Contemporary N2 and SF6 multiple breath washout in infants and toddlers with cystic fibrosis.

INTRODUCTION: Multiple breath washout (MBW) is used for early detection of cystic fibrosis (CF) lung disease, with SF6 MBW commonly viewed as the reference method. The use of N2 MBW in infants and toddlers has been questioned for technical and physiological reasons, but a new correction of the N2  signal has minimized the technical part. The present study aimed to assess the remaining differences and the contributing mechanisms for the differences between SF6 and N2 MBW,corrected-such as tidal volume reduction during N2 washout with pure O2 . METHOD: This was a longitudinal multicenter cohort study. SF6 MBW and N2 MBW were performed prospectively at three CF centers in the same visits on 154 test occasions across 62 children with CF (mean age: 22.7 months). Offline analysis using identical algorithms to the commercially available program provided outcomes of N2,original and N2,corrected for comparison with SF6 MBW. RESULTS: Mean functional residual capacity, FRCN2,corrected was 14.3% lower than FRCN2, original , and 1.0% different from FRCSF6 . Lung clearance index, LCIN2,corrected was 25.2% lower than LCIN2,original , and 7.3% higher than LCISF6 . Mean (SD) tidal volume decreased significantly during N2 MBWcorrected , compared to SF6 MBW (-13.1 ml [-30.7; 4.6], p < 0.0001, equal to -12.0% [-25.7; 1.73]), but this tidal volume reduction did not correlate to the differences between LCIN2,corrected and LCISF6 . The absolute differences in LCI increased significantly with higher LCISF6 (0.63/LCISF6 ) and (0.23/LCISF6 ), respectively, for N2,original and N2,corrected , but the relative differences were stable across disease severity for N2,corrected , but not for N2,original . CONCLUSION: Only minor residual differences between FRCN2,corrected and FRCSF6 remained to show that the two methods measure gas volumes very similar in this age range. Small differences in LCI were found. Tidal volume reduction during N2 MBW did not affect differences. The corrected N2 MBW can now be used with confidence in young children with CF, although not interchangeably with SF6 .

Socioeconomic inequality in cancer survival - changes over time. A population-based study, Denmark, 1987-2013.

Background: Socioeconomic inequality in survival after cancer have been reported in several countries and also in Denmark. Changes in cancer diagnostics and treatment may have changed the gap in survival between affluent and deprived patients and we investigated if the differences in relative survival by income has changed in Danish cancer patients over the past 25 years. Methods: The 1- and 5-year relative survival by income quintile is computed by comparing survival among cancer patients diagnosed 1987-2009 to the survival of a cancer-free matched sample of the background population. The comparison is done within the 15 most common cancers and all cancers combined. The gap in relative survival due to socioeconomic inequality for the period 1987-1991 is compared the period 2005-2009. Results: The relative 5-year survival increased for all 15 cancer sites investigated in the study period. In general, low-income patients diagnosed in 1987-1991 had between 0% and 11% units lower 5-year relative survival compared with high-income patients; however, only four sites (breast, prostate, bladder and head & neck) were statistically different. In patients diagnosed 2005-2009, the gap in 5-year RS was ranging from 2% to 22% units and statistically significantly different for 9 out of 15 sites. The results for 1-year relative survival were similar to the 5-year survival gap. An estimated 22% of all deaths at five years after diagnosis could be avoided had patients in all income groups had same survival as the high-income group. Conclusion: In this nationwide population-based study, we observed that the large improvements in both short- and long-term cancer survival among patients diagnosed 1987-2009. The improvements have been most pronounced for high-income cancer patients, leading to stable or even increasing survival differences between richest and poorest patients. Improving survival among low-income patients would improve survival rates among Danish cancer patients overall and reduce differences in survival when compared to other Western European countries.

Radiation Therapy for Treatment of Adolescent and Young Adult Hodgkin Lymphoma and Risk for Cardiovascular Disease and Cancer.

