Chemobrain in blood cancers: How chemotherapeutics interfere with the brain's structure and functionality, immune system, and metabolic functions.

Cancer treatment brings about a phenomenon not fully clarified yet, termed chemobrain. Its strong negative impact on patients' well-being makes it a trending topic in current research, interconnecting many disciplines from clinical oncology to neuroscience. Clinical and animal studies have often reported elevated concentrations of proinflammatory cytokines in various types of blood cancers. This inflammatory burst could be the background for chemotherapy-induced cognitive deficit in patients with blood cancers. Cancer environment is a dynamic interacting system. The review puts into close relationship the inflammatory dysbalance and oxidative/nitrosative stress with disruption of the blood-brain barrier (BBB). The BBB breakdown leads to neuroinflammation, followed by neurotoxicity and neurodegeneration. High levels of intracellular reactive oxygen species (ROS) induce the progression of cancer resulting in increased mutagenesis, conversion of protooncogenes to oncogenes, and inactivation of tumor suppression genes to trigger cancer cell growth. These cell alterations may change brain functionality, as well as morphology. Multidrug chemotherapy is not without consequences to healthy tissue and could even be toxic. Specific treatment impacts brain function and morphology, functions of the immune system, and metabolism in a unique mixture. In general, a chemo-drug's effects on cognition in cancer are not direct and/or in-direct, usually a combination of effects is more probable. Last but not least, chemotherapy strongly impacts the immune system and could contribute to BBB disruption. This review points out inflammation as a possible mechanism of brain damage during blood cancers and discusses chemotherapy-induced cognitive impairment.

[Chemotherapy-related Cognitive Impairment in Patients with Hodgkin Lymphoma - Pathophysiology and Risk Factors]. / Poskození kognitivních funkcí po chemoterapii u pacientu s Hodgkinovým lymfomem - patofyziologie a rizikové faktory.

BACKGROUND: Cognitive impairment (impairment of memory, attention, or concentration) is documented in 17-75% of patients with various malignancies treated with chemotherapeutic agents that worsen quality of life. CRCI affects patients of all ages. The impairment of cognitive function in connection with chemotherapy is usually mild, but an event. relationship with dementia remains to be confirmed. Chemotherapy in combination with radiotherapy in Hodgkin lymphoma can cure 80-90% of patients. AIM: This review summarizes the most frequently observed changes in cognitive function in patients suffering from CRCI. The article further describes the possible pathophysiological mechanisms behind these changes and the risk factors that can increase the likelihood of cognitive functional impairment after chemotherapy of malignant tumors. Special attention is given to how this relates to Hodgkins lymphoma. We also discuss the neuroprotective factors involved in chemotherapy-related cognitive impairment and its treatment options. CONCLUSION: Changes occur mainly in the ability to learn and remember, in the speed of reactions, and in attention and executive functions. Although CRCI pathophysiological mechanisms are complex and not yet fully understood, the involvement of neurotoxicity, such as that induced by treatment, anemia, higher levels of oxidative stress and inflammatory responses, genetic factors, and reduced brain connectivity is discussed. CRCI is further modified by comorbidities and patient age. Pharmacological and nonpharmacological treatment options for CRCI are outlined.Key words: Hodgkin lymphoma - chemotherapy - cognitive impairment - risk factors The project was supported by the grant of the Agency for the Czech Republic Health Research of the Ministry of Health of the Czech Republic 16-29857A and by the project Sustainability for the National Institute of Mental Health No. LO1611 with a financial support of the Ministry of Education, Youth and Sports of the Czech Republic in the frame of the National Sustainability Programme I. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 9. 2016Accepted: 12. 2. 2017.

On a simple way to calculate electronic resonances for polyatomic molecules.

We propose a simple method for calculation of low-lying shape electronic resonances of polyatomic molecules. The method introduces a perturbation potential and requires only routine bound-state type calculations in the real domain of energies. Such a calculation is accessible by most of the free or commercial quantum chemistry software. The presented method is based on the analytical continuation in a coupling constant model, but unlike its previous variants, we experience a very stable and robust behavior for higher-order extrapolation functions. Moreover, the present approach is independent of the correlation treatment used in quantum many-electron computations and therefore we are able to apply Coupled Clusters (CCSD-T) level of the correlation model. We demonstrate these properties on determination of the resonance position and width of the (2)Πu temporary negative ion state of diacetylene using CCSD-T level of theory.

[Prevalence of selected congenital anomalies in the Czech Republic: congenital anomalies of the central nervous system and gastrointestinal tract]. / Prevalence vybraných vrozených vad v Ceské republice - vývojové vady centrálního nervového systému a zazívacího traktu.

