Epidemiological Trends for Childhood and Adolescent Cancers in the Period 1994-2016 in the Czech Republic.

BACKGROUND: Our study aimed to evaluate incidence and mortality trends for childhood and adolescent cancers in the period 1994-2016 in the Czech Republic. MATERIAL AND METHODS: Data on childhood cancers, which are recorded in the Czech National Cancer Registry, were validated using a clinical database of childhood cancer patients and combined with data from the National Register of Hospitalised Patients and with data from death certificates. These validated data were used to establish cancer incidence. Data from death certificates were used to evaluate long-term trends in mortality. Incidence and mortality trends were assessed by the average annual percentage change. RESULTS: The age-standardised incidence trend for childhood cancers (i.e. those diagnosed in patients aged 0-19 years) showed a statistically significant slight long-term increase in the number of new cases, +0.5% annually on average (p < 0.01), more specifically an increase of +0.6% in girls and a statistically insignificant decrease of 0.1% in boys. In children aged 0-14 years, other malignant epithelial neoplasms and malignant melanomas showed the largest statistically significant average annual increase in incidence (+4.9%; p < 0.01), followed by central nervous system neoplasms (+1.3%; p < 0.05). Lymphomas, by contrast, showed a statistically significant average annual decrease in incidence in children aged 0-14 years (2.1%; p < 0.01). In adolescents aged 15-19 years, other malignant epithelial neoplasms and malignant melanomas also showed a statistically significant average annual increase in incidence (+5.2%; p < 0.01), followed by central nervous system neoplasms (+1.5%; p < 0.05). Mortality trends showed a statistically significant long-term decrease: on average, 5.1% annually in children aged 0-14 years (p < 0.01), and 3.7% annually in adolescents aged 15-19 years (p < 0.01). CONCLUSION: Available data make it possible to analyse long-term trends in childhood cancer incidence and mortality.

[Profile of Activation of Tyrosine Kinases and MAP Kinases in Therapy of Maffucci Syndrome]. / Profil aktivace receptorových tyrozinkináz a mitogenem aktivovaných proteinkináz v terapii Maffucciho syndromu.

BACKGROUND: Maffucci syndrome is a rare congenital nonhereditary disease characterized by multiple hemangiomas and enchondromas, which may progress into malignancy. The causal therapy does not exist, and therapy is aimed at complications. The determination of appropriate therapy is complicated, and a multidisciplinary approach is often essential. CASE: Authors are presenting the case of a 20-year -old patient with Maffucci syndrome. During her life, multiple enchondromas and progressing hemangiomas have been revealed and they have caused many complications, such as limited movement, growth failure, pain, fluidothorax and ascites. A profile of phosphorylation of selected tyrosine kinases and MAP kinases from progressing hemangioma was performed and with consideration of the result, it led to change of treatment strategy with encouraging clinical response lasting for six months.

Metronomic chemotherapy with the COMBAT regimen in advanced pediatric malignancies: a multicenter experience.

BACKGROUND: The outcome of children with refractory/relapsed malignancies remains poor and novel therapies are urgently required. One of the promising approaches is metronomic chemotherapy. We present the clinical results of 74 children with advanced solid tumors treated according to treatment recommendation with data registry in three European pediatric centers. METHODS: COMBAT (Combined Oral Metronomic Biodifferentiating Antiangiogenic Treatment) included low-dose daily temozolomide, etoposide, celecoxib, vitamin D, fenofibrate and retinoic acid. From 2004 to 2010, 74 children were enrolled. RESULTS: The 2-year overall survival (OS) was 43.1% (median 15.4, range 1.3-69.9 months). Of the 74 patients, 50 patients (68%) died and 24 are alive: 6 (8%) with progressive disease, 7 (9%) with stable disease/partial response and 11 (15%) in complete response. Median time to response was 6 months. Of 62 patients with initially measurable disease, 25 (40%) had radiological response or stable disease. Fourteen of 25 showing clinical benefit responded within the first 6 months. The treatment was well tolerated on an outpatient basis. Regarding non-hematological toxicity of grade ≥2, hepatotoxicity of grade 3 occurred in 8 children and grade 3 cheilitis in 16 children. CONCLUSION: COMBAT is a feasible and effective treatment option for patients with relapsing/refractory malignancies. The treatment is well tolerated with a low acute toxicity profile.

Rhabdomyosarcoma: molecular analysis of Igf2, MyoD1 and Myogenin expression.

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. There are two major histopathological types of RMS ­ embryonal (eRMS) and alveolar (aRMS). A molecular study of Igf2, MyoD1 and Myogenin was performed to determine the expression profiles and to assess the possible utility of these genes as potential treatment targets. Patients with RMS showed up to 100-fold increase of Igf2 transcription in comparison with normal skeletal muscle. Our data suggest that overexpression of Igf2 occurs in RMS of both histological subtypes. No correlation between the results of Igf2 mRNA expression and LOH at the 11p15 region (p= 0.12) was observed, but there was a trend of a higher expression of Igf2 mRNA in RMS samples with LOH. We observed a high level of MyoD1 mRNA in both aRMS and eRMS, and we detected a similar level of MyoD1 mRNA in RMS and normal skeletal muscles. There was a correlation between the results of MyoD1 mRNA expression and LOH at the 11p15 region.We did not observe any statistical difference in the level of Myogenin mRNA in the subgroups of RMS. Analogous to MyoD1, we observed a similar level of Myogenin mRNA in RMS and normal skeletal muscles.

[Treatment of invasive candidiasis--recommendations of professional]. / Lécba invazivní kandidózy--doporucení odborných spolecností.

