Citations

PURPOSE Germline CDH1 pathogenic variants (PV) are associated with hereditary diffuse gastric cancer and lobular breast cancer. Although prevalence of CDH1 PV is low in the general population, detection of these variants is increasing with the growing use of multigene panel testing. Little is known about the experiences of individuals tested for CDH1 variants in the multigene panel testing era. METHODS Participants recruited from the Prospective Registry of Multiplex Testing completed a cross-sectional self-report survey regarding CDH1 genetic testing experiences, medical management, and psychosocial adaptation. RESULTS Discordance existed in interpretations of CDH1 results; 13.3% of cases had disagreements in variant classifications among commercial laboratories, and 21.4% had disagreements between participant self-report and ClinVar classification. Survey data were available from 57 individuals reporting either PV (n = 16) or variants of uncertain significance (VUS; n = 41). Those with PV were more likely than those with VUS to report receiving a recommendation for prophylactic gastrectomy, although only 40.0% of those with PV received this recommendation. Participants with VUS were less satisfied with their health care providers’ knowledge and reported less CDH1 knowledge, distress, and worry about discrimination. Participants with PV perceived greater breast cancer risks, but similar gastric cancer risks, as those with VUS. CONCLUSION Few individuals with CDH1 PV report receiving recommendations for prophylactic gastrectomy, and no differences in perceived gastric cancer risk were observed based on participants’ CDH1 results, suggesting serious unmet informational needs.

Background: Two-staged implant-based reconstruction (IBR) is the most common breast reconstructive modality. Recently, technological and surgical advances have encouraged surgeons to revisit prepectoral IBR. Data comparing prepectoral against subpectoral IBR in women under the age of 40 are lacking. Methods: Retrospective chart review of patients under the age of 40 years old, who underwent immediate 2-staged IBR at our institution, was performed. Patient’s demographics, clinical characteristics, operative details, and early surgical outcomes of prepectoral and subpectoral reconstruction were compared. Data with values of P < 0.05 were considered statistically significant. Results: Between 2012 and 2016, 100 patients (187 breasts) who underwent prepectoral and 69 patients (124 breasts) who underwent subpectoral IBR were included. Median follow-up was 17.9 and 17.5 months in the prepectoral and subpectoral groups, respectively. Total number of complications including both stages of reconstruction was 20 (10.7%) and 19 (15.3%) in the prepectoral and subpectoral groups, respectively (P = 0.227). Specific complications, including hematoma, seroma, skin flap necrosis, wound dehiscence, and breast infections, were not significantly different among groups. Ten (5.4%) devices, including implants and tissue expander, required explantation in the prepectoral group and 8 (6.5%) in the subpectoral group (P = 0.683). Explantation was most commonly due to infection (n = 14), and all of them occurred during the first stage (P < 0.001). Conclusions: Early complications and implant explantation rates are comparable among prepectoral and subpectoral breast reconstruction in women under 40 years old. Based on these results, we believe that prepectoral IBR is a safe, reliable, and promising reconstructive option.

Abstract Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker‐based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood‐brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.