Nephrotic syndrome and Hodgkin lymphoma in children. Report of two cases.

BACKGROUND: The association of nephrotic syndrome (NS) and Hodgkin's lymphoma (HL), although rare, is well recognised. In the majority of cases of HL, minimal change NS is detected. DESCRIPTION OF CASES: This report presents the occurrence of NS in two children with HL. In the first case, NS preceded the diagnosis of lymphoma by 3 months, while in the other child, the two disorders occurred simultaneously. In both cases, clinical manifestations and laboratory parameters (proteinuria) of NS resolved after effective treatment for active HL. CONCLUSION: Prolonged proteinuria may be a paraneoplastic syndrome and HL should be considered in the diagnosis as it is crucial for the management of both entities.

The state of research into children with cancer across Europe: new policies for a new decade.

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.

Changes in children's fatigue during the course of treatment for paediatric cancer.

BACKGROUND: Fatigue is described as one of the most distressing symptoms of cancer therapy; yet it has received limited clinical attention. Children are suffering from a symptom that is under-diagnosed during their treatment. AIM: The aim of this study is: (a) to assess the change in fatigue scores during cancer treatment according to children's perspectives, and (b) to describe the possible causes of fatigue from children's points of view. SAMPLE AND METHODS: The present study is part of an ongoing prospective study. The research group consisted of 40 (n = 40) children aged 7-12 years with cancer who are being followed up in the oncology clinic of a Greek children's hospital. After parental consent was obtained, data were collected using the Child Fatigue Scale and a sociodemographic data form. RESULTS: The children with cancer reported a statistically significant increase in fatigue scores during their treatment (F = 6.846, P = 0.003). Gender was the only demographic factor associated with a significant increase in the fatigue scores (F = 4.857, P = 0.034). CONCLUSIONS: Cancer treatment was found significantly to increase children's fatigue levels. Medical procedures and the hospital environment seemed to be major causative factors of the fatigue experienced by children with cancer during their treatment.

Long-term effects of chemotherapy for acute lymphoblastic leukemia on the medial olivocochlear bundle: effects of different cumulative doses of gentamicin.

OBJECTIVE: The treatment of acute lymphoblastic leukemia (ALL) often combines a neurotoxic chemotherapeutic protocol such as Berlin-Frankfurt-Munster-95 (BFM-95) with gentamicin, an antibiotic known to have an early and quickly reversed impact on olivocochlear reflex in animal studies. This study investigates whether this combination has any long-term side effects on the medial olivocochlear bundle (MOCB). METHODS: In all 47 children of the study suppression of distortion product otoacoustic emissions (DPOAEs) by contralateral application of white noise (WN) was used to assess the function of the MOCB. The population was divided into three groups depending on the time interval between the end of therapy and examination. The group examined shortly after chemotherapy included 12 children who had received low gentamicin doses (less than 13 days). The group evaluated 2 years after therapy involved another 12 children who had required medium gentamicin doses (more than 13, less than 23 days). The group examined 3 years after therapy included a subgroup of 12 children to whom low gentamicin doses were infused and another 11 children with high gentamicin doses (more than 23 days). RESULTS: Three years after therapy the olivocochlear reflex was efficiently produced in both subgroups of low and high gentamicin doses. Two years after therapy, contralateral WN induced increase of DPOAEs at 4 of the 12 examined frequencies. Shortly after therapy, WN increased, instead of suppressing, DPOAEs at five frequencies. CONCLUSION: This abnormal result of contralateral noise application perceived as impaired cochlear efferent innervation may indicate that ALL-BFM-95 exerts a toxic effect on the MOCB, which is slowly reversed within the first 3 years after chemotherapy and does not seem to be affected in the long term by different cumulative doses of gentamicin.

Improving the quality of life for children with cancer. European School of Oncology Advisory Group.

