Background: Neuroblastoma (NB) is the second most common malignancy diagnosed in infants, accounting for 15% of pediatric tumor deaths. Half of children with NB receive an intensive regimen including high-dose chemotherapy with 50% survival, resulting in acute and long term toxicities. One of the challenges of chemotherapy is irregular tumor vasculature. Thus, increasing targeted drug delivery without increasing drug dosage can result in enhanced drug efficacy and improved patient outcomes. We have shown that sonoporation (focused ultrasound-guided gas-filled microbubbles) increases high dose liposomal doxorubicin (L-DOX) uptake in NB xenografts by increasing tumor perfusion. However, these studies used polydisperse microbubbles (PMB), which were developed for imaging purposes. We hypothesized that MB size restriction would control their response to ultrasound pressure, yielding a higher L-DOX payload despite using using lower L-DOX dosages. Methods: Nude mice received 1x10^6 NGP cells (NB cells) intrarenally. When tumors reached 1 gram, NB xenografts received an intravenous polydisperse (PMB) or 4-5uM (SIMB) microbubble infusion with or without 1mg/kg liposomal doxorubicin (L-DOX) under focused ultrasound. Tumors were measured over 7 days with calipers, others sacrificed 24 hours after treatment for histology and immunohistochemistry. We assessed endomucin and isolectin-B4 (endothelium), Zona occludens-1 (ZO-1) (tight junction), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL, apoptosis). Results: Tumors receiving low dose L-DOX alone or PMB sonoporation with L-DOX were not different from untreated controls after 7 days. SIMB alone resulted in a slower tumor growth than control tumors (20 vs 100% p<0.05); L-DOX coupled with SIMB resulted in further tumor growth restriction 7 days after treatment (0 vs 100% p<0.05). SIMB increased tumor apoptosis (TUNEL staining) in the absence of L-DOX compared to controls (7 vs 58% of area p=0.003) as well as in the presence of L-DOX (7 vs 78% of area p<0.001). PMBs did not change TUNEL levels regardless of L-DOX. Tumor vascular lumens (widest axis within the endothelial marker endomucin) confirmed PMB duplicates lumen diameter compared to controls (p<0.05), and revealed SIMB triplicates lumen diameter (p<0.01) regardless of L-DOX. SIMB resulted in loss of tight junction protein ZO-1 both in vasculature and tumor cells and widespread L-DOX uptake. Together, our data shows SIMB sonoporation increases tumor blood volume and vascular permeability leading to higher chemotherapy uptake and apoptosis. Conclusions: Together, our data shows SIMB sonoporation enables chemotherapy uptake in poorly perfused NB xenografts by increasing perfusion and permeability, potentiating apoptotic effects. SIMB sonoporation could reduce acute and long term toxicities. Citation Format: Sonia L. Hernandez, Rachael Sundland, Donia Ballan, Aditi Bellary, Jessica J. Kandel, Jameel Feshitan, Shashank Sirsi. Sonoporated size selected microbubblesand liposomal doxorubicinadditively induce apoptosis in neuroblastoma xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 376.
With the rise of the coronavirus disease 2019 (COVID-19) respiratory pandemic, there has been an increased need to consider the use of extracorporeal membrane oxygenation (ECMO) technology. In the early phases of the pandemic, adults constituted most of the critically ill patients, and ECMO management strategies were developed for use in this population. During the course of the pandemic, there has been a rise in the number of critically ill children infected with COVID-19. Although ECMO has been used in the care of pediatric patients for more than half a century, it has been challenging to apply the lessons learned from adult patients with COVID-19 directly to critically ill children for whom ECMO is under consideration. This article reviews ECMO technology and highlights a number of important changes in pediatric ECMO regarding those patients infected with COVID-19. [ Pediatr Ann . 2022;51(7):e281–e285.]
Globally, there have been more than 285 million confirmed cases of coronavirus disease 2019 (COVID-19), with nearly 5.5 million deaths. Centers for Disease Control and Prevention data report that in the United States alone, there have been more than 59 million cases of COVID-19 with more than 800,000 lives lost as of January 2022. Similar to other health care specialties, pediatric surgery departments have modified their treatment approach to delivering timely care while respecting resource allocation during the pandemic. In this review, we focus on the surgical management of pediatric patients, with specific attention to childhood cancer. The primary subject of this review is the development of triaging methods for patients with childhood cancer for surgical procedures and precautionary measures for operating on patients with COVID-19. [ Pediatr Ann . 2022;51():e270–e276.]
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