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The objective of this nation-wide study was to evaluate the epidemiology and profile of bacterial (BI), viral (VI), and invasive fungal disease (IFD) in patients treated for non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) between the years 2013-2015. In the analyzed period of time, within the studied group of 328 children diagnosed and treated for lymphomas, at least one infectious complication (IC) was diagnosed i.e. 39.3% children. In these patients there were 350 episodes of IC, therein 80.6% episodes of BI, 11.1% episodes of VI, and 8.3% episodes of IFD. In both groups, NHL and HL patients, a stable level of bacterial infections, with an increase in resistance rates, and increased levels of viral and fungal infections were observed. Profile of BI does not depend on lymphoma type, with predominance of Gram-negative bacteria and higher prevalence of MDR pathogens. The overall survival of lymphoma patients with IC was comparable for different types of infections.

The aim of the study was to asses QoL in Medulloblastoma (MB) survivors according to risk groups. MATERIAL AND METHOD: Between 2005-2015 132 patients (40 girls, 92 boys aged 2 9/12 – 17 6/12) were treated of MB. 44 patients were standard risk and 88 high risk. Patients in SR group received radiotherapy to CNS 25Gy whereas HR - 36Gy. Age at analysis 6 1/12 to 29. Analysis included 5 year EFS/OS and assessment of: weight/height in percentiles according to risk groups and age at diagnosis, hearing loss, hearing aids, hair loss and occurrence of posterior fossa syndrome(PFS). Psychosocial assessment, including IQ, education, work, physical and social activities, interpersonal relationships was performed and compared in risk groups. RESULTS: 5 years EFS was 83% in SR and 76,6% HR (p=0,112), OS 89,7% and 82,3%. There was no significant difference in hearing loss between risk groups, but there was greater use of hearing aids in the latter (p=0,003), hair loss was markedly worse in HR (p=0,022). SR patients and those older than 10 years at diagnosis were higher as compared to other survivors. PFS occurred more often in HR group (p=0,005). IQ, educational achievements, physical and social activity and interpersonal relationships were significantly better in SR group (p

Mesenchymal chondrosarcoma (MC) is an infrequent, highly malignant neoplasm of the soft tissues and bone. It is very rare in the pediatric age group, especially in the intraspinal location. Only 24 cases have been reported to date. The authors present a case of a 14-year-old boy with an intraspinal MC who died of the disease 50 months from the initial diagnosis and after the third local recurrence. The patient was treated with a combination of chemotherapy, radiotherapy, and surgery. The authors review the clinical presentation, diagnostics, and the efficacy of treatment of pediatric patients with MC reported in the literature from 1978 to 2010.

A phase II study of temsirolimus was conducted in children and adolescents with high-grade glioma, neuroblastoma or rhabdomyosarcoma.Temsirolimus 75 mg/m(2) was administered once weekly until disease progression or intolerance. Using the Simon 2-stage design, further enrolment in each disease cohort required ≥ 2 objective responses within the first 12 weeks for the first 12 evaluable patients (those who received ≥ 3 temsirolimus doses).Fifty-two heavily pretreated patients with relapsed (12%) or refractory (88%) disease, median age 8 years (range 1-21 years), were enroled and treated. One patient with neuroblastoma achieved confirmed partial response within the first 12 weeks; thus, none of the 3 cohorts met the criterion for continued enrolment. Disease stabilisation at week 12 was observed in 7 of 17 patients (41%) with high-grade glioma (5 diffuse pontine gliomas, 1 glioblastoma multiforme and 1 anaplastic astrocytoma), 6 of 19 (32%) with neuroblastoma and 1 of 16 (6%) with rhabdomyosarcoma (partial response confirmed at week 18). In the three cohorts, median duration of stable disease or better was 128, 663 and 75 d, respectively. The most common treatment-related adverse events were thrombocytopaenia, hyperlipidaemia and aesthenia. Pharmacokinetic findings were similar to those observed in adults.Temsirolimus administered weekly at the dose of 75 mg/m(2) did not meet the primary objective efficacy threshold in children with high-grade glioma, neuroblastoma or rhabdomyosarcoma; however, meaningful prolonged stable disease merits further evaluation in combination therapy.

AimThe aim of this study was to evaluate toxicity and response to fractionated reirradiation (FR) of relapsed primary brain tumors in children.BackgroundThe treatment options for recurrent brain tumors in children previously irradiated are limited. Reirradiation is performed with fear due to the cumulative late CNS toxicity and the lack of a significant chance of cure.Materials and methodsBetween 2008 and 2009, eight children with a median age of 14.5 years with a diagnosis of a recurrent brain tumor underwent reirradiation. Initially, all patients were treated with surgery, chemotherapy and radiotherapy. The median time to the first recurrence after the initial treatment was 19.5 months. Intervals between radiotherapy courses were in the range of 5–51 mos. All retreatments were carried out with 3D image-based conformal methods. The total prescription dose was 40Gy in a fraction of 5×2Gy/week. The total cumulative dose ranged from 65 to 95Gy (median: 75Gy). The median cumulative biologically effective dose was 144Gy (range: 126–181Gy).ResultsThe median overall survival and progression free survival measured from the beginning of reirradiation was 17.5 and 6.5 months, respectively. During the first evaluation, four patients showed a complete or partial response, two did not respond radiologically. Two children were progressive at the time of reirradiation. Among children with progression that occurred during the first year after reirradiation, only two progressed in the treatment area. The repeated irradiation was well tolerated by all patients. No late complications have been observed.ConclusionIn the absence of other treatment possibilities, the fractionated reirradiation with highly conformal three-dimensional planning could be a therapeutic choice in case of recurrent brain tumors in children. The control of craniospinal dissemination remains to be the main problem.

HER receptor family plays an important role in normal embryonic development and is involved in pathogenesis and progression of some types of cancer. Neuroblastic tumors (NT) are common pediatric neoplasms with a poor outcome in a significant number of patients. The biological and prognostic role of HER family in NT is not well established. In the current study we evaluated HER1-4 receptors expression, their prognostic significance and clinicopathological correlations in a series of 103 NTs by immunohistochemical assessment of HER1-4 expression and FISH analysis of EGFR and HER2 copy number status. HER receptors are commonly expressed in NT but it was not due to EGFR or HER2 amplification. EGFR, HER2 and HER4 show correlation with tumor histology. It seems that these receptors take part in neuroblastic cell differentiation and Schwannian stroma development. EGFR and HER2 positivity are more frequently found in favorable histological risk group of tumours (P = 0.004 and P = 0.01 respectively) while high expression of HER4 is significantly more often found in patients with metastatic disease (P = 0.03). Moreover tumors with HER2 polysomy were more often found in children ≤ 18 months, with localized disease, and favorable histological group. Our study showed that the role of HER family members in NT biology is interrelated and complex but their expression level may present a novel prognostic factor for NT patients outcome.

is caused by decreased or absent secretion of antidiuretic hormone. Neurogenic DI results from: brain tumors, neurosurgical interventions, congenital organic lesions, genetic defects, trauma, inflammatory or infiltrative processes. We describe a 19-year-old boy with a central DI caused by a sellar-suprasellar tumor. Based on characteristic history (4 years of polydipsia and polyuria), biochemical tests and imaging studies, DI was diagnosed in this boy at the age of 15 years. On his first MRI examination nodular thickening within the pituitary stalk was observed and treatment with desmopressin was started. After 4months, MRI revealed a large tumor within a sellarsuprasellar region. Based on the characteristic localization of the tumor and increased serum concentration of biomarkers [human choriongonadotropin β (β-hCG) and alpha fetoprotein (AFP)] germ cell secreting tumor was diagnosed. The boy underwent chemoand radiotherapy with a good outcome. Currently, at the age of 19 years, he is in remission. This patient is an example of diagnostic difficulties in case of DI, which can be caused by developing germ cell tumor. In each case of DI it is strongly advised to perform imaging studies (MRI) and repeat themwhen any abnormalities are found.