There are now more than one million new cases of cancer every year in the European Community (EC) including the children to whom particular needs should be addressed. Besides the disease-free survival other outcomes reflecting the impact of treatment on the patient and their families must also be assessed and include their physical, psychological and social functioning throughout their care: during therapy, after completion of treatment or, for some, in the terminal phase of their illness. To provide optimal care and thus improve the quality of life for these children needs: a) an appropriately structured Paediatric Cancer Unit; b) well trained and permanent staff members: comprising doctors, nurses, psychologists, social workers and other health care professionals; c) facilities such as a specific out-patient clinic, a hospital school, a residence for parents; d) a well defined programme for the terminally ill children; e) a well defined programme for controlling the late effects of therapy.

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.

Reported influenza in pregnancy and childhood tumour.

The present study was conducted to test the hypothesis that exposure to influenza in pregnancy increases the risk of tumour of certain type in childhood. Children ages 17 years or less diagnosed in Greece with brain tumours or neuroblastomas from 1982 to 1993 (n = 94) were contrasted to 210 controls selected from the same hospitals. Mothers of these children were interviewed about a variety of possible etiologic factors. The prevalence of influenza in Greece for each year during the period 1984-1992 was also compared with the number of children born during the same year who subsequently developed brain tumour or neuroblastoma. The results indicate a significant association between influenza in pregnant women and occurrence of tumour in index child (OR: 3.15, 95% CI: 1.13-8.77). These results persisted when adjustment for potential confounding factors was made. The findings should be interpreted cautiously because of lack of serologic documentation of information about infection obtained in interviews. A positive correlation (r = 0.74) of the number of tumour births by year of birth with the prevalence of influenza during the same year was also noted. This exploratory study is one of the few case-control studies of the epidemiology of childhood tumours in children, and the results suggest directions for future epidemiologic studies in this relatively uncharted field.

Supportive care in children with cancer our experience at "A. Kyriakou" Children's Hospital in Athens, Greece.

The various aspects of supportive care in children suffering from cancer, diagnosed at the Children's Hospital Aglaia Kyriakou, in Athens, are presented from the diagnosis to each step of therapy, and afterwards. It is stressed that cultural, religious and social parameters are crucial in defining the way to approach the family as a whole.

Guidelines for a therapeutic alliance between families and staff: a report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

This, the fifth official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, develops another important topic: the Therapeutic Alliance between families and staff. This is addressed to the Pediatric Oncology Community as Guidelines that could be followed. Every parent, medical staff member, and psychosocial professional involved in the care of the child should be responsible for cooperating in the child's best interest. Everyone must work together toward the common goal of curing the cancer and minimizing its medical and psychosocial side-effects.

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.

SIOP Working Committee on psychosocial issues in pediatric oncology: guidelines for communication of the diagnosis.

This is the fourth official document of the SIOP Working Committee on psychosocial issues in pediatric oncology constituted in 1991. This document develops another topic discussed and approved by the SIOP Committee: "communication of the diagnosis" is addressed to the pediatric oncology community as guidelines that could be followed. The highly stressful nature of the diagnostic period must be acknowledged, and communication involving the staff and all family members should cover both medical and psychosocial issues. A well-planned and extensive initial session should be followed by continuing discussions. The goal is a knowledgeable family that can talk openly with its members and with the staff.

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.

Infant leukaemia after in utero exposure to radiation from Chernobyl.

There has been no documented increase in childhood leukaemia following the Chernobyl accident. However, different forms of childhood leukaemia may not be equally susceptible to radiation carcinogenesis. Infant leukaemia is a distinct form associated with a specific genetic abnormality. Outside the former Soviet Union, contamination resulting from the Chernobyl accident has been highest in Greece and Austria and high also in the Scandinavian countries. All childhood leukaemia cases diagnosed throughout Greece since 1 January 1980 have been recorded. Here we report that infants exposed in utero to ionizing radiation from the Chernobyl accident had 2.6 times the incidence of leukaemia compared to unexposed children (95% confidence interval, 1.4 to 5.1; P approximately 0.003), and those born to mothers residing in regions with high radioactive fallout were at higher risk of developing infant leukaemia. No significant difference in leukaemia incidence was found among children aged 12 to 47 months. Preconceptional irradiation had no demonstrable effect on leukaemia risk at any of the studied age groups.

Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology.

The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature.

Death of a child at home or in hospital: experiences of Greek mothers.

The purpose of this study was to investigate the experiences of Greek mothers who cared for a child dying of cancer at home or in the hospital, and to highlight some of their major needs during the terminal period. Fifteen mothers were interviewed and both quantitative and qualitative procedures were used to analyze the findings. Ten families (67%) chose to care for the child at home without having access to home care services, while the remaining five sought hospital care. Their decision was primarily based upon the child's expressed wish and parental preference. The family network played a significant role in supporting the mother-child unit, especially when death occurred at home. Mothers assessed positively the services provided by nurses and social workers, and had expectations that physicians would support them on a psychological level during the terminal period. The care of the dying child is influenced by cultural factors predominant in Greek society and some of the findings are discussed in this light.

Survival from childhood leukemia depending on socioeconomic status in Athens.

One hundred and twenty children first diagnosed as having acute leukemia between 1988 and 1992 in Athens, Greece, were followed until May 15, 1993. The socioeconomic status of the children's families was assessed by means of paternal occupation, paternal schooling, maternal schooling, ownership of a car, ability to choose a private medical facility and freedom in the choice of the attending physician. The analysis was done by proportional-hazards modelling, controlling for age and gender. All six socioeconomic indicators, alternatively evaluated, showed that fatality rates were higher in the lower socioeconomic groups, although nominal statistical significance was reached for only one of them. With respect to family ownership of a private car, the fatality rate ratio between children of families who own a car and children of families who do not was 0.29 with a 95% confidence interval of 0.13-0.62 (p = 0.002). These results suggest that in Greece, socially disadvantaged children have a less favorable survival from childhood leukemia.

Trends and geographical distribution of childhood leukemia in Greece in relation to the Chernobyl accident.

Parts of Greece have been exposed to fallout radiation from the Chernobyl accident as much as any of the countries boardering with the former Soviet Union, because of the direction of the prevailing winds after the accident. Although fallout radiation did not reach levels expected to be associated with measurable effects, there is widespread concern in Greece that the incidence of childhood leukemia may be rising in the more heavily affected parts of Greece. Patient discharge data from all Greek hospitals treating childhood leukemia were used to calculate the annual incidence of the disease from January 1980 to June 1986 (preaccident period), from July 1986 to June 1988 (immediate postaccident period) and from July 1988 to June 1991 ("relevant" post-accident period, that accommodates the presumed latent period of the disease). Fallout radiation measurements (in Bq/kg Cs-137) were used to create 17 regions of similar (within regions) but highly variable (between regions) levels of fallout deposition. Background radiation (in Bq/kg Ra-226) and annual incidence of childhood leukemia by region were also estimated. There was no evidence of increased incidence of childhood leukemia during the immediate or the "relevant" post-Chernobyl period in any part of the country. Furthermore, regression analyses did not show any significant or suggestive association of childhood leukemia by region with either background or fallout radiation. These results indicate that the Chernobyl accident did not affect noticeably the incidence of childhood leukemia in Greece during the five-year post accident period.

Establishment and characterization of a hepatoblastoma cell-line from a patient with secondary acute myeloid-leukemia.

A girl who had been treated, apparently successfully, with surgery and chemotherapy for a hepatoblastoma, fell ill two years later with what was diagnosed as an AMF M(4). A cell line was established from her peripheral blood. This cell line had epithelial morphology and grew both in suspension culture and as a monolayer. The cells were positive for epithelial surface markers, including the liver-specific alpha-fetoprotein, but not for leukocyte markers. The cell-line's karyotype was markedly abnormal. It did not have any specific aneuploidies or any other aberrations characteristic of leukemias; instead it had gains of 2q and chromosome 20, the most common cytogenetic changes in hepatoblastoma. It is most likely that the patient had a relapse of hepatoblastoma with massive seeding of the blood leading to a leukemia-like picture without, of course, excluding other possibilities.