We describe a preclinical model that investigates progression of early-stage ductal carcinoma in situ (DCIS) and report that compromised myoepithelial cell differentiation occurs before transition to invasive disease. Human breast cancer MCF10DCIS.com cells were delivered into the mouse mammary teat by intraductal injection in the absence of surgical manipulations and accompanying wound-healing confounders. DCIS-like lesions developed throughout the mammary ducts with full representation of human DCIS histologic patterns. Tumor cells were incorporated into the normal mammary epithelium, developed ductal intraepithelial neoplasia and DCIS, and progressed to invasive carcinoma, suggesting the model provides a rigorous approach to study early stages of breast cancer progression. Mammary glands were evaluated for myoepithelium integrity with immunohistochemical assays. Progressive loss of the myoepithelial cell differentiation markers p63, calponin, and a-smooth muscle actin was observed in the mouse myoepithelium surrounding DCISinvolved ducts. p63 loss was an early indicator, calponin loss intermediate, and a-smooth muscle actin a later indicator of compromised myoepithelium. Loss of myoepithelial calponin was specifically associated with gain of the basal marker p63 in adjacent tumor cells. In single time point biopsies obtained from 16 women diagnosed with pure DCIS, a similar loss in myoepithelial cell markers was observed. These results suggest that further research is warranted into the role of myoepithelial cell p63 and calponin expression on DCIS progression to invasive disease. Clinical evidence is compelling for histologic progression of breast cancer through atypical hyperplasia, ductal carcinoma in situ (DCIS), invasive ductal carcinoma, and metastatic stages. 1 Such histopathologic progression studies and mutational profiling of epithelial cancers 2,3 suggest that acquisition of invasive potential is a relatively late event. However, genomic data analyses have revealed that most tumor cell gene expression changes occur at the transition from normal to DCIS, with few additional changes in expression occurring at the transition from DCIS to overt invasive disease. 4,5 These observations implicate key roles for nonepithelial cells in progression to invasive disease. 6,7 The lack of relevant model systems has hindered our understanding of the DCIS to invasive transition.The clinical definition of invasive breast cancer is spread of malignant tumor cells from the confines of the mammary duct into the adjacent tissue stroma. In the normal mammary gland, epithelial ductal and alveolar structures are

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BACKGROUND AND PURPOSE The effect of coronavirus disease 2019 (COVID‐19) pandemic on performance of neuroendovascular procedures has not been quantified. METHODS We performed an audit of performance of neuroendovascular procedures at 18 institutions (seven countries) for two periods; January‐April 2019 and 2020, to identify changes in various core procedures. We divided the region where the hospital was located based on the median value of total number of COVID‐19 cases per 100,00 population‐into high and low prevalent regions. RESULTS Between 2019 and 2020, there was a reduction in number of cerebral angiograms (30.9% reduction), mechanical thrombectomy (8% reduction), carotid artery stent placement for symptomatic (22.7% reduction) and asymptomatic (43.4% reduction) stenoses, intracranial angioplasty and/or stent placement (45% reduction), and endovascular treatment of unruptured intracranial aneurysms (44.6% reduction) and ruptured (22.9% reduction) and unruptured brain arteriovenous malformations (66.4% reduction). There was an increase in the treatment of ruptured intracranial aneurysms (10% increase) and other neuroendovascular procedures (34.9% increase). There was no relationship between procedural volume change and intuitional location in high or low COVID‐19 prevalent regions. The procedural volume reduction was mainly observed in March‐April 2020. CONCLUSIONS We provided an international multicenter view of changes in neuroendovascular practices to better understand the gaps in provision of care and identify individual procedures, which are susceptible to change.

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Infection can be a common complication following bifrontal craniotomy with skull base osteotomies given the potential violation of sinuses and entry into the nasal structures. Our objective was to examine our series of patients who underwent a bifrontal craniotomy with skull base osteotomies and describe the infection rate. We propose the bifrontal osteoplastic flap as an adjunct to infection prevention. A retrospective single-center study of a patient database was performed. Twenty patients were identified. Fifty-five percent were male. The mean age was 55.7 ± 13.9 years. The most common indications for surgery were esthesioneuroblastomas (35%) and anterior skull base meningiomas (30%). Six patients (30%) developed an infection, 1 patient (5%) developed a CSF leak, and no patients developed a mucocele. All 6 infected cases had nasal pathology with intracranial extension, they all received chemoradiation post-operatively and were all combined cases with otorhinolaryngology. Eighty-three percent of these patients required a craniectomy and all of them required long-term IV antibiotics. Infection is not uncommon after a bifrontal craniotomy with skull base osteotomies and the use of the bifrontal osteoplastic flap in cases where the risk of infection is high, i.e., esthesioneuroblastomas surgery, may help reduce said risk and lead to better patient outcomes.

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Young African American women have an increased risk of developing aggressive forms of breast cancer (i.e. triple negative/basal-like) than young non-Hispanic white women. Recent epidemiological data show increased risk of basal-like breast cancer with increased childbearing in African American women (Millikan et al 2008; Palmer et al 2011). Breast cancers associated with a recent pregnancy (pregnancy-associated breast cancer) are more likely to be metastatic (Lyons et al 2011). We predict that the triple negative/basal-like breast cancer subtype is promoted by a recent pregnancy, accounting in part, for the poor prognosis of young African American breast cancer patients. We have developed a murine intraductal mammary model to examine the effect of host reproductive status on the progression of early stage human breast cancer. Our model delivers human mammary tumor cells directly through the intact mouse teat into the correct anatomical location for ductal carcinoma in situ (DCIS) without surgical manipulations. MCF10ADCIS.com (triple negative/basal cell line) or HCC70 (triple negative cell line derived from a young African American woman) cells were delivered into the mammary gland via intraductal injection to assess influence of host reproductive state (nulliparity, pregnancy, active post-partum involution) on tumor progression. Lesions from both cell lines displayed the full representation of human DCIS histologic subtypes, which progressed to DCIS through an atypical ductal hyperplasia stage. Although the MCF10ADCIS.com cell line is typically triple negative in vitro and other in vivo models, established tumors in the intraductal model were observed to re-express estrogen receptor. HCC70 tumors maintained the triple negative phenotype in our model. Using the MCF10ADCIS.com model to assess the effects of host reproductive status on DCIS progression, we found tumor burden in the pregnancy group was not significantly different than nulliparous controls. Within the pregnant group, tumors appear to be less proliferative and have slightly lower ER expression than nulliparous control tumors. Tumor burden in the postpartum involution group is significantly greater than the respective nulliparous control group; however, the Ki67 proliferative index is lower 4 weeks post injection in comparison to nulliparous controls. DCIS progression to locally invasive disease occurred with progressive loss of myoepithelial cell differentiation markers. In both cell line models, the loss of p63 was identified as an early indicator of compromised myoepithelium. Further, our data suggest that the protective myoepithelial cell layer may be preferentially compromised by tumors formed in postpartum involuting mammary glands. Our murine mammary intraductal model of human breast cancer provides a rigorous approach to study early stage-tumor progression, and is well suited to study the effect of the host reproductive state on DCIS progression. Since occult tumors in women develop within ducts, we propose that this teat injection model will aid research of early disease progression, a requisite for research focused on breast cancer prevention and inhibition of local invasion. Further, this model may provide a unique opportunity to address and study tumor growth disparities among African American and non-Hispanic white women. Citation Format: Tanya D. Russell, Samiat Agunbiade, Sonali Jindal, Jaime Fornetti, Virginia Borges, Pepper Schedin. A novel mammary intraductal delivery model that permits study of human ductal carcinoma in situ progression. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B29.