Wireless phone use in childhood and adolescence and neuroepithelial brain tumours: Results from the international MOBI-Kids study.

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk.

Geographical variability in survival of European children with central nervous system tumours.

Survival for childhood central nervous system (CNS) tumours varies across Europe, partly because of the difficulty of distinguishing malignant from non-malignant disease. This study examines bias in CNS tumours survival analysis to obtain the reliable and comparable survival figures. We analysed survival data for about 15,000 children (age <15) diagnosed with CNS between 2000 and 2007, from 71 population-based cancer registries in 27 countries. We selected high-quality data based on registry-specific data quality indicators and recorded observed 1-year and 5-year survival by countries and CNS entity. We provided age-adjusted survival and used a Cox model to calculate the hazard ratios (HRs) of death, adjusting by age, site and grading by country. Recording of non-malignant lesions, use of appropriate morphology codes and completeness of life status follow-up differed among registries. Five-year survival by countries varied less when non-malignant tumours were included, with rates between 79.5% and 42.8%. The HRs of dying, for registries with good data, adjusting by age and grading, were between 0.7 and 1.2; differences were similar when site (supra- and infra-tentorial) was included. Several sources of bias affect the correct definition of CNS tumours, the completeness of incidence series and the goodness of follow-up. The European Network of Cancer Registries needs to improve childhood cancer registration and stress the need to update the International Classification for Cancer. Since survival differences persisted even when restricting the analysis to registries with satisfactory data, and since diagnosis of CNS tumours is difficult and treatment complex, national plans must aim for the revision of the diagnosis and the coordination of care, with adequate national and international networks.

Are dietary reports in a case-control study on thyroid cancer biased by risk perception of Chernobyl fallout?

BACKGROUND: In retrospective case-control studies performed following nuclear tests or nuclear accidents, individual thyroid radiation dose reconstructions are based on fallout and meteorological data from the residential area, demographic characteristics, and lifestyle as well as dietary information. Collecting the latter is a controversial step, as dietary declarations may be affected by the subjects' beliefs about their risk behavior. This report analyses the potential for such bias in a case-control study performed in eastern France. METHODS: The study included 765 cases of differentiated thyroid carcinoma matched with 831 controls. Risk perceptions and beliefs of cases and controls were compared using Chi2 tests and differences in dietary reports were analyzed using a two-way ANOVA. RESULTS: In general, atmospheric pollution and living near a nuclear power plant were the two major risks that may influence thyroid cancer occurrence cited by cases and controls. When focusing in particular on the consequences of the Chernobyl accident, cases were more likely to think that the consequences were responsible for thyroid cancer occurrence than controls. Vegetable consumption during the two months after the Chernobyl accident was correlated with the status of subjects, but not to their beliefs. Conversely, consumption of fresh dairy products was not correlated with the status or beliefs of subjects. CONCLUSION: We found no evidence of systematic bias in dietary reports according to the status or beliefs held by subjects about the link between thyroid cancer occurrence and Chernobyl fallout. As such, these dietary reports may be used in further studies involving individual dosimetric reconstructions.

Cervical trophoblasts for non-invasive single-cell genotyping and prenatal diagnosis.

OBJECTIVE: We aimed at developing a method to recover trophoblastic cells from the cervix through a completely non-invasive approach and obtaining a genetic proof of their fetal nature implying that they can be used for non-invasive prenatal diagnosis (NIPD). METHODS: We studied obstetrical samples from 21 pregnant women between 8 and 12 weeks of gestation scheduled for chorionic villus sampling or undergoing elective termination of pregnancy. A cytobrush was used to extract cells from the external parts of the cervix and transferred to 10 ml of preservative solution. Cells were layered on filters with 8 microns pores using the ISET system (Isolation by SizE of Tumor/Trophoblastic cells) and stained. Putative fetal cells were collected by single cell laser-assisted microdissection and identified as fetal or maternal cells by Short Tandem Repeat genotyping. NIPD was blindly performed on 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy. RESULTS: Trophoblastic cells were recovered from all tested cervical samples with a frequency of 2-12 trophoblasts per 2 ml. NIPD was blindly obtained and verified in 6 mothers at risk of having a fetus with Cystic Fibrosis or Spinal Muscular Atrophy. DISCUSSION: Although larger confirmation studies are required, this is the first report providing a solid proof of principle that trophoblasts can be consistently and safely recovered from cervical samples. Since they are a source of pure fetal DNA, i.e. fetal DNA not mixed with maternal DNA, they constitute an ideal target to develop NIPD of recessive diseases, which is a technical challenge for methods based on cell free DNA.

