Lege Artis Medicinae

[Fulvestrant in metastatic breast cancer]

BITTNER Nóra

OCTOBER 20, 2011

Lege Artis Medicinae - 2011;21(10)

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Lege Artis Medicinae

[How diabetogenic is statin therapy?]

CSÁSZÁR Albert

[According to the latest guidelines, the goal in cardiovascular prevention is to achieve an LDL-cholesterol level no higher than 1.8 mmol/l in the high risk and extra high risk groups. According to international recommendations, statin should be used at the highest tolerable dose rather than any combination treatments. In a number of cases, higher doses are associated with increased side effects, which rarely affect liver enzymes and CK-parameters. A metaanalysis published in 2011 made it clear that higher statin doses compared with low-medium doses can increase the occurence of newonset diabetes by about 12%. This is presumably a class effect, which is not significant according to the guidelines, and which is much lesser than the benefits of this therapy in the prevention of cardiovascular events, thus, it obviously does not question the justification of statin treatment. However, the observed association implies that during statin therapy of nondiabetic patients, blood glucose control should be performed every year, and, if needed, an oral glucose tolerance test should be performed to detect the potential development of diabetes.]

Lege Artis Medicinae

[The Generous Patron: Marcell Nemes]

NAGY Zsuzsanna

Lege Artis Medicinae

[Neurological effects of tolperisone]

KOVÁCS Tibor

[Spasticity, as a result of cortical motor neuron injury, is a frequent symptom in neurological disorders. Tolperisone is a centrally acting muscle relaxant, which has been used for 50 years in clinical practice. Tolperisone has a membrane-stabilising effect and it inhibits voltage-gated sodium and calcium channels. Although it targets the central neural system, it has no sedative side effects, in contrast to other muscle relaxants. Besides clinical experiences of past decades, the efficacy of tolperisone has also been proved in a study fulfilling evidencebased criteria. In this double-blind, placebo- controlled, randomised, parallel group study, 78.3% of tolperisone-treated patients had an at least one-point reduction on the Asworth scale (a 5-grade scale used the measure spasticity), compared with 45% in the placebo-treated group. The excellent tolerability of tolpe-risone is demonstrated by the finding that the number of adverse events was greater in the placebo group than in the tolpe-risone group. Taking these facts in consideration, tolperisone is a safe and effective drug to treat spasticity.]

Lege Artis Medicinae

[Shipwreck at the Island of the Glad People ]

GAJDOS Ágoston

Lege Artis Medicinae

[Societal burden of blindness in Hungary]

NÉMETH János, NAGYJÁNOSI László, NAGYISTÓK Szilvia, TOLNAYNÉ Csattos Márta, SZABÓNÉ Berta Irén, KINCSE Éva, SZULYÁK Eleonóra, BOÉR Ibolya, HUNDZSA Gyula, KALÓ Zoltán, BERTA András

[OBJECTIVES - Blindness represents a significant health and economic burden worldwide as well as in Hungary. The aim of this research was to estimate medical and nonmedical expenses related to blindness of elderly patients (>60 years) in Hungary so that the results can be used for further analyses. METHODS - The data required for determining the socioeconomic burden of disesase were derived from the published literature, statistical databases and estimations of relevant experts. We divided the social burden of elderly blindness into public and private medical and nonmedical costs. In addition to direct costs (social care and subvention, conduct recourse, medical costs) indirect costs and lost revenues (unemployment, support to activities of daily living) were also calculated. RESULTS - The social burden of elderly blind patients was estimated as 53.35 million USD in 2009, 0.03% of the Hungarian GDP (1 USD = 128.19 HUF in purchasing power parity exchange rate). Social care and subventions (20.04 million USD) and support to everyday activities (15.91 million USD) represented the largest proportion of expenses of the 6051 elderly blind people. The burden on the public sector was 55% of the total burden, which means that the population bears almost half of the burden. Social subventions represented two-third of the public burden. CONCLUSION - Blindness of the elderly means a significant economic burden, which is further exacerbated by the health loss - excess mortality, deterioration of quality of life - not evaluated in our study. Prevention and treatment of blindness in the elderly and social integration of blind people is an important task from a social as well as a health policy aspect.]

