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We review the diagnostic tools, treatment options, and clinical management for brain tumors diagnosed in pregnancy with consideration for management approaches that are best suited to preserve maternal and fetal health.Women of child-bearing age are at risk of developing brain tumors and are at increased risk compared with male counterparts for tumors that are hormonally driven. Brain tumors are rare neoplasms, and diagnosis of brain tumors in pregnancy is uncommon, such that management guidelines and treatment recommendations are lacking for most tumor types. We discuss the standard treatment options for brain tumors and the relative risks and safety when these treatments are considered during pregnancy. We review the neoplasms most commonly affecting pregnant women and the existing literature and guidelines.Pregnancy is a unique phase of life in which hormonal, immunologic, and vascular changes may impact tumor growth and presentation. Treatment decisions should consider the symptoms and stability of the pregnant patients, the gestational age and health of the fetus, and the location and behavior of the neoplasm.

Diffusely infiltrating gliomas are associated with high morbidity and mortality due to the infiltrative nature of tumor spread. They are morphologically complex tumors, with a high degree of proteomic variability across both the tumor itself and its heterogenous microenvironment. The malignant potential of these tumors is enhanced by the dysregulation of proteins involved in several key pathways, including processes that maintain cellular stability and preserve the structural integrity of the microenvironment. Although there have been numerous bulk and single-cell glioma analyses, there is a relative paucity of spatial stratification of these proteomic data. Understanding differences in spatial distribution of tumorigenic factors and immune cell populations between the intrinsic tumor, invasive edge, and microenvironment offers valuable insight into the mechanisms underlying tumor proliferation and propagation. Digital spatial profiling (DSP) represents a powerful technology that can form the foundation for these important multilayer analyses. DSP is a method that efficiently quantifies protein expression within user-specified spatial regions in a tissue specimen. DSP is ideal for studying the differential expression of multiple proteins within and across regions of distinction, enabling multiple levels of quantitative and qualitative analysis. The DSP protocol is systematic and user-friendly, allowing for customized spatial analysis of proteomic data. In this experiment, tissue microarrays are constructed from archived glioblastoma core biopsies. Next, a panel of antibodies is selected, targeting proteins of interest within the sample. The antibodies, which are preconjugated to UV-photocleavable DNA oligonucleotides, are then incubated with the tissue sample overnight. Under fluorescence microscopy visualization of the antibodies, regions of interest (ROIs) within which to quantify protein expression are defined with the samples. UV light is then directed at each ROI, cleaving the DNA oligonucleotides. The oligonucleotides are microaspirated and counted within each ROI, quantifying the corresponding protein on a spatial basis.

BACKGROUND AND PURPOSE: Children with shunted hydrocephalus have been undergoing surveillance neuroimaging, generally in the form of head CT, for evaluation of ventricular size. As the life expectancy of these children has improved due to better shunt technology and medical care, risks related to the ionizing radiation incurred during multiple head CT examinations that they are expected to undergo throughout their lifetime have become a concern. The purpose of this study is to estimate the LAR of developing fatal cancer due to head CT for ventricular size assessment in children with shunted hydrocephalus and to assess the impact of instituting a rapid brain MR imaging protocol in reducing radiation exposure. MATERIALS AND METHODS: Retrospective review of medical records yielded 182 patients who underwent neuroimaging for assessment of ventricular size. Available neuroimaging studies (head CT and rapid brain MR) were counted and annual neuroimaging frequency was calculated. It was assumed that these patients undergo a similar number of neuroimaging studies annually through 20 years of age. A risk estimate was calculated based on the BEIR VII report and effective doses obtained using the International Commission on Radiologic Protection Report 103 organ weighting factors. RESULTS: The mean annual neuroimaging study frequency was 2.1. Based on the average age of 1.89 years, it was assumed neuroimaging surveillance commences in the second year of life. LAR was calculated assuming that a patient undergoes neuroimaging in the form of head CT at this frequency (2/year) through 20 years of age. Assuming 2 scans are performed per year and the low-dose head CT protocol is used, approximately 1 excess lifetime fatal cancer would be generated per 230 patients; with standard head CT, there would be 1 excess lifetime fatal cancer per 97 patients. CONCLUSIONS: Children with shunted hydrocephalus are at increased risk of developing fatal cancer if they are to undergo surveillance using head CT. Implementation of a rapid brain MR imaging protocol with no radiation detriment will reduce this risk.

BACKGROUND Fragmented cancer care (FC), or care received from multiple institutions, increases systemic health care costs and potentiates cancer care disparities. There is a paucity of data on mechanisms contributing to FC and the resulting effect on patient outcomes. This study characterized patient- and hospital-level factors associated with FC, time to treatment (TTT), and overall survival (OS) in patients with hepatocellular carcinoma (HCC). METHODS Patients newly diagnosed with HCC from 2004 to 2015 and receiving treatment were identified in the Texas Cancer Registry. Patient- and hospital-level factors were compared across 2 cohorts: an FC treatment group and a nonfragmented cancer care (NFC) treatment group. Covariate-adjusted treatment use and OS were compared between the 2 treatment groups. RESULTS Among 4329 patients with HCC, 1185 (27.4%) received FC, and 3144 (72.6%) received NFC. Compared with NFC patients, FC patients had larger tumors (median size ≥4 cm, 52.6% vs 35.2%; P

Background Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. Methods During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0 to 5 dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2 nM) or valproic acid (0, 0.5, 5.0 or 50 μM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). Results There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. Conclusions Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed.

Gene annotations, such as those in GENCODE, are derived primarily from alignments of spliced cDNA sequences and protein sequences. The impact of RNA-seq data on annotation has been confined to major projects like ENCODE and Illumina Body Map 2.0. We aligned 21,504 Illumina-sequenced human RNA-seq samples from the Sequence Read Archive (SRA) to the human genome and compared detected exon-exon junctions with junctions in several recent gene annotations. We found 56,861 junctions (18.6%) in at least 1000 samples that were not annotated, and their expression associated with tissue type. Junctions well expressed in individual samples tended to be annotated. Newer samples contributed few novel well-supported junctions, with the vast majority of detected junctions present in samples before 2013. We compiled junction data into a resource called intropolis available at http://intropolis.rail.bio . We used this resource to search for a recently validated isoform of the ALK gene and characterized the potential functional implications of unannotated junctions with publicly available TRAP-seq data. Considering only the variation contained in annotation may suffice if an investigator is interested only in well-expressed transcript isoforms. However, genes that are not generally well expressed and nonetheless present in a small but significant number of samples in the SRA are likelier to be incompletely annotated. The rate at which evidence for novel junctions has been added to the SRA has tapered dramatically, even to the point of an asymptote. Now is perhaps an appropriate time to update incomplete annotations to include splicing present in the now-stable snapshot provided by the SRA.

We aligned 21,504 publicly available Illumina-sequenced human RNA-seq samples from the Sequence Read Archive (SRA) to the human genome and compared detected exon-exon junctions with junctions in several recent gene annotations. 56,865 junctions (18.6%) found in at least 1,000 samples were not annotated, and their expression associated with tissue type. Newer samples contributed few novel well-supported junctions, with 96.1% of junctions detected in at least 20 reads across samples present in samples before 2013. Junction data is compiled into a resource called intropolis available at http://intropolis.rail.bio. We discuss an application of this resource to cancer involving a recently validated isoform of the ALK gene.