormone (ACTH) excess and there were physical features of CS. There was deep hypokalemia. Basal hormone profile, dexamethasone suppression tests, midnight cortisol, and 24-hour urine cortisol levels were suggestive of ectopic CS. The pituitary magnetic resonance imaging revealed a 5 mm cystic lesion and the patient refused inferior petrosal sinus sampling. Thorax computerized tomography showed an anterior mediastinal mass. A fluorodeoxyglucose-positron emission tomography showed the same mediastinal lesion (suvmax: 11.4), and no other tumor focus was detected. There was an aggressive cortisol excess causing acute respiratory distress syndrome, making it difficult to perform the surgery. We immediately started fluconazole and octreotide therapy and were successful in lowering the cortisol level. Then a complete resection of the tumor had been able to be surgically performed and tumor cells showed strong cytoplasmic immunopositivity with ACTH. A definitive diagnosis of "ACTH secreting atypical thymic carcinoid tumor" was rendered based on the histopathological and immunohistochemical features. There was only surrounding vessel invasion, and no lymphoid or other organ metastases were detected. As there were surrounding vessel invasions, a two-cycle regimen cisplatin-etoposide chemotherapy and radiotherapy were employed. After surgical and medical therapy, the cortisol and ACTH levels turned to normal. The patient is in biochemical and clinical remission and has no tumor recurrence yet. Ectopic ACTH-producing thymic carcinoids are rare but life-threatening tumors because of the underlying malignancy and severe hypercortisolemia. It is important to consider this disease and perform appropriate treatment at the right time. Today, surgery is the standard therapeutic modality if it is possible to perform, but there is not a clear and constant recommendation for nonsurgical therapeutic modalities. Further studies are needed for the optimal treatment strategies.

Protective Effects of Adropin in Experimental Subarachnoid Hemorrhage.

PURPOSE: We aimed to investigate early effects of exogenously administered adropin (AD) on neurological function, endothelial nitric oxide synthase (eNOS) expression, nitrite/nitrate levels, oxidative stress, and apoptosis in subarachnoid hemorrhage (SAH). METHODS: Following intracerebroventricular AD administration (10 µg/5 µl at a rate of 1 µl/min) SAH model was carried out in Sprague-Dawley rats by injection of autologous blood into the prechiasmatic cistern. The effects of AD were assessed 24 h following SAH. The modified Garcia score was employed to evaluate functional insufficiencies. Adropin and caspase-3 proteins were measured by ELISA, while nitrite/nitrate levels, total antioxidant capacity (TAC) and reactive oxygen/nitrogen species (ROS/RNS) were assayed by standard kits. eNOS expression and apoptotic neurons were detected by immunohistochemical analysis. RESULTS: The SAH group performed notably lower on the modified Garcia score compared to sham and SAH + AD groups. Adropin administration increased brain eNOS expression, nitrite/nitrate and AD levels compared to SHAM and SAH groups. SAH produced enhanced ROS/RNS generation and reduced antioxidant capacity in the brain. Adropin boosted brain TAC and diminished ROS/RNS production in SAH rats and no considerable change amongst SHAM and SAH + AD groups were detected. Apoptotic cells were notably increased in intensity and number after SAH and were reduced by AD administration. CONCLUSIONS: Adropin increases eNOS expression and reduces neurobehavioral deficits, oxidative stress, and apoptotic cell death in SAH model. Presented results indicate that AD provides protection in early brain injury associated with SAH.

Challenging treatment of parameningeal rhabdomyosarcoma with leptomeningeal metastasis: Case report and review of literature.