Nasal polyposis and cystic fibrosis(CF): review of the literature.

The aim of this study was to address whether NP might be a predictive factor for severity of CF. The authors collected data from the literature on NP as a unique or associated sign in CF and reviewed the clinical and molecular aspects of CF associated with NP. CF genotypes and clinical severity in NP(+) vs. NP(-) patients were reviewed, taking into account pulmonary function, frequency of P. aeruginosa lung infection, frequency of allergy, nutritional status, and exocrine pancreatic function. The CFTR gene was also analyzed in a patient with isolated severe NP as the unique feature of CF. This review of the literature showed a `milder` phenotype in `NP+` vs. `NP-` CF patients, contrasting with a marked association between NP and `severe` CF mutations. In addition, a complex genotype was identified, associating four heterozygous variants, namely p.Q493X (a severe mutation) on the paternal allele, and p.V562I, p.A1006E, and (TG)11(T)5 (IVS8-5T) on the maternal allele, in a case of CF presenting as isolated NP. The authors speculate that genetic/environmental factors associated with NP might attenuate the functional impact of `severe` CF mutations. The overrepresentation of CF carriers among patients with isolated NP also advocates the need for CFTR molecular screening in such populations for genetic counselling purposes.

[Epidemiology and management of rare paediatric tumours within the framework of the French Society for Children Cancer]. / Tumeurs rares en pédiatrie : particularités épidémiologiques et organisation de leur prise en charge dans le cadre de la Société française des cancers et des leucémies de l'enfant et de l'adolescent (SFCE).

Less than 1% of cancer occurs in children. With the progress made by national and international cooperative groups 75% of them are actually cured. However some entities have an incidence so weak that we can't actually establish standardized therapeutics guidelines. To improve our knowledge on these rare tumours a national organisation become necessary as well as an international collaboration. A French rare tumour committee was created within the French Society for Children Cancer (SFCE). Others European countries have such organisation. The objectives of these tasks groups are to enhance our knowledge of the real incidence of these rare tumours, their evolution, and to propose therapeutic recommendations for each of them. This article focuses on the specific French organization for rare tumours treatment. It also describes the draft for the creation of a new data base for prospective registry of clinical, therapeutics and follow up data. To provide a better understanding of these pathologies, the "Bulletin du Cancer's" editorial board decided to regularly publish an update on a rare paediatric tumour in a specific section.

[2,8-dihydroxyadenine nephrolithiasis: from diagnosis to therapy]. / Lithiase de 2,8-dihydroxyadénine: du diagnostic à la prise en charge thérapeutique.

Adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency is an enzymopathy of purine metabolism, which is inherited as an autosomal recessive trait. APRT is a salvage enzyme that normally catalyzes the conversion of adenine to adenosine monophosphate. APRT deficiency results in adenine accumulation with oxidation by xanthine dehydrogenase (XDH; EC 1.1.1.204) to 2,8-dihydroxyadenine (2,8-DHA) then excreted in urine. This compound is extremely insoluble and its crystallization can lead to stone formation and renal failure. The diagnosis of the disease is based on stone analysis by infrared spectroscopy or microscopic examination of urine, which may reveal typical 2,8-DHA crystals. The enzyme activity measurements in erythrocyte lysates will identify both homozygotes and heterozygotes for APRT deficiency. Molecular approach can identify mutations which are responsible of this inherited disease. Two types of deficit are commonly distinguished, depending on the level of residual APRT activity: type I, mainly observed in Caucasian subjects, in whom the enzyme activity is undetectable in homozygous patients and type II, found in Japanese patients who are able to form APRT but the enzyme activity is strikingly reduced because a low affinity for phosphoribosylpyrophosphate. The crystallization of 2,8-DHA and subsequent renal damages may be prevented with allopurinol therapy, a xanthine oxidase inhibitor. The role of the laboratory is crucial to detect APRT deficiency and to assess the efficacy of therapy, the objective being to avoid 2,8-DHA crystal formation.

Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas.