PURPOSE: To estimate the risk for hospitalizations among survivors of Hodgkin lymphoma diagnosed in adolescence or young adulthood according to exposure to treatment with radiation therapy. METHODS: Through the files of the Danish Cancer Registry, we identified 1684 five-year survivors of Hodgkin lymphoma, diagnosed at age 15-39 years during the period 1943-2004, and for whom information on radiation therapy was available in the Cancer Registry. Population-based comparisons were identified through the Danish Civil Registration System and matched to the survivors on year of birth and sex. Survivors of Hodgkin lymphoma and comparisons were linked to the Danish National Patient Register for information on hospitalizations. Standardized hospitalization rate ratios (RR) and absolute excess rates (AERs) were estimated for total number of hospitalizations and for hospitalizations for cardiovascular disease, cancer and several other disease groups. RESULTS: Overall, survivors of Hodgkin lymphoma who received radiation therapy had higher risk (RR 2.0) and AER (AER 588) of hospitalization than survivors not treated with radiation therapy (RR 1.8; AER 399). Especially, the risk for cardiovascular disease and cancer was high among survivors who received radiation therapy (RR 2.8 and 3.6) compared with survivors who did not receive this type of treatment (RR 2.2 and 2.3). CONCLUSION: Survivors of adolescent and young adult Hodgkin lymphoma treated with radiation therapy had a higher risk of diseases requiring hospitalization than survivors not treated with radiation therapy. Irrespective of the type of treatment received, initiatives that prevent and minimize hospital-requiring late effects in survivors of Hodgkin lymphoma are needed.

Neurologic disorders in 4858 survivors of central nervous system tumors in childhood-an Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study.

Background: A comprehensive overview of neurologic complications among survivors of central nervous system (CNS) tumors in childhood is lacking. We aimed to investigate the risk for these disorders in a large, population-based study with outcome measures from nationwide hospital registries. Methods: We identified 4858 five-year survivors with diagnoses of CNS tumor in childhood in Denmark, Iceland, Finland, and Sweden in 1943-2007, and 166658 matched population comparison subjects. Inpatient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). Results: A neurologic disorder was verified in 1309 survivors, while 92.4 were expected, yielding an overall RR of 14.2 (95% confidence interval [CI]: 13.3-15.1) and an AER of 20 hospitalizations per 1000 persons per year. The risks remained increased more than 20 years after diagnosis (RR: 6.3, 95% CI: 5.6-7.2; AER: 11, 9-12). The most frequent diagnoses were epilepsy (affecting 14.1% of all survivors) followed by hydrocephalus (9.5%) and paralytic syndromes (4.2%), with RRs of 28.7 (95% CI: 26.0-31.6), 243 (95% CI: 190-311), and 40.3 (95% CI: 33.1-49.2), respectively. Of these outcomes, 30%-40% were diagnosed prior to or synchronously with the CNS tumor. The survivors had highly increased RRs for infectious diseases of the CNS, disorders of cranial nerves, and degenerative diseases of the nervous system. Conclusions: Survivors of childhood CNS tumors are at markedly increased risk for neurologic disorders throughout their lives. Health care professionals must be aware of survivors who might benefit from preventive interventions and intensive follow-up.

Liver diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS): A population-based cohort study of 32,839 one-year survivors.

Information on late onset liver complications after childhood cancer is scarce. To ensure an appropriate follow-up of childhood cancer survivors and reducing late liver complications, the need for comprehensive and accurate information is presented. We evaluate the risk of liver diseases in a large childhood cancer survivor cohort. We included all 1-year survivors of childhood cancer treated in the five Nordic countries. A Cox proportional hazards model was used to estimate hospitalisation rate (hazard) ratios (HRs) for each liver outcome according to type of cancer. We used the risk among survivors of central nervous system tumour as internal reference. With a median follow-up time of 10 years, 659 (2%) survivors had been hospitalised at least once for a liver disease. The risk for hospitalisation for any liver disease was high after hepatic tumour (HR = 6.9) and leukaemia (HR = 1.7). The Danish sub-cohort of leukaemia treated with haematopoietic stem cell transplantation had a substantially higher risk for hospitalisation for all liver diseases combined (HR = 3.8). Viral hepatitis accounted for 286 of 659 hospitalisations corresponding to 43% of all survivors hospitalised for liver disease. The 20-year cumulative risk of viral hepatitis was 1.8% for survivors diagnosed with cancer before 1990 but only 0.3% for those diagnosed after 1990. The risk of liver disease was low but significantly increased among survivors of hepatic tumours and leukaemia. Further studies with focus on the different treatment modalities are needed to further strengthen the prevention of treatment-induced late liver complications.

