Long-term risk and characteristics of cerebrovascular events after upper body radiotherapy among childhood cancer survivors in the DCCSS-LATER cohort.

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed View Article and Find Full Text PDF

Bone health in childhood cancer survivors, is there really a problem? Pitfalls of assessment, calculating risk, and suggested surveillance and management for osteonecrosis and low and very low bone mineral density.

Childhood cancer survivors are at increased risk of developing (long-term) skeletal adverse effects, such as osteonecrosis, impaired bone mineral density, and fractures. This paper provides an overview of the current understanding of bone health in these survivors, examining whether it represents a significant concern. It focusses on the challenges of assessing and managing bone health in childhood cancer survivors, highlighting diagnostic pitfalls, methods for accurately identifying those at high risk, and suggested strategies for the surveillance and management of osteonecrosis and impaired bone mineral density.

Risk and Protective Factors of Psychosocial Functioning in Survivors of Childhood Cancer: Results of the DCCSS-LATER Study.

Objective: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS).

Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.

Growth Hormone Receptor Antagonist Markedly Improves Gemcitabine Response in a Mouse Xenograft Model of Human Pancreatic Cancer.

Chemotherapy treatment against pancreatic ductal adenocarcinoma (PDAC) is thwarted by tumoral activation of multiple therapy resistance pathways. The growth hormone (GH)-GH receptor (GHR) pair is a covert driver of multimodal therapy resistance in cancer and is overexpressed in PDAC tumors, yet the therapeutic potential of targeting the same has not been explored. Here, we report that GHR expression is a negative prognostic factor in patients with PDAC.

The impact of clinically relevant health conditions on psychosocial outcomes in survivors of childhood cancer: results of the DCCSS-LATER study.

Purpose: Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS).

Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5 years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.

Progress, challenges and perspectives in the management of hypopituitarism.

Hypopituitarism is a rare endocrine disorder characterized by insufficient hormone secretion from the pituitary gland. This condition leads to deficient production of one or more pituitary hormones, including growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotropic hormone (ACTH), and antidiuretic hormone (ADH), also called arginine vasopressin (AVP). Symptoms vary widely and are often not, late recognized.

A Biomarker-Based Diagnostic Model for Cardiac Dysfunction in Childhood Cancer Survivors.

Background: Childhood cancer survivors at risk for heart failure undergo lifelong echocardiographic surveillance. Previous studies reported the limited diagnostic accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) in detecting left ventricular (LV) dysfunction. However, potential enhanced diagnostic accuracy through the combination of biomarkers and clinical characteristics has been suggested.

Different subtypes of chronic fatigue in childhood cancer survivors: A DCCSS LATER study.

Introduction: The aim of the current study was to investigate whether subtypes of chronic fatigue (CF) can be identified in childhood cancer survivors (CCS), and if so, to determine the characteristics of participants with a specific subtype.

Methods: Participants were included from the nationwide DCCSS LATER cohort. The Checklist Individual Strength (CIS) was completed to assess fatigue.

[F]FET PET/MRI: An Accurate Technique for Detection of Small Functional Pituitary Tumors.

Small functional pituitary tumors can cause severely disabling symptoms and early death. The gold standard diagnostic approach includes laboratory tests and MRI, with or without inferior petrosal sinus sampling (IPSS). In up to 40% of patients, however, the source of excess hormone production remains unidentified or uncertain.

Presence and utility of electrocardiographic abnormalities in long-term childhood cancer survivors.

Background: We assessed the prevalence and diagnostic value of ECG abnormalities for cardiomyopathy surveillance in childhood cancer survivors.

Methods: In this cross-sectional study, 1381 survivors (≥5 years) from the Dutch Childhood Cancer Survivor Study part 2 and 272 siblings underwent a long-term follow-up ECG and echocardiography. We compared ECG abnormality prevalences using the Minnesota Code between survivors and siblings, and within biplane left ventricular ejection fraction (LVEF) categories.

The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin.

This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

The cumulative burden of self-reported, clinically relevant outcomes in long-term childhood cancer survivors and implications for survivorship care: A DCCSS LATER study.

Background: The aim of this study is to evaluate how cumulative burden of clinically relevant, self-reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications.

Methods: The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self-reported medication use or medical record review.

