Feasibility and tolerability of bevacizumab in children with primary CNS tumors.

BACKGROUND: Bevacizumab, an antibody to the vascular endothelial growth factor, has demonstrated anti-cancer activity in a number of solid tumors. Fear of intratumoral hemorrhage, however, has slowed its introduction into the treatment of central nervous system (CNS) tumors. Currently, only a small number of children with gliomas received bevacizumab. METHODS: We retrospectively analyzed 30 patients who received bevacizumab between January 2007 and August 2009. The median age at start of bevacizumab treatment was 9.9 years (range: 1.5-18). Most patients had recurrent/progressive disease, 25 high-grade and 5 low-grade tumors. The median dose of bevacizumab was 9.5 mg/kg (range 5-15 mg/kg) every 2-3 weeks. In total, 478 courses were administered (median/patient 15.9, range: 2-52). The median duration of bevacizumab treatment was 10.0 months (range: 1.6-30.4). Twenty-nine of 30 patients received additional therapy concomitant to bevacizumab. RESULTS: No bevacizumab related intratumoral hemorrhage occurred in any of our 30 patients. Grade III hypertension was seen in two patients. One patient developed nephrotic syndrome requiring cessation of treatment. Grade III and I proteinuria were observed in one and five patients, respectively. New onset lymphopenia occurred in 12/30 and new onset hypothyroidism in 7/30 patients. Impaired wound healing was manageable. No immediate bevacizumab-related cardiotoxicity was observed as evidenced by echocardiography. CONCLUSIONS: Bevacizumab appears to be safe for children with primary CNS tumors. Adverse effects did occur but were manageable. No treatment-related death occurred. Long-term monitoring is advisable to detect lymphopenia and hypothyroidism. Hypertension occurred less frequently than in adult patients. Further prospective studies including more patients are warranted.

Hazard in ductal stenting: helicoid open cell stents.

Stent implantation in the arterial duct has achieved great acceptance as an alternative to an aortopulmonary shunt procedure. Despite challenging, also tortuous arterial ducts as in ToF and pulmonary atresia with VSD can be addressed, since flexible open cell coronary stents are available. We describe two patients with ToF and Ebstein's anomaly where a special helicoid open cell stent was implanted to cross a highly stenotic sigmoid arterial duct. In both patients, the stent design resulted in extremely kinked stent segments with minor or absent flow through the stent lumen. While in one patient early ToF-repair was required, in the other recrossing and restenting with another open cell but not helicoid tubular design type of stent allowed adequate pulmonary perfusion. Although mimicking of the natural course even in tortuous ducts is not mandatory, kinking of the stent is likely to occur in these types of arterial ducts. On the basis of our experience, we can not recommend helicoid manufactured stents in the scenario of ductal stenting, especially in congenital heart disease with completely duct dependent pulmonary circulation.

Serum lipid pattern unifies following renal transplantation in children.

Hyperlipidemia is a common problem in solid organ transplant recipients. In this study we evaluated the role of pre-transplant renal replacement therapy on early and late changes of serum lipid levels in children following renal transplantation. In 46 children with chronic renal failure (median age 10.3 years) and 12 children with heart failure (median age 5.0 years), cholesterol and triglycerides were measured before and during follow-up after transplantation. Children with renal failure had significantly higher serum lipids than controls ( n=34, median age 9.2 years) and patients with heart failure. Pre transplantation, cholesterol and triglycerides were significantly lower in the hemodialysis than in the peritoneal dialysis population, whereas conservatively treated children had intermediate levels. After transplantation, serum cholesterol converged towards a mean level of 208 mg/dl and triglyceride levels converged towards a uniform level of 195 mg/dl at 9 months post transplant. The ratio of cholesterol/high-density lipoprotein significantly decreased from 4.7 to 3.8. The pattern of "post-transplant hyperlipidemia" was similar in both renal and cardiac allograft recipients. Hence, the early post-transplant changes of serum lipid pattern are markedly dependent on the mode of pre-transplant renal replacement therapy. Later, serum lipid levels were no longer influenced by prior renal replacement therapy and showed a new pattern of "post-transplant hyperlipidemia" in all children.

Glucagon therapy as a possible cause of erythema necrolyticum migrans in two neonates with persistent hyperinsulinaemic hypoglycaemia.

UNLABELLED: Erythema necrolyticum migrans (ENM) usually presents as a cutaneous paraneoplastic phenomenon which is in most cases associated with a glucagon-producing tumour. Here it is for the first time described as a side-effect of glucagon treatment in persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI). In both patients, the skin lesions disappeared after discontinuation of glucagon administration. In the first child the erythema resolved without scarring within 10 days after glucagon was substituted with other medication while in the second patient healing followed subtotal pancreatectomy which rendered glucagon infusion unnecessary. Initially the clinical resemblance to atopic dermatitis is prone to cause diagnostic errors, especially in this age group. CONCLUSION: erythema necrolyticum migrans should be considered as a differential diagnosis in patients who develop erythematosquamous skin lesions under glucagon treatment.