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This study presents current recommendations of the Polish Association of Pediatric Surgeons (PTChD) regarding diagnostics and treatment of ovarian lesions in girls. They are based on many years of the authors' clinical experience as well as a review of international literature and include practical clinical guidelines. The recommendations were formulated in cooperation with the Polish Association of Pediatric Oncology and Hematology (PTOHD), Polish Pediatric and Adolescent Gynecology Section of the Polish Society of Gynecologists and Obstetricians (PTG) and Polish Pediatric Section of the Polish Society of Radiology (PLTR). Only better understanding of prepubertal ovarian biology and natural history of its pathology may help to introduce efficient and safe diagnostic and therapeutic strategies for girls. The prepared document has been supplemented with treatment algorithms. [ABSTRACT FROM AUTHOR]

Abstract Introduction Valproic acid is a commonly used anti-epileptic drug. Hematological toxicities are among the occasionally observed adverse effects of this medication. Case presentation We present the case of a 13-year-old Caucasian boy who demonstrated mild anemia 12 months after the introduction of valproic acid therapy. A bone marrow biopsy revealed maturation arrest of proerythroblasts. Conclusion Prompt diagnosis and valproic acid discontinuation resulted in the patient’s recovery.

Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992–2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72–125.75; p = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS. [ABSTRACT FROM AUTHOR]

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing. [ABSTRACT FROM AUTHOR]

Introduction: The authors aimed to answer the following questions: 1) What level of knowledge of type 1 diabetes do the parents of children and young adults with this disease have? 2) Will this level of knowledge increase after 1 year of observation? 3) Does improving the knowledge of young adults and their parents result in better metabolic control of the patients?Material and methods: This study included 227 patients between the ages of 5 and 20 years with type 1 diabetes. The research was conducted from March 2009 to June 2011. The following two time points were examined: the beginning of the study (test 1a) and one year later (test 1b). The knowledge levels of the patients and parents were obtained using a survey and a knowledge test.Results: Comparison of the results from the two study time points showed that the respondents had a significantly higher level of knowledge after 1 year (p = 0.001). The comparison of glycated hemoglobin levels between the two time points in patients with type 1 diabetes revealed that the levels were significantly higher at test 1b compared to test 1a (p = 0.0005).Conclusions: The parents of children and young adults with type 1 diabetes demonstrate a satisfactory level of theoretical knowledge of therapeutic conduct and self-monitoring principles. The test 1b results demonstrated a higher level of theoretical knowledge in all respondents and poorer metabolic control. Poorer metabolic control in some patients suggests that metabolic control in type 1 diabetes depends on factors other than education. Further research is necessary to determine these additional factors. [ABSTRACT FROM AUTHOR]

Iron overload resulting from the mutation of genes involved in iron metabolism or excess dietary intake has been reported to negatively influence human physical performance. The aim of this study was to test the hypothesis that adolescents bearing a hemochromatosis gene (HFE) mutation in contrast to adults with the same mutation will not experience iron accumulation and their aerobic capacity will be similar to that of age-matched controls. Thirteen boys participated in the study. Seven of them are carriers of H63D mutation in the HFE gene and six were wild type. Fitness levels were assessed using the cardiopulmonary exercise test. In addition, iron status and inflammatory markers were determined. We observed that cardiovascular fitness was significantly lower in the group bearing the HFE mutation compared to the control group. Moreover, the HFE mutation group achieved lower maximal power output compared to the control group. There were no differences in blood ferritin concentrations between the two groups which indicates similar amounts of stored iron. Obtained data do not confirm our hypothesis. On the contrary, it was demonstrated that HFE mutation is associated with a lower level of aerobic capacity, even in the absence of iron accumulation. [ABSTRACT FROM AUTHOR]

Background MYCN oncogene amplification is the most important prognostic factor in neuroblastoma. 25% neuroblastoma tumors have somatic amplifications at this locus but little is known about its constitutional aberrations and their potential role in carcinogenesis. Here, we have performed an array-CGH and qPCR characterization of two patients with constitutional partial 2p trisomy including MYCN genomic region. Results One of the patients had congenital neuroblastoma and showed presence of minute areas of gains and losses within the common fragile site FRA2C at 2p24 encompassing MYCN. The link between 2p24 germline rearrangements and neuroblastoma development was reassessed by reviewing similar cases in the literature. Conclusions It appears that constitutional rearrangements involving chromosome 2p24 may play role in NB development. [ABSTRACT FROM AUTHOR]

Context: The roles of interleukin 10 (IL-10) and IL-12 in regulation of cancer growth and Th1/Th2 immune responses towards cancer are unclear. Objective: To establish the prognostic significance of serum IL-10 and IL-12 in paediatric soft tissue sarcomas (STS). Materials and methods: ELISA determinations of cytokines were performed as pre-treatment in 59 children with STS and 30 healthy controls. Results: Elevated IL-10 and decreased IL-12 serum levels correlated with advanced disease, poor response to chemotherapy and poor outcome. IL-10 ≥ 9.5 pg/ml, IL-12 ≤ 65 pg/ml and lymph nodes involvement independently predicted poor overall survival (OS) in multivariate Cox analysis. Conclusion: Serum IL-10/IL-12 balance determination may facilitate to assess risk groups and prognosis in childhood STS. [ABSTRACT FROM AUTHOR]

