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Background: Optimal timing for resection of asymptomatic congenital lung malformations (CLMs) remains controversial. The aim of this study is to define optimal timing for surgical intervention of patients with CLMs and define clinical variables that affect surgical outcomes.Methods: An IRB-approved retrospective analysis was conducted for patients undergoing surgery for CLMs between 2012 and 2017. Subjects were divided into cohorts based on timing of operative intervention. “Early intervention” was defined as surgery within 4 months of birth; “intermediate intervention”—between 4 and 6 months; and “late intervention”−6–12 months. Surgical outcomes including intraoperative estimated blood loss (EBL), surgical time, post-operative pneumothorax, length of time chest tube stayed in, and hospital length of stay were compared among the three groups using Fisher's exact test or Chi-squared test for categorical variables and one-way analysis of variance test for continuous variables.Results: We analyzed 63 patients who underwent surgery for CLM. There were no significant differences in baseline characteristics. Timing of surgery did not significantly correlate with post-operative outcomes. Specifically, there was no difference in operative time, EBL, post-operative pneumothorax, or length of hospital stay among the early, intermediate, and late intervention groups. Even after controlling for cyst-volume ratio (CVR), timing of surgery still did not affect post-operative outcomes.Conclusions: Surgical outcomes for resection of CLMs are not significantly affected by timing of surgery. We advocate for early intervention to decrease the incidence of associated complications that can occur with later intervention.

High grade serous ovarian cancer (HGSC) is the most common and deadly type of ovarian cancer, largely due to difficulties in early diagnosis and rapid metastasis throughout the peritoneal cavity. Previous studies have shown that expression of Notch3 correlates with worse prognosis and increased tumorigenic cell behaviors in HGSC. We investigated the mechanistic role of Notch3 in a model of metastatic ovarian cancer using the murine ovarian surface epithelial cell line, ID8 IP2. Notch3 was activated in ID8 IP2 cells via expression of the Notch3 intracellular domain (Notch3IC). Notch3IC ID8 IP2 cells injected intraperitoneally caused accelerated ascites and reduced survival compared to control ID8 IP2, particularly in early stages of disease. We interrogated downstream targets of Notch3IC in ID8 IP2 cells by RNA sequencing and found significant induction of genes that encode adhesion and extracellular matrix proteins. Notch3IC ID8 IP2 showed increased expression of ITGA1 mRNA and cell-surface protein. Notch3IC-mediated increase of ITGA1 was also seen in two human ovarian cancer cells. Notch3IC ID8 IP2 cells showed increased adhesion to collagens I and IV in vitro. We propose that Notch3 activation in ovarian cancer cells causes increased adherence to collagen-rich peritoneal surfaces. Thus, the correlation between increased Notch3 signaling and poor prognosis may be influenced by increased metastasis of HGSC via increased adherence of disseminating cells to new metastatic sites in the peritoneum.