Perilobar nephroblastomatosis: natural history and management.

Nephroblastomatosis (NB) has been considered as a precursor of Wilms tumor (WT). The natural history of NB seems to present significant variation as some lesions may regress spontaneously, while others may grow and expand or relapse and develop into WT later in childhood. Although, most investigators suggest adjutant chemotherapy, the effect and duration of treatment are not well established. Children with diffuse perilobar NB, Beckwith-Wiedemann syndrome, and hemihypertrophy seem to particularly benefit from treatment. We discuss our experience on two cases of NB and we review the literature for the management of this rare condition.

Alterations of bone mineral metabolism of children with different cell lineage types of acute lymphoblastic leukaemia under chemotherapy.

BACKGROUND: Children with haematological malignancies such as acute lymphoblastic leukaemia (ALL) may have alteration of bone mineral metabolism therefore increased risk for osteopenia and osteoporosis. PATIENTS AND METHODS: The purpose of this study was to examine the alterations of bone mineral metabolism in two groups of children (n=42) according to immunophenotyping (B-cell type, T-cell type) both quantitative (bone mineral density z-scores) and qualitative (serum osteocalcin - OC and carboxyl-terminal telopeptide of human type I collagen - ICTP) during diagnosis (T=0), after the intensified chemotherapy period (T=0.5) and the consolidation period (T=1). RESULTS: According to our results 15 patients had osteopenia and 1 child developed osteoporosis at T=0.5 and 13 patients had osteopenia at T=1. Mean BMD z-score was significantly decreased in both groups during chemotherapy and especially statistically significant decline of T-cell type ALL group compared with B-cell type ALL patients. OC mean level remains in low levels for both groups reaching in plateau during chemotherapy and ICTP level was increased in T-cell type ALL group of patients compared with B-cell type in both periods of chemotherapy. CONCLUSIONS: It seems that not only the combination of chemotherapeutic agents but also the cell lineage of ALL are important parameters of altering bone mineral metabolism.

Primary atypical teratoid/rhabdoid tumor of the spine in an infant.

Atypical teratoid/rhabdoid tumor of the spine is a rare pediatric neoplasm with poor prognosis. We report a case of an atypical teratoid/rhabdoid tumor of the cervical spine in a 2-months-old infant. The patient presented with rapidly progressing tetraparesis and respiratory failure. Magnetic resonance imaging of the spinal cord revealed an intradural, extramedullary mass occupying the spinal canal on the right at the level of C1-C5. Tumor cells were immunohistochemically positive for epithelial membrane antigen, vimentin, cytokeratins, S-100 protein, and CD57/Leu-7 antigen. Despite chemotherapy, the infant presented with progressive neurological deterioration and died 6 months after initial diagnosis. We review the literature on spinal malignant rhabdoid tumor and discuss the pathology, treatment, and outcome of these rare neoplasms.

Pulmonary Zygomycosis caused by Cunninghamella bertholletiae in a child with acute lymphoblastic leukemia.

Zygomycosis is an invasive mycotic disease caused by fungi of the class Zygomycetes. Infections caused by zygomycetes, are known for their difficulty of diagnosis and treatment. Cunninghamella bertholletiae (Cb), is a saprobic fungus commonly found in the soil of temperate climates. Pulmonary infections caused by Cb are being identified with increasing frequency among patients on immunosuppressive therapy, and these infections usually have a fatal outcome. We present a rare case of pulmonary zygomycosis caused by Cb in a 10 year old male child with acute lymphoblastic leukemia. In spite of intensive antifungal chemotherapy (iv liposomal amphotericin B 7 mg/Kg once daily) following clinical diagnosis, he died of pulmonary failure.

Childhood leukaemias and lymphomas in Greece (1996-2006): a nationwide registration study.

