Explore the vast range of titles available.

Cisplatin is an effective treatment for hepatoblastoma but often leads to lifelong irreversible hearing loss. The addition of sodium thiosulfate 6 hours after cisplatin administration preserved the antitumor effect and led to a lower risk of hearing loss (33% vs. 63%).

Background Survival after Wilms tumor has significantly increased and focus on late effects has become increasingly important. However, knowledge about long‐term renal function in survivors of Wilms tumor is missing. Our aim was to investigate evidence of kidney disease in 20‐ or more‐year survivors of Wilms tumor in a clinical setting, with siblings as comparisons. Methods In this cross‐sectional study, we established a cohort of Danish 20‐plus‐year survivors of Wilms tumor and siblings as controls. Participants answered a comprehensive health questionnaire supplemented by measurements of estimated glomerular filtration rate (eGFR), urine albumin‐to‐creatinine ratio, and blood pressure and were categorized according to the chronic kidney disease classification. Multiple linear regression analysis, taking family membership into account, was used to describe the differences in eGFR. Logistic regression analysis was performed to describe risk factors for the development of kidney disease. Results We included 99 survivors of Wilms tumor and 38 sibling controls with a median of 37 years of follow‐up. The eGFR of Wilms tumor survivors was 13 ml/min/1.73 m2 (95% CI –20; −5) lower when compared to sibling control. Evidence of kidney disease, with risk factors as hypertension and diabetes, was found in 19% of the Wilms tumor survivors and 2% developed end‐stage renal disease. Ninety‐two percent of the Wilms tumor survivors had an eGFR >60 ml/min/1.732. Conclusion Long‐term Wilms tumor survivors have on average a significantly decreased renal function along with the increased prevalence of kidney disease and end‐stage renal disease when compared to sibling controls. Still, most survivors had kidney function within the normal range. Long‐term Wilms tumor survivors have on average a significantly decreased renal function along with increased prevalence of kidney disease and end stage renal disease when compared to sibling controls. Still, most survivors had kidney function within normal range.

Survivors of childhood cancer are known to be at risk for long-term physical and mental effects. However, little is known about how cancers can affect mental health in the siblings of these patients. We aimed to assess the long-term risks of mental disorders in survivors of childhood cancer and their siblings. Hospital contact for mental disorders was assessed in a population-based cohort of 7085 Danish children treated for cancer by contemporary protocols between 1975 and 2010 and in their 13 105 siblings by use of data from the Danish Psychiatric Central Research Registry. Hazard ratios (HRs) for first hospital contact were calculated using a Cox proportional hazards model. We compared these sibling and survivor cohorts with two population-based cohorts who were not childhood cancer survivors or siblings of survivors. Survivors of childhood cancer were at increased risk of hospital contact for mental disorders, with HRs of 1·50 (95% CI 1·32–1·69) for males and 1·26 (1·10–1·44) for females. Children younger than 10 years at diagnosis had the highest risk, and increased risks were seen in survivors of CNS tumours, haematological malignancies, and solid tumours. Survivors had higher risk of neurodevelopmental, emotional, and behavioural disorders than population-based comparisons and siblings, and male survivors had higher risk for unipolar depression. Overall, siblings had no excess risk for mental disorders. However, our data suggest that siblings who were young at the time of cancer diagnosis of the survivor were at increased risk for mental disorders, whereas those older than 15 years at diagnosis were at a lower risk than the general population. Childhood cancer survivors should be followed up for mental late effects, especially those diagnosed in young age. Further, clinicians should also be aware that siblings who were young at the time of cancer diagnosis might be at increased risk for mental health disorders. Danish Childhood Cancer Foundation, Danish Agency for Science, Technology and Innovation, Danish Cancer Society, Gangsted Rasmussen Foundation, Rosalie Petersen Foundation, University Hospital Rigshospitalet's Fund for Cancer Rehabilitation, and the Otto Christensen Foundation.

The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high-dose methotrexate infusions in children with leukemia. All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00-DD48. Cancer type, extent of disease, treatment, participation in international studies, recurrence of malignant disease, survival, yearly follow-up status, causes of death, and development of secondary malignancies. Type of CVC, causes for removal of the CVC, type of blood stream infection, pathogens isolated, antimicrobial sensitivity, and outcome of antimicrobial chemotherapy. Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985 and is now 86%. The median number of days from diagnosis to initiation of therapy is 7 days and in 80% of the children less than 14 days. Clinical data of 95% of the patients are reported to open international studies. The survival of Danish children with cancer since 2003 compares favorably with other international population-based studies. The annual reports support the collaboration within pediatric oncology in Denmark.

The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy. We analysed 89 873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21 144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study. In 24 989 (27·8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64 884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19·4% (95% CI 13·2–27·0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identifed seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0·19 per 1000, and no false-negatives were found. The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.

Nausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time. Our objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use. We used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child's own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app. The app's most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient's chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis. The user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.