HER2 is essential for normal embryonic development and has a critical function in oncogenesis and progression of some types of cancer. Neuroblastic tumors create a heterogenous group of pediatric embryonal tumors of sympathoadrenal lineage. The biological and prognostic function of HER2 in these tumors is not well established. In this study, we evaluated the status of HER2, its prognostic significance, and clinicopathological correlations in series of 79 untreated neuroblastoma. The immunohistochemical assessment of HER2 and Ki-67 (proliferation index) as well as HER2 copy number status were performed on tissue microarrays. HER2 expression characterized 63 tumors, including 34 with low and 29 with high level, showing either membranous or mixed membranous-cytoplasmic pattern. Sixteen cases were HER2 immunonegative. The pattern of immunolabeling depended on the maturity of neuroblastic cells, being the most intense in differentiating neuroblasts. None of the tumors revealed HER2 amplification. In the examined group, 20% of patients died of disease from 4 to 107 months (median 18) from the diagnosis, and the survivors were followed up for 14-149 months (median 59). Patients' age, stage of disease, tumor location, mitosis/karyorrhexis index (MKI), and presence of HER2 expression were statistically significantly related to survival probability as detected by the Cox proportional hazard model. In the univariate analysis, Kaplan-Meier curves revealed significantly poorer outcome of HER2 negative than HER2-positive tumors (either low or high expression). The immunonegativity was associated with adverse clinicopathological parameters, including poor survival, metastatic stage of disease, un- or poorly differentiated histology, high MKI, and higher proliferation index. In conclusion, HER2 expression, not accompanied by gene amplification, is common in neuroblastic tumors. HER2 positivity seems to have a positive prognostic significance. HER2 expression with a variable pattern is a marker of the stage of neuroblastic cells differentiation.

Background Due to small number of patients with Nijmegen Breakage Syndrome (NBS) and Non-Hodgkin lymphoma (NHL) experience in their treatment is limited. Procedure Since 1996, 17 patients with a median age of 9.5 years who had NBS, were treated for NHL. NHL type, stage, chemotherapy, dose modifications, chemotherapy delays, response to chemotherapy, toxicity, outcome and correlation of drug reduction with response to treatment and outcome were analyzed. Results Nine patients had TNHL, eight BNHL. TNHL patients received BFM and BNHL LMB type protocols. Doses of cytostatics were reduced in the first chemotherapy courses. Further modifications depended on severity of complications. None of the patients complied with timing of chemotherapy. Complete remissions after induction were achieved in 8 of 9 TNHL and 3 out 8 of BNHL patients. All patients experienced grade 4 toxicities. Two patients died from complications. Six of 17 patients are alive. All received more than 80% of recommended doses of chemotherapy. No differences in the type, number of responses or grade 3 and 4 toxicities between patients receiving less or more than 80% of drug doses were observed. Treatment related deaths concerned patients who received less than 80% of drug doses. Conclusions Patients with NBS develop both T and B cell lymphomas. Treatment outcome is poor and might be improved by administering over 80% of drug doses. Although toxicity often depends upon drug doses, our patients experienced equal grade 3 and 4 toxicities whether they received more or less than 80% of the chemotherapeutic agents. Pediatr Blood Cancer 2009;52:186–190. © 2008 Wiley-Liss, Inc.

This analysis shows that the use of micafungin was successful in preemptive and targeted therapy in children with IFD in 85% pediatric hemato-oncology (PHO) and 60% allogeneic hematopoietic stem ce...

Background and purpose Craniospinal irradiation for medulloblastoma is one of the most complex techniques employed in radiotherapy. Many reports stress the impact of irradiation quality on survival in these patients. Our report presents the outcome and patterns of failure for 95 patients treated with 3D conformal radiotherapy (3D-CRT). Materials and methods From 1998 to 2003, 95 children with medulloblastoma received 3D conformal radiotherapy. All of them were previously treated with surgery and chemotherapy. The brain and upper spinal cord were treated with two lateral 6 MV photon fields. In four patients, the cribriform plate was irradiated by the additional field. For primary tumour bed we applied two or three photon beams. Spinal cord was irradiated either with 18–20 MeV electron fields or with a mixed beam. Results With a median follow-up of 48 months, 32/95 patients suffered a multifocal (21) or isolated (11) recurrence. We evaluated every primary site of failure. In all patients, the recurrence appeared within the isodose level of 95–100%. Conclusions Patterns of failure in medulloblastoma patients treated with 3D conformal radiotherapy indicated that the relapse was mainly associated with poor response to pre-irradiation chemotherapy. We believe that 3D conformal radiotherapy allows avoiding failures, related to radiotherapy uncertainties.

BACKGROUND Oral propranolol has been used to treat complicated infantile hemangiomas, although data from randomized, controlled trials to inform its use are limited. METHODS We performed a multicenter, randomized, double-blind, adaptive, phase 2-3 trial assessing the efficacy and safety of a pediatric-specific oral propranolol solution in infants 1 to 5 months of age with proliferating infantile hemangioma requiring systemic therapy. Infants were randomly assigned to receive placebo or one of four propranolol regimens (1 or 3 mg of propranolol base per kilogram of body weight per day for 3 or 6 months). A preplanned interim analysis was conducted to identify the regimen to study for the final efficacy analysis. The primary end point was success (complete or nearly complete resolution of the target hemangioma) or failure of trial treatment at week 24, as assessed by independent, centralized, blinded evaluations of standardized photographs. RESULTS Of 460 infants who underwent randomization, 456 received treatment. On the basis of an interim analysis of the first 188 patients who completed 24 weeks of trial treatment, the regimen of 3 mg of propranolol per kilogram per day for 6 months was selected for the final efficacy analysis. The frequency of successful treatment was higher with this regimen than with placebo (60% vs. 4%, P

Objective To analyze the incidence and outcome of infections with Staphylococcus spp. in children with malignancies treated in pediatric hematology and oncology (PHO) centers or undergoing hematopoietic stem cell transplantation (HSCT) over a period of 24 months. Patients and methods A total number of 1768 patients with malignancies and 308 patients undergoing HSCT in 2012–2013 were analyzed for microbiologically documented infection with Staphylococcus spp. Results During 24 consecutive months the incidence of Staphylococcus spp. infection was 6.7% in children with malignancy and 8.4% in patients undergoing HSCT (p = 0.3). At least two episodes of infection occurred in 11/118 PHO and in 7/26 HSCT patients. The first episode of infection occurred much earlier in HSCT than in PHO patients (p Conclusions The first episode of infection occurred much earlier in HSCT than PHO patients. The incidence of Staphylococcus spp. infection was similar in both groups of patients. Favorable outcome of the infection reached 96.4% and 95.1% episodes in PHO and HSCT patients, respectively.

Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13;q12) resulting in a chimeric EWS/ATF1 gene in which the 3'-terminal part of EWS at 22q is replaced by the 3'-terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases, 7 of which showed the characteristic t(12;22). As an initial step in the characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an exon/intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred, was to a large extent (83%) composed of repetitive elements. RT-PCR amplified EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10 patients. Four types of EWS/ATF1 chimeric transcript, designated types 1-4, were identified. The most frequent chimeric transcript (type 1) was an in-frame fusion of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5 patients but found together with other variants in 3 tumors. The type 2 transcript of EWS/ATF1, an in-frame fusion of exon 7 of EWS with exon 5 of ATF1, was detected in 4 patients, as the only transcript in 1 case and together with other variants in 3 cases. An in-frame fusion of exon 10 of EWS with exon 5 of ATF1 (type 3) was found in 1 patient as the only transcript, and an out-of-frame fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10, resulting in an out-of-frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon 4) was fused with EWS exon 8; at the junction, there was an insertion of 4 nucleotides, also resulting in an out-of-frame transcript. Genomic extra long PCR and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS and intron 3 and exon 4 of ATF1. While a simple end-to-end fusion was observed in 2 cases, additional nucleotides were found at the junctions in 2 other cases. In addition, topoisomerase I consensus sequences were found close to the junctions, suggesting that this enzyme may participate in the genesis of the EWS/ATF1 fusion.

We report a rare case of a mucosa-associated lymphoid tissue (MALT)-type lymphoma of the bladder, incidentally found on sonography in a 17-year-old girl during the workup of arterial hypertension. The diagnosis was established by a transurethral biopsy. Treatment consisted of transurethral resection of the bladder tumor and subsequent chemotherapy. To the best of our knowledge, this is the youngest patient with asymptomatic MALT-type lymphoma of the urinary bladder. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011

Ganglioglioma (GG) is a low-grade neoplasm, often associated with intractable epilepsy in pediatric patients. Available data suggest a relationship between GG and other glioneuronal lesions. So far, little is known about activation of kinases belonging to the mTor (mammalian target of rapamycin) pathway, although its upregulation is often found in brain tumors. Involvement of mTor kinase is responsible for excessive proliferation. In the current study we focused on the possible role of the Erk/Mapk (extracellular-signal-regulated kinase/mitogen-activated protein kinase) pathway in GG development. Eight GG tumors were resected from pediatric patients. Collected data reveal activation of proteins from the Erk pathway: Mek (extracellular regulated protein kinase kinase/mitogen-activated protein kinase kinase), Erk, Rsk1 (ribosomal S6 kinase 1), Rheb (Ras homolog enriched in brain) and Msk1 (mitogen- and stress-activated protein kinase 1), as detected by the western blot method. Moreover, activation of other proteins upstream of mTor - IGF-1R β (insulin-like growth factor 1β receptor), INR β (insulin receptor β), Akt/PKB (protein kinase B) - or downstream - 4E-BP1 (eukaryotic translation initiation factor 4E-binding protein 1) and rpS6 (ribosomal protein S6) - was also confirmed.

Background Undifferentiated embryonal sarcoma of the liver (UESL) represents less than 5% of all malignant hepatic tumors in childhood. It is considered an aggressive neoplasm with an unfavorable prognosis. The aim of this paper is to present a single center experience in the treatment of children with UESL. Materials and methods Ten children with UESL were treated between 1981 and 2012. Age at diagnosis ranged from 4 months to 17 years (median age, 6 years and 9 months). Surgery after neoadjuvant chemotherapy (CHT) was performed in 7 patients, and in 3 patients primary surgery was done. Adjuvant chemotherapy was administered in all 10 patients (CYVADIC, CAV, CAV/ETIF/IF + ADM, CDDP/PLADO). Right hemihepatectomy was performed in 1 patient, extended right hemihepatectomy in 6, and partial resection of the right lobe (segments V-VI, segment V) in 2 patients. One patient with unresectable tumor affecting both lobes was listed for liver transplantation (LTx). Results Follow-up from diagnosis ranged from 50 to 222 months (mean 138 months). Among 9 patients treated with partial liver resection, distant metastases/local recurrence was not observed in any, and disease-free survival in this group is 100% (9 patients alive). The patient that underwent liver transplantation died of multiorgan failure 4 months postoperatively. However, this patient was misdiagnosed as having hepatoblastoma (HBL) and received PLADO chemotherapy. The overall survival rate is 90%. Conclusion Excellent results with long-term survival can be achieved in children with UESL with conventional therapy, including a combination of neoadjuvant and adjuvant chemotherapy and surgery, even in large extensively growing tumors.

Molecular sub-classification is rapidly informing the clinical management of medulloblastoma. However, the disease remains associated with poor outcomes and therapy-associated late-effects, and the majority of patients are not characterized by a validated prognostic biomarker. Here, we investigated the potential of epigenetic DNA methylation for disease sub-classification, particularly in formalin-fixed biopsies, and to identify biomarkers for improved therapeutic individualization. Tumor DNA methylation profiles were assessed, alongside molecular and clinical disease features, in 230 patients primarily from the SIOP-UKCCSG PNET3 clinical trial. We demonstrate by cross-validation in frozen training and formalin-fixed test sets that medulloblastoma comprises four robust DNA methylation subgroups (termed WNT, SHH, G3 and G4), highly related to their transcriptomic counterparts, and which display distinct molecular, clinical and pathological disease characteristics. WNT patients displayed an expected favorable prognosis, while outcomes for SHH, G3 and G4 were equivalent in our cohort. MXI1 and IL8 methylation were identified as novel independent high-risk biomarkers in cross-validated survival models of non-WNT patients, and were validated using non-array methods. Incorporation of MXI1 and IL8 into current survival models significantly improved the assignment of disease-risk; 46% of patients could be classified as ‘favorable-risk’ (>90% survival) compared to 13% using current models, while the high-risk group was reduced to 16% from 30%. DNA methylation profiling enables the robust sub-classification of four disease sub-groups in frozen and routinely-collected/archival formalin-fixed biopsy material, and the incorporation of DNA methylation biomarkers can significantly improve disease-risk stratification. These findings have important implications for future risk-adapted clinical disease management.