BACKGROUND: Monitoring time trends in the incidence of childhood leukaemias and lymphomas requires efficient and continuous data collecting systems. In countries without official cancer registries, such as Greece, ad hoc nationwide registration of incident childhood leukaemias and lymphomas could help elucidate the underlying aetiology and monitor socioeconomic differentials in health care delivery. METHODS: We registered all cases and produced age, gender, type and immunophenotype specific figures and overall crude and age adjusted annual incidence rates and secular trends for 863 leukaemia and 311 lymphoma incident cases diagnosed in children <15 years of age across Greece during 1996-2006, namely the first 11 years of the Nationwide Registry for Childhood Hematological Malignancies. RESULTS: The epidemiological profiles of leukaemias/lymphomas in Greece are similar to those in industrialised countries. No secular trends are observed for either malignancy during the studied period. However, the calculated incidence for leukaemia (46.60 cases per 1 million children annually) is among the highest in the EU-27 (19% higher than average; p<0.001), whereas that for lymphoma (16.8 cases per 1 million children annually) is around the EU-27 average. CONCLUSIONS: Minimal secular changes in childhood leukaemias/lymphomas have been noted recently in the EU-27, which cannot be easily explained in countries with small populations. Therefore, centralised EU databases such as the Automated Childhood Cancer Information System (ACCIS) should be enlarged to generate sufficient statistical power for monitoring time trends. It would be interesting to explore whether different lifestyle patterns across the EU might be responsible for the observed excess leukaemia incidence in countries such as Greece.

Alveolar soft-part sarcoma of the extremity: a case report.

Alveolar soft-part sarcoma (ASPS) is a rare form of soft tissue sarcoma and is most often seen in adolescents and young adults. Surgical excision of the primary tumor and pulmonary metastases has resulted in prolonged survival in some patients while the benefit of adjuvant chemotherapy and/or radiotherapy has been disputed. An 11- year-old boy with ASPS which presented with a markedly vascular tumor in the left thigh, and multiple bilateral pulmonary metastases 8 months after diagnosis is described. The patient has remained disease-free for over 5 years since the initial diagnosis.

Expression of multidrug resistance 1 (MDR1), multidrug resistance-related protein 1 (MRP1), lung resistance protein (LRP), and breast cancer resistance protein (BCRP) genes and clinical outcome in childhood acute lymphoblastic leukemia.

The aim of this prospective study was to analyze the expression of messenger RNA of genes, such as MDR1, MRP1, BCRP, and LRP, implicated in the mechanism of multidrug resistance (MDR) in relation to the response to induction chemotherapy and relapse and these genes' correlation with each other and with pretreatment laboratory and clinical characteristics. We prospectively studied 49 children (26 boys and 23 girls) with acute lymphoblastic leukemia (ALL) (median age, 5.5 years; range, 15 months to 12.5 years) who were treated with the BFM95 chemotherapy protocol. We used bone marrow mononuclear cells from 7 healthy children as controls. The expression of MDR genes and the beta-actin housekeeping gene was detected by the reverse transcription-polymerase chain reaction with the appropriate primers. The mean expression of each MDR gene was significantly higher in the patients than in the control group (P < .01). We found statistically significant correlations between MRP1 and LRP expression and between MRP1 or LRP expression and MDR1 expression (P < .05). High expression for the MDR1 gene was found in 18 patients (36.7%), and their prognoses were significantly worse than those with low expression (event-free survival, 55.56% versus 86.67%; P = .03, log-rank test). Expression of each of the MDR genes was independent of the initial white blood cell count, immunophenotype, National Cancer Institute risk classification, and prednisone response. Interestingly, MDR1 expression was significantly higher at relapse than at diagnosis for 4 sample pairs. Evaluation of MDR1 expression at diagnosis of childhood ALL may contribute to the early identification of patients at risk of treatment failure.

Heart rate is the major determinant of diastolic filling pattern during growth: a radionuclide ventriculography assessment.

Left ventricular diastolic filling is a fundamental constituent of cardiac performance. Diastolic function in both adults and children can be routinely assessed by radionuclide ventriculography (RNV). It has previously been shown that factors such as heart rate (HR) and age can significantly modify diastolic performance in adults, thus limiting the clinical applicability of RNV diastolic indices. The aim of this study was to investigate various factors that may affect diastolic function in childhood. Seventy-nine children, aged 40 days to 15 years, were enrolled in the study; their HR ranged from 45 to 160 beats per minute (bpm). All had intact cardiac function and were submitted to baseline RNV prior to chemotherapy initiation for malignancies. Using stepwise linear regression analysis, HR was identified as the major factor affecting RNV diastolic indices during growth. Applying univariate regression models, diastolic indices were corrected for a referrence HR of 100 bpm; this substantially reduced variability of RNV diastolic indices along age increments, allowing for the establishment of reference ranges. In conclusion, HR was shown to be the major determinant of RNV diastolic indices during growth. Adjustment for this variable alone can offer reference ranges for the assessment of left ventricular filling in childhood.

