Pediatric Cancer: Environmental and Genetic Aspects

One in 600 children 0-16 years of age develop cancer, and 60% to 70% of them are cured. Projection of the data indicates that by the turn of the century, 1 of every 900 individuals between the ages of 16 and 44 years will be a cancer survivor. In the adult population, carcinogens and irradiation play a major role in oncogenesis. In the pediatric population other factors are probably dominant. Children of low socioeconomic groups, with nutritional deficiencies, are more exposed to viral infections at a very early age and have a greater chance of developing tumors such as Burkitt lymphoma or mixed cellularity Hodgkin disease. Other factors such as hormone-assisted conception or in vitro fertilization may have carcinogenic potential, although this has yet to be determined. Maternal diet during pregnancy, especially low folic acid consumption periconception, may have bearing on the fetus's risk of developing malignancy. The hazards of exposure to electric and magnetic fields from high-voltage transmission lines, home electric appliances, video display terminals, or residence near nuclear plants, although very doubtful, are included in the list of cancer promoters in children. Activated oncogenes, mutated suppressor genes, mismatch repair genes, nucleotide excision genes, and loss of imprinting genes are beginning to evolve as important factors in carcinogenesis. The more in-depth information on genetic and environmental factors should provide new data on the evolution of pediatric tumors and possibly on their prevention.     

Brain Natriuretic Peptide Levels in Pediatric Cancer Patients with Febrile Neutropenia

Brain natriuretic peptide (BNP) is considered as a prognostic marker in patients with sepsis, but no data are available on BNP in pediatric cancer patients with febrile neutropenia (FN). Twenty-five pediatric cancer patients with FN were included in this study. Serum BNP level was measured. The mean BNP level was 330.8 ± 765.3 pg/mL (5.9–3806 pg/mL). BNP levels of 12 patients were found over the normal level. High BNP levels were related to some conditions of the patients, and these were statistically significant (P < .05). These conditions were required erythrocyte suspension, had pneumonia, time stayed in hospital, and neutropenia time. When regression test was done, required erythrocyte suspension for anemia and had pneumonia were found to be statistically significant. In conclusion, this is one of the first studies on BNP levels in pediatric cancer patients with FN. However, further studies with large sample sizes are needed to confirm the results and provide new data about this issue.     

Radiation Exposure and the Risk of Pediatric Thyroid Cancer

It has been more than three years since the unprecedentedly massive earthquake and tsunami struck eastern Japan on March 11, 2011, and the large accident occurred at the Fukushima Daiichi Nuclear Power Plant. To investigate the influence of radiation exposure, thyroid ultrasonography has been provided preliminarily for 360,000 children who lived in Fukushima Prefecture at the time of the accident. As of September 2013, 59 children had been diagnosed with thyroid cancer by fine-needle aspiration cytology, and 34 children had been treated surgically and ultimately diagnosed with papillary thyroid cancer. Here, I would like to describe the characteristics of pediatric thyroid cancer and typical thyroid images obtained by ultrasonography.     

Seasonality of birth in sporadic cretinism

The seasonal distribution of birth dates of 31 patients with sporadic cretinism due to thyroid dysgenesis was analyzed in Osaka area for 14 years. The incidence was statistically high in the summer months. A hypothesis that some environmental factors such as viral infection may cause the disease is proposed.     

Rhabdomyosarcoma Treatment and Outcome at a Multidisciplinary Pediatric Cancer Center in Lebanon