Ototoxicity is a common side effect of platinum treatment and manifests as irreversible, high-frequency sensorineural hearing loss. Genetic association studies have suggested a role for SNPs in genes related to the disposition of cisplatin or deafness. In this study, 429 pediatric patients that were treated with cisplatin were genotyped for 10 candidate SNPs. Logistic regression analyses revealed that younger age at treatment (≤5 years vs >15 years: OR: 9.1; 95% CI: 3.8–21.5; P = 5.6 × 10−7) and higher cumulative dose of cisplatin (>450 vs ≤300 mg/m2: OR: 2.4; 95% CI: 1.3–4.6; P = 0.007) confer a significant risk of ototoxicity. Of the SNPs investigated, none of them were significantly associated with an increase of ototoxicity. In the meta-analysis, ACYP2 rs1872328 (OR: 3.94; 95% CI: 1.04–14.03; P = 0.04) and SLC22A2 rs316019 (OR: 1.46; 95% CI: 1.07–2.00; P = 0.02) were associated with ototoxicity. In order to increase the understanding of the association between SNPs and ototoxicity, we propose a polygenic model, which takes into account multiple interacting genes of the cisplatin pathway that together confer an increased risk of ototoxicity.

Survivors of malignant bone tumors in childhood are at risk of long-term adverse health effects. We comprehensively reviewed cases of somatic diseases that required a hospital contact in survivors of osteosarcoma and Ewing sarcoma. In a population-based cohort study, 620 five-year survivors of osteosarcoma (n = 440) or Ewing sarcoma (n = 180), diagnosed before the age of 20 years in Denmark, Finland, Iceland, and Sweden during 1943–2008, were followed in the national hospital registers. Overall rates of hospital contacts for any somatic disease and for 12 main diagnostic groups and 120 specific disease categories were compared with those in a matched comparison cohort (n = 3049) randomly selected from the national population registers. The rate of hospital contact for any somatic disease was 80% higher in survivors of malignant bone tumors than in comparisons and remained elevated up to 30 years after diagnosis. The rate of hospital contacts was higher after Ewing sarcoma (rate ratio (RR) 2.24; 95% confidence interval (CI) 1.76–2.85) than after osteosarcoma (RR 1.67; 95% CI 1.41–1.98). Elevated rates were observed for 11 main diagnostic groups, including infections, second malignant neoplasms, and diseases of the skin, bones, and circulatory, digestive, endocrine, and urinary systems. Survivors of malignant bone tumors in childhood are at increased risk of somatic diseases many years after diagnosis. This comprehensive study contributes new insight into the risk of late effects in survivors of osteosarcoma and Ewing sarcoma, which is an essential basis for optimal patient counseling and follow-up care.

Background: Malignant liver tumours in children are rare and national outcomes for this tumour entity are rarely published. This study mapped paediatric liver tumours in Denmark over 35 years and reported on the incidence, outcomes and long-term adverse events. Methods: We identified all liver tumours from the Danish Childhood Cancer Registry and reviewed the case records for patient and tumour characteristics, treatment and clinical outcome. Results: We included 79 patients in the analyses. Overall crude incidence was ~2.29 per 1 million children (<15 yr) per year, with 61 hepatoblastomas (HB), 9 hepatocellular carcinomas and 9 other hepatic tumours. Overall 5-year survival was 84%, 78% and 44%, respectively. Nine patients had underlying liver disease or predisposition syndrome. Seventeen children underwent liver transplantation, with two late complications, biliary stenosis and liver fibrosis. For HB, age ≥ 8 years and diagnosis prior to 2000 were significant predictors of a poorer outcome. Adverse events included reduced renal function in 10%, reduced cardiac function in 6% and impaired hearing function in 60% (19% needed hearing aids). Behavioural conditions requiring additional support in school were registered in 10 children. Conclusions: In Denmark, incidences of malignant liver tumours during the last four decades have been increasing, as reported in the literature. HB survival has improved since the year 2000 and is comparable with international results. Reduced hearing is the major treatment-related side effect and affects approximately 60% of patients.

Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline. Because they are rare, histology of paediatric GCTs is poorly documented, and it remains unclear to what extent they differ from adult GCTs. We have analysed 35 paediatric germ cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients aged 0–15 years, to gain further knowledge, elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2 γ , SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal tumour (PDPN, GATA4). All YSTs expressed AFP and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2 and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma markers AP-2 γ , OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We further report a previously unrecognised pathogenetic relationship between AFP and SALL4 in YST in that different populations of YST cells express either SALL4 or AFP, which suggests variable differentiation status. We also show that AP-2 γ is expressed in the granulosa layer of ovarian follicles and weakly expressed in immature but not in mature granulosa cell tumours. Our findings indicate that the expression pattern of these antigens is similar between paediatric and adult GCTs, even though they develop along different developmental trajectories.