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PurposeCongenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy.MethodsWe retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017.ResultsFifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old.ConclusionOur study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes.Type of StudyRetrospective Treatment Study.Level of EvidenceLevel IV.  相似文献   
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PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted.  相似文献   
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