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Outcome of patients treated on standard protocols, in a multidisciplinary cancer center setting outside of clinical trials, is not well reported. We reviewed characteristics and outcome of 23 pediatric patients treated at a single, multidisciplinary cancer center in Lebanon, between April 2002 and December 2010. Median follow-up was 41 months. The most commonly affected primary site was the head and neck (48%, n = 11). Nineteen tumors (82.6%) were of embryonal histology. Tumor size was ≥5 cm in eight (34.8%) patients. Sixteen patients (69.6%) had localized disease, and one (4.4%) had metastatic disease. Fifteen (65.2%) had Group III tumors. All patients received chemotherapy, for a duration ranging 21–51 weeks. Upfront surgical resection was performed in 10 patients (43.5%). Eighteen patients (78.3%) received radiation therapy. The 5-year overall and disease-free survival rates were 83% and 64%, respectively. Relapse correlated with absence of surgery. Treatment of childhood RMS in a multidisciplinary cancer center in Lebanon results in similar survival to that in developed countries when similar protocols are applied. There was a higher incidence of local relapse, but those were salvageable with further therapy and surgical local control.     

Seasonality of invasive Candida infection in neonates

AIM: To evaluate season of birth as a risk factor for the development of invasive Candida in our population of preterm low-birthweight infants. METHODS: Retrospective identification of Candida-positive blood or cerebrospinal fluid (CSF) cultures in infants < 32 wk over an 8-y period. RESULTS: There were 1400 admissions of infants < 32 wk gestation, of whom 52 (3.7%) developed invasive Candida infection. Thirty-eight of 52 (73%) occurred during the months September to February. CONCLUSIONS: It may be appropriate to consider seasonal associations when targeting selective antifungal chemoprophylaxis.     

Pharmacokinetic Analysis of Gentamicin Thrice and Single Daily Dosage in Pediatric Cancer Patients

Fifty-two children suffering from different types of malignancies were included and evaluated for the pharmacokinetics of gentamicin thrice or single daily dosage protocols. All the study population received a total dose of 5 mg/kg daily. Thirty children received gentamicin thrice daily, and 22 were treated using the single daily protocol; all had fever and neutropenia when included. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood gentamicin samples. The mean (SD) ^t1/2 (h), clearance (mL/min/BSA), V_ss (L/kg), C_max (μg/mL), and C_min (μg/mL) were 3.05 (1.0) and 3.9 (0.6) h, 136 (61.3) and 99.9 (65.3) mL/min/BSA, 0.4035 (0.167) and 0.457 (0.17) L/kg, 5.2 (2.0) and 11.5 (4.2) μg/mL, 0.8 (0.6) and 0.18 (0.1) μg/mL for thrice and single daily dosage schedules, respectively. The single gentamicin daily dose protocol had a significantly longer t_1/2 shorter clearance normalized to BSA, higher C_max and lower C_min in comparison with the thrice daily schedule. We recommend the use of gentamicin at 5 mg/kg daily delivered as a single daily dose for pediatric cancer patients with fever and neutropenia, in spite of the measured pharmacokinetic differences, which in our opinion have no clinical significance.     

Seasonality in lower leg length velocity in prepubertal children

Despite low measuring error, annual growth is poorly predicted by short-term measurements of the lower leg. In order to study if this low correlation can be explained by seasonal changes in lower leg length (LLL) velocity, we followed short-term growth longitudinally in 50 prepubertal children with normal height and growth velocities. Height measurements were performed at 4-week intervals and LLL measurements at 1–2-week intervals. Analysis of annual growth showed seasonality in the monthly mean height velocity values: 5.06 (SD 5.02) cm/year during the autumn and 8.15 (SD 5.22) cm/year in the spring. Similarly, the monthly mean LLL velocity values changed from 1.80 (SD 1.07) cm/year in the autumn to 2.63 (SD 0.92) cm/year in the spring. The correlation between monthly LLL and annual height velocity was low (r = 0.27). The technical error of the LLL measurement was 7–8% of the mean monthly LLL velocity, while the mean values changed by 31 % over the seasons. The annual height velocity was virtually independent of the variation in growth rate over the seasons. It is concluded that there is significant seasonality both in height and LLL velocity and that it takes place at the same time for both measures. Seasonality in LLL has not been reported previously and must be considered when studying short-term growth, for example when LLL is used for prediction of annual height velocity or when a short-term treatment effect is examined using LLL.