[More than 3 hours and less than 3 years: Safety of anaesthetic procedures in infants less than 3 years old subected to surgery for more the 3 hours]. / Más de 3 horas y menos de 3 años: Seguridad de procedimientos anestésicos en menores de 3 años sometidos a cirugía de más de 3 horas.

An FDA alert in December 2016 on the safety of general anesthesia and sedations in patients less than 3 years of age and pregnant women has raised doubts in relation to the attitude that professionals implicated in these procedures should adopt in relation to these specific group of patients. Confronted with this situation, the following medical scientific societies: Sociedad Española de Anestesia y Reanimación (SEDAR), Sociedad Española de Cirugía Pediátrica (SECP), Sociedad Española de Cuidados Intensivos Pediátricos (SECIP) y Sociedad Española de Neonatología (SENeo), have established a working group to analyze and clarify the safety of these techniques. In the present article we conclude that at present both general anesthesia and profound sedation are considered safe procedures because there is no evidence of the opposite in studies with human beings. However, this ascertained safety should not obviate the problem which still needs to be followed with attention, especially in patients less than 3 years of age undergoing anesthetic procedures for more than 3 hours or prolonged sedation in the Neonatal or Pediatric Intensive Care Units.

Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo.

BACKGROUND & AIMS: Multidrug resistance presents a major problem in hepatoblastoma (HB), and new anti-tumor strategies are desperately needed. The substance P (SP)/neurokinin-1 receptor (NK1R) complex has been discovered to be pivotal in the development of a variety of human cancers, and NK1R antagonists, such as the clinical drug aprepitant, are promising future anticancer agents. Yet, the role of the SP/NK1R complex as a potential anticancer target in HB is unknown. METHODS: Human HB cell lines HepT1, HepG2, and HuH6, human tumor samples from 17 children with HB as well as mice xenografted with human HB cell line HuH6 were analyzed regarding the SP/NK1R complex as a potential new anti-tumor target in HB. RESULTS: Therapeutic targeting with the NK1R antagonists aprepitant, L-733,060, and L-732,138 led to growth inhibition and apoptosis in HepT1, HepG2, and HuH6 cells in a dose-dependent manner. Intriguingly, HB cells predominantly expressed the truncated splice variant of NK1R. Human fibroblasts showed only dismal NK1R expression and were significantly more resistant. Stimulation of HB cells with SP, NK1R's natural ligand, caused increased growth rates and abrogated the anti-proliferative effect of NK1R antagonists. Expression analysis of 17 human HB samples confirmed the clinical relevance of NK1R. Most importantly, oral treatment of a HuH6 xenograft mouse model with 80mg/kg/day aprepitant for 24days resulted in a striking reduction of tumor growth, as evidenced by reduced tumor volume and weight, lowered tumor-specific alpha-fetoprotein (AFP) serum levels, and decreased number of Ki-67 positive cells. Furthermore, aprepitant treatment inhibited in vivo angiogenesis. CONCLUSIONS: For the first time, we describe the NK1R in its truncated splice variant as a potent target in human HB and an inhibitory effect in vivo and in vitro by NK1R antagonists. Therefore, NK1R antagonists should be considered promising new candidates for innovative therapeutic strategies against HB.