Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity.

BACKGROUND: Neuroblastoma is an aggressive pediatric malignancy with significant chemotherapeutic resistance. We assessed triptolide as a potential therapy. METHODS: SH-SY5Y and IMR-32 neuroblastoma cell lines were treated with triptolide. Viability, intracellular calcium, caspase activation, protein, and mRNA levels were measured. Autophagy was evaluated with confocal microscopy. Nuclear factor-kappa B (NF-κB) activation was measured using a dual luciferase assay. RESULTS: Triptolide treatment resulted in death in both cell lines within 72 hours, with sustained increases in intracellular calcium. IMR-32 cells underwent cell death by apoptosis. Conversely, light chain 3II (LC3II) protein levels were elevated in SH-SY5Y cells, which is consistent with autophagy. Confocal microscopy confirmed increased LC3 puncta in SH-SY5Y cells compared with control cells. Heat shock pathway protein and mRNA levels decreased with treatment. NF-κB assays demonstrated inhibition of tumor necrosis factor (TNF)-α-induced activity with triptolide. CONCLUSIONS: Triptolide treatment induces cell death in neuroblastoma by different mechanisms with multiple pathways targeted. Triptolide may serve a potential chemotherapeutic role in advanced cases of neuroblastoma.

Comparing apples to apples: a call for unification of complication reporting across health systems.

The formalization of assessment of surgical outcomes across health care systems for complex procedures is a significant problem in the surgical literature. Low and colleagues present support for the use of the Accordion Severity Grading System as a tool to provide simple and comprehensive assessment of postoperative complications.

Esophageal stenting in children: indications, application, effectiveness, and complications.

BACKGROUND: Use of esophageal stents is uncommon in children, and there are few reports. We report the first experience in predominantly small children and infants with retrievable, flexible stents designed for tracheobronchial use. OBJECTIVE: Evaluation of initial experience with placement of esophageal stents for benign esophageal disorders in children. DESIGN: A retrospective study. SETTING: A pediatric, academic, tertiary-referral center. PATIENTS: This study involved 7 pediatric patients. INTERVENTIONS: Covered tracheobronchial stents were endoscopically placed in pediatric patients with benign esophageal conditions. Removal involved using forceps to pull the purse-string suture into the endoscope channel and collapsing the top of the stent for easy removal. MAIN OUTCOME MEASUREMENTS: To evaluate the safety and feasibility of performing endoscopic stent placement in children and to establish criteria for early stent removal. RESULTS: Six of 7 patients benefitted from stenting. There were no complications of placement. Novel techniques were developed for difficult retrievals. One patient did not benefit from esophageal stent placement, because the stent migrated downward from the uppermost part of the esophagus. One patient had some gagging, which led to early removal of the stent. A stent was removed emergently in 1 patient for respiratory distress. LIMITATION: Small number of patients. CONCLUSIONS: Retrievable, covered stents are easily placed and removed from the esophagus in small children. They should be considered for severe unrelenting strictures, especially when associated with esophageal leaks. A need exists for development of esophageal stents designed for pediatric use.