BackgroundThis multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.MethodsPatients received temozolomide 100–125 mg/m2/day (days 1–5) and irinotecan 10 mg/m2/day (days 1–5 and 8–12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.ResultsSixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%–48.0%). Median duration of response was 27.0 weeks (7.7–44.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3% (95% CI, 22.0%–46.3%), and 68.3% (95% CI, 55.3%–79.4%) experienced clinical benefit. Median survival was 16.7 months (95% CI, 13.3–19.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and lymphopenia (9%).ConclusionsThe planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting.

This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.

We present two different cases of congenital intramedullary tumours, one of a patient in whom treatment was started without pathological confirmation of a malignant tumour and the other of a primitive neuroectodermal tumour. Magnetic resonance imaging is the most useful tool in the diagnosis of malignant intramedullary tumours and differentiation from other types of spinal cord lesions.

Central nervous system tumors diagnosed before the end of the first year of life differ from those found in older children and in adults. The differences include mode of clinical presentation, anatomical distribution, histopathological diagnoses, response to therapy, and outcome.The material consists of 56 children (23 girls and 33 boys), aged at recognition 32 Hbd-12 months. We reviewed charts and MR exams according to age of the onset of symptoms, location of tumors, treatment, histopathology, and outcomes. Data of the outcome were analyzed using Kaplan-Meier plots and chi-square test.Eleven cases were recognized before 6 weeks of life, 24 before the age of 6 months, and 21 were diagnosed up to the end of 1 year of age. Thirty-eight tumors were located in the supratentorial compartment; 18 were infratentorial. Median age of tumors' recognition was 5.2 months; 4.3 months for supratentorial and 7.2 months for infratentorial tumors. We found 18 glial cell tumors (high and low grade), 15 embryonal tumors, and 12 choroid plexus tumors.The outcome of congenital CNS tumors depends on the size, location, time of diagnosis, histological type of the tumor, and therapeutic option. Neurosurgical procedures are necessary in most cases. Despite the notable advances in therapy, the outcome remains poor.

Retinoblastoma is the most common pediatric intraocular neoplasm and accounts for ∼3% of pediatric malignant tumors, affecting approximately 1 in 18,000 children under 5 years of age in the U.S. It is a highly malignant tumor of the primitive neural retina. Histologically, retinoblastoma develops from immature retinal cells and replaces the retina and other intraocular tissues. Neoplastic cell proliferation is caused by the inactivation of both copies of a tumor suppressor gene (Rb1) that participates in the control of cell cycling. Occasionally patients with ocular hereditary retinoblastoma have an associated independent primary midline intracranial neuroblastic tumor. This syndrome is called trilateral retinoblastoma. Midline intracranial tumors are typically located in the pineal region, but occurrences in the sellar and suprasellar regions are also found. The prognosis for trilateral retinoblastoma is markedly worse, with a high rate of subarachnoid tumor spread. The mean survival in this group of patients after treatment is about 9 months. An association between pineal cysts and hereditary retinoblastoma has been described in the recent literature, found that the prevalence of pineal cysts in children with bilateral, hereditary retinoblastoma was statistically significant compared with that in patients with unilateral retinoblastoma. Pineal cysts are supposed to be a benign variant of trilateral retinoblastoma. MR imaging has become a very useful diagnostic tool in evaluation of patients with retinoblastoma. MR is the imaging modality of choice in detection of leptomeningeal spread of the tumor and evaluation of primary intracranial tumors that can be associated with retinoblastoma. On the basis of some cases in which intracranial midline tumors were diagnosed earlier than intraocular lesions, we strongly recommend very careful ophthalmologic and imaging examinations of orbits in all children below 4 years of age with a intracranial midline primary tumor.

Background/Purpose The aim of the study was to analyze changing management and survival of children with hepatoblastoma (HBL) treated in one center. Materials and Methods Over the last 20 years, 51 children with HBL were treated. Surgery was performed in 48 children (94.1%), conventional liver resection in 38 (of those, 2 received a rescue liver transplantation [LTx] for relapse), and total hepatectomy and primary LTx in 10 patients. The remaining 3 patients received only palliative treatment. Patient data were analyzed for survival with respect to PRETreatment EXTent of disease (PRETEXT), metastases, histopathology, conventional resection, and LTx. Results Survival of children with HBL treated with liver resection is 71% and 80% for primary LTx. Favorable prognostic factors for patient survival was tumor histology as epithelial-fetal subtype and mixed epithelial and mesenchymal type, without teratoid features, and good response to chemotherapy (necrosis, fibrosis). Unfavorable prognostic factors were small cells undifferentiated, transitional liver cell tumor, α -fetoprotein level above 1,000,000 IU/mL and below 100 IU/mL at diagnosis, lung metastases, and local recurrence after initial resection. Survival was related to PRETEXT stage. However, among patients with PRETEXT III and IV, LTx resulted in better survival. Conclusion Liver transplantation is a good option for children with advanced HBL. Early referral of children with potentially unresectable tumors to centers where combined treatment (chemotherapy, surgery including LTx) is available is crucial.

We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. The patient underwent several partial tumor resections complicated by intraoperative cardiac arrest. The tumor has been regrowing and produced severe clinical symptoms. Everolimus treatment resulted in marked tumor regression, significant improvement in patient's ambulation and cessation of seizures. Moreover, the therapy was well tolerated. These findings indicate that everolimus treatment should be considered as a therapeutic option alternative to surgery in patients with tuberous sclerosis complex.

Neuroblastoma (NB) represents one of the most common paediatric tumours. Despite advance in NB research and treatment, the outcome of the patients from the high-risk group remains poor. PI3K/AKT/mTOR signalling pathway which is involved in oncogenesis and cancer progression of many tumours, in parallel constitutes the target for the biologically based oncological therapy. In this study we analyzed the status of PI3K/AKT/mTOR signalling route in the primary tumour tissue samples from a group of 39 high-risk NB. The pathway activation state was assessed immunohistochemically using antibodies with specificity towards PI3Kp85, PI3Kp110, phospho-AKT, phospho-mTOR, phospho-p70S6K and phospho-4EBP1. Moreover, expression of PTEN, bcl2 and cyclin D1 was examined. We found that most of tumours were positive for PI3Kp85 and PI3Kp110, as well as for p-AKT, p-mTOR and its downstream effectors p-p70S6K and p-4EBPI. PTEN was expressed in all cases, bcl2 and cyclin D1 staining was found in more than 90% of examined NB. Statistical analysis revealed that p-AKT expression was correlated with p-mTOR and strong cyclin D1 labelling. Furthermore, high expression of p-4EBP1 was significantly associated with p-p70S6K expression, high cyclin D1 and lower differentiation of the tumour. PI3K/AKT/mTOR signalling pathway activation is a common event in high-risk NB and it seems that this group of patients may benefit from targeted therapy with kinase inhibitors.