Long-term inpatient disease burden in the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study: A cohort study of 21,297 childhood cancer survivors.

BACKGROUND: Survivors of childhood cancer are at increased risk for a wide range of late effects. However, no large population-based studies have included the whole range of somatic diagnoses including subgroup diagnoses and all main types of childhood cancers. Therefore, we aimed to provide the most detailed overview of the long-term risk of hospitalisation in survivors of childhood cancer. METHODS AND FINDINGS: From the national cancer registers of Denmark, Finland, Iceland, and Sweden, we identified 21,297 5-year survivors of childhood cancer diagnosed with cancer before the age of 20 years in the periods 1943-2008 in Denmark, 1971-2008 in Finland, 1955-2008 in Iceland, and 1958-2008 in Sweden. We randomly selected 152,231 population comparison individuals matched by age, sex, year, and country (or municipality in Sweden) from the national population registers. Using a cohort design, study participants were followed in the national hospital registers in Denmark, 1977-2010; Finland, 1975-2012; Iceland, 1999-2008; and Sweden, 1968-2009. Disease-specific hospitalisation rates in survivors and comparison individuals were used to calculate survivors' standardised hospitalisation rate ratios (RRs), absolute excess risks (AERs), and standardised bed day ratios (SBDRs) based on length of stay in hospital. We adjusted for sex, age, and year by indirect standardisation. During 336,554 person-years of follow-up (mean: 16 years; range: 0-42 years), childhood cancer survivors experienced 21,325 first hospitalisations for diseases in one or more of 120 disease categories (cancer recurrence not included), when 10,999 were expected, yielding an overall RR of 1.94 (95% confidence interval [95% CI] 1.91-1.97). The AER was 3,068 (2,980-3,156) per 100,000 person-years, meaning that for each additional year of follow-up, an average of 3 of 100 survivors were hospitalised for a new excess disease beyond the background rates. Approximately 50% of the excess hospitalisations were for diseases of the nervous system (19.1% of all excess hospitalisations), endocrine system (11.1%), digestive organs (10.5%), and respiratory system (10.0%). Survivors of all types of childhood cancer were at increased, persistent risk for subsequent hospitalisation, the highest risks being those of survivors of neuroblastoma (RR: 2.6 [2.4-2.8]; n = 876), hepatic tumours (RR: 2.5 [2.0-3.1]; n = 92), central nervous system tumours (RR: 2.4 [2.3-2.5]; n = 6,175), and Hodgkin lymphoma (RR: 2.4 [2.3-2.5]; n = 2,027). Survivors spent on average five times as many days in hospital as comparison individuals (SBDR: 4.96 [4.94-4.98]; n = 422,218). The analyses of bed days in hospital included new primary cancers and recurrences. Of the total 422,218 days survivors spent in hospital, 47% (197,596 bed days) were for new primary cancers and recurrences. Our study is likely to underestimate the absolute overall disease burden experienced by survivors, as less severe late effects are missed if they are treated sufficiently in the outpatient setting or in the primary health care system. CONCLUSIONS: Childhood cancer survivors were at increased long-term risk for diseases requiring inpatient treatment even decades after their initial cancer. Health care providers who do not work in the area of late effects, especially those in primary health care, should be aware of this highly challenged group of patients in order to avoid or postpone hospitalisations by prevention, early detection, and appropriate treatments.

