Sentinel nodes (SNs), the nodes nearest a primary tumor on the direct lymphatic drainage path, are the site of earliest metastases, and in melanoma show striking immune modulation. We evaluated SNs from breast cancer patients for evidence of similar immune perturbation. The purpose of this study was to evaluate whether SNs from patients with breast cancer show the alterations in the histology and cytology of the paracortical areas seen in SNs from patients with melanoma. Formalin-fixed and paraffin-embedded sections from 32 SNs and 32 nonsentinel nodes (NSNs) from patients with breast cancer were evaluated. Sections were stained with hematoxylin and eosin and with antibodies to S-100 protein and HLA-DR, DQ, and DP to identify interdigitating dendritic cells (IDCs), and by an antibody to CD43RA to delineate T lymphocytes. By computerized image analysis we evaluated the distribution, frequency, immunophenotype, and activation status of IDCs and associated T lymphocytes in SNs and NSNs. Average areas occupied by S-100-positive dendritic cells (DCs) in SNs and NSNs were 0.13% and 19.98%, respectively, of total nodal area (p < 0.0001). The average density of S-100-positive IDCs in SNs was 11.00/mm2 and in NSNs was 257.88/mm2 (p < 0.0001). In SNs 43.55% of DCs (4.93/mm2) were nondendritic, 51.92% (5.69/mm2) had short dendrites, and 5.2% were mature with long dendrites (0.62/mm2). In SNs the ratio of immature to mature IDCs was 7.95:1. In NSNs, 8.09% of DCs (8.5/mm2) were nondendritic, 28.22% (67.46/mm2) had short dendrites, and 63.07% (145.96/mm2) were mature DCs with long dendrites. The ratio of immature to mature DCs in NSNs was 1:6.66. The average areas occupied by HLA class II-positive DCs in SNs and NSNs were 4.21% and 31.82%, respectively, of total nodal area. The frequency of coexpression of S-100 and HLA class II by immature IDCs without dendrites was 11.27% in SNs and 15.00% in NSNs. In both SNs and NSNs (p < 0.001) all mature S-100-positive IDCs with long dendrites expressed HLA class II. CD43RA-positive T lymphocytes occupied 20.06% of total nodal area in SNs and 63.57% in NSNs (p < 0.0001). The SNs from breast cancer patients are profoundly immune modulated with, by comparison to NSNs, markedly reduced paracortical areas, densities of paracortical DCs, frequency of S-100-positive IDCs coexpressing HLA class II, and a predominance of immature nondendritic and poorly dendritic DCs.
BackgroundDerived from multiple disciplines and established in industries outside of medicine, Implementation Science (IS) seeks to move evidence-based approaches into widespread use to enable improved outcomes to be realized as quickly as possible by as many as possible.MethodsThis review highlights selected IS theories and models, chosen based on the experience of the authors, that could be used to plan and deliver medical education activities to help learners better implement and sustain new knowledge and skills in their work settings.ResultsIS models, theories and approaches can help medical educators promote and determine their success in achieving desired learner outcomes. We discuss the importance of incorporating IS into the training of individuals, teams, and organizations, and employing IS across the medical education continuum. Challenges and specific strategies for the application of IS in educational settings are also discussed.ConclusionsUtilizing IS in medical education can help us better achieve changes in competence, performance, and patient outcomes. IS should be incorporated into curricula across disciplines and across the continuum of medical education to facilitate implementation of learning. Educators should start by selecting, applying, and evaluating the teaching and patient care impact one or two IS strategies in their work.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.