BACKGROUND: Prognosis for most types of childhood tumours has improved during the last few decades. In this article we estimate up-to-date period survival for less common, but important childhood malignancies in Europe. METHODS: Using the database of the Automated Childhood Cancer Information System we calculated period estimates of 10-year survival for the 1995-1999 period for children aged 0-14 years diagnosed during 1985-1999 with tumours of the sympathetic nervous system (NS), retinoblastoma, renal tumours, bone tumours and soft tissue sarcomas in four European regions. RESULTS: Ten-year period survival for 1995-1999 was 66% in children with tumours of the sympathetic NS, 96% for retinoblastoma, 87% for renal tumours, 58% for bone tumours and 61% for soft tissue sarcomas. The higher period estimates, as compared with cohort and complete estimates indicate recent improvement in survival for tumours of the sympathetic NS and to a lesser extent for retinoblastoma and renal tumours. Region-specific period survival estimates were lowest for Eastern Europe for renal, bone and soft tissue tumours, but not for the other two tumour groups. CONCLUSION: There have been further improvements in the 1990s in long-term survival of children diagnosed with several malignancies, albeit to a different extent in different European regions.

Quality, comparability and methods of analysis of data on childhood cancer in Europe (1978-1997): report from the Automated Childhood Cancer Information System project.

In collaboration with 62 population-based cancer registries contributing to the Automated Childhood Cancer Information System (ACCIS), we built a database to study incidence and survival of children and adolescents with cancer in Europe. We describe the methods and evaluate the quality and internal comparability of the database, by geographical region, period of registration, type of registry and other characteristics. Data on 88,465 childhood and 15,369 adolescent tumours registered during 1978-1997 were available. Geographical differences in incidence are caused partly by differences in definition of eligible cases. The observed increase in incidence rates cannot be explained by biases due to the selection of datasets for analyses, and only partially by the registration of non-malignant or multiple primary tumours. Part of the observed differences in survival between the regions may be due to variable completeness of follow-up, but most is probably explained by resource availability and organisation of care. Further standardisation of data and collection of additional variables are required so that this study may continue to yield valuable results with reliable interpretation.

Thyroid cancer incidence and survival among European children and adolescents (1978-1997): report from the Automated Childhood Cancer Information System project.

Data on 1690 childhood and adolescent cases of thyroid cancer registered in 61 European cancer registries were extracted from the database of the Automated Childhood Cancer Information System (ACCIS) and included in analyses of incidence and survival. In 1988-1997, the age-standardised incidence rates (ASR) for children aged 0-14 years varied in European regions from 0.5 to 1.2 per million and the age-specific incidence in adolescents aged 15-19 years ranged from 4.4 to 11.0 per million. Over the age-span 0-19 years, the female to male ratio increased from 1 to around 3. Papillary thyroid cancer accounted for almost 65% of cases in children and 77% in adolescents. In the childhood population of Belarus, the ASR for 1989-1997 was 23.6 per million and the proportion of papillary tumours was 87%. No association was found between thyroid cancer risk and national dietary iodine status across 16 countries. Incidence of thyroid carcinoma among children and adolescents in Europe (excluding Belarus) increased during 1978-1997 by 3% per year, largely due to papillary carcinoma. Survival of children and adolescents was high over the entire study period and in all regions of Europe. Children with medullary carcinoma had slightly lower 5-year survival (95%, 95% CI 81-99), than those with papillary carcinoma (99%, 95% CI 95-100). More than 90% of patients survived 20 years after diagnosis. Further standardisation of diagnostic, classification and registration criteria will be fundamental for future studies of thyroid carcinomas in young people.

[Lorraine childhood cancer registry: incidence, survival 1983-1999]. / Le registre lorrain des cancers de l'enfant: incidence, survie 1983-1999.

BACKGROUND: Cancer in childhood account for less than 1% of all cancers and for the second most important cause of death for children aged less than 15 years in France, injuries being the leading cause. Compared to adult cancers, childhood cancers' particularities justify to create pediatric registries. The first French population-based registry was created in Lorraine in 1983. The incidence and survival results from a 17 year-period are presented. METHODS: In Lorraine region, all children (0-14 years) with cancer diagnosed between 1983 and 1999 were included. Crude, age-standardized (world population) and cumulative incidence rates were calculated just as overall, specific-disease and event-free survival rates, using Kaplan-Meier methods. RESULTS: With 1086 registered cases, the crude incidence rate per million children is 132.4, the age-standardized incidence rate per million is 137.5; 1 out of every 500 children will develop cancer before the age of 15 years. The incidence of all cancers combined is slightly higher in males than in females with a M/F ratio of 1.13. For this 17 years-period, no trend in childhood cancer incidence is observed. The main cancer groups are leukemia (30.7%), brain and spinal tumors (23.2%) and lymphomas (12.9%), sympathetic nervous system tumors (7.4%), soft-tissue sarcomas (6.1%), renal tumors (5.2%), and bone tumors (5.0%). Five-year specific survival rates for all cancers combined is 71.4% [95% CI: 68.5-74.3]. The prognosis is significatively worse for the<1 year age group (55%) and for some histologic types: brain stem gliomas (27%), hepatic tumors (43%), osteosarcomas (57%), neuroblastomas (65%), rhabdomyosarcomas (55%). DISCUSSION: Relative distribution of histologic groups, incidence and survival rates observed in Lorraine registry are compatible with the general pattern in the European Union cancer registries. The lack of significative trend in incidence unlike others country may be explained by too small numbers. CONCLUSION: The acquired experience in developping this regional registry allowed us to create a national registry of childhood solid tumors and contribute to valid national data.