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 AG (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 AT in PTEN. Polymorphism PIK3CA c.1060-17 CA was significantly more frequent in extra-adrenal tumours. Polymorphism PIK3CA c.1145+54 AG 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 differentiation. 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 PTEN expression is a common feature of NB.

Ependymomas are relatively rare neoplasms of the central nervous system that typically develop along cerebral ventricles and central canal of spinal cord. Occasionally, the tumours of ependymal origin arise supratentorially in brain parenchyma as ectopic cortical mass without any connection to the ventricular system. Ependymomas are heterogeneous group of tumours including cellular, papillary, clear cell and tanacytic histology. The papillary ependymoma is an unusual variant of ependymoma characterized by distinct morphology resembling other papillary tumours and corresponding to WHO grade II malignancy. We present an unique case of ependymoma with distinctive papillary morphology at ectopic superficial cortical localization. The tumour occurred in eleven-years-old girl as a large, well-circumscribed mass in the left parietal lobe without continuity with the ventricular system. The patient presented with severe headache, vomiting and sudden-onset right hemiparesis. Histopathologically, the tumour revealed distinct papillary pattern with numerous pseudorosettes. Immunohistochemically, the neoplastic cells of both papillary structures and pseudorosettes were positive for glial fibrillary acidic protein and vimentin, whereas they were only slightly immunoreactive for epithelial membrane antigen and negative for cytokeratins. Ultrastructural findings revealed the presence of cilia usually located in the neoplastic cell bodies and intermediate glial-like filaments. The final diagnosis of papillary ependymoma at ectopic superficial localization was based on both, immunophenotypic profile and ultrastructural features that confirmed ependymal nature of neoplastic cells.

We report a case of a 13-year-old girl with a tumour of the right fronto-parietal region of the brain. The tumour consisted of two components: a well-differentiated astroglial component with Rosenthal fibres and a neoplastic neuronal component. The final histopathology established diagnosis of ganglioglioma WHO grade I. The patient was selected from a group of children with central nervous system (CNS) tumours screened for the most common molecular variants in the NBN gene (exons 5 and 6). Molecular analysis revealed the presence of c.511AG (p.Ile171Val) substitution on one allele. This is the first patient with ganglioglioma and confirmed mutation in the NBN gene.

The NBN (NBS1) gene belongs to a group of double-strand break repair genes. Mutations in any of these genes cause genome instability syndromes and contribute to carcinogenesis. NBN gene mutations cause increased tumor risk in Nijmegen breakage syndrome (NBS) homozygotes as well as in NBN heterozygotes. NBS patients develop different types of malignancies; among solid tumors, medulloblastoma (MB), an embryonal tumor of the cerebellum, has been reported most frequently. The majority of medulloblastomas occur sporadically, some of them manifest within familial cancer syndromes. Several signaling pathways are known to be engaged in hereditary and sporadic MB. The aim of our study was to identify mutations in selected exons of the NBN gene and to determine the frequency of the most common NBN gene mutations in pediatric patients with different types of medulloblastoma. We screened a total of 104 patients with MB and identified 7 heterozygous carriers (6.7%) of two different germ-line mutations of NBN gene; all of them had classic MB. Our results indicate that heterozygous carriers of the germ-line NBN gene mutations (c.511A>G and c.657_661del5) may exhibit increased susceptibility to developing MB. The risk of medulloblastoma is estimated to be 3.0 (for c.511A>G) and 4.86 (for c.657_661del5) times higher than in the general Polish population (p

HCC constitutes 25-30% of primary malignant liver tumors in children. Conventional surgical excision is not possible in more than 50% of patients. LTx has recently become an important therapeutic option for adults and children with primary liver tumors. The aim of this study was a retrospective analysis of the clinical and pathological data of children with HCC treated with LTx in relation to Milan criteria assessed at diagnosis and then immediately before transplantation, in comparison with a group of patients treated conventionally. Between 1990 and 2007 we have treated 21 children diagnosed with HCC. Patients were divided into two groups: group I, 10 children treated conventionally and group II, 11 children treated with LTx regardless of previous therapy. The outcome of our patients treated conventionally with resection and chemotherapy is very poor--the disease-free survival rate is 30%. In contrast, despite that only 3 children having fulfilled adult Milan criteria, early clinical results of LTx are much superior. Total hepatectomy followed by LTx is the main treatment option for the majority of children with HCC. Decisions on the type of surgical treatment is made individually, but very early in the course of treatment.

Gliomas, particularly those of astrocytic origin, are the most frequent primary central nervous system tumors that develop in children. The majority of them are benign and slow growing, with relatively good prognosis. Several genomic and gene alterations are known to be involved in astrocytoma development, but the precise mechanisms remain poorly understood. The NBN gene, which participates in DNA double-strand break repair and maintenance of genome stability, has been postulated to be a susceptibility factor for a number of cancers. Here we report the results of NBN gene analyses performed in 127 children with various astrocytic tumors. PCR-SSCP analysis followed by DNA sequencing was used for molecular variant screening. Three carriers (2.37%) of different germline mutations on one NBN allele were found. The common Slavic deletion c.657_661del5 (p.K219fsX19) was detected in a patient with pilocytic astrocytoma; a known mutation, c.643C>T (p.R215W), and a new substitution, c.565C>G (p.Q189E), were identified in two patients with primary glioblastoma. The risk of developing astrocytic malignancies is estimated to be 1.33 times higher for c.657_661del5 and 3.2 times higher for c.643C>T than in the general Polish population (P > 0.05). Because of the low frequency of the mutations identified in the studied group, we were unable to determine the exact role of NBN in the development of astrocytoma in children. The presence of two potentially pathogenic NBN molecular variants among 16 glioblastoma cases (12.5%) could be a remarkable finding in our study. We thus cannot exclude a possible role of NBN in the tumorigenesis of a certain type of astrocytic tumors.

Purpose: Brain tumours are the most common solid tumours in children and adolescents. The increasing survival rate of these patients makes their follow-up and quality of life assessment an important task. The evaluation of the negative influence of anti-cancer treatment on their balance is the aim of this study. Material and Methods: The balance assessment was performed on patients who completed the treatment of CNS tumours and were disease-free at the time of the study. Eighty-eight patients aged 5 to 24 years participated in the study. Postural sway was recorded using Kistler force plate. Balance test parameters from two conditions: eyes open and eyes closed were calculated and compared with reference data. The severity of the balance disorders was scored for both conditions. Results: The balance disorders were generally not dependent on the localisation of the tumour. Only patients treated for posterior fossa tumours had a higher score (indicating pronounced balance deficit) in eyes closed condition comparing to others. The patients treated for spinal cord tumours seemed to have increased total sway path in comparison to others. The severity of the balance deficits tended to diminish in time. Conclusions: These results suggest that the repair mechanisms of the CNS could overcome the problems inflicted by the illness and therapy.