OBJECTIVE: Analysis of the prevalence of selected congenital anomalies in the Czech Republic in 1994-2009. DESIGN: Retrospective epidemiological analysis of the postnatal and overall (including prenatally diagnosed cases) prevalence of congenital anomalies from the database of the National Registry of Congenital Anomalies of the Czech Republic. MATERIAL AND METHODS: Data from the National Registry of Congenital Anomalies (NRCA) maintained by the Institute of Health Information and Statistics of the Czech Republic (IHIS CR) were used. The analysis was carried out for the entire Czech Republic, based on the data from 1994 to 2009. Additional data on prenatally diagnosed anomalies were obtained from medical genetics centres and laboratories in the Czech Republic. This study analyzed the postnatal and overall (including prenatally diagnosed cases) prevalence of congenital anomalies. More detailed analysis was carried out for the following diagnoses: anencephaly, spina bifida, encephalocoele, congenital hydrocephalus, omphalocoele, gastroschisis, oesophageal atresia and stenosis, anorectal anomalies, and diaphragmatic hernia. Prevalence trends were analysed using Poisson regression. RESULTS: In 2009, a total of 118 348 live births were recorded in the Czech Republic, 60 368 boys and 57 980 girls. Of this total, 4 653, i.e. 2 745 boys and 1 908 girls, were diagnosed with congenital anomalies. In 2007-2009, the total of life births with congenital anomalies ranged between 4.6 and 4.8 thousand per year. The respective ranges in this three-year period were in the order of 2.7 and 2.8 thousand per year for boys and 1.9 thousand per year for girls. The prevalence of postnatally diagnosed anencephaly was minimal, as most cases were diagnosed prenatally, and the data did not vary significantly. The prevalence of postnatally diagnosed cases remained at the same level. The effectiveness of the prenatal diagnosis of spina bifida increased and thus the prevalence of postnatally diagnosed cases decreased. The prevalence of prenatally diagnosed encephalocoele increased and that of postnatally diagnosed cases varied between years, with no clear trend. The prevalence of omphalocoele varied for both prenatally and postnatally diagnosed cases; nevertheless, the effectiveness of prenatal diagnosis of this defect increases. The prevalence of gastroschisis remained unchanged, but the number of live births with this diagnosis showed a non-significant upward trend. If the trend reflects the real situation, it could be a result of a changed approach to prenatal diagnosis due to advances in corrective surgery of this defect. The prevalence of live births with congenital hydrocephalus showed a downward trend in the second half of the period 1994-2009 thanks to the improved diagnosis. The prevalence rates of live births with congenital esophageal and anorectal anomalies were slightly increasing. The prevalence of congenital diaphragmatic hernia varied between years but the overall prevalence appeared to be slightly increasing. CONCLUSION: The prevalence of some congenital anomalies (spina bifida, omphalocoele, and congenital hydrocephalus) showed a downward trend over the study period 1994-2009, mainly as a result of effective prenatal diagnosis. The prevalence of other congenital anomalies such as anencephaly or encephalocoele remained unchanged in live births. As for anencephaly, postnatally diagnosed cases were rare as the prenatal diagnosis was close to 100 %. The trend in encephalocoele is explained by the low incidence of this diagnosis in the population. The third group of postnatally diagnosed congenital anomalies such as gastroschisis or esophageal and anorectal anomalies were on the rise. As for gastroschisis, the reason was the changed approach to prenatal diagnosis due to good prognosis of this operable defect. The prevalence of congenital esophageal and anorectal anomalies varied between years, with a slowly increasing trend, similarly to diaphragmatic hernia.

[Implementation of arrays in first trimester prenatal diagnosis]. / Implementace array vysetrení do prenatální diagnostiky v I. trimestru.

OBJECTIVE: Array technology in chorionic villus sampling (CVS) - analysis of clinical benefit and a proposal of a more effective 1st trimester genetic testing policy. DESIGN: Retrospective study. SETTING: Gennet, Center of Medical Genetics and Reproductive Medicine, Prague. MATERIAL AND METHODS: Total of 913 CVS were performed at Gennet between 2010-2014. All 913 samples were tested by QF-PCR rapid test for aneuploidy of chromosomes 13, 18, 21, X and Y and karyotyping following standard long term culture. Microarray analysis (Illumina HumanCytoSNP12 v2.1) was performed on 179 samples with normal result from both - QF-PCR and karyotyping. RESULTS: At 229 samples the common chromosomal aneuploidy was detected using rapid QF-PCR (25% from 911 successful rapid tests). Conventional karyotyping revealed 239 unbalanced chromosome aberrations (27% from 897 successful cultivations). 227/239 (95%) positive karyotypes confirmed QF-PCR finding of common aneuploidies. 10 unbalanced chromosome aberrations were not covered by rapid QF-PCR test. Microarray analysis of samples with normal result from both- QF-PCR and karyotyping- revealed 13 clinically relevant chromosome aberrations (7.5%). CONCLUSION: New policy for chorionic villi testing at Gennet was established. Based on evaluation of the results of karyotyping, array and QF-PCR and analysis of published data we decided to replace karyotyping by microarray analysis in all cases of foetuses with normal results from QF-PCR. More effective detection of pathological and clinically relevant chromosome aberrations in examined foetuses is expected.