National working group representing clinicians (hematologists, oncologists, infection diseases and ICU specialists), microbiologists, and different special medical societies and working groups prepared evidence-based guidelines for the treatment established fungal infection--invasive candidiasis in the adult hematology and ICU patients. These guidelines updated those published in the Czech Republic in 2003-2004. Evidence criteria of the Infectious Diseases Society of America (IDSA) were used for assessing the quality of clinical trials, and EORTC/MSG Consensus Group for definitions of invasive fungal disease.

[Treatment for invasiveness aspergillosis--recommendations of professionals]. / Lécba invazivní aspergilózy--doporucení odborných spolecností.

An increasing incidence of invasive aspergillosis is observed in most immunocompromised patients, and especially patients with acute leukemia and after hematopoietic stem cell transplantation. In order to decrease the mortality due to this infection, the clinicians need to optimise their treatment choice. The objective of these guidelines is to summarize the current evidence for treatment of invasive aspergillosis. The recommendations have been developed by an expert panel following an evidence-based search of literature with regard to current recommendation of European Conference in Infections in Leukemia and Infectious Diseases Society of America.

[Malignant tumors of long bones in children: differential diagnosis and the role of imaging methods]. / Maligní tumory dlouhých kostí u detí, diferenciální diagnostika, prínos zobrazovacích metod.

PURPOSE OF THE STUDY: The aim of the study was to analyze primary malignant tumors and tumor-like lesions of long bones, in relation to their localization, characteristics and distribution in age groups, in children and young adults, and to assess the role of radiography and magnetic resonance imaging (MRI) in their diagnosis. MATERIAL: Sixty-four patients, aged between 3 and 20 years, who were referred to us with the diagnosis of a suspected malignant long-bone tumor of osseous or cartilage origin in the period from 2000 to 2004 were included in the study. METHODS: Plain radiography and MRI were carried out on the same day. For MRI, the Magnetom Open Viva system (magnetic field strength of 0.2 T) was used and examination comprised a conventional STIR (corresponding to fat saturation) and a T-weighed sequence. Most patients also underwent post-contrast examination with paramagnetic contrast medium infusion. RESULTS: In 26 children (40.6 %) a primary malignant tumor of osseous or cartilage origin was diagnosed; one child (1.5 %) had a giant-cell tumor. The definitive diagnoses in 37 children (57.9 %) included osteomyelitis in 12, fatigue fracture in 11, posttraumatic myositis ossificans in three children, and miscellaneous diagnoses in the remaining 11 children (one, cartilaginous exostosis; three, unicameral bone cyst; two, non-ossifying fibroma; one, fibrous dysplasia; one, subperiosteal abscess; one, histiocytosis; one, foreign body; one, negative MRI findings). CONCLUSIONS: To confirm the diagnosis of a malignant long-bone tumor, high quality X-ray and MRI are essential; CT examination is recommended in specific indications. The results of imaging methods cannot be assessed without reference to each other. Primary malignant tumors of long bones usually involve a large soft-tissue mass, and an exclusively intraosseous localization is rare. Osteosarcoma often invades the epiphysis. In making the differential diagnosis of primary malignant bone tumors, special attention must be paid to differentiation from osteomyelitis or fatigue fractures. The majority of juvenile bone lesions of any origin are usually detected between 10 and 13 years of age. These pathologic lesions are most frequently localized in the distal or proximal transition zones between the diaphysis and metaphysis.

[Mirko Grmek, medical friend and professor]. / Mirko Grmek, medicus amicus professorque.

Some personal and professional memories about Mirko Grmek in Switzerland.

[Observations on Roman medicine]. / Réflexions sur la médecine romaine.

How far are we entitled to speak of Roman medicine at all? After the arrival of Greek medicine at Rome, the genuine medicine of the earlier Romans, the only one that may be qualified as authentically Roman, survived in rural areas only. Otherwise, medicine in Rome and her Empire was Greek by language and doctrine as well as by its practitioners. Nevertheless, there exists an important medical literature in Latin. Although its inspiration, its sources and its models are Greek, this literature reveals, here and there, the intention to bend that medicine imported from Greece towards the Roman medicine of the old times. It shows, too, a certain reshaping of the Greek substance according to specific Roman elements. This paper, which is just the beginning of a broader investigation, is based on the major work of Latin medical literature, i. e. Celsus's De medicina.

Peripheral venous complications of a hyperosmolar (960 mOsm) nutritive mixture: The effect of heparin and hydrocortisone. A multicenter double-blinded random study in 98 patients.

Peripheral intravenous nutrition with hyperosmolar solutions usually results in a high rate of venous complications. The aim of this multicenter double blind randomised study in 98 patients has been to measure: (a) tolerance by the peripheral veins being perfused with a protein-glucose-lipid nutritive mixture of 960 mOsm/l (group A, n = 33), (b) the protective effect of the additive to the nutritive mixture of either heparin: 1000 IU/1 (group B, n = 32) or heparin with hydrocortisone (5 mg/l) group C, n = 33). Tolerance by the veins was evaluated on a single vein site during a 48 h perfusion with 21 per day. The following complications: oedema, erythema, induration, thrombophlebitis led to the interruption of the perfusion. The rate of interruptions of perfusions for total venous complications and for thrombophlebitis has been respectively: at 24 h, in group A: 39 and 15%, in group B: 6 and 3%, in group C: 12 and 0%; at 48 h: in group A: 82 and 42%, in group B: 53 and 18%, in group C: 36 and 6%. Venous complication rates for 24 and 48 h were significantly lower in groups B and C (p<0.05) than in group A and there was no inter group difference between groups B and C. These results suggest that peripheral venous nutrition infusing 14.1 g of nitrogen and 8.5 MJ per day can be performed with a hyperosmolar solution of 960 mOsm/1, if that heparin be added to the nutritive mixture and the perfusion site be changed daily. Under these conditions the observed venous complications rate is equal to or less than 6% of cases.