Long-term hospitalisation rates among 5-year survivors of Hodgkin lymphoma in adolescence or young adulthood: A nationwide cohort study.

In the present study, we report on the full range of physical diseases acquired by survivors of Hodgkin lymphoma diagnosed in adolescence or young adulthood. In a Danish nationwide population-based cohort study, 1,768 five-year survivors of Hodgkin lymphoma diagnosed at ages 15-39 years during 1943-2004 and 228,447 comparison subjects matched to survivors on age and year of birth were included. Hospital discharge diagnoses and bed-days during 1977-2010 were obtained from the Danish Patient Register for 145 specific disease categories gathered in 14 main diagnostic groups. The analysis was conducted separately on three subcohorts of survivors, that is, survivors diagnosed 1943-1976 for whom we had no information on rehospitalisation for Hodgkin lymphoma and survivors diagnosed 1977-2004, split into a subcohort with no expected relapses and a subcohort for whom a rehospitalisation for Hodgkin lymphoma indicated a relapse. The overall standardised hospitalisation rate ratios (RRs) were 2.0 [95% confidence interval (CI), 1.9-2.1], 1.5 (1.4-1.6) and 2.9 (2.6-3.1) respectively, and the corresponding RRs for bed-days were 3.5 (3.4-3.5), 1.8 (1.8-1.9) and 10.4 (10.3-10.6). Highest RRs were seen for nonmalignant haematological conditions (RR: 2.6; 3.1 and 9.7), malignant neoplasms (RR: 3.2; 2.5 and 4.7) and all infections combined (RR: 2.5; 2.2 and 5.3). Survivors of Hodgkin lymphoma in adolescence or young adulthood are at increased risk for a wide range of diseases that require hospitalisation. The risk depends on calendar period of treatment and on whether the survivors were rehospitalised for Hodgkin lymphoma, and thus likely had a relapse.

Long-term risk of renal and urinary tract diseases in childhood cancer survivors: A population-based cohort study.

BACKGROUND: Childhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries. METHODS: We identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference. RESULTS: We observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4-2.7) and an AER of 229 (95% CI 210-248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs. CONCLUSION: Survivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours.

Low risk of solid tumors in persons with Down syndrome.

PURPOSE: The aim of this study was to investigate cancer incidence in a large cohort of persons with Down syndrome. METHODS: Down syndrome was identified from the Danish Cytogenetic Register. Cancer occurrence was identified by linkage to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated based on observed and expected numbers from rates for all Danish residents. The cohort consisted of 3,530 persons with Down syndrome contributing 89,570 person-years at risk. RESULTS: Acute leukemia risk was highest from 1-4 years of age and remained elevated until age 30. The overall risk of solid tumors was decreased (SIR 0.45; 95% CI 0.34-0.59), especially in persons 50 years or older (SIR 0.27; 95% CI 0.16-0.43). We found a significantly lower risk of lung cancer (SIR 0.10; 95% CI 0.00-0.56), breast cancer (SIR 0.16; 95% CI 0.03-0.47), and cervical cancer (SIR 0.0; 95% CI 0.00-0.77). Testicular cancer was the only solid tumor with an increased SIR (2.9; 95% CI 1.6-4.8). CONCLUSIONS: The risk of all major groups of solid tumors was decreased, except testicular cancer. Altered screening strategies should be considered for persons with Down syndrome. This unusual pattern of cancer occurrence may help understanding carcinogenesis in the general population.Genet Med 18 11, 1151-1157.

Long-term Risk of Hospitalization for Somatic Diseases in Survivors of Adolescent or Young Adult Cancer.

