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Clinical Oncology

FEBRUARY 28, 2020

[Non-surgical treatment of ovarian cancer]

PIKÓ Béla, LACZÓ Ibolya,, MARIK László

[The primary surgery with an optimal cytoreduction is an essential step during the treatment of the epithelial ovarian cancer because it determines the effectiveness of other therapeutic options as well. Immediately after the surgery a cytostatic infusion typically 40-42.5 degrees Celsius is pumped directly to the abdomen. During the systemic therapy the main point is the 6 months progression free survival because beyond this time the disease could be considered as platinum sensitive, inside this time as platinum refracter or resistant disease. The cytostatic treatment improved during the years from the alkylating agents through the platinum derivates to the administration of paclitaxel with several combinations of them and with more and more signifi cant results and less side effects. The most signifi cant targeted agents are the angiogenesis inhibitors (mainly the bevacizumab) and the PARP-inhibitors which prevents DNA repairs. In order to a PARP-inhibitor could be administered a platinum sensitivity is required while BRCA mutation not. Recently there are promising clinical researches with immunotherapy as well. The main benefi t of the hormonal therapy is the tolerability. Besides the signifi cant improvement in the systemic agents the role of radiotherapy is more and more decreasing, however the treatment of the whole peritoneal surface – mainly with the modern radiation techniques – could be an alternative solution for the chemotherapy. The palliative irradiation which relieve the symptoms could extend the drug-free period and the combination of radiation and chemotherapy could provide further possibilities.]

Clinical Neuroscience

NOVEMBER 30, 2020

The applications of transcranial Doppler in ischemic stroke


Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in­crea­sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro­em­boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en­chan­ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt.

Lege Artis Medicinae

JULY 01, 2020

[The significance of the identification of SARS-CoV-2 virus and the possible errors of the sampling method]


[The COVID-19 pandemic caused by SARS-CoV-2 virus while emerging suddenly and spreading throughout the globe challenged seriously also the modern medicine. Diag­nostic methods recognising viral infections of the upper airways developed essentially in the last 20 years, and it was specifically progressing during the SARS and MERS epidemics thus facilitating the recognition and identifica­tion of infections by influenza, RS- and adenoviruses as well. Nevertheless the present novel coronavirus (SARS-CoV-2) also de­mon­strated that the relatively simple procedures of naso- and oropharyngeal sampling are fallible too. Thus they may have a relatively high risk of false-negative outcomes. However the correct sampling prior the RT-PCR tests provides reliable diagnosis by high sensitivity and specificity. Thus improving the quality of sampling and avoiding failures by correct training and education of the personnel make more reliable the detection of viral infection or indicate recovery after the infection. Finally, this is a key issue while overcoming the present pan­demic.]

Clinical Neuroscience

MARCH 30, 2016

[Hungarian adaptation of a short eating disorder questionnaire (SCOFF)]

DUKAY-SZABÓ Szilvia, SIMON Dávid, VARGA Márta, SZABÓ Pál, TÚRY Ferenc, RATHNER Günther

[Aim - Eating disorders are becoming an increasingly relevant health issue, therefore the fast and accurate screening of people at risk is of great practical importance. The aim of SCOFF questionnaire is to assess this risk and the extent to which a person is affected, by using five simple yes or no questions. The objective of our study was to assess the validity of the Hungarian version of the test Methods - 777 medical students (210 men, 567 women, mean age 22.3±2.33 years) participated in the survey. The online questionnaire contained anthropometric data, the Eating Behaviour Severity Scale and, beside the SCOFF, the Eating Disorder Inventory (EDI). Results - The SCOFF is excellent at screening clinical eating disorders. Its sensitivity was 100% and specificity 85.1%. It is less efficient at detecting subclinical cases, but it does not show worse results than EDI. According to the data SCOFF is better at identifying more serious cases. Applying on the same sample SCOFF had higher sensitivity and lower specificity than EDI. Discussion - SCOFF is suitable for primary screening of eating disorders with a non-diagnostic purpose, taken two “yes” answers out of five as the critical margin, specified by the authors.]

Clinical Neuroscience

JANUARY 30, 2020

[Correction of the physiological artefacts at pre-surgical clinical functional MR]

KISS Máté, GÁL Andor Viktor, KOZÁK Lajos Rudolf, MARTOS János, NAGY Zoltán

[Introduction/aim of the study - Pre-surgical functional MRI (fMRI) is an important modality of examinations before brain surgery. There are several artefacts (e.g. motion, susceptibility) which may hinder the evaluation of fMRI data. Physiological artefacts (breathing, pulsation) also affect the sensitivity and specificity of anatomical localization. The aim of this study is to demonstrate the efficiency of physiological artefact identification and removal methods for presurgical evaluation. Materials and methods - Siemens Magnetom Verio 3T MRI scanner was used to collect data. The physiological parameters (breathing, pulse) were recorded with the MRI system’s built-in devices. Data from fourteen patients - with primary brain tumour - were evaluated with SPM12 utilizing the RETROICOR/RVHR tool to detect and decrease the effect of physiological artefacts. We compared the statistical maps obtained with and without the physiological correction using the Jaccard similarity coefficient, and ROI analyses. Results - Significant differences were found in the mean ROI values (p<0.0016) and the extensions of eloquent activations (p<0.0013), when using the physiological correction (RETORICOR/RVHR) based on convolution method. On the other hand, no significant differences were found between the ROIs’ standard deviations (F=0.28). The RETROICOR/ RVHR method helps to define the precise localisation of eloquent areas (p<0.009). The number of irrelevant (non-significant) voxels were increased (p<0.001). Conclusions - Minimising of physiological artefacts in fMRI data calculations, the (RETROICOR/RVHR) method based on convolution has been successfully adapted. This algorithm could be helpful before neurosurgical intervention. The activity pattern became more reliable. ]