Differences in onset of disease and severity of psychopathology between toxoplasmosis-related and toxoplasmosis-unrelated schizophrenia.

OBJECTIVE: Toxoplasmosis is a lifelong parasitic disease that appears to be associated to schizophrenia. However, no distinguishing attributes in Toxoplasma-infected schizophrenia patients have been described as yet. METHOD: We searched for differences in symptom profile, cognitive performance and treatment response between 194 Toxoplasma-free and 57 (22.7%) Toxoplasma-infected schizophrenia patients treated in Prague Psychiatric Centre between 2000 and 2010. RESULTS: Infected and non-infected patients differed in severity of symptoms (P = 0.032) measured with the Positive and Negative Symptom Scale (PANSS). Infected patients scored higher in positive subscale of PANSS, but not in the general and negative subscales. Infected men scored higher also in Total PANSS score, and negative, reality distortion, disorganisation and cognitive scores. Higher PANSS scores of positive, negative and disorganised psychopathology were associated with the lower titres of anti-Toxoplasma antibodies suggesting that psychopathology deteriorates with duration of parasitic infection. Infected patients remained about 33 days longer in hospital during their last admission than uninfected ones (P = 0.003). Schizophrenia started approximately 1 year earlier in infected men and about 3 years later in infected women, no such difference was observed in uninfected subjects. CONCLUSION: Latent toxoplasmosis in schizophrenia may lead to more severe positive psychopathology and perhaps less favourable course of schizophrenia.

Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia.

OBJECTIVES: The aim of the presented study was to assess plasma glycogen phosphorylase BB (GPBB) concentrations in acute leukemia patients treated with anthracycline containing chemotherapy. BACKGROUND: Anthracyclines represent the highest risk for development of cardiotoxicity. GPBB belongs to proposed biomarkers of cardiac injury with a very limited experience in this context. METHODS: Totally, 24 adult patients with acute leukemia were enrolled. Plasma GPBB concentrations were measured by ELISA at diagnosis (before chemotherapy), after first chemotherapy with anthracyclines and 6 months after the completion of treatment. The cut-off value for GPBB positivity was 10.00 µg/L as recommended by the manufacturer. RESULTS: Before chemotherapy, the mean plasma GPBB concentration was 5.25±3.81 µg/L, increased above the cut-off in 1 patient (4.2 %). After the first chemotherapy, the mean GPBB was 6.61±5.54 µg/L, positive in 7 (29.2 %) patients. Six months after treatment, the mean GPBB was 10.06±11.41 µg/L, positive in 8 (33.3 %) patients. Six months after treatment, we found a significant correlation between elevation in GPBB and diastolic left ventricular dysfunction on echocardiography (r=0.621; p<0.0001). The differences in plasma GPBB between healthy blood donors and patients treated for acute leukemia were statistically significant (p<0.01 in all cases). CONCLUSION: Our results suggested that GPBB could become a potential biomarker for detection of acute and chronic cardiotoxicity associated with anthracycline containing chemotherapy. The predictive value for development of treatment-related cardiomyopathy in future is not clear and will be evaluated during the follow-up. Further studies are needed to define the potential role of GPBB and other biomarkers in the assessment of chemotherapy-induced cardiotoxicity (Ref. 21). Text in PDF www.elis.sk.

[Improving the quality of histopathological examination of colorectal cancer specimens through standard protocol implementation]. / Zvýsení kvality histopatologického hodnocení preparátu kolorektálního karcinomu prostrednictvím zavedení standardního protokolu.

