The use of clinical examination and cranial ultrasound in the diagnosis and management of post-hemorrhagic ventricular dilation in extremely premature infants.

OBJECTIVES: The objective of this study is to describe clinical and ultrasound changes in a cohort of premature newborns with post-hemorrhagic ventricular dilation (PHVD), and to correlate these changes with outcome. STUDY DESIGN: Premature newborns <29 weeks gestational age (GA) and ≤ 1,500 g birth weight with intraventricular hemorrhage were retrospectively reviewed. Clinical signs and cranial ultrasound (CUS) findings between time after birth and time before first cerebrospinal fluid temporizing intervention were compared with GA-equivalent newborns without interventions. White matter injury was assessed on brain magnetic resonance imaging. RESULTS: Between 2011 and 2014, 64 newborns met inclusion criteria; 23% had PHVD. The growth rates of the ventricles on CUS and the head circumference (HC) were higher in newborns with PHVD (p < 0.01 and p = 0.04, respectively) and correlated inversely with white matter injury (p = 0.006 and p < 0.001, respectively). CONCLUSION: Progression of PHVD in premature newborns as demonstrated by CUS and the HC correlated with outcome. Consistent measurement of these simple parameters will allow for much needed treatment comparisons, to define optimal protocols that decrease the risk of cerebral palsy in extremely preterm populations.

Whole exome sequence analysis of serous borderline tumors of the ovary.

OBJECTIVE: Serous borderline tumor (SBT) is a unique histopathologic entity of the ovary, believed to be intermediate between benign cystadenoma and invasive low-grade serous carcinoma. While somatic mutations in the KRAS or BRAF, and rarely ERBB2, genes have been well characterized in SBTs, other genetic alterations have not been described. Toward a more comprehensive understanding of the molecular genetic architecture of SBTs, we undertook whole exome sequencing of this tumor type. METHODS: Following pathologic review and laser capture microdissection to enrich for tumor cells, whole exomes were prepared from DNA of two independent SBTs and subjected to massively parallel DNA sequencing. RESULTS: Both tumors contained an activating mutation of the BRAF gene. A total of 15 additional somatic mutations were identified, nine in one tumor and six in the other. Eleven were missense mutations and four were nonsense or deletion mutations. Fourteen of the 16 genes found to be mutated in this study have been reported to be mutated in other cancers. Furthermore, 12 of these genes are mutated in ovarian cancers. The FBXW7 and KIAA1462 genes are noteworthy candidates for a pathogenic role in serous borderline tumorigenesis. CONCLUSIONS: These findings suggest that a very small number of somatic genetic mutations are characteristic of SBTs of the ovary, thus supporting their classification as a relatively genetically stable tumor type. The mutant genes described herein represent novel candidates for the pathogenesis of ovarian SBT.