The aim of the study was to determine microscopic angiogenic parameters of neuroblastoma (NB) Schwannian stroma-poor tumours. Furthermore the associations between vascular parameters and clinicopathological features of tumours and basic prognostic factors were analysed. Examined tissue samples from 62 NB came from 39 untreated and 23 chemotherapy pretreated tumours. The clinicopathological data comprised: patients' age, gender, survival, tumour site and stage, tumour histology and MYCN status.The morphological analysis of the angiogenic potential concentrated on examination of vascular patterns - classical type or pathological angiogenesis with mural microvascular proliferation (MVP). The quantitative study included semi-automatic assessment of vascular density (VD) in CD34 stained tumour sections. Pathologic angiogenesis with MVP, including simple and/or glomeruloid type, was encountered in 25 cases and was more frequent in differentiating histology subtype and extraadrenal tumours. VD value ranged from 56 to 385 vessels/mm2 (median 149). Higher VD was connected with younger patient's age. In untreated tumours VD was significantly higher in infants than in children over one year of age. Pathologic type angiogenesis and lower VD were found to be associated with shorter survival. Our study confirmed high vascularization of NB and revealed common occurrence of vascular pattern with MVP. Angiogenic potential in the analysed group showed diversity related to some clinicopathological tumour features. This points toward heterogeneity of NB tumours in vascular aspects, possibly affecting tumours' reactivity to antiangiogenic therapy.

To describe the incidence and type of central venous catheters (CVC) complications in children treated for solid tumours.Between 1997-2005, 500 paediatric patients were treated for cancer. The CVC complications were analyzed according to the CVC type, blood product transfusion (BT) and parenteral nutrition (TPN). Chi-square test was used for statistics.For 566 surgically inserted CVCs: 147 (25.8%) were ports, 413 (73,6%) tunnelled catheters: Broviacs--227 (39.9%), Groshongs--186 (32.7%) and other--6 (1%). total number of CVC days was 288 944, (median: 422, range: 2-2583). 297 complications (rate of 1.02/1000 CVC days) were observed: 81 catheter infections (0.28), 77 mechanical complications (0.266), 59 no aspiration events (0.204), 52 thrombotic occlusions (0.179) and 28 tunnel infections (0.096). At the end of the study period 121 (28%) CVCs were prematurely removed due to: infection (52), mechanical cause (49), thrombotic occlusion (14), no aspiration (6). Mechanical complications in catheters comparing to ports were more frequent (p= 0.007). There were more infections in Broviacs than Groshongs catheters (p=0.022) and in children receiving BT and TPN (p=0.046 and 0.003).CVC's related complications were relatively rare. Most common were infections and concerned catheters and these complications were most frequent in patients receiving BP and TPN. Risk of mechanical complications was higher in catheters than ports.

Neurofibromatosis type I (NF1) is a relatively frequent autosomal dominant disorder with different manifestations from mild cosmetic problems to severe disease requiring multidisciplinary treatment. THE AIM of our study was lo analyze types of disorders in paediatric population of NF1 patients treated in the Children's Memorial Health Institute and to present the schedule of care adopted in our institution.Medical records of 130 children, 70 girls and 60 boys aged from 1 year to 20 years 3 ms treated in the Children's Memorial Health Institute were analyzed. Type of mutation (familial or sporadic), age at diagnosis, type and frequency of disorders in the whole group of patients and in the familial and sporadic types were assessed.The familial type of NF1 was found in 58 patients, among whom there were, 23 patients from 10 families. It was sporadic in 40 pts and in 32 the type of mutation is unknown. The age at diagnosis ranged from 3 months to 17 years, median 6 years. The most frequent disorders were: T2-weighted hyperintensities of the white matter in 77 pts (59%), schooling problems in 60 pts (46%), skeletal deformations in 49 pts (37%), dysmorphia in 39 pts (30%), hyperactivity in 34 pts (26%), epilepsy in 29 pts (22%). There was a correlation between white matter hyperintensities and the presence of optic nerves gliomas (71%), schooling problems (58%), hyperactivity (77%) and dysarthria (85%). In 65 pts (53%) optic nerve gliomas were found, 45 patients required treatment. Plexiform neurofibroma requiring treatment was found in 25 pts (19%,), 6 had intraspinal penetration and in 4 spine compression was observed. Two patients were diagnosed with ganglioneuroma. Malignant tumours were found in 7 pts (5%), with a prevalence of soft tissues sarcomas. Skeletal disorders occurred more frequently in tNFl sporadic type than in familial cases (p=0.05). Based on our experience a management protocol was formulated. At the time of diagnosis this includes examination by the oncologist, neurologist, ophthalmologist, geneticist and additional investigations: abdominal ultrasound, chest X-rays, MR of the brain; found disorders indicate further consultations and studies. The check-up should be repeated annually and include all previous studies that revealed any abnormalities.1. Diagnosis of NF1 is delayed until complications of the disease occur. 2. In the studied group skeletal disorders were more frequent in the sporadic than in the familial type. 3. The paediatric population with NF1 varies from the adult NF1 patients in type of disorders, diagnostic and treatment requirements. Therefore there is a need for different care standards in the two groups. 4. The knowledge about NF1 and the standards of care should be transferred to general practitioners in order to diagnose these patients early and to refer them to specialized centres.

To assess selected angiogenic markers; microvascular density and the expression of VEGF and Flk-1 in relation to clinical features and morphologic types of neuroblastoma.Eighty-two children with neuroblastoma were studied. Morphological assessment was performed in paraffin embedded tissues of the primary tumours. Microvessels within tumour tissue were counted on immunohistochemically stained sections using anti CD34 antibody. The expression of VEGF and Flk-1 was estimated semiquantitively in immunohistochemically stained sections with adequate antibodies. The results of angiogenic studies were referred to the clinical data: age, clinical stage, localization and site of the primary tumour, serum LDH and ferritin at diagnosis. The correlation between angiogenic markers and morphological type of neuroblastoma was also evaluated.Microvascular density varies in a wide range (32-325/mm(2)). There was no significant statistical difference between previously untreated and tumours assessed after chemotherapy. Analyzing the correlations between the angiogenic markers and clinical features we found a converse relation between the age and microvascular density. The highest expression of VEGF was found in adrenal tumours in comparison to other localizations. Undifferentiated and poorly differentiated tumours presented a higher expression of VEGF and higher vascular density. Non significant higher expression of VEGF and higher vascular density was noticed in smaller5 cm tumours.Correlations were found between the microvascular density and the age, diameter and the localisation of the primary tumour. Expression of VEGF depends on the localisation of the tumour. Neuroblastoma tumours arising in small children and poorly differentiated types of neuroblastoma indicate higher angiogenic activity.