INTRODUCTION: Detailed, high-quality histopathological examination of colorectal carcinoma is an essential component of accurate disease staging. The aim of this study was to evaluate the influence of standard pathological protocol implementation on the quality of colorectal cancer specimen evaluation. MATERIAL AND METHODS: The standard protocol for colorectal cancer specimens evaluation was created on the basis of the NCCN guidelines for colorectal carcinoma and in accordance with the American Joint Committee on Cancer (AJCC) recommendations. The protocol has been implemented into the practice of University Hospital Ostrava since 1 January 2013. All patients who underwent resection for colorectal cancer in University Hospital Ostrava between 1 January 2011 and 30 June 2013 were included into the study. Histopathological reports (before and after protocol implementation) were analysed with a focus on the presence of the parameters being monitored; the differences underwent statistical analysis. RESULTS: In total, 235 patients who underwent resection of colorectal cancer (184 patients before and 51 patients after protocol implementation) were included into the study. The mean number of investigated lymph nodes was 12.5±6.3 (colon) and 12.6±6.2 (rectum) before protocol implementation. The mean number of lymph nodes was 15.0±4.6 (colon) and 16.8±6.7 (rectum) after protocol implementation; the differences are statistically significant. Before protocol implementation, the limit of 12 investigated lymph nodes was not reached in 49 patients with colon carcinoma (43.8%) and in 32 patients with rectal carcinoma (44.4%). Statistically significant improvement was noted after protocol implementation - the limit of 12 lymph nodes was not reached in 5 patients (18.5%) with colon and 4 patients (16.7%) with rectal carcinoma. There were also differences in the number of macroscopic mesorectal excision quality evaluation, circumferential resection margin reports and signs of microscopic tumour aggressiveness, in favour of histopathological reports after standard protocol implementation. CONCLUSIONS: Our retrospective study proved that the implementation of the standard protocol for colorectal cancer resection specimens leads to an improved quality of definitive histopathological reports.

Alterations of sleep initiation in NREM parasomnia after sleep deprivation - A multimodal pilot study.

Objectives: NREM parasomnias also known as disorders of arousal (DOA) are characterised by abnormal motor and autonomic activation during arousals primarily from slow wave sleep. Dissociative state between sleep and wake is likely responsible for clinical symptoms of DOA. We therefore investigated potential dissociation outside of parasomnic events by using simultaneous 256-channel EEG (hdEEG) and functional magnetic resonance imaging (fMRI). Methods: Eight DOA patients (3 women, mean age = 27.8; SD = 4.2) and 8 gender and age matched healthy volunteers (3 women, mean age = 26,5; SD = 4.0) were included into the study. They underwent 30-32 h of sleep deprivation followed by hdEEG and fMRI recording. We determined 2 conditions: falling asleep (FA) and arousal (A), that occurred outside of deep sleep and/or parasomnic event. We used multimodal approach using data obtained from EEG, fMRI and EEG-fMRI integration approach. Results: DOA patients showed increase in delta and beta activity over postcentral gyrus and cuneus during awakening period. This group expressed increased connectivity between motor cortex and cingulate during arousals unrelated to parasomnic events in the beta frequency band. They also showed lower connectivity between different portions of cingulum. In contrast, the greater connectivity was found between thalamus and some cortical areas, such as occipital cortex. Conclusion: Our findings suggest a complex alteration in falling asleep and arousal mechanisms at both subcortical and cortical levels in response to sleep deprivation. As this alteration is present also outside of slow wave sleep and/or parasomnic episodes we believe this could be a trait factor of DOA.

Treatment of adult patients with acute lymphoblastic leukemia in the Czech Republic in the period 2007-2020.

BACKGROUND: Pediatric-inspired protocols with prospective monitoring of minimal residual disease (MRD) are considered the standard of intensive treatment for adults with acute lymphoblastic leukemia (ALL). They have been used in the Czech Republic since 2007. PATIENTS AND METHODS: Two hundred and ninety-seven patients aged 18-65 years were treated at five hematology centers between 2007-2020 according to the GMALL 07/2003 protocol. This is a retrospective analysis of their treatment outcomes. RESULTS: In the Ph-negative cohort, 189 (93.1%) patients achieved complete remission, 5 (2.4%) patients were refractory, and early mortality was 3.0%. Seventy (34.5%) patients experienced relapse in a median of 10.6 months. Overall survival (OS) at 3 and 5 years was 63.5% and 55.9%, disease-free survival (DFS) at 3 and 5 years was 54.5% and 49.7%, respectively. Young adults under 35 years of age (P = 0.015), patients without initial CNS infiltration (P = 0.016), with MRD negativity before consolidation treatment (P < 0.001), transplanted in the 1st complete remission (P < 0.001), and subjects treated after 2012 (P = 0.05) had significantly better overall survival. In a multivariate analysis, MRD at week 11 was the only independent factor affecting OS (HR 3.06; P = 0.006). For DFS, baseline CNS infiltration (HR 2.08; P = 0.038) and MRD at week 11 (HR 2.15; P = 0.020) were significant. In the Ph-positive cohort, 84 (89.4%) patients achieved complete remission, 1 (1.0%) patient was refractory, early mortality was 4.3%. Twenty-six (27.7%) patients relapsed in a median of 8.6 months. Survival at 3 and 5 years was 57.2% and 52.4% for OS and 50.2% and 44.9% for DFS, respectively. Transplanted patients and patients diagnosed after 2012 had statistically better overall survival (P < 0.001). CONCLUSION: The introduction of pediatric-inspired protocols with treatment intensification according to MRD levels resulted in a significant improvement in the survival outcomes of adult patients with ALL.