Background: Since 1983 four consecutive unified regimens: acute myeloid leukemia-Polish pediatric leukemia/lymphoma study group (AML-PPLLSG) 83, AML-PPLLSG 94, AML-PPLLSG 98 and AML-BFM 2004 Interim, for AML have been conducted by the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG). In this paper, we review four successive studies on the basis of acute myeloid leukemia-Berlin-Frankfurt-Munster (AML-BFM) protocol, in which a stepwise improvement of treatment outcome was observed. Treatment results of the last protocol AML-BFM 2004 Interim are presented in detail. Methods: Three hundred and three patients with de novo AML were treated according to the AML-BFM 2004 Interim at 15 Polish centers from January 1, 2005 to June 30, 2011. A confrontation with previous treatment periods was based upon historical, already published data. Results: In four consecutive periods, 723 children were eligible for evaluation (208, 83, 195, and 237, respectively). Complete remission rates in consecutive periods were: 71, 68, 81 and 87 %, respectively. The 5-year overall survival rates, event-free survival rates, and relapse-free survival rates were 33, 32, and 45%, respectively for AML-PPLLSG 83 regimen; 38, 36, and 53 % respectively for AML-PPLLSG 94 regimen; 53, 46, and 65 % respectively for AML-PPLLSG 98 regimen, and 63, 52, and 64 % for AML-BFM Interim 2004, respectively. Incidence of early deaths and that due to complications (mainly infections) in the first remission decreased over time from 22 to 4.6 % and from 10 to 5.9 %, respectively. Conclusions: Despite continuous improvement in the treatment outcome, the number of failures still remains too high. Further progress seemed to be possible due to continued cooperation of oncology centers within large international study groups. [ABSTRACT FROM AUTHOR]

Introduction:Pre-treatment serum IL-10/IL-12 balance has been recently found deregulated in childhood soft tissue sarcomas (STS). Its role in STS monitoring and assessment of response to therapy is unknown. Objective:To establish whether serum IL-10 and IL-12 levels and their reciprocal ratios reflect childhood STS course and actual activity and whether G-CSF therapy and central vein catheter (CVC)- -related sepsis influence the interleukins levels. Materials and methods:ELISA determinations of serum interleukins were performed before treatment, in remission without complications (CR), at relapse and after treatment in 59 STS patients and during G-CSF administration and CVC-related sepsis (in 18) and also in 30 healthy controls. Results:In CR IL-10 declined and IL-12 increased as compared to pretreatment levels; in relapse IL-10 rose and IL-12 decreased significantly as compared to levels in CR. Also rates of IL-10, IL-12, and IL-10/IL-12 ratios recently estimated by us as of prognostic significance reflected well the STS course. During G-CSF therapy and CVC-related sepsis, IL-10 increased and IL-12 decreased significantly from levels in CR without complications. IL-10 levels and rates of IL-10 ⩾11 pg/ml in sepsis could falsely suggest relapse. However, IL-12 levels, rates of IL-12 ⩽60 pg/ml and/or simultaneous determination of both interleukins differed significantly from levels at relapse. Conclusion:Serial determinations of serum IL-10 and IL-12 reflected well the course of STS in children and enabled remission and relapse phases to be distinguished. To avoid G-CSF and sepsis influence, IL-12 and IL-10/IL-12 ratio and not IL-10 alone should be analysed [ABSTRACT FROM AUTHOR]

PI3K/AKT/mTOR pathway signalling is often upregulated in cancer, usually by the constitutional activation of growth factor receptors, amplification or mutation of PIK3CA and loss of tumour suppressor PTEN function. The way of PI3K/AKT/mTOR pathway activation in neuroblastoma (NB) is not well established. The study was performed on paraffin-embedded tissue sections from 106 patients with NB. The aim of the study was to analyse the mutational status of EGFR (exons 18-21), PIK3CA (exons 5, 6, 10 and 21) and PTEN (all exons) genes, as well as to assess expression of their protein products by immunohistochemistry. A novel mutation in exon 5 of PIK3CA, c.931 A>G (p.I311V), in two infantile tumours (2.7%) was identified. In addition some polymorphisms were found in all examined genes, including a novel one, c.285 A>T in PTEN. Polymorphism PIK3CA c.1060-17 C>A was significantly more frequent in extra-adrenal tumours. Polymorphism PIK3CA c.1145+54 A>G showed a tendency to be more frequent in children older than 18 months and in extra-adrenal tumours. Expression of EGFR was present in 95% of cases, PI3Kp110 in 92% of tumours and PTEN in all tumours (low in 39%) and did not correlate with the genetic alterations. EGFR and PTEN expression showed an association with tumour diffe rentiation. Mutations in the EGFR, PIK3CA and PTEN genes are infrequent in neuroblastoma. Both newly detected mutations in exon 5 of PIK3CA occurred in very low risk neuroblastic tumours in infants. EGFR, PI3Kp110 and TEN expression is a common feature of NB. [ABSTRACT FROM AUTHOR]