The Value of IgM Memory B-Cells in the Assessment of Splenic Function in Childhood Cancer Survivors at Risk for Splenic Dysfunction: A DCCSS-LATER Study.

Background: Childhood cancer survivors (CCS) who received radiotherapy involving the spleen or total body irradiation (TBI) might be at risk for splenic dysfunction. A comprehensive screening test for examining splenic dysfunction is lacking.

Objective: We investigated whether IgM memory B-cells could be used to assess splenic dysfunction in CCS who received a splenectomy, radiotherapy involving the spleen, or TBI.

Leptin Increase During Dexamethasone and Its Association With Hunger and Fat in Pediatric Acute Lymphoblastic Leukemia.

Context: During treatment, children with acute lymphoblastic leukemia (ALL) receive high doses dexamethasone, which induce acute side effects.

Objective: To determine the influence of a 5-day dexamethasone course on changes in leptin, fat mass, BMI, hunger, sleep, and fatigue and to explore associations between these changes.

Methods: Pediatric ALL patients were included during maintenance treatment.

Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement.

This Consensus Statement from an international, multidisciplinary workshop sponsored by the Pituitary Society offers evidence-based graded consensus recommendations and key summary points for clinical practice on the diagnosis and management of prolactinomas. Epidemiology and pathogenesis, clinical presentation of disordered pituitary hormone secretion, assessment of hyperprolactinaemia and biochemical evaluation, optimal use of imaging strategies and disease-related complications are addressed. In-depth discussions present the latest evidence on treatment of prolactinoma, including efficacy, adverse effects and options for withdrawal of dopamine agonist therapy, as well as indications for surgery, preoperative medical therapy and radiation therapy.

Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors: A DCCSS LATER Study.

Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity.

Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors.

Methods: This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings.

Structure and function of a dual antagonist of the human growth hormone and prolactin receptors with site-specific PEG conjugates.

Human growth hormone (hGH) is a pituitary-derived endocrine protein that regulates several critical postnatal physiologic processes including growth, organ development, and metabolism. Following adulthood, GH is also a regulator of multiple pathologies like fibrosis, cancer, and diabetes. Therefore, there is a significant pharmaceutical interest in developing antagonists of hGH action.

Sex Differences in the Association Between Serum Testosterone and Kidney Function in the General Population.

Introduction: Testosterone might prevent kidney function decline, although evidence is limited in men and lacking in women from the general population. We investigated the association between serum testosterone and kidney function in men and women from a large population-based cohort study.

Methods: Participants aged ≥45 years with available measurements of serum testosterone, sex hormone-binding globulin (SHBG), creatinine, and cystatine C were included.

Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer: DCCSS-LATER 2 psycho-oncology study.

Objective: To describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes.

Methods: Siblings of survivors (diagnosed <18 years old, between 1963 and 2001, >5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests.

Germline loss-of-function variants are enriched in subjects with pituitary hypersecretion.

Introduction: Pituitary adenomas (PAs) are common, usually benign tumors of the anterior pituitary gland which, for the most part, have no known genetic cause. PAs are associated with major clinical effects due to hormonal dysregulation and tumoral impingement on vital brain structures. PAM encodes a multifunctional protein responsible for the essential C-terminal amidation of secreted peptides.

Psychosexual development, sexual functioning and sexual satisfaction in long-term childhood cancer survivors: DCCSS-LATER 2 sexuality substudy.

Objectives: Childhood cancer may negatively impact childhood cancer survivors' (CCS) sexuality. However, this is an understudied research area. We aimed to describe the psychosexual development, sexual functioning and sexual satisfaction of CCS, and identify determinants for these outcomes.

Self-reported outcomes on oral health and oral health-related quality of life in long-term childhood cancer survivors-A DCCSS-LATER 2 Study.

Purpose: The present study aimed to determine the prevalence of self-reported oral problems and the oral health-related quality of life (OHRQoL) in childhood cancer survivors (CCS).

Methods: Patient and treatment characteristics of CCS have been collected in a cross-sectional study, part of the multidisciplinary DCCSS-LATER 2 Study. To assess self-reported oral health problems and dental problems, CCS filled out the 'Toegepast-Natuurwetenschappelijk Onderzoek' (TNO) oral health questionnaire.