[Course of congenital malformation incidences and their changes over time in children born in the Czech Republic]. / Vývoj a zmeny incidencí vrozených vad u narozených detí v Ceské republice.

AIM OF STUDY: An analysis of incidences of selected birth defects in the Czech Republic in 2000 - 2008 period. TYPE OF STUDY: Retrospective epidemiological analysis of birth defects incidences in births and total birth defects incidences (including prenatally diagnosed cases) from the Czech National Birth Defects Register database. MATERIAL AND METHODS: Data from the National Birth Defects Register (Institute for Health Information and Statistics) in the Czech Republic in the 2000 - 2008 period were used along with data on prenatally diagnosed defects from particular departments of medical genetics. Sixteen selected defects (anencephaly, spina bifida, encephalocele, congenital hydrocephalus, coarctation of aorta, transposition of great vessels, hypoplastic left heart syndrome, Fallot tetralogy, omphalocele, gastroschisis, diaphragmatic hernia, oesophageal atresia and stenosis, anorectal malformations, Down syndrome, Edwards syndrome and Patau syndrome) were analyzed in detail. RESULTS: There were 119 570 live births (61 326 boys and 58 244 girls) in 2008. In the same period, 4664 live births with a birth defect (under the age of one year) were reported, out of which 2754 boys and 1910 girls. Mean incidence was 390.06 (449.08 in boys and 327.93 in girls) per 10 000 live births. In 1994 - 2006, totally 1 238 398 children were born, out of which more than 42 000 with a birth defect. In the 2000 - 2006 period, absolute numbers of diagnosed live births with birth defect varied between 3600 - 3800 cases per year while in 2007 and 2008 years absolute numbers raised over 4600 cases per year. During 2000 - 2008 period following mean incidences (per 10 000 live births) of selected defects were ascertained (total incidences including prenatal diagnostics in brackets): anencephaly 0 - 0.3 (1.9 - 3.7), spina bifida 0.7 - 2.3 (3.2 - 5.2), encephalocele 0.1 - 0.4 (0.9 - 2.4), congenital hydrocephalus 1.6 - 3.5 (5.3 - 7.0), coarctation of aorta 3.9 - 5.2 (4.8 - 6.1), transposition of great vessels 2.9 - 4.5 (3.2 - 5.0), hypoplastic left heart syndrome 0.7 - 2.3 (2.2 - 4.3), Fallot tetralogy 2.6 - 4.0 (3.2 - 4.4), omphalocele 1.0 - 1.7 (1.8 - 3.8), gastroschisis 0.2 - 1.2 (2.4 - 3.4), diaphragmatic hernia 1.3 - 2.9 (1.5 - 3.9), Down syndrome 3.3 - 6.5 (15.8 - 22.2), Edwards syndrome 0.2 - 1.0 (3.5 - 5.8) and Patau syndrome 0.2 - 1.0 (1.2 - 2.6). CONCLUSIONS: There has been no major change in birth defect incidences in live births in the Czech Republic in last years. Number of non-viable defects has decreased in stillbirths and in perinatal mortality in the Czech Republic. An incidence of some defects has decreased mostly due to a nation-wide system of prenatal diagnostics; some incidences remain stable in live-birth population in others incidences have increased. A total incidence has mostly increased (anencephaly being an exception) mostly due to an earlier prenatal diagnostics. In chromosomal syndromes, an increasing maternal age as well as a growing number of mothers of 35 years of age and over has contributed to the increased incidences.

[Prenatal diagnostics of birth defects in the Czech Republic--a fifteen-year period]. / Prenatální diagnostika vrozených vad v CR - patnáctileté období

