Setting: A tertiary-referral urban children's hospital.Patients: A total of 131 patients younger than 18 years with a preoperative diagnosis of perforated appendicitis.Interventions: Early appendectomy (within 24 hours of admission) vs interval appendectomy (6-8 weeks after diagnosis).Main Outcome Measures: Time away from normal activities (days). Secondary outcomes included the overall adverse event rates and the rate of predefined specific adverse events (eg, intra-abdominal abscess, surgical site infection, unplanned readmission).Results: Early appendectomy, compared with interval appendectomy, significantly reduced the time away from normal activities (mean, 13.8 vs 19.4 days; PϽ.001). The overall adverse event rate was 30% for early appendectomy vs 55% for interval appendectomy (relative risk with interval appendectomy, 1.86; 95% confidence interval, 1.21-2.87; P=.003). Of the patients randomized to interval appendectomy, 23 (34%) had an appendectomy earlier than planned owing to failure to improve (n=17), recurrent appendicitis (n=5), or other reasons (n=1).
Conclusions:Early appendectomy significantly reduced the time away from normal activities. The overall adverse event rate after early appendectomy was significantly lower compared with interval appendectomy.
Purpose
Ionizing radiation, an important component of glioma therapy, is critically dependent on tumor oxygenation. However, gliomas are notable for areas of necrosis and hypoxia, which foster radioresistance. We hypothesized that pharmacologic manipulation of the typically dysfunctional tumor vasculature would improve intratumoral oxygenation and, therefore, the anti-glioma efficacy of ionizing radiation.
Methods and Materials
Orthotopic U87 xenografts were treated with either continuous interferon-beta (IFN-β) or bevacizumab, alone, or in combination with cranial irradiation (RT). Tumor growth was assessed by quantitative bioluminescence imaging; tumor vasculature, with immunohistochemical staining; and tumor oxygenation, with hypoxyprobe staining.
Results
Both IFN-β and bevaziumab profoundly affected the tumor vasculature, albeit with different cellular phenotypes. IFN-β caused a doubling in the percent area of perivascular cell staining while bevacizumab caused a rapid decrease in the percent area of endothelial cell staining. However, both agents increased intratumoral oxygenation, although with bevacizumab the effect was transient, being lost by five days. Administration of IFN-β or bevacizumab prior to RT was significantly more effective than any of the three modalities as monotherapy or when RT was administered concomitantly with IFN-β or bevacizumab, or five days after bevacizumab.
Conclusions
Bevacizumab and continuous delivery of IFN-β each induced significant changes in glioma vascular physiology, improving intratumoral oxygenation and enhancing the anti-tumor activity of ionizing radiation. Further investigation into the use and timing of these and other agents that modify vascular phenotype, in combination with radiation, is warranted in order to optimize cytotoxic activity.
Very few articles provided definitive recommendations for care of the patient with a CPAM and none reported Level I or II evidence. Based on available information, CPAMs are usually resected early in life if at all. A prenatally diagnosed congenital lung lesion should be evaluated postnatally with CT, and prenatal counseling should be undertaken in patients at risk for hydrops.
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