IMPORTANCE: Survivors of adolescent and young adult cancers are at risk for treatment-induced late adverse effects; however, to our knowledge, the long-term risk of hospitalization in this specific group of cancer survivors has not been thoroughly evaluated. OBJECTIVE: To examine relative and absolute excess risk for hospitalizations up to 34 years after diagnosis of adolescent and young adult cancer compared with population comparisons. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study, conducted in Denmark, of 33,555 five-year survivors of adolescent or young adult cancer, diagnosed from 1943 through 2004, when they were 15 to 39 years of age, and 228,447 population comparisons, matched to the survivors by sex and year of birth. MAIN OUTCOMES AND MEASURES: Cancer survivors and comparisons were followed up for hospitalizations in the Danish Patient Register through December 2010. Standardized hospitalization rate ratios (RRs) and absolute excess risks (AERs) were calculated. RESULTS: After a median follow-up of 14 years, we identified 53,032 hospitalizations in cancer survivors, whereas 38,423 were expected, resulting in an overall RR of 1.38 (95% CI, 1.37-1.39). The data analysis was started in January 2015 and ended in June 2015. Additional data analyses requested by the reviewers were conducted in August 2015. The highest risks were found for the main diagnostic groups of diseases of blood and blood-forming organs (RR, 2.00; 95% CI, 1.87-2.14), infectious and parasitic diseases (RR, 1.69; 95% CI, 1.61-1.77), and malignant neoplasms (RR, 1.63; 95% CI, 1.59-1.68). The overall AER was 2803 (95% CI, 2712-2893) per 100,000 person-years; the highest AERs were found for malignant neoplasms, diseases of digestive organs, and diseases of the circulatory system (18%, 15%, and 14% of total AER, respectively). Survivors of the 10 most common cancers in adolescents and young adults were at significantly increased risk for diseases in the 12 main diagnostic groups. The highest risks were those of survivors of leukemia (RR, 2.21; 95% CI, 2.02-2.42), brain cancer (RR, 1.93; 95% CI, 1.86-2.00), and Hodgkin lymphoma (RR, 1.87; 95% CI, 1.80-1.94). CONCLUSIONS AND RELEVANCE: The large number of survivors and the use of hospital discharge diagnoses made it possible to draw a comprehensive picture of the complex inpatient disease burden experienced by survivors of adolescent and young adult cancer. The findings underscore a great diversity of cancer-related health problems that physicians and patients should be knowledgeable about.

Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS).

OBJECTIVES: The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries. METHODS: From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated. RESULTS: Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4). CONCLUSIONS: Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors.

Residential exposure to extremely low-frequency magnetic fields and risk of childhood leukaemia, CNS tumour and lymphoma in Denmark.

BACKGROUND: We previously reported that children exposed to elevated extremely low-frequency magnetic fields (ELF-MF) had a five to six times higher risk of leukaemia, central nervous system (CNS) tumour and malignant lymphoma. Here we extend the study from 1968 to 1986 through 2003. METHODS: We included 3277 children with leukaemia, CNS tumour or malignant lymphoma during 1968-2003 recorded in the Danish Cancer Registry and 9129 controls randomly selected from the Danish childhood population. ELF-MF from 50 to 400 kV facilities were calculated at the residences. RESULTS: For recently diagnosed cases (1987-2003), the relative risk (RR) was 0.88 (95% confidence interval (CI): 0.32-2.42), while for the total period (1968-2003) it was 1.63 (95% CI: 0.77-3.46) for leukaemia, CNS tumour and malignant lymphoma combined for exposures ⩾0.4 µT compared with <0.1 µT. These results were based on five cases (recent period) and 11 cases (total period) in the highest exposure group. CONCLUSIONS: We did not confirm the previous finding of a five- to six-fold higher risk for leukaemia, CNS tumour and malignant lymphoma when including data from the more recent time period. For the total time period, the results for childhood leukaemia were in line with large pooled analyses showing RRs between 1.5 and 2.

Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries.