AIM OF STUDY: An analysis of prenatal and postnatal incidences of selected birth defects and secondary prevention efficiency in the Czech Republic in 1994 - 2008 period. TYPE OF STUDY: Retrospective epidemiological analysis of birth defects data from particular centers of clinical genetics and prenatal diagnostics (prenatal data) and from the Czech National Birth Defects Register database (birth data). MATERIAL AND METHODS: Data from the National Birth Defects Register (Institute for Health Information and Statistics of the Czech Republic) were used along with data from particular centers of clinical genetics and prenatal diagnostics covering the whole area of the Czech and the 1994 - 2008 period. Total prenatal diagnostics efficiency and an efficiency of prenatal diagnostics of 5 selected defects (anencephaly, spina bifida, omphalocele, gastroschisis and Down syndrome) were studied. RESULTS: In the period under study the number of prenatally diagnosed birth defects has increased. In 1994, the incidence of prenatally diagnosed (and selectively terminated) birth defects was 27.40 per 10 000 live births while in 2008 it was 73.26 per 10 000. In prenatally diagnosed but not terminated defects the corresponding numbers were 8.91 in 1994 and 32.87 in 2008. In last years, a quality change in prenatal birth defects screening has taken place in the Czech Republic. A first trimester screening with an increased efficiency not only for Down syndrome (DS) has been used more often implicating a wider application of chorionic villi sampling (CVS). An increased screening efficiency also made possible a relative decrease of invasive prenatal diagnostics procedures necessary to diagnose a single case of Down syndrome. When comparing CVS and amniocentesis from this particular point of view a higher CVS efficiency (about 12 CVS versus some 120 amniocenteses per 1 case of DS). Prenatal diagnostics efficiency has increased in all defects under study over the 1994 - 2008 period, being about 80% in DS almost 10% in anencephaly, 65 - 68% in omphalocele and gastroschisis and 80% in spina bifida in last years. CONCLUSIONS: Chromosomal aberration (DS especially) are among the most frequent prenatally diagnosed birth defects, further being heart defects, neural tube defects (anencephaly, encephalocele, spina bifida), hydrocephalus, congenital skeletal system defects, abdominal wall defects (omphalocele, gastroschisis) and renal defects. In some defects, prenatal diagnostics has also significantly influenced their incidence in births (anencephaly, gastroschisis and DS e.g.).

[Validity of the oncological cytodiagnostics and colposcopy examination versus biopsy in cervical carcinoma prevention]. / Validita onkologické cytodiagnostiky a kolposkopie versus biopsie v prevenci rakoviny cervixu.

THE AIM OF THE STUDY: The basic praebioptic methods detecting the precancerous lesions of the uterine cervix are oncologic cytology (PAP smears) and colposcopy. However in the Czech Republic the incidence of the invasive carcinomas during the last 10 years did not considerably decrease. Therefore the goal of our study is to estimate the validity of the prebioptic methods and compare the results of praebioptic methods (procedures) versus biopsy. TYPE OF THE STUDY: Analysis of the results of the oncologic cervical cytology comparing with the results of cervical biopsies performed during the years 2002-2003 were compared to those of the year 2009. THE SUBJECT AND METHODS OF THE STUDY: evaluation of the prebioptic methods (cytology, colposcopy) versus biopsy prior and during the start of the National Screening in the Czech Republic. SETTING: 1. Centre for Gynaecological Oncological prevention, 1st Faculty of Medicine, Charles University Prague, Department of Gynaecology and Obstetrics. 2. Institute of Physiology, Department of cybernetics, 1st Faculty of Medicine, Charles University, Prague. 3. Institute of Pathology, University of Ostrava. 4. Institue for Mother and Child Care, Prague. SUMMARY: We screened the documentation related to the treatment of 423 women with cervical lesions, examined at the Oncological prevention centre of the Obstetrical and Gynaecological Department of the 1st Faculty of Medicine Charles University Prague and the General Teaching Hospital in Prague 2. Results of the oncologic cytology, colposcopy and biopsy were compared. The comparison revealed differences related to the time of examinations. During the years 2002 and 2003 the agreement between cytologic diagnosis and biopsies in the group of HSIL was 40 %. In the year 2009 the agreement between HSIL and CIN was 68% the colposcopic diagnosis of precancerous lesions with those of bioptic specimens, during the years 2002 and 2003 was 90% while in the year 2009, during the National Screening, the agreement reached 98%.

[Primary hepatic neuroendocrine carcinoma]. / Primární neuroendokrinní karcinom jater.

UNLABELLED: Primary neuroendocrine carcinoma of the liver is a rare tumour, probably arising from scattered neuroendocrine cells of the bile duct. We present the case of a 72-year-old male who experienced gradual weight loss and diarrhoea. Given the fact that he had stayed in the Dominican Republic, a parasitic disease was initially suspected. However, this was not confirmed. Further examination showed tumour infiltration of the liver. Fine needle aspiration cytology of the tumour site was performed. The diagnostic procedure revealed neuroendocrine carcinoma. The tumour cells expressed the following neuroendocrine markers (chromogranin, synaptophysin, CD56 and NSE) as well as the epithelial marker AE1-AE3. The tumour was considered metastasis of the primary tumour located in the gastrointestinal tract. A thorough clinical examination was performed including gastroscopy, colonoscopy, In-111 Octreoscan scintigraphy, computed tomography and magnetic resonance imaging. These methods revealed metastases in the vertebrae, pelvis, long bones and skull. No other tumour sites were found in the lungs, gastrointestinal tract or pancreas. The patient became increasingly cachexic and later died. An autopsy showed massive multicentric tumour infiltration of the liver. Histological examination revealed well differentiated neuroendocrine carcinoma which transformed into intermediate and small cells. The autopsy found no tumour sites in the gastrointestinal tract, lungs or pancreas. The results were suggestive of primary neuroendocrine carcinoma of the liver. KEYWORDS: neuroendocrine carcinoma - liver - primary tumour.