[Clinical value of crystalluria study]. / Intérêt clinique de l'étude de la cristallurie.

Crystalluria is a marker of urine supersaturation present in both normal and pathological conditions. Indeed, nature and characteristics of the spontaneous crystalluria are of clinical interest for detecting and following biological disorders involved in renal diseases. Method. Crystalluria examination should preferably be performed on first morning urine or fresh fasting voiding samples by polarised microscopy in a Malassez cell. Urine samples must be stored at 37 degrees C or at room temperature and examined within two hours following voiding. Results and discussion. Crystalluria should be interpreted according to various criteria: 1) chemical nature of crystals for abnormal crystals such as struvite, ammonium urate, cystine, dihydroxyadenine, xanthine or drugs; 2) crystalline phase of common chemical species as calcium oxalates, calcium phosphates and uric acids; 3) crystal morphology (calcium oxalates); 4) crystal size (calcium oxalates); 5) crystal abundance (calcium oxalates, calcium phosphates, uric acids, cystine); 6) crystal aggregation (calcium oxalates); 7) frequency of crystalluria assessed on serial first morning urine samples, a very useful tool for long-term surveillance of patients. Within calcium oxalate crystalluria, presence of whewellite is a marker of elevated oxalate concentration (urine oxalate > 0.3 mmol/L); a crystal number > 200/mm 3 is highly suggestive of heavy hyperoxaluria of genetic or absorptive origin. Predominant weddellite crystalluria is most often indicative of an excessive urine calcium concentration (> 3.8 mmol/L); a dodecahedric aspect of the crystals is a marker for heavy hypercalciuria (> 6 mmol/L) while an increased crystal size (>or= 35 microm) is indicative of simultaneous hypercalciuria and hyperoxaluria. Calculation of the global crystal volume, especially when applied to calcium oxalates or cystine, is a clinically useful tool for the monitoring of patients suffering from primary hyperoxaluria or cystinuria. Lastly, presence of crystalluria in more than 50% of serial first voided morning urine samples is in our experience the most reliable biological marker for detecting the risk of stone recurrence in lithiasic patients. Conclusion. Crystalluria examination is an essential laboratory test for detecting and following pathological conditions, which may induce renal stone disease or alter kidney function due to urine crystals.

Prenatal diagnosis of spinal muscular atrophy by genetic analysis of circulating fetal cells.

Spinal muscular atrophy (SMA) has a prevalence of one in 6000 births and a one in 40 heterozygote frequency. We aimed to develop a routine test for non-invasive prenatal diagnosis. We tested blood with ISET (isolation by size of epithelial tumour or trophoblastic cells) in 12 pregnant women whose babies were at risk of SMA. Using genetic analysis of fetal cells, we identified SMA in all nine isolated from the three mothers carrying an affected child. There was no mutation in any of the 26 fetal cells isolated from the nine women with an unaffected child. Our results show that non-invasive detection of genetic diseases by the analysis of maternal blood is feasible.

Effect of ethanol and ether in the prevention of calcification of bioprostheses.

BACKGROUND: Lipids play a significant role in the process of calcification of bioprostheses. We assessed whether lipid extraction by ethanol, ether, or a surfactant could mitigate calcification of glutaraldehyde-treated bioprostheses. METHODS: On 200 bovine pericardium samples pretreated with 0.6% glutaraldehyde, lipid extraction was carried out by ethanol, ether, or the tween 80 surfactant, and combinations thereof. The treated tissues were implanted subcutaneously in 50 juvenile rats for 4 and 6 months. Lipids were analyzed by Fourier transform infrared spectrophotometer and chromatography before implantation. Calcium content of implanted tissues was assessed by atomic absorption spectrometer. RESULTS: Ethanol, ether, or surfactant did mitigate calcification. The most efficient pretreatments were the combination of ethanol and surfactant (calcium content: 15.5+/-6.8 microg/mg dry tissue after 6 months implantation) or the combination of ethanol, ether, and surfactant (13.1+/-6.2 microg/mg dry tissue) when compared with surfactant alone (42.9+/-12.7 microg/mg dry tissue). CONCLUSIONS: Ethanol or the combination of ethanol and ether added to the currently used glutaraldehyde-surfactant treatment further mitigates calcification.