Parameningeal rhabdomyosarcomas (PM RMSs) are rarely seen childhood tumors. Their treatment might be challenging and prognosis is poor compared to other head and neck RMS. Here we report a PM RMS presenting with leptomeningeal seeding metastasis a year after diagnosis. A five-year-old girl presented with an enlarging mass protruding from the right ear and right facial paralysis. Magnetic resonance imaging (MRI) revealed a large mass extending from right external auditory canal to the temporal lobe, pterygoid fossa and nasopharynx with an intracranial component indenting the right temporal lobe and extending into the right cavernous sinus. Trucut biopsy revealed embryonal rhabdomyosarcoma. Cerebrospinal fluid (CSF) cytology was negative for malignant cells. Chemotherapy was started since it was found unresectable. At second week of chemotherapy, radiotherapy was applied to primary tumor location with intensity-modulated radiation therapy (IMRT) technique in 1.8 Gy fractions to total dose of 50.4 Gy. At week 27, MRI showed significant response. At week 36, the patient presented with vomiting and tendency to sleep. MRI was found to be compatible with meningitis and antibacterial therapy was started. At week 39, chemotherapy was stopped. But MRI performed one month later revealed linear contrast enhancements around the spinal cord compatible with leptomeningeal metastases. Chemotherapy and craniospinal irradiation were applied. But the patient did not improve and received palliative treatment. Six months after the completion of radiotherapy the patient died. Treatment of parameningeal rhabdomyosarcomas require multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Prognosis is poor for patients with leptomeningeal spread.

The effect of amifostine on pathophysiological changes in vasogenic brain edema induced by an experimental cold injury model.

AIM: To investigate the effects of amifostine, a cytoprotective agent, on pathophysiological changes in vasogenic brain edema induced by an experimental cold injury model and to compare these changes with dexamethasone. MATERIAL AND METHODS: A total of 138 rats divided into 6 groups. Brain water content (BWC), malondialdehyde (MDA) concentration and myeloperoxidase (MPO) activity in brain tissue were calculated to evaluate the pathophysiological changes following experimental cold injury. In addition, effects of cold injury on cell structure were assessed with direct light and transmission electron microscopy (TEM). RESULTS: Extent of edema, MDA and MPO levels were significantly higher in cold injury groups than in controls. Although a decrease was noted in these parameters in both the amifostine and dexamethasone groups, the differences were significant only for MDA concentration in dexamethasone group, and for MPO activity in both groups. In addition, there was a significant difference between the group in which amifostine was administered prior to cold injury and dexamethasone group for MPO activity. Histopathologically, positive effects were observed in treatment groups. CONCLUSION: Despite several positive effects of amifostine, its superiority to dexamethasone could not be clearly demonstrated. Further experimental and clinical studies are warranted to better delineate the neuroprotective effects of amifostine.

Experimental investigation of the effects of a blood stopper agent (ankaferd blood stopper) on bone surfaces.

OBJECTIVE: This study aims to experimentally investigate the efficiency of Ankaferd Blood Stopper (ABS) on early and long-term bone healing and its effects on bone surfaces. MATERIALS AND METHODS: Thirty adult male Wistar albino rats were used in the study. These rats were randomly divided into three groups, and bilaterally bone defects were created in the femur of each rat. A 3.0-mm-deep monocortical circular defect was created with a 3.0 mm diameter trephine drill on the proximal part of the femur, and 0.05 mL ABS was applied to the experimental group while the control group was left untreated. Group 1, group 2, and group 3 rats were sacrificed on days 7, 28, and 42, respectively. Trabecular bone area (Tb.Ar), medullary bone diameter (Me.Dm), osteoblast area (Ob.Ar), osteoid area (O.Ar) and mineralized bone area (Md.Ar) were examined in the histomorphometric analysis. Also new bone formation was scored according to the histologic evaluation Results: The results showed that while new the to day 7 experimental group showed much more bone formation than the to day 7 control group, there was no significant difference between the to day 28 and day 42 experimental groups and to day 28 and day 42 control groups. Accordingly, ABS applied in bone cavities only had a larger accelerator effect on bone healing for the seventh-day to day 7 experimental group. In clinical observations, no allergic or inflammatory reactions were observed on the skin and other preoperative and postoperative periods. Moreover in, the histomorphometric study, necrotic areas and infection areas were not observed. CONCLUSION: ABS has an acceleratory effect on the short-term bone healing process and is a reliable agent for routine use. However, its effects on the long-term bone healing process are insignificant. We think that a wide series of research projects are required to confirm the effects of ABS speeding up the healing process in addition to its characteristic as a blood stopping agent. CONFLICT OF INTEREST: None declared.

Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report.

Ectopic intrathyroidal thymus tissue that may be present as a thyroid nodule is rarely reported. We present a case of a 4-year-old boy with a solitary thyroid nodule. Real-time thyroid ultrasound showed a calcified nodule in the right lobe. Complete blood count, serum calcitonin, and thyroglobulin concentration were normal and antithyroid antibodies were negative. Fine-needle aspiration (FNA) biopsy was revealed as inadequate for cytological examination. During his follow-up, nodular enlargement was found, and the patient was subjected to surgical total excision of the right lobe of the thyroid gland. Pathological examination showed an ectopic intrathyroidal thymus tissue. In childhood, ectopic intrathyroidal thymus tissue can present as an enlarging microcalcified thyroid nodule that may mimic thyroid cancer and may grow during follow-up.

A case of extraventricular neurocytoma of the spinal cord.

Central neurocytoma is a rare neuroectodermal tumor generally found in young adults. It mainly originates from lateral ventricles. Extraventricular location of this kind of tumor, especially spinal cord involvement, is extremely rare. This article is the ninth case of central neurocytoma derived from the spinal region, and includes a review of the literature. The patient in this case is a 49-year-old woman presenting with C3-C5 spinal mass with typical histopathologic findings and low MIB-1 index.

Primary atypical teratoid/rhabdoid tumor of the clival region. Case report.

An atypical teratoid/rhabdoid tumor of the central nervous system (CNS) is a rare, aggressive neoplasm found in infants and children that has similar characteristics to CNS primitive neuroectodermal tumors/medulloblastomas. The authors present the case of a patient with an atypical teratoid/rhabdoid tumor and discuss the imaging, histopathological, immunohistochemical, and cytogenetic findings. Tumor cells displayed positive reactions for vimentin, epithelial membrane antigen, and cytokeratin, and they displayed no reaction for glial fibrillary acidic protein, desmin, and actin. The karyotype was 46, XY. The phenotype of an atypical teratoid/rhabdoid tumor appears heterogeneous when examined by histological, immunohistochemical, and genetic analysis. The authors describe the case of a 4-year-old boy who harbored an atypical teratoid/rhabdoid tumor in the clivus, which appeared as a chordoma on neuroimages. To their knowledge, this location of an atypical teratoid/rhabdoid tumor has not been described in the literature.

Epithelioid hemangioendothelioma derived from the spine region: case report and review of the literature.

Epithelioid hemangioendotheliomas (EHE) are rare vascular tumors which generally originate from soft tissues and visceral organs. Primary bone EHEs, especially those occurring in the spine region, are extremely rare. Our case is that of a 30-year-old man who was admitted to hospital with low back pain, difficulty in walking, post-voiding urinary incontinence and numbness in the caudal area. X-ray showed a lytic process affecting the vertebra L2 and collapse of L1. Vertebrectomy of L1 and gross total tumor resection were performed. Histopathological and immunohistochemical findings of the tumor tissue supported the diagnosis of EHE. The case, which to the best of our knowledge is only the fifth such reported case, is presented with its clinicopathological findings and a review of the literature.

Modified experimental mild traumatic brain injury model.

