Metabolic syndrome in pediatric cancer survivors: a mechanistic review.

Pediatric cancer survivors have increased risk of obesity, hypertension, dyslipidemia, and type 2 diabetes, leading to premature cardiovascular disease (CVD). Multiple tissues that are involved in glucose homeostasis and lipid metabolism are adversely affected by chemotherapy. This review highlights the relevant tissue and molecular end-organ effects of therapy exposures and synthesizes the current understanding of the mechanisms underlying CVD risk in this vulnerable population. The review also approaches the topic from a developmental perspective, with the goal of providing a translational approach to identifying the antecedents of overt CVD among survivors of pediatric cancer.

Vitamin D levels differ by cancer diagnosis and decline over time in survivors of childhood cancer.

BACKGROUND: The aim of this study was to evaluate serum 25-hydroxyvitamin D (25OHD) concentrations in survivors of childhood cancer and compare levels by underlying diagnosis and as a function of time. PROCEDURE: A retrospective review of 201 pediatric cancer survivors enrolled in a hospital-based cancer survivor registry. Demographic characteristics and 25OHD levels were extracted from the registry. Vitamin D status was determined during routine clinical care and was categorized as normal, insufficient, or deficient. RESULTS: 25OHD levels differed significantly across diagnoses (P = 0.017), with the lowest levels found in patients treated for osteosarcoma, retinoblastoma, hepatoblastoma, and myeloid leukemias. Age was inversely correlated with 25OHD levels (P = 0.03). Average 25OHD level at study entry was 29.8 ng/ml (range: 5-79.7), with 14.4% vitamin D deficient, 39.3% insufficient, and 46.3% normal. 25OHD concentrations decreased 11.4% over time (P < 0.00001). CONCLUSION: Fewer than half of childhood cancer survivors have normal 25OHD concentrations, which further declined over time. Patients with solid tumors were the most affected, despite their lack of routine exposure to glucocorticoids. Future investigations should focus on why vitamin D level varies by diagnosis and how best to replete in this population.

Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution.

The purpose of this study was to determine the incidence of fungal infections in pediatric hematology and oncology (PHO) patients and to describe variations regarding site of infection, organisms, and mortality. The records of 1,052 patients presenting to the UCLA PHO service with various malignancies from 1991 to 2001 were retrospectively reviewed. No patient received invasive antifungal prophylaxis. Transplant patients were excluded. The 11-year incidence of fungal infections in this pediatric oncology cohort was 4.9%. There was a linear increase in the incidence of fungal infections from 2.9% to 7.8% between 1996 and 2001 (P = 0.001). Patients with acute leukemia represented 36% of the population but had a disproportionate incidence (67%) of fungal infections. Adolescents had twice the expected incidence of infection (P < 0.0001). Overall, Candida sp. was the major pathogen. Over time, a trend of fewer infections caused by Candida and more due to Aspergillus was noted. Blood-borne infections decreased over time, while those in the urinary and respiratory tracts increased (P = 0.04). Sixty-two percent of infections occurred in neutropenic patients. PHO patients had an overall mortality of 21%, but those with fungal infections experienced a 2.6-fold higher mortality that was not attributable to infections alone. Empiric antifungal therapy had no effect on mortality rates. Concurrent nonfungal infections did not increase mortality rates. The incidence of fungal infections increased over time, possibly as a result of advances in antibacterial and chemotherapeutic regimens. Adolescents and patients with leukemia were especially at risk. Fungal infections are a poor prognostic factor, independent of fungal-related mortality. New diagnostic methods allowing for early detection and treatment as well as more effective therapies are needed.