Oxidative stress and haemodialysis: role of inflammation and duration of dialysis treatment.

BACKGROUND: Oxidative stress has long been demonstrated in haemodialysis patients. However, the factors influencing their oxidative status have not been characterized extensively in these patients. Therefore, the present study was designed to investigate the influence of a large number of factors known to be associated with oxidative stress. METHODS: In the present cross-sectional study, we determined the plasma levels of lipid and protein oxidation markers in 31 non-smoking haemodialysis patients and 18 non-smoking healthy subjects, together with various components of the antioxidant system at the plasma and erythrocyte level. RESULTS: No influence of age, diabetes or iron overload on oxidative markers and plasma and erythrocyte antioxidant systems was detected in these haemodialysis patients. The lack of an association between iron overload and oxidative status may be related to the lower level of plasma ascorbate in haemodialysis patients, since ascorbate favours the generation of free iron from ferritin-bound iron. Interestingly, plasma C reactive protein (CRP) levels measured by highly sensitive CRP assay were correlated positively with plasma levels of thiobarbituric acid reactive substances (r=0.38, P<0.04) and negatively with plasma alpha-tocopherol levels (r=-0.46, P<0.01). Moreover, significant inverse correlations were observed between duration of dialysis treatment and plasma levels of alpha-tocopherol (r=-0.49, P<0.02) and ubiquinol (r=-0.40, P<0.05). CONCLUSIONS: Our results suggest that inflammatory status and duration of dialysis treatment are the most important factors relating to oxidative stress in haemodialysis patients.

Caspase-dependent apoptosis in THP-1 cells exposed to oxidized low-density lipoproteins.

Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogenesis. We investigated the apoptotic process in human monocytic THP-1 cell line, exposed to oxLDL generated by treatment of native LDL either with hypochlorous acid (HOCl), mainly affecting the protein moiety, or with copper sulfate (CuSO(4)), mainly affecting the lipid moiety. After incubation with both types of oxLDL, we observed: (i) microscopy signs of apoptosis in THP-1 cells, (ii) a significant increase of apoptotic cells proportional to LDL protein concentration, either by annexin V or by cell cycle phase analysis with propodium iodide flow cytometry, (iii) a reduction of THP-1 cell apoptosis in presence of the caspase inhibitor Z-VAD.fmk, (iv) the resistance of THP-1 cells apoptosis after PMA-elicited differentiation. In conclusion, HOCl-oxLDL are as potent as Cu-oxLDL to induce high rates of apoptosis in monocytes through a caspase-dependent pathway. Moreover, the resistance of differentiated THP-1 cells to oxLDL-induced apoptosis is compatible with the hypothesis that mature macrophages have prolonged survival and thereby enhance the atherogenic process.

Detection of circulating prostate derived cells in patients with prostate adenocarcinoma is an independent risk factor for tumor recurrence.

PURPOSE: To determine whether the presence of prostate-derived cells in the peripheral blood circulation is a marker of prostate cancer and to define the clinical impact of the test. MATERIALS AND METHODS: We tested the peripheral blood of 99 patients with prostate adenocarcinoma (PAC), 79 of them undergoing radical prostatectomy, and 92 controls (31 healthy volunteers, 50 patients with adenoma and 11 with prostatitis) using a highly controlled procedure including reverse-transcriptase polymerase chain reaction (RT-PCR) targeted to prostate-specific antigen (PSA) mRNA. Patients were followed for 26 +/- 12 (range: 4 to 49) months. Forty tumor tissues were analyzed by immunohistochemistry for expression of p53 and E-cadherin antigens. RESULTS: Thirty three (33%) patients with PAC and 2 (2%) controls scored positive (p <0.0001) for the test. Detection of circulating prostatic cells was associated with development of metastases (p <0. 001), with relapse (p <0.001) and with a serum PSA level at diagnosis higher than 15 ng./ml. (p = 0.009). The rate of development of metastases according to time was significantly higher in patients who scored positive for the test (p <0.04). In a multivariate analysis, only the RT-PCR test was an independent risk factor associated with relapse (RR: 6.7). Finally, E-cadherin expression was significantly lower in the tumor tissues of positive patients as compared with those who scored negative for the test (p <0.01). CONCLUSIONS: This RT-PCR procedure, performed at diagnosis and with appropriate controls, is a clinically useful assay in evaluating the risk of tumor recurrence after radical prostatectomy in patients with PAC.