Clinical Oncology

FEBRUARY 20, 2019

[Molecular subtypes and the evolution of treatment decisions in metastatic colorectal cancer]

RODRIGO Dienstmann, RAMON Salazar, JOSEP Tabernero

[Colorectal cancer (CRC) has clinically-relevant molecular heterogeneity at multiple levels: genomics, epigenomics, transcriptomics and microenvironment features. Genomic events acquired during carcinogenesis remain drivers of cancer progression in the metastatic setting. For example, KRAS and NRAS mutations defi ne a population refractory to EGFR monoclonal antibodies, BRAFV600E mutations associate with poor outcome under standard therapies and response to targeted inhibitors in combinations, while HER2 amplifi cations confer unique sensitivity to double HER2 blockade. Multiple rare gene alterations driving resistance to EGFR monoclonal antibodies have been described with signifi cant overlap in primary and acquired mechanisms, in line with a clonal selection process. In this context, sequential analysis of circulating tumor DNA has the potential to guide drug development in a treatment refractory setting. Rare kinase fusion events and complex alterations in genes involved in DNA damage repair have been described, with emerging evidence for targetability. On the other hand, transcriptomic subtypes and pathway activation signatures have also shown prognostic and potential predictive value in metastatic CRC. These markers refl ect stromal and immune microenvironment interactions with cancer cells. For example, the microsatellite instable (MSI) or POLE ultramutant CRC population is particularly sensitive to immune checkpoint inhibitors, while tumors with a mesenchymal phenotype are characterized by activation of immunosuppressive molecules that mandate stratifi ed development of novel immunotherapy combinations. In this manuscript we review the expanding landscape of targetable oncogenic alterations and signatures in metastatic CRC and discuss the clinical implementation of novel molecular diagnostic tests.]

Lege Artis Medicinae

OCTOBER 20, 2019

[Population-level QALY gain estimates with the use of cariprazine for patients with negative symptoms of schizophrenia in Hungary]

BENDES Rita, NÉMETH Bertalan, PITTER János György, KÓCZIÁN Kristóf, GÖTZE Árpád, KALÓ Zoltán

[INTRODUCTION - The loss in quality of life caused by mental illnesses has been growing in developed countries. This study aims to quantify the possible gains in quality of life by advantages of cariprazine therapy while treating patients with negative symptoms of schizophrenia in Hungary. Comparator therapy was defined as the currently available second-generation oral antipsychotic drugs. METHODS - In order to estimate the reachable gain in quality of life with cariprazine, an 8-state deterministic Markov cohort model was developed. Data was gathered from relevant scientific literature and public databases. The main assumptions regarding patient pathways have been validated by clinical experts, based on their real-life experience. The number of patients with negative symptoms of schizophrenia was estimated by the same methods as well. Sensitivity analyses were conducted on the input parameters. RESULTS - When compared with currently available second-generation oral antipsychotics, cariprazine generated an estimated increase of 0.05 quality-adjusted life years per patient in 2 years run. The deterministic sensitivity analysis confirmed the robustness of the results. Based on data of the National Health Insurance Fund and the scientific literature, a total gain of 450 quality-adjusted life years is expected at national level over a time horizon of 2 years. Even higher gains of QALY can be expected for longer time horizons. CONCLUSION - Based on conservative estimates significant health gain can be ge­ne­rated, if all patients with negative symp­toms of schizophrenia would receive the adequate cariprazine therapy in Hungary in­stead of the currently used se­cond-ge­ne­ration oral antipsychotic drugs. ]

Clinical Neuroscience

MAY 30, 2019

Somatosensory amplification absorption contribute to electrosensitivity


Background - Two trait-like characteristics, somatosensory amplification and absorption, have been associated with symptom reports and idiopathic environmental intolerances in past research. Purpose - As the two constructs are not connected with each other, their independent contribution to symptom reports and electromagnetic hypersensitivity, as well as their interaction can be expected. Methods - On-line questionnaire. Patients - 506 college students completed an on-line questionnaire assessing absorption, somatosensory amplification, negative affect, somatic symptoms, and electromagnetic hypersensitivity. Results - Somatosensory amplification (β = 0.170, p < 0.001) and absorption (β = 0.128, p < 0.001) independently contributed to somatic symptoms after controlling for gender and negative affect (R2 = 0.347, p < 0.001). Similarly, somatosensory amplification (OR = 1.082, p < 0.05) and absorption (OR = 1.079, p < 0.01) independently contributed to electromagnetic hypersensitivity after controlling for somatic symptoms, gender, and negative affect (Nagelkerke R2 = 0.134, p < 0.001). However, no interaction effects were found. Discussion - Somatosensory amplification and absorption independently contribute to symptom reports and electromagnetic hypersensitivity. Conclusion - The findings suggest that psychological mechanisms underlying symptom reports and electromagnetic hypersensitivity might be heterogeneous.