[Surgical treatment of complicated hepatic echinococcosis in two Bulgarian citizens at two surgical departments in the Czech Republic]. / Chirurgické resení komplikované jaterní echinokokózy u dvou bulharských obcanu na dvou pracovistích v Ceské republice.

Echinococcosis, also referred to as hydatidosis, is a parasitic infection caused by the tapeworm Echinococcus in its larval stage. It has worldwide distribution and endemic areas in Europe include especially the regions surrounding the Mediterranean Sea. In the Czech Republic, its incidence tends to be quite rare. Although it may affect any organ or tissue in the human body, the liver (60%) and lungs (20%) are the most frequently affected sites. The authors present two cases of Bulgarian patients with hepatic echinococcosis operated on the same day at two different surgical departments in the Czech Republic. Treatment is based on the surgical removal of the cysts in combination with anti-parasite treatment by benzimidazoles (Albendazol, Mebendazol). Treatment with anti-parasitic drugs needs to be started preoperatively and should continue for at least 1-2 months after surgery. The success of the treatment can be monitored by imaging methods, especially PET/CT and serology. Patients after surgical as well as conservative therapy need to be followed up on an outpatient basis due to the long-term risk of recurrence.

Novel concept suppressing plasma heat pulses in a tokamak by fast divertor sweeping.

One of the remaining challenges in magnetic thermonuclear fusion is survival of the heat shield protecting the tokamak reactor vessel against excessive plasma heat fluxes. Unmitigated high confinement edge localized mode (ELM) is a regular heat pulse damaging the heat shield. We suggest a novel concept of magnetic sweeping of the plasma contact strike point fast and far enough in order to spread this heat pulse. We demonstrate feasibility of a dedicated copper coil in a resonant circuit, including the induced currents and power electronics. We predict the DEMO ELM properties, simulate heat conduction, 3D particles motion and magnetic fields of the plasma and coil in COMSOL Multiphysics and Matlab. The dominant system parameter is voltage, feasible 18 kV yields 1 kHz sweeping frequency, suppressing the ELM-induced surface temperature rise by a factor of 3. Multiplied by other known mitigation concepts, ELMs might be mitigated enough to ensure safe operation of DEMO.

[Application of SNP array method in prenatal diagnosis]. / Aplikace metody SNP array v prenatální diagnostice.

OBJECTIVES: SNP array (array method using Single Nucleotide Polymorphisms) enables to detect cytogenetically undetectable submicroscopic alterations (microdeletions, microduplications), which could be also causative for ultrasonographic anomalies of fetus. This article describes the principle, advantages, disadvantages and application possibilities of the SNP array method in prenatal diagnosis. The ten month experience with SNP array use in prenatal diagnosis is presented. DESIGN: Prospective study. SETTINGS: Gennet, Prague. MATERIAL AND METHODS: During the period from April 2010 to January 2011 we performed 110 SNP array analyses of fetal DNA: 14 chorionic villi samples (CVS), 88 amniotic fluid samples (AMC), 1 cord blood sample and 7 miscarriage samples. Laboratory tests were carried out on DNA from both cultured and uncultured fetal cells. Examinations were performed in fetuses with sonographic abnormal findings having normal karyotype. In addition 14 fetal cytogenetic abnormalities were solved. SNP array analysis was performed using Illumina InfiniumHD HumanCytoSNP-12 chip. All data were analysed by Illumina KaryoStudio and GenomeStudio software. RESULTS: SNP array analysis was performed in 108 fetuses (only 2 examination failures, 1.8%). In total, we detected CNV (copy number variation) in 29 samples (29/108 = 27%). 15% (16/108) of fetuses with abnormal ultrasound findings were found to carry clinically relevant CNV. Probably benign CNVs were found in 8 samples (8/108 = 7%) and in additional 5 CNVs parental samples have not been analysed yet. Excluding karyotypically abnormal cases clinically relevant CNVs were found in 10% of fetuses (9/94). In all cases with de novo chromosomal aberration the clinical relevancy was clarified (imbalances in 50%). CONCLUSION: Our data suggest that SNP array analysis is a relevant and useful technique in prenatal diagnosis.