Despite progress in neuro-oncology, treatment results of children and adolescents with brain stem tumours remain poor. There are also controversies concerning the role of chemotherapy in the treatment of these tumours. THE AIM of our study was to analyze treatment results of patients with brain stem tumours treated with radiotherapy alone and with the addition of chemotherapy and to assess which chemotherapy protocol is the most efficient.Between 1981-2004, 126 patients were treated in our department. The patients were divided into 2 groups according to treatment methods applied. The first group consisted of 49 patients treated with radiotherapy alone. In the second group 77 patients were irradiated and received chemotherapy. Overall survival (OS) at 1 and 5 years was analyzed in both groups. The efficacy of treatment of patients from the second group was assessed by evaluating reaction to radiotherapy, to different chemotherapy protocols and duration of tumour regression. Additionally OS was assessed separately for patients with low grade gliomas treated in the second group.Seven out of 49 patients from the first group are alive with a follow up from 8 years 9 months to 24 years, median 6 years 7 months. In the second group, 25 out of 77 patients are alive with the follow up from 7 months to 8 years 2 months, median--l year 7 months. OS at l and 5 years for patients treated with radiotherapy alone is 48 and 14% and for those receiving additionally irradiation 59 and 18% respectively (statistically insignificant). Best tumour response was achieved in 42% of patients with radiotherapy but in 75% of cases regression lasted from 2 weeks to l year 3 months, median 4 months. Addition of chemotherapy consisting of cisplatinum and temozolamide resulted in tumour regression in 27% of patients lasting from 4 weeks to 4 years 5 months, median 4 months. OS for patients with LGG was 34.6% at 5 years.1. Radiotherapy in brain stem tumours allows to achieve tumour regression but short duration of remission and poor final outcome forces to search for other, effective treatment. 2. Patients with brain stem tumours may benefit from chemotherapy in terms of prolonging survival. 3. Chemotherapy consisting of temozolamide and cisplatinum seems to be promising and might add to improvement of treatment results, but further clinical studies are needed. 4. Patients with low grade gliomas of the brain stem constitute a separate group with a better prognosis.

Non-rhabdomyosarcoma soft tissue sarcomas (NR STS) are a rare group of neoplasms of mesenchymal origin. The incidence of these tumours in children is low and due to it's heterogeneity and different response to chemotherapy and radiotherapy, unified treatment methods have not yet been established. THE AIM of our study was to analyze methods and treatment results of patients with NR STS treated in our centre.Between 1996 and 2004, 64 patients with NR-STS, aged 2.5-21.5 yrs, were treated in our institution. Treatment protocol included primary tumour resection or biopsy, induction (neoadjuvant) chemotherapy, local treatment: surgery and/or radiotherapy and adjuvant chemotherapy. Results of treatment were analyzed in relation to stage, tumour diameter, extent of surgery and response to chemotherapy.Out of 64 patients, 48 are alive (75%), with a median observation time 4 yrs 3 m. Sixteen patients died: 1 of treatment complications, the rest from basic disease. Four years overall (OS) and event free survival (EFS) are 75% and 64% respectively. Early stage, tumour size less than 5 cm in diameter, radical surgery, complete and very good response to induction chemotherapy had a significant influence on survival.Our results indicate that besides stage and tumour size, radical surgery played key role in the treatment of NRMSSTS and that radical resections were possible to perform after induction chemotherapy in 33% of patients with primarily unresectable tumours. High number of patients with stage IV disease at diagnosis, occurrence of distant relapses and good response to chemotherapy indicate the necessity for the use of chemotherapy in patients with NR STS.

Newborns and infants up to three months of life are a specific group of population in paediatric oncology due to immaturity of tissues and organs and rarity of neoplastic diseases in this group of patients (pts). There are no strict therapeutic procedures established for these children. THE AIM of our study was to examine distribution of tumours in newborns and infants up to 3 months of age treated in our institution and to present our own experience in the treatment of these patients.Medical records of 71 pts (37 boys and 34 girls) treated from 1996 to 2004 were reviewed. Distribution of tumour types in newborns and babies from 1 to 3 months of age was analyzed separately. Due to similar growth pattern, response to treatment and it's side effects in newborns and small infants, treatment results were evaluated for the whole group.there were 50 newborns. The most common diagnosis in this group was germ cell tumours (GCT) which constituted 60% of all tumours, amongst them 52% were mature teratomas (MT). The second most common was neuroblastoma (NBL) 22%. There were also 3 cases of soft tissue sarcomas (STS), 2 central nervous system tumours (CNS), 2 retinoblastoma (RB), 2 hepatoblastoma (HB). In the group of 21 babies aged 1-3 months NBL was the commonest (37%) followed by RB, CNS tumours (14% of each) HB and MT (10% of each) and Wilms tumour (WT) and immature teratoma (IT) each 5%. Surgery alone was performed in 48 pts. It concerned pts with MT--28, IT--3 pts, yolk sac tumour (YST)--1 pt and malignant tumours (stage I and II): 8-NBL, 2-CNS tumours, 2 STS, 3-HB, 1-WT. Forty two pts from this group are alive. Six pts died: 2 from surgical complications, 1 from sepsis, 1 of congenital heart defect and 1 from unknown reason at the age of 18 months. It was a patient with severe infantile cerebral palsy. One pt died of disease--relapse of yolk sac tumour, 2 years 4 months after surgery of MT. Eleven pts underwent combined treatment of chemotherapy and surgery: 5 with stage III and IV NBL, 6 with other tumours. One pt with STS at the age of 1 yr 6 months was the tumour bed irradiated after surgery for microscopic tumour residual. Four pts are alive, 4 with NBL and 5 with other tumours. Two pts died from disease: one with NBL and one with IT. Chemotherapy alone was administered to 7 pts in whom local advancement of disease enabled surgery and to pts with RBL. Three out of 7 pts are alive all with RBL. Four pts died: 3 from disease, 1 from infectious complications. Four pts with NBL (2 stage IV and 2 stage IVS) were treated with irradiation to the liver only. Two pts (st. IV) died and 2 (st. IVS) pts are alive. One pt relapsed at age of 2 yrs 3 mths, probably at the primary site which was not visualized at primary diagnosis. One pt, critically ill, died before any treatment. Fifty six out of 70 pts (80%) are alive with a follow up from 1 year to 9 yrs 11 months (median- 4 yrs 4 months). Fourteen pts died (20%), 8 from disease and 6 of other reasons.1. GCT and neuroblastoma are the most common tumours in newborns and infants up to 3 months of age. 2. Newborns and small infants with advanced neoplastic disease, similarly to older children can be cured with chemotherapy. 3. Individual approach is warranted in newborns and small infants and treatment should be carried out in specialized centres. 4. All patients who completed treatment of any tumour type should be followed up by a pediatric oncologist.