Clinical Neuroscience

MAY 30, 2019

[F-DOPA PET/MR based target definiton in the 3D based radiotherapy treatment of glioblastoma multiforme patients. First Hungarian experiences ]

SIPOS Dávid, TÓTH Zoltán, LUKÁCS Gábor, BAJZIK Gábor, HADJIEV Janaki, CSELIK Zsolt, REPA Imre, KOVÁCS Árpád

[Introduction - Radiotherapy plays important role in the complex oncological treatment of glioblastoma multiforme (GBM). The modern 3D radiotherapy treatments are based on cross-sectional CT and MR information, however more attention is being paid to functional hybrid imaging describing the biological and functional morphology of tumor lesions. 18F-DOPA is an amino acid tracer with high specificity and sensitivity, which may play an important role in the precise definition of target volume in the irradiation process of GBM patients. Our study presents the first experiences with 18F-DOPA based PET/CT/MR 3D irradiation planning process. Methods - In Hungary the 18F-DOPA radiotracer has been available for clinical use since September 2017. Between September 2017 and January 2018, at the Somogy County Kaposi Mór Teaching Hospital Dr. József Baka Diagnostic, Radiation Oncology, Research and Teaching Center 3 histologically verified glioblastoma multiforme patients received 18F-DOPA based 3D irradiation treatment. In the contouring process the native planning CT scanes were fused with the PET/MR series (T1 contrast enhanced, T2 and 18F-DOPA sequences). We defined 18F-DOPA uptake volume (BTV-F-DOPA), the T1 contrast enhanced MRI volume (GTV-T1CE), and the volume of the area covered by oedema on the T2 weighted MRI scan (CTV-oedema) in all patients. We also registered the BTV-F-DOPA volumes not covered by the conventional MR based target volumes. Results - Examining the 3 cases, the average volume of 18F-DOPA tumor was 22.7 cm3 (range 15.3-30.9; SD = 7.82). The average GTV T1 CE was found to be 8.7 cm3 (range 3.8-13.2; SD = 4.70). The mean CTV oedema volume was 40.3 cm3 (range 27.7-57.7; SD = 15.36). A non-overlapping target volume difference (BTV-F-DOPA not covered by CTV oedema area) was 4.5 cm3 (range 1-10.3; SD = 5.05) for PTV definition. Conclusion - Based on our results the tumor area defined by the amino acid tracer is not fully identical with the MRI defined T2 oedema CTV. 18F-DOPA defined BTV can modify the definiton of the PTV, and the radiotherapy treatment. ]

Clinical Neuroscience

MARCH 30, 2019

L-arginine pathway metabolites can discriminate paroxysmal from permanent atrial fibrillation in acute ischemic stroke

CSÉCSEI Péter, VÁRNAI Réka, NAGY Lajos, KÉKI Sándor, MOLNÁR Tihamér, ILLÉS Zsolt, FARKAS Nelli, SZAPÁRY László

Background - Atrial fibrillation (AF) is the most common arrhythmia diagnosed in clinical practice. We aimed to measure the L-arginine pathway metabolites as well as their ratios in patients with different types of AF or sinus rhythm and to explore the relationship among the markers and clinical variables in the subacute phase of acute ischemic stroke (AIS). Methods - A total of 46 patients with AIS were prospectively enrolled. The patients were divided into three groups based on diagnosis of either sinus rhythm, paroxysmal or permanent AF. Plasma concentration of the L-arginine pathway metabolites were analyzed at post-stroke 24 hours in the three rhythm groups. Besides, clinical variables and laboratory data were recorded. Results - Asymmetric dimetylarginine (ADMA) was significantly higher in patients with permanent AF compared to sinus rhythm (p<0.001). Both ADMA (p<0.001) and symmetric dimethylarginine (SDMA) (p<0.002) at 24 hours were significantly higher among patients with permanent AF compared to those with paroxysmal AF. The L-arginine/SDMA (p<0.031) ratios at 24 hours were significantly higher among patients with sinus rhythm compared to those with permanent AF. ROC analysis also revealed that plasma SDMA cut-off level over 0.639 μmol/L discriminated permanent AF from paroxysmal AF or sinus rhythm with a 90.9% sensitivity and 77.1% specificity. Neutrophil-lymphocyte ratio also showed significantly higher value in individuals with both paroxysmal and permanent AF (p=0.029). Conclusions - Plasma level of SDMA could discriminate permanent from paroxysmal AF in the subacute phase of ischemic stroke. In addition, an increased neutrophil-lymphocyte ratio may suggest inflammatory process in the evolution of atrial fibrillation.