BACKGROUND: Experimental models of traumatic brain injury (TBI), using a variety of techniques and species, have been devised with the aim of producing repeatable lesions resembling those found in head injuries. There are various TBI models mentioned in the literature. In experimental head trauma models, emphasis has been placed on the severe head injuries. There are only a few models developed to study mild traumatic brain injury (MTBI). In fact, MTBI is as important a problem as severe head injuries for neurosurgeons. METHODS: Fifty-six male Sprague-Dawley rats were subjected to MTBI with a weight-drop device, which was described by Marmarou et al. The said model was used in its original form as well as in modified forms by employing different weights dropped from the same height. Animals were divided into four groups of 14 rats as follows: Group I (n=14), head injury was induced using 450 g-1 m weight-height impact; Group II (n=14), head injury was induced using 350 g-l m weight-height impact; Group III (n=14), head injury was induced using 300 g-1 m weight-height impact; Group IV (n=14), control group, no injury was applied. Animals were evaluated neurologically, physiologically, electrophysiologically, and histopathologically. RESULTS: Group I and II animals (450 and 350 g-1m weight-height impact, respectively) showed the symptoms of severe head injury, whereas Group III animals (300 g-l m) showed more MTBI symptoms. CONCLUSION: We recommend the application of the modified MTBI model used for group III (300 g-l m weight-height impact) as the most appropriate and the simplest model for future MTBI studies.

Effect of systemic creatine monohydrate supplementation on denervated muscle during reinnervation: experimental study in the rat.

The purpose of this experimental study was to evaluate possible upgrading effects of systemic creatine monohydrate administration on the reinnervation of denervated muscle. At the same time, the protective effect of the agent on denervated muscle until ultimate reinnervation after nerve repair was quantified. The functional outcome of muscle reinnervation after creatine monohydrate application was compared with a control group. Forty adult Wistar rats weighing 180 to 220 g were used. The right sciatic nerve was dissected, exposed, and cut at the level of the midthigh in all rats. The experimental design consisted of two groups: experimental (animals were fed creatine monohydrate) and control (gavage feeding was provided by saline). Both groups were divided into two subgroups: subgroups A and B for the experimental group, and subgroups C and D for the control group. In subgroups A and C, the nerves were repaired with four 10-0 epineurial stitches. In subgroups B and D, both the proximal and distal ends of the nerves were ligated and no neural anastomosis was performed. In the experimental groups (subgroups A and B), the rats were fed by daily supplementation of oral creatine monohydrate, 300 mg/kg body weight. In the controls (subgroups C and D), oral supplementation was provided by saline. Functional recovery was evaluated using walking track analysis, pinching test, and limb circumference and toe contracture measurements at the end of 6 months, after which the rats were sacrificed and nerve specimens from both ends of the repair sites and the whole gastrocnemius muscle were obtained to document the results of the histomorphometric and histochemical studies, including light microscopic examinations and muscle weight measurements. The mean functional recovery values in subgroups A, B, C, and D were 91 percent, 80 percent, 87 percent, and 59 percent, respectively. Functional recovery improved significantly in the experimental groups (in both the surgically repaired and unrepaired subgroups), compared with the control groups (p<0.05). The pinching test revealed a statistically significant difference in nerve conduction between the experimental and control groups (p<0.05). The limb circumference ratio of the surgically treated side to the untouched side in subgroups A, B, C, and D were noted as 0.95, 0.89, 0.91, and 0.87, respectively, and the difference between the experimental and the control groups was statistically significant (p<0.05). The differences between subgroups A and B, C and D, A and C, and B and D were also significant. The surgically repaired and creatine-supplemented subgroups demonstrated the best results in toe contracture index. The muscle weight measurement results were concordant with the results of the limb circumference ratio. In both surgically repaired subgroups (subgroups A and C), there were qualitatively significant amounts of myelinated fibers in the nerve distal to the anastomotic site; there were no myelinated fibers in the distal stumps of subgroups B and D. Histochemical analyses of the contents of the muscle fiber types also revealed no significant difference. Overall, the results showed the useful effect of oral creatine supplementation on both surgically repaired and unrepaired nerve injuries. The best results were obtained from surgically repaired nerve injuries and also from the systemic creatine-supplemented subgroups. This study confirms that systemic administration of creatine monohydrate has a protective and upgrading effect on the functional properties of denervated muscle, especially in surgically reinnervated subjects.