Adolescents aged 15-19 years are variably included in analyses of childhood cancer. They should be considered separately because tumours that occur in adolescents differ from those in younger children.To describe the distribution of tumour types and treatment results in this group of patients treated in the Department of Pediatric Oncology at The Children's Memorial Health Institute.Retrospective analysis of medical records of patients aged 15-19 years treated in our institution was performed. It included demographic data, tumour types and treatment results.Between 1998-2004, 207 pts, 110 boys and 97 girls aged 15-19 yrs (median--16.5 yrs) were treated. Distribution of tumours was as follows: CNS tumours--74 pts (35.7%), HD -18 pts (8.7%), NHL--13 pts (6.3%), bone tumours--31 pts (15%), STS--23 pts (11.1%), gonadal tumours--12 pts (5.8%), carcinomas--16 pts (7.7%), hepatomas--5 pts (2.4%), neuroblastoma--3pts (1.5%) and other 12 pts (5.8%). Out of 207 pts 130 are alive (62.8%). Seventy seven (37.2%) pts died--64 (83.1%) from disease, 9 (11.6%) from chemotherapy complications, 4 due to other reasons. 111 pts completed treatment and are disease free for 11 months to 7 yrs (median 3 yrs 11 mos) from diagnosis. Nineteen patients are still treated. Treatment results are as follows: CNS tumours--58.1%, HD - 88.8%, NHL--69.2%, bone tumours--51.6%, STS--65.2%, gonadal tumours--83.3%, carcinomas-- 56.25%.Spectrum of malignancies that occur in adolescents 15-19 years of age differs from younger children. Unlike younger patients epithelial carcinomas of adults are observed in this age group. Outcome of treatment is inferior to younger patients. Adolescents should be offered optimal treatment. This specific group should be studied in many aspects.

THE AIM of our study was to evaluate results of conservative treatment of patients with unilateral retinoblastoma.Twenty one patients, 11 boys and 10 girls aged 2 months to 4, 5 years (median age 1 year) were studied. Local disease advancement according to Reese-Elsworth was defined in all patients. Neoadjuvant chemotherapy consisting of Vincristine, Etoposide and Carboplatin was administered. After every 2 courses tumour response was evaluated. Sixteen patients were treated with chemotherapy alone. Local treatment including brachytherapy, thermochemotherapy and cryotherapy was implemented and the choice of the method depended on the tumour's localization, size and response to chemotherapy. Statistical analysis using demographic data and survival curves were performed.On completion of treatment all patients achieved tumour regression. Eleven patients are progression free with a follow-up from 10 months to 6 years 4 months (median--2 yrs 5m). In 10 patients relapse was observed. A total of seven enucleations were performed in the examined group. In histopathological examination viable tumour cells were present in all removed eye balls. Distant metastases were not observed in any of these patients. All patients are alive with a follow-up from 10 months to 9 yrs 6 months (median--4 yrs 7 months) from diagnosis. Disease free survival and ocular survival is 44% and 54% respectively.Neoadjuvant chemotherapy in unilateral retinoblastoma allows to avoid enucleation in some patients.

We report a case of anaplastic cancer of thyroid in 14-year-old male. The diagnosis was supported on: pace of changes, clinical image, disease course, no effect of therapy, histopathological examination.

Malignant vascular tumours represent a rare group of neoplasms, usually treated according to protocols for soft tissue sarcomas.To assess the clinical characteristics, disease course and outcome in Polish children with malignant vascular neoplasms.The Polish Paediatric Rare Tumours Study retrospectively analysed multicentre data on 32 children with vascular tumours, registered between 1992 and 2002. On the basis of the histological type of the neoplasm these patients have been divided into three groups: group I -- 10 patients with angiosarcoma (ASA), group II -- 7 children with haemangioendothelioma (HE) and group III- 15 patients with haemangiopericytoma (HP), of both infantile (7 children) and adult-types (8 patients).Group I: 5 patients presented with local, 3 with systemic and 2 with regional disease. Primary complete resection (PRC) was performed in 7 patients, not resulting in local control in any of them. Radiotherapy (RTX) was administered in 5 patients, chemotherapy (CHT) in all. 7 patients relapsed, 3 never entered clinical remission. 9 of the 10 patients of group I, died of disease progression. Group II: PRC was performed in 5 patients and led to local control in 2. Adjuvant RTX was used in 2 and CHT in 4 patients. 2 children relapsed and died of the disease. Infantile HP: PRC was performed in 3 children, remaining 4 patients received adjuvant CHT All children entered complete remission and are disease-free. Adult-type HP: PRC was performed in 5 patients, resulting in local control in 4. Five children were given adjuvant RTX and six CHT Three patients relapsed and died of disease progression.The effectiveness of primary complete resection in all groups was doubtful. The high rate of metastatic relapses suggests that the currently given systemic therapy is not satisfactory. The only tumour with excellent prognosis was infantile type HP (all patients are alive and free of disease). Adequate treatment for children with angiosarcoma remains still unknown -- 9 of 10 patients died of disease progression. Prognosis in patients with haemangioendothelioma is intermediate, however the role of immunotherapy should be further investigated.

The functional status of 41 paediatric patients after treatment for a malignant central nervous system (CNS) tumour was assessed using gait analysis and balance studies. Parameters of balance were obtained from stabilograms registered during “eyes-opened” and “eyes-closed” conditions. The patients could be divided into two groups: first, those with no deficits of balance, and second those with a balance deficit. The functional deficits exhibited by patients were not dependent on the tumour localization or age of onset of their illness. The mean time between the end of the treatment and the time of the study was 5.8 years in the non-deficit balance group, and 3.7 years in the balance deficit group (p = 0.023). Children with a balance deficit tended to walk with a slightly higher speed, due to increased cadence. Their step width was slightly increased, as well as the percentage of the stance phase. They walked with increased external rotation at the hips and knee flexion at initial contact was slightly increased. The results suggest that patients can compensate the problems caused by oncology treatment, and indicate the need for early rehabilitation of CNS tumour patients.

Retrospective analysis of 29 children with bilateral Wilms' Tumour, 14 boys and 15 girls, aged 4m-5 years, from regional centres of paediatric oncology in Poland, treated according to the O1-92 PPGL Protocol of Wilms' tumour, was performed. All patients were treated with two (ACT + VCR) or three (ACT, VCR, DOX) cytostatic drugs preoperatively, and 26 were operated upon after cytoreductive pretreatment. In 12 children nephrectomy was performed. In 28, kidney sparing surgery was possible and made with success. 2 patients who presented disseminated disease and 1 with nephroblastomatosis were given chemotherapy. 19 out of 29 (65.5%) are alive including 1 patient with nephroblastoma. EFS calculated according to Kaplan-Meier analysis for this group, was 58% at 67 months.

Primary central nervous system (CNS) neoplasms are the most common solid tumors in children. During the last two decades progress in diagnostic procedures and treatment has been made. New techniques of imaging (CT, MRI), neurosurgery, intensive care and the introduction of intensive chemotherapy and refined radiotherapy had the greatest impact on this progress. Nevertheless, out of all pediatric malignancies this group of patients has the worst prognosis. To improve survival optimal treatment modalities are searched for. This paper presents brain tumors epidemiology, etiology aspects, classification, clinical symptoms, diagnostic procedures and current treatment strategies in CNS tumors in children such as: medulloblastoma/PNET, high and low grade gliomas, ependymomas, germ cell tumors and brain stem tumors. Age of the patients is considered in all tumors as there is a specific philosophy of treatment in small children. We are also presenting directions of recent clinical trials and the aims of pediatric oncologists in improving the effectiveness of treatment and quality of life of a cured child.