We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by relationship, histology, age at diagnosis, and sex. A cohort of 57,475 first-degree relatives of 13,922 HL patients diagnosed between 1955 and 2009 in 5 European countries was observed for HL incidence. The overall lifetime cumulative risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence interval [CI], 2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 95% CI, 4.8- to 7.4-fold) was significantly higher than in parents and/or children (2.1-fold; 95% CI, 1.6- to 2.6-fold). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 95% CI, 2.8- to 39-fold) and for same-sex twins (57-fold; 95% CI, 21- to 125-fold). We found high familial risks between some concordant histologic subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30- to 177-fold) and nodular sclerosis (4.6-fold; 95% CI, 2.9- to 7.0-fold) and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9- to 14-fold) was higher than in brothers (4.5-fold; 95% CI, 2.9- to 6.7-fold) or unlike-sex siblings (5.9-fold; 95% CI, 4.3- to 8.1-fold). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30 years). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical HL by oncologists and genetic counselors.

Collaborative Research in Childhood Cancer Survivorship: The Current Landscape.

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salient findings from these large collaborative initiatives, emphasizing the need for life-long follow-up of survivors of childhood cancer, and describing the development of several guidelines and efforts toward harmonization. Finally, the review reinforces the need to identify populations at highest risk, facilitating the development of risk prediction models that would allow for targeted interventions across the entire trajectory of survivorship.

The Adult Life After Childhood Cancer in Scandinavia (ALiCCS) Study: Design and Characteristics.

BACKGROUND: During the last five decades, survival of childhood cancer has increased from 25% to 80%. At the same time, however, it has become evident that survivors experience a broad range of therapy-related late adverse health effects. The aim of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study is to investigate long-term health consequences of past and current therapies in order to improve follow-up care of survivors and to reduce treatment-related morbidity of future patients. PROCEDURE: Childhood cancer survivors were identified through the five Nordic cancer registries and a comparison cohort was established through random selection of cancer-free individuals from the civil registration systems. A unique personal identification number was used to link between different health registries. Abstraction of treatment information for a subset of survivors allows investigation of the association between the various components of cancer therapy and late occurring comorbidity. RESULTS: The childhood cancer survivor cohort comprises 33,160 1-year survivors and the comparison cohort comprises 212,892 cancer free individuals from the general population. In the childhood cancer survivor cohort, all types of childhood cancer are represented including leukemia (21%), lymphoma (14%), central nervous system tumors (24%), sarcomas (5%), retinoblastoma (3%), and neuroblastoma (4%). Among the survivors, 22% have been followed beyond the age of 40 years. CONCLUSION: The ALiCCS study constitutes a new large resource for research on late effects of childhood cancers that include all types of childhood malignancies and has followed a large proportion of the survivors well into late adulthood.

European Code against Cancer 4th Edition: 12 ways to reduce your cancer risk.

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

Cancer Incidence among Patients with Anorexia Nervosa from Sweden, Denmark and Finland.

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.

Lifestyle, family history, and risk of idiopathic Parkinson disease: a large Danish case-control study.

The relationship between Parkinson disease (PD) and smoking has been examined in several studies, but little is known about smoking in conjunction with other behaviors and a family history of PD. Using unconditional logistic regression analysis, we studied individual and joint associations of these factors with idiopathic PD among 1,808 Danish patients who were diagnosed in 1996-2009 and matched to 1,876 randomly selected population controls. Although there was a downward trend in duration of smoking, this was not observed for daily tobacco consumption. A moderate intake of caffeine (3.1-5 cups/day) was associated with a lower odds ratio for PD (0.45, 95% confidence interval: 0.34, 0.62), as was a moderate intake of alcohol (3.1-7 units/week) (odds ratio = 0.60, 95% confidence interval: 0.58, 0.84); a higher daily intake did not reduce the odds further. When these behaviors were studied in combination with smoking, the odds ratios were lower than those for each one alone. Compared with never smokers with no family history of PD, never smokers who did have a family history had an odds ratio of 2.81 (95% confidence interval: 1.91, 4.13); for smokers with a family history, the odds ratio was 1.60 (95% confidence interval: 1.15, 2.23). In conclusion, duration of smoking seems to be more important than intensity in the relationship between smoking and idiopathic PD. The finding of lower risk estimates for smoking in combination with caffeine or alcohol requires further confirmation.

The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease.

A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Aß42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Aß42 suggesting that TREM2's role in AD may involve tau dysfunction.