Comparison of isepamicin with amikacin for the empirical treatment of febrile neutropenic children with malignancies.

The efficacy and safety of isepamicin at 7.5 mg/kg i.v. q 12 h was prospectively compared with that of amikacin at the same dose for the treatment of febrile neutropenic children with malignancies. Thirty-nine patients were enrolled in the study; 25 received isepamicin and 14 amikacin. Clinical and bacteriological response rates were 100% for both groups. No adverse events occurred. Median peak serum levels were 19.7 mg/l for isepamicin and 19.20 mg/l for amikacin. Median trough serum levels were 0.72 mg/l for isepamicin and 0.68 mg/l for amikacin. It was concluded that isepamicin was as effective and safe as amikacin for the treatment of febrile neutropenic children with malignancies, and might be used in areas where resistance to other aminoglycosides is a problem.

Comparison of efficacy and safety of teicoplanin and vancomycin in children with antineoplastic therapy-associated febrile neutropenia and gram-positive bacteremia.

To compare their efficacy and safety, teicoplanin and vancomycin were randomly administered to 32 children for 52 gram-positive bacteremias during malignancy-associated neutropenia (<1000/microl). Patients mainly suffered from hematological malignancies. Twenty-five episodes were treated with teicoplanin (10 mg x kg(-1) x d(-1)) and 21 with vancomycin (40 mg x kg(-1) x d(-1)) plus ceftazidime and netilmicin. Six episodes were treated with teicoplanin because of previous "red man" reaction to vancomycin. Staphylococci (12% Staphylococcus aureus) were isolated from 50 episodes and viridans streptococci from 2. Defervescence on 3rd-4th day occurred in 29/31 (93.5%) teicoplanin-treated and 18/21 (85.7%) vancomycin-treated episodes. All 12 teicoplanin-treated and 13/13 vancomycin-treated episodes with repeat blood cultures on 3rd-4th day showed microbiological response. Two teicoplanin-treated and 3 vancomycin-treated patients required antifungals. Mild renal insufficiency appeared in 5 vancomycin-treated patients that was corrected without drug discontinuation. While both glycopeptides exhibit equal clinical and microbiological efficacy, teicoplanin is less likely to induce allergic reactions or nephrotoxicity in children.

Insulin-like growth factor-I and binding protein-3 in relation to childhood leukaemia.

The aetiology of most cases of childhood leukaemia remains unknown, but several studies have indicated that increased birthweight and height are risk factors for the disease. Since insulin-like growth factor-I (IGF-I) mediates the effect of growth hormone and has been positively associated with prostate cancer, we have evaluated the role of this hormone and its principal binding protein, IGFBP-3, in the aetiology of childhood leukaemia. Incident cases of childhood leukaemia from those recorded by a national network of childhood oncologists were enrolled in our study. Controls were children hospitalised for acute conditions of no more than moderate severity with matching for gender, age and maternal place of residence. Blood measurements of IGF-I and IGFBP-3 were undertaken using commercially available radioimmunoassays. Serum IGF-I values decreased by about 1.7% per month, and the rate of decline was higher, though not significantly so, among cases (2.1% per month) than among controls (1.4%). There was no significant association between IGF-I and the likelihood of childhood leukaemia, but an increment of 1 microg/ml of IGFBP-3 was associated with a substantial and statistically significant reduction of childhood leukaemia by 28% (95% confidence interval 7% to 45%). Because IGFBP-3 is essentially a binding protein, we interpret our findings as indicating that bioavailable IGF-I may play an important role in the aetiology of childhood leukaemia. The much smaller quantities and the inherent instability of IGF-I in the blood in comparison to those of IGFBP-3 are likely to hinder documentation of an underlying positive association of IGF-I with the disease.

Outbreak of varicella in a pediatric oncology unit.

