Maria Florencia Varela

Purpose Congenital diaphragmatic hernia (CDH) pathogenesis is poorly understood. We hypothesize that fetal CDH lungs are chronically hypoxic because of lung hypoplasia and tissue compression, affecting the cell bioenergetics as a possible explanation for abnormal lung development. Methods To investigate this theory, we conducted a study using the rat nitrofen model of CDH. We evaluated the bioenergetics status using H1 Nuclear magnetic resonance and studied the expression of enzymes involved in energy production, the hypoxia-inducible factor 1α, and the glucose transporter 1. Results The nitrofen-exposed lungs have increased levels of hypoxia-inducible factor 1α and the main fetal glucose transporter, more evident in the CDH lungs. We also found imbalanced AMP:ATP and ADP:ATP ratios, and a depleted energy cellular charge. Subsequent transcription levels and protein expression of the enzymes involved in bioenergetics confirm the attempt to prevent the energy collapse with the increase in lactate dehydrogenase C, pyruvate dehydrogenase kinase 1 and 2, adenosine monophosphate deaminase, AMP-activated protein kinase, calcium/calmodulin-dependent protein kinase 2, and liver kinase B1, while decreasing ATP synthase. Conclusion Our study suggests that changes in energy production could play a role in CDH pathogenesis. If confirmed in other animal models and humans, this could lead to the development of novel therapies targeting the mitochondria to improve outcomes.

Purpose To analyze the role of laparoscopic surgery for the management of pediatric adrenal tumors (AT). Methods Retrospective analysis of children diagnosed with AT, operated laparoscopically during 2003–2020. The strategy differed according to tumor extension. AT < 6 cm were resected. Locally advanced tumors (L2) or > 6 cm were biopsied. Results N = 28. Complete tumor resection (R0) in 20 (71%), tumor biopsy in 8 (R2). Age (median): 28.8 months (2 months–18 years). 14/28 left-sided, 2 bilateral. Median operating time: 78 min (45–180). Mean tumor size (for resections): 4 cm (2.5–6). Tumor pathology: neuroblastoma (n = 17), Ganglioneuroma (n = 7), Adrenocortical carcinoma (n = 1), Osteosarcoma metastasis (n = 1), Pheochromocytoma (n = 1), Venous malformation (n = 1). Mean hospital stay: 2.5 days (1–3). Mean follow up: 65.5 months (24–192). Overall survival and event-free survival were 86 and 75%, respectively (5 years event-free survival for neuroblastoma: 33% [intermediate risk], 16.6% [high risk]. No surgery-related mortality. Conclusion Laparoscopic surgery for adrenal tumors is safe. Laparoscopic biopsy is useful for unresectable tumors when a percutaneous approach is not possible. With the proposed selection criteria, the laparoscopic approach should be the first option for resection of small and localized AT in pediatrics.

Congenital diaphragmatic hernia (CDH) is characterized by the herniation of abdominal contents into the thoracic cavity during the fetal period. This competition for fetal thoracic space results in lung hypoplasia and vascular maldevelopment that can generate severe pulmonary hypertension (PH). The detailed mechanisms of CDH pathogenesis are yet to be understood. Acknowledgment of the lung metabolism during the in-utero CDH development can help to discern the CDH pathophysiology changes. Timed-pregnant dams received nitrofen or vehicle (olive oil) on E9.5 day of gestation. All fetal lungs exposed to nitrofen or vehicle control were harvested at day E21.5 by C-section and processed for metabolomics analysis using nuclear magnetic resonance (NMR) spectroscopy. The three groups analyzed were nitrofen-CDH (NCDH), nitrofen-control (NC), and vehicle control (VC). A total of 64 metabolites were quantified and subjected to statistical analysis. The multivariate analysis identified forty-four metabolites that were statistically different between the three groups. The highest Variable importance in projection (VIP) score (>2) metabolites were lactate, glutamate, and adenosine 5′-triphosphate (ATP). Fetal CDH lungs have changes related to oxidative stress, nucleotide synthesis, amino acid metabolism, glycerophospholipid metabolism, and glucose metabolism. This work provides new insights into the molecular mechanisms behind the CDH pathophysiology and can explore potential novel treatment targets for CDH patients.