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Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Extraskeletal, intradural, non-metastatic Ewing’s sarcoma. Case report

OTTÓFFY Gábor, KOMÁROMY Hedvig

Intracranial localization of Ewing’s sarcoma is considerably very rare. Herein, we present clinical and neuroimaging findings regarding a 4-year-old boy with intracranial Ewing’s sarcoma. He was born prematurely, suffered intraventricular haemorrhage, posthaemorrhagic hydrocephalus developed, and a ventriculoperitoneal shunt was inserted in the newborn period. The patient endured re­gular follow ups, no signs of shunt malfunction nor increased intracranial pressure were observed. The last neuroima­ging examination was performed at 8 months of age. Upon reaching the age of 4 years, repeated vomiting and focal seizures began, and symptoms of increased intracranial pressure were detected. A brain MRI depicted a left frontoparietal space-occupying lesion infiltrating the superior sagittal sinus. The patient underwent a craniotomy resulting in the total excision of the tumour. The histological examination of the tissue revealed a small round blue cell tumour. The diagnosis was confirmed by the detection of EWSR1 gene translocation with FISH (fluorescent in situ hybridization). No additional metastases were detected during the staging examinations. The patient was treated in accordance to the EuroEwing 99 protocol. Today, ten years onward, the patient is tumour and seizure free and has a reasonably high quality of life.

Clinical Neuroscience

[Vinpocetin in neurological diseases]

SZAPÁRY László, KÉSMÁRKY Gábor, TÓTH Kálmán, MISNYOVSZKY Melinda, TÓTH Tímea, BALOGH Ágnes, NAGY Krisztián, NÉMETH György, FEHÉR Gergely

[Introduction - Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused territories may be associated with benefitial clinical states. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. Aims - The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. Results - Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheological variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. Summary - Based on the above mentioned results vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.]

Clinical Oncology

[Complications of infusion treatment with emphasis on extravasation of cytostatics]

HARISI Revekka

[The extravasation of cytostatics is the most signifi cant complication of infusion therapy in cancer treatment. Extravasation refers to the inadvertent infi ltration of cytostatic drugs into subcutaneous or subdermal tissues surrounding the intravenous or intraarterial administration site. According to literature data incidence estimates between 0,01-7%. Extravasated drugs are classifi ed according to their potential for causing damage as vesicant, irritant and nonvesicant. Knowledge of risk factors, the patientrelated and treatment-related ones is important to minimize the occurrence of extravasation. In order to reduce the risk of extravasation, the staff involved in the tumor infusion therapy must be specially trained to implement several preventive and therapeutical protocols. In 2012, ESMO-EONS has put together a new comprehensive treatment protocol on the topic of cytostatics extravasation. Protocol recommended that every oncological department, who administers chemotherapy have to have extravasation trained team and a standby extravasation kit. According to the new ESMO-EONS guideline subcutaneous corticoids are not recommended, anymore. In case of mechloretamine extravasation the recommendation is immediate subcutaneous injection of sodium thiosulfate. After extravasation of anthracyclines, mitomycin C and platin salts the best treatment opportunity is subcutan dimethyl sulfoxide administration. In case of anthracyclines’ extravasation intravenous dexrazoxane treatment is also effective. Hyaluronidase, injected into or under the skin, facilitates absorption of extravasated drugs because of increases connective tissue permeability, promotes the spreading and reduces the local concentration of the extravasated citostatic agents. Hyaluronidase might be effi cacious in preventing skin necrosis by extravasation due to vinca alkaloids. The treatment of unresolved tissue necrosis or pain lasting more than 10 days is surgical debridement. Because of the medical and juristic importance of the extravasation event, it is necessary to establish uniform guidelines for treatment of extravasation, in all Hungarian Oncological Centers.]

Clinical Neuroscience

[Occurence and molecular pathology of high grade gliomas]

MURNYÁK Balázs, CSONKA Tamás, HEGYI Katalin, MÉHES Gábor, KLEKNER Álmos, HORTOBÁGYI Tibor

[Background - Glial tumours represent the most frequent type of primary brain cancers. Gliomas are characterized by heterogeneity that makes the diagnosis, histological classification and the choosing of correct therapy more difficult. Despite the advances in developing therapeutic strategies patients with malignant gliomas have a poor prognosis; therefore glial tumours represent one of the most important areas of cancer research. There are no detailed data on the epidemiology of gliomas in Hungary. Methods - In the first section of our publication, we analysed the histological diagnosed cases between 2007 and 2011 at the Institute of Pathology, University of Debrecen Medical and Health Science Centre. We analyzed the incidence of 214 high-grade gliomas by tumor grades, gender, age, and the anatomical localization. Results - The majority of cases were glioblastoma (182 cases), and the remaining 32 cases were anaplastic gliomas. The mean age of patients was 57 years (±16.4), and the male:female ratio was 1.1:1. The most frequent area of tumors was the frontal lobe followed by the temporal, parietal and occipital lobe. We include new findings published recently about glioma patogenesis, molecular pathways, mutant genes and chromosomal regions. We explain briefly the role of selected important genes in glioma genesis and give an update on knowledge provided by modern molecular methods, which could beneficially influence future therapy and the diagnosis of gliomas.]