BACKGROUND: Varicella-zoster virus (VZV) infection is usually benign but immunocompromised patients are at great risk for visceral dissemination and fatal outcome. During a nationwide varicella outbreak, several of our patients contracted the disease. We undertook studies of the epidemiology and the efficacy of antiviral treatment and immunoprophylaxis. PROCEDURE: During a 9-month period, 52 patients were exposed to cases of active varicella. Twenty-seven of these children were reexposed to active varicella > 1 month after their initial exposure. The exposure concerned 7 VZV waves of varying intimacy. In all cases, prophylaxis with intravenous immunoglobulin (IVIG), varicella zoster globulin (VZIG), or both was given. The spread of the disease was limited and only 6 patients (all immunosuppressed) developed varicella (7.6%). Three of 6 had been given IVIG and 3 VZIG + IVIG. All patients with varicella received acyclovir 30 mg/kg/day for 14 days. The disease was mild and all patients were ultimately cured. RESULTS: Our results show that prophylaxis was not 100% effective, but appearance to reduce the rate of spread. The differences in incidence among the regimens used were not significant. CONCLUSIONS: For the moment, immunoprophylaxis and acyclovir administration appear to be quite satisfactory in managing immunocompromised children exposed to VZV. This may change with the wider use of the varicella vaccine.

Electrical power lines and childhood leukemia: a study from Greece.

Residential proximity to electrical power lines of different voltage in relation to childhood leukemia was investigated through a case-control study undertaken in Greece during 1993-1994. The study comprised 117 incident cases of childhood leukemia and 202 age-, gender- and place-of-residence-matched controls. Four measures of exposure to magnetic fields were developed, using data provided by the Public Power Corporation of Greece: Voltage (V) divided by the distance (d), V/d2, V/d3 and an adaptation of the Wertheimer-Leeper code. Conditional-logistic-regression modeling was used to adjust for potential confounding influences of 18 variables. No significant trends of childhood leukemia risk with increasing exposure levels were noted, nor were there statistically significant elevations of disease risk at the higher exposure levels in each measure of exposure. These results do not support a causal link between residential proximity to electrical high-voltage wires and childhood leukemia risk, but in themselves do not refute a weak empirical association.

Aggregation of childhood leukemia in geographic areas of Greece.

A total of 872 children aged up to 14 years, who were diagnosed with leukemia in Greece during the decade 1980-89, were allocated by place of residence to the 601 administrative districts of the country. Evaluation of spatial clustering was done using the Potthoff-Whittinghill method, which validly assesses heterogeneity of leukemia risk among districts with variable expected numbers of cases. There was highly significant evidence for spatial clustering occurring particularly among children living in urban and, to a lesser extent, semi-urban areas. The evidence was stronger for children younger than 10 years old, applied also to children in different five-year age groups, and persisted when cases of acute lymphoblastic leukemia were analyzed separately. These findings provide support to the hypothesis that localized environmental exposures could contribute to the etiology of childhood leukemia, but they cannot distinguish between exposures of physical or chemical nature, nor can they exclude socially conditioned patterns of exposure to infectious agents.

The risk profile of childhood leukaemia in Greece: a nationwide case-control study.

The risk profile of childhood leukaemia in Greece was studied through a case-control investigation that included all 153 incident cases of the disease, ascertained throughout the country during 1993 and 1994, and two hospital controls for every case matched for gender, age and place of residence. The data were analysed using conditional logistic regression and the associations are expressed in terms of adjusted odds ratios (OR) and their 95% confidence intervals. Cases were born to mothers of a higher standard education, the OR for an increment of four schooling years being 1.48 (1.17-1.87) and had higher birth weight, the OR for an increment of 500g being 1.36 (1.04-1.77). Pet ownership and birth after a pregnancy with anaemia were associated with increased risk, the ORs being 2.18 (1.14-4.16) and 2.60 (1.39-4.86) respectively. From the frequency analyses, indicative inverse associations were found with birth order, household crowding and previous hospitalization with allergic diseases, whereas indicative positive associations were found with diabetes mellitus during pregnancy and with neonatal jaundice. Substantial or significant elevations were not found with respect to maternal smoking and coffee drinking during pregnancy, diagnostic radiography and ultrasonographic examinations or blood transfusions. A significant inverse association with maternal consumption of alcohol could be due to multiple comparisons, but a detrimental effect can probably be excluded. A non-significant positive association with total shots of viral vaccinations and a weak non-significant inverse association with breast feeding were also found. We interpret the findings of this study as being compatible with acute childhood leukaemia being linked with delayed development of herd immunity to fairly common infectious agents, in conjunction with accelerated perinatal and early post-natal growth.