[Predictive factors for non-sentinel lymph nodes affection in breast carcinoma--outcomes of a Czech multicenter study of sentinel lymph nodes]. / Prediktivní faktory postizení nonsentinelových uzlin u karcinomu prsu--závery ceské multicentrické studie sentinelových uzlin.

BACKGROUND: The aim of the study was to assess positivity nonsentinel lymph nodes in patients with macro, micro and submicrometastases in sentinel lymph nodes and find predictive factors of positivity nonsentinel lymph nodes. Study was conducted at the Department of Surgery in Pardubice, Pilsen, Ostrava and Zlín. MATERIAL AND METHODS: Sentinel lymph nodes were assessed based on standards of Czech Pathological Society. Detection of sentinel lymph nodes was performed based on radionavigation or combination of radionavigation and blue dye method. RESULTS: In group N1 (macrometastases) there was found positivity of nonsentinel lymph nodes in 50% (45 from 90 patients). In group N1 Mi (micrometastases) there was found positivity of nonsentinel lymph nodes in 26.7% (16 from 60 patients). In group NO I+ (sub-micrometastases) there was found positivity of nonsentinel lymph nodes in 6.7% (1 from 15 patients). Predictive factors were size of metastasis, number of positive sentinel lymph nodes and grading. Size of tumor was not found to be a predictive factor of positivity nonsentinel lymph nodes. DISCUSSION: High positivity of nonsentinel lymph nodes in pacients with macro and micrometastases in sentinel lymph nodes advocates to perform axillary lymph nodes dissection. Due to small number of patients with submicrometastases it is not possible to assess if axillary dissection is necessary or not. Predictive factors of positivity of nonsentinel lymph nodes are size of metastasis in sentinel lymph nodes, number of positive sentinel lymph nodes and grading. Size of tumor was not found to be a predictive factor due to small tumors in the study. In spite of this it is necessary to consider it like a predictive factor of positivity nonsentinel lymph nodes. CONCLUSION: In patients with macro and micrometastases it is necessary to perform axillary dissection. In patients with submicrometastases in sentinel lymph nodes it is necessary to consider predictive factors.

Evaluation of serum levels of selected cytokine receptors in adult B-cell precursor acute lymphoblastic leukemia and their association with prognostic factors and survival.

AIM: To evaluate serum levels of selected cytokine receptors in B-cell precursor acute lymphoblastic leukemia (B-ALL) and their association with acknowledged prognostic factors, relapse-free survival (RFS) and overall survival (OS). MATERIALS AND METHODS: A total of 42 de novo adult B-ALL patients, 19 BCR/ABL positive, were included in this study. Soluble receptor α for IL-2 (sIL-2Rα), soluble receptor for IL-6 (sIL-6R), soluble receptor for TNF-α type I and II (sTNFR-1, sTNFR-2) and matrix metalloproteinase-9 (MMP-9) were measured by biochip array technology at diagnosis and in complete remission (CR). RESULTS: At diagnosis of B-ALL, we found significantly higher levels of sIL-2Rα, sIL-6R, sTNFR-1, sTNFR-2 and significantly lower levels MMP-9 in comparison with CR (p < 0.001 in all cases). BCR/ABL positive patients had higher levels of sIL-2Rα at diagnosis (r = 0.484; p = 0.014). Serum levels of evaluated cytokines were not associated with achievement of CR after one cycle of induction therapy, RFS or OS. CONCLUSION: Serum levels of all evaluated cytokines are significantly altered in newly diagnosed B-ALL reflecting activity of the disease. No significant correlations with response to first induction therapy, RFS or OS were found. Further studies with a longer follow-up will be needed.

Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect.

BACKGROUND: Theta cordance is a novel quantitative electroencephalography (QEEG) measure that correlates with cerebral perfusion. A series of clinical studies has demonstrated that the prefrontal theta cordance value decreases after 1 week of treatment in responders to antidepressants and that this effect precedes clinical improvement. Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has a unique rapid antidepressant effect but its influence on theta cordance is unknown. METHOD: In a double-blind, cross-over, placebo-controlled experiment we studied the acute effect of ketamine (0.54 mg/kg within 30 min) on theta cordance in a group of 20 healthy volunteers. RESULTS: Ketamine infusion induced a decrease in prefrontal theta cordance and an increase in the central region theta cordance after 10 and 30 min. The change in prefrontal theta cordance correlated with ketamine and norketamine blood levels after 10 min of ketamine infusion. CONCLUSIONS: Our data indicate that ketamine infusion immediately induces changes similar to those that monoamineric-based antidepressants induce gradually. The reduction in theta cordance could be a marker and a predictor of the fast-acting antidepressant effect of ketamine, a hypothesis that could